J. Clin. Med., Volume 15, Issue 2 (January-2 2026) – 514 articles

Background: Primary Biliary Cholangitis (PBC) requires early diagnosis and specialized management to prevent progression to cirrhosis. This study evaluates the awareness levels of Turkish physicians from various specialties regarding the clinical features, diagnostic criteria, and current treatment protocols of PBC. Methods: A multi-regional cross-sectional survey was conducted with 269 physicians across Türkiye. Knowledge levels were assessed through a 28-item instrument covering epidemiology, diagnosis and therapy. Data distribution was non-normal (Skewness: −1.296, Kurtosis: 2.857), necessitating the use of the Kruskal–Wallis H test and Dunn–Bonferroni post hoc procedure for inter-group comparisons. Internal consistency was confirmed with a Cronbach’s alpha of 0.80. Results: The overall mean awareness score was 62.6%. Item-level analysis revealed a near-universal understanding of the non-mandatory role of liver biopsy in diagnosis (99.1%) yet identified a critical knowledge gap regarding second-line therapies, particularly the use of steroids (6.8%). Significant disparities were observed among specialties (p < 0.001). Gastroenterologists (Median: 91.07%) and gastroenterology fellows (Median: 85.71%) exhibited significantly higher proficiency compared to general practitioners (64.29%) and family medicine residents (67.86%). Internal medicine specialists outperformed primary care providers, while no significant differences were found among other subgroups after Bonferroni adjustment. Conclusions: Professional specialization is the primary determinant of PBC awareness. While core diagnostic knowledge is stable, significant gaps exist in pharmacological management among non-specialists. Targeted medical education for primary care physicians is essential to ensure timely referral and optimize patient outcomes. Full article

Background: Stroke and subclinical cerebral ischemia remain important neurological complications of transcatheter aortic valve replacement (TAVR). The Sentinel cerebral embolic protection (CEP) device is designed to capture embolic debris during TAVR, but its impact on clinical and imaging outcomes remains incompletely characterized. Methods: PubMed, Embase, and Cochrane databases were systematically searched for randomized controlled trials (RCTs) comparing Sentinel CEP versus no protection when TAVR was performed. Outcomes of interest included all stroke, disabling stroke, infarct volume by diffusion-weighted MRI in protected and unprotected areas, all-cause mortality, acute kidney injury, and major vascular complications. Risk ratios (RRs) and median differences with 95% confidence intervals (CIs) were calculated using random-effects models and trial sequential analysis (TSA) assessed evidence robustness. Results: Four RCTs including 10,986 patients were analyzed. Sentinel CEP did not significantly reduce clinical stroke (RR 0.88, 95% CI 0.69–1.12) or disabling stroke (RR 0.68, 95% CI 0.41–1.14). Pooled DW-MRI data showed a significant reduction in new ischemic lesion volume within Sentinel CEP-protected territories (difference in medians −75.7 mm³; 95% CI −130.4 to −21.0). Subgroup analyses in elderly, female, and high-surgical-risk patients revealed no benefit with Sentinel CEP. Additionally, TSA indicated that current data are underpowered for definitive conclusions. Conclusions: The Sentinel CEP device during TAVR did not significantly reduce clinical stroke but was associated with lower MRI-detected ischemic lesion volumes compared with no protection. Further adequately powered RCTs integrating clinical and imaging endpoints are needed to define its role in neuroprotection during TAVR. Full article

Background/Objectives: Cellulite is a common aesthetic condition in women, traditionally assessed using visual inspection and palpation-based scales that are inherently subjective. Therefore, image-based methods that may support standardized severity grading are of growing interest. To evaluate infrared thermography as an imaging-based method for grading cellulite severity and to perform methodological validation of a newly developed thermographic classification scale by comparing it with clinical palpation and anthropometric parameters. Methods: This retrospective, non-interventional study analyzed anonymized clinical and thermographic data from 81 women with clinically assessed cellulite. Cellulite severity was evaluated using the Nürnberger–Müller palpation scale and a newly developed five-point thermographic scale based on skin surface temperature differentials and histogram pattern analysis. The associations between the assessment methods were evaluated using ordinal statistical measures, and agreement was assessed using weighted Cohen’s kappa statistics. Results: Thermographic grading demonstrated high agreement with palpation-based assessment, with a percentage agreement of 93.8% and an almost perfect agreement based on weighted Cohen’s κ. A strong ordinal association was observed between the methods. Thermography consistently classified a subset of cases as one grade higher compared with palpation. No statistically significant associations were observed between thermographic grade and body mass index or waist-to-hip ratio. Conclusions: Infrared thermography enables image-based grading of cellulite severity and shows a strong concordance with established palpation scales. The proposed thermographic classification provides preliminary methodological validation of an imaging-based grading approach. Further multicenter studies involving multiple assessors and diverse populations are required to assess reproducibility, specificity, and potential clinical applicability. Full article

Background/Objectives: Pauls Stradins Clinical University Hospital in Riga, Latvia, introduced an ECMO program in 2008. Since the program’s start, countless patients have had their lives saved by this necessary technology. Our goal was to review the ECMO program results and gain insight into the organization’s operations. We wanted not only to assess the program’s efficiency in terms of time, but also to visualize patient outcomes at least a month after decannulation from ECMO and discharge from the hospital. Methods: A retrospective observational study was performed using hospital patient data files from October 2024 to October 2025. The selected patient group was those who had suffered an in-hospital cardiac arrest and successfully had ECMO inserted; this criterion fit fifteen patients. Data were collected on multiple factors, including from collapse to flow time, the number of days spent in the ICU, and post-ECMO complications. Afterwards, the data were analyzed to understand the program’s and patients’ outcomes. Results: Of the fifteen patients analyzed, seven did not survive to hospital discharge. The statistically significant quantitative results were the first lactate levels after ECMO cannulation and the first troponin levels after cardiac arrest. In terms of qualitative results, CHF, survival to ECMO decannulation, cannulation failure, and survival to ICU discharge were statistically significant. Conclusions: The ECMO program at Pauls Stradins Clinical University Hospital provides patients with a necessary technology after an intra-hospital cardiac arrest. This study highlights data about these patients and their outcomes, as well as areas for improvement within the hospital’s ECMO/ECPR program. Full article

Background/Objectives: Isolated cleft lips and/or palates often require orthognathic treatment. Traditional planning based on 2D images and plaster models limits precision; therefore, virtual surgical planning (VSP) and Computer-Aided Design and Computer-Aided Manufacturing (CAD/CAM) technologies are increasingly being used. The aim of this scoping review was to analyze the techniques, outcomes, and gaps in research on VSP in orthognathics for patients with isolated (non-syndromic) clefts. Methods: Searches were conducted in July 2025 in seven databases (including PubMed, Scopus, and Cochrane) without language restrictions, in accordance with the PRISMA guidelines for scoping reviews. Of the 2836 records, 36 publications were eligible after deduplication and full-text screening, and their Level of Evidence (LoE) was assessed using the Oxford CEBM scale. A risk of bias assessment was also conducted according to JBI tools. Results: The identified studies primarily comprised LoE III and IV; there were no systematic reviews or randomized controlled trials (LoE I). Descriptions of bimaxillary procedures and LeFort I osteotomies dominated. The most commonly used software was ProPlan CMF, Dolphin 3D, and Rhinoceros, although other tools have emerged in recent years. The available studies suggest that VSP increases translational and rotational accuracy and facilitates individualized treatment, and bimaxillary procedures bring better functional and aesthetic outcomes in patients with severe maxillary hypoplasia. Conclusions: Despite the growing interest in VSP in orthognathics, the scientific evidence is limited and mostly of lower quality. Well-designed prospective studies are needed to assess the long-term stability, quality of life, and cost-effectiveness of modern technologies. Full article

Background: Complications after proximal humerus osteosynthesis are not uncommon. The aim of this study was to compare the outcomes of osteosynthesis using PHILOS with fresh-frozen femoral head allograft augmentation and without it, and to assess the influence of risk factors and their impact on the occurrence of postoperative complications. Methods: This retrospective study evaluates the radiological outcomes and complications of treating proximal humerus fractures (Neer III–IV) in 116 patients over 50 years of age treated between 2017 and 2021. Results: Osteosynthesis without allograft was performed in 84 patients and with allograft in 32 patients. In total, 42 patients (36%) had a three-part fracture and 74 (64%) had a four-part fracture. The Deltoid Tuberosity Index was comparable between the groups (1.59 ± 0.25 vs. 1.50 ± 0.26; p = 0.802). The average duration of surgery was 101.3 ± 21.3 min with allograft and 86.0 ± 31.9 min without allograft (p = 0.004). AVN was verified in four patients (3.5%), head collapse in nine (8%), cut-out in six (5%), reoperation in eight (7%), infection in three (2.5%), and pseudoarthrosis in one (1%) case. Conclusions: An allograft augmentation improves construct stability, but cannot compensate for inadequate surgical technique. None of the risk factors significantly influenced the development of AVN and pseudoarthrosis. The greater tubercle comminution (p = 0.005), calcar loss (p = 0.020, p = 0.112), allograft augmentation (p < 0.001), and medial hinge restoration (p = 0.012, p = 0.002) were significant risk factors associated with HC and screw cut-out, respectively. The greater tubercle redislocation was influenced by its comminution, calcar loss, and the use of allograft augmentation. HFZ and DTI had no significant impact on surgery results or complications. Full article

Introduction: Massage therapy delivers structured mechanosensory input that can influence brain function, yet the central mechanisms and potential for neuroplastic change have not been synthesized across neuroimaging modalities. This mechanistic review integrates evidence from electroencephalography (EEG), functional MRI (fMRI), and functional near-infrared spectroscopy (fNIRS) to map how massage alters human brain activity acutely and over time and to identify signals of longitudinal adaptation. Materials and Methods: We conducted a scoping, mechanistic review informed by PRISMA/PRISMA-ScR principles. PubMed/MEDLINE, Cochrane Library, Google Scholar, and ResearchGate were queried for English-language human trials (January 1990–July 2025) that (1) delivered a practitioner-applied manual massage (e.g., Swedish, Thai, shiatsu, tuina, reflexology, myofascial techniques) and (2) measured brain activity with EEG, fMRI, or fNIRS pre/post or between groups. Non-manual stimulation, structural-only imaging, protocols, and non-English reports were excluded. Two reviewers independently screened and extracted study, intervention, and neuroimaging details; heterogeneity precluded meta-analysis, so results were narratively synthesized by modality and linked to putative mechanisms and longitudinal effects. Results: Forty-seven studies met the criteria: 30 EEG, 12 fMRI, and 5 fNIRS. Results: Regarding EEG, massage commonly increased alpha across single sessions with reductions in beta/gamma, alongside pressure-dependent autonomic shifts; moderate pressure favored a parasympathetic/relaxation profile. Connectivity effects were state- and modality-specific (e.g., reduced inter-occipital alpha coherence after facial massage, preserved or reorganized coupling with hands-on vs. mechanical delivery). Frontal alpha asymmetry frequently shifted leftward (approach/positive affect). Pain cohorts showed decreased cortical entropy and a shift toward slower rhythms, which tracked analgesia. Somatotopy emerged during unilateral treatments (contralateral central beta suppression). Adjuncts (e.g., binaural beats) enhanced anti-fatigue indices. Longitudinally, repeated programs showed attenuation of acute EEG/cortisol responses yet improvements in stress and performance; in one program, BDNF increased across weeks. In preterm infants, twice-daily massage accelerated EEG maturation (higher alpha/beta, lower delta) in a dose-responsive fashion; the EEG background was more continuous. In fMRI studies, in-scanner touch and reflexology engaged the insula, anterior cingulate, striatum, and periaqueductal gray; somatotopic specificity was observed for mapped foot areas. Resting-state studies in chronic pain reported normalization of regional homogeneity and/or connectivity within default-mode and salience/interoceptive networks after multi-session tuina or osteopathic interventions, paralleling symptom improvement; some task-based effects persisted at delayed follow-up. fNIRS studies generally showed increased prefrontal oxygenation during/after massage; in motor-impaired cohorts, acupressure/massage enhanced lateralized sensorimotor activation, consistent with use-dependent plasticity. Some reports paired hemodynamic changes with oxytocin and autonomic markers. Conclusions: Across modalities, massage reliably modulates central activity acutely and shows convergent signals of neuroplastic adaptation with repeated dosing and in developmental windows. Evidence supports (i) rapid induction of relaxed/analgesic states (alpha increases, network rebalancing) and (ii) longer-horizon changes—network normalization in chronic pain, EEG maturation in preterm infants, and neurotrophic up-shifts—consistent with trait-level recalibration of stress, interoception, and pain circuits. These findings justify integrating massage into rehabilitation, pain management, mental health, and neonatal care and motivate larger, standardized, multimodal longitudinal trials to define dose–response relationships, durability, and mechanistic mediators (e.g., connectivity targets, neuropeptides). Full article

Background: Macrocytosis commonly develops during imatinib therapy, but its relationship with cytogenetic and molecular outcomes in chronic myeloid leukemia (CML) remains unclear. We investigated whether increases in mean corpuscular volume (MCV) during imatinib treatment are associated with response depth and treatment persistence. Methods: In this retrospective study, we analyzed 101 adults with chronic-phase CML treated with a stable imatinib dose of 400 mg/day for at least 12 months. Patients with conditions that could confound MCV (hydroxyurea exposure, megaloblastic anemia, hypothyroidism, chronic liver disease, alcoholism) were excluded. Complete cytogenetic response (CCyR) and major molecular response (MMR) were assessed by conventional karyotyping and the BCR-ABL1 International Scale, respectively. Increased MCV was defined as MCV > 100 fL after six months of therapy, persisting thereafter. Associations between MCV dynamics, response, and switching to second-generation tyrosine kinase inhibitors were evaluated. Results: Twenty patients (20%) developed increased MCV. Overall, 86 patients (85%) achieved CCyR and 70 (69%) achieved MMR. All patients with increased MCV attained CCyR, compared with 66 of 81 (81%) without MCV elevation (p = 0.037), while MMR rates were 90% versus 64% (p = 0.030). During a median follow-up of 69 months, treatment modification was required in 1 of 20 (5%) patients with increased MCV versus 25 of 81 (31%) in the non-increased group (p = 0.018). Conclusions: MCV elevation during imatinib therapy is associated with deeper molecular response and reduced need for treatment modification. MCV dynamics may serve as an inexpensive pharmacodynamic marker to support risk assessment and guide monitoring in chronic-phase CML. Full article

Background: T2 low asthma in children is an emerging yet underexplored endotype that challenges traditional views of type 2 inflammation. Recent data suggest that it is more prevalent than previously thought and is defined by low type 2 biomarkers, non-allergic clinical profiles, and strong associations with modifiable comorbidities such as obesity, passive smoke exposure, and recurrent respiratory infections. This phenotype often shows a poor response to standard inhaled corticosteroid therapy and T2-targeted biologics, underscoring the urgent need for improved diagnostic and therapeutic approaches. Methods: This narrative review conducted a literature search from PubMed and WoS databases (2020–2025), focusing on T2-low asthma defined by low blood eosinophils (<150–300/µL), FeNO (<20–25 ppb), and absent atopy in children under 18. Results: This review highlights the heterogeneity of T2-low asthma, including subtypes from neutrophilic/Th 17-high to paucigranulocytic airway remodeling and metabolic driven forms, as well as diagnostic challenges from biomarker supresssion by high-dose therapies. Pragmatic phenotyping algorithms using routine tests enable identification, directing comorbidity management over ineffective biologics. Conclusions: Systematic T2-low phenotyping in pediatric practice, alongside prospective studies and non-T2 therapy trials, promises precision medicine to enhance outcomes for these children, moving beyond eosinophil-centric care. Full article

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder frequently associated with impairments in executive functions (EF). These deficits have been linked to difficulties across various cognitive domains, including metaphonological skills (MS), essential for phonological awareness and processing abilities. Background/Objectives: This pilot study examines the correlations between EF and MS in ADHD children. Methods: A total of 84 children aged 6–14 years, diagnosed with ADHD and an IQ ≥ 70, were assessed using the NEPSY-II test to evaluate executive functions and the Assessment of Metaphonological Skills Test to assess phonological processing abilities. Results: Correlational analyses and multiple regression models were employed to explore the relationships between EF and MS, focusing on attention, cognitive flexibility, and response inhibition. Rhyme was positively correlated with processing speed and negatively correlated with response inhibition. Phonemic segmentation was significantly related to auditory attention and response inhibition. Age emerged as a significant predictor of phonemic synthesis and final syllable deletion, consistent with the developmental maturation of executive and phonological abilities. Conclusions: The findings suggest that deficits in executive functioning in ADHD children are closely linked to metaphonological abilities, which play a crucial role in the acquisition of reading and writing skills. Integrating EF training into phonological interventions can help reduce learning difficulties and improve cognitive and language outcomes. Full article

Background/Objectives: Under general anesthesia, maintaining patients’ blood pressure (BP) is important to prevent organ ischemia. When bleeding occurs, it is sometimes difficult to increase BP with boluses of fluids or transfusions, and vasoconstrictors must be administered. This study investigated circulatory dynamic changes in patients who bled during surgery and were administered phenylephrine, particularly left ventricular end-diastolic volume (EDV), effective arterial elastance (Ea), and left ventricular end-systolic elastance (Ees), calculating each value from the left ventricular–arterial coupling (Ees/Ea). Methods: We calculated Ees/Ea using electrocardiograms, arterial pressure waveforms, and phonocardiograms using an esophageal stethoscope. We investigated the changes in patients’ EDV, Ea, and Ees during two periods: phenylephrine administration and after BP elevation. Results: The seven participants comprised three men and four women. Between the two periods, linear mixed-model analysis revealed that mean arterial pressure (MAP), Ea, and Ees significantly increased over time (MAP; β = 8.7, p < 0.01, Ea; β = 0.22, p < 0.05, Ees; β = 0.73, p < 0.05), while no significant changes were observed in other parameters such as heart rate and EDV. Conventional parameters demonstrated that stroke volume variation significantly decreased (β = −2.0, p = 0.01), systemic vascular resistance index significantly increased (β = 200, p < 0.01), while no significant change was observed in cardiac index (β = −0.03, p = 0.7). In patients administered phenylephrine due to BP decrease from bleeding, significant changes in afterload and cardiac contractility occurred without changes in preload. Conclusions: Our noninvasive method for calculating EDV, Ea, and Ees can be valuable for monitoring hemodynamics under anesthesia. Full article

Objectives: We aimed to assess sex differences in benefits from cardiac rehabilitation and the impact of comorbidities. Methods: We analyzed 3239 individuals with cardiovascular diseases (81.2% males) who participated in a three-week cardiac rehabilitation program at Bad Schallerbach center (Upper Austria). Training success was measured by maximal oxygen consumption (VO₂ max). Sex-specific differences in baseline characteristics were assessed using t-tests/chi² tests. Associations between covariates and the outcome were evaluated with baseline-adjusted univariate analysis of variance/linear regression models. Covariates significant at α = 0.05 were included in a multivariable linear regression model, which was refined by backward selection based on the best Akaike information criterion. The final model was used to test the relationship between sex and the outcome. Results: The mean age and BMI were 63.9 years and 27.5 kg/m² for males and 67.2 years and 27.4 kg/m² for females. Males had higher baseline VO₂ max compared to females (26.18 mL/min/kg vs. 23.55 mL/min/kg, p < 0.001), and a greater change in VO₂ max after rehabilitation was seen in males compared to females (3.64 mL/min/kg vs. 2.77 mL/min/kg, p < 0.001). Female sex was associated with a 1.4-point-lower change in VO₂ max after adjustment for comorbidities, sex, and training intensity (β coefficients = −1.409; CI 95% −0.410, −0.104; p < 0.001). Heart valve surgery (β coefficients = −0.90; CI 95% −1.444, −0.366; p < 0.001) and diabetes mellitus (β coefficients = −1.207; CI 95% −1.926, −0.488; p < 0.0001) were associated with lower changes in VO₂ max in both sexes. Conclusions: Our findings suggest that females and individuals with specific comorbidities benefit less from cardiac rehabilitation and support the creation of personalized rehabilitation programs. Full article

Coronary artery disease (CAD) remains the leading cause of cardiovascular morbidity and mortality worldwide, with plaque composition and morphology being as key determinants of disease progression and clinical outcomes. Accurate plaque characterization is essential for risk stratification and therapeutic decision-making, yet conventional image interpretation is limited by inter-observer variability and time-intensive workflows. Artificial intelligence (AI) models have emerged as a transformative tool for automated coronary plaque analysis across multiple imaging modalities. AI-driven models demonstrate high diagnostic accuracy for plaque detection, segmentation, quantification, and vulnerability assessment. Integration of AI-derived imaging biomarkers with clinical risk scores can further enhance prediction of major adverse cardiovascular events and supports personalized management. These advances position AI-enhanced imaging as a powerful adjunct for both invasive and non-invasive evaluation of CAD. Despite its promise, important barriers to widespread clinical adoption remain, including data heterogeneity, algorithmic bias, limited model transparency, insufficient prospective validation, regulatory challenges, and incomplete integration into clinical workflows. Addressing these challenges will be essential to ensure safe, generalizable, and cost-effective implementation of AI in routine cardiovascular care. Full article

Background/Objectives: Recent public and scientific discussions have raised concerns about a possible link between prenatal paracetamol exposure and autism spectrum disorder (ASD). However, pharmacovigilance-based evidence remains scarce, and the role of reporting bias has not been systematically assessed. This study aimed to characterize ASD-related adverse event reports involving paracetamol in the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) and to evaluate potential disproportionality signals, considering demographic, temporal, and geographic patterns. Methods: FAERS data from January 2010 to September 2025 were screened for reports listing paracetamol as the suspect drug and ASD-related Preferred Terms. After excluding duplicates and concomitant drugs, 1776 unique cases were analyzed. Patient demographics, reporter type, and country of origin were summarized descriptively. Disproportionality was calculated using four algorithms: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Information Component (IC), and Empirical Bayes Geometric Mean (EBGM). Results: Among 172,129 paracetamol-associated reports, 1776 (1.03%) included ASD-related terms. All were classified as serious and mostly submitted by consumers (98.6%). Gender was available in 47.7% of cases, showing male predominance (68.8%). Most reports referred to fetal exposure during pregnancy. Nearly all originated from the United States (98.4%). A marked rise was observed after 2022, with 562 reports in 2023 and 1051 in 2025. Disproportionality analyses revealed consistently elevated signals (ROR = 69.8, PRR = 69.2, IC025 = 5.60, EB05 = 48.3). Conclusions: The strong disproportionality signal likely reflects increased public attention and reporting dynamics rather than a causal association. Further integration of pharmacovigilance and epidemiologic data is warranted to clarify the clinical significance of these findings. Full article

Congenital dyserythropoietic anaemia type-I (CDA-I) is a rare autosomal recessive disease characterised by ineffective erythropoiesis, haemolysis and non-haematological developmental abnormalities. Its treatment is multifactorial, including the management of anaemia, iron overload and prevention of osteoporosis. The only treatment specific to CDA-I is subcutaneous interferon alpha (IFNα) 2A. This study presents the first summary of all published cases of CDA-I patients (n = 33) treated with IFNα and categorises their outcome. We also present new unpublished cases (n = 7). Overall, we find that IFNα administration causes a statistically significant mean increase in haemoglobin of 30.7 g/L (p < 0.001). However, we note that previous studies do not assess the impact of IFNα therapy on providing symptomatic benefit to patients with CDA-I, or the weight of side effects on their quality of life. We collaborate directly with patients through the organisation Congenital Anaemia Network to establish patient preferences regarding IFNα treatment. We propose a classification framework for the use of IFNα in CDA-I that includes patient-reported outcome measures in addition to grading response according to changes in Hb levels. We believe that the use of this framework will aid standardisation in measuring response to therapy, improve clinical practice and assist in future research. Full article

Background: Perforator flaps improved the reconstruction paradigm in the lower extremity, increasing coverage possibilities. This study aims to quantify how added perforators could enhance standard geometrical patterns (compared to random flaps). Methods: A total of 29 cases of lower limb soft tissue reconstruction (STR)—52% trauma, 21% osteomyelitis with skin fistulas, 21% healing disorders with unstable scarring and 6% cancer-related surgery—were performed in our institution between 2012 to 2023 with geometric random (GR) local flaps (34%), geometric perforator-enhanced (GP) flaps (32%) or pure propeller perforator (PP) flaps (34%), were retrospectively analysed. Patients with proximal thigh defects, a follow up of less than 3 months and those who received an axial, muscle or free flap were excluded. Geometric patterns (as length:width ratio (L:W)) were compared among groups, analysing healing outcomes and complications. Results: Leg defects were categorized into 62% distal, 14% middle, 14% proximal third and 10% distal thigh. No significant difference in defect size was detected among groups. Mean flap size was significantly larger for GP (70.5 cm², (p < 0.05)) and PP (74.4 cm², (p < 0.01)) than GR (53.7 cm²). The L:W ratio was significantly higher in GP (L:W 2.2:1, (p < 0.05)) and PP (L:W 2.8:1, (p < 0.01)) than in GR (1.5:1), but no significant difference was found between GP and PP. A reduced complications rate (partial flap loss, infection, healing, revision surgery, etc.) was observed in the GP group, when compared to GR. Conclusions: Flap geometric design can be significantly improved by the inclusion of perforators, maintaining spatial advantages with larger ductility and improved vascular solidity. Full article

Background/Objectives: Respiratory dysfunction in Parkinson’s disease (PD) is frequently underrecognized, particularly when resting oxygen saturation is preserved. Dynamic stress testing, however, may reveal exercise-induced oxygen desaturation, reflecting a latent functional respiratory impairment. The relationship between exertional oxygen desaturation and cognitive performance in PD remains insufficiently explored. Objective: To investigate the association between exercise-induced oxygen desaturation and global cognitive performance in patients with PD, and to explore the contribution of pulmonary gas exchange impairment assessed by diffusing capacity of the lung for carbon monoxide (DLCO). Methods: This prospective, cross-sectional, single-center observational study with consecutive enrollment included 50 patients with idiopathic Parkinson’s disease undergoing multidisciplinary respiratory evaluation following neurological assessment. Participants underwent cognitive evaluation using the Romanian version of the Montreal Cognitive Assessment (MoCA), pulmonary function testing including DLCO and total lung capacity (TLC), and a supervised 6-min walk test (6MWT) with continuous pulse oximetry. Exercise-induced oxygen desaturation was defined as a decrease in SpO₂ of ≥4% from baseline. Correlation analyses and multivariable regression models were applied. Results: Exercise-induced oxygen desaturation was frequent, with 60% of patients exhibiting a ≥4% decrease in SpO₂ during the 6MWT. Greater desaturation was significantly associated with lower MoCA scores (Spearman’s r = −0.383, p = 0.006). No significant associations were found between exertional desaturation and resting pulmonary function parameters, including DLCO and TLC. In multivariable analysis, lower MoCA score and levodopa–carbidopa intestinal gel treatment independently predicted greater oxygen desaturation during exercise. Conclusions: Exercise-induced oxygen desaturation is common in patients with PD despite preserved resting oxygenation and is associated with poorer cognitive performance. These findings suggest that exertional desaturation may reflect a dynamic functional impairment and may be associated with increased physiological vulnerability. Functional exercise testing with oxygen saturation monitoring may provide complementary information beyond resting pulmonary assessments. Full article

Background: Long-term cognitive impairment is common among ICU patients who required invasive mechanical ventilation (IMV). Its etiology is likely multifactorial. This preregistered study examined the association between the duration of IMV and cognitive function post-ICU, as well as the moderating effects of age and cognitive reserve. Methods: A secondary analysis was conducted using data from a published study of COVID-19 ICU survivors. One year after discharge, participants underwent a neuropsychological assessment. Linear regression models were used to evaluate associations between the variables. Results: Among patients who received IMV via endotracheal intubation, ventilation duration was not significantly associated with cognitive performance. In contrast, among tracheostomized patients, longer IMV duration was associated with better cognitive outcomes (Cohen’s f² = 0.21). Age had a small negative main effect; in combination with IMV duration, f² increased to 0.31. Cognitive reserve showed a strong positive association with cognitive outcome; in combination with IMV duration, f² increased to 0.67. The interaction terms were negligible in both cases. Conclusions: We hypothesize that, compared to endotracheal intubation, IMV via tracheostoma may not only reduce the need for sedation, but also provide a more efficient respiratory support, therefore contributing to positive cognitive outcomes. However, IMV via tracheostomy still represents a form of positive pressure ventilation (PPV), which carries risks, such as ventilator-induced lung injury and reduced cardiac output and brain perfusion. These concerns about PPV, combined with our findings, indicate that alternative, non-invasive modes, such as negative pressure ventilation (NPV), warrant evaluation in future trials. Full article

Background: Anterior cervical discectomy and fusion (ACDF) is widely performed and has a low incidence of postoperative infection. Anterior cervical abscess is a rare but potentially life-threatening complication, typically caused by skin or oral flora. Identification of atypical pathogens has important implications for diagnostic vigilance and antimicrobial management. Case Presentation: We report a 56-year-old man with degenerative cervical myelopathy and significant respiratory comorbidity who underwent single-level ACDF and developed progressive dysphagia and neck pain in the early postoperative period. Imaging demonstrated a prevertebral abscess requiring urgent surgical drainage. Intraoperative cultures identified Moraxella catarrhalis, a respiratory tract commensal rarely implicated in postoperative spinal infections. No evidence of esophageal perforation or superficial wound contamination was identified. The patient was treated with surgical washout and prolonged culture-directed antibiotic therapy, with full clinical recovery. To contextualize novelty, we performed a focused review of the available literature on M. catarrhalis spinal infections. Conclusions: This case expands the spectrum of pathogens implicated in postoperative cervical spine infections and highlights the need to consider respiratory tract organisms in high-risk patients, particularly those with chronic pulmonary disease or immunosuppression. Early imaging in the presence of dysphagia, prompt source control, and culture-directed antimicrobial therapy are essential to optimizing outcomes. Full article

Background/Objectives: Craniopharyngiomas (CPs) are rare, generally benign tumors predominantly located in the sellar and suprasellar regions, associated with significant morbidity and complex surgical management. Despite high overall survival rates, patients frequently experience complications including visual impairment, pituitary dysfunction, diabetes insipidus (DI), and hypothalamic syndrome. Among these, hypothalamic obesity (HO) represents one of the most clinically challenging sequelae, often occurring early, lacking standardized medical treatment, and leading to substantial comorbidity and reduced quality of life. This study reports a single-center experience focusing on the relationship between skull base anatomy, surgical approach selection, and endocrinological outcomes. Methods: A retrospective analysis was conducted on patients diagnosed with CPs who underwent surgery by a dedicated team at our Department from January 2014 to January 2024. The approaches used were endoscopic (ER) and transcranial (TR). Preoperative imaging (volumetric MRI and CT scans) was analyzed using 3DSlicer (open-source software) for anatomical modeling of the tumor and skull base. Clinical outcomes were evaluated through follow-up assessments by a team of neuroendocrinologists. Data on BMI changes, DI onset, and hypopituitarism were collected. Statistical analyses consisted of descriptive comparisons and exploratory regression models. Results: Of 18 patients reviewed, 14 met the inclusion criteria. Larger sphenoid sinus volumes were associated with selection of an endoscopic endonasal approach (p = 0.0351; AUC = 0.875). In ER cases, the osteotomy area was directly related to tumor volume, independent of other anatomical parameters. Postoperatively, a significant increase in BMI (22.39 vs. 26.65 kg/m²; p = 0.0049) and in the incidence of DI (three vs. nine cases; p-value 0.0272) was observed. No clear differential association between surgical approach and endocrinological outcomes emerged in this cohort. Conclusions: Quantitative assessment of skull base anatomy using 3D modeling may support surgical approach selection in patients with craniopharyngiomas, particularly in identifying anatomical settings favorable to endoscopic endonasal surgery. Endocrinological outcomes appeared more closely related to tumor characteristics and hypothalamic involvement than to the surgical route itself. These findings support the role of individualized, anatomy-informed surgical planning within a multidisciplinary framework. Full article

Background/Objectives: Following lumbar fusion procedures, adjacent segment degeneration (ASD) at cranial levels presents as a well-documented long-term complication, manifesting through recurrent pain, neurological deficits, and progressive functional decline. The prone single-position technique for lateral lumbar interbody fusion (PSP-LLIF) streamlines surgical workflow by eliminating the need for intraoperative patient repositioning; however, comprehensive evidence supporting its clinical and radiological effectiveness in managing cranial ASD remains insufficient. Material and Methods: This retrospective cohort study examined 30 consecutive patients presenting with symptomatic cranial adjacent segment disease who were treated with PSP-LLIF at a single institution. Patient-reported outcome measures included visual analog scale (VAS) assessments for axial and radicular pain, alongside the Oswestry Disability Index (ODI) for functional status evaluation. Radiological parameters included overall and segmental lumbar lordotic measurements, anterior and posterior disk height, fusion status, and instrumentation-related complications. Results: At 12-month postoperative evaluation, substantial clinical improvements were demonstrated. Mean VAS reductions measured 4.7 points for axial pain and 6.5 points for radicular pain, while ODI decreased by 28.5 points (p < 0.05). Radiological assessment demonstrated mean increases of 6.3° in lumbar lordosis and 5.1° in segmental lordosis, along with significant gains in both anterior and posterior disk height (p < 0.05). Solid fusion was radiographically confirmed at all instrumented levels. Temporary postoperative neurological symptoms developed in several patients but resolved spontaneously without requiring revision surgery. Conclusions: PSP-LLIF yields substantial clinical benefit and reliable radiological correction in patients with symptomatic cranial ASD. Optimal outcomes necessitate rigorous adherence to position-specific technical modifications, particularly maintenance of perpendicular fluoroscopic trajectories and implementation of continuous neural monitoring to account for prone-induced anatomical shifts. This approach represents a viable treatment strategy for patients with symptomatic cranial ASD. Full article

Background/Objectives: In recent decades, new technologies have been progressively integrated into various areas of mental health care. Mobile applications are potentially effective tools that allow psychiatric patients themselves to access self-management resources and tools within the community setting. Mental health nursing plays a key role in enabling patients to take an active role in their care and in promoting activities that foster their involvement and empowerment. The primary aim of this pilot study was to develop the PsyAPP mobile application to support both nurses and individuals with mental illness in managing care and improving health outcomes, and to assess its feasibility within a real-world clinical setting. Methods: A mobile application (PSYAPP) and a complementary web-based nursing management platform were designed and implemented. A total of 20 psychiatric patients enrolled in a partial hospitalization program in Soria (Spain) participated. Participants were assigned to experimental (app users) and control groups. Psychological empowerment, global functioning, and suicide risk were assessed before and after the intervention. Results: Patients who used the application showed significantly greater psychological empowerment (W = 2.04, p ≤ 0.04) compared with the control group. Statistically significant improvements were observed in psychological, social, and occupational functioning. Regarding suicide risk, no statistically significant changes were detected between pre- and post-intervention measurements in either group. Overall, PSYAPP demonstrated feasibility and potential utility as an innovative tool to support mental health care follow-up. Conclusions: This study developed and implemented a mobile application designed to enhance mental health care by supporting both patients and psychiatric nurses. Results showed significant improvements in global functioning in both the app and control groups, suggesting that rehabilitative treatment contributed to overall progress. Suicide risk did not significantly change within groups, although improvements were seen in the full sample, likely due to clinical care rather than app use. Only the experimental group demonstrated increased psychological empowerment, indicating that the app may effectively enhance patient engagement and involvement in their own care. Full article

Background: Hyaluronic acid (HA) injections have become a cornerstone of minimally invasive aesthetic medicine. While the demand for these procedures continues to grow globally, large-scale longitudinal analyses of patient demographics and specific injection site trends remain limited, particularly in Asian populations. Existing data in Japan are largely confined to aggregate procedure numbers. This study aimed to elucidate the transition in patient demographics and site-specific treatment trends using a nationwide big-data approach. Methods: This retrospective study analyzed 299,413 treatment sessions (417,590 injection sites) from patients who underwent facial HA injections at 110 clinics across Japan between October 2020 and December 2024. Data were analyzed by year, patient age, and injection site to evaluate demographic shifts and treatment patterns. Results: The annual number of treatment sessions increased steadily during the study period. A significant demographic shift was observed: while patients in their 20s were predominant in 2020–2022, the proportion of patients aged ≥ 40 years increased markedly from 2023 onward, accounting for more than half of all cases (63.7% in 2024). Treatment preferences varied distinctly by age; younger patients favored localized contouring (e.g., pretarsal fullness, chin), whereas older patients required multi-site rejuvenation. By 2024, the orbital rim became the most frequently treated site (22.6%). Statistical analysis confirmed that age was a significant predictor for multi-site treatments (p < 0.001). Conclusions: This large-scale analysis reveals a clear transition in the Japanese aesthetic market from contour enhancement in younger demographics to anatomy-based rejuvenation in middle-aged and older populations. Full article

Background/Objective: The risk of bleeding is part of blood flow pathophysiology in diabetes mellitus (DM), and there may be potential for the relationship between blood cell indices and estimated whole blood viscosity (eWBV) in DM. However, red blood cell (RBC) indices, platelet ratios, and lymphocyte ratios have been part of routine haematology tests in clinical medicine including diabetes management. This study investigated two research questions. Firstly, how does eWBV correlate with RBC indices, platelet ratios, and lymphocyte ratios? Secondly, which parameters of RBC in routine full blood count (FBC) correlate more with glycated haemoglobin (HbA1c) changes? Methods: This was a laboratory-based clinical observational cohort study using secondary data from ongoing research. Data collected included FBC and biochemistry (HbA1c and serum protein level). Dependent variables were platelet and lymphocyte ratios as well as eWBV. Results: Averages for all parameters in the cross-sectional data were within normal range, except high HbA1c (7.67%) and marginally high monocyte-to-lymphocyte ratio. In the periodic cohort analysis, only RBC distribution width showed a significant difference (p < 0.04) between cohort groups, but least correlated with HbA1c changes. Further analysis for correlations among change scores showed that RBC had the strongest positive linearity for HbA1c (r = 0.30) and among the top three for eWBV (r = 0.54), while mean cell volume (MCV) has the strongest inverse for HbA1c (r = −0.47). Conclusions: The ongoing clinical use of RBC variables is superior to profiles of platelet and/or lymphocyte ratios in assessing the potential risk of bleeding (i.e., hypo-viscosity) in diabetes. Full article

Background/Objectives: The aim of our study was to evaluate the transverse stiffness of selected soft tissues in the knee joint region on the previously injured and uninjured sides of female handball players and non-athlete women, in the lying and standing positions, and to investigate the relationship between stiffness, age, sporting practice, and clinical assessments of the knees. Methods: A total of 25 young female handball players (the SPORT group) and 27 healthy non-athletic individuals (the CONTROL group) were examined. The MyotonPRO device was used to measure the stiffness of the patellar tendon (PT), rectus femoris (RF), and biceps femoris (BF) muscles on both sides and in both positions. The function of the knee joints was clinically assessed using the Knee Outcome Survey—Sports Activities Scale and the Lysholm Knee Scoring Scale. Results: ANOVA indicated a significant effect of group (p < 0.003) on the PT’s stiffness, and a significant effect of position (p < 0.0001) on the PT, RF, and BF muscle stiffness. The SPORT group demonstrated significantly higher PT transverse stiffness when lying down (p < 0.01), but not when sitting up (p > 0.05), compared to the CONTROL group. Significant negative correlations were found between PT stiffness and both clinical scales in the SPORT group (rho from −0.39 to −0.71, p < 0.05). Conclusions: In female handball players, only the patellar tendon transverse stiffness was higher than in the control group. While this higher stiffness could indicate an adaptive rebuilding process, it was negatively correlated with the clinical assessment of joint function, meaning poorer knee joint function. Full article

Background: Mucosal malignant melanoma (MMM) is a rare and aggressive malignancy with a dismal prognosis. While the Systemic Immune-Inflammation Index (SII) has emerged as a prognostic marker in various solid tumors, its specific value in MMM remains undefined. This study investigated the association between pretreatment SII and overall survival (OS) in patients with MMM. Methods: We retrospectively analyzed 106 adults with histologically confirmed MMM treated at six oncology centers in Turkey between 2005 and 2025. The baseline SII was calculated as platelet × neutrophil/lymphocyte counts obtained before definitive treatment. A receiver operating characteristic (ROC) analysis identified an optimal SII cutoff of 776 for overall survival (OS), defining low (<776) and high (≥776) SII groups. Results: Gastrointestinal and head and neck mucosa were the most frequent primary sites, and one-third of patients presented with metastatic disease. The median OS for the entire cohort was 23.3 months. Patients with a high versus low SII had a shorter OS (16.2 vs. 35.2 months; HR 2.71, 95% CI 1.67–4.40; p < 0.001). In multivariable analysis, a high SII (HR 1.88, 95% CI 1.12–3.14; p = 0.016), gastrointestinal primary site (HR 1.99, 95% CI 1.23–3.23; p = 0.005), and metastatic disease at diagnosis (HR 4.01, 95% CI 2.32–6.94; p < 0.001) independently predicted a worse OS. Conclusions: The SII is a novel, independent prognostic biomarker in MMM. Elevated pretreatment SII correlates with aggressive clinicopathologic features and inferior survival. As a readily accessible and cost-effective marker, SII may facilitate improved risk stratification in routine clinical practice for MMM patients. Full article

Diabetes is known to affect metabolic, vascular, and nervous systems, although its influence on auditory function in children remains poorly defined. Understanding this association is essential due to its implications for cognitive, language, and social development. Numerous studies have found that children with Type 1 Diabetes Mellitus (T1DM) exhibit higher hearing thresholds at high frequencies (4000–8000 Hz) and lower speech understanding scores compared to healthy controls. Poor glycemic control and longer disease duration are consistently associated with worse auditory outcomes. The proposed mechanisms include microangiopathy and diabetic neuropathy affecting the auditory pathway. Many affected children do not report noticeable auditory symptoms, indicating a risk of underdiagnosis. Early identification is crucial, as hearing difficulties in children may be related to underlying diabetic conditions and are likely associated with poor glycemic control. Regular audiometric screening should be incorporated into the routine care of pediatric diabetes patients to identify hearing deficits before they affect communication and cognitive development. Full article

Background/Objectives: Recent research highlights Vitis vinifera seeds as a rich source of bioactive proanthocyanidins (PACs) with antioxidant and immunomodulatory effects. Poorly absorbed PACs are metabolized by gut microbiota into active phenolic metabolites. This pilot study in ulcerative colitis patients assessed grape seed extract effects on microbiota, zonulin-related permeability, and quality of life. Methods: This prospective pilot study, conducted at the University Hospital of Padua, evaluated the effects of an eight-week treatment with proanthocyanidins (ECOVITIS^®) on gut microbiota, intestinal permeability (zonulin), and well-being in patients with ulcerative colitis in remission (IBDQ). Fecal and serum samples were collected at T0 and T1. Microbiota analysis was performed through 16S rRNA gene sequencing (QIIME2), zonulin was quantified using an ELISA kit for pre-haptoglobin gene2 (pre-HP2), and HP1/HP2 genotyping was conducted by quantitative PCR. Statistical analyses (Wilcoxon, ALDEx2, PERMANOVA) assessed microbial diversity and taxonomic changes between pre- and post-treatment samples. Results: Twenty-five ulcerative colitis patients completed the study. IBDQ scores significantly improved after treatment (mean Δ = +11.2, p < 0.001), especially in the 11 best IBDQ responders (Δ = +24.2, p < 0.001). Microbiota analysis showed increased Lachnospiraceae and Sutterellaceae in responders, while overall diversity remained unchanged. Zonulin levels were unaffected. Conclusions: PAC treatment improved quality of life in ulcerative colitis patients, as shown by increased IBDQ scores. Serum zonulin levels remained unchanged. Microbiota analysis revealed enrichment of Lachnospiraceae and Sutterellaceae families, suggesting beneficial modulation. Limitations include lack of metabolic assessment and a control group, and caution is needed in interpreting zonulin measurements. Full article

Background/Objectives: Subcondylar mandibular fractures represent a challenging subset of maxillofacial trauma due to their proximity to the temporomandibular joint and the facial nerve. The retromandibular approach can be performed through either an anteroparotid or a transparotid route, but comparative clinical data remain limited. This study aimed to evaluate clinical outcomes, complication profiles, and operative parameters associated with the retromandibular anteroparotid versus transparotid approach for open reduction and internal fixation (ORIF) of subcondylar fractures. Methods: A retrospective analysis was conducted on 80 consecutive patients treated for subcondylar mandibular fractures at the Department of Maxillofacial Surgery, Umberto I General Hospital, Sapienza University of Rome, between 2018 and 2025. All patients underwent ORIF via a retromandibular approach (anteroparotid or transparotid) with a minimum follow-up of 6 months. Demographic data, trauma etiology, fracture morphology (classified as simple or complex), associated fractures, surgical approach, fixation details, operative time, hospital stay, and postoperative complications were collected. Facial nerve function was clinically assessed and graded using the House–Brackmann scale. Associations between fracture type, surgical approach, number of plates, and complications were evaluated using Chi-square or Fisher’s exact tests, while operative time was compared using one-way ANOVA and Kruskal–Wallis tests (p < 0.05). Results: The cohort had a mean age of 41.9 years and was predominantly male (67.5%). The anteroparotid route was used in 54 patients (67.5%) and the transparotid route in 26 (32.5%). Overall, 10 patients (12.5%) developed postoperative complications, including transient facial nerve weakness, malocclusion, visible scarring, and sialocele. All cases of sialocele occurred in the transparotid subgroup, whereas no salivary complications were observed after the anteroparotid approach. No permanent facial nerve deficits, temporomandibular joint ankylosis, or long-term facial asymmetry were recorded at 6 months. No significant association was found between surgical approach and overall complication rate, but complex fracture patterns were significantly associated with increased operative time. Conclusions: The retromandibular approach is a safe and effective option for ORIF of subcondylar mandibular fractures. Both anteroparotid and transparotid routes provided reliable exposure and stable fixation with low complication rates. The anteroparotid route appears to minimize parotid-related complications, such as sialocele, while maintaining comparable functional outcomes. These findings support the retromandibular anteroparotid approach as a valuable alternative in the surgical management of subcondylar fractures. Full article

Background/Objectives: Dynamic computer-assisted surgery (dCAS) has emerged as a promising tool, particularly in implantology, enabling real-time procedural adjustments through 3D image-based tracking. However, their application in other areas of oral surgery remains limited. This systematic review aims to evaluate the advantages, limitations, clinical implications, and complications associated with the use of dCAS in oral surgery (excluding implants or miniscrew insertion) beyond implant placement, in comparison to conventional freehand (FH) techniques. Methods: A systematic review was conducted in accordance with the PRISMA guidelines. A focused PICO question was developed, and a comprehensive literature search was performed in PubMed, Scopus, and the Cochrane Library between February and March 2025, and supplemented by manual screening. The risk of bias of the included studies was evaluated using the Cochrane Risk of Bias tool (RoB 2) for randomized controlled trials (RCTs) and the ROBINS-I tool for non-randomized controlled trials (NRCTs). Data were summarized in tables and analyzed through qualitative synthesis. Results: Ten studies evaluating dCAS in several oral surgical procedures, including complex tooth extractions and endodontic surgery, were included. A substantial improvement was observed in accuracy of endodontic procedures. Operator experience was a key factor in surgical outcomes. Regarding postoperative complications, no significant differences were observed, although the trend indicated an equal or lower risk in comparison with conventional FH techniques. Conclusions: dCAS may significantly improve accuracy and efficiency in endodontic surgery and reduce operative time in complex mandibular third molar (M3M) extractions. The complication rate is comparable to that of conventional FH techniques. However, current evidence remains limited, heterogeneous, and mainly experimental. Further studies are recommended to validate the benefits of dCAS in clinical settings. Full article