Clinics and Practice doi: 10.3390/clinpract16070134

Authors: Sonata Čerkauskaitė Alina Liepinaitienė

Background/Objectives: Chronic non-communicable diseases remain one of the main public health problems. Increasing multimorbidity and the importance of health literacy (HL) emphasize the need for a comprehensive assessment of health indicators. The aim of this study was to assess the main health indicators of the Lithuanian population and trends in the use of healthcare services and to discuss the relevance of these indicators in the context of HL, based on the links between HL and these indicators described in the scientific literature. Methods: A retrospective longitudinal descriptive study was performed using publicly available Lithuanian population health statistics of 2005–2024. Mortality, morbidity, avoidable hospitalizations, subjective health assessment, and utilization of healthcare services and preventive programs were analyzed using descriptive statistical analysis. HL was not directly measured but was used as a conceptual framework for interpreting the findings. Results: In Lithuania, the highest mortality rate is due to cardiovascular diseases (CVDs) (~50.8%). CVD and infectious diseases also dominate the structure of avoidable hospitalizations, and their rates vary greatly across municipalities, being higher in less urbanized areas. The assessment of the population’s health is improving over time, but gender differences remain in the use of healthcare services and preventive programs. Conclusions: The findings demonstrate a high burden of chronic diseases and regional disparities in healthcare utilization in Lithuania. HL may provide a useful context for interpreting these findings, although it was not directly assessed. Future studies should directly evaluate HL and its association with health indicators in the Lithuanian population.

Clinics and Practice doi: 10.3390/clinpract16070133

Authors: Sedeek Mosaid Yousif Jihad Mostafa Jihad Ashok Marudanayagam Paul Lee

Background/Objectives: Total ankle arthroplasty (TAA) is increasingly used to treat end-stage ankle arthritis, but comprehensive cross-registry data on revision patterns remain limited. This study describes indications, causes, and patient risk factors for revisions using three national registries. Methods: Aggregate data were extracted from the UK National Joint Registry (NJR; 22nd Annual Report 2025; n = 11,321), the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR; 2025 Ankle Supplementary Report; n = 5379), and the Swedish Ankle Registry (SwedAnkle; Annual Report 2024; n = 1852; survival estimates from a published sub-cohort, n = 1226). Metrics were compared descriptively without inferential pooling. Results: Across registries, 18,552 primary TAAs were identified. Ten-year cumulative per cent revision (CPR) was 9.54% (95% confidence interval [CI], 8.75–10.39) in the NJR, 13.5% (95% CI, 12.1–15.1) in the AOANJRR osteoarthritis sub-cohort, and approximately 26% (author-derived from Kaplan–Meier curves; see Methods) in SwedAnkle (1993 onwards implants). Aseptic loosening was the predominant cause of revision in all three registries; the rank of subsequent causes differed between registries (infection was second in the NJR and AOANJRR; in SwedAnkle, infection ranked below insert wear/breakage at 11.5%). AOANJRR Cox analysis identified younger age (hazard ratios (HRs), 2.00 for <55 vs. ≥75 years; 95% CI, 1.30–3.07; p = 0.001), earlier surgical era (HR, 1.91 for pre-2015 vs. 2015–2024; 95% CI, 1.53–2.38; p < 0.001), and obesity (HR, 1.52 for body mass index (BMI) ≥ 30; 95% CI, 1.06–2.19; p = 0.023) as significant independent predictors in AOANJRR Cox proportional hazards models (osteoarthritis sub-cohort for age, sex, BMI and ASA; all-diagnoses primary cohort for surgical era). Sex and American Society of Anesthesiologists (ASA) scores were not significant. Conclusions: Aseptic loosening was the predominant cause of revision in all three registries. The rank of subsequent causes differed: in the NJR and AOANJRR, infection was the second most frequent cause; in SwedAnkle, infection ranked below insert wear/breakage. Younger age, obesity, and earlier surgical era were independent predictors of revision in AOANJRR Cox proportional hazards models. The post-2015 era was associated with approximately 48% lower revision hazard; this association cannot be interpreted causally, as the independent contributions of implant design, surgical technique, patient selection, and other secular changes cannot be isolated from registry data. These findings may inform preoperative counselling, implant selection, and registry harmonisation efforts.

Clinics and Practice doi: 10.3390/clinpract16070132

Authors: Savoia Fabiana La Verde Marco Giudicepietro Antonia Minnella Gian Piero Fantasia Ilaria Sarno Laura Quaresima Paola Gerbino Martina Volpe Grazia Dall’Asta Andrea Morlando Maddalena

Background/Objectives: This study aimed to compare the visualization rates of fetal anatomical structures with standard 2D ultrasound examination versus a single 3D volume acquired during the first trimester. Methods: This multicenter prospective study was performed in nine tertiary referral centers, by experienced sonographers. A standard protocol was adopted in both 2D and 3D modalities to assess the 17 anatomical structures listed in the national and international guidelines. The included cases were non-anomalous fetuses from women booked for combined screening test between 11 + 0 and 13 + 6 weeks. Results: Two hundred and thirty-nine women were included in the study. The mean gestational age at ultrasound examination was 12 weeks ± 5 days (±5.4 SD). All the 17 structures were seen in 155/239 fetuses (64.85%) at 2D evaluation and in 84/239 (35.15%) at 3D evaluation (p = 0.001). Comparing 2D and 3D visualization, the following anatomical structures showed a statistical difference: posterior fossa (92% vs. 74%, p < 0.005); neck (94.2% vs. 87.2%, p < 0.001); orbits (93% vs. 85.6%, p < 0.001); nasal bone (93% vs. 88.8%, p = 0.016); lung fields (99.5% vs 96.7%, p = 0.046); cardiac axis (99.5% vs. 83.9%; p < 0.001); bladder (97.5% vs. 91.7%, p < 0.001); abdominal wall (98.7% vs. 94.2%, p < 0.001). For the other anatomical portion, no statistically significant differences were found. Conclusions: Our study demonstrates that a full assessment of fetal anatomy is best performed using 2D ultrasound, while 3D ultrasound showed lower overall visualization rates, with comparable performance for selected structures, suggesting a potential supplementary use in specific clinical contexts.

Clinics and Practice doi: 10.3390/clinpract16070131

Authors: Fabrizio Lucente Lucia Filippi Arian Zaboli Alessandra Eugenia Bionda Michael Maggi Marta Parodi Alice Bresolin Arianna Pretto Martina Da Meda Silvia Greselin Francesca Fulghesu Gianni Turcato

Background: Delirium is an under-recognized complication in hospitalized acute care patients, associated with worse outcomes including increased length of stay, higher ICU admission rates and greater mortality. Although screening tools exist for early diagnosis, the absence of admission-based tools limits early risk stratification and timely prevention strategies. Aim: To identify early risk factors for delirium development in IMCU patients and quantify its prognostic role on 30-day mortality. Methods: In this prospective single-center study, 651 consecutive IMCU patients without delirium at admission were enrolled. Admission variables were analyzed using multivariable logistic regression and Classification and Regression Tree (CART) analysis to identify clinically relevant risk phenotypes. The association between delirium and 30-day mortality was assessed in adjusted models. Results: Delirium developed in 18.6% of patients within 96 h. Key independent risk factors included age (OR 1.04), male sex (OR 1.75), alcohol use disorder (OR 3.59), cognitive impairment (OR 3.35), COPD (OR 1.68), NEWS (OR 1.18), and need for NIV (OR 3.83). CART analysis identified NIV as the dominant early discriminator, followed by cognitive vulnerability and acute severity. 30-day mortality was significantly higher in patients with delirium (22.3% vs. 9.8%, p = 0.001). Delirium remained an independent risk factor after adjustment (OR 2.53). CART analysis further corroborates delirium as a significant determinant, enhancing prognostic stratification beyond its role as a mere surrogate of disease severity. Conclusions: Admission-level clinical variables and exploratory CART analysis identified clinically interpretable delirium risk phenotypes in IMCU patients. Delirium was independently associated with increased 30-day mortality. These findings provide a preliminary framework for future validation studies and development of IMCU-specific risk-stratification approaches.

Clinics and Practice doi: 10.3390/clinpract16070130

Authors: Eleni Charitopoulou Angeliki Bolou Vikentia Harizopoulou Antigoni Sarantaki Athina Diamanti Irene Athina Avramidou Giannoula Kyrkou

Background: Sexual health is a key component of quality of life and an essential aspect of holistic maternity care. During pregnancy, changes in sexual function are often accompanied by fears and misconceptions, which are influenced by healthcare professionals’ counseling. Objectives: The present study aimed to investigate the knowledge, attitudes, and perceptions of midwives and obstetricians/gynecologists in Greece regarding sexual activity during pregnancy. Methods: A cross-sectional study was conducted using an anonymous, self-administered questionnaire. Participants included 121 healthcare professionals (73 midwives and 48 obstetricians/gynecologists). Data were analyzed using appropriate non-parametric statistical tests and multiple linear regression analysis. Results: The majority of participants (97.5%) considered sexual activity during pregnancy to be beneficial. Midwives demonstrated significantly higher scores on the knowledge assessment compared to obstetricians/gynecologists (67.7 ± 18.0 vs. 54.8 ± 24.2, p = 0.001) and more frequently selected the questionnaire response indicating benefits for both the couple and the fetus (46.6% vs. 27.1%, p = 0.031). A higher proportion of midwives perceived that pregnant women do not receive adequate information regarding their sexual health (93.2% vs. 68.8%, p < 0.001). Obstetricians/gynecologists were more likely to recommend restrictions even in low-risk pregnancies. Conclusions: The findings highlight the need for improved education and standardized counseling protocols on sexual health during pregnancy, with particular emphasis on strengthening the role of midwives in delivering holistic, woman-centered care.

Clinics and Practice doi: 10.3390/clinpract16070129

Authors: Francesco Saverio Ludovichetti Serena Zanatta Davide Scettri Valentina Brun Sergio Mazzoleni Edoardo Stellini Christian Bacci

Background: Infective endocarditis is a serious disease affecting cardiac tissues and may arise following episodes of transient bacteremia. Oral prosthetic pressure lesions, characterized by mucosal ulcerations, may facilitate the entry of pathogenic microorganisms into the systemic circulation. In predisposed individuals, the presence of such lesions may therefore contribute to the development of infective endocarditis. The objective of this study was to assess dental professionals’ knowledge, awareness, and self-reported clinical practices related to the possible relationship between oral prosthetic pressure lesions and infective endocarditis. Materials and Methods: A cross-sectional observational study was conducted using an anonymous online questionnaire specifically developed for this study and subjected to preliminary content validation and pilot assessment before administration. The survey was distributed online to oral health professionals working in the Italian public and private sectors; for the present analysis, only complete responses provided by licensed dental professionals practicing in Italy were included. Results: Among the 268 dental professionals analyzed, an overall limited awareness of the possible relationship between oral prosthetic pressure lesions and infective endocarditis emerged. Only 16.8% of participants reported being familiar with the most recent guidelines for the prevention of infective endocarditis. Conclusions: The findings suggest the need to strengthen continuing education, improve familiarity with current infective endocarditis prevention guidelines, and promote more structured clinical protocols for the assessment and management of prosthetic pressure lesions in patients at risk.

Clinics and Practice doi: 10.3390/clinpract16070128

Authors: Tareq Nafea Alharby Sultan Almuntashiri Majd Habib Alshammari Shahad Hassan Alshammari Ahad Fhaid Alzabni Asyah Awad Alnomassi Hanadi Saleh Alrashidi Saleh Alghamdi Nafees Ahemad Sirajudheen Anwar

Background: Hypothyroidism is a globally prevalent disorder with variations in its occurrence. However, few studies have reported its prevalence in Saudi Arabia. This study aimed to establish the prevalence, characteristics, and predictors of subclinical and overt hypothyroidism in a clinical cohort from the Hail region of Saudi Arabia. Methods: A retrospective cross-sectional design was used. Electronic medical records of adults (aged ≥18 years) who underwent thyroid function testing (TSH, FT4, and FT3) at the study institution were reviewed. Participants with missing laboratory or demographic data and those with hyperthyroidism (TSH < 0.4 mIU/L) were excluded. Hypothyroidism was classified biochemically using internationally accepted TSH and FT4 thresholds. The final analysis cohort comprised 724 participants. Results: Of 724 participants, 471 (65.1%) were euthyroid, 234 (32.3%) had subclinical hypothyroidism, and 19 (2.6%) had overt hypothyroidism, yielding a total biochemical hypothyroidism prevalence of 34.9% (n = 253). Women were over-represented (89.6%), and obesity was prevalent (69%). The biochemical results confirmed that overt hypothyroidism showed significantly elevated TSH and decreased FT4 compared to subclinical hypothyroidism. There were non-significant associations between gender, BMI, and hypertension with thyroid status. Age was an independent predictor of hypothyroid status (OR = 0.983, 95% CI: 0.970–0.995, p = 0.008), and systolic blood pressure was also independently associated (OR = 1.011, 95% CI: 1.002–1.019, p = 0.016). Multiple regression showed age, hypertension, gonarthrosis, and chest pain were independently associated with TSH levels. Hierarchical clustering suggested potential regional patterns in hypothyroidism prevalence. Conclusions: Hypothyroidism, mostly subclinical, was prevalent in this clinical cohort. Age and systolic blood pressure were independent predictors, while BMI and gender were not. Biochemical assessment is essential for detection, and larger prospective studies are recommended.

Clinics and Practice doi: 10.3390/clinpract16070127

Authors: Cristina Gena Dascalu Diana Tatarciuc Magda Ecaterina Antohe

Background/Objectives: This study analyzes the temporal and spatial evolution of type 2 diabetes prevalence in Romanian counties over a 10-year period (2012–2021), based on the time series autocorrelation and cross-correlation coefficients. Methods: The autocorrelation coefficients were calculated within each county’s data series, in order to identify the internal temporal dependencies, and the cross-correlation coefficients were calculated on administrative regions, in order to identify epidemiological patterns. Results: The type 2 diabetes prevalence rates in most counties follow autoregressive series, with significant positive correlations at lag 1, indicating cyclical fluctuations. Cross-correlation analysis revealed 3 regional patterns: North-East and West regions showed highly synchronized dynamics with cross-correlations exceeding 0.9, South-East and South regions showed mixed synchronization, with temporal lags of 1–2 years between counties, while the other regions (Center, South-West and North-West) revealed a synchronized core and an isolated county, with atypical dynamics (e.g., Cluj, Alba, Mehedinți, Ialomița). Conclusions: These findings highlight the utility of time series analysis in understanding the specificity of such data and their practical applicability in customizing the required public health interventions.

Clinics and Practice doi: 10.3390/clinpract16070126

Authors: Spyridon Lygeros Alkmini Gatsounia Ioanna Athanasiadou Aris I. Giotakis Foteini Tsapardoni Gerasimos Danielides

Background/Objectives: Sinonasal osteomas are benign, slow-growing tumors that are typically asymptomatic and incidentally detected. However, in rare cases, they may present with atypical and potentially serious complications involving other sinonasal, orbital, or intracranial structures. This review aims to synthesize these unusual manifestations and to highlight the underlying mechanisms, diagnostic challenges, and management implications. Methods: A narrative review of the literature was conducted, focusing on reported cases of sinonasal osteomas with rare or complicated presentations. Studies were analyzed with emphasis on clinical features, imaging findings, pathophysiological mechanisms, and treatment strategies. Results: Unusual presentations of sinonasal osteomas are primarily driven by sinus obstruction, progressive expansion, and skull-base erosion. These processes may result in complications such as pneumocephalus, intracranial mucoceles, cerebrospinal fluid leaks, orbital compression, and secondary infections. Clinical manifestations are often nonspecific, including headache, seizures, visual disturbances, or focal neurological deficits, which may delay diagnosis. High-resolution computed tomography is essential for identifying the osseous lesion and associated bone changes, while magnetic resonance imaging is critical for assessing soft-tissue involvement and intracranial extension. Management is individualized, with surgical resection indicated in most symptomatic or complicated cases, using endoscopic, open, or combined approaches. Conclusions: Although rare, atypical manifestations of sinonasal osteomas can result in significant morbidity. A mechanism-based understanding, supported by appropriate imaging, is essential for accurate diagnosis and timely management. Increased clinical awareness is crucial to improving outcomes in these uncommon but clinically significant cases.

Clinics and Practice doi: 10.3390/clinpract16070125

Authors: Koji Nozaka Shohei Murata Naohisa Miyakoshi

Background: Congenital fibular deficiency is a rare longitudinal deficiency of the lower extremity associated with limb-length discrepancy, ankle and foot deformity, soft-tissue imbalance, and functional impairment. Reconstruction may be challenging because bone healing, regenerate maturation, and mechanical stability can be less predictable in selected patients. Case Presentation: A man with congenital fibular deficiency developed chronic distal tibial nonunion after corrective osteotomy at another institution. The nonunion persisted for four years, and the patient presented to our hospital with inability to bear weight and wheelchair dependence. A comprehensive salvage strategy was performed, including Achilles tendon lengthening using the Vulpius technique, removal of retained fixation material, debridement and refreshment of the nonunion site, negative bacteriological cultures, autologous cancellous iliac bone grafting, acute shortening and compression of the docking site, circular external fixation, proximal tibial osteotomy, and gradual lengthening. Low-intensity pulsed ultrasound was applied postoperatively as an adjunctive biological stimulus. Results: Bone union was achieved, and the external fixator was removed approximately one year after surgery. A total lengthening of 78 mm was achieved. At 12-year follow-up, the AOFAS ankle-hindfoot score was 90, ankle range of motion was 5° dorsiflexion and 40° plantarflexion, and the JOA knee score was 95. The patient walked independently without assistive devices and continued to work. Mild residual varus deformity of the proximal tibia was present, but the patient reported no knee pain, ankle pain, or ankle instability, and radiographs showed no progressive osteoarthritic changes. Conclusions: In selected patients with congenital fibular deficiency and chronic nonunion after previous treatment, durable limb salvage may be achieved using an individualized strategy that addresses both biological and mechanical factors.

Clinics and Practice doi: 10.3390/clinpract16070124

Authors: Maxwell A. Barffour Elizabeth Karanja Mustafa Gandhi Susan S. Kais Saurabh Kapur Yezaz A. Ghouri

Background: Over 30% of patients with inflammatory bowel disease (IBD) experience primary non-response to tumor necrosis factor-α antagonists (anti-TNFs). Oncostatin M (OSM), a TNF-α-independent pro-inflammatory signaling cytokine, is emerging as a potential predictive biomarker of treatment response. Through a systematic review and meta-analysis, we assessed the utility of baseline serum or plasma OSM for predicting anti-TNF response in IBD patients. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science through March 2026 for studies reporting associations between baseline serum/plasma OSM and endoscopic or clinical response to anti-TNF therapy in adult IBD patients. We used a bivariate random-effects model to estimate pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the receiver operating characteristic (ROC) curve (AUC). Quality was assessed using QUADAS-2. Results: Data from four studies (n = 441 patients) were pooled. We estimated a pooled sensitivity of 82.8% (95% CI 71.4–90.3%) and a specificity of 88.4% (95% CI 82.7–92.4%) for predicting anti-TNF non-response. The pooled AUC was 0.899 (95% CI 0.858–0.940), with low heterogeneity (I2 = 16.0%). The pooled DOR was 36.7 (95% CI 15.7–85.8), with a positive likelihood ratio of 7.1 and a negative likelihood ratio of 0.19. Risk of bias was low across the studies. Conclusions: Higher serum OSM was associated with treatment failure in IBD patients receiving anti-TNF therapy, with a pooled AUC of 0.899 in assay-stratified analysis and 0.820 when all studies were included. However, the small number of available studies, substantial variability in OSM cutoffs (14–233.6 pg/mL) and assay heterogeneity limit the robustness and generalizability and call for additional prospective data to more-robustly characterize the clinical utility of OSM.

Clinics and Practice doi: 10.3390/clinpract16070123

Authors: Zülküf Akdemir Amed Çekdar Altındağ Rıdvan Çeçen Harun Arslan

Purpose: To determine the prevalence and subtype distribution of accessory navicular (AN) on adult ankle MRI and to evaluate MRI factors associated with AN-related bone marrow edema (BME); bilaterality was explored in patients with available contralateral MRI data. Methods: In this retrospective cross-sectional study, consecutive adult patients (≥18 years) who underwent ankle MRI between January 2022 and January 2025 at a single institution in Van, eastern Türkiye, were identified from the institutional archive. Two blinded readers assessed AN presence, classified subtypes using Coughlin criteria, measured maximal ossicle dimension for types 1–2, and recorded BME on fluid-sensitive sequences. Prevalence with 95% CIs was estimated, and multivariable logistic regression assessed factors associated with BME in patients with types 1–2. Results: Among 1988 unique patients (mean age: 42.2 ± 14.2 years; 42.6% male and 57.4% female), AN prevalence was 24.4% (95% CI: 22.6–26.4%), and type 2 predominated (50.2%). In the subgroup of AN-positive patients with available contralateral MRI data, AN was bilateral in 61 of 69 patients (88.4%). Interobserver agreement was excellent for AN detection and subtype classification (κ = 1.00 and κ = 0.98). Among types 1–2 included in the BME analysis (n = 385), BME occurred in 81 patients (21.0%). In the multivariable model, the adjusted ORs for BME were 4.46 for type 2 morphology, 1.24 per 1 mm increase in maximal dimension, 2.08 for female sex, and 0.71 per 10-year increase in age; concomitant os trigonum was not associated with BME. Conclusions: AN was common on ankle MRI, and type 2 was most strongly associated with BME; however, because this was a retrospective, cross-sectional, symptom-blinded study, causality and clinical correlation could not be established. Clinical Significance: Type 2 AN, particularly with a larger ossicle dimension, should prompt careful evaluation for MRI-detected BME, which should be interpreted as an imaging finding requiring clinical correlation.

Clinics and Practice doi: 10.3390/clinpract16070122

Authors: Ioana Ioniță Mădălina Iuliana Mușat Bogdan Cătălin Dan Adrian Lutescu Constantin Alexandru Ciobanu Adela Magdalena Ciobanu

Background and Objectives: Gambling disorder (GD) is a behavioral addiction associated with distress, comorbidity, and functional impairment. This exploratory cross-sectional study examined associations between DSM-5-TR symptom burden, personality dimensions, cognitive emotion regulation, quality of life, and sociodemographic variables in a Romanian clinical sample. Materials and Methods: The sample included 122 adults with psychiatrist-confirmed pathological gambling/GD recruited from “Prof. Dr. Alexandru Obregia” Clinical Hospital of Psychiatry, Bucharest. Personality was assessed with the Personality Clinical Form (PCF; 109 valid profiles), cognitive emotion regulation with the Cognitive Emotion Regulation Questionnaire, and quality of life with the Quality of Life Inventory. Symptom burden was measured using a nine-item binary DSM-5 symptom burden index. Results: The symptom burden index showed a pronounced ceiling effect: median = 9.00 (IQR = 9.00–9.00; range = 4–9), with 91.0% classified as severe and 77.9% meeting all nine criteria. In PCF analyses, symptom burden was positively associated, after Benjamini–Hochberg correction, with broad personality pathology, including maladaptive personality dimensions, personality-functioning indicators, and personality-disorder feature scales; the strongest association involved borderline features. Catastrophizing and Blaming Others were positively associated with severity, whereas Positive Reappraisal, Putting into Perspective, and Positive Refocusing were negatively associated. Quality of life was very low overall and associated with personality and coping variables, but not directly with symptom burden. Criterion-count rank distributions differed by marital status and perceived social support; occupational status showed an omnibus distributional difference, but no pairwise contrast survived correction. Conclusions: GD was characterized by severe symptom burden and restricted score variability. Findings support multidimensional assessment of personality functioning, emotion regulation, quality of life, and social–contextual vulnerability.

Clinics and Practice doi: 10.3390/clinpract16070121

Authors: Cosmin Marian Banceu Diana Mariana Banceu Marius Mihai Harpa Daiana Cristutiu Mihai Calinescu Horatiu Suciu

Acute aortic syndrome (AAS) comprises acute aortic dissection, intramural haematoma, penetrating atherosclerotic ulcer, and limited intimal tear, conditions that require rapid recognition because mortality and resource use are strongly influenced by time to diagnosis, anatomical extent, malperfusion, and the need for emergency surgical or endovascular intervention. This revised narrative review synthesizes contemporary evidence on clinical, genetic, environmental, and health-system determinants of prolonged hospitalisation, intensive care unit (ICU) utilisation, bed occupancy, and costs in patients with AAS. Beyond summarising established risk factors, the review adds a resource-oriented framework that links hypertension, advanced age, female sex, smoking-related comorbidity, hereditary aortopathies, haemodynamic instability, malperfusion, delayed diagnosis, operative complexity, and postoperative complications to measurable downstream outcomes such as ICU length of stay, total hospital length of stay, reoperation, readmission, and longitudinal imaging surveillance. We searched PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar for relevant studies, registries, guideline documents, and cost analyses published between January 2000 and May 2026, with particular emphasis on studies from the last five years. The review was not designed as a meta-analysis; therefore, effect estimates are interpreted according to study design and generalisability. AAS imposes a disproportionate burden on hospital systems because high-risk patients often require advanced imaging, prolonged haemodynamic monitoring, complex open or endovascular repair, ICU care, and lifelong follow-up. Earlier diagnosis, structured risk stratification, targeted genetic evaluation, aggressive control of modifiable risk factors, and system-level pathways such as dedicated aortic networks may shorten hospital stay and reduce avoidable costs.

Clinics and Practice doi: 10.3390/clinpract16070120

Authors: Nicoleta Dubei Larisa Anghel Laura-Cătălina Benchea Radu Andy Sascău Cristina Prisacariu Mircea Ovanez Balasanian Bogdan-Sorin Tudurachi Bianca-Ștefania Profire Cristian Stătescu

Background/Objectives: As population aging increases the prevalence of atrial fibrillation (AF), the use of direct oral anticoagulants (DOACs) has expanded for thromboembolism prevention. Although DOACs offer advantages over vitamin K antagonists (VKAs), gastrointestinal bleeding (GIB) remains the most common extracranial adverse event. Current guidelines address global bleeding risk but provide limited guidance on site-specific gastrointestinal risk assessment and prevention. This narrative review aims to summarize current evidence on the mechanisms, etiologies, and risk factors for DOAC-associated gastrointestinal bleeding and to propose a pragmatic, risk-based framework to support clinicians in individualized bleeding prevention. Methods: A narrative review of studies published between 2004 and 2025 was conducted, including randomized clinical trials, real-world evidence, meta-analyses, and major society guidelines. Evidence addressing DOAC safety profiles, gastrointestinal bleeding etiologies, patient-level risk factors, medication interactions, and preventive strategies was analyzed. Results: Gastrointestinal bleeding in patients treated with DOAC is strongly influenced by underlying gastrointestinal pathology, comorbid conditions, and concomitant medications. Established risk factors include prior gastrointestinal hemorrhage, Helicobacter pylori infection, gastrointestinal malignancy, diverticulosis, and angiodysplasia, as well as the use of nonsteroidal anti-inflammatory drugs (NSAIDs), antiplatelet therapy, or selective serotonin reuptake inhibitors (SSRIs). DOACs differ in gastrointestinal safety: apixaban consistently demonstrates the most favorable profile, whereas rivaroxaban and high-dose dabigatran show higher GIB rates. Preventive strategies such as H. pylori testing and eradication, proton pump inhibitor use in high-risk individuals, avoidance of NSAIDs and unnecessary antiplatelet therapy, and individualized DOAC selection may help reduce bleeding risk. Conclusions: Gastrointestinal bleeding risk in patients receiving DOAC therapy should be assessed using a site-specific and dynamic approach. A structured strategy integrating baseline risk evaluation, correction of modifiable factors, tailored anticoagulant selection, and risk-adapted follow-up may improve the safety of anticoagulation. The proposed framework may provide a pragmatic approach to individualized bleeding risk mitigation while preserving the benefits of DOAC therapy; however, prospective validation is required before its routine implementation can be recommended.

Clinics and Practice doi: 10.3390/clinpract16070119

Authors: Giuseppe P. A. Gemma Nicoletta Bernardini Francesca Paola Sasso Giacomo Caldarola Eleonora De Luca Maria Elisabetta Greco Viviana Lora Annamaria Mazzotta Emanuele Miraglia Diego Orsini Gianluca Pagnanelli Antonio Giovanni Richetta Nevena Skroza Annunziata Dattola

Background: Guselkumab, a selective interleukin-23 inhibitor, is effective in moderate-to-severe plaque psoriasis, but real-world long-term data in elderly patients remain limited. Objective: To evaluate the long-term effectiveness of guselkumab in elderly patients with moderate-to-severe psoriasis in a real-world setting. Methods: This retrospective, multicenter study included 102 patients aged 65 years or older treated with guselkumab across seven Italian centers. PASI scores and PASI 75/90/100 responses were assessed as observed cases at weeks 4, 16, 28, and 52, and annually up to 4 years, with last-observation-carried-forward and non-responder imputation as sensitivity analyses. Subgroups by biologic experience and BMI were analyzed. Results: Mean PASI decreased from 12.4 to 0.3 at week 52, remaining low through year 4 (p < 0.001). At week 52 and year 4, PASI 90 was achieved by 89.7% and 86.5%, and PASI 100 by 79.3% and 73.0%, respectively. Responses were comparable between biologic-naïve and biologic-experienced patients. Obese patients had higher baseline PASI; after adjustment for baseline severity, responses did not differ from non-obese patients. Conclusions: Guselkumab was associated with high and durable PASI improvement in elderly patients, regardless of prior biologic exposure or body weight. The retrospective design and absence of systematic safety data warrant cautious interpretation.

Clinics and Practice doi: 10.3390/clinpract16070118

Authors: Stipe Vidović Egon Biuk Greta Biuk Marija Jelić Vuković Maja Vinković Andrijana Kopić Dubravka Biuk

Objective: To report a rare case of bilateral iris metastasis from small cell lung carcinoma (SCLC) and systematically review the literature on SCLC-associated iris metastases, with emphasis on clinical presentation, management, and outcomes. Materials and Methods: A systematic literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, ScienceDirect, Scopus, and Web of Science were comprehensively searched on 10 July 2025. Eligible studies included English-language reports of iris metastasis originating from SCLC in human subjects. Case report: A 58-year-old woman with previously treated SCLC developed bilateral iris metastases one year after complete remission of the primary tumor. Ophthalmic examination revealed whitish-gray, vascularized iris masses with iridocorneal angle involvement, associated with secondary angle-closure glaucoma and markedly elevated intraocular pressure (48 mm Hg) in the left eye. Cyclocryotherapy, preceded by systemic and topical antiglaucoma therapy, resulted in pain relief and a reduction in intraocular pressure; the patient died four months later due to pneumonia. Results (Systematic Review): Seventeen studies comprising 17 patients were included; the median age was 60 years, and 64.7% were male. The median interval from SCLC diagnosis to ocular presentation was 4 months, although iris metastasis was occasionally the initial or concurrent manifestation of disease. The most common presenting features were visual impairment (58.8%), ocular pain (41.2%), and elevated intraocular pressure (41.2%), while iris neovascularization (35.3%) and synechiae (29.4%) were also frequent. Bilateral involvement was reported in only one previous case. Treatment approaches were heterogeneous and included antiglaucoma therapy, systemic chemotherapy, local radiotherapy, anti-VEGF therapy, and enucleation. Among patients with available follow-up (n = 12), 58.3% died within a median follow-up of 7.5 months. Conclusions: Bilateral iris metastasis from SCLC is rare and may occur as a manifestation of recurrent disease after remission. It is an aggressive condition characterized by nonspecific ocular symptoms, variable management, and poor survival, underscoring the importance of early recognition and the need for evidence-based diagnostic and therapeutic strategies.

Clinics and Practice doi: 10.3390/clinpract16060117

Authors: Ilias Prentzas Vasileios Leivaditis Chrysa Andrikopoulou Konstantinos Nikolakopoulos Chrysanthi Papageorgopoulou Kate Tabaku Melina Stathopoulou Zafeiria Papathanassiou Polyzois Tsantrizos Francesk Mulita Konstantinos Katsanos Spyros Papadoulas

Background/Objectives: Type II endoleaks (T2ELs) remain one of the most frequent causes of aneurysm sac enlargement following endovascular abdominal aortic aneurysm repair (EVAR). While embolization may be effective in typical T2ELs with a clearly identifiable feeding vessel, management becomes more challenging when no visible communication with a side branch can be demonstrated. Emerging evidence suggests that hypertrophic vasa vasorum may contribute to aneurysm sac expansion in these atypical cases. We present a case of refractory atypical T2EL treated by open conversion and discuss the potential role of the vasa vasorum network in its pathophysiology. Case Presentation: A 77-year-old man presented with lumbar pain ten years after EVAR for a symptomatic abdominal aortic aneurysm. Computed tomography angiography demonstrated progressive aneurysm sac enlargement to 8.5 cm despite three previous translumbar embolization procedures. Multiple areas of contrast pooling were identified within the aneurysm sac, but no clear communication with a feeding side branch was observed. Owing to persistent sac expansion and symptoms, open conversion was performed with partial endograft explantation and reconstruction using a bifurcated PTFE graft. Results: After opening the aneurysm sac and evacuating the thrombus, diffuse bleeding was observed from numerous small vascular orifices distributed throughout the inner sac surface. These findings were considered consistent with a prominent vasa vasorum network. Hemostasis was achieved using a combination of figure-of-eight sutures and electrocautery. The postoperative course was uneventful, and the patient was discharged on postoperative day five. Follow-up imaging demonstrated normal graft patency without complications. Conclusions: This case supports the hypothesis that an extensive vasa vasorum network may contribute to aneurysm sac expansion in atypical T2ELs and possibly endotension after EVAR. In patients with refractory sac enlargement, open conversion remains a definitive treatment option. Further research is needed to clarify the underlying mechanisms and to explore targeted therapeutic strategies aimed at modulating angiogenesis and vascular remodeling.

Clinics and Practice doi: 10.3390/clinpract16060116

Authors: Baraah Ghssan AlHassan Maujid Masood Malik Ahmed Mohamedain Adnan Jehangir Farhana Ayub Omer Musa Ahmed Ibrahim Habib Ahmad Qureshi Hayder A. Giha

Background: Post-thyroxine treatment of thyroid dysfunction remains a clinical concern, especially in Middle Eastern populations. Methods: This descriptive cross-sectional study was conducted in 2023 at King Fahad Hospital, Hufof, Kingdom of Saudi Arabia. Of the 237 patients treated with L-thyroxine (L-T4) for hypothyroidism, 163 patients, almost exclusively females (152 females, 11 males), met the inclusion criteria and were enrolled. Thyroid hormones, lipid profiles, and 25-hydroxyvitamin D (25OH-D) were measured using standard laboratory assays. Results: Only 57% of patients achieved euthyroid status following L-T4 treatment, while 12.3% developed post-thyroxine-treatment (PTT) hyperthyroidism, and 30.7% developed PTT hypothyroidism. Older age was significantly associated with dysthyroidism (p = 0.018), whereas obesity (p = 0.937) and vitamin D levels (p = 0.982) were not. Total cholesterol (TC) and LDLc positively correlated with TSH levels, while elevated triglycerides (TGs) were significantly associated with PTT hyperthyroidism. The two dysthyroid subgroups were comparable across all non-thyroid parameters, including age, BMI, 25(OH)D levels, and lipid fractions. However, free T4 was significantly higher in PTT hyperthyroidism (p < 0.001); free T3 showed a trend toward higher levels in PTT hyperthyroidism (p = 0.052); and TSH was significantly higher in PTT hypothyroidism (p < 0.001). Conclusions: The proportions of patients with PTT hypo- and hyperthyroidism are aligned with international observations. Furthermore, the age was significantly associated with dysthyroidism, and dyslipidemia is the most consistent biochemical correlate of suboptimal thyroid status; however, the associations of PTT dysthyroidism with hypovitaminosis D and BMI were not noticed in this setting.

Clinics and Practice doi: 10.3390/clinpract16060115

Authors: Daniela Trotta Rossella Ferrante Michele Sallese Marianna Viele Claudia Rossi Vincenzo Scorrano Sara Savelli Milena Catenaro Vincenzo De Laurenzi Maurizio Aricò

Background: Pycnodysostosis is a rare autosomal recessive skeletal disorder caused by biallelic pathogenic variants in CTSK, which encodes cathepsin K, a lysosomal cysteine protease required for osteoclast-mediated degradation of bone matrix. Case Report: We describe a girl with short stature, skeletal deformities, osteosclerosis, craniofacial features, clavicular dysplasia, and radiological evidence of fractures. Clinical exome sequencing identified two heterozygous CTSK variants, c.85T > C (p.Trp29Arg) and c.679A>T (p.Ile227Phe), both currently classified as variants of uncertain significance. Segregation analysis showed that the variants were inherited in trans. Computational modeling and in silico prediction tools supported a possible deleterious effect on cathepsin K structure or function. Serum cathepsin K was higher in the patient than in two age-matched controls; this result is reported as an exploratory observation only. Increased serum cathepsin K may reflect altered expression, secretion, clearance, or accumulation of dysfunctional protein, but cannot be interpreted as proof of compensatory upregulation. Conclusions: The patient’s clinical and radiographic features, the biallelic trans configuration of the CTSK variants, their rarity in population databases, and computational predictions support p.Trp29Arg and p.Ile227Phe as strong candidate disease-associated variants. Functional studies are required to confirm their effect on cathepsin K expression, maturation, and enzymatic activity.

Clinics and Practice doi: 10.3390/clinpract16060114

Authors: Mohammed Alqwaifly Samer A. Almuqairsha Emad Alwashmi Yousef M. Alharbi Adi A. Aldubaiyan Raghad H. Aldligan Abdulmajeed A. Alkhamees Ayham Abazid Rehana Khalil Osama Al-Wutayd

Background: Over the years, it has become increasingly clear that neurological conditions, such as multiple sclerosis (MS), commonly exhibit other health problems. Therefore, this is the first study aimed at investigating the prevalence of and factors associated with three binary outcomes: depression, anxiety, and an overactive bladder (OAB) among MS patients in the Qassim region, Saudi Arabia. Methods: This cross-sectional study was conducted in the neurological department of King Fahad Specialist Hospital in the Qassim region, Saudi Arabia, from January to December 2024. Data on age, sex, marital status, occupation, body mass index (BMI), MS duration, comorbidities, anxiety, depression, and OAB symptoms (frequency, nocturia, urgency, and urge incontinence) were obtained. Results: Of the 262 MS patients in this study, 184 (70.2%) were females, and 78 (29.8%) were males. The median values [IQR] of age and MS duration were 34 [26–40] and 5 [2–9] years, respectively. The prevalence of depression, anxiety, and OAB were 53.4%, 43.9%, and 50%, respectively. Nocturia was the most frequent urinary symptom, and urge incontinence was significantly higher among females. Multiple logistic regression analyses were conducted to assess factors associated with three binary outcomes: depression, anxiety, and OAB. For depression, being single and anxiety were associated with increased risk. Regarding anxiety, being a student was related to decreased risk, while being female and having depression were associated with increased risk. For OAB, only anxiety was associated with increased risk. Conclusions: Approximately one in two MS patients experience either depression or OAB, while anxiety was reported by fewer than half of the patients. This high prevalence of the three outcomes has critical implications for healthcare policy and resource allocation. Thus, screening, early diagnosis, and intervention, as well as integrated care, should be prioritized by healthcare institutions and practitioners to address these conditions and improve MS patients’ quality of life.

Clinics and Practice doi: 10.3390/clinpract16060113

Authors: Luisa Jiménez Reyes José Javier Jareño Esteban Lara Almudena Fernández Bermejo Carlos Gutiérrez Ortega Javier de Miguel-Díez

Background/Objectives: Recent trends show a rising incidence of venous thromboembolism (VTE) that does not correlate with increased mortality; however, population aging and the proliferation of comorbidities are fundamentally reshaping the VTE patient landscape. The aim of this study is to evaluate potential differences in clinical characteristics, comorbidities, and survival rates between patients diagnosed with pulmonary embolism (PE) during the pre-pandemic period (2018–2019) and those diagnosed during the pandemic era (2020–2022). Additionally, as a secondary objective, we analyze the clinical profiles, risk factors, and survival outcomes of patients with and without COVID-19 infection during the 2020–2022 period. Methods: A retrospective observational study was conducted to analyze survival and comorbidities in patients admitted for PE at the Hospital Central de la Defensa ‘Gómez Ulla’ between 2018 and 2022, comparing two periods (2018–2019 and 2020–2022). In addition, a sub-analysis was performed within the second period group comparing patients with and without COVID-19. Results: It was observed that the majority of patients in the first period were men, while in the second period, 55% were women. With regard to comorbidity and risk factors, thrombophilia and dementia were more prevalent in the first period, while asthma was more prevalent in the second period. No differences were found with regard to mortality. Conclusions: Significant differences were observed between the two periods of the study with regard to some comorbidities. Patients with COVID-19 showed a greater tendency toward immobilization and a higher prescription of thromboprophylaxis during hospitalization.

Clinics and Practice doi: 10.3390/clinpract16060112

Authors: Sanjana R. Salwi Thilan Tudor Oleg Shekhtman Georgios S. Sioutas Pious D. Patel Irina-Mihaela Matache Mohamed Salem Sonia Ajmera Sandeep Kandregula Jan-Karl Burkhardt Visish M. Srinivasan

Background: Aneurysm treatment options are rapidly evolving, as evidenced by the recent introduction and widespread adoption of flow diversion and intrasaccular devices. However, there is a need to understand how these newer technologies are used for difficult-to-treat aneurysms. The main aims of this study were to investigate the variation in aneurysm treatment recommendations among neurosurgeons, interventional radiologists, and interventional neurologists and to generally describe trends in endovascular treatment. Methods: In this survey-based study conducted from June to September 2024, participants were presented with clinical vignettes and asked to choose preferred treatment options, with responses analyzed based on demographic variables including specialty, age, and training prior to and after the introduction of flow diversion. Results: A total of 108 respondents completed the study with a representative mix of specialties—(45 (42.5%) radiologists, 22 (20.8%) neurologists, and 39 (36.8%) neurosurgeons. Sixty-six (61.1%) trained after the introduction of flow diversion. Treatment recommendations were significantly different by specialty (p < 0.001). The Kappa statistic to assess variation in responses showed significant variation in treatment preferences across aneurysm subtypes, ranging from poor (κ = 0.07) to fair (0.31). Treatment of ruptured aneurysms varied by specialty with radiologists opting for stent-assisted coiling at a higher rate than neurologists or neurosurgeons (p < 0.001). There was no significant difference in rates of recommending flow diversion or intrasaccular devices between those who had trained before and after their introduction (p = 0.97). Conclusion: The study highlights the dynamic nature of aneurysm management and considerable variability among different specialties. Further exploration into the rationale for each decision is needed to understand how specialty training affects these decisions.

Clinics and Practice doi: 10.3390/clinpract16060111

Authors: Giuseppe Messina Francesco Mantia Pietro Cataldo Angelo Iovane

Background/Objectives: This preliminary pilot case series aims to evaluate the feasibility and temporal evolution of pain and function following an ultrasound-guided infiltration technique with hyaluronic acid and methylprednisolone in a specific patient population with Temporomandibular Disorders (TMD) characterized by MRI-confirmed retrodiscal tissue hyperemia. Given the absence of a control group, this study represents a preliminary exploration of a clinical approach utilizing individualized interocclusal devices during infiltration. Methods: Twenty-eight patients (16 females, 12 males) with TMD and MRI evidence of retrodiscal tissue hyperemia were enrolled in this prospective, uncontrolled study. A unique protocol was employed, utilizing individualized interocclusal devices to optimize joint space access during bilateral ultrasound-guided infiltration of a mixture containing low-molecular-weight hyaluronic acid, lidocaine, and methylprednisolone acetate. Pain intensity (VAS 0–100 mm) and associated symptoms (tinnitus, vertigo, headache, joint clicking) were assessed at baseline and at 30, 60, and 90 days’ follow-up. Results: A statistically significant temporal reduction in pain was observed at all follow-up points (p < 0.001), with the mean VAS score decreasing from 70.5 ± 11.4 mm at baseline to 43.0 ± 11.1 mm at 90 days. Joint clicking disappeared in 80% of patients immediately after treatment. Conclusions: The ultrasound-guided infiltration technique, combined with personalized interocclusal support, demonstrated preliminary feasibility and short-term temporal improvement in pain and joint clicking in this specific patient cohort. Due to the lack of a control group and the multimodal nature of the intervention, these findings should be considered preliminary and do not allow for causal inferences regarding the efficacy of individual components.

Clinics and Practice doi: 10.3390/clinpract16060110

Authors: Ana María de Granda-Beltrán Alejandro Porras-Segovia Daniel Núñez-Arias Alba Rodríguez-Jover Maria Paula Jassir Acosta Philippe Courtet Enrique Baca-García Inmaculada Peñuelas-Calvo

Background: Treatment-resistant depression (TRD) poses a major clinical challenge, particularly when accompanied by suicidal behavior. Intranasal esketamine has demonstrated rapid antidepressant effects in TRD, but real-world comparative evidence remains limited. Methods: We conducted a six-month naturalistic prospective cohort study in two Spanish mental health centers, including 62 TRD patients with high suicide risk undergoing fourth-line treatment. Thirty patients received intranasal esketamine and thirty-two alternative pharmacological interventions. Suicidal ideation (C-SSRS), depressive symptoms (HAM-D-17) and functional status (FAST) were assessed at baseline and at 1-, 3- and 6-month follow-ups. Results: Both groups showed significant improvement during follow-up; however, esketamine-treated patients exhibited a faster and greater reduction in suicidal ideation and depressive symptoms than those receiving alternative pharmacological strategies. The number needed to treat to prevent one case of high suicide risk was 1.35. Functional improvement was comparable between groups. Conclusions: In real-world clinical settings, intranasal esketamine was associated with a faster and greater reduction in suicidal ideation and depressive symptoms among TRD patients with high suicide risk, supporting its role as a rapid-acting therapeutic option within comprehensive and closely monitored care.

Clinics and Practice doi: 10.3390/clinpract16060109

Authors: Szabolcs André Daniela Dobru Árpád-Olivér Vida Miheler Dora Rares-Florin Vascul Călin Chibelean Lorand Tibor Reman Raul-Dumitru Gherasim Edva Anna Frunda Orsolya Katalin Ilona Martha

Hydronephrosis caused by malignant ureteral obstruction or radiotherapy-induced ureteral stenosis is a frequent complication in patients with cervical cancer. Effective management requires continuous urinary drainage, which can be achieved either internally through ureteral stent placement or externally via percutaneous nephrostomy. Among available devices, the AlliumTM fully covered nitinol mesh ureteral stent is designed to treat ureteral or urethral strictures while allowing safe and easy removal. However, serious complications have been reported, including uretero-enteric, uretero-arterial, and uretero-vaginal fistulas, pseudoaneurysm, ureteral perforation and sepsis. We report the case of a 44-year-old woman diagnosed in 2020 with stage IIIC1 cervical cancer (FIGO classification) who underwent surgery followed by adjuvant radiotherapy. In 2021, a right metallic ureteral stent was placed to treat ureteral obstruction. Two years later, she presented with right lumbar pain, and abdominal ultrasonography revealed grade III right hydronephrosis. CT scan demonstrated migration of the metallic ureteral stent into the rectal wall. Endoscopic extraction of the migrated stent was successfully performed via colonoscopy. Retrograde pyelography and CT imaging confirmed the presence of a recto-ureteral fistula. A 6 Ch/26 cm double-J ureteral stent was subsequently placed with good positioning and drainage. At the six-month follow-up, replacement of the double-J stent was performed. Imaging studies showed only minor residual hydronephrosis. Although metallic ureteral stents are effective for managing malignant ureteral obstruction, particularly in complex oncologic cases, they are not free of severe complications. The risk appears increased in patients who have undergone radiotherapy, emphasizing the need for careful monitoring and long term follow-up.

Clinics and Practice doi: 10.3390/clinpract16060108

Authors: Koji Nozaka Naohisa Miyakoshi

Background: Septic Charcot neuroarthropathy is a limb- and life-threatening condition characterized by the coexistence of neuropathic joint destruction and infection. In patients with severe systemic compromise, major amputation is often considered inevitable. Case Presentation: A 47-year-old man with untreated diabetes mellitus presented with progressive painless swelling of the left foot. He had morbid obesity (120 kg, 165 cm; body mass index 44.1 kg/m2), severe hypoalbuminemia, and chronic kidney disease associated with nephrotic syndrome. Laboratory tests showed marked inflammation and poor glycemic control, and blood cultures were positive for methicillin-resistant Staphylococcus aureus (MRSA). Radiographs and computed tomography demonstrated destructive changes involving the talonavicular and subtalar joints, consistent with septic Charcot neuroarthropathy involving the midfoot. Because of sepsis, pulmonary edema, and heart failure, below-knee amputation was proposed at the referring hospital. However, limb salvage was attempted using aggressive debridement, continuous local antibiotic perfusion (CLAP; gentamicin 1200 μg/mL) administered for 14 days, and temporary circular external fixation. Serum gentamicin concentrations and renal function were regularly monitored to ensure systemic safety and avoid nephrotoxicity. Results: Repeat irrigation and final debridement were performed 20 days after the index surgery, at which time the external fixator was removed and intraoperative cultures were negative. The patient was discharged 2 months after surgery without evidence of recurrent infection. At 4-year follow-up, no recurrence had occurred, and the patient was able to walk independently. Conclusions: Limb salvage may be feasible even in severely compromised patients with septic Charcot midfoot and MRSA bacteremia when aggressive debridement, CLAP, and temporary external fixation are combined with careful systemic safety monitoring. This case suggests that limb salvage may be considered in selected high-risk patients, although further studies are required.

Clinics and Practice doi: 10.3390/clinpract16060107

Authors: Stefan Ivanovic Ljubomir Srbinovic Milica Ivanovic Dragana Maglic Nenad Kokošar Rastko Maglic

Background: Ectopic pregnancy remains a significant cause of maternal morbidity in early pregnancy. While most ectopic pregnancies happen within the fallopian tube, implantation may rarely occur in atypical locations such as the ovary or abdominal cavity. These rare forms often present with nonspecific clinical findings and may represent a considerable diagnostic challenge. Methods: We report a case series of three rare ectopic pregnancies managed at a tertiary referral center. Two cases involved ovarian pregnancy, and one case represented an exceptionally rare hepatic ectopic pregnancy. Clinical presentation, diagnostic pathway, surgical management, and outcomes were analyzed and compared with available literature. Results: In the first two cases, ovarian pregnancy was confirmed intraoperatively and treated surgically, with ovarian preservation in one patient and adnexectomy in the other due to active bleeding. The third case had an unusual course: initial surgery was performed for hemoperitoneum caused by a ruptured corpus luteum cyst, while persistent β-hCG elevation later led to identification of hepatic ectopic pregnancy, confirmed by imaging and surgery. All patients recovered favorably, with complete β-hCG negativization. Conclusions: Rare ectopic implantation sites may mimic acute abdominal conditions and remain difficult to diagnose preoperatively. High clinical suspicion, serial β-hCG monitoring, and appropriate imaging are essential. Surgical management remains central, particularly in life-threatening bleeding. Standard algorithms for tubal ectopic pregnancy may not be fully applicable and should be adapted to the clinical context.

Clinics and Practice doi: 10.3390/clinpract16060106

Authors: Vaidyanathan Subramanian Bakulesh Madhusudan Soni Peter Lyndon Hughes Tun Oo

Objectives: To present novel strategies in the diagnosis and management of spondylodiscitis in a patient with tetraplegia. Case Presentation: A 44-year-old man presented with increased spasms despite having a SynchroMed II Medtronic for intrathecal infusion of baclofen. The C-reactive protein level was raised. Infection was suspected, but there were no localising signs. Positron Emission Tomography (PET) was performed to identify the focus of infection. PET showed an increased Fluorodeoxyglucose uptake in the L-5 vertebral body and the associated ill-defined soft tissue anteriorly. There was significant erosion and destruction of the S-1 vertebra. Magnetic Resonance Imaging of the lumbo-sacral spine revealed destruction and collapse of the S-1 vertebral body and a 6 cm × 2 cm anterior paravertebral abscess collection. This patient was managed in his home. Intravenous administration of 1 g of Ertapenem daily was provided by community nurses for eight weeks. Blood tests were performed in the community setting, and the patient was monitored by spinal unit doctors. Results: Follow-up CT revealed abnormal soft tissue, expanding and replacing the S-1 vertebral body, with appearances in keeping with an infective process. Using CT guidance and the Madison bone biopsy kit, multiple cores were obtained from the left sacral bone. Four of the five specimens showed no growth after extended incubation. Propionibacterium acnes were isolated after 10 days of incubation from the tissue from the sacral bone biopsy only. A shared decision was made towards active surveillance. Follow-up CT of the abdomen showed a stable appearance of the lumbar and sacral spine. Conclusions: A complex case of spondylodiscitis can be diagnosed and managed while the patient stays mainly in their home, avoiding prolonged admission to the spinal unit, in alignment with the “hospital to community” aspect of the National Health Service’s 10-year Health Plan for England. A diagnostic pathway with PET-CT as the first approach proved useful when the site of infection was unclear. Active surveillance obviated the need for extended periods of antibiotic therapy, which could have led to complications such as antibiotic-induced toxicity and microbial resistance to antibiotics.

Clinics and Practice doi: 10.3390/clinpract16060105

Authors: Ioana Maria Otilia Lică Iulia Florentina Țincu Anca Cristina Drăgănescu Doina Anca Pleșca

Background: Long COVID in children is increasingly recognized, yet its clinical predictors and objective biological correlates remain insufficiently characterized. Objectives: The objective was to compare clinical, demographic, and laboratory characteristics between children with and without long COVID and to identify associated variables. Methods: We conducted a retrospective observational case–control study at the “Dr. Victor Gomoiu” Children’s Clinical Hospital, including pediatric patients with confirmed SARS-CoV-2 infection. Cases were defined as children with symptoms persisting ≥12 weeks after acute infection, while controls had no persistent symptoms at ≥12 weeks. Results: Eighty-nine children with long COVID and 88 matched controls were included. Children with long COVID were significantly older (1.79 ± 0.90 vs. 1.14 ± 0.80 years, p < 0.001) and more frequently from urban areas (86.5% vs. 69.3%, p = 0.0099). Lymphocyte, monocyte, and basophil counts were significantly lower in the Long COVID group, while D-dimer, ferritin, serum iron, urea, and creatinine levels were significantly higher. A multivariate predictive model demonstrated excellent discrimination (AUC = 0.94), with optimal sensitivity (84.3%) and specificity (89.8%) at a probability threshold of 0.48. Conclusions: Long COVID in children was associated with identifiable clinicobiological features. An exploratory composite model showed good discrimination but requires external validation.

Clinics and Practice doi: 10.3390/clinpract16060104

Authors: Juan Ramón de-Moya-Romero Alexis Caballero-Bonafé Laura Fernández-Puerta Raquel Valera-Lloris Antonio Martínez-Sabater

Background: Ageism is a global public health concern associated with poorer health outcomes and inequities in care. Culturally adapted instruments are needed to assess ageist attitudes among healthcare professionals in Spain. This study aimed to cross-culturally adapt and evaluate the preliminary psychometric properties of the Spanish version of the Fraboni Scale of Ageism (FSA-SV). Methods: A methodological study was conducted, including translation and back-translation, expert review, and a pilot test. Content validity was assessed using the content validity index (CVI), the modified kappa coefficient, and Aiken’s V. A descriptive cross-sectional pilot study was conducted with 101 healthcare professionals from a single health department in Valencia to evaluate comprehension and reliability. Internal consistency was examined using Cronbach’s alpha and McDonald’s omega. Results: Content validity indices indicated acceptable agreement among experts (S-CVI = 0.745; Aiken’s V = 0.770). All items were retained to preserve conceptual and structural equivalence with the original instrument. The FSA-SV demonstrated high internal consistency (Cronbach’s alpha = 0.903; McDonald’s omega = 0.915). The mean total score was 51.2 (SD = 9.62), with no significant associations observed between ageism and participants’ sociodemographic or professional variables. Conclusions: This pilot study represents a first step in the cross-cultural adaptation and preliminary psychometric evaluation of the FSA-SV for use among healthcare professionals in Spain. The results suggest that the instrument shows promising initial properties for the preliminary assessment of ageism, supporting its potential utility in future research and in evaluating educational and organizational interventions aimed at reducing ageism and improving the quality and safety of care for older adults. Further studies with larger, more diverse samples are required to evaluate additional psychometric properties, including the factorial structure.

Clinics and Practice doi: 10.3390/clinpract16060103

Authors: Gabriela-Florentina Țapoș Dan Iliescu Mihaela Cristina Negru Florin Borcan Silvia Luca Simina Crișan Constantin Tudor Luca

Background/Objectives: Cardiovascular diseases are a major cause of morbidity and mortality worldwide. Acute chest pain is a frequent reason for emergency department presentation and requires structured evaluation to identify life-threatening conditions. This study evaluated clinical characteristics, cardiovascular risk profile, risk stratification patterns, and hospitalization status in adults with acute chest pain. Methods: We conducted a retrospective study using registry data from Arad County Clinical Emergency Hospital between January 2021 and December 2024. Adult patients with documented acute chest pain were included according to predefined criteria. Demographics, comorbidities, clinical presentation, troponin values, hospitalization status, and HEART, and EDACS categories were extracted when available. The Marburg Heart Score was also assessed as an exploratory complementary score. Statistical analysis used descriptive statistics, contingency tables, and chi-square testing, with available-case analysis. Results: Overall, 2070 patients were included. Most patients were aged 35–54 or 55–69 years. Hypertension and diabetes mellitus were the most common comorbidities, and pressure-like chest pain predominated. In unadjusted analyses, HEART and EDACS categories were significantly associated with hospitalization status across all study years. Score categories were significantly associated with hospitalization status across all study years. Age was consistently associated with cardiovascular comorbidity burden and higher-risk score categories. Conclusions: Structured risk stratification scores were associated with hospitalization status, while age was associated with cardiovascular risk burden.

Clinics and Practice doi: 10.3390/clinpract16060102

Authors: Ivan Budimir Borna Vojvodić Rado Žic Zlatko Vlajčić Domagoj Eljuga Božo Gorjanc Željka Roje Hrvoje Tucaković Željka Godeč Marko Barić Josip Jaman Rhea Marie Mužar Krešimir Martić

Background: The latissimus dorsi free flap is a workhorse for extensive lower-extremity soft tissue defects. Conventionally, the skin paddle is designed according to the anticipated defect and left in place on the muscle as a single composite unit. This report describes an alternative approach in which the skin paddle is secondarily mobilized through subcutaneous undermining and rotated as a separate propeller-type local extension flap on random-pattern vascularization, without a specifically identified perforator—a technique that has not been previously reported. Case Presentation: A 38-year-old male with a high-energy distal lower-extremity defect exposing bone, Achilles tendon, and hardware underwent free latissimus dorsi reconstruction with an empirically designed skin paddle over the constant perforator zone. The skin paddle was subsequently mobilized and rotated as a separate propeller-type extension flap to cover the Achilles region, with additional areas managed using split-thickness skin graft and a reverse soleus flap. Results: The latissimus dorsi flap and skin paddle remained viable, providing stable coverage of the defect. The additional reverse soleus flap achieved durable medial coverage, and the limb was ultimately preserved with satisfactory soft-tissue stability. Conclusion: A random-pattern latissimus dorsi skin paddle designed within the anatomically constant perforator zone can provide a feasible new option offering intraoperative flexibility in complex lower-extremity trauma when perforator mapping is impractical.

Clinics and Practice doi: 10.3390/clinpract16060101

Authors: Charat Thongprayoon Francesco Pesce Wisit Cheungpasitporn

Rare diseases affect over 300 million individuals worldwide yet remain underdiagnosed and poorly characterized due to fragmented data, small cohorts, and phenotypic heterogeneity. Advances in artificial intelligence (AI) are enabling integration of genomics, imaging, electronic health records, and patient-generated data to support diagnosis, phenotyping, prognosis, and therapeutic discovery. In kidney care, these capabilities are reflected in tools for genomic variant prioritization, AI-assisted histopathology, and integrated risk stratification models for rare and complex kidney diseases. This review synthesizes current AI applications across the rare disease continuum and proposes a clinically grounded framework to distinguish exploratory models from systems that are methodologically robust and operationally deployable. We highlight advances that address data sparsity and heterogeneity, alongside persistent challenges in validation, generalizability, equity, and workflow integration. Finally, we outline future directions, including federated learning, digital twins, and AI-driven clinical decision agents, as pathways toward precision-guided, workflow-integrated rare disease care.

Clinics and Practice doi: 10.3390/clinpract16060100

Authors: Loredana Deaconu Romulus Zorin Timar Cristiane Dragomir Edward Seclaman Anca Marcu Diana Nitusca

Background and Objectives: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have emerged as potential biomarkers in type 2 diabetes mellitus and its complications. This pilot exploratory study aimed to identify circulating miRNAs with differential expression in plasma from patients with newly diagnosed type 2 diabetes mellitus compared to age- and sex-matched healthy controls. Materials and Methods: Peripheral venous blood samples were collected from diabetic patients (n = 24) and controls (n = 12). Due to the exploratory nature of the study and limited sample material, samples were pooled within each group prior to plasma separation. Total RNA, including miRNAs, was extracted from plasma and analyzed using a high-throughput qPCR panel. Two normalization methods were applied to assess miRNA expression, and overlapping results were used for downstream analysis. Fold regulation was calculated using the 2^(−ΔCt) method. Results: A total of 33 and 42 miRNAs were identified as differentially expressed using the first and second normalization methods, respectively. Fourteen miRNAs were consistently downregulated across both methods. Several of these miRNAs, including hsa-miR-26a-5p, hsa-miR-146a-5p, hsa-miR-186-5p, hsa-miR-19a-3p, and hsa-miR-652-3p, have been previously associated with glucose metabolism, inflammation, and diabetic complications, such as retinopathy, neuropathy, and endothelial dysfunction. The pooling strategy enabled an efficient exploratory assessment of miRNA expression patterns while reducing inter-individual variability. Conclusions: This exploratory pilot study identifies a panel of circulating miRNAs with altered expression in pooled plasma samples from patients with newly diagnosed type 2 diabetes mellitus. These findings provide preliminary insights that warrant further validation in larger, individual-level studies to assess their diagnostic and prognostic potential.

Clinics and Practice doi: 10.3390/clinpract16060099

Authors: Matteo Zanchetta Natale Calomino Giuseppe Ietto Vanessa Borgogni Giorgio Micheletti Sergio Antonio Tripodi Daniele Marrelli Franco Roviello Gian Luigi Adani

Background: Segmental arterial mediolysis (SAM) is a rare, non-inflammatory, non-atherosclerotic, non-hereditary arteriopathy of unknown etiology that typically affects medium-sized visceral arteries. The absence of reliable diagnostic criteria poses a significant challenge. Consequently, the diagnosis of SAM should be considered in the setting of a distinctive combination of clinical features, angiographic findings, and histopathology. Renal artery involvement is uncommon, and its occurrence in the donor graft during kidney transplantation (KT) has not previously been reported. Case presentation: We report the case of a kidney graft from a deceased donor in her seventh decade of life, transplanted into a recipient in her seventh decade of life. Donor–recipient ABO compatibility was confirmed, and both complement-dependent cytotoxicity crossmatch and flow cytometry crossmatch were negative. Cold ischemia time was 14 h, and warm ischemia time was 20 min. Immediately after declamping, massive thrombosis of the graft renal artery was observed and confirmed using an intraoperative flowmeter. The arterial anastomosis was taken down, the thrombus was removed, the artery was flushed with heparin, and the anastomosis was reconstructed using interrupted sutures. Despite revision, no arterial flow was detected, and the graft was deemed unsalvageable and explanted. Histopathological examination showed thinning of the tunica media, reduced smooth muscle cells on desmin staining, medial-adventitial dissection, and occlusive thrombosis, findings considered likely attributable to SAM. Conclusions: This case suggests that occult donor arterial wall disease compatible with SAM may present catastrophically during KT and may lead to immediate graft loss despite standard surgical salvage attempts. Although no validated strategy currently exists to screen for or prevent occult SAM in asymptomatic donors, awareness of this entity may assist transplant surgeons and pathologists in the evaluation of unexplained early graft arterial thrombosis, donor-graft vascular pathology, and communication with centres receiving paired organs from the same donor.

Clinics and Practice doi: 10.3390/clinpract16060098

Authors: Orsolya Sáfár Viktor Horváth Árpád Kézdi Péter Kevei Ákos Géza Pethő

Background: Cardiovascular complications are the leading cause of death in patients with end-stage renal disease (ESRD). Hemodialysis involves rapid electrolyte shifts and sudden fluid removal, which can affect ventricular repolarization and trigger arrhythmias in patients with ESRD. To enhance patient care, it is crucial to regularly assess cardiac function using noninvasive and painless methods, such as Holter electrocardiography (ECG) and routine cardiac ultrasound. These evaluations may inform improved prevention strategies to reduce the risk of elevated cardiovascular mortality rates. Methods: In total, 40 patients with ESRD on chronic hemodialysis (HD) were approached, and only 18 were enrolled from September 2024 to July 2025. Detailed medical information was provided, and written informed consent was obtained from the patient. The median duration of Holter ECG recording was 84.65 h, and cardiac ultrasound examinations were conducted. Blood gas samples were collected hourly during the second dialysis session. Results: Surprisingly, one-third of the patients opted to withdraw their consent for this painless investigation. No significant differences were observed in the QT and QTc intervals between the dialysis and non-dialysis days (p = 0.184 and p = 0.446, respectively). However, a significant increase was observed during the first 3 h of dialysis when analyzing the intradialytic period. Conclusion: Some patients showed clinically significant changes in QT and QTc intervals during treatment, which could not be confirmed statistically. Although we did not formulate a hypothesis, it is essential to recognize that patient compliance significantly influences the cardiovascular outcomes of individuals undergoing hemodialysis.

Clinics and Practice doi: 10.3390/clinpract16050097

Authors: Magdalena Lixandru George Maniu Cosmin Ionut Lixandru Florin Grosu

Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASH) is frequently accompanied by disturbances in coagulation and metabolic homeostasis, partly related to impaired handling of vitamin K-dependent pathways. Although vitamin K is often administered to correct abnormal coagulation tests, its biochemical impact in hospitalized patients with MASH remains insufficiently characterized. This study aimed to evaluate changes in coagulation and metabolic parameters in hospitalized patients with MASH receiving vitamin K supplementation. Methods: We conducted a retrospective study of 84 hospitalized MASH patients who received vitamin K supplementation. Biochemical parameters were recorded at admission and discharge to assess short-term changes during hospitalization. Results: Vitamin K supplementation was associated with modest changes in coagulation parameters, including reductions in PT, INR, and aPTT (e.g., PT decreased from 13.00 s to 11.00 s). Small numerical changes in transaminases, fasting glucose, and total cholesterol were observed during hospitalization, with limited clinical relevance. These patterns were comparable across fibrosis stages, with no significant differences between groups. Discussion: The observed biochemical findings are likely in-hospital factors rather than a direct metabolic effect of vitamin K. Conclusions: Vitamin K supplementation was associated with modest changes in coagulation parameters and small, clinically negligible variations in selected metabolic markers in patients with MASH, irrespective of fibrosis stage. These findings suggest a supportive biochemical effect in selected contexts; further prospective studies are needed to clarify their clinical relevance.

Clinics and Practice doi: 10.3390/clinpract16050096

Authors: Isidro Miguel Martín Pérez Sebastián Eustaquio Martín Pérez

Background: Growth disorders, including central precocious puberty and delayed puberty, can significantly affect linear growth, skeletal maturation, metabolic regulation, and psychosocial development during childhood and adolescence. This systematic review synthesizes the current evidence regarding the effectiveness and safety of hormone-based therapies used in children with disorders of pubertal maturation. Methods: A PRISMA-guided systematic search was carried out between January 2016 and March 2026 in different databases, such as MEDLINE (PubMed), EMBASE, CENTRAL, Scopus, Web of Science, CINAHL, LILACS and OpenGrey; the protocol was previously registered in the PROSPERO database (CRD420251068048). Non-randomized, randomized controlled trials and observational research including participants aged 0–18 years receiving hormone therapies were eligible. Risk of bias was assessed using validated, design-specific tools. Results: Twenty studies involving 21,812 participants were included. GnRHa therapy improved final adult height (+3.5 to +4.5 cm) and reduced bone age advancement (−0.6 to −1.3 years) in children with central precocious puberty. rhGH therapy increased growth velocity (+3.0 to +5.0 cm/year) and height SDS (+0.3 to +0.9), particularly in idiopathic short stature and Prader–Willi syndrome. Combined GnRHa plus rhGH therapy showed greater short-term growth benefits than GnRHa alone. Both therapies showed favorable safety profiles, with predominantly mild adverse events and discontinuation rates below 2%. However, the evidence was limited by substantial heterogeneity and moderate-to-serious risk of bias. Conclusions: GnRHa and rhGH therapies are generally effective and safe for improving growth and pubertal outcomes in pediatric endocrine disorders. However, further long-term studies are needed to clarify their metabolic and psychosocial effects in adulthood. Nevertheless, these conclusions should be interpreted with caution due to the study’s moderate-to-serious risk of bias and heterogeneity.

Clinics and Practice doi: 10.3390/clinpract16050095

Authors: Rosana Troskot Perić Branko Bakula Nensi Orlandini Tomislav Pavlović Mato Perić Gabrijela Stanić

Background: Intestinal neuronal dysplasia type B is an entity characterized by disturbances in the enteric plexus, it most often occurs in childhood and can appear as an isolated disease or in combination with other neuropathies. The main symptoms are chronic constipation and intestinal obstruction. Case presentation: This paper presents the diagnostic work-up of a 40-year-old patient who was referred to a tertiary center due to refractory chronic constipation. A diagnosis of intestinal neuronal dysplasia type B was made after a surgical procedure based on pathohistological findings. Discussion: In a further multi-year follow-up, the patient was symptom-free with regular bowel movements, with a significant quality of life improvement. Conclusion: This confirmed that the chosen type of surgical procedure was appropriate.

Clinics and Practice doi: 10.3390/clinpract16050094

Authors: Felix Pitka Florian Böhrnsen

Objective: To develop an individual assessment for patients suffering from medication-related osteonecrosis of the jaw (MRONJ), we developed a scoring system that integrates anamnestic, clinical, and radiological parameters to facilitate the process of therapeutic decisions during MRONJ therapy. Methods: In this study, clinical data as well as diagnostic CT scans from 41 MRONJ patients undergoing antiresorptive therapy were analyzed to develop an Osteonecrosis Scoring Clinical Assessment and Radiological Report (OSCAR). Results: Total OSCAR scores ranged from 4 to 30, with lower scores demonstrating less severe disease progression following a de-escalated therapy. OSCAR scores above 15 were associated with higher bone density and an increased need for surgical intervention, with 70% of Denosumab and 71% of bisphosphonate patients requiring surgical intervention. Conclusions: Patients with an OSCAR below 12 were unlikely to require multiple surgical interventions. Since OSCAR parameters are routinely collected during hospitalization, this opens the possibility for future AI-assisted patient assessment and treatment planning.

Clinics and Practice doi: 10.3390/clinpract16050093

Authors: Charalampia Pylarinou Francesk Mulita Efstratios Koletsis Vasileios Leivaditis Elias Liolis Lefteris Gortzis Dimosthenis Mavrilas

Background: Post-surgical cardiovascular monitoring places a heavy information burden on clinical teams, requiring the rapid synthesis of patient history, intraoperative data, monitoring streams, and surgical outcome evidence. Existing clinical decision support systems handle this integration poorly, and most offer little visibility into their reasoning. We present a Retrieval-Augmented Generation (RAG) architecture designed specifically for this domain, with a focus on evidence traceability and practical workflow integration. Methods: We describe a three-layer RAG architecture comprising a retrieval layer that creates 768-dimensional representations of clinical scenarios; an augmentation layer using a stacking ensemble (Random Forest and XGBoost base learners with a logistic-regression meta-learner) to integrate patient-specific data with retrieved evidence and produce calibrated probability estimates; and a generative layer using a fine-tuned BERT classifier together with Gemini 2.5 Pro to synthesise actionable clinical recommendations. Components were prototyped on publicly available, de-identified data from MIMIC-III and the MIMIC-III-Ext-PPG benchmark to verify pipeline integrity. Proposed Evaluation Framework: This paper presents a system architecture rather than a clinically validated implementation. We outline a structured evaluation framework to assess the technical performance and clinical applicability of the RAG architecture, encompassing the technical validation of system components, expert assessment of clinical workflow integration potential, and analysis of interpretability features essential for healthcare deployment. Specific technical targets include retrieval precision >90% for relevant evidence, query response time <3 s, and a clinical appropriateness rating of >85% from expert review. Conclusions: We describe a RAG architecture for post-surgical cardiovascular monitoring in which every recommendation is linked to retrievable source documents, making the reasoning visible and challengeable. A structured evaluation framework is proposed to guide the system towards clinical validation.

Clinics and Practice doi: 10.3390/clinpract16050092

Authors: Marco La Verde Eleonora Braca Antonio Cerillo Maria Fatigati Pasquale De Franciscis Davide Pisani Mario Fordellone Mariavictoria De Simone Carlo Pietro Campobasso Alessandro Feola

Background and objective: Umbilical cord abnormalities (UCAs) such as hypercoiling, velamentous or marginal cord insertion, or reduced Wharton’s jelly are associated with umbilical thrombosis. UCAs increase the risk of vascular obstruction and impaired fetal blood flow, resulting in hypoxia or stillbirth. We examined the association between the UCAs and the umbilical cord thrombosis. Methods: According to PRISMA, five electronic databases (PubMed, Scopus, Embase, Cochrane Library, and Clinicaltrial.gov) were screened. Only studies that analyzed umbilical cord insertion abnormalities and abnormalities of the umbilical cord associated with thrombosis were included in this systematic review. Studies without thrombosis were excluded (PROSPERO ID: CRD420251087525). Results: Only 12 articles out of 1105 screened records satisfied the inclusion criteria, comprising 3 retrospective cohort studies, 3 case series and 6 case reports. The publication years ranged from 1983 to 2025. A total of 126 cases of umbilical vascular thromboembolism (UVTE) were identified, among which 84 cases of UCAs represented by 16 cases of stricture, 14 cases of hypercoiling, 16 cases of too-short cords (≤40 cm), 11 cases of too-long cords (≥70 cm), 5 cases of velamentous or furcate cord insertions, 12 cases of nuchal cord insertions, 13 cases of funistisis, 11 cases of true knots, and 3 cases of Wharton jelly abnormalities. Conclusions: UCAs, including true knots, abnormal coiling, and furcate or velamentous cord insertion, were highly associated with UVTE. Future studies should involve developing standardized criteria for the diagnosis and reporting of UCAs.

Clinics and Practice doi: 10.3390/clinpract16050091

Authors: Gulzar Shah Anjana Kalathimekkattu Indira Karibayeva Bobbie J. Newell

Background/Objectives: Cost-related delays hinder access to dental care in the United States, while the growing use of telehealth has an uncertain impact on population-level access to dental services. The study examined factors associated with cost-related delays in dental care among U.S. adults and whether telemedicine use in the past year was associated with these delays. Methods: This cross-sectional study utilized nationally representative data from the 2023 National Health Interview Survey (NHIS) to examine the association between telehealth use and oral health services utilization in the past 12 months. All analyses were performed using R version 4.5.1 within the RStudio IDE (version 2025.09.0+387). Results: Adults who visited a dental provider within the past 12 months had lower odds of cost-related dental care delay, whereas telemedicine users had higher odds of delay. Higher odds of delayed dental care were observed among women, those aged below 65 years, Hispanics, those with poorer health, and those living in the Midwest, South, and West. Education and family income-to-poverty ratio were not significantly associated with delay in the adjusted analysis. Conclusions: Cost-related delays in dental care remain common and reflect persistent sociodemographic inequities and patterns of healthcare engagement. Telemedicine use alone does not appear to contribute to overcoming barriers to dental care access. Policies that reduce financial barriers and connect telehealth encounters with oral health referral pathways may improve equitable access to dental services.

Clinics and Practice doi: 10.3390/clinpract16050090

Authors: Maria Sobol Ewelina Sielska-Badurek Mariusz Cięciara Artur Wrzosek Justyna Tomaszewska Beata Roman

Purpose: The aim of this study was to investigate the safety and efficacy, as well as relief of symptoms after regular use, of 0.5% lidocaine hydrochloride solution in anhydrous glycerol (Auridol) in the form of ear drops, in patients with symptoms of otitis externa (OE) in a real-world setting. Methods: This real-world pre–post study included 64 subjects aged 1 to 69 years with symptoms as follow: swelling, pain due to regular exposure to water or caused by frequent use of detergents, pain due to prolonged wearing of earphones, or earwax clogging the external auditory canal. In each subject, following an otoscopic examination and interview given by an ENT, the Auridol treatment was initiated. The product was administered as two drops into the affected ear up to three times daily in patients with symptoms of OE. During each visit, physical and functional symptom were evaluated. In addition, the efficacy of using the product was assessment using a VAS scale. At the end of the study, subjects rated the product according to a Likert scale. Results: A statistically significant reduction in perceived pain was observed at t = 30′ as well as t = 3 days after application. For physical symptoms assessed by an ENT, a statistically significant difference was observed between consecutive scores for two of the assessed parameters (redness and swelling.) The product was rated very highly by the subjects. Conclusions: The results suggest that a combination of anhydrous glycerol and 0.5% of lidocaine in the form of ear drops has a positive effect in the treatment of symptoms of OE.

Clinics and Practice doi: 10.3390/clinpract16050089

Authors: Luciano Cellura Anna Maria Grugnetti Stefano Gabriele Scaglia Attilio Quaini Silvia Natoli Giuseppina Grugnetti

Introduction/Aim: Nursing care constitutes a fundamental determinant of patient outcomes in intensive care units (ICUs); however, the absence of standardised nursing-sensitive indicators constrains the objective evaluation of care quality within this setting. The present study aimed to develop an evidence-informed core set of nursing-sensitive patient outcomes (NSPOs) specific to intensive care nursing. Methods: A Delphi consensus study was conducted between September 2023 and February 2025 at the IRCCS Policlinico San Matteo Foundation, Pavia, Italy. The process comprised a preliminary scoping review, followed by two iterative Delphi rounds and a final consensus meeting aimed at refining conceptual domains without modifying item ratings. Thirty-eight ICU nurses evaluated 35 evidence-based NSPOs using a five-point Likert scale. Consensus was defined a priori as ≥75% agreement (scores 4–5), with a minimum response rate of ≥80%. Reliability was assessed using a two-way random-effects Intraclass Correlation Coefficient (ICC). Results: Fifteen NSPOs achieved the predefined consensus threshold and demonstrated moderate-to-excellent reliability (ICC = 0.65–0.85). The validated core set was organised into four domains—safety, clinical, functional, and perceptual—reflecting both preventive–technical and holistic dimensions of ICU nursing care. Conclusions: This study produced the first ICU-specific evidence-based NSPO core set in Italy, providing a measurable and reproducible framework to support systematic outcome monitoring, and quality improvement in critical care practice.

Clinics and Practice doi: 10.3390/clinpract16050088

Authors: Elena Maria Domsa Ioana Para Adela Viviana Sitar Taut Teodora Atena Pop Elena Ofelia Mosteanu Laura Elena Gligor Mihaela Elvira Cîmpianu Antonia Gabriela Nitescu Viorel Lucian Marina Bogdan Nicolae Mucea Vasile Andreica

Background/Objectives: Celiac disease (CD) is a chronic immune-mediated enteropathy triggered by gluten ingestion in genetically predisposed individuals, with a highly heterogeneous clinical presentation encompassing both intestinal and extraintestinal manifestations. Despite growing clinical awareness, diagnostic delay remains a significant challenge, and the evolution of clinical and histopathological features following gluten-free diet (GFD) initiation remains incompletely characterized. This study aimed to compare the clinical, serological, and histopathological profile of adults with newly diagnosed CD and those maintained on a long-term GFD. Methods: This prospective observational study enrolled 50 adult patients with biopsy-confirmed CD: 16 at the time of diagnosis (gluten-consuming) and 34 on a GFD for at least one year. All participants underwent standardized clinical assessment, serological testing (IgA anti-tissue transglutaminase [tTG] and/or IgA anti-endomysial antibodies [EMAs]), upper digestive endoscopy with duodenal biopsies graded according to the Marsh–Oberhuber classification, and evaluation for Helicobacter pylori co-infection. Between-group comparisons were performed using the Mann–Whitney U test, Fisher’s exact test, and chi-square test, as appropriate. Results: Newly diagnosed patients exhibited a significantly longer median duration from symptom onset to diagnosis compared to the GFD group (p = 0.03). Histopathological severity was greater in the newly diagnosed group, with more advanced Marsh–Oberhuber grades (p = 0.03). Among individual symptoms, bloating was significantly more frequent in newly diagnosed patients (p = 0.02). Notably, thrombocytosis was identified significantly more often in the newly diagnosed group compared to GFD patients (p = 0.02), representing a potentially underrecognized extraintestinal marker of active CD. Overall rates of intestinal and extraintestinal manifestations and CD-specific seropositivity did not differ significantly between groups. Conclusions: The clinical and histopathological profile of adults with celiac disease differs meaningfully between the time of diagnosis and during GFD adherence. Bloating and thrombocytosis were significantly more prevalent at diagnosis, with thrombocytosis emerging as a potentially underrecognized marker of active disease. Conversely, several manifestations persisted despite dietary treatment, underscoring the heterogeneous nature of CD across its clinical course. These findings may support earlier disease recognition and more individualized follow-up strategies in routine clinical practice.

Clinics and Practice doi: 10.3390/clinpract16050087

Authors: Yakup Özgüngör Burak Emre Gilik Emre Karagöz Hicret Yeniay Mensure Çakırgöz Özlem Melis Korkmaz Özgüngör İhsan Birol Sıla Seven

Background: Non-thyroidal illness syndrome is frequent in critically ill patients, but the prognostic value of dynamic changes in thyroid function tests remains unclear. This study evaluated whether serial measurements of thyroid-stimulating hormone (TSH) and free triiodothyronine (FT3) provide additional predictive value for 30-day mortality beyond conventional severity scores in ICU patients. Methods: This single-center retrospective observational study included 74 adult patients treated for ≥72 h in a general ICU who had TSH and FT3 measured within 24 h of admission and repeated at 48–72 h. Patients aged 18 years or above admitted to the intensive care unit were included in the study. Demographic characteristics, comorbidities, APACHE II, SOFA, modified NUTRIC (mNUTRIC) scores, and routine laboratory data (including albumin, CRP, and lactate) were recorded. The primary outcome was 30-day mortality. Between-group comparisons were performed using t-tests, Mann–Whitney U, and Chi-square tests. Variables significant in univariate analyses were entered into binary logistic regression models, and predictive performance was assessed using receiver operating characteristic (ROC) curves and the Youden index. Results: The mean age was 68.7 ± 14.7 years, and 41.9% (n = 31) of the patients died within 30 days. Non-survivors had higher APACHE II, SOFA, and mNUTRIC scores and lower albumin, lymphocyte count, and second FT3 levels compared with survivors (all p ≤ 0.003). Baseline FT3 and TSH were not associated with mortality, whereas both the subsequent FT3 measurements and the ΔT3 (variance in former to latter FT3) were remarkably predictive. The latter FT3 < 1.63 pg/mL produced an AUC of 0.835 (sensitivity: 77%, specificity: 74%), and a ΔT3 log ratio threshold of −0.09 (≈20% early FT3 decline) produced an AUC of 0.835 (sensitivity: 71%, specificity: 81%). The APACHE II + ΔT3 (numeric) model showed the best discrimination (AUC: 0.921; sensitivity: 87.1%, specificity: 81.4%), outperforming APACHE II alone (AUC: 0.861). Conclusions: In critically ill adult patients, dynamic T3 kinetics—particularly premature decline in FT3 within the first 72 h—provide incremental prognostic value for 30-day mortality beyond APACHE II. Serial FT3 monitoring may help identify high-risk patients whose endocrine adaptation to critical illness is failing.

Clinics and Practice doi: 10.3390/clinpract16050086

Authors: Jelena Stojsavljevic Rafael R. Perez Emilia Petcu Celestine Odenigbo Cristian Madrid Igor Dumic Charles W. Nordstrom

Background: Acute transverse myelitis (ATM) is an inflammatory disorder of the spinal cord with heterogeneous etiologies, including autoimmune, infectious, paraneoplastic, and drug-induced causes. Tumor necrosis factor-alpha (TNF-α) inhibitors have been infrequently associated with inflammatory central nervous system events, including transverse myelitis. TNF-inhibitor-associated myelitis typically presents with short-segment lesions, a normal brain MRI, and partial responsiveness to corticosteroids. Longitudinally extensive transverse myelitis (LETM) and steroid-refractory cases are uncommon. Case Presentation: A 39-year-old woman with psoriatic arthritis treated with etanercept for two years presented with subacute progressive bilateral lower-extremity sensory loss and weakness. MRI revealed a T2 hyperintense spinal cord lesion extending from T11 to L1 with gadolinium enhancement, consistent with transverse myelitis, while brain MRI was normal. Cerebrospinal fluid analysis showed lymphocytic pleocytosis, elevated protein, oligoclonal bands, and increased kappa free light chains. Extensive infectious, metabolic, paraneoplastic, and autoimmune testing, including aquaporin-4 and MOG antibodies, was negative. Despite high-dose intravenous corticosteroids and the discontinuation of etanercept, the patient experienced clinical worsening with lesion expansion, meeting criteria for LETM, and developed urinary retention. She subsequently underwent plasma exchange, resulting in radiologic improvement and moderate clinical recovery. Conclusions: This case highlights an atypical presentation of TNF-inhibitor-associated myelitis characterized by a biphasic course, longitudinally extensive spinal cord involvement, steroid refractoriness, and responsiveness to plasma exchange. These features suggest either an unusually severe TNF-inhibitor-related inflammatory phenotype or a TNF-inhibitor-triggered antibody-mediated demyelinating process. Reports of TNF-inhibitor-associated myelitis evolving into longitudinally extensive, steroid-refractory disease remain limited, and this presentation may broaden the recognized clinical spectrum of TNF-α-related CNS inflammatory events. Close neurologic follow-up and heightened awareness of severe CNS complications associated with TNF-α inhibitors are warranted.

Clinics and Practice doi: 10.3390/clinpract16050085

Authors: Lucian Șerbănescu Sebastian Mirea Paris Ionescu Ionuț Iorga Traian-Virgiliu Surdu Vadym Rotar Stere Popescu Elena Mocanu Luana Alexandrescu Cosmin Nișcoveanu Radu-Andrei Baz

Background/Objectives: Urinary incontinence (UI) is a frequent condition in postmenopausal women and is associated with a substantial negative impact on quality of life. Conservative management can include pelvic floor muscle training (PFMT) and high-intensity focused electromagnetic stimulation (HIFEM); however, data regarding the potential benefit of combining these modalities remain limited. This study aimed to evaluate whether the addition of a structured Kegel exercise program to EMSELLA-based electromagnetic stimulation is associated with enhanced clinical outcomes in postmenopausal women with urinary incontinence. Methods: This prospective comparative study included 99 postmenopausal women with stress, urgency, or mixed urinary incontinence and an International Consultation on Incontinence Questionnaire–Urinary Incontinence Short Form (ICIQ-UI SF) score ≥ 6. Participants received either EMSELLA therapy alone (Group A, n = 49) or EMSELLA combined with a standardized Kegel exercise program (Group B, n = 50) over a three-month period. Symptom severity was assessed at baseline and at three months using the ICIQ-UI SF. Between-group comparisons were performed using analysis of covariance, adjusting for baseline scores. Results: Both therapeutic approaches were associated with clinically meaningful improvement in urinary incontinence symptoms. After adjustment for baseline severity, lower follow-up ICIQ-UI SF scores, greater mean symptom reduction, and higher response rates were observed in the combined-therapy group. Across all menopausal-duration subgroups, outcomes consistently favored the association of EMSELLA therapy with Kegel exercises. No treatment-related adverse events were reported. Conclusions: The association of EMSELLA electromagnetic stimulation with a structured Kegel exercise program was associated with greater symptom improvement than electromagnetic stimulation alone, suggesting an additive therapeutic effect of voluntary pelvic floor muscle training. This combined conservative approach was well tolerated and may represent a useful management strategy for postmenopausal urinary incontinence.

Clinics and Practice doi: 10.3390/clinpract16050084

Authors: Isabella Oliveira do Lago Bruna Moura Medina Diniz Daniela Vieira Buchaim Rogerio Leone Buchaim

In the original publication [...]

Clinics and Practice doi: 10.3390/clinpract16050083

Authors: Hasan M. Al-Dorzi Abdulaziz R. Al-Qwizani Turki F. Al-Saikhan Yousef Alshahwan Bandar F. Bindayel Raed Alharthi Raymond Khan

Background: Patients with traumatic brain injury (TBI) are often underfed and frequently experience enteral feeding (EF) intolerance. We examined the association between EF timing, caloric intake and EF intolerance, and mortality. Methods: We retrospectively evaluated adult patients with moderate-to-severe TBI in a tertiary-care ICU. In the first 7 days, we recorded daily caloric intake from EF and the occurrence of EF intolerance—defined as a gastric residual volume > 500 mL or >250 mL with vomiting. Results: Among 298 patients, 210 (70.4%) received early EF. The median 7-day cumulative caloric intake was 7766 kcal for the early EF group (64.7% of caloric requirement) and 2783 kcal (23.1% of caloric requirement) for the late (after 48 h) EF group (p < 0.001). EF intolerance occurred in only 24 patients (8.1%), with no significant difference between the early and late groups. Hospital mortality was 13.8% with early EF versus 30.7% with late EF (p = 0.001), 8.5% with caloric intake ≥ 80% of requirement versus 21.3% with lower caloric intake (p = 0.02) and 50% in patients with EF intolerance versus 16.1% in those without intolerance (p < 0.001). In multivariable logistic regression analysis, early EF was associated with lower mortality (odds ratio 0.326; 95% confidence interval 0.165–0.644), whereas EF intolerance was associated with higher mortality (odds ratio 7.451; 95% confidence interval 2.787–19.922). Conclusions: In patients with moderate-to-severe TBI, early EF was associated with higher caloric intake and lower mortality compared to late EF. EF intolerance was uncommon but strongly associated with higher mortality.

Clinics and Practice doi: 10.3390/clinpract16050082

Authors: Borislava Atanasova Mariya Tokmakova Angel M. Dzhambov Rafiela Chitak Penka Atanassova

Objectives: Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, and cardiometabolic comorbidity, have been increasingly associated with cognitive impairment and dementia. These associations, however, remain underexplored and underappreciated in middle-aged individuals with AF. This study aimed to explore the associations of early cognitive impairment with the presence of cardiometabolic comorbidities and potential associations with echocardiographic markers in middle-aged patients with and without AF. Methods: Between 2023–2024, fifty-six consecutive outpatients with a diagnosis of AF aged 45–65 years underwent clinical evaluation, transthoracic echocardiography, and comprehensive neuropsychological assessment using the Montreal Cognitive Assessment (MoCA) and the Consortium to Establish a Registry for Alzheimer’s Disease battery (CERAD). A control group of 58 age group-matched individuals without known cardiometabolic disease was included in comparative cognitive analyses. Results: Patients with AF and cardiometabolic comorbidities demonstrated early cognitive deficits, particularly in episodic memory and visuospatial functions, detectable even in individuals with normal MoCA scores, compared with the control group. However, no associations were observed between cognitive performance and conventional echocardiographic parameters in the group with AF. Conclusions: This study corroborated prior evidence of an association between cardiometabolic impairment and subtle cognitive impairment, but did not identify a specific contribution of echocardiography markers. More extensive and sensitive biomarkers of left atrial structure and function may be required to detect harmful associations with subtle cognitive impairment in middle-aged individuals. Further prospective studies, with a more balanced control for comorbidities, are warranted to clarify the clinical relevance of atrial structural remodeling in this context.

Clinics and Practice doi: 10.3390/clinpract16040081

Authors: Silvia Iannelli Melania Scarcella Antonella Cusano Federica Feleppa Ylenia Pancione Luigi Michele Pavone Pasquale Cocchiaro

Background/Objectives: Serum protein electrophoresis (SPE) is a widely used laboratory test for the detection and monitoring of monoclonal gammopathies, including multiple myeloma (MM). Although SPE is usually recommended in the presence of specific clinical or laboratory abnormalities, monoclonal gammopathies may occasionally develop rapidly and without typical symptoms. This case report aims to emphasize the diagnostic value of SPE in identifying an unexpected and fast-evolving monoclonal gammopathy. Methods: We report the clinical and laboratory eight-month follow-up of a 58-year-old male who initially underwent SPE for unrelated clinical conditions. Serial SPE analyses were performed using capillary zone electrophoresis. When abnormalities emerged, immunotyping and serum free light chain (FLC) assays were conducted. The diagnostic workup was completed with bone marrow aspiration, flow cytometry, and imaging studies according to current international diagnostic criteria. Results: The initial SPE (November 2023) showed a normal protein profile. After eight months, follow-up SPE revealed a prominent monoclonal spike in the gamma region (2.9 g/dL), associated with increased total serum proteins (91 g/L; range 64–82 g/L), elevated IgA levels (20.0 g/L; range 0.4–3.5 g/L), and a markedly abnormal κ/λ FLC ratio (54.00; range 0.31–1.56). Bone marrow analysis demonstrated >18% plasma cell infiltration, confirming the diagnosis of IgA-κ MM. The patient underwent standard therapy followed by autologous stem cell transplantation, achieving disease remission. Conclusions: This case highlights that clinically relevant monoclonal gammopathies may arise rapidly in the absence of classical diagnostic features. Routine SPE represents a cost-effective and accessible screening tool that can identify subtle protein abnormalities, prompting the timely use of more specific and invasive diagnostic procedures for aggressive plasma cell disorders.

Clinics and Practice doi: 10.3390/clinpract16040080

Authors: Dirk Rades Maria Karolin Streubel Laura Doehring Stefan Janssen Sabine Bohnet Christian F. Schulz Hanne Falk Grauslund Charlotte Kristiansen

Background/Objectives: Radiation therapy is a common treatment modality for non-small-cell and small-cell lung cancer that can be associated with considerable side effects, mainly reactions of healthy tissues in the radiation field. Radiation therapy may lead to significant fatigue, which can potentially be mitigated by maintaining or increasing physical activity during treatment. Since achieving this goal may be a challenge for patients, they may benefit from a mobile application reminding them daily to perform a predefined number of steps. Such a reminder app will be investigated prospectively in a phase 2 trial. The current APART-LUNG study (NCT07380815) is a mandatory study for designing the prospective trial. Methods: The main objective of the APART-LUNG (exploratory non-interventional) study is to report patterns of physical activity during radiation therapy for lung cancer patients and generate hypotheses based on our findings. Our primary endpoint is the within-patient difference in weekly average steps per wear hour of the smartphone (week 5 minus week 1 of radiation therapy), and our secondary aim is to estimate differences in operational measures (wear time of the smartphone) between week 5 and week 1. The sample size of approximately 20 patients (full analysis set) allows us to detect a moderate-to-large standardized within-patient difference and is driven by feasibility and the intent to obtain preliminary estimates of effect size and variability. The results of the APART-LUNG study will be very important for appropriately designing a phase 2 trial.

Clinics and Practice doi: 10.3390/clinpract16040079

Authors: Mallika Sathitwat Surat Tanprawate Atiwat Soontornpun Chayasak Wantaneeyawong Chutithep Teekaput Nopdanai Sirimaharaj Angkana Nudsasarn Chatree Chai-Adisaksopha Kitti Thiankhaw

Background: The clinical outcomes of patients with intracranial haemorrhage (ICH) whilst using direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) are uncertain. This study aimed to assess outcomes and management in patients receiving DOACs compared with those receiving VKAs. Methods: In this retrospective study, patients hospitalised during the period from 1 January 2017 to 31 December 2023 for traumatic and non-traumatic ICH and using oral anticoagulants (OACs) were included. The primary outcomes were mortality and functional outcomes, as measured by the modified Rankin Scale (mRS) during admission and 90-day follow-up. ICH management and complications were studied and compared between the two OAC groups. Results: A total of 171 eligible patients were included, comprising 24 patients on DOACs and 147 patients on VKAs. Patients receiving DOACs were older (79.1 vs. 66.8, p < 0.001) and had a higher proportion of traumatic ICH (75.0% vs. 46.3%, p = 0.009) than those receiving VKAs. In-hospital and 90-day outcomes were not statistically different between the two groups, with an adjusted odds ratio (aOR) of 1.30 (0.39–4.36) for in-hospital mortality, p = 0.67, and an aOR of 0.89 (0.33–2.41) for mRS 0–2 at 90 days, p = 0.83. In total, 81.3% of patients received at least one reversal agent; fresh frozen plasma was commonly used in the VKA group (78.9% vs. 33.3%, p < 0.001), whereas prothrombin complex concentrate was significantly prescribed in patients with DOAC-associated ICH (29.2% vs. 3.4%, p < 0.001). Conclusions: Patients with DOAC-associated ICH had comparable in-hospital and long-term clinical outcomes to those with VKA use.

Clinics and Practice doi: 10.3390/clinpract16040078

Authors: Sanjana Arun Joaquin Cardozo Andre Shon Hirakawa Teresa Anh Tran Van Dexter Calo Robert Fauer

Background: Unhoused individuals face disproportionately high rates of preventable chronic disease due to fragmented access to care and prolonged exposure to environmental stressors. Street medicine programs offer a mobile, low-barrier model to assess and address these unmet needs. Despite well-documented disparities, no publications in the current literature provide numerically specific screening recommendation guidelines tailored to unhoused populations. This study fills that gap using clinical data from Street Medicine Phoenix (SMP), a mobile healthcare initiative serving urban Arizona. Methods: We retrospectively reviewed 1322 clinical encounters recorded by SMP between August 2023 and October 2024. Diagnoses and treatments were manually categorized. Blood pressure (BP) and glucose values were analyzed using descriptive statistics and compared against national norms (CDC 50th percentile and ADA guidelines). Kruskal–Wallis and Dunn’s tests assessed age-based differences, while chi-square and Mann–Whitney U tests examined glucose patterns. Results: The mean patient age was 51.4 years; 34.5% identified as female. Cardiovascular issues (39.4%) and routine screenings (39.6%) were most frequently documented. Systolic and diastolic BP values were significantly elevated across all age groups except those 60+, with even the 18–39 group showing median systolic BP above CDC norms (124.0 mmHg). Among 60 patients with fasting glucose data, 41.4% met ADA criteria for diabetes, and 10.7% of those without a known diagnosis had diabetic-range values. Conclusions: Our findings suggest that cardiometabolic disease may emerge earlier and more aggressively among unhoused individuals than in the general U.S. population, reflecting patterns of accelerated biological aging. The elevation of cohort-based BP percentiles suggests that current national benchmarks may underrepresent clinical risk in this group. We propose initiating blood pressure screening at age 18 and fasting glucose screening by age 35 in unhoused individuals—adaptations of existing USPSTF recommendations based on cohort-specific trends. These screening thresholds can be feasibly implemented in street medicine settings to promote earlier detection and improve long-term health outcomes.

Clinics and Practice doi: 10.3390/clinpract16040077

Authors: Yibo Liu Christopher Khatchadourian Luke Sanders Quincy Eweroke Cyvannah Warner-McCutcheon Jackson Lewis Joaquin Santos Vishwanath Venketaraman

Background: Myocarditis is an uncommon but recognized adverse event following mRNA COVID-19 vaccination, with risk varying by age, sex, dose number, and vaccine product. Clarifying the magnitude of risk, clinical course, and recovery—relative to myocarditis following SARS-CoV-2 infection—is essential for risk–benefit assessment and public health guidance. Methods: We performed a systematic PubMed and Embase search (January 2020–December 2024) and synthesized cohort, registry, and surveillance data on myocarditis incidence and outcomes following mRNA COVID-19 vaccination. Outcomes included incidence, observed-to-expected (OE) or incidence rate (IRRs) ratios, hospitalization, and short-term recovery. Study selection followed PRISMA 2020 systematic review guidelines. Results: Myocarditis following mRNA COVID-19 vaccination was identified as a rare adverse event, most commonly occurring after the second dose and in younger male individuals. Across multiple cohort and registry-based studies, cases were generally mild and self-limited, with most patients recovering without complication. In contrast, myocarditis following SARS-CoV-2 infection was consistently associated with more severe outcomes, including higher rates of hospitalization and mortality. Conclusions: Vaccine-associated myocarditis is rare, typically mild, and self-limited, with excellent short-term recovery; vaccinated individuals also exhibit lower odds of in-hospital death and intubation. In contrast, infection-associated myocarditis is more frequent and severe. Overall, the benefit–risk profile of mRNA vaccination remains strongly favorable.

Clinics and Practice doi: 10.3390/clinpract16040076

Authors: Anca Tătaru-Copos Florin Szasz Anca Carmen Huniadi Rodica Georgeta Negrini Mircea Ioachim Popescu Paula Trif Gelu Florin Murvai Radu Galiș Cristian Sava Romina Viorela Murvai

Background: Preeclampsia is a heterogeneous multisystem disorder characterized by endothelial dysfunction and angiogenic imbalance. While the sFlt-1/PlGF ratio is widely used for diagnostic purposes, its role in defining biological phenotypes of preeclampsia remains insufficiently explored. This study aimed to investigate whether angiogenic imbalance is associated with distinct multisystem phenotypes of preeclampsia and with perinatal outcomes. Methods: We conducted a retrospective cohort study including 320 pregnant women, of whom 68 were diagnosed with preeclampsia. Multisystem phenotypes were defined using laboratory markers reflecting renal, hepatic, and hematologic involvement. The sFlt-1/PlGF ratio was compared across phenotypes. Associations with gestational age at delivery, birth weight, Apgar score, and neonatal intensive care unit (NICU) admission were evaluated. Receiver operating characteristic (ROC) analysis assessed the discriminatory performance of the sFlt-1/PlGF ratio for identifying the renal-dominant phenotype. Results: The mean sFlt-1/PlGF ratio was higher in preeclampsia compared to normotensive pregnancies (58.5 ± 20.3 vs. 34.6 ± 15.9). Within preeclampsia, the renal-dominant phenotype showed the highest ratio (66.0 ± 22.5), followed by hepatic (55.9 ± 18.2) and hematologic phenotypes (52.0 ± 16.8). The renal phenotype was associated with earlier delivery (34.6 weeks), lower birth weight (2196 g), higher NICU admission (10.7%), and lower Apgar scores. The sFlt-1/PlGF ratio demonstrated moderate discrimination for the renal phenotype (AUC = 0.69). Conclusions: Angiogenic imbalance varies across multisystem phenotypes of preeclampsia and is associated with meaningful perinatal differences. The sFlt-1/PlGF ratio may contribute to phenotype-based risk stratification, supporting a move toward precision obstetrics. Prospective studies are needed to validate phenotype-oriented classification models.

Clinics and Practice doi: 10.3390/clinpract16040075

Authors: María Ángeles Ventura-García Tesifón Parrón-Carreño David Lozano-Paniagua Bruno José Nievas-Soriano Antonio Fernando Murillo-Cancho Elena María Gázquez-Aguilera Delia Cristobal-Cañadas

Background/Objectives: Despite being a standard biological therapy for knee osteoarthritis, inconsistent results across studies—due to varied protocols—have obscured the clinical standing of platelet-rich plasma. This meta-analysis evaluates the efficacy and safety of PRP for pain, function, and adverse events, and examines the potential benefits of combining it with hyaluronic acid. Methods: An umbrella review was conducted following the PRIOR (Preferred Reporting Items for Umbrella Reviews) and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. Meta-analyses evaluating PRP in knee osteoarthritis were included. Quantitative estimates of pain, function, and safety were extracted. Random-effects models were applied when possible. Methodological quality was assessed using AMSTAR 2, and study overlaps were assessed using the CCA method. Publication bias was analyzed using a funnel plot. Results: The meta-analyses included consistently showed the superiority of PRP over hyaluronic acid and placebo in reducing pain and improving function. Pooled estimates indicated clinically relevant improvements, especially in mild-to-moderate osteoarthritis. The combination of PRP and hyaluronic acid demonstrated superior functional recovery and a potential reduction in adverse events compared to PRP monotherapy. The overall safety profile was favorable. Conclusions: PRP is an effective and safe therapy for knee osteoarthritis, with consistent evidence of superiority over conventional intra-articular treatments. Combined PRP and HA administration suggests superior clinical efficacy compared to monotherapy. Standardization of protocols and appropriate patient selection will be key in future clinical guidelines.

Clinics and Practice doi: 10.3390/clinpract16040074

Authors: Ariane P. Lallès Luisa Cedin Markus A. Wimmer

Background/Objectives: Knee joint instability is frequently reported in individuals with knee osteoarthritis (OA) and may persist after total knee replacement (TKR), where it represents a leading cause of revision. However, neuromuscular factors associated with knee instability remain poorly understood. This systematic review and meta-analysis aimed to compare neuromuscular characteristics between individuals with stable and unstable knees in OA and TKR populations. Methods: PubMed, CENTRAL, Scopus, and EMBASE were searched from inception to 10 January 2025. Studies comparing neuromuscular outcomes between stable and unstable knees were included. Neuromuscular parameters included: muscle strength, muscle power, muscle activation pattern, and joint stiffness. Where appropriate, pooled standardized mean differences (SMD) were calculated using random-effects models. Certainty of evidence was evaluated using the GRADE approach. Results: Nineteen studies (16 OA, 3 TKR; n = 7369 participants) were included, with eleven studies eligible for meta-analysis. OA individuals with unstable knees demonstrated significantly lower limb muscle strength compared with stable counterparts (SMD = −0.49, 95% CI −0.81 to −0.16, p = 0.003). Muscle co-contraction did not differ significantly between groups (SMD = 0.12, 95% CI −0.70 to 0.94, p = 0.77). The overall certainty of evidence was rated as very low. Conclusions: Knee instability in OA populations is associated with reduced lower limb muscle strength, although evidence quality is limited and findings regarding neuromuscular control strategies remain inconclusive. Evidence in TKR populations is scarce. Future studies should investigate muscle activation patterns and dynamic joint stabilization during functional tasks to clarify the neuromuscular mechanisms underlying knee instability.

Clinics and Practice doi: 10.3390/clinpract16040073

Authors: Camila Baas-Yama Eduardo Rivera-Huerta Ivan Zepeda-Quiroz Carlos A. Guzmán-Martín Demian Trueba-Lozano Sebastian Toledo-Ramirez Ana Ortega-Gonzalez Irma Archundia-Riveros Brenda Barrera-Mota María Jimenez-Baez Ciria Vázquez-Macias Daniel Juárez-Villa

Background: Urgent-start peritoneal dialysis (UPD) has emerged as an alternative modality for initiating kidney replacement therapy when immediate hemodialysis is not available. However, early initiation after catheter placement may increase the risk of mechanical complications. Evidence from real-world settings, particularly in resource-limited healthcare systems, remains limited. Objective: To determine the frequency of early complications associated with urgent-start peritoneal dialysis and to identify clinical factors associated with their occurrence. Methods: We conducted a prospective observational cohort study including adult patients with chronic kidney disease who initiated peritoneal dialysis within 14 days after catheter placement at a public hospital in Mexico. Patients were followed for 30 days after dialysis initiation. The primary outcome was the occurrence of any dialysis-related complication within 30 days after initiation of peritoneal dialysis. Comparisons were performed according to dialysis initiation timing (<72 h vs. ≥72 h). Multivariable logistic regression was used to identify independent predictors of complications. Results: Sixty-five patients were included, of whom 29 (44.6%) developed complications within the first 30 days. Mechanical complications predominated, particularly pericatheter leakage (18.5%) and drainage failure (10.8%). Patients who initiated dialysis within 72 h after catheter placement experienced a significantly higher complication rate. In multivariable analysis, initiation of peritoneal dialysis within <72 h remained independently associated with complications (OR 5.75, 95% CI 1.06–31.29, p = 0.043). Conclusions: Initiating peritoneal dialysis within 72 h after catheter placement was associated with a significantly increased risk of early complications. When clinically feasible, delaying dialysis initiation beyond 72 h may reduce mechanical complications in urgent-start peritoneal dialysis programs.

Clinics and Practice doi: 10.3390/clinpract16040072

Authors: Claudiu C. Popescu Luminița Enache Carmen Ștențel Corina Mogoșan Cătălin Codreanu

Objective: The objective of this study was to characterize real-world distributions of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) across major rheumatic diagnoses and to quantify concordance/discordance patterns and combined CRP-ESR inflammatory phenotypes. Methods: We retrospectively extracted all CRP and ESR tests performed in a tertiary university rheumatology hospital (January 2018–December 2023), including ICD-10-coded diagnoses. Analyses were conducted at the measurement level and patient level (medians across repeated tests). CRP and ESR were expressed as raw values and multiples of ULN and categorized into severity strata. CRP and ESR datasets were merged by patient identifier and calendar date to define same-day pairs; paired analyses used Spearman correlations and ULN-based phenotype classes. Sensitivity analyses tested alternative pairing windows, first-pair-only analyses, phenotype persistence rules, and tertile/quartile discordance definitions. Results: Among 16,921 patients with ≥1 CRP and 17,126 with ≥1 ESR, CRP was more disease-discriminative and only negligibly age-related, whereas ESR increased modestly with age and showed marked sex shifts across severity categories. Inflammatory burden was highest in gout and rheumatoid arthritis, intermediate in psoriatic arthritis and ankylosing spondylitis, and lower in connective tissue diseases (systemic lupus erythematosus, mixed connective tissue disease, Sjogren’s disease, systemic sclerosis, and dermato/polymyositis) and osteoarthritis; CRP distributions were more strongly right-tailed than ESR. Merging yielded 44,427 same-day CRP-ESR pairs from 16,824 patients (99.1% match). CRP and ESR were moderately correlated at measurement and patient levels, yet discordance was common: 27.3% of pairs showed isolated elevation of a single marker. Conclusions: In routine rheumatology care, CRP and ESR provide complementary information. CRP-ESR dissociation is frequent, persists at the patient level, and follows diagnosis-dependent phenotype patterns.

Clinics and Practice doi: 10.3390/clinpract16040071

Authors: Daniel Schiltz Mahsa Bagheri Borgolte Stephan Schreml Philipp Lamby Adrian Vater Lukas Prantl Uwe von Fritschen

Background: Groin lymphoceles are common postoperative complications after vascular interventions that can be difficult to treat, especially in recurrent or complex cases. While lymphovenous anastomosis (LVA) is a potential, minimally invasive option, its limited flow capacity may not provide sufficient drainage in large lymphoceles. We present a novel high-volume LVA technique that uses larger veins to directly drain the lymphocele cavity. Methods: Five patients with six groin lymphoceles, all previously treated unsuccessfully with conventional methods (mean 3.3 surgeries), underwent high-volume LVA (HV-LVA). The technique involved direct anastomosis of a large regional vein to the lymphocele cavity. Lymphatic inflow points were identified with Patent Blue or ICG when possible. Outcomes were assessed over 6–14 months. Results: In total, seven HV-LVAs were performed. Three lymphoceles (50%) were successfully treated with a single operation; three required revisions due to venous occlusion. All patients were successfully treated without recurrence. The average number of surgeries per patient was 2.2. Conclusions: High-volume LVA may be an effective option for therapy-resistant inguinal lymphoceles, providing greater drainage capacity than standard techniques. Further studies are needed to confirm its long-term efficacy and safety.

Clinics and Practice doi: 10.3390/clinpract16040070

Authors: Dora Martic Martin Miskovic Antonija Palac Bzik Ana Glavina Ivan Kovacic Antonija Tadin

Objectives: Temporomandibular disorders (TMDs) are common but often underrecognized and inadequately managed in primary healthcare, which may delay diagnosis and appropriate care. This study aimed to compare TMD-related knowledge, awareness, and clinical practices between dentists and physicians working in primary care and to identify factors associated with higher diagnostic confidence. Methods: A cross-sectional survey was conducted among dentists and physicians working in Croatian primary healthcare. TMD-related knowledge, clinical confidence, screening practices, and referral patterns were assessed using a structured questionnaire. Results: Dentists demonstrated significantly higher overall knowledge scores than physicians (15.6 ± 1.7 vs. 13.2 ± 4.1; p < 0.001), as well as greater diagnostic and therapeutic confidence (all p < 0.001). Routine TMD screening was reported by only 21.8% of participants, more frequently by dentists than physicians (36.1% vs. 8.2%; p < 0.001). Most respondents preferred referral rather than independent management. Regression analysis identified profession as the only independent predictor of higher TMD-related knowledge (p = 0.003). Insufficient knowledge, experience, and lack of confidence were the most reported barriers, particularly among physicians. Conclusions: The findings indicate clinically relevant gaps in TMD preparedness within primary healthcare, especially among physicians, despite frequent patient contact. Strengthening undergraduate and continuing education, promoting interdisciplinary training, and establishing clearer referral pathways may enhance early recognition and improve primary-level management of TMD.

Clinics and Practice doi: 10.3390/clinpract16040069

Authors: Carlos Ramon Hölzing Tristan Ernst Thomas Wurmb Tobias Grundgeiger Patrick Meybohm Oliver Happel

Background/Objectives: The success of cardiopulmonary resuscitation relies on both technical and non-technical skills. Cognitive aids, such as checklists, have been shown to enhance technical performance in emergencies. The aim of this study was to evaluate the capabilities of a cognitive aid app (CA-App) in improving non-technical skills. Methods: In this single-centre randomised controlled trial, 62 teams, each consisting of an experienced physician and a specialised nurse, were randomised either to CA-App or control (No-App) groups performing cardiopulmonary resuscitation. The study was registered with the German Clinical Trials Register (DRKS) on 4 November 2025 (DRKS00038336). The primary outcome was the team leader’s performance in non-technical skills, assessed via the validated Team Emergency Assessment Measure (TEAM™) questionnaire by two raters. Secondary analyses examined TEAM™ subdomains (leadership, teamwork, task management) and the correlation between app usage duration and performance. Results: 62 out of 67 teams were finally randomised, with 31 teams in each group. The CA-App group demonstrated a marginally elevated median TEAM™ total score (83.33%) in comparison to the control group (79.33%), although this difference was not statistically significant (p = 0.190). The leadership subgroup score was significantly higher in the app group (p = 0.006). There was no significant correlation between the time spent using the app and improved team performance (r = 0.260, p = 0.166). Conclusions: The CA-App demonstrated potential for improving leadership skills, a critical component of non-technical skills in emergency scenarios. These findings highlight the potential capability of cognitive aids to improve non-technical skills and the need for further research to explore their optimal design and integration into clinical practice to enhance team performance and patient safety.

Clinics and Practice doi: 10.3390/clinpract16040068

Authors: Isabella Oliveira do Lago Bruna Moura Medina Diniz Daniela Vieira Buchaim Rogerio Leone Buchaim

Fibromyalgia (FM) is a chronic pain syndrome characterized by central sensitization and impaired pain modulation, involving dysfunctional descending inhibitory pathways and altered nociceptive processing. These processes contribute to persistent musculoskeletal pain, difficulties with sleep, feelings of depression, and ongoing fatigue. Serotonin and norepinephrine are key mediators of pain control, and evidence indicates that dual reuptake inhibition provides superior analgesia compared to single-pathway approaches. Accordingly, serotonin–norepinephrine reuptake inhibitors (SNRIs), including milnacipran and duloxetine, approved for FM treatment, show favorable efficacy and tolerability compared with tricyclic antidepressants. This integrative literature review aimed to evaluate the impact of SNRIs on musculoskeletal pain, fatigue, depression, and quality of life in patients with FM by analyzing randomized clinical trials (RCTs), identified via PubMed/MEDLINE searches (2015–2025) in English/Portuguese using descriptors: “Fibromyalgia”, “Serotonin and Norepinephrine Reuptake Inhibitors”, “Duloxetine” and “Milnacipran”. From 195 records screened, 18 studies met inclusion criteria (9.2% inclusion rate); duloxetine evaluated in 16 studies (88.9%), milnacipran in 2 (11.1%); SNRIs demonstrated superior efficacy vs. placebo: pain reduction 30–40%, fatigue improvement 25%, quality of life enhancement 20%. SNRIs were overall more effective than placebo but did not achieve high levels of analgesia, underscoring the need for further research on long-term efficacy and comparisons with combination pharmacological and non-pharmacological therapies. SNRIs significantly alleviate musculoskeletal pain (30–50% of patients), fatigue, depression symptoms, and improve quality of life in FM versus placebo. Duloxetine showed superior efficacy for pain/depression; milnacipran excelled in sleep quality. Long-term studies and combination therapies warrant further investigation.

Clinics and Practice doi: 10.3390/clinpract16040067

Authors: Paulina Rabiej-Krzys Karolina Szczygiel Rafal Lenard Francesco Perone Joanna Popiolek-Kalisz

Background: Atrial fibrillation (AF) is a common arrythmia in post-myocardial infarction (MI) cardiac rehabilitation (CR) cohorts, and beta-adrenergic signaling remodeling and rate-control pharmacotherapy may influence functional capacity. Methods: We retrospectively studied 117 consecutive male post-MI patients referred to outpatient CR. Functional capacity was assessed with a 6 min walk test (6MWT). AF was identified from clinical records, and beta-blocker exposure was unified as carvedilol-equivalent daily dose. Results: Beta-blockers were used in 94.1% of patients and AF was present in 10.3%. Patients with AF were older (72.7 ± 6.6 vs 58.1 ± 9.3 years) and walked shorter distances (430.0 [375.0–497.5] vs. 540.0 [480.0–570.0] m). In the prespecified interaction model, age remained independently associated with lower 6MWT (−4.29 m/year; p < 0.001), AF was associated with lower 6MWT (−137.21 m; p = 0.01), and the beta-blocker dose × AF interaction was positive (+6.78; p = 0.02; R2 = 0.44). Importantly, the beta-blocker dose was not associated with 6MWT in patients without AF, whereas a positive association was observed in AF (B = 7.55, p = 0.04). Conclusions: In this exploratory analysis, AF identified a subgroup with markedly reduced functional capacity in early post-MI CR, supporting the potential of phenotype-informed assessment. Additionally, the association between beta-blocker dose and 6MWT distance differed by rhythm status. These preliminary findings require confirmation in larger prospective cohorts.

Clinics and Practice doi: 10.3390/clinpract16040066

Authors: Charles A. Odonkor Muhammad Uzair Siddique Sarvesh Palaniappan Jacob Locklear Sreekrishna Pokuri Alexandra Adler Peju Adekoya Annie W. Hsu Jonathan Paek Hari Prabhakar Yuri Chaves Martins Christina Smith Uzondu Osuagwu Frederick K. Comrie Alaa Abd El Sayed

Background: Peripheral nerve stimulation (PNS) is increasingly used in selected patients with neuropathic pain, and many individuals seek supplemental online information to clarify procedural expectations and postoperative care. Large language models such as ChatGPT may provide scalable patient education; however, their performance for PNS-related questions has not been evaluated. This study assessed the reliability, accuracy, and comprehensibility of ChatGPT-5.0 responses to common PNS patient questions. Methods: We conducted a cross-sectional evaluation of ChatGPT-5.0 responses to 21 standardized questions derived through expert consensus, spanning pre-implantation, implantation, and post-implantation domains. Sixteen board-certified interventional pain specialists and a nurse educator independently rated each response using validated scales for reliability (1–6), accuracy (1–3), and comprehensibility (1–3). Descriptive statistics were calculated, and domain-level patterns were examined. Results: Clinician ratings demonstrated generally strong performance across all domains. Mean reliability was 4.7 ± 1.4, mean accuracy 2.6 ± 0.6, and mean comprehensibility 2.8 ± 0.5. Foundational questions addressing mechanisms, expectations, and postoperative care received the highest ratings. Lower ratings were observed for implantation-focused items requiring procedural nuance. No response fell below predefined acceptability thresholds, and sensitivity analyses confirmed that including one partial evaluator did not alter the observed trends. Conclusions: ChatGPT-5.0 generated responses to PNS-related patient questions that clinicians rated as generally reliable, accurate, and understandable, particularly for foundational and postoperative topics. Performance was more variable for procedural questions, underscoring the need for clinician oversight and verification. These findings provide a benchmark of current LLM capabilities and highlight the importance of ongoing evaluation as models evolve and as patients access versions with differing functionalities.

Clinics and Practice doi: 10.3390/clinpract16040065

Authors: Hyunhwa Lee Haehyun Lee Jinyoung Park Jessica Gill

Background: Mild traumatic brain injury (mTBI) is frequently associated with persistent cognitive and psychosocial symptoms, yet biological correlates of recovery remain poorly understood, particularly among Asian and Pacific Islander (API) populations. Pre-injury psychosocial adversity may further shape post-injury recovery trajectories. This pilot study examined associations between participation in a 2-week, home-based, dual-task cognitive–walking intervention (Daily Brain Exercise; DBE) and changes in cognitive, psychological, and salivary microRNA (miRNAs) measures among APIs with and without a self-reported history of mTBI. Methods: API participants completed remote cognitive testing (CNS Vital Signs), psychosocial assessments (Neuro-QoL), and saliva collection before and after DBE participation. Salivary RNA was purified, and miRNA expression was profiled using nCounter® Human v3 miRNA Expression Panels (NanoString). Differential expression analyses were conducted using ROSALIND® platform (OnRamp Bioinformatics, San Diego, CA, USA), a cloud-based bioinformatics analysis system, to calculate fold changes and p-values. Pre-injury psychosocial adversity was assessed via the Trauma History Screen and examined descriptively as a contextual modifier of functional outcomes. Results: Twenty-one APIs (mean age 22.9 years; 76.7% female) were enrolled, including 14 individuals with a self-reported history of mTBI (mean 4.64 years post-injury; 50% with multiple injuries). Following DBE participation, increases in cognitive flexibility and executive function scores were observed in both mTBI and control groups. Additional increases in psychomotor speed, processing speed, sleep disturbance, and depressive symptoms were observed descriptively within the mTBI group. Subgroup analyses suggested variability in pre–post patterns across combinations of mTBI history and pre-injury psychosocial adversity. Exploratory miRNA analyses identified seven miRNAs that were differentially expressed in the mTBI group following DBE (unadjusted p < 0.005), including hsa-miR-7-5p, previously reported in association with neurodevelopmental and neurological pathways. Conclusions: In this pilot, feasibility-focused study, participation in a brief, home-based, dual-task intervention was associated with descriptive changes in selected cognitive and psychosocial measures among APIs, particularly those with a history of mTBI and pre-injury adversity. The observed subgroup patterns warrant confirmation in adequately powered, controlled studies. Exploratory changes in salivary miRNAs co-occurred with functional improvements, thus generating a hypothesis for a future investigation.

Clinics and Practice doi: 10.3390/clinpract16040064

Authors: Maria E. Ramos-Nino

Background: Herpes simplex virus (HSV), Epstein–Barr virus (EBV), and cytomegalovirus (CMV) establish lifelong latency in sensory neurons, lymphoid tissue, and myeloid–endothelial cells, respectively. A substantial proportion of adults worldwide are infected with all three viruses and may experience concurrent herpesvirus latency, yet they have largely been studied independently. This review examined whether latent and intermittently reactivating herpesviruses share overlapping inflammatory signatures and whether their combined presence contributes to chronic inflammatory burden. Methods: A narrative integrative review was conducted using MEDLINE, Embase, and Google Scholar (inception–October 2025). Evidence from thirty-one cohort studies and mechanistic investigations spanning virology, immunology, neurology, and clinical medicine was synthesized. Results: Herpesvirus reactivation rates ranged from 23% in general Intensive Care Unit (ICU) populations to 85% in severe COVID-19. Concurrent reactivation of multiple viruses occurred in 34–63% of critically ill patients and was associated with worse clinical outcomes. Notably, simultaneous CMV and EBV reactivation independently predicted mortality (adjusted hazard ratio, 3.17; 95% CI, 1.41–7.13). Across infections, overlapping inflammatory biomarkers, including IL-6, TNF-α, CRP, and PGE2, were consistently elevated, reflecting convergent activation of IFN and NF-κB signaling pathways. Mechanistic studies suggest cross-compartment immune priming, where CMV-driven T-cell exhaustion facilitates EBV reactivation, and viral cytokine signaling enhances HSV-associated neuroinflammation. Conclusions: HSV, EBV, and CMV triple latency may represent an underrecognized contributor to chronic inflammation in immunocompetent hosts. Understanding this multi-virus inflammatory network may inform mechanistic research, biomarker-guided risk stratification, and therapeutic strategies targeting convergent inflammatory pathways. Prospective interventional studies incorporating concurrent multi-virus monitoring are needed to clarify causal relationships.

Clinics and Practice doi: 10.3390/clinpract16030063

Authors: Laurence Boillat Laure Pache-Wannaz Guillaume Maitre Frida Rizzati Maria Pérez Marin Vivianne Chanez Stefano Di Bernardo Maria-Helena Perez

Background: Low cardiac output syndrome (LCOS) is a significant cause of postoperative morbidity and mortality in children with congenital heart disease. Prophylactic levosimendan is increasingly used to prevent LCOS, but its superiority to other strategies remains unproven. Based on the pharmacokinetics of levosimendan, we hypothesize that preoperative administration is beneficial for preventing LCOS in a specifically at-risk population. Methods: This is a retrospective single-center cohort study in a tertiary pediatric intensive care unit. All patients under one year of age undergoing surgery for congenital heart disease using cardiopulmonary bypass and receiving levosimendan within 24 h before or after surgery were included and classified into two groups: preoperative and postoperative administration. Results: Overall, 107 patients were included. Fifty-three patients (49.5%) received levosimendan before surgery, with significantly lower mortality, fewer LCOS markers, and lower LCOS scores compared to patients receiving levosimendan after surgery. Although not significant, the use of extracorporeal membrane oxygenation, renal replacement therapy, and temperature control was also lower in the preoperative group. There was no difference in mechanical ventilation duration and length of stay. Conclusions: Preoperative administration of levosimendan seems associated with a lower incidence of LCOS and reduced mortality in high-risk children with congenital heart surgery.

Clinics and Practice doi: 10.3390/clinpract16030062

Authors: Filippo Murina Cecilia Fochesato Dario Recalcati Valeria Savasi

Background/Objectives: More than 50% of adult women experience at least one urinary tract infection (UTI) during their lifetime, and approximately 25% develop recurrent UTIs (rUTIs), defined as ≥2 episodes within six months. Management of rUTI is challenging and often requires long-term, multimodal preventive strategies. Escherichia coli Nissle 1917 (EcN) is a non-pathogenic probiotic strain with demonstrated antagonistic activity against pathogenic enterobacteria. This study evaluated the efficacy and safety of EcN in preventing symptomatic recurrences in premenopausal women with rUTI. Methods: In this prospective observational study, 40 premenopausal women with rUTI were enrolled. Twenty patients received EcN prophylaxis (twice daily for four weeks, followed by once daily for eight weeks), while 20 patients received no prophylaxis and served as controls. Patients were followed for six months (three months of treatment and three months post-treatment). The primary outcome was the frequency of symptomatic rUTI episodes during follow-up. Results: Forty patients were analyzed (20 EcN; 20 controls). During the six-month observation period, 55% (11/20) of patients in the EcN group remained UTI-free compared with 35% (7/20) in the control group. Two patients (10%) in the EcN group experienced a single recurrence versus three (15%) in the control group. Recurrent episodes (≥2 UTIs) occurred in 35% (7/20) of EcN-treated patients compared with 50% (10/20) of controls. Overall, EcN prophylaxis was associated with a lower proportion of patients experiencing multiple recurrences. Conclusions: Prophylaxis with E. coli Nissle 1917 was associated with a reduced rate of recurrent UTIs compared with no prophylaxis in premenopausal women, supporting its potential role as a non-antibiotic preventive strategy in rUTI management.

Clinics and Practice doi: 10.3390/clinpract16030061

Authors: Alessandro Guffanti Matteo Leonardi Natascia Brondino Bernardo Dell’Osso Vassilis Martiadis Miriam Olivola

Introduction: Major depressive disorder (MDD) is a leading cause of disability worldwide and contributes significantly to the global burden of disease. Recent data show an increasing prevalence of treatment-resistant depression (TRD). Patients with autism spectrum disorder (ASD) often exhibit MDD as a comorbidity and it is often resistant to conventional treatments. ASD determines emotional dysregulation and a reduced ability to understand mental states (mentalization). These features can lead to suicidal ideation and/or behavior. Intranasal esketamine may offer a novel therapeutic option for this population. Methods: This case series focuses on the clinical response to intranasal esketamine in patients with autism and TRD; esketamine is approved in Italy as an add-on therapy in TRD, so our case study is based on an in-label treatment. Three young patients (n = 3, F/M 2:1, age range 20–25 y) with light to moderate autism (Level 1 or 2) were treated. Esketamine was administered in augmentation with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in accordance with EMA/AIFA guidelines. A structured follow-up protocol was set to monitor depressive symptoms, social cognition, and mentalization. Follow-up during treatment was maintained for six months, and psychometric evaluations were performed at six time points: baseline (T0), 1 week (T1), 1 month (T2), 2 months (T3), 3 months (T4), and 6 months (T5). Also, subjective quality of life was investigated before and after the observation period. Results: Despite differences in clinical profile, all patients showed good efficacy of esketamine in reducing depressive symptoms: two patients experienced clinical remission at T5 (MADRS < 10), one patient showed partial response (dMADRS = 43.24%). No major side effects were reported. Significant improvements were observed after the first week of treatment (P1: MADRS_T0 = 37, MADRS_T1 = 12; P2: MADRS_T0 = 32, MADRS_T1 = 21; P3: MADRS_T0 = 25, MADRS_T1 = 12). Depressive relapses occurred (e.g., P1, T3–T4), but they were not associated with hospitalizations and/or suicidal attempts. Suicidal ideation, when present, decreased by the end of the follow-up period. Lack of mentalization and in social cognition was noted, with just mild improvements during therapy. Subjective quality of life improved significantly for all patients (P1: 28% at T0, 73% at T5. P2: 25% at T0, 71% at T5. P3: 35% at T0, 80% at T5). Conclusions: Intranasal esketamine showed a favorable efficacy and safety in these three cases of TRD in comorbidity with ASD (at six months: total remission = 66.66%, partial remission = 33.33%, inefficacy = 0%, drop-out = 0, severe adverse events = 0). Besides improvements in depressive symptoms, esketamine was associated with a constant decrease in suicidal thoughts. A case series is unfit to form statistical conclusions; preliminary data warrant further investigation in randomized controlled studies to validate the therapeutic potential of esketamine in this population.

Clinics and Practice doi: 10.3390/clinpract16030060

Authors: Jissy Cyriac Richa Sood

Background and Objectives: Genitourinary syndrome of menopause (GSM), previously known as vulvovaginal atrophy, is a chronic, progressive hypoestrogenic condition affecting vulvovaginal, urinary and sexual health in women. Common symptoms include vaginal dryness, itching, dyspareunia, urinary urgency and recurrent urinary tract infections (UTIs). Despite the high prevalence, GSM is underdiagnosed and undertreated, thereby negatively impacting women’s quality of life. To illustrate the practical aspects of GSM diagnosis and provide evidence-based management, we present a case-based narrative review synthesizing recently published, high-quality evidence. Materials and Methods: Evidence was drawn from multiple sources through targeted searches of databases, and included the 2025 AUA/SUFU/AUGS guideline (AUA), the 2024 NICE network meta-analyses (NICE), a 2025 systematic review/meta-analysis in breast-cancer survivors, the 2020 Menopause Society GSM Position Statement, the 2018 NAMS/ISSWSH breast cancer consensus, several primary source citations and other high quality peer-reviewed publications. Results: Five illustrative composite case vignettes of GSM are presented to highlight the evaluation strategy and evidence-supported treatment choices. Nonhormonal options are the first line treatments for mild GSM symptoms, either with or without the addition of vaginal estrogen therapy. For moderate to severe GSM, low-dose vaginal estrogen, vaginal DHEA, and ospemifene are all effective FDA-approved options. In breast cancer survivors, individualized decisions with oncology input are warranted. Maximal caution and a shared decision-making approach is required for women using Aromatase Inhibitors (AIs) for breast cancer risk reduction when choosing treatments for GSM. Conclusions: Treating GSM improves vaginal, sexual and urinary outcomes and quality of life of women. Clinicians need to proactively screen for GSM and offer evidence-based treatment options. The treatment decisions in breast cancer survivors are nuanced, requiring a shared-decision approach.

Clinics and Practice doi: 10.3390/clinpract16030059

Authors: Andreea-Talida Tirziu Maria-Alexandra Preda Aimee Rodica Chis Ionela-Iasmina Yasar Norberth-Istvan Varga Florin George Horhat Mihnea Munteanu Rosca Cosmin

Background/Objectives: The ocular surface is continuously exposed to microorganisms, and disruption of host–microbial balance may lead to infection or postoperative complications. Increasing antimicrobial resistance and biofilm formation have highlighted the need for alternative or complementary non-antibiotic strategies to control ocular surface microbial burden. Liposomal ozonated oil eyedrops have demonstrated antimicrobial and antibiofilm activity in preclinical and preliminary clinical studies. The aim of this study was to evaluate changes in ocular surface microbiological culture results before and after treatment with liposomal ozonated oil eyedrops in a real-world clinical setting. Methods: This was a prospective, observational, real-world pre–post study including 101 eyes from 101 patients undergoing ocular surface microbiological sampling in routine clinical practice. Two samples were obtained per patient: Sample I immediately before treatment and Sample II at the routine follow-up visit after short-course treatment with liposomal ozonated oil eyedrops (1 drop, four times daily, for 4 days). The interval between samples ranged from 3 to 5 days (median 3 days). Microbiological cultures were classified as positive or showing no growth. Paired changes in culture positivity were analyzed using McNemar’s exact test. Results: At baseline, 87 of 101 samples (86.1%) yielded positive cultures, while 14 (13.9%) showed no growth. Following treatment, culture positivity decreased to 11 of 101 samples (10.9%), with 90 samples (89.1%) showing no growth. Among baseline-positive samples, microbiological clearance was observed in 76 cases (87.4%). No cases converted from culture-negative to culture-positive at follow-up. The reduction in culture positivity after treatment was statistically significant (McNemar’s exact test, p < 0.001). Recent antibiotic exposure within 14 days prior to baseline sampling was reported in 8 patients (7.9%). Persistent positive cultures were observed in a minority of cases and were mainly associated with common ocular surface pathogens. Conclusions: In routine clinical practice, short-term treatment with liposomal ozonated oil eyedrops was associated with a significant reduction in ocular surface culture positivity over a short follow-up interval.

Clinics and Practice doi: 10.3390/clinpract16030058

Authors: Maria Spyraki Evanthia Dimitriou Panagiotis Antzoulas Georgios Karpetas Francesk Mulita Vasileios Leivaditis Ejona Shaska John Lakoumentas Diamanto Aretha Andreas Panagopoulos

Background: Delirium is a frequent and serious complication in elderly patients with hip fractures and is associated with adverse outcomes. Early identification requires a brief and reliable screening tool suitable for routine clinical practice. The 4 ‘A’s Test (4AT) is a rapid instrument for delirium detection that requires minimal training. Objective: To translate, culturally adapt, and validate the Greek version of the 4AT in elderly patients with hip fractures. Methods: A total of 103 patients aged ≥65 years who were admitted with hip fracture were enrolled. The 4AT was translated using a forward–backward translation process and culturally adapted according to established guidelines. Delirium diagnosis was established using DSM-5 criteria by trained clinicians, serving as the reference standard. The 4AT was administered independently within 3 h. Diagnostic accuracy was assessed by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). The optimal cut-off was determined using Youden’s index. Results: At a cut-off score ≥4, the Greek 4AT demonstrated a sensitivity of 87.5% and specificity of 91.1%, with PPV 75% and NPV 96%. The AUC was 0.94, indicating excellent diagnostic performance. Conclusions: The Greek version of the 4AT is a valid and reliable screening tool for detecting delirium in elderly patients with hip fractures.

Clinics and Practice doi: 10.3390/clinpract16030057

Authors: Ivana Pantic Nikola Grubor Sofija Lugonja Nina Rajovic Svetlana Miltenovic Marija Brankovic Tijana Gmizic Tamara Milovanovic

Background and Aims: Chronic liver diseases (CLD) represent a significant healthcare burden, mostly due to late diagnosis and numerous co-morbidities. We evaluated the effect of co-morbidities, cirrhosis, and disease etiology on hospitalization duration. Methods: Hospitalizations due to alcohol-related, viral, autoimmune, and overlapping liver disease in Belgrade, Serbia (2016–2022), were identified using pre-defined discharge codes. We investigated the hospitalization trend descriptively by plotting the relative mean change in the hospitalization length against time. Assuming the covariate relationship in the directed acyclic graph, we estimated the direct causal effect of the diagnosis type on the length of stay (LOS) by fitting pre-specified Bayesian distributional lognormal models based on domain knowledge. We conducted a post hoc analysis of the impact of cirrhosis on LOS per primary diagnosis. Results: The empirical data show a decrease in the estimated average LOS (8.25–5.51 days). For the same period, the median LOS decreased (4 days (IQR 0–12) to 1 day (IQR 1–7)). In 2021, the share of short-term hospitalizations rose to 46.94%, while the median long-term hospitalization peaked at 11.5 days (IQR 7–21). The expected LOS was the highest for the primary diagnosis of autoimmune liver disease (15.89, 95% CI [14.74, 17.2] days), followed by alcohol-related liver disease (14.22, 95% CI [13.68, 14.79] days). The largest impact of cirrhosis on LOS was observed among patients hospitalized due to viral disease (4.19, 95% CI [2.29, 6.33] days). Conclusions: The presence of co-morbidities and cirrhosis significantly affects LOS. In order to provide better treatment and reduce healthcare costs, there is the need to detect liver disease at earlier stages and better manage its associated co-morbidities.

Clinics and Practice doi: 10.3390/clinpract16030056

Authors: Ioana Ioniță Mădălina Iuliana Mușat Bogdan Cătălin Adela Magdalena Ciobanu

Background/Objectives: Gambling disorder (GD) is a behavioral addiction characterized by persistent and repetitive gambling behaviors that cause significant psychological distress and functional impairment. Increasing evidence indicates that difficulties in emotion regulation are a key factor in the development and persistence of GD. This systematic review aimed to summarize and critically evaluate the existing literature on the relationship between emotion regulation strategies and gambling disorder, with a specific focus on studies using the Emotion Regulation Questionnaire (ERQ) and the Cognitive Emotion Regulation Questionnaire (CERQ). Methods: The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. Systematic searches were performed in PubMed and Scopus databases for studies published between 25 October 2015 and 25 October 2025. The methodological quality and risk of bias of the included studies were evaluated using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist and JBI Checklist for Randomized Controlled Trials. Data extraction and synthesis were performed manually by two independent reviewers. Eligible studies included adult participants (≥18 years) diagnosed with gambling disorder or pathological gambling and using the ERQ or CERQ to assess emotion regulation. Results: Nine studies met the inclusion criteria, comprising a total of 607 patients with GD. Across studies, individuals with GD consistently showed reduced cognitive reappraisal, greater expressive suppression, and higher use of maladaptive cognitive strategies such as rumination, catastrophizing, and self-blame. All studies identified impulsivity, emotion dysregulation, alexithymia, or gambling-related cognitive distortions as significant predictors of gambling severity. Neuroimaging evidence from one study further revealed altered activation of frontal regions during negative emotion regulation. Conclusions: This review highlights the central role of emotion regulation in GD. However, the limited available ERQ/CERQ studies in GD were mostly cross-sectional, limiting causal inferences. Second, samples were predominantly male, reducing generalizability to women. Finally, only one study used neurobiological measures, hindering integration of self-report and neural data. These findings emphasize the importance of integrating emotion regulation-based interventions within therapeutic programs for gambling disorder, with ERQ and CERQ being useful tools to assess the pathology.

Clinics and Practice doi: 10.3390/clinpract16030055

Authors: Alberto Cordero Mª Amparo Quintanilla Cristina Torres Natalia López Carles Bodí Germán Bixquert José Mª Lopez-Ayala

Introduction: Clinical diagnosis of chronic heart failure (HF) in ambulatory patients can be difficult. Echocardiography is the most widespread diagnostic imaging technique, although the usefulness of the global longitudinal strain (GLS) of the left ventricle (LV) in this clinical setting is less clear. Methods: We performed a cross-sectional study of stable outpatients and GLS was obtained with an automatic software that uses the three apical planes of the LV. We analyzed the improvement of the diagnostic capacity of including GLS above all the clinical and echocardiographic parameters using reclassification indexes. Results: We included 1362 patients, including 12.9% with HF who presented lower values of ejection fraction (EF) and GLS and worse diastolic function. Most patients (92.8%) with HF had a GLS < −14 as compared to patients without HF (36.1%). LV EF (OR: 0.93) and GLS (OR: 1.27 CI 95% 1.20–1.35) were associated with the presence of HF. The AUC was significantly higher (p < 0.001) in the logistic model that included GLS vs. without GLS, and the reclassification index for GLS was 19.8%. GLS was more affected in patients with HFpEF vs. controls as well as diastolic function parameters. The logistic regression model only identified age (OR: 1.07 95% CI 1.02–1.06) and GLS (OR: 1.29 95% CI 1.21–1.38) as independently associated with the presence of HFpEF. The AUC of the model for the presence of HFpEF with GLS was significantly higher (p < 0.01). The reclassification index for GLS was 38.8%. Conclusions: LV GLS assessment increased the diagnostic discrimination of chronic HF in stable patients.

Clinics and Practice doi: 10.3390/clinpract16030054

Authors: Giuseppe Cota Gaetano Scaramozzino Marco Chiesa Lelio Gennaro Maurizio Pascadopoli Andrea Scribante Marco Colombo

Background: Dental radiographs are essential for diagnosis and treatment planning in modern dentistry. However, their manual interpretation is time-consuming and subject to variability, highlighting the need for automated tools to improve efficiency and consistency. This study aims to validate ORTHOSEG, a deep learning-based system designed to automate the segmentation of anatomical, pathological, and non-pathological elements in radiographs, including orthopantomograms, bitewings, and periapical images. Methods: ORTHOSEG’s performance was evaluated using a rigorously curated dataset of 150 dental radiographs, including 50 orthopantomograms, 50 bitewings, and 50 periapical images, with manual annotations by expert clinicians serving as the ground truth. The system’s segmentation performance was assessed using standard evaluation metrics, including mean Dice Similarity Coefficient (mDSC) and mean Intersection over Union (mIoU), and inference time was also recorded. Results: The system achieved high accuracy, with mDSC and mIoU values of 0.635 ± 0.233 and 0.576 ± 0.214, respectively. In particular for orthopantomograms, it achieved an mDSC of 0.756 ± 0.174 and an mIoU of 0.684 ± 0.172, surpassing existing benchmarks. Its segmentation capabilities extend to approximately 70 distinct elements, underscoring its comprehensive utility. The system demonstrated efficient computational performance, with processing times of 19.745 ± 3.625 s for orthopantomograms, 8.467 ± 0.903 s for bitewings, and 5.653 ± 0.897 s for periapical radiographs on standard clinical hardware. Conclusions: ORTHOSEG demonstrates efficiency suitable for integration into routine workflows. This study confirms ORTHOSEG’s reliability and potential to improve diagnostic workflows, offering clinicians a valuable tool for faster and more detailed radiograph analysis. Future research will focus on extending validation across diverse clinical scenarios to ensure broader applicability. However, this study has limitations, including the use of a dataset derived from a European population and the absence of usability and clinical workflow evaluation, which should be addressed in future studies.

Clinics and Practice doi: 10.3390/clinpract16030053

Authors: Eirini Stavrou Georgios Vasilopoulos Dionyssios Leftheriotis Panagiota Flevari Maria Polikandrioti

Background/Objectives: Permanent cardiac pacemakers (PPMs) are small electronic implanted devices that regulate cardiac rhythm. Measurement of quality of life (QoL) serves as a powerful tool for gaining in-depth insights into pacing therapy and ultimately guiding patient-centered management strategies. The aim of the present study was to evaluate factors affecting QoL among PPM patients by applying the two generic questionnaires: SF-36 and EQ-5D-5L. Materials and Methods: A total of 120 patients with PPM were enrolled. QoL data were collected through interviews using the 36-Item Short Form Health Survey (SF-36) and the Euro QoL 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L). Patients’ characteristics were also recorded. Results: The majority of participants were male (54.2%), retired (83.3%) residents in urban areas (75.5%), had a DDD pacemaker (82.5%), had rate response programmed on (77.5%), and had comorbidities (83.3%). Regarding QoL measured by SF-36, the Physical Component Summary Score (PCS) was significantly associated with programming rate response in their pacemaker (p = 0.046), comorbidities (p = 0.047), and the NYHA functional class (p = 0.047). The Mental Component Summary Score (MCS) was significantly associated with sex (p = 0.034), place of residence (p = 0.003), NYHA functional class (p = 0.001), and patients’ level of information about the device (p = 0.039). Patients’ QoL, as measured by the EQ-5D-5L, was significantly associated with sex (p = 0.001), age (p = 0.019), occupation (p = 0.040), pacing mode (p = 0.034), comorbidities (p = 0.019), NYHA functional class (p = 0.047), and level of information about the device (p = 0.005). Conclusions: NYHA functional class, comorbidities, and level of information as reported by patients were the factors associated with QoL, as shown by the two scales. All three factors guide a personalized care plan since NYHA class shows the burden of disease, comorbidities add to the complexity, and patient information determines the effectiveness of management.

Clinics and Practice doi: 10.3390/clinpract16030052

Authors: Yazan Jumah Alalwani Munira Abdullah Aldossari Layan Adeeb Alzahrani Nouf Ibrahim Alhatlani Sarah Musaad Albarrak Waleed Khalid Moosa Raghad Ali Aloufi Ibtisam Heji AlBader Sadeem Khalid Almulhim Nurah Jamel Alnbi Leen Awad Alkahtani Fatimah Mohammed Alsayoud Ahmed Y. Azzam Ghada Fouad Al Yousif

Introduction: Falls and subsequent fractures represent a major public health concern among older adults. While fall prevention interventions have demonstrated efficacy in reducing falls, their impact on fracture outcomes remains unclear. Methods: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. We searched multiple databases up to 7 June 2025 for studies investigating fall prevention interventions and fracture outcomes in community-dwelling older adults. A primary outcome was hip fractures; secondary outcomes included any fractures, falls, and serious fall injuries. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated, using random-effects meta-analysis where appropriate. Results: Seventeen studies were included, spanning over 25,000 participants. Interventions included exercise programs, multifactorial approaches, medication optimization, and vitamin D supplementation. For hip fractures, only two randomized controlled trials (RCTs) reported extractable outcome data (12,489 participants; 132 events); both showed non-significant reductions favoring intervention (RR 0.80–0.87), precluding pooled meta-analysis. For any fractures, five studies (18,519 participants; 1343 events) demonstrated no significant effect (RR 0.91, 95% CI 0.72–1.14; p-value = 0.40) with significant heterogeneity (I2 = 65%). Fall prevention interventions significantly reduced falls across 14 studies. GRADE assessment indicated very low certainty for both hip fractures and any fractures due to limited studies, inconsistency, and imprecision. Conclusions: Current evidence suggests fall prevention interventions may reduce hip fractures but do not significantly prevent fractures overall. Despite consistent fall reduction, the translation to fracture prevention remains uncertain, highlighting the need for integrated interventions targeting both fall risk and bone health.

Clinics and Practice doi: 10.3390/clinpract16030051

Authors: Nicolas Nassar Karim Corbani Rim Bourgi Roland Kmeid Carlos Enrique Cuevas-Suárez Ahmed A. Holiel

Objectives: This systematic review evaluated enamel surface alterations and residual composite following the removal of clear aligner attachments, with particular emphasis on the influence of removal techniques, instrument selection, operator experience, and the use of magnification on enamel preservation and cleaning efficiency. Methods: A comprehensive electronic search was performed in PubMed, Scopus, Embase, Web of Science, and Scielo up to October 2025. In vitro, ex vivo, and clinical studies assessing enamel loss, residual composite, surface roughness, or removal time after clear aligner attachment removal were included. Study selection, data extraction, and methodological assessment followed the PRISMA 2020 guidelines and Cochrane Handbook recommendations. Risk of bias was evaluated using a modified Joanna Briggs Institute checklist for laboratory-based studies. Due to substantial methodological heterogeneity, a narrative synthesis was conducted. Results: Of 656 identified records, three in vitro/ex vivo studies were assessed for eligibility. Reported enamel loss ranged from approximately 15 µm to more than 50 µm, depending on the removal protocol and visualization conditions. Residual composite covered approximately 20–40% of the treated enamel surface. Multi-step protocols combining tungsten carbide burs with silicone polishers under magnification demonstrated the most favorable balance between composite removal efficiency and enamel preservation. Fiberglass burs were associated with smoother enamel surfaces but increased enamel loss, whereas one-step polishing systems (OneGloss, Enhance, SM104) resulted in reduced surface roughness and shorter procedural time. The use of magnification loupes (≥2.5×) consistently improved removal precision and reduced residual composite. Meta-analysis was not feasible due to heterogeneity in outcome measures and testing methodologies. Overall risk of bias was deemed acceptable. Conclusions: Based on the limited number of available in vitro/ex vivo studies, removal of clear aligner attachments appears to be associated with measurable enamel loss and residual composite, largely influenced by the instruments and visualization aids used. Sequential carbide–silicone polishing protocols performed under magnification appear promising based on limited in vitro/ex vivo evidence, demonstrating a favorable balance between composite removal and enamel preservation under controlled laboratory conditions. However, given the scarcity of evidence and absence of clinical trials, these findings cannot be directly extrapolated to routine clinical practice. Further well-designed studies are required before definitive clinical recommendations can be established.

Clinics and Practice doi: 10.3390/clinpract16030050

Authors: Eva van der Meer Ven Yin Leong Gregory M. Peterson Woldesellassie M. Bezabhe

Background: Australian guidelines recommend conducting thyroid function tests (TFTs) before commencing amiodarone and every six months subsequently. This study sought to investigate thyroid monitoring in Australian general practice patients with atrial fibrillation (AF) who commenced amiodarone. Methods: We performed a retrospective observational analysis using a nationwide primary care dataset to examine whether TFTs were conducted according to guidelines following amiodarone initiation in euthyroid patients aged 18 years or older with AF. Secondary outcomes included the prevalence of amiodarone-induced thyroid dysfunction (AITD) and the identification of factors associated with its development. Results: In total, 12,932 patients with AF were included. Of these, 1306 (10.1%) had commenced long-term amiodarone. Two hundred twenty-six (17.3%) of the patients commenced on amiodarone did not have any recorded TFT results during an 18-month follow-up period. During follow-up, 18.1% and 4.4% of patients developed hypothyroidism in the amiodarone-treated and amiodarone-untreated groups, respectively (p < 0.0001). The corresponding values for hyperthyroidism were 7.3% and 2.5% in the amiodarone-treated and amiodarone-untreated groups, respectively (p < 0.0001). In the subset of patients commenced on amiodarone, after controlling for the number of TFTs within the follow-up, the risk factors independently associated with the development of hypothyroidism were baseline thyroid stimulating hormone (TSH) level (adjusted odds ratio/AOR: 3.80 (95% confidence interval: 3.00–4.82)) and the comorbidities heart failure (AOR: 1.64 (1.09–2.46)) and chronic kidney disease (AOR: 2.29 (1.26–4.18)). Baseline TSH (AOR: 0.43 (0.28–0.63)) was significantly associated with the development of hyperthyroidism in patients taking amiodarone. Conclusions: AITD was relatively common, occurring in one-quarter of patients within 18 months of initiation of amiodarone. Increased awareness is required amongst both clinicians and patients of the need for regular thyroid monitoring during therapy with amiodarone.

Clinics and Practice doi: 10.3390/clinpract16030049

Authors: Vanessa Castellanos-Arreola Ana Cristina Castañeda-Márquez Raúl Fernando Guerrero-Castañeda Dulce Milagros Razo-Blanco-Hernández Luís Ricardo Vázquez-García Juan Carlos Fernando Sánchez-Velázquez María del Carmen Velázquez-Núñez María Yazmin Castañeda-Ramírez José Ángel Hernández-Mariano

Background/Objectives: Cardiovascular diseases represent a considerable burden on healthcare systems. In coronary intensive care units (CICU), nursing staff play a key role in the care of critically ill patients. Nursing diagnoses (NDs) based on the NANDA-I (North American Nursing Diagnosis Association-International) taxonomy enable the identification of human responses to various clinical conditions. However, their association with adverse outcomes, such as in-hospital mortality, remains understudied. Therefore, we evaluated the association between NDs and in-hospital mortality in patients with cardiac disease. Methods: A retrospective cohort study was conducted in a tertiary care hospital. The paper clinical records of 195 patients admitted to the CICU for at least 48 h between January 2023 and March 2025 were reviewed. The association of interest was assessed using Poisson regression models adjusted for confounding variables. Results: Mortality was 24.1%. NDs focusing on cardiac and extracardiac responses, such as fluid volume excess (risk ratio [RR] = 2.67; 95% confidence interval [CI] = 1.23, 5.76), impaired cardiac output (RR = 1.84; 95% CI = 1.50, 2.25), risk of shock (RR = 3.12; 95% CI = 1.91, 5.11), risk for impaired cardiovascular function (RR = 2.01; 95% CI = 1.28, 3.17), and impaired gas exchange (RR = 2.67; 95% CI = 1.64, 4.34) were significant predictors of mortality. In contrast, diagnoses such as anxiety (RR = 0.46; 95% CI = 0.23, 0.91), impaired psychological comfort (RR = 0.31; 95% CI = 0.09, 0.95), and risk of unstable glycemia (RR = 0.46; 95% CI = 0.23, 0.91) were associated with a lower risk of death. Conclusions: NDs are independently associated with in-hospital mortality in critically ill patients with cardiac disease and may represent useful clinical markers for risk stratification in intensive care settings.

Clinics and Practice doi: 10.3390/clinpract16030048

Authors: Maria Ladisa Juan Luís Cabanilla-Moruno Lara Estefanía Jiménez-Ortega Manuel Delgado-Calderón Emilio García-Cabrera Julia Romero-Barranca Ángel Vilches-Arenas

Background: During the first wave of the COVID-19 pandemic, the importance of the recognition of vulnerable workers was well-established, but the specific impact of the timing of their recognition remains less understood. Objective: This study evaluates the impact of early recognition of vulnerable healthcare workers (VHCWs) and identifies factors associated with SARS-CoV-2 infection. Methods: We performed a retrospective cohort study at the Virgen Macarena University Hospital (HUVM) in Seville and included employees classified as VHCWs between January 2020 and December 2021. All data, including demographic, occupational, and clinical data, were collected from occupational health records and the Andalusian digital health system. The incidence of COVID-19 was analyzed using descriptive, bivariate statistics, and Cox regression. Results: A total of 471 VHCWs were included. Most of the VHCWs were women (79.8%) with a median age of 50 years. The most common vulnerability criteria were pregnancy (32.9%) and age > 60 (28.7%). During the study period, 58 VHCWs (12.3%) were diagnosed with COVID-19, compared to 18.35% of the general workforce. Recognition of VHCW status after the pandemic was declared was strongly associated with higher infection risk (HR = 48.84; 95% CI: 26.21–90.99; p < 0.001). Conclusions: The timing of vulnerability recognition emerged as the most critical protective factor in this cohort. Healthcare workers whose vulnerability was not proactively identified before the pandemic onset faced a substantially higher risk of infection (HR = 44.68; 95% CI: 26.21–90.99; p < 0.001) compared to those recognized early. These findings underscore that pre-pandemic identification facilitated the immediate implementation of task adaptations and workplace restrictions, effectively mitigating high-risk exposure during the most critical early stages of the crisis.

Clinics and Practice doi: 10.3390/clinpract16030047

Authors: Fabiana Di Duca Giancarlo Biondi Elvira De Rosa Alessandro Venuta Salvatore Di Sarno Alfonso Nardo Bartolomeo Ferrante Giovanni Mazzei Stefano Scippa Immacolata Russo Maria Triassi Paolo Montuori

Background: In recent years, aesthetic medicine and cosmetic surgery have seen significant growth, reflecting changing sociocultural views on beauty and self-care; however, public knowledge and awareness of associated risks remain inconsistent. This study aimed to assess knowledge, attitudes, and behaviours toward aesthetic medicine and cosmetic surgery in a large metropolitan population in Southern Italy using the Knowledge–Attitude–Practice (KAP) framework. Methods: A cross-sectional survey was conducted between June 2021 and January 2022 among 1079 adults aged 18–72 years residing in the metropolitan area of Naples. A structured questionnaire collected socio-demographic data and assessed knowledge, attitudes, and behaviours related to surgical and non-surgical aesthetic procedures. Descriptive statistics and multiple linear regression analyses were performed to identify predictors of knowledge, attitudes, and behaviours. Results: Overall, 66.8% of participants reported having undergone general beauty treatments, while 9.8% declared the use of cosmetic medicine procedures. A total of 5.1% had undergone botulinum toxin treatments, 11% reported filler injections, and 9.8% had experienced plastic surgery. A majority had strong knowledge, especially on non-surgical procedures, but there were gaps in their knowledge on side effects, regulations, age limits, and qualifications. Most viewed appearance as important, though with critical views of excessive aesthetic treatments and claimed limited social media influence. Female sex and parental status were positively associated with aesthetic behaviours, while attitudes emerged as the strongest predictor of engagement. Conclusions: Aesthetic practices are widely accepted within this urban population, yet important informational deficiencies persist. Targeted educational interventions based on the KAP framework are warranted to enhance health literacy, promote safe decision-making, and foster realistic expectations regarding aesthetic medicine and cosmetic surgery.

Clinics and Practice doi: 10.3390/clinpract16030046

Authors: Annunziata Dattola Raimondo Rossi Giuseppe Rizzuto Giacomo Caldarola Eleonora De Luca Viviana Lora Domenico Giordano Severino Persechino Claudio Bonifati Diego Orsini Dario Graceffa Arianna Zangrilli Gianluca Pagnanelli Paola Tribuzi Annamaria Mazzotta Gaia Moretta Adriana Micheli Alessia Provini Salvatore Zanframundo Vincenzo Panasiti Giovanni Pellacani Concetta Potenza Antonio Giovanni Richetta Nicoletta Bernardini

Objectives: To evaluate the impact of non-invasive imaging techniques such as dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) to monitor the efficacy of risankizumab on plaque psoriasis of the legs by analyzing morpho-histological changes. Materials and Methods: Multicentre, real-world retrospective study involving 37 adults with moderate-to-severe plaque psoriasis. Assessments performed during routine visits at baseline, Week 4 and Week 12 included clinical response, dermoscopy, RCM and OCT. Results: Thirty-seven patients were included (mean age 52.1 years; 54% male; mean BMI 27.0 kg/m2). Dermoscopy showed progressive vascular normalization: at Week 12, 94.29% of lesions had minimal or no vascular pattern. White and yellow scales decreased significantly. On RCM, dilated vessels, inflammatory infiltrate, and papillomatosis progressively normalized. OCT showed reduction in epidermal and stratum corneum thickness and a decline in vascular intensity at multiple depths. Baseline haemorrhagic dots predicted early complete response: 44.8% of lesions with dots achieved complete clearance at Week 4 versus 0% without. Conclusions: Risankizumab induced rapid, significant regression of psoriatic changes, normalizing vascular patterns and skin architecture and reducing epidermal thickness. Findings support its efficacy and rapid onset of action in difficult-to-treat areas and highlight the value of non-invasive imaging for monitoring.

Clinics and Practice doi: 10.3390/clinpract16030045

Authors: Waleed Alharbi Turki Alasmari Najla Al Rasheed Jamila A. Alonazi Naif K. Alaqil Meshari Al Samih Nawaf S. Alzahrani Abdulaziz Bin Akrish Soliman Alaraidh

Background/Objectives: Inflammatory bowel disease (IBD) is associated with significant morbidity worldwide. While global epidemiological trends are well-documented, data on the clinical and demographic characteristics of IBD patients in Saudi Arabia remain limited. This study aimed to evaluate the distribution of multimorbidity among IBD patients in a tertiary Saudi hospital and assess associated clinical features and outcomes. Methods: A retrospective cross-sectional study of IBD patients treated at the National Guard Hospital over a seven-year period was conducted. Data on demographics, body mass indices (BMIs), hospitalizations, comorbidities, complications, and surgical interventions were extracted from medical records. Associations between categorical and continuous variables were analyzed using chi-square and t-tests, respectively, with significance being set to p < 0.05. Results: A total of 465 patients were included: 54.6% had Crohn’s disease (CD) and 45.4% had ulcerative colitis (UC). CD predominated in males (60.6%), while UC was more common in females (55.5%, p = 0.001). BMI distribution differed significantly between groups (p = 0.004). Hospital admission rates and length of stay were higher among CD patients (p = 0.032). CD patients experienced greater complication rates, including fistulas (41.3% vs. 7.1%, p < 0.001) and strictures (26.1% vs. 1.4%, p < 0.001). Surgical interventions such as fistulotomy (4.3% vs. 0.5%, p = 0.009) and stricturoplasty (9.1% vs. 1.9%, p = 0.001) were more frequent in patients with CD. Conclusions: This study characterizes IBD patients in Saudi Arabia, highlighting gender differences, BMI variations, and the greater severity of CD compared with UC. The higher rates of complications and surgical interventions among CD patients emphasize the need for tailored management strategies. Future prospective studies are warranted to investigate disease progression and optimize care for this population.

Clinics and Practice doi: 10.3390/clinpract16020044

Authors: John K. Triantafillidis Konstantinos Malgarinos Loukas Kaklamanis Emmanouil Kritsotakis Victoria Polydorou Konstantinos Pantos Konstantinos Sfakianoudis Agni Pantou Konstantinos Bramis Manousos M. Konstantoulakis Apostolos E. Papalois

Background: Ulcerative colitis (UC) and sarcoidosis are chronic inflammatory diseases that share immunological pathways but rarely coexist. The increasing use of biologic agents in inflammatory bowel disease (IBD) has raised concerns regarding paradoxical inflammatory manifestations, including sarcoidosis-like reactions. Case presentation: We report the case of a 63-year-old man with long-standing UC treated with vedolizumab who developed systemic sarcoidosis characterized by bilateral hilar lymphadenopathy, mediastinal and abdominal lymph node enlargement, pulmonary involvement, and erythema nodosum. Extensive diagnostic work-up, including imaging and histopathology, confirmed non-necrotizing granulomatous disease consistent with sarcoidosis, while alternative infectious, malignant, and drug-induced causes were excluded. Vedolizumab was temporarily discontinued, leading to UC relapse, and subsequently reintroduced with rapid clinical remission of UC. Discussion: Sarcoidosis remained clinically and radiologically stable despite vedolizumab re-initiation, suggesting a coincidental association rather than a direct causal relationship. This case highlights the diagnostic challenges and therapeutic dilemmas in patients with immune-mediated diseases receiving biologic therapy. Conclusion: The coexistence of UC and sarcoidosis during vedolizumab therapy is rare. Although causality cannot be established, our findings suggest that vedolizumab may be safely continued in selected patients under close multidisciplinary monitoring.

Clinics and Practice doi: 10.3390/clinpract16020043

Authors: Rosita Rupa Anastasios Tsogkas Dalibor Bockelmann Christopher Nimsky Benjamin Voellger

Background/Objectives: To estimate, against the background of the upcoming German healthcare reform, current access to neurosurgery for patients in Germany, and to derive improvement strategies from geographic information mapping. Methods: We defined access to neurosurgery on a geographical basis as the sum of all points from which one can reach a neurosurgical department within 40 min by car (A2N40). We identified 182 departments of neurosurgery, and we retrieved population numbers and geodetic information from open sources. We processed data and conducted statistical analyses in R. Results: Population density and A2N40 per square kilometer were significantly positively correlated (Spearman’s rho = 0.82, p = 0.0001). Population density is significantly lower (Wilcoxon rank sum test, p = 0.009) and A2N40 per square kilometer is significantly worse (Wilcoxon rank sum test, p = 0.005) in the new federal states (without Berlin) as compared to the rest of the country. Geographic information mapping yielded 3 distinct improvement strategies. Conclusions: In Germany, population density and A2N40 per square kilometer are significantly positively correlated, with significantly less A2N40 per square kilometer in the new federal states. Geographic mapping may inform tailored regional improvement policies.

Clinics and Practice doi: 10.3390/clinpract16020042

Authors: Adrian C. Chen Amit S. Rao Alisha Oropallo

Introduction: Chronic wounds affect approximately six million people in the United States. Despite established multidisciplinary wound care protocols, patient adherence to follow-up care remains suboptimal. We aimed to understand the impact of social drivers of health on patient decision-making for improving wound care follow-up adherence. Methods: We conducted a retrospective review of all hospitalized patients who consulted in-house wound care staff at a tertiary care center between August 2017 and June 2020, regardless of primary admission diagnosis. Referred patients received standardized care from a multidisciplinary team at an outpatient wound care facility. Primary endpoints were pre-discharge scheduling and follow-up rates. Follow-up efficacy was assessed through 90-day hospital readmission rates. Results: Of 444 patients, 205 (46.2%) were readmitted or expired within 90 days. Adjusted analysis identified lack of follow-up care reception as an independent predictor of hospital readmission (hazard ratio 2.39; 95% CI, 1.45–3.89; p < 0.001). Among 156 (35.1%) patients who scheduled follow-up, 110 (70.5%) adhered to their appointment. Patients not scheduling follow-up were older (median age 79 vs. 70 years, p < 0.001), longer hospital stays (median 9 vs. 6 days, p < 0.0001), and more frequently discharged to skilled nursing facilities (47.6% vs. 26.3%, p < 0.0001). Among scheduled patients, skilled nursing home residents demonstrated lower follow-up adherence (OR 0.3; 95% CI, 0.14–0.65; p < 0.01). Conclusions: Pre-hospital discharge communication for scheduling follow ups serves as a critical intervention point in patient decision-making for wound follow-up. Considering the limitations of a retrospective single-center study, we find that pre-discharge education about follow-up scheduling for high-risk groups, including patients ≥ 80 years and skilled nursing facility residents, may improve follow-up adherence and reduce readmissions.

Clinics and Practice doi: 10.3390/clinpract16020041

Authors: Maria Grazia Bocci Giulia Capecchi Antonio Lesci Dorotea Rubino Ilaria Caravella Giorgia Taloni Valerio Sabatini Candido Porcelli Giulia Valeria Stazi Gabriele Garotto Elena Mattiucci Emanuele Nicastri Tommaso Ascoli Bartoli Gaetano Maffongelli Emiliano Cingolani Fabrizio Albarello Giulia Anello Paolo Campioni Stefania Ianniello Daniele Guerino Biasucci

Background: Meningoencephalitis is a complex inflammatory condition of the CNS that can result in significant morbidity and mortality in critically ill adults. Accurate and timely neuromonitoring is essential for guiding management and improving outcomes. This study aimed to descriptively evaluate the prognostic value of early TCCD monitoring, particularly the pulsatility index, and its integration with conventional and perfusion MRI in patients with meningoencephalitis. Methods: We present an observational, retrospective, cohort study involving ten adult patients (median age 56 years, IQR 45.5–68.5; mean 55.9, range 35–76) with neurological syndromes caused by suspected or confirmed infectious meningoencephalitis. Etiologies included bacterial meningitis/meningoencephalitis (50%), viral meningoencephalitis (10%), neurotoxoplasmosis (10%), progressive multifocal leukoencephalopathy (10%), and undetermined origin (20%). Patients underwent TCCD and MRI within 24 h. In five cases, standard MRI sequences were acquired, while in the remaining five, perfusion imaging was performed using Arterial Spin Labelling (ASL). A favorable outcome was defined as survival with neurological recovery (Glasgow Outcome Scale > 5) at ICU discharge. Results: TCCD-derived PI provided valuable information on cerebral hemodynamics. PI values ≤ 1.25 were associated with favorable clinical outcomes and symmetrical MRI findings. Conversely, PI > 1.25 correlated with poor prognosis and often preceded MRI-detectable structural damage. When combined with ASL, PI mirrored the detected perfusion asymmetries and was associated with poor prognosis in fatal cases. Conclusions: Bedside TCCD can offer real-time assessment of cerebrovascular dynamics and, when integrated with conventional and ASL MRI, could enhance the understanding of pathophysiological processes in meningoencephalitis, supporting timely and informed decisions in neurocritical care.

Clinics and Practice doi: 10.3390/clinpract16020040

Authors: Gustavo Christofoletti Gabriela Maria da Silva Béé Otávio Reginato Nathalia Oliveira Rodrigues Sidineia Silva Pinheiro Cavalcante Franco Ana Beatriz Gomes de Souza Pegorare

Background: Previous studies have demonstrated the benefits of virtual reality (VR) as an intervention tool guided by specialists. However, little is known about whether VR may pose risks in uncontrolled environments. Considering its implications for clinics and practice, this study aimed to assess the potential risks of a 3D VR simulation on postural control in young adults. Methods: Seventy-nine community-dwelling young adults completed a VR program using a head-mounted display that simulated a 3D roller-coaster ride while standing. Postural control was assessed using a force platform measuring frontal and lateral sway, center-of-pressure sway area, and frontal and lateral imbalance speed. The assessments were conducted with and without VR. Statistical analyses were performed using paired comparisons. Significance was set at 5%. Effect sizes (ESs) are reported. Results: Engaging in a VR roller-coaster simulation increased the participants’ imbalance in terms of frontal sway (p = 0.001; ES = 0.919), center-of-pressure sway area (p = 0.001; ES = 0.849), frontal imbalance speed (p = 0.001; ES = 0.910), and lateral imbalance speed (p = 0.001; ES = 0.663). No significant difference was observed in the lateral sway (p = 0.383). During VR exposure, 25% of the participants showed a clinically significant increase in postural instability. Despite having normal baseline parameters, participants with higher postural instability showed greater deterioration in postural control during VR exposure than those with lower postural instability. Conclusions: A 3D VR simulation affected several measures of postural control in community-dwelling young adults. Precautions should be taken when engaging in VR without appropriate specialist supervision.

Clinics and Practice doi: 10.3390/clinpract16020039

Authors: Khaled Abdulalem Jonah Teich Erika Martinez Samuel D. Saibil

Background/Objectives: Cancer of unknown primary (CUP) remains a significant challenge in the field of oncology. Despite advances elsewhere in the field, there have been few advances in the treatment of CUP and correspondingly no improvements in patient survival. Recent studies utilizing molecular profiling, including next-generation sequencing (NGS), and molecularly targeted treatment of CUP have shown some promising initial results, but have yet to be integrated into the standard of care in most jurisdictions. This study aimed to assess the use of molecular characterization and targeted treatment of patients with CUP treated at Princess Margaret Cancer Centre (PMCC). Methods: This study is a retrospective audit of patients with CUP treated between January 2019 and April 2024 to build understanding of the accessibility and use of these molecular tools. Results: We found that 82% of the 28 patients identified received NGS analysis, though all received the results late in their disease course and all accessed molecular profiling via either clinical trials, a charitable access programme, or a privately source outside of the hospital network. Only 13% of the patients who received molecular analysis received any modification of care as a result of this profiling, and only as third line of treatment. Conclusions: Our data highlights a lag between current understanding and current practice, and identifies a possible area for improvement of patient care by standardizing the use of molecular analysis in the early workup and targeted therapy in the treatment of CUP.

Clinics and Practice doi: 10.3390/clinpract16020038

Authors: Pavol Vigláš Jan Raupach Aleš Hejčl David Černík Pavla Bradáčová Patrik Matras Filip Cihlář

Objectives: The goal of this study is to establish the incidence of high on-treatment platelet reactivity (HTPR) to aspirin and clopidogrel in patients undergoing carotid stenting and to evaluate the efficacy of ticagrelor and ticlopidine in patients with HTPR to clopidogrel. Methods: In a single institutional setting spanning eight years, every consecutive patient who underwent carotid artery stenting was incorporated into a study. Subsequently, a retrospective analysis of their platelet function was executed. Prevalence of high on-treatment reactivity to aspirin, clopidogrel, ticlopidine and ticagrelor was assessed. Platelet function testing was conducted by light transmission aggregometry and Multiplate®. Results: A total of 216 patients were tested for antiplatelet therapy efficacy. The high on-treatment reactivity to clopidogrel was observed in 68 patients (31.4%). No patients with high on-treatment reactivity to ticagrelor or ticlopidine were observed. There was a significant reduction in platelet reactivity with ticagrelor (p < 0.000) and ticlopidine (p < 0.000) in patients with HTPR to clopidogrel. Conclusions: High on-treatment platelet reactivity to clopidogrel is common in patients undergoing carotid artery stenting. Ticagrelor is a viable alternative to overcome HTPR to clopidogrel. These findings suggest that platelet function testing can identify patients who may benefit from tailored antiplatelet therapy in reducing thromboembolic complications after carotid stenting.

Clinics and Practice doi: 10.3390/clinpract16020037

Authors: Adriana-Luciana Luca Felicia Militaru Mădălina Iuliana Mușat Ion Udriștoiu Eugen Moța

Background/Objectives: Chronic kidney disease (CKD) progresses with the gradual and irreversible loss of renal function. In Romania, given the increasing number of patients undergoing hemodialysis (HD), the prevalence of psychiatric symptoms and disorders in this population has become particularly significant. Although important advances have been made in the management of psychiatric conditions in HD patients, their mental health remains relatively poor. The aim of this study was to observe the severity temporal trends of depression, anxiety and stress symptoms and correlations among HD patients. Methods: A total of 173 patients, underwent a detailed anamnesis, with emphasis dialysis duration, comorbidities and a complex psychiatric evaluation, followed by the application of the Socio-economic Scale (SES-3); Mini Mental State Examination (MMSE); and the Depression, Anxiety and Stress Scale 21R (DASS-21R). The dialysis performance (spKt/V) and Charlson Comorbidity (CCI) indices were provided by DIAVERUM Nephrology and Dialysis Center in Craiova. Results: The severity of depression and anxiety symptoms significantly increased over six months, 0.248 ± 1.432 vs. 0.453 ± 1.488 (p < 0.0001; rrb = 0.296) for depression, and −0.090 ± 1.004 vs. 0.089 ± 1.047 (p < 0.0001; rrb = 0.252) for anxiety; while stress-like symptoms remained stable 0.080 ± 1.318 vs. 0.164 ± 1.357 (p = 0.0661; rrb = 0.123), despite improvements in dialysis adequacy (spKt/V). Depression scores were moderately correlated with anxiety and weakly correlated with stress and spKt/V. Anxiety results were moderately correlated with stress, while both anxiety and stress showed negligible correlations with spKt/V. Clinical variables assessed showed moderate predictive value for psychological outcomes in this cohort. Conclusions: Our study confirms the temporal trend of severity of mental symptoms and their persistence among HD patients, highlighting the urge to integrate mental health screening and intervention programs and a multidisciplinary team adapted for each case.

Clinics and Practice doi: 10.3390/clinpract16020036

Authors: Iva Bešlić Alen Vrtarić Ivana Škrinjar Ema Barac Ana-Karla Vodanović Liborija Lugović-Mihić

Background: For the majority of chronic spontaneous urticaria (CSU) sufferers, nocturnal itch has a profound effect on quality of life (QoL), as it leads to sleep disturbances. To ensure good sleep quality (SQ), the body must produce an adequate amount of melatonin, which regulates the sleep cycle. Methods: This study examines the levels of salivary melatonin in 38 CSU patients and 38 healthy controls, as well as the relationship between CSU severity, QoL and SQ. The Enzyme-Linked Immunosorbent Assay (ELISA), Dermatology Quality of Life Index (DLQI), and Pittsburgh Sleep Quality Index (PSQI) were used to determine salivary melatonin levels, QoL, and SQ. In addition, the CSU participants were given the Urticaria Activity Score (UAS) and the Urticaria Control Test. Results: The median value of salivary melatonin in CSU patients was lower than that in healthy individuals (0.2 vs. 15.985 pg/mL; p < 0.001). A decreased melatonin level was seen in 90% of CSU patients and 18% of healthy individuals. Individuals with lower melatonin levels were significantly more likely to have CSU compared with those with higher melatonin levels (OR = 37.6; 95% CI 10.0–141.1). Melatonin was linearly related to QoL and sleep quality in the whole sample (r = −0.606 and −0.536; p < 0.001) but not in CSU patients. Impaired QoL in patients correlated with itch intensity and the number of hives (r = 0.740 and 0.646). The severity and activity of CSU are linearly related to impaired QoL and sleep quality (r = −0.606 and −0.536; p < 0.001). Sleep quality acts as the mediator of the association between QoL and salivary melatonin, when controlling for the effect of age and gender (B = −0.347; 95% CI = −0.679 to −0.080). Conclusions: The data suggest that melatonin may be more a non-specific marker of sleep disturbance than the severity of CSU. Sleep quality may act as a mediator linking dermatology-related QoL, circadian dysregulation and reduced melatonin secretion.

Clinics and Practice doi: 10.3390/clinpract16020035

Authors: Paul Carroll Alyson Boudreau Haoning Hu Ryan P. Lin Bilal Louzati Eddie Davis

Background: Ledderhose Disease, or plantar fibromatosis, is a fibroproliferative disorder affecting the plantar fascia with limited effective treatment options. Although hyaluronidase has a long history of clinical use, it has not been previously used for Ledderhose Disease. This study explores the use of combined hyaluronidase and triamcinolone acetonide enzymatic injections as a novel and promising technique for managing Ledderhose Disease. Methods: This paper investigates the use of combination therapy with hyaluronidase, triamcinolone acetonide, and lidocaine injections in three patients with Ledderhose Disease. Injection protocols, dosage, frequency, and patient outcomes are all discussed. Additionally, this study explores the underlying mechanisms of hyaluronidase action in Ledderhose Disease, shedding light on its potential to modulate fibrotic tissue and alleviate symptoms. Results: All three patients treated with a series of hyaluronidase, triamcinolone acetonide, and lidocaine anesthetic injections experienced either a significant reduction in or elimination of nodules and associated pain within 6 weeks after initial injection. Patients were asymptomatic at two years follow-up after injections. Conclusions: The combination of hyaluronidase and triamcinolone acetonide injections significantly decreased pain and softened fibromas faster than triamcinolone acetonide injection alone, as explored in previous studies. Large prospective studies are needed to further compare enzymatic injection therapies in the management of Ledderhose Disease.