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Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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21 pages, 322 KB  
Review
Current and Emerging Strategies for Myopia Control in Children: A Comprehensive Evidence-Based Review
by Aldo Vagge, Matteo Baldi, Maria Musolino, Veronica Rivarone, Carlo Catti and Michele Iester
J. Clin. Med. 2026, 15(4), 1545; https://doi.org/10.3390/jcm15041545 - 15 Feb 2026
Cited by 2 | Viewed by 2161
Abstract
Myopia has emerged as a global public health crisis, with prevalence exceeding 80% in East Asian urban populations and rising rapidly worldwide. High myopia substantially increases the lifetime risk of sight-threatening complications, including myopic macular degeneration, retinal detachment, and glaucoma. Multiple interventions have [...] Read more.
Myopia has emerged as a global public health crisis, with prevalence exceeding 80% in East Asian urban populations and rising rapidly worldwide. High myopia substantially increases the lifetime risk of sight-threatening complications, including myopic macular degeneration, retinal detachment, and glaucoma. Multiple interventions have been investigated to slow myopia progression in children. Behavioral strategies, particularly increased outdoor exposure, demonstrate protective effects against myopia onset and may modestly slow progression, whereas several historically used approaches show no clinically meaningful benefit. Spectacle lens interventions include simultaneous defocus designs (e.g., DIMS, HALT, CARE) and contrast-modulating diffusion optics (DOT) lenses; collectively, these technologies have demonstrated consistent and clinically meaningful reductions in axial elongation across randomized clinical trials. Contact lens modalities, including dual-focus soft lenses and orthokeratology, have also demonstrated substantial efficacy in slowing progression in controlled studies. Low-dose atropine remains a cornerstone pharmacological therapy, particularly at concentrations between 0.01% and 0.05%, offering significant efficacy with minimal side effects. Repeated low-level red-light therapy has shown promising short-term reductions in axial elongation, although long-term safety and rebound effects remain uncertain. Combination therapy targeting complementary optical and pharmacological pathways shows additive benefits, particularly in children inadequately controlled with monotherapy. Contemporary clinical management emphasizes risk stratification based on axial length, age-specific growth targets, and structured longitudinal monitoring. The goal of modern myopia management is not merely to slow progression, but to prevent high myopia and reduce the lifetime burden of vision-threatening complications through a proactive, individualized approach increasingly regarded as the standard of care. Full article
11 pages, 234 KB  
Review
Topical Losartan in Ophthalmology: Rationale, Experimental and Clinical Evidence, and Emerging Clinical Applications
by Barbara Burgos-Blasco, Mercedes Molero-Senosiain, Pilar Perez-Garcia, Mayte Ariño-Gutierrez, Pedro Arriola-Villalobos and David Diaz-Valle
J. Clin. Med. 2026, 15(4), 1354; https://doi.org/10.3390/jcm15041354 - 9 Feb 2026
Cited by 1 | Viewed by 1226
Abstract
Corneal fibrosis remains a major cause of visual morbidity, with transforming growth factor-β (TGF-β) signaling playing a central role in this process. Losartan, an angiotensin II type 1 receptor blocker widely used systemically for cardiovascular indications, has recently attracted interest in ophthalmology due [...] Read more.
Corneal fibrosis remains a major cause of visual morbidity, with transforming growth factor-β (TGF-β) signaling playing a central role in this process. Losartan, an angiotensin II type 1 receptor blocker widely used systemically for cardiovascular indications, has recently attracted interest in ophthalmology due to its antifibrotic properties through indirect inhibition of TGF-β signaling. In recent years, increasing experimental and early clinical evidence has suggested that topical ophthalmic formulations of losartan may attenuate corneal fibrosis following diverse injuries such as descemetorhexis, alkali burns, and photorefractive keratectomy-related injury. Topical losartan represents a promising, non-cytotoxic antifibrotic strategy in ophthalmology, although human evidence is limited and further randomized controlled clinical trials are required to define its clinical efficacy, optimal indications, timing, posology, formulations, and long-term safety. This review summarizes the biological rationale for the use of topical losartan in ophthalmology, including its molecular mechanisms of action, pharmacologic considerations, and safety profile. We critically review preclinical studies in corneal models, as well as emerging clinical applications. Full article
(This article belongs to the Section Ophthalmology)
15 pages, 946 KB  
Article
Predictors of Mortality in Peripheral Arterial Disease After Endovascular Lower Limb Revascularization and Development of a Risk Score Based Solely on Clinical Presentation
by Gladiol Zenunaj, Lorenzo Ciofani, Luca Erbazzi and Aaron Thomas Fargion
J. Clin. Med. 2026, 15(4), 1364; https://doi.org/10.3390/jcm15041364 - 9 Feb 2026
Cited by 1 | Viewed by 514
Abstract
Background: Patients with peripheral arterial disease (PAD) undergoing endovascular revascularization remain at high risk of long-term mortality. While anatomical characteristics such as the length of the lesion, chronic total occlusions and multi-segmental distribution strongly influence revascularization strategy and limb outcomes, their prognostic [...] Read more.
Background: Patients with peripheral arterial disease (PAD) undergoing endovascular revascularization remain at high risk of long-term mortality. While anatomical characteristics such as the length of the lesion, chronic total occlusions and multi-segmental distribution strongly influence revascularization strategy and limb outcomes, their prognostic impact on survival is less clearly defined. The combination of clinical comorbidities, clinical limb presentation and anatomical factors may help to better predict mortality rate before endovascular lower limb revascularization. The primary endpoint of this study was to identify independent predictors of mortality in PAD patients, and the secondary endpoint was to develop a simple clinical risk score for individualized prognostic stratification. Methods: We conducted a single-center retrospective observational study including 476 consecutive PAD patients undergoing endovascular revascularization over a 6-year period. The endpoint target considered was all-cause mortality. Cox proportional hazards regression was used to identify independent predictors of mortality. A prognostic model was derived and subsequently simplified into a point-based clinical risk score (GZ-PAD Mortality Score). Model performance was assessed within the study cohort using Kaplan–Meier survival stratification and receiver operating characteristic (ROC) analysis. Results: Multivariable analysis identified age (HR 1.041 per year, p < 0.001), coronary artery disease (CAD) (HR 1.56, p < 0.001), chronic kidney disease (CKD) (HR 1.52, p = 0.038), dialysis dependence (HR 2.50, p < 0.001), and tissue loss (Rutherford 5–6; HR 5.33, p < 0.001) as independent predictors of mortality, whereas anatomical variables such as lesion length, chronic total occlusions and poor run-off vessel lost prognostic significance. For each patient, the linear predictor (XBETA) was calculated from the coefficients of the final Cox regression model and used to build the mortality score. Based on the 33rd and 66th percentiles of the XBETA distribution, patients were stratified into three prognostic categories: low risk (XBETA ≤ −0.43081), moderate risk (−0.43080 to 0.50835), and high risk (>0.50836). Kaplan–Meier analysis showed a significant discrimination (log-rank χ2 = 102.441; p < 0.001) and good discriminative performance (AUC 0.752). Next the model based on the XBETA predictor was simplified into the global ischemic-systemic risk score (GZ-PAD) assigned for ages 60–69 years = 1 point; 70–79 years = 2 points; ≥80 years = 3 points, CAD = 2 points; CKD = 1 point; Dialysis dependence = 3 points; and tissue loss = 6 points. The new model assessed with survival curves provided robust risk stratification across low-, moderate-, and high-risk groups (log-rank χ2 = 88.883; p < 0.001) and preserved predictive accuracy (AUC 0.769). Conclusions: In PAD patients undergoing successful endovascular revascularization, long-term survival appeared to be related to systemic clinical factors and ischemic severity rather than anatomical lesion complexity. The GZ-PAD Mortality Score offers a simple and clinically applicable tool for mortality risk stratification. Further studies, including external validation in independent and multicenter cohorts, are needed to confirm the robustness and generalizability of the proposed risk score. Full article
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11 pages, 581 KB  
Article
How Likely Do Patients After Total Knee Arthroplasty with a Posterior-Stabilized Knee System Meet Their Desired Sport Activity Level?
by Tobias Scheidl, Oliver Haider, Martin Faschingbauer, Christian Manuel Sterneder, Friedrich Boettner and Maximilian F. Kasparek
J. Clin. Med. 2026, 15(3), 1255; https://doi.org/10.3390/jcm15031255 - 4 Feb 2026
Cited by 1 | Viewed by 482
Abstract
Background/Objectives: While most patients resume sports within one year after total knee arthroplasty (TKA), data on whether patients achieve their desired level of sports activity remain limited. This study aimed to evaluate the relationship between desired sports activity levels and postoperative outcomes [...] Read more.
Background/Objectives: While most patients resume sports within one year after total knee arthroplasty (TKA), data on whether patients achieve their desired level of sports activity remain limited. This study aimed to evaluate the relationship between desired sports activity levels and postoperative outcomes after TKA and to identify factors associated with achieving the desired activity level. Methods: This retrospective cohort study included 280 patients (63.9% female; mean age, 65.7 years) who underwent primary TKA with a mean follow-up of 28.2 months. The University of California and Los Angeles (UCLA) activity score was used pre- and postoperatively to assess the desired and the achieved activity level. Results: The mean UCLA activity score improved significantly after surgery (from 4.6 to 5.6; p < 0.001). However, the mean preoperative desired UCLA score was significantly higher than the mean postoperative achieved UCLA score (7.1 vs. 5.6; p < 0.001). Overall, 34.6% of patients reached their desired activity level. These patients demonstrated a significantly lower preoperative desired UCLA score (6.1 vs. 7.6; p < 0.001) and a higher postoperative achieved UCLA score (6.7 vs. 5.0; p < 0.001) compared with patients who did not. Male sex, higher preoperative UCLA scores, and lower preoperative desired UCLA scores were identified as independent predictors of achieving the desired activity level. Conclusions: The present study demonstrated that despite excellent Knee Society function and WOMAC scores only 1/3 of patients reach their sport-related desired activity level. Surgeons must ensure that they communicate realistic expectations to patients prior to surgery, in order to avoid dissatisfaction that may arise from unmet expectations. Full article
(This article belongs to the Special Issue Hip and Knee Arthroplasty: Update on Clinical Management)
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11 pages, 503 KB  
Systematic Review
The Ocular and Gut Microbiome Axis in Understanding Glaucoma: A Systematic Review
by Bruno Songel-Sanchis, Laura Morales-Fernández, Javier García-Bardera, Noemí Güemes-Villahoz, José María Martínez-de-la-Casa and Julián García-Feijoo
J. Clin. Med. 2026, 15(3), 1245; https://doi.org/10.3390/jcm15031245 - 4 Feb 2026
Cited by 1 | Viewed by 909
Abstract
Background: Glaucoma is a neurodegenerative disease and the second leading cause of irreversible blindness in developed countries. It is characterized by progressive loss of retinal ganglion cells (RGCs) and optic nerve axons, leading to permanent vision impairment. Although elevated intraocular pressure (IOP) is [...] Read more.
Background: Glaucoma is a neurodegenerative disease and the second leading cause of irreversible blindness in developed countries. It is characterized by progressive loss of retinal ganglion cells (RGCs) and optic nerve axons, leading to permanent vision impairment. Although elevated intraocular pressure (IOP) is the main recognized risk factor, recent evidence suggests that ocular and gut microbiota may play a significant role in the onset and progression of glaucoma. Objectives: This study aimed to characterize ocular and gut microbiota alterations in patients with different types of glaucoma. Methods: Five searches were conducted between June and September 2025 using selected keywords. A total of 121 articles were identified, of which 14 met the inclusion criteria following the PRISMA 2020 guidelines. Results: Findings indicate a Mendelian genetic predisposition influencing microbiota composition associated with glaucoma development. Patients treated with benzalkonium chloride (BAK) showed increased Gram-negative and Alphaproteobacteria on the ocular surface, along with enhanced lipopolysaccharide synthesis. Compared with controls, glaucoma patients exhibited reduced Corynebacterium mastiditis and Actinobacteria and increased Firmicutes, Proteobacteria, and Verrucomicrobiota. Dysbiosis was more pronounced in patients with concurrent dry eye disease, characterized by higher Gram-negative taxa and pro-inflammatory microbial activity. Conclusions: Significant differences in ocular and gut microbiota were observed between glaucoma patients and controls, as well as among glaucoma subtypes such as pseudoexfoliation and primary open-angle glaucoma. Age-related dysbiosis and epigenetic factors appear to contribute to disease development. Microbiota profiling may offer new opportunities for improved prediction, management, and treatment of glaucoma. Full article
(This article belongs to the Special Issue Recent Advances in Glaucoma Management)
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14 pages, 3154 KB  
Article
Transvenous Lead Extraction Complicated by Lead Breakage: A Predictive Model Based on Analysis of the EXTRACT Registry
by Michal Joniec, Joanna Stachanczyk, Rafal Gardas, Sylwia Gladysz-Wanha, Eugeniusz Pilat, Anna Drzewiecka, Jolanta Biernat, Andrzej Weglarzy, Wojciech Wanha, Danuta Loboda and Krzysztof S. Golba
J. Clin. Med. 2026, 15(3), 1216; https://doi.org/10.3390/jcm15031216 - 4 Feb 2026
Cited by 1 | Viewed by 475
Abstract
Background: The lead breakage (LB) during transvenous lead extraction (TLE) increases procedural complexity, increases the risk of complications, and decreases procedural efficiency. This study aimed to identify protective and risk factors for the breakage of cardiac electronic device leads during extraction. Methods [...] Read more.
Background: The lead breakage (LB) during transvenous lead extraction (TLE) increases procedural complexity, increases the risk of complications, and decreases procedural efficiency. This study aimed to identify protective and risk factors for the breakage of cardiac electronic device leads during extraction. Methods: Data were sourced from the EXTRACT prospective registry for TLE procedures conducted between January 2016 and June 2025. A total of 702 consecutive TLE procedures involving 1375 leads were enrolled. Multivariate logistic regression was used to identify independent protective and risk factors and develop a model to predict the occurrence of LB during TLE. Results: In the analysed group, 56 (7.98%) of 702 TLE procedures were disrupted by the breakage of at least one lead. The model showed a lower lead breakage rate in procedures when an atrial lead was simultaneously extracted, a locking stylet was used, and when the procedure was conducted in older patients or those who had undergone prior cardiac surgery. Higher risk of LB was proven in the following cases: the extraction of leads implanted a long time ago; the extraction of VDD-type leads; the extraction of abandoned leads; extraction during a prolonged procedure. Occurrence of lead breakage may lead to pericardial effusion requiring intervention, acute kidney injury, or leaving remnants of the leads. Conclusions: Lead breakage is an underestimated procedural difficulty that can occur during transvenous lead extraction. In this study, several clinical and procedural variables were independently associated with lead breakage. Abandoned leads, VDD leads, and prolonged procedure time were associated with increased risk. In contrast, older age, use of a locking stylet, atrial lead extraction, prior cardiac surgery, and later year of implantation demonstrated independent protective associations. Full article
(This article belongs to the Section Cardiology)
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22 pages, 8032 KB  
Review
Advanced Diagnostic Technologies and Molecular Biomarkers in Periodontitis: Systemic Health Implications and Translational Perspectives
by Sebastian Biesiadecki, Monika Janeczko, Joanna Kozak, Magdalena Homaj-Siudak, Lukasz Szarpak and Mansur Rahnama-Hezavah
J. Clin. Med. 2026, 15(3), 1142; https://doi.org/10.3390/jcm15031142 - 2 Feb 2026
Cited by 1 | Viewed by 856
Abstract
Background/Objectives: Periodontitis is a chronic inflammatory disease with marked inter-individual heterogeneity and well-established links to cardiometabolic and other systemic conditions. Conventional clinical diagnostics remain indispensable. However, they provide limited real-time insight into molecular activity and host-response biology. This review aimed to synthesize recent [...] Read more.
Background/Objectives: Periodontitis is a chronic inflammatory disease with marked inter-individual heterogeneity and well-established links to cardiometabolic and other systemic conditions. Conventional clinical diagnostics remain indispensable. However, they provide limited real-time insight into molecular activity and host-response biology. This review aimed to synthesize recent advances in point-of-care diagnostics and emerging molecular biomarkers relevant to periodontal disease and its systemic associations. Methods: We performed a state-of-the-art narrative review of literature published between 2018 and 2026. The focus was on point-of-care biosensing technologies and molecular biomarkers assessed in oral and related biological matrices. These included saliva, gingival crevicular fluid, blood, and dental plaque. Evidence was prioritized based on analytical performance, clinical validity, and translational readiness. Results: Substantial progress has been made in multiplex optical and electrochemical point-of-care platforms. These include microfluidic systems and early intraoral wearable sensors. Such technologies enable quantification of host-response proteins, including MMP-8, cytokines, and chemokines. In parallel, omics-derived biomarkers are emerging as clinically informative adjuncts for diagnosis and monitoring. MicroRNAs, cell-free DNA, extracellular vesicle–derived signals, proteomic profiles, and microbiome classifiers demonstrate promising discrimination. They also provide mechanistic links to systemic inflammation. Clinical translation remains limited by study heterogeneity, spectrum bias, and insufficient external validation. Conclusions: Near-term clinical value lies in adjunctive risk stratification and longitudinal disease monitoring. Replacement of conventional periodontal examination is not currently justified. Meaningful clinical and public-health impact will require standardized disease definitions. Harmonized sampling and reporting protocols are essential. Multicenter validation across comorbidity strata is needed. Regulatory-grade evidence must be generated for in vitro diagnostics and artificial intelligence software classified as medical devices. Full article
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16 pages, 702 KB  
Article
Combined Burden of Heart Failure and Arterial Hypertension as Predictors of Adverse Outcomes in Hospitalized COVID-19 Patients
by Ana-Maria Pah, Ana-Olivia Toma, Camelia-Oana Muresan, Diana-Maria Mateescu, Ioana-Georgiana Cotet, Luchian Iancu-Ciorbagiu, Adrian-Cosmin Ilie, Daian Ionel Popa, Dragos-Mihai Gavrilescu, Stela Iurciuc, Maria-Laura Craciun, Simina Crisan and Adina Avram
J. Clin. Med. 2026, 15(3), 1143; https://doi.org/10.3390/jcm15031143 - 2 Feb 2026
Cited by 1 | Viewed by 518
Abstract
Background: Cardiovascular comorbidities are major determinants of poor outcomes among patients admitted with COVID-19. However, the prognostic role of arterial hypertension alone remains uncertain. Little is known about the cumulative impact of concomitant hypertension and heart failure. This study assessed whether the [...] Read more.
Background: Cardiovascular comorbidities are major determinants of poor outcomes among patients admitted with COVID-19. However, the prognostic role of arterial hypertension alone remains uncertain. Little is known about the cumulative impact of concomitant hypertension and heart failure. This study assessed whether the combined burden of arterial hypertension and pre-existing heart failure identifies a high-risk phenotype for adverse in-hospital outcomes among COVID-19 patients. Methods: In this retrospective, real-world cohort study, 395 consecutive adults hospitalized with confirmed COVID-19 at a single infectious diseases center between March 2020 and December 2024 were included. We categorized patients into three cardiovascular phenotype groups: no hypertension or heart failure (n = 23), hypertension without heart failure (n = 193), and concomitant hypertension and heart failure (n = 178). The primary outcome was in-hospital all-cause mortality, while ICU admission served as a secondary outcome, invasive mechanical ventilation, and length of hospital stay. Multivariable logistic regression included age, sex, BMI, diabetes mellitus, and vaccination status to evaluate independent associations between the cardiovascular risk group and outcomes. Results: Overall in-hospital mortality was 7.3% (29/395). Mortality increased stepwise across the cardiovascular risk groups: 8.7% in patients without hypertension or heart failure, 3.1% in those with hypertension only, and 11.8% in patients with concomitant hypertension and heart failure (p = 0.004). In adjusted analyses, concomitant hypertension and heart failure were linked to higher adjusted odds of in-hospital death than no cardiovascular disease (odds ratio, 3.49; 95% confidence interval, 1.46–8.35). Isolated hypertension was not significantly associated with mortality. ICU admission and length of hospital stay also increased with cumulative cardiovascular burden. Patients with combined hypertension and heart failure showed more pronounced inflammatory and renal abnormalities at admission. Conclusions: Among hospitalized COVID-19 patients, the coexistence of arterial hypertension and heart failure identifies a vulnerable cardiovascular phenotype associated with higher in-hospital mortality and resource use than either no cardiovascular disease or hypertension alone. These findings support evaluating cardiovascular comorbidities cumulatively rather than in isolation. These findings are exploratory and require external validation in independent, larger multicentre cohorts. Findings may support careful use for short-term risk stratification and closer monitoring strategies during COVID-19 hospitalization. Full article
(This article belongs to the Special Issue Therapies for Heart Failure: Clinical Updates and Perspectives)
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16 pages, 895 KB  
Systematic Review
Prolonged Grief-Related Symptoms Among Young Individuals After Loss of a Parent or Sibling to Cancer: A Systematic Review and Meta-Analysis
by Chen Ee Low, Jia Yang Tan, Weiling Amanda Tan, Jayanth Jayabaskaran, Emily Chen Fei Ni, Ga Eun Pang, Dawn Yi Xin Lee, Sean Loke, Hon Jen Wong, Chun En Yau, Ainsley Ryan Yan Bin Lee and Cyrus Su Hui Ho
J. Clin. Med. 2026, 15(3), 1060; https://doi.org/10.3390/jcm15031060 - 29 Jan 2026
Cited by 1 | Viewed by 1430
Abstract
Background/Objectives: Bereavement in childhood, adolescence, and young adulthood is associated with a range of grief responses, and a subset of bereaved individuals develop persistent or severe grief symptoms. Understanding the prevalence and risk factors of prolonged grief symptoms is important for guiding supportive [...] Read more.
Background/Objectives: Bereavement in childhood, adolescence, and young adulthood is associated with a range of grief responses, and a subset of bereaved individuals develop persistent or severe grief symptoms. Understanding the prevalence and risk factors of prolonged grief symptoms is important for guiding supportive care. Methods: We systematically searched PubMed, MedLine, Embase and PsycINFO for all studies comparing the prevalence and prognostic factors of prolonged grief-related symptoms among young individuals following parental or sibling death from cancer. Young individuals were defined as those not more than 25 years old before losing a parent or sibling to any cancer. Prolonged grief-related symptoms were defined as the presence of grief symptoms at least six months following the death of a parent or sibling of the bereaved person. Retrospective cross-sectional studies were included for evaluating prognostic factors affecting prolonged grief-related symptoms, but were not used for meta-analyses. Random-effects meta-analyses were conducted for the primary analysis. Results: From 1561 records identified, thirteen studies were included with five for quantitative pooling in meta-analysis. The pooled prevalence of self-reported prolonged grief-related symptoms was 48% (95% CI: 29–67%). Stratified analyses suggested a prevalence of 28% (95% CI: 7–65%) after parental death and 59% (95% CI: 45–72%) after sibling death. Factors associated with elevated prolonged grief-related symptoms included pre-existing depression, emotional difficulties, and insomnia. As no included studies conducted diagnostic clinical interviews, prolonged grief disorder according to the ICD-11 or DSM-5-TR criteria could not be assessed. Conclusions: Prolonged grief-related symptoms appear common among young individuals bereaved by loss of a parent or sibling to cancer, especially after sibling loss. However, interpretation remains limited by substantial heterogeneity, such as outcome measures, symptom thresholds, assessment time window, non-validated symptom measures, and predominance of cross-sectional studies. Future larger and methodologically rigorous studies using validated grief instruments across diverse settings are needed to clarify grief trajectories and guide developmentally appropriate intervention strategies. Full article
(This article belongs to the Section Mental Health)
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18 pages, 665 KB  
Review
Comprehensive Approaches to Endometriosis Management and Targeted Strategies for Bowel Endometriosis
by Arrigo Fruscalzo, Alexandre Vallée, Carolin Marti, François Pugin, Jean-Marc Ayoubi, Michael D. Mueller and Anis Feki
J. Clin. Med. 2026, 15(3), 1040; https://doi.org/10.3390/jcm15031040 - 28 Jan 2026
Cited by 1 | Viewed by 899
Abstract
Background: Deep infiltrating endometriosis (DIE) and, in particular, bowel endometriosis stand out for their complexity. While surgery for bowel endometriosis has proven to be effective, there is a lack of standardization concerning the technique used and the reported outcomes. Objectives: The [...] Read more.
Background: Deep infiltrating endometriosis (DIE) and, in particular, bowel endometriosis stand out for their complexity. While surgery for bowel endometriosis has proven to be effective, there is a lack of standardization concerning the technique used and the reported outcomes. Objectives: The objective is to perform a review aiming to summarize the state of the art of bowel endometriosis and to point out the gaps to be addressed by future research. We also propose a novel classification of surgical procedures to fill these gaps and improve management. Methods: A literature search was performed on PubMed from inception to October 2025. Results: The following three major procedures for the excision of bowel endometriosis have been proposed: the nodule shaving, the discoid excision, and the segmental intestinal resection. One further technique, NOSE (natural orifice specimen extraction), can be applied for the removal of the specimen in cases of discoid or segmental resection. To reduce surgical morbidity, current data support the choice of most conservative surgical options, namely nodule dissection and discoid resection, as well as the use of nerve-sparing techniques in case of segmental resection. Nonetheless, there is little evidence concerning the indication and the most appropriate technique to be used, including their relative risks and benefits in terms of pain control, urinary and gastrointestinal function, risk of future relapse, and fertility outcomes. Conclusions: Significant barriers in comparing surgical outcomes due to unclear definitions, lack of standardization, and incomplete reporting are some of the most relevant issues frequently encountered. To fill these gaps, we propose a new classification system for bowel surgery that describes the dimension and the number of the lesions, as well as the type of surgical technique used, supplemented by the information if vaginal opening was necessary for complete lesion resection. This proposition aims to open a discussion on this topic and boost focused research to evaluate the utility of a new classification in clinical practice. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Endometriosis)
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20 pages, 1473 KB  
Article
Clinical and Sociodemographic Characteristics Associated with Access to Early Intervention Programs for Infants with Prodromes of Autism
by Natasha Chericoni, Eugenia Conti, Valeria Costanzo, Francesca Ieri, Ilaria Colombino, Giulia Guainai, Benedetta Riva, Fabio Apicella, Andrea Guzzetta, Sara Calderoni and Costanza Colombi
J. Clin. Med. 2026, 15(3), 1044; https://doi.org/10.3390/jcm15031044 - 28 Jan 2026
Cited by 1 | Viewed by 1333
Abstract
Background/Objectives: Increasing scientific evidence supports the importance of early diagnosis of autism spectrum disorder (ASD), followed by timely intervention, in optimizing developmental trajectories. Despite these advances, achieving an early diagnosis remains challenging, and substantial delays in the diagnostic process continue to be reported [...] Read more.
Background/Objectives: Increasing scientific evidence supports the importance of early diagnosis of autism spectrum disorder (ASD), followed by timely intervention, in optimizing developmental trajectories. Despite these advances, achieving an early diagnosis remains challenging, and substantial delays in the diagnostic process continue to be reported worldwide. This study aimed to describe the clinical and sociodemographic characteristics associated with early referral to a telehealth parent-mediated intervention program for infants at high likelihood for ASD, under 18 months of age, with the broader goal of informing clinical services in the field of neurodevelopmental disorders. Methods: Infants were evaluated by a multidisciplinary team using standardized measures to assess autism risk, developmental functioning, adaptive behavior, and parental stress. Potential differences in age at access to the program were examined by comparing families who were referred before versus after 12 months of age. Results: Of the 78 families who expressed interest in the program, 69 consented and 60 met eligibility criteria (male/female ratio = 40/20; mean age = 10.0 months). Families were evenly distributed across Italy, and 66% of parents held a university degree. Self-referral accounted for 62% of cases. Higher parental concern was associated with earlier referral and children referred after 12 months of age showed significantly lower developmental and adaptive functioning scores. Conclusions: These findings support the feasibility of identifying prodromes of autism within the first year of life and highlight gaps in specialized services for infants at elevated likelihood in Italy. Maternal concern and self-referral drove early consultation, underscoring the need for improved pediatric training. Future studies should assess longitudinal population-based screening and the feasibility and long-term impact of timely interventions in routine care. Full article
(This article belongs to the Section Clinical Pediatrics)
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21 pages, 5402 KB  
Article
Sensorized Vascular High-Fidelity Physical Simulator for Robot-Assisted Surgery Training: A Multisite Pilot Evaluation
by Giulia Gamberini, Alessandro Dario Mazzotta, Angela Durante, Selene Tognarelli, Niccolò Petrucciani, Gianluca Mennini, Gianfranco Silecchia and Arianna Menciassi
J. Clin. Med. 2026, 15(3), 1054; https://doi.org/10.3390/jcm15031054 - 28 Jan 2026
Cited by 1 | Viewed by 534
Abstract
Background/Objectives: Robot-Assisted Surgery poses challenges in skill acquisition due to the lack of haptic feedback, which may lead to adverse intraoperative events. This study focused on a multisite pilot evaluation on the simulator’s ability to discriminate between different levels of expertise and [...] Read more.
Background/Objectives: Robot-Assisted Surgery poses challenges in skill acquisition due to the lack of haptic feedback, which may lead to adverse intraoperative events. This study focused on a multisite pilot evaluation on the simulator’s ability to discriminate between different levels of expertise and the ability to explore potential differences between surgical specialties. Methods: We built a simulator that can replicate anatomies of vascular and adipose tissue. A resistive stretching sensor was integrated into a silicone vessel to objectively measure its deformation. A total of 18 males and 12 females, aged between 26 and 64 years old, participated to the study. In total, there were 30 participants, (21 general surgeons, 2 thoracic surgeons, 4 gynecologists, 3 urologists) and they performed two repetitions of a surgical task and filled in a questionnaire about face- and content validities and a system usability scale. The tests were conducted between February and October 2023. Results: The discriminant validity was positively assessed, considering the maximum deformation value (p-value = 0.0479) and the mean deformation value (p-value = 0.0317). Differences were found between urologists, (i) general surgeons (p-value = 0.0167) and, (ii) gynecologists (p-value = 0.0495). The face- and content validity of the simulator received 80% and 90% of positive answers, respectively. Conclusions: Future works will deal with the evaluation of the simulator abilities in surgical training by comparing surgeons trained on the simulator to those who are not. Full article
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20 pages, 345 KB  
Review
Drug-Induced Osteoporosis
by Rudolf Wolfgang Gasser, Roland Kocijan, Afrodite Zendeli and Heinrich Resch
J. Clin. Med. 2026, 15(3), 993; https://doi.org/10.3390/jcm15030993 - 26 Jan 2026
Cited by 3 | Viewed by 1952
Abstract
The administration of various medications can induce bone loss as an adverse effect and may result in drug-induced osteoporosis, an important and clinically relevant form of secondary osteoporosis associated with an increased fracture risk. This review summarizes the skeletal effects of selected commonly [...] Read more.
The administration of various medications can induce bone loss as an adverse effect and may result in drug-induced osteoporosis, an important and clinically relevant form of secondary osteoporosis associated with an increased fracture risk. This review summarizes the skeletal effects of selected commonly used drugs with respect to bone metabolism, bone mineral density, and fracture outcomes. Medications may exert direct effects on osteoblasts and/or osteoclasts, leading to impaired bone remodeling and reduced bone mass. Alternatively, indirect mechanisms may contribute to skeletal damage, including disturbances in calcium and vitamin D metabolism with subsequent secondary hyperparathyroidism, as well as therapy-induced hypogonadism. Drug classes frequently associated with drug-induced osteoporosis during long-term use include glucocorticoids, aromatase inhibitors, androgen-deprivation therapy, thyroxine, proton pump inhibitors, anticoagulants (heparin and vitamin K antagonists), antidepressants, neuroleptics, and thiazolidinediones. Importantly, this overview represents a selection of relevant agents and does not aim to provide an exhaustive list. When prescribing potentially bone-damaging medications over extended periods, particularly in older individuals, bone health should be proactively considered. Evaluation should include laboratory assessment, fracture risk estimation (e.g., FRAX®), and bone mineral density measurement when appropriate. Adequate calcium and vitamin D intake should be ensured, and guideline-based osteoporosis therapy initiated when indicated. Full article
21 pages, 1536 KB  
Review
Ultra-Sensitive Mutation Detection Technology in Myeloid Neoplasms: New Tools for Patient Monitoring
by Alessandro Ferrando, Valentina Bonuomo, Arianna Savi and Daniela Cilloni
J. Clin. Med. 2026, 15(3), 998; https://doi.org/10.3390/jcm15030998 - 26 Jan 2026
Cited by 2 | Viewed by 576
Abstract
The clinical management of myeloid neoplasms increasingly relies on the accurate detection and longitudinal monitoring of disease-defining genetic alterations. Many clinically relevant mutations are often present at very low variant allele frequencies, below the detection limits of conventional approaches routinely used in diagnostic [...] Read more.
The clinical management of myeloid neoplasms increasingly relies on the accurate detection and longitudinal monitoring of disease-defining genetic alterations. Many clinically relevant mutations are often present at very low variant allele frequencies, below the detection limits of conventional approaches routinely used in diagnostic workflows. In recent years, a growing number of ultra-sensitive molecular technologies have been developed to overcome these limitations, enabling the detection of rare variants with unprecedented precision, offering complementary strengths in terms of sensitivity, quantification, throughput, and clinical applicability. This review provides a comprehensive overview of established and emerging ultra-sensitive technologies for the diagnosis and molecular monitoring of myeloid neoplasms, discussing their technical principles, advantages, and limitations. Full article
(This article belongs to the Special Issue Blood Disorders: Diagnosis, Management, and Future Opportunities)
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18 pages, 5163 KB  
Review
Intracardiac Echocardiography in Structural Heart Interventions: A Comprehensive Overview
by Francesco Leuzzi, Ciro Formisano, Enrico Cerrato, Antongiulio Maione, Tiziana Attisano, Francesco Meucci, Michele Ciccarelli, Carmine Vecchione, Gennaro Galasso and Francesca Maria Di Muro
J. Clin. Med. 2026, 15(3), 926; https://doi.org/10.3390/jcm15030926 - 23 Jan 2026
Cited by 2 | Viewed by 933
Abstract
Intracardiac echocardiography (ICE) is increasingly recognized as a valuable imaging modality in structural heart interventions, offering high-resolution, real-time visualization from within the cardiac chambers. Originally developed for electrophysiologic procedures, ICE has expanded its use across a broad spectrum of structural interventions, including atrial [...] Read more.
Intracardiac echocardiography (ICE) is increasingly recognized as a valuable imaging modality in structural heart interventions, offering high-resolution, real-time visualization from within the cardiac chambers. Originally developed for electrophysiologic procedures, ICE has expanded its use across a broad spectrum of structural interventions, including atrial septal defect (ASD) and patent foramen ovale (PFO) closure, left atrial appendage occlusion (LAAO), transseptal puncture guidance, transcatheter edge-to-edge repair (TEER), balloon mitral valvuloplasty, and both mitral and tricuspid valve therapies. This review outlines the current role and technical principles of ICE, with an emphasis on catheter design, image acquisition protocols, and the emerging potential of 3D ICE. Comparisons with transesophageal echocardiography (TEE) and fluoroscopy are discussed, highlighting ICE’s ability to support minimally invasive, sedation-sparing procedures while maintaining procedural precision. We provide a focused analysis of ICE-guided applications in specific clinical scenarios, emphasizing its role in anatomical assessment, device navigation, and intra-procedural monitoring. Data from recent clinical studies and registries are reviewed to assess safety, feasibility, and outcomes. Practical considerations including operator learning curve, workflow integration, and limitations such as cost and field of view are also addressed. Lastly, we explore future directions including advanced 3D imaging, fusion imaging, artificial intelligence integration, and robotic catheter systems. Full article
(This article belongs to the Special Issue Interventional Cardiology: Recent Advances and Future Perspectives)
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15 pages, 1209 KB  
Article
Association Between Donor Kidney Function and Post-Transplant Graft Function in Deceased-Donor Kidney Transplantation
by Arefeh Sadat Pezeshk, Maximilian Nösser, Leke Wiering, Otajan Bobonov, Kim Tehyung, Brigitta Globke, Paul Viktor Ritschl, Andreas Kahl, Klemens Budde, Mira Choi, Fabian Halleck, Johann Pratschke, Robert Öllinger and Tomasz Dziodzio
J. Clin. Med. 2026, 15(3), 939; https://doi.org/10.3390/jcm15030939 - 23 Jan 2026
Viewed by 438
Abstract
Background/Objectives: Donor kidney function measured by glomerular filtration rate (GFR) is widely used as a selection criterion in kidney transplantation (KT). This study addresses the knowledge gap regarding the relationship between donor GFR at organ procurement and graft function in deceased donor KT. [...] Read more.
Background/Objectives: Donor kidney function measured by glomerular filtration rate (GFR) is widely used as a selection criterion in kidney transplantation (KT). This study addresses the knowledge gap regarding the relationship between donor GFR at organ procurement and graft function in deceased donor KT. Methods: We retrospectively analyzed 918 deceased donor KTs and compared donor GFRs at procurement and recipient GFRs after KT at hospital discharge and in the one-year follow-up. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was used to estimate and compare GFRs. Donor baseline GRF was defined as the last available estimated GRF prior to organ procurement. The Kaplan–Meier analysis was used to estimate recipient and graft survival. Results: The median donor GFR was 92.8 mL/min/1.73 m2, while the median recipient GFR at hospital discharge was 37.5 mL/min/1.73 m2 (−60% to donor baseline, p < 0.001), increasing to 51.4 mL/min/1.73 m2 (+37%, p < 0.001) at one-year follow-up. One-year graft and patient survival rates were 95.3% and 98.1%, respectively. Except for grafts from donors with a GFR < 15 mL/min/1.73 m2 due to acute renal failure that resulted in a significantly higher delayed graft function (DGF) rate and inferior graft survival (71.4%), no correlation was observed between baseline GFRs and DGF occurrence nor graft survival. Conclusions: Excellent results can be achieved in KT with subnormal donor GFR. The decision to refuse a kidney offer for KT should not solely be based on donor GFR. Kidneys from donors with very low GFR (<15 mL/min/1.73 m2) may be transplanted, but our observation is based on a very small sample (n = 7) and should therefore be interpreted with caution, particularly given the associated higher risk of DGF and lower graft survival. Full article
(This article belongs to the Special Issue Kidney Transplantation: Challenges, Advances and Lessons Learnt)
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23 pages, 910 KB  
Systematic Review
Screening Tools for the Early Identification of Palliative Care Needs in Patients with Advanced Chronic Conditions: An Updated Systematic Review
by Ana Bustamante-Fermosel, Agustín Diego Chacón-Moreno, Laetitia Hennekinne, Fuensanta Gil-Gil, Helena Notario-Leo, Ricardo Larrainzar-Garijo, Juan Torres-Macho, Anabel Franco-Moreno, Gerardo García Melcón and on behalf of the Research in Palliative Care HUIL-Group
J. Clin. Med. 2026, 15(3), 919; https://doi.org/10.3390/jcm15030919 - 23 Jan 2026
Cited by 1 | Viewed by 899
Abstract
Background/Objectives: Earlier initiation of palliative care improves clinical outcomes, including better symptom relief, enhanced quality of life, and decreased use of healthcare resources in advanced disease. This systematic review aimed to identify and critically appraise existing tools, both conventionally developed and based [...] Read more.
Background/Objectives: Earlier initiation of palliative care improves clinical outcomes, including better symptom relief, enhanced quality of life, and decreased use of healthcare resources in advanced disease. This systematic review aimed to identify and critically appraise existing tools, both conventionally developed and based on artificial intelligence, designed to identify patients eligible for early palliative care interventions. Methods: Six electronic databases were examined for primary research studies published between 2000 and 2025. Studies that described or evaluated screening instruments developed to support the early identification of adult patients with palliative care needs underwent dual reviewer screening and data extraction. Results: A total of 35 studies were included. Of these, 13 reported the development of screening tools and 22 focused on the external validation of these instruments. Nine tools were developed using traditional methods, and four instruments were created using artificial intelligence techniques. Significant heterogeneity was observed in tool design and target populations. Most screening tools used death prediction as a proxy, with limited integration of psychological and spiritual dimensions. External validation studies primarily focused on predicting mortality. Overall, all the tools showed moderate predictive ability. Conclusions: The ability of current screening tools to identify patients with advanced diseases who are likely to have palliative care needs remains limited. Further research is needed to develop standardized screening processes that address not only mortality prediction but also disease trajectory and functional decline. Full article
(This article belongs to the Special Issue Clinical Research in Palliative Care)
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17 pages, 2610 KB  
Review
Limitations and Blind Spots of Diffusion-Weighted Imaging in the Evaluation of Acute Brain Ischemia: A Narrative Review
by Ioannis Nikolakakis, Ioanna Koutroulou, Michail Mantatzis, Stefanos Finitsis, Nikolaos Grigoriadis and Theodoros Karapanayiotides
J. Clin. Med. 2026, 15(2), 885; https://doi.org/10.3390/jcm15020885 - 21 Jan 2026
Cited by 1 | Viewed by 946
Abstract
Diffusion-weighted imaging (DWI) has been increasingly utilized in the emergent evaluation of acute ischemic stroke (AIS) patients. DWI enhances sensitivity and specificity and enables the use of delayed reperfusion treatments in selected cases. However, DWI is not devoid of limitations. DWI-negative AIS is [...] Read more.
Diffusion-weighted imaging (DWI) has been increasingly utilized in the emergent evaluation of acute ischemic stroke (AIS) patients. DWI enhances sensitivity and specificity and enables the use of delayed reperfusion treatments in selected cases. However, DWI is not devoid of limitations. DWI-negative AIS is not uncommon in clinical practice and is reported in up to 1 of 4 AIS patients. We reviewed the relevant literature and searched the PubMed and Google Scholar databases for studies reporting on DWI-negative AIS prevalence during the 2021–2025 time period. Additionally, we included cases from our practice to highlight key points. DWI-negative AIS prevalence was 16% in one meta-analysis and ranged from 6.9% to 23.2% in identified studies that met our inclusion criteria. The biological, pathophysiological, technical, epidemiological and clinical factors that contribute to DWI-negative stroke are presented in detail. Overall, the application of diffusion imaging modalities for stroke is not bereft of blind spots despite enhanced sensitivity. Over-reliance on advanced neuroimaging and unfamiliarity with its limitations predispose DWI to errors in AIS assessment. Awareness of the predisposing factors, treatment effect, and prognosis guides appropriate decision-making, promoting good outcomes. Prospective appropriately designed trials should address the lingering questions identified, such as the association between time of imaging and DWI negativity. Full article
(This article belongs to the Special Issue Ischemic Stroke: Diagnosis and Treatment)
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17 pages, 1235 KB  
Review
Severe Asthma Exacerbations: From Risk Factors to Precision Management Strategies
by Marina Paredes, Jeisson Osorio, Alberto García de la Fuente, Elena Rodríguez, César Picado, Iñigo Ojanguren and Ebymar Arismendi
J. Clin. Med. 2026, 15(2), 857; https://doi.org/10.3390/jcm15020857 - 21 Jan 2026
Cited by 1 | Viewed by 2272
Abstract
Background: Severe asthma exacerbations (SAEs) significantly contribute to asthma-related morbidity, mortality, and healthcare burden. Despite therapeutic advances, a subset of patients remains exacerbation-prone. This review aims to summarize current evidence on risk factors, phenotypes, and biomarkers associated with SAEs, and explore personalized [...] Read more.
Background: Severe asthma exacerbations (SAEs) significantly contribute to asthma-related morbidity, mortality, and healthcare burden. Despite therapeutic advances, a subset of patients remains exacerbation-prone. This review aims to summarize current evidence on risk factors, phenotypes, and biomarkers associated with SAEs, and explore personalized strategies for their acute management. Methods: We conducted a comprehensive literature review focusing on clinical, inflammatory, and environmental drivers of SAE. Special attention was given to Type 2 (T2) biomarkers—blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO)—as tools for phenotyping and treatment guidance. Emerging evidence on the use of biologics during exacerbations was also analyzed. Results: SAEs are heterogeneous in etiology and inflammatory profile. Respiratory infections, allergen exposure, obesity, and comorbidities increase exacerbation risk. T2-high SAEs respond well to corticosteroids and biologics, whereas T2-low SAEs show limited treatment benefit. BEC and FeNO reliably predict exacerbation risk and corticosteroid responsiveness. Recent case reports suggest potential roles for anti-IL-5 and anti-thymic stromal lymphopoietin (TSLP) biologics in acute care. Conclusions: Biomarker-guided management of SAEs may enhance therapeutic precision and avoid overtreatment. Integrating phenotypic (observable characteristics) and endotypic (biological markers) assessment into acute care could improve patient outcomes and optimize resource use. Prospective trials are needed to confirm these approaches. Full article
(This article belongs to the Special Issue Advances in the Management of Chronic Cough and Severe Asthma)
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29 pages, 2077 KB  
Review
KRAS Inhibition in Pancreatic Ductal Adenocarcinoma
by Roshini Pradeep, Nooredeen Jamal Isbeih, Freya F. Abraham, Ehsan Noori, Zachary P. Yeung and Madappa N. Kundranda
J. Clin. Med. 2026, 15(2), 873; https://doi.org/10.3390/jcm15020873 - 21 Jan 2026
Cited by 2 | Viewed by 1823
Abstract
KRAS alterations are a hallmark of pancreatic ductal adenocarcinoma (PDAC) found in >90% of tumors. This review examines the historical evolution of the understanding of RAS and its central role in PDAC biology. We summarize the various downstream effectors, feedback loops, and resistance [...] Read more.
KRAS alterations are a hallmark of pancreatic ductal adenocarcinoma (PDAC) found in >90% of tumors. This review examines the historical evolution of the understanding of RAS and its central role in PDAC biology. We summarize the various downstream effectors, feedback loops, and resistance mechanisms that play a pivotal role in PDAC oncogenesis. Our review explores the early development of covalent inhibitors of KRAS G12C and efforts at specific inhibition of other codons and newer approaches of targeted protein degradation. We subsequently summarize the development of panRAS inhibitors and allosteric and switch-region targeting before focusing on rational therapeutic blockade of crosstalk and upstream signaling, with attention to synthetic lethality approaches transitioning from preclinical to early-phase in-human clinical trials. This review elaborates on ongoing KRAS-specific siRNA research and evolving KRAS-directed immunotherapies. We conclude by outlining the current KRAS clinical trial landscape and future areas of investigation. Full article
(This article belongs to the Special Issue Diagnosis, Treatment, and Management of Gastrointestinal Oncology)
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13 pages, 809 KB  
Article
Antenatal Imaging and Neonatal Outcome in Infants with Congenital Cytomegalovirus Infection: The Effect of Valaciclovir
by Francesca Arcieri, Adele Vasta, Sara Sorrenti, Gregorio Volpe, Valentina D’Ambrosio, Daniele Di Mascio, Fabio Natale, Lucia Manganaro, Giuseppina Liuzzi, Maria Caterina Corigliano, Sara Bertolini, Stella Borza, Carla Camerino, Giuseppe Rizzo and Antonella Giancotti
J. Clin. Med. 2026, 15(2), 809; https://doi.org/10.3390/jcm15020809 - 19 Jan 2026
Cited by 2 | Viewed by 613
Abstract
Background: Congenital cytomegalovirus (cCMV) infection is a leading cause of neonatal morbidity. This retrospective study aimed to evaluate the efficacy of valacyclovir in reducing vertical transmission after primary maternal CMV infection and to assess the diagnostic performance of amniocentesis and prenatal imaging. Methods: [...] Read more.
Background: Congenital cytomegalovirus (cCMV) infection is a leading cause of neonatal morbidity. This retrospective study aimed to evaluate the efficacy of valacyclovir in reducing vertical transmission after primary maternal CMV infection and to assess the diagnostic performance of amniocentesis and prenatal imaging. Methods: Eighty-two pregnant women with confirmed primary CMV infection were included. Maternal CMV serology and viral DNA were assessed in blood and urine, with standardized prenatal care including serial ultrasound examinations and fetal MRI when indicated. Amniocentesis was offered to confirm fetal infection. Valacyclovir (8 g/day) was administered before 24 weeks’ gestation, and neonatal infection was diagnosed by CMV DNA detection in urine at birth. Statistical analyses were performed using SPSS version 27.0. Results: Most infections (62.2%) were diagnosed in the first trimester. Valacyclovir was administered in 97.6% of cases, and amniocentesis was performed in 81.7%, with CMV DNA detected in 19.4%. Among 74 live births, 23% of neonates were CMV-positive and 6.8% symptomatic. Seven infected neonates had negative amniocentesis (false-negative rate, 13.2%). Prenatal ultrasound and MRI failed to detect abnormalities in symptomatic cases. Conclusions: Valacyclovir may reduce, but does not eliminate, the risk of cCMV transmission. Negative amniocentesis does not fully exclude fetal infection, highlighting postnatal follow-up. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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11 pages, 463 KB  
Article
Comparison of the Surgical Treatment for Strabismus According to Its Type: Esotropia Versus Exotropia
by Antonio Martínez-Abad, Ana Siverio-Colomina, Maria Alejandra Amesty, Rosa Díez-de-la-Uz and Mario Cantó-Cerdán
J. Clin. Med. 2026, 15(2), 795; https://doi.org/10.3390/jcm15020795 - 19 Jan 2026
Cited by 1 | Viewed by 577
Abstract
Background: The direction of deviation in strabismus may influence the predictability of the surgical procedure, but this factor remains insufficiently investigated. The aim of this study was to compare postoperative changes in ocular deviation, measured by video oculography, following surgical treatment in [...] Read more.
Background: The direction of deviation in strabismus may influence the predictability of the surgical procedure, but this factor remains insufficiently investigated. The aim of this study was to compare postoperative changes in ocular deviation, measured by video oculography, following surgical treatment in patients with concomitant exotropia and esotropia. Methods: A prospective longitudinal study included 49 patients with horizontal strabismus. All patients underwent an eye examination before and after surgery, with ocular deviation measured in nine gaze positions using video oculography. Preoperative and postoperative results were analyzed separately for esotropias and exotropias to assess surgical efficacy in both conditions. Results: Ocular deviation significantly improved after strabismus surgery in both esotropia and exotropia across all nine gaze positions (p < 0.05). The greatest improvement was observed in the primary position, with an efficacy rate of 75% in exotropia (mean reduction of 14.93 prism diopters) and 78% in esotropia (mean reduction of 17.50 prism diopters). Residual postoperative deviation was similar between the two types of strabismus (p > 0.05). In non-primary gaze positions, surgical efficacy was lower—particularly during complex eye movements—in both groups. Conclusions: Strabismus surgery resulted in a significant reduction in ocular deviation across all gaze positions in patients with concomitant horizontal strabismus, as objectively assessed by video oculography. Postoperative improvements were comparable between exotropia and esotropia, with the highest surgical efficacy observed in the primary gaze position. These findings support the use of objective multigaze evaluation to more comprehensively characterize postoperative alignment and to inform future assessments of surgical outcomes. Full article
(This article belongs to the Special Issue Clinical Investigations into Diagnosing and Managing Strabismus)
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14 pages, 6217 KB  
Article
A Multimodal Analysis of Serum and Tear Crystallization Patterns in Patients with Obesity
by Cosmin Victor Ganea, Anisia Iuliana Alexa, Nicoleta Anton, Calina Anda Sandu, Madalina Ioana Bilha, Vlad Constantin Donica, Irina Andreea Pavel, Roxana Elena Ciuntu and Camelia Margareta Bogdanici
J. Clin. Med. 2026, 15(2), 773; https://doi.org/10.3390/jcm15020773 - 17 Jan 2026
Cited by 1 | Viewed by 528
Abstract
Objectives: The study examined tear and serum alterations using the ferning test and quantified the number of branches formed during the controlled drying of these biological fluids (tears and serum), in order to identify a potential diagnostic patterning test in individuals with [...] Read more.
Objectives: The study examined tear and serum alterations using the ferning test and quantified the number of branches formed during the controlled drying of these biological fluids (tears and serum), in order to identify a potential diagnostic patterning test in individuals with obesity. Methods: A total of 61 patients aged between 25 and 72 years were enrolled (median age [interquartile range] = 39.0 [26] years). BMI values ranged from 19.1 to 47.5 kg/m2, with a median BMI (interquartile range) of 29.3 (12.1) kg/m2. Results: The Kruskal–Wallis test showed statistically significant differences among at least two Schirmer classes with respect to the number of branches observed in dried tears at a brightness threshold of 220 (H(2) = 8.485, p = 0.014). According to the Dunn post hoc test, Schirmer Class 1 showed a markedly lower number of branches compared with Classes 2 and 3 (p < 0.031 and p < 0.021), whereas no significant difference was found between Classes 2 and 3. The Kruskal–Wallis test further suggested the presence of statistically significant differences in the number of branches in dried serum, quantified using ImageJ2 at a brightness threshold of 190, across visceral fat classes (H(2) = 9.583, p = 0.008). Dunn’s post hoc tests revealed that the number of branches in serum analyzed at a brightness threshold of 190 was significantly higher in visceral fat class 3 compared to class 1 (pholm = 0.006), while no statistically significant differences were observed between classes 1 and 2 or between classes 2 and 3 (pholm > 0.05). Conclusions: In addition to other obesity-specific complications patients with obesity exhibit an increased risk of developing dry eye syndrome. The combined assessment of DPT in both the tear film and serum may represent a new method for analyzing obesity-associated biomarkers. Further studies are required to determine the sensitivity and specificity of these approaches in diagnosing systemic alterations induced by excess adipose tissue. Full article
(This article belongs to the Special Issue Latest Advances in Ocular Surface Diseases)
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13 pages, 1504 KB  
Article
Adult-Acquired Esotropia: Clinical Characteristics, Risk Factors and Outcomes of a Novel Surgical Approach
by Diego José Torres García, Beatriz Pérez Morenilla, Ana Álvarez Gómez, Timoteo González-Cruces, Vanesa Díaz-Mesa, David Cerdán Palacios and Ana Morales Becerra
J. Clin. Med. 2026, 15(2), 747; https://doi.org/10.3390/jcm15020747 - 16 Jan 2026
Cited by 1 | Viewed by 724
Abstract
Objective: We aimed to study acquired esotropia in adults and its risk factors, compile treatments performed and describe surgical technique used, with a novel indication. Methods: We conducted a retrospective study of patients with insidious distant esotropia along with distant horizontal diplopia (angles [...] Read more.
Objective: We aimed to study acquired esotropia in adults and its risk factors, compile treatments performed and describe surgical technique used, with a novel indication. Methods: We conducted a retrospective study of patients with insidious distant esotropia along with distant horizontal diplopia (angles 2–30 PD with wide fusion amplitude): Refractively emmetropic, moderately myopic and mildly hyperopic. No systemic alterations. Results: 30 cases were included, average age: 38.13 ± 14.95. Mean time elapsed from the onset of symptoms to surgical treatment was 22.52. Mean spherical equivalent is −3.19 ± 2.83. Mean preoperative horizontal deviation was 18.58 ± 5.45 PD in distant vision and 5.48 ± 8.35 PD in close vision (p < 0.001). 100% of cases reported diplopia in distance vision. 20% required prismatic treatment (<10 PD) and 80% surgical (>10 PD) by lateral rectus resection, with an average of 4.82 ± 1.23 mm. Sensory result was successful in 100% of the cases and motor in 75%. Conclusions: We are facing a new type of acquired esotropia in adults that can be individualized by its clinical and therapeutic characteristics. Our prismatic and surgical treatment has been successful. Full article
(This article belongs to the Special Issue Clinical Investigations into Diagnosing and Managing Strabismus)
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23 pages, 349 KB  
Review
WADD-SEPD Consensus on Psychological Treatment of Dual Disorders I: General Recommendations, Most Used Therapies, and Severe Mental Disorders
by Ana Benito, Susana Jiménez-Murcia, Judit Tirado-Muñoz and Ana Adan
J. Clin. Med. 2026, 15(2), 730; https://doi.org/10.3390/jcm15020730 - 16 Jan 2026
Cited by 1 | Viewed by 1126
Abstract
Background/Objectives: The treatment of dual disorders (DDs) must be comprehensive and multidisciplinary. There is evidence supporting the effectiveness of psychotherapy in their treatment. However, clinical guidelines, consensus statements, and reviews on the treatment of DDs typically devote considerably less space to psychological [...] Read more.
Background/Objectives: The treatment of dual disorders (DDs) must be comprehensive and multidisciplinary. There is evidence supporting the effectiveness of psychotherapy in their treatment. However, clinical guidelines, consensus statements, and reviews on the treatment of DDs typically devote considerably less space to psychological therapy than to pharmacological therapy. Therefore, this work aimed to synthesize the available evidence, recommendations, and clinical experience on the psychological treatment of DDs to reach a consensus. Methods: Two consensus methods were sequentially implemented: the nominal group technique and the Delphi method. Results: The first part of this consensus review encompassed a compilation of general recommendations for the psychological treatment of DDs, evidence on the efficacy of the most frequently used therapies, and recommendations for the psychological treatment of severe dual mental disorders. These disorders include schizophrenia and other psychotic disorders, bipolar disorders, depressive disorders, and obsessive compulsive disorders. Conclusions: (1) Psychological treatment is effective; (2) integrated psychological treatment is more effective; (3) motivational interviewing, cognitive behavioral therapy, and relapse prevention are the psychological interventions with the most supporting evidence; (4) the best alternative is multicomponent strategies; (5) the most frequently studied severe mental disorders are schizophrenia and depression; (6) for dual schizophrenia, motivational interviewing and integrated cognitive behavioral therapy combined with other components are recommended; (7) for dual depression, cognitive behavioral therapy with relapse prevention or motivational interviewing is recommended; (8) for dual bipolar disorder, group therapies with psychoeducation or relapse prevention and inclusion of the family, contingency management, and family intervention are recommended; (9) more empirical evidence is needed, especially for obsessive compulsive and schizoaffective disorders; and (10) more randomized clinical trials are needed to improve current methodological limitations. Full article
32 pages, 510 KB  
Review
Perioperative Blood Biomarkers of Infectious and Non-Infectious Postoperative Pulmonary Complications: A Narrative Review
by Simona Gigliotti, Giuseppe Guerriero, Giuseppe Mazza, Eugenio Garofalo, Grazia Pavia, Angela Amaddeo, Antonia Rizzuto, Nadia Marascio, Angela Quirino, Federico Longhini and Giovanni Matera
J. Clin. Med. 2026, 15(2), 699; https://doi.org/10.3390/jcm15020699 - 15 Jan 2026
Cited by 1 | Viewed by 900
Abstract
Background/Objectives: Postoperative pulmonary complications (PPCs) remain frequent and increase morbidity, mortality, and resource use. Preoperative risk scores (ARISCAT, NSQIP-derived calculators) use mostly static variables and may miss the dynamic perioperative host response preceding respiratory deterioration or infection. We address the gap in clinically [...] Read more.
Background/Objectives: Postoperative pulmonary complications (PPCs) remain frequent and increase morbidity, mortality, and resource use. Preoperative risk scores (ARISCAT, NSQIP-derived calculators) use mostly static variables and may miss the dynamic perioperative host response preceding respiratory deterioration or infection. We address the gap in clinically interpretable syntheses of perioperative blood biomarker trajectories that distinguish infectious from non-infectious PPCs and clarify bedside-ready versus exploratory markers. Methods: We conducted a narrative review with a structured Medline search (inception to 1 November 2025) plus reference screening. We included English-language adult surgical studies (observational or interventional) evaluating perioperative blood biomarkers in relation to PPCs or postoperative pulmonary infection; case reports, editorials, and reviews were excluded. No formal risk-of-bias assessment or quantitative meta-analysis was performed. Results: Across 298 cited publications, serial patterns of routinely available biomarkers (C-reactive protein, procalcitonin, lactate, albumin, and leukocyte-derived indices) were most consistently associated with PPC risk and helped separate expected postoperative inflammation from evolving infection when interpreted longitudinally rather than as single values. Mechanistic biomarkers (cytokines/immune-function assays, endothelial injury and coagulation/fibrinolysis markers, oxidative stress indicators) add biological insight but are limited by assay availability, heterogeneous sampling windows, and absent standardized cut-offs. Omics signatures and machine learning models combining biomarker kinetics with clinical variables are promising but require prospective, transportable validation. Conclusions: Key barriers to implementation include biological variability, non-specificity across postoperative syndromes, heterogeneous sampling windows, and lack of standardized cut-offs. Integrating multimarker panels into validated, dynamic predictive frameworks represents a promising direction for perioperative precision medicine. Full article
(This article belongs to the Section Anesthesiology)
21 pages, 860 KB  
Review
Understanding the Inflammatory Aspect of Osteoarthritis: Lessons from Immune Checkpoint Inhibitors
by Daniel M. Portnoy, Matthieu Paiola, Carly Tymm, Robert Winchester, Adam Mor and Yevgeniya Gartshteyn
J. Clin. Med. 2026, 15(2), 658; https://doi.org/10.3390/jcm15020658 - 14 Jan 2026
Cited by 1 | Viewed by 858
Abstract
Osteoarthritis (OA) is the most prevalent form of arthritis and is a major global health burden. OA is a heterogeneous condition with multiple contributing mechanisms that characterize different subtypes and stages of the disease. In this review, we examine the insights gained into [...] Read more.
Osteoarthritis (OA) is the most prevalent form of arthritis and is a major global health burden. OA is a heterogeneous condition with multiple contributing mechanisms that characterize different subtypes and stages of the disease. In this review, we examine the insights gained into the immunological characteristics of OA that have emerged from the increasingly widespread use of checkpoint inhibitors in the immunotherapy of malignancies. We discuss how the conventional view of OA as a degenerative disease is changing in view of the evidence suggesting that OA has an inflammatory component along with the presence in joint tissue of peripherally tolerized autoreactive resident memory T cells, which upon release of their inhibition by immunotherapy mediate immune-related adverse event arthritis (irAE-arthritis). We review clinical trials evaluating the efficacy of immunosuppressive therapies in modifying the course of OA, thereby providing an additional perspective on the presence and nature of the inflammation in OA. In summary, we argue that a shift from the traditional understanding of OA as a mechanical disease to one that incorporates the role of synovial immune cells and mechanisms of self-tolerance is necessary to guide future therapies, including the use of immune checkpoints for patients with OA. Full article
(This article belongs to the Special Issue Targeted Treatment in Chronic Inflammatory Arthritis)
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16 pages, 482 KB  
Article
Respiratory and Related Comorbidities’ Role in the Risk of Acute Sinusitis: A 15-Year Longitudinal Clinical Study
by Omar Abdel-Fattah Ahmed, Amr Sayed Ghanem, Marianna Móré and Attila Csaba Nagy
J. Clin. Med. 2026, 15(2), 660; https://doi.org/10.3390/jcm15020660 - 14 Jan 2026
Cited by 2 | Viewed by 931
Abstract
Background/Objectives: Acute sinusitis (AS) is a common infection of the upper respiratory tract that places considerable clinical and economic burden worldwide. Although frequently encountered in practice, the factors that predispose individuals to AS remain poorly understood. This study examined how different respiratory [...] Read more.
Background/Objectives: Acute sinusitis (AS) is a common infection of the upper respiratory tract that places considerable clinical and economic burden worldwide. Although frequently encountered in practice, the factors that predispose individuals to AS remain poorly understood. This study examined how different respiratory disorders and comorbidities influence the likelihood of developing AS, aiming to clarify its underlying risk profile. Methods: A longitudinal analysis was performed using electronic health records from the Clinical Center of the University of Debrecen Hospital. The study cohort (2007–2022) encompassed 37,164 observations. To evaluate the risk of AS progression, Log-Rank tests and Cox proportional hazards regressions were applied whilst adjusting for covariates. Results: The risk of developing AS was significantly higher among individuals with preceding respiratory conditions. Patients with common cold demonstrated a 2.3-fold increased risk of developing AS (95% CI [1.51–3.40]). Compared to those without such disorders, participants with acute bronchitis had a 2.5-fold higher hazard of AS (95% CI 1.90–3.26). The strongest association was observed for allergic rhinitis (HR = 4.04, 95% CI 3.18–5.13), followed by chronic sinusitis (HR = 3.10, 95% CI 2.13–4.51). Chronic obstructive pulmonary disease was also identified as a significant predictor for AS (HR = 1.62, 95% CI 1.04–2.52), whereas dental pathologies were associated with a modest protective effect (HR = 0.69, 95% CI 0.48–0.97). Conclusions: Patients with allergic rhinitis, chronic sinusitis, acute bronchitis, common cold, or chronic obstructive pulmonary disease have a markedly higher risk of developing AS. Clinicians should actively screen for these conditions when assessing patients with recurrent or severe sinus infections. Early recognition and management of underlying respiratory disorders may reduce AS episodes, promote symptom control, and lessen healthcare burdens. Future research should concentrate on precision medicine to leverage AS preventive and management strategies. Full article
(This article belongs to the Special Issue Insight into Infectious Disease Epidemiology and Public Health)
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11 pages, 455 KB  
Article
Value of Routine Follow-Up After Pleomorphic Adenoma Surgery
by Yehonatan Adler, Eyal Yosefof, Ben Giladi, Mor Shukrun and Aviram Mizrachi
J. Clin. Med. 2026, 15(2), 656; https://doi.org/10.3390/jcm15020656 - 14 Jan 2026
Cited by 1 | Viewed by 605
Abstract
Objective: Pleomorphic Adenoma (PA) is the most common benign salivary gland tumor. The need and duration of follow-up post resection is debatable. The aim of our study was to examine the need for routine follow-up after PA resection. Methods: Retrospective case-series analysis of [...] Read more.
Objective: Pleomorphic Adenoma (PA) is the most common benign salivary gland tumor. The need and duration of follow-up post resection is debatable. The aim of our study was to examine the need for routine follow-up after PA resection. Methods: Retrospective case-series analysis of adult patients with PA, between 1990 and 2023. Numbers of office examinations, imaging studies, time from first surgery to recurrence and recurrence detection modality were collected. Results: Overall, 301 patients had undergone surgery for PA, of which 28 experienced recurrence (9.3%). Mean time from surgery to first recurrence was 119.5 months (range, 33–274). Of the 40 recurrences, 36 were self-discovered (90%), 2 by clinical examination (5%) and 2 by imaging (5%). A total of 618 office examinations and 155 imaging studies were performed. Conclusions: Routine examinations and imaging appear to be of low yield in most PA patients, specifically in the first 3 years. Patients should be counseled about self-detection and ominous symptoms necessitating evaluation. Full article
(This article belongs to the Section Otolaryngology)
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14 pages, 1068 KB  
Systematic Review
Use of CAD/CAM Workflow and Patient-Specific Implants for Maxillary Reconstruction: A Systematic Review
by Diana D’Alpaos, Giovanni Badiali, Francesco Ceccariglia, Ali Nosrati and Achille Tarsitano
J. Clin. Med. 2026, 15(2), 647; https://doi.org/10.3390/jcm15020647 - 13 Jan 2026
Cited by 1 | Viewed by 568
Abstract
Background: Reconstruction of the maxilla and midface remains one of the most demanding challenges in craniofacial surgery, requiring precise planning and a clear understanding of defect geometry to achieve functional and esthetic restoration. Advances in computer-assisted surgery (CAS) and virtual surgical planning [...] Read more.
Background: Reconstruction of the maxilla and midface remains one of the most demanding challenges in craniofacial surgery, requiring precise planning and a clear understanding of defect geometry to achieve functional and esthetic restoration. Advances in computer-assisted surgery (CAS) and virtual surgical planning (VSP), based on 3D segmentation of radiologic imaging, have significantly improved the management of maxillary deformities, allowing for further knowledge of patient-specific information, including anatomy, pathology, surgical planning, and reconstructive issues. The integration of computer-aided design and manufacturing (CAD/CAM) and 3D printing has further transformed reconstruction through customized titanium meshes, implants, and surgical guides. Methods:This systematic review, conducted following PRISMA 2020 guidelines, synthesizes evidence from clinical studies on CAD/CAM-assisted reconstruction of maxillary and midfacial defects of congenital, acquired, or post-resection origin. It highlights the advantages and drawbacks of maxillary reconstruction with patient-specific implants (PSISs). Primary outcomes are represented by accuracy in VSP reproduction, while secondary outcomes included esthetic results, functions, and assessment of complications. Results: Of the 44 identified articles, 10 met inclusion criteria with a time frame from April 2013 to July 2022. The outcomes of 24 treated patients are reported. CAD/CAM-guided techniques seemed to improve osteotomy accuracy, flap contouring, and implant adaptation. Conclusions: Although current data support the efficacy and safety of CAD/CAM-based approaches, limitations persist, including high costs, technological dependency, and variable long-term outcome data. This article critically evaluates the role of PSISs in maxillofacial reconstruction and outlines future directions for its standardization and broader adoption in clinical practice. Full article
(This article belongs to the Special Issue Innovations in Head and Neck Surgery)
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19 pages, 979 KB  
Article
Long-Term Auditory, Tinnitus, and Psychological Outcomes After Cochlear Implantation in Single-Sided Deafness: A Two-Year Prospective Study
by Jasper Karl Friedrich Schrader, Moritz Gröschel, Agnieszka J. Szczepek and Heidi Olze
J. Clin. Med. 2026, 15(2), 644; https://doi.org/10.3390/jcm15020644 - 13 Jan 2026
Cited by 1 | Viewed by 827
Abstract
Background/Objectives: Single-sided deafness (SSD) impairs speech perception, reduces spatial hearing, decreases quality of life, and is frequently accompanied by tinnitus. Cochlear implantation (CI) has become an established treatment option, but long-term prospective evidence across multiple functional and psychological domains remains limited. This [...] Read more.
Background/Objectives: Single-sided deafness (SSD) impairs speech perception, reduces spatial hearing, decreases quality of life, and is frequently accompanied by tinnitus. Cochlear implantation (CI) has become an established treatment option, but long-term prospective evidence across multiple functional and psychological domains remains limited. This study investigated auditory performance, subjective hearing outcomes, tinnitus burden, and psychological well-being over a two-year follow-up in a large SSD cohort. Methods: Seventy adults with SSD underwent unilateral CI. Assessments were conducted preoperatively and at 6 months, 1 year, and 2 years postoperatively. Outcome measures included the Freiburg Monosyllable Test (FS), Oldenburg Inventory (OI), Nijmegen Cochlear Implant Questionnaire (NCIQ), Tinnitus Questionnaire (TQ), Perceived Stress Questionnaire (PSQ), Generalized Anxiety Disorder scale (GAD-7), and General Depression Scale (ADS-L). Longitudinal changes were analyzed using Wilcoxon signed-rank tests with effect sizes; Holm-adjusted p-values were applied for baseline-to-follow-up comparisons. Results: Speech perception improved markedly within the first 6 months and remained stable through 2 years, with large effect sizes. All OI subdomains demonstrated early and sustained improvements in subjective hearing ability. Several hearing-related quality-of-life domains assessed by the NCIQ, particularly social interaction, self-esteem, and activity participation, showed medium-to-large long-term improvements. Tinnitus severity decreased substantially, with marked reductions observed by 6 months and maintained thereafter; the proportion of tinnitus-free patients increased at follow-up, although tinnitus symptoms persisted in a substantial subset of participants. Perceived stress was reduced initially at the early follow-up and remained below baseline thereafter. Anxiety and depressive symptoms mostly stayed within nonclinical ranges, showing no lasting changes after adjusting for multiple comparisons. Conclusions: In this prospective cohort, cochlear implantation was associated with durable improvements in auditory outcomes, tinnitus burden, and selected patient-reported quality-of-life domains over two years. Although significant functional and patient-centered improvements were noted, persistent tinnitus and diverse psychosocial outcomes underscore the need for personalized counseling and comprehensive follow-up that incorporate patient-reported outcomes and psychological assessments. Full article
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9 pages, 428 KB  
Article
Body Composition Changes After Bariatric Surgery: Magnitude, Timing, and Determinants of Excessive Fat-Free Mass Loss
by Noelia Perez-Romero, Montse Adell Trapé, Assumpta Caixàs, Ariadna Cidoncha Secilla, Christian Jose Herrero Vicente, Marina Luengo Moral, Alba Hernandez-Lazaro and Alexis Luna Aufroy
J. Clin. Med. 2026, 15(2), 630; https://doi.org/10.3390/jcm15020630 - 13 Jan 2026
Cited by 1 | Viewed by 1015
Abstract
Background: Bariatric surgery effectively treats severe obesity, but postoperative weight loss includes reductions in both fat mass (FM) and fat-free mass (FFM). Excessive FFM loss may increase the risk of sarcopenia, frailty, and long-term weight regain, yet its magnitude and determinants are not [...] Read more.
Background: Bariatric surgery effectively treats severe obesity, but postoperative weight loss includes reductions in both fat mass (FM) and fat-free mass (FFM). Excessive FFM loss may increase the risk of sarcopenia, frailty, and long-term weight regain, yet its magnitude and determinants are not fully established. Methods: We conducted a retrospective analysis of a prospectively collected cohort of 179 patients who underwent laparoscopic or robotic Roux-en-Y gastric bypass between January 2020 and December 2022. Anthropometric parameters and body composition (bioelectrical impedance analysis) were measured preoperatively and at 6 and 12 months. The proportion of FFM loss relative to total weight loss (%FFML/WL) was calculated, and excessive FFM loss was defined using published cut-offs (≥25%, ≥30%, and ≥35%). Predictors of FFM preservation were assessed through stepwise regression. Results: Baseline BMI was 44.1 ± 4.6 kg/m2, FM 54.6 ± 10.7 kg, and FFM 61.1 ± 11.9 kg. At 6 and 12 months, BMI decreased to 31.0 ± 4.2 and 28.8 ± 4.4 kg/m2, respectively; FM decreased to 35.6 ± 11.0 and 22.0 ± 10.0 kg; and FFM to 54.7 ± 9.5 and 50.1 ± 7.0 kg (all p < 0.001). Most FFM loss occurred within the first 6 months (mean − 6.4 kg). Median %FFML/WL was 26.4% at 6 months and 28.7% at 12 months. Excessive FFM loss affected 41–46% of patients (≥25%), 27–31% (≥30%), and 14% (≥35%). In multivariable analysis, FFM at 6 months was the only independent predictor of FFM at 12 months (p < 0.001). Conclusions: Bariatric surgery leads to substantial FM and FFM reductions, with nearly half of patients exceeding established %FFML/WL alert thresholds. Early postoperative body composition monitoring may help identify individuals at higher risk of FFM depletion and guide preventive strategies such as adequate protein intake and resistance training. Full article
(This article belongs to the Special Issue Clinical Updates on Metabolic and Bariatric Surgery)
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21 pages, 504 KB  
Review
Effectiveness of Nutritional Interventions in Pre-Frail or Frail Older Adults: A Scoping Review
by Izolde Bouloukaki, Antonios Christodoulakis, Antonia Aravantinou-Karlatou, Dimitrios Vavoulas, Sevasti Peraki and Ioanna Tsiligianni
J. Clin. Med. 2026, 15(2), 604; https://doi.org/10.3390/jcm15020604 - 12 Jan 2026
Cited by 1 | Viewed by 1355
Abstract
Background/Objectives: Frailty is a complex geriatric syndrome that requires a comprehensive evaluation. This approach should consider not only physical symptoms but also cognitive, psychological, functional, nutritional, and social aspects. Nutritional status is a critical and modifiable factor, making it a key area for [...] Read more.
Background/Objectives: Frailty is a complex geriatric syndrome that requires a comprehensive evaluation. This approach should consider not only physical symptoms but also cognitive, psychological, functional, nutritional, and social aspects. Nutritional status is a critical and modifiable factor, making it a key area for intervention in the prevention and management of frailty. Therefore, a scoping review was conducted to determine the effectiveness of nutritional intervention in frail/pre-frail older adults. Methods: We adopted the PRISMA-Scoping approach, and we sought studies published in MEDLINE and Scopus databases. Results: We screened 3038 studies and finally we included a total of 19 studies. The interventions included nutritional education, counseling, and supplementation, most in combination with exercise. Nutritional interventions improved frailty status, physical performance, functional status, and quality of life in older adults. Conclusions: Consequently, this scoping review indicates that multifactorial interventions combining nutritional interventions with physical activity are clearly more effective than a single approach in improving the quality of life of older patients with frailty. These provisional findings may generate hypotheses for policymakers to consider multifaceted interventions for older patients with frailty. Full article
(This article belongs to the Special Issue Clinical Management of Frailty)
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21 pages, 1238 KB  
Review
Beyond the Usual Suspects: A Narrative Review of High-Yield Non-Traditional Risk Factors for Atherosclerosis
by Dylan C. Yu, Yaser Ahmad, Maninder Randhawa, Anand S. Rai, Aritra Paul, Sara S. Elzalabany, Ryan Yu, Raj Wasan, Nayna Nanda, Navin C. Nanda and Jagadeesh K. Kalavakunta
J. Clin. Med. 2026, 15(2), 584; https://doi.org/10.3390/jcm15020584 - 11 Jan 2026
Cited by 1 | Viewed by 912
Abstract
Background: Cardiovascular risk models, such as the Framingham and atherosclerotic cardiovascular disease (ASCVD) calculators, have improved risk prediction but often fail to identify individuals who experience ASCVD events despite low or intermediate predicted risk. This suggests that underrecognized, non-traditional risk factors may [...] Read more.
Background: Cardiovascular risk models, such as the Framingham and atherosclerotic cardiovascular disease (ASCVD) calculators, have improved risk prediction but often fail to identify individuals who experience ASCVD events despite low or intermediate predicted risk. This suggests that underrecognized, non-traditional risk factors may contribute significantly to the development of atherosclerosis. Objective: This narrative review synthesizes and summarizes recent evidence on high-yield non-traditional risk factors for atherosclerosis, with a focus on clinically significant, emerging, and applicable contributors beyond conventional frameworks. This review is distinct in that it aggregates a wide array of non-traditional risk factors while also consolidating recent data on ASCVD in more vulnerable populations. Unlike the existing literature, this manuscript integrates in a single comprehensive review various domains of non-traditional atherosclerotic risk factors, including inflammatory, metabolic, behavioral, environmental, and physical pathways. An additional unique highlight in the same manuscript is the discussion of non-traditional risk factors for atherosclerosis in more vulnerable populations, specifically South Asians. We also focus on clinically actionable factors that can guide treatment decisions for clinicians. Results: Key non-traditional risk factors identified include inflammation and biomarker-based risk factors such as C-reactive protein or interleukin-6 levels, metabolic and microbial risk factors, behavioral factors such as E-cigarette use, and environmental or infectious risk factors such as air and noise pollution. We explore certain physical exam findings associated with atherosclerotic burden, such as Frank’s sign and Achilles tendon thickness. Conclusions: Atherosclerosis is a multifactorial process influenced by diverse and often overlooked factors. Integrating non-traditional risks into clinical assessment may improve early detection, guide prevention and personalize care. Future risk prediction models should incorporate molecular, behavioral, and environmental data to reflect the complex nature of cardiovascular disease. Full article
(This article belongs to the Section Cardiovascular Medicine)
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19 pages, 1472 KB  
Article
Learning Curve in Endoscopic Pituitary Surgery: Is Progress over Time Always Guaranteed? A Consecutive Series of 123 Cases from a Single Center
by Marta Koźba-Gosztyła, Anastasija Krzemińska, Tomasz Szczepański and Bogdan Czapiga
J. Clin. Med. 2026, 15(2), 569; https://doi.org/10.3390/jcm15020569 - 10 Jan 2026
Cited by 1 | Viewed by 484
Abstract
Objectives: To characterize the learning curve of endoscopic transsphenoidal pituitary adenoma surgery performed by a single neurosurgeon, assess how operative time, resection rates, and clinical outcomes evolved with experience, and identify tumor-related factors influencing surgical performance. Methods: This retrospective study included 123 consecutive [...] Read more.
Objectives: To characterize the learning curve of endoscopic transsphenoidal pituitary adenoma surgery performed by a single neurosurgeon, assess how operative time, resection rates, and clinical outcomes evolved with experience, and identify tumor-related factors influencing surgical performance. Methods: This retrospective study included 123 consecutive endoscopic transsphenoidal pituitary adenoma resections performed between 2018 and 2025. Cases were divided into quartiles according to chronological order. Clinical, radiological, endocrinological, and operative variables were analyzed. Gross total resection (GTR), biochemical remission, postoperative complications, and visual and cranial nerve outcomes were compared between quartiles. A segmented linear regression model was applied to identify changepoints in the operative-time learning curve. Statistical significance was set at p < 0.05. Results: The mean operative time decreased by 31.8%, from 160.8 min in Quartile 1 to 109.7 min in Quartile 4. Segmented regression revealed two changepoints at cases 47 and 85, defining three learning phases: a steep improvement phase, a consolidation phase, and a plateau. GTR was achieved in 51.2% of patients and did not significantly differ across quartiles. For Knosp 0–2 tumors, GTR was 76.1% overall; for Knosp 3–4 tumors, 30%. Tumor diameter, Knosp grade, and sphenoid sinus invasion were strongly associated with lower GTR rates (all p < 0.05). Biochemical remission was achieved in 74.2% of patients with functional adenomas. New or worsened postoperative pituitary insufficiency significantly decreased across quartiles (p < 0.001). Rates of postoperative diabetes insipidus (30.8%) and CSF leak (6.5%) were comparable with published literature and showed no consistent temporal trend. Conclusions: A clear learning curve exists in endoscopic pituitary surgery, with operative proficiency achieved after approximately 50 cases and an experienced plateau after ~90 cases. Surgical experience significantly reduced operative time and postoperative pituitary insufficiency but did not influence GTR rates, likely due to a high and increasing proportion of large tumors with cavernous sinus invasion. Tumor size, Knosp grade, and sphenoid sinus invasion were identified as major determinants of surgical complexity and should be accounted for when evaluating learning curves and surgical outcomes. Full article
(This article belongs to the Section Oncology)
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16 pages, 2004 KB  
Article
Suitability of Single-Branched Thoracic Endografts for the Treatment of Acute Type B Aortic Dissection—An Anatomical Feasibility and Comparative Study
by Julius Lang, Lorenz Meuli, Philip Dueppers, Alexander Zimmerman and Benedikt Reutersberg
J. Clin. Med. 2026, 15(2), 558; https://doi.org/10.3390/jcm15020558 - 9 Jan 2026
Cited by 1 | Viewed by 622
Abstract
Objectives: This study evaluated the anatomical suitability of two single-branched thoracic stent grafts—the Castor (Endovastec, China) and the Thoracic Branch Endoprosthesis (TBE, Gore, USA)—for proximal landing in aortic arch zone 2, including the left subclavian artery (LSA), in patients with acute type [...] Read more.
Objectives: This study evaluated the anatomical suitability of two single-branched thoracic stent grafts—the Castor (Endovastec, China) and the Thoracic Branch Endoprosthesis (TBE, Gore, USA)—for proximal landing in aortic arch zone 2, including the left subclavian artery (LSA), in patients with acute type B aortic dissection (TBAD). While the TBE is currently available as an off-the-shelf device (26 main bodies, 8 branch configurations), the study also aimed to define the minimal number of configurations needed to treat most patients. The same approach was applied to the Castor stent graft, currently only available as a custom-made device (CMD), to assess its potential for off-the-shelf adaptation. Methods: A retrospective analysis was performed on computed tomographic angiographies of TBAD patients treated between 2004 and 2023. Exclusion criteria included type A or non-A-non-B dissections, isolated abdominal dissections, intramural hematomas, and lack of consent. Morphometric measurements were conducted using centerline analysis software. Suitability was defined per manufacturers’ criteria and reported with 95% confidence intervals. Results: Among 100 TBAD cases, 82% (95% CI: 73.3–88.3%) were suitable for the Castor CMD with 74 configurations. Main causes of exclusion were short landing zones and atypical arch anatomies. With adjunctive procedures, 13 Castor configurations covered all morphologies; 34% could be treated off-the-shelf, and 48% required additional interventions. For the TBE, off-the-shelf suitability was 22%, increasing to 78% with adjunctive procedures (six main bodies, five branches). Conclusions: Both stent grafts are promising for proximal extension in TBAD. Reduced configuration availability necessitates more adjunctive procedures, impacting efficiency and cost. Full article
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17 pages, 839 KB  
Review
Adjunctive Use of Platelet-Derived Concentrates (Platelet-Rich Plasma, Platelet-Rich Fibrin, Concentrated Growth Factor, Platelet-Poor Plasma) in Non-Surgical Periodontal Therapy: Current Evidence and Comparative Analysis
by Sebastian Gawlak-Socka, Kinga Jeżewska, Natalia Bielecka-Kowalska and Sebastian Kłosek
J. Clin. Med. 2026, 15(2), 554; https://doi.org/10.3390/jcm15020554 - 9 Jan 2026
Cited by 1 | Viewed by 575
Abstract
Background: Periodontitis is a multifactorial, chronic inflammatory disease that leads to progressive destruction of the periodontal apparatus. Despite the effectiveness of scaling and root planing (SRP), residual inflammation and limited regenerative potential justify the search for adjunctive biologic therapies. Platelet-derived concentrates, including [...] Read more.
Background: Periodontitis is a multifactorial, chronic inflammatory disease that leads to progressive destruction of the periodontal apparatus. Despite the effectiveness of scaling and root planing (SRP), residual inflammation and limited regenerative potential justify the search for adjunctive biologic therapies. Platelet-derived concentrates, including platelet-rich plasma (PRP), platelet-rich fibrin (PRF), concentrated growth factors (CGF), and platelet-poor plasma (PPP), have gained attention as autologous sources of growth factors enhancing periodontal regeneration. Aim: This narrative review provides a comparative analysis of the biological mechanisms, preparation protocols, and clinical outcomes associated with the adjunctive use of platelet-derived concentrates in non-surgical periodontal therapy. Methods: A narrative literature review was conducted using English-language publications retrieved from PubMed and Google Scholar, covering studies published from 2012 onward. The search strategy was based on combinations of keywords related to platelet-derived concentrates and non-surgical periodontal therapy. In vitro, in vivo, and clinical studies, as well as relevant narrative, systematic, and umbrella reviews evaluating the adjunctive use of platelet-derived concentrates (PRP, PRF, CGF, and PPP) were considered. Studies focusing on biological mechanisms, preparation protocols, and clinical periodontal outcomes were included, whereas case reports, studies unrelated to periodontal therapy, and publications lacking relevant clinical or biological outcome data were excluded. Results: Most clinical studies reported improvements in probing depth reduction, clinical attachment level gain, and bleeding indices following adjunctive use of platelet-derived concentrates with SRP. PRF tended to demonstrate more consistent clinical outcomes compared to PRP, potentially related to its simplified preparation and sustained release of bioactive molecules. CGF showed promising osteogenic and angiogenic properties in preclinical and early clinical studies. PPP, although less extensively investigated, exhibited regenerative and antimicrobial potential in preliminary reports. Conclusions: Platelet-derived concentrates may serve as valuable adjuncts in non-surgical periodontal therapy; however, the current evidence is characterized by methodological heterogeneity and variable study quality. While PRF appears to yield more consistent clinical results, definitive conclusions regarding superiority among different platelet concentrates cannot be drawn. Further well-designed randomized controlled trials are required, particularly for CGF and PPP. Full article
(This article belongs to the Special Issue Advances in Periodontitis and Other Periodontal Diseases)
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14 pages, 1550 KB  
Article
Macrotrabecular-Massive Subtype Is Associated with a High Risk of the Recurrence of Hepatocellular Carcinoma
by Sung Hwan Yoo, Ji Hae Nahm, Hye Young Chang, Jung Il Lee, Jin Hong Lim and Hyun Woong Lee
J. Clin. Med. 2026, 15(2), 502; https://doi.org/10.3390/jcm15020502 - 8 Jan 2026
Cited by 1 | Viewed by 657
Abstract
Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide, mainly due to its high recurrence rate after curative treatments. The macrotrabecular-massive (MTM) subtype has recently been recognized as an aggressive histologic variant associated with vascular invasion and [...] Read more.
Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide, mainly due to its high recurrence rate after curative treatments. The macrotrabecular-massive (MTM) subtype has recently been recognized as an aggressive histologic variant associated with vascular invasion and poor differentiation. This study aimed to investigate the prognostic impact of the MTM subtype on recurrence after surgical resection of HCC. Methods: We retrospectively reviewed 171 patients who underwent curative hepatic resection for HCC between January 2007 and December 2017 at Gangnam Severance Hospital, Seoul, Korea. Clinicopathologic parameters, including immune-related features such as lymphoid infiltration and tertiary lymphoid structures (TLSs), were evaluated. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan–Meier and Cox regression analyses. Results: During a median follow-up of 4.4 ± 3.4 years, 74 patients (43.3%) experienced recurrence. The MTM subtype was significantly more frequent in the recurrence group than in the non-recurrence group (47.3% vs. 21.6%, p < 0.001). Multivariate analysis identified MTM subtype as an independent predictor of recurrence (hazard ratio, 1.88; 95% CI, 1.14–3.10; p = 0.013). Lymphoid infiltration and TLSs were not associated with prognosis. Kaplan–Meier analysis showed higher recurrence in MTM-positive cases (p = 0.001), whereas OS did not differ significantly (p = 0.094). Conclusions: The macrotrabecular-massive subtype is an independent histopathologic predictor of recurrence after curative resection in HCC. Incorporating MTM subtype recognition into postoperative risk assessment may enhance patient stratification and inform future adjuvant therapy strategies. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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12 pages, 634 KB  
Article
The Impact of ABO Blood Type on Hemoglobin Decline After Total Hip Arthroplasty
by Toshiyuki Kawai, Yaichiro Okuzu, Koji Goto, Yutaka Kuroda, Yugo Morita and Shuichi Matsuda
J. Clin. Med. 2026, 15(2), 515; https://doi.org/10.3390/jcm15020515 - 8 Jan 2026
Cited by 1 | Viewed by 665
Abstract
Background: ABO blood type was reported to have a profound influence on hemostasis. This study aimed to determine the association between ABO blood type and the hemoglobin drop after total hip arthroplasty (THA). Methods: We retrospectively reviewed the changes in hemoglobin [...] Read more.
Background: ABO blood type was reported to have a profound influence on hemostasis. This study aimed to determine the association between ABO blood type and the hemoglobin drop after total hip arthroplasty (THA). Methods: We retrospectively reviewed the changes in hemoglobin after elective primary THA. Demographic characteristics were analyzed for 794 eligible THAs. Changes in hemoglobin at postoperative days 1, 7, and 14 relative to the preoperative level were analyzed for 777 THAs that did not require allogenic blood transfusion (ABT). The effects of blood type were examined using a multivariate regression model and a propensity score matching model. Results: The hemoglobin drop was largest at 7 days, and the values differed significantly between type O cases and non-type O cases (2.68 ± 1.08 g/dL vs. 2.41 ± 1.02 g/dL; p = 0.0013). In the multivariate model, blood type O was identified as an independent factor for larger hemoglobin drop at 7 days (p = 0.015). Lower body mass index, non-hybrid THA, higher preoperative hemoglobin level, direct lateral approach, and prophylactic use of factor Xa inhibitor were also identified as independent risk factors for larger hemoglobin drop. After successful matching of 232 THAs in type O patients with 232 THAs in non-type O patients, hemoglobin drop at 7 days was significantly larger in type O patients (−2.44 ± 1.05 g/dL vs. −2.70 ± 1.05 g/dL, p = 0.0092). Conclusions: Blood type O was independently associated with a slightly greater postoperative hemoglobin decline after primary THA; however, the absolute between-group difference was small and was not accompanied by a higher allogenic transfusion rate. Therefore, ABO blood type may represent a minor risk marker and should be interpreted in the context of clinically more relevant bleeding- and hemodilution-related factors (e.g., perioperative anticoagulant/antiplatelet therapy and underlying coagulopathies). Full article
(This article belongs to the Special Issue Advanced Approaches in Hip and Knee Arthroplasty)
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21 pages, 748 KB  
Review
Uremic Pruritus in Hemodialysis: Mechanisms, Burden, and Emerging Therapies
by Marina Kljajić, Ena Parać, Armin Atić and Nikolina Bašić-Jukić
J. Clin. Med. 2026, 15(2), 494; https://doi.org/10.3390/jcm15020494 - 8 Jan 2026
Cited by 1 | Viewed by 2009
Abstract
Background/Objectives: Uremic pruritus is a common complication in patients with end-stage kidney disease undergoing maintenance hemodialysis. Despite its high prevalence and substantial impact on sleep, psychological well-being, and overall quality of life, its pathophysiology remains multifactorial and incompletely understood. This narrative review summarizes [...] Read more.
Background/Objectives: Uremic pruritus is a common complication in patients with end-stage kidney disease undergoing maintenance hemodialysis. Despite its high prevalence and substantial impact on sleep, psychological well-being, and overall quality of life, its pathophysiology remains multifactorial and incompletely understood. This narrative review summarizes contemporary evidence (2015–2025) on therapeutic strategies for uremic pruritus, with an emphasis on emerging treatments and evolving mechanistic insights. Methods: A PubMed search was conducted for original clinical studies published between 1 January 2015, and 31 October 2025, evaluating treatments for uremic pruritus in adult hemodialysis patients. Eligible study designs included randomized controlled trials and observational interventional studies. Non-English articles, pediatric studies, peritoneal dialysis studies, reviews, case reports, and studies of mixed-etiology pruritus were excluded. Earlier literature was reviewed to contextualize epidemiology and pathophysiology. Results: The review identifies multiple interacting mechanisms—including uremic toxins, immune dysregulation, mineral abnormalities, xerosis, neuropathic changes, and dysregulated opioid signaling—contributing to itch generation. Topical therapies, especially emollients and humectants, consistently improved symptoms with excellent safety profiles. Optimization of dialysis adequacy and membrane selection showed benefit in selected patients. Among systemic therapies, gabapentinoids demonstrated the most robust efficacy but required cautious dosing. Sertraline, nalbuphine, and difelikefalin showed significant antipruritic effects in controlled trials. Emerging therapies, including AST-120, omega-3 fatty acids, and the biologic dupilumab, demonstrated promising but preliminary results. Conclusions: Management of uremic pruritus requires a multifaceted, individualized approach integrating skin-directed therapies, dialysis optimization, and targeted systemic treatments. Ongoing research is needed to identify reliable biomarkers and to develop safer, more effective, mechanism-based therapies. Full article
(This article belongs to the Section Nephrology & Urology)
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12 pages, 632 KB  
Article
CLR (CRP to Lymphocytes) Score for Differentiating Simple and Complicated Appendicitis in Pediatric Patients
by Adir Alper, Ariel Galor, Mathias Lerner, Omer Levy and Osnat Zmora
J. Clin. Med. 2026, 15(1), 393; https://doi.org/10.3390/jcm15010393 - 5 Jan 2026
Cited by 3 | Viewed by 1124
Abstract
Background: Acute appendicitis, a frequent pediatric surgical emergency, requires distinguishing simple from complicated cases for treatment decisions. Current tools, such as clinical scores and ultrasound, are sometimes ineffective. This study evaluates the biomarkers: neutrophils to lymphocytes ratio (NLR), monocytes to lymphocytes ratio [...] Read more.
Background: Acute appendicitis, a frequent pediatric surgical emergency, requires distinguishing simple from complicated cases for treatment decisions. Current tools, such as clinical scores and ultrasound, are sometimes ineffective. This study evaluates the biomarkers: neutrophils to lymphocytes ratio (NLR), monocytes to lymphocytes ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophils to monocytes ratio (NMR), neutrophils to platelet ratio (NPR), pan-immune-inflammation value (PIV) ratio, and C-Reactive Protein (CRP) to lymphocytes ratio (CLR) for differentiation between simple and complicated appendicitis. Methods: A retrospective study of 878 pediatric patients (<18 years) who underwent appendectomy (2018–2024) at a tertiary medical center, with appendicitis classified as simple (SA, n = 696) or complicated (CA, n = 182) using intraoperative findings. Biomarkers were calculated from preoperative blood counts and CRP. Diagnostic accuracy was assessed using Mann–Whitney U tests, ROC curves, and logarithmic regression. Results: Patients with CA had higher neutrophils counts (13.61 ± 4.92 vs. 11.39 ± 4.29 K/μL), monocytes counts (1.23 ± 1.41 vs. 0.95 ± 0.48 K/μL), platelet counts (294.31 ± 72.73 vs. 270.15 ± 72.08 K/μL), CRP levels (88.55 ± 97.75 vs. 27.15 ± 44.74 mg/L), and elevated biomarker ratios as compared to those with SA: NLR (≥10.15, OR = 2.45), MLR (≥0.645, OR = 2.78), PLR (≥224.38, OR = 2.502), NMR (≥6.38, OR = 2.34), NPR (≥0.0405, OR = 1.876), PIV (≥2433.85, OR = 3.348), and CLR (≥11.77, OR = 5.935), all at p < 0.01. CLR demonstrated the highest accuracy (AUC = 0.772, sensitivity 78%, specificity 62.6%), outperforming established biomarkers, followed by PIV (AUC = 0.679). NPR was the least effective marker (AUC = 0.569). Conclusions: CLR, a promising biomarker, can aid in distinguishing complicated from simple appendicitis in children, and may offer accessible tools for resource-limited settings. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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11 pages, 1713 KB  
Review
Feasibility of Laparoscopic Radical Colpectomy in Locally Advanced Vaginal Cancer: A Case Report and Literature Review
by Davut Dayan, Hannes Endres, Stefan Lukac, Wolfgang Janni, Florian Ebner, Mandana Shirin Khodawandi and Jasmina Veta Darkovski
J. Clin. Med. 2026, 15(1), 385; https://doi.org/10.3390/jcm15010385 - 5 Jan 2026
Cited by 1 | Viewed by 728
Abstract
Objectives: Due to the rarity of primary vaginal carcinoma, standardized treatment approaches are limited. Radical surgery is rare, especially in advanced stages. This report evaluates the feasibility, technical aspects and outcomes of laparoscopic en bloc resection in advanced vaginal carcinoma. Case presentation [...] Read more.
Objectives: Due to the rarity of primary vaginal carcinoma, standardized treatment approaches are limited. Radical surgery is rare, especially in advanced stages. This report evaluates the feasibility, technical aspects and outcomes of laparoscopic en bloc resection in advanced vaginal carcinoma. Case presentation: A 67-year-old woman presented with pain and vaginal bleeding. Clinical examination revealed a stenosing vaginal tumour up to 2 cm above the introitus, extending to the urethra and right vulva. Biopsies confirmed invasive squamous cell carcinoma with VAIN/VIN III. Imaging revealed enlarged pelvic lymph nodes, but no distant metastases. Methods: The surgical procedure comprised laparoscopic en bloc resection, including bilateral pelvic lymphadenectomy, radical hysterectomy with bilateral salpingo-oophorectomy, and total vaginal excision down to the pelvic floor. Additionally, inguinal bilateral ICG-guided sentinel lymph node dissection, vulvectomy with clitoral preservation, and partial urethral resection were performed, followed by transvaginal specimen removal. Vaginal closure was achieved via combined transvaginal and laparoscopic pelvic floor reconstruction. The postoperative course was uneventful, with early recovery of urinary and bowel function. Final histology confirmed complete tumor resection with clear margins (pT3, pN0, L0, V0, Pn0, R0). Functional outcomes remained excellent, with no recurrence or functional impairment at one-year follow-up. Conclusions: Laparoscopic en bloc resection appears to be a feasible option for selected patients with locally advanced vaginal carcinoma, enabling complete tumour removal with preservation of pelvic floor function and resulting in favourable postoperative and oncological outcomes. Full article
(This article belongs to the Section Oncology)
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11 pages, 242 KB  
Article
Noninvasive BCL6 Preoperative Screening and Anatomic Patterns of Endometriosis in Patients with Unexplained Infertility
by Farrah Khoyloo, Camran Nezhat, Zahra Najmi, Quincy Harding, Dahnia Zarroug, Angie Tsuei and Farr Nezhat
J. Clin. Med. 2026, 15(1), 377; https://doi.org/10.3390/jcm15010377 - 4 Jan 2026
Cited by 1 | Viewed by 792
Abstract
Background/Objectives: Endometriosis is a chronic, inflammatory, estrogen-dependent disease that has historically been underdiagnosed, especially in patients with unexplained infertility. On average, diagnosis is delayed by 11 years, underscoring the need for precision medicine to improve outcomes. To compare disease severity and anatomical distribution [...] Read more.
Background/Objectives: Endometriosis is a chronic, inflammatory, estrogen-dependent disease that has historically been underdiagnosed, especially in patients with unexplained infertility. On average, diagnosis is delayed by 11 years, underscoring the need for precision medicine to improve outcomes. To compare disease severity and anatomical distribution of endometriosis between patients with unexplained infertility who underwent noninvasive Receptiva BCL6 testing before surgery and those who did not. Methods: A cross-sectional analysis was conducted on 195 women with unexplained infertility and histologically confirmed endometriosis following diagnostic video laparoscopy, with or without robotic assistance. Disease severity was staged using updated guidelines. Anatomical sites of endometriosis were documented. Patients were grouped based on whether they had undergone the Receptiva BCL6 overexpression test prior to surgery. Results: Of the 195 patients, 43 underwent Receptiva testing; 41 of them tested positive and were confirmed to have endometriosis during surgery. These patients had fewer affected anatomical regions (3.14 ± 2.09) compared to those without testing (3.93 ± 2.26; p = 0.04). The No Receptiva group also had more high-stage cases (70.39% vs. 65.12%, p-value: 0.038). In both groups, endometriosis most frequently involved the periureteral region, rectovaginal septum, and ovaries, though ovarian tissue was rarely excised to preserve fertility. Conclusions: Among patients with unexplained infertility and confirmed endometriosis, those who had preoperative Receptiva testing showed lower disease burden and severity. These findings support the potential utility of noninvasive testing to enrich diagnostic accuracy and guide earlier, more targeted intervention. Full article
(This article belongs to the Section Obstetrics & Gynecology)
16 pages, 675 KB  
Systematic Review
Clinical and Laboratory Performance of ACTIVA BioACTIVE Restorative in Primary Teeth: A Systematic Review of Pediatric Evidence
by Malina Popa, Stefania Dinu, Magda Mihaela Luca, Bogdan Andrei Bumbu, Edita Maghet and Romina Georgiana Bita
J. Clin. Med. 2026, 15(1), 373; https://doi.org/10.3390/jcm15010373 - 4 Jan 2026
Cited by 3 | Viewed by 1022
Abstract
Background and Objectives: ACTIVA BioACTIVE Restorative is a resin–ionomer hybrid marketed as a bioactive material for pediatric restorations, yet its specific performance in primary teeth has not been systematically synthesized. The study aim was to evaluate clinical and laboratory outcomes of ACTIVA in [...] Read more.
Background and Objectives: ACTIVA BioACTIVE Restorative is a resin–ionomer hybrid marketed as a bioactive material for pediatric restorations, yet its specific performance in primary teeth has not been systematically synthesized. The study aim was to evaluate clinical and laboratory outcomes of ACTIVA in primary dentition compared with established restorative materials. Methods: Following a PRISMA-aligned, OSF-registered protocol, PubMed, Scopus, and Web of Science were searched to 18 October 2025 for full-text clinical trials and in vitro studies involving ACTIVA in primary teeth or primary dentin. Eligible designs included randomized or prospective clinical studies and standardized in vitro experiments. Primary outcomes were clinical and radiographic success; secondary outcomes included placement time, shear bond strength, and calcium-ion release. Results: Three randomized clinical trials (86 children, 305 restorations) and one in vitro study met the inclusion criteria. At 12 months, clinical success with ACTIVA ranged from 97.5 to 97.8% versus 95.0–97.8% for bulk-fill and conventional composites. At 24 months, a split-mouth trial reported clinical success of 93.0% for ACTIVA and 95.3% for compomer, with radiographic success of 86.0% and 88.3%, respectively, remaining within the predefined non-inferiority margin. ACTIVA required a mean of 2.4 ± 0.6 min less placement time than compomer. In vitro, shear bond strength to primary dentin was higher for ACTIVA than for an RMGIC (4.29 ± 0.65 vs. 2.47 ± 0.32 MPa), with greater calcium-ion release at 21 days (0.77 ± 0.13 vs. 0.53 ± 0.12 ppm). Conclusions: Within 1–2 years of follow-up, ACTIVA shows clinical performance in primary molars comparable to compomer, bulk-fill, and conventional composites, while offering shorter placement time and favorable bio-interactive behavior. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
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14 pages, 666 KB  
Article
The Obesity Paradox Reconsidered: Evidence from a Multicenter Romanian Hemodialysis Cohort
by Alexandru Catalin Motofelea, Radu Pecingina, Nicu Olariu, Luciana Marc, Lazar Chisavu, Flaviu Bob, Adelina Mihaescu, Adrian Apostol, Oana Schiller, Nadica Motofelea and Adalbert Schiller
J. Clin. Med. 2026, 15(1), 357; https://doi.org/10.3390/jcm15010357 - 3 Jan 2026
Cited by 1 | Viewed by 692
Abstract
Background and Objectives: The obesity paradox in maintenance hemodialysis (MHD) patients (better survival of obese as compared to non-obese patients in MHD) remains controversial, with many published papers supporting the idea that higher BMI is protective. Data from Eastern Europe, in particular [...] Read more.
Background and Objectives: The obesity paradox in maintenance hemodialysis (MHD) patients (better survival of obese as compared to non-obese patients in MHD) remains controversial, with many published papers supporting the idea that higher BMI is protective. Data from Eastern Europe, in particular from the elderly population on hemodialysis, are limited. The aim of this study was to describe the distribution of body weight status and cardiometabolic comorbidities and to evaluate the association of BMI categories with all-cause mortality in a multi-center Romanian hemodialysis cohort. Materials and Methods: We conducted a retrospective cohort study of 679 patients with end-stage kidney disease (ESKD) undergoing maintenance haemodialysis in eight Romanian centers. All patients received thrice-weekly treatments (≥4 h/session) using high-flux dialysers. Baseline demographic, clinical, laboratory, and echocardiographic data were extracted from dialysis records. Survival across BMI groups was assessed using Kaplan–Meier curves and the log-rank test. Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause mortality, with normal weight as the reference category. Multivariable models incorporated progressive adjustment for age, sex, dialysis vintage, diabetes, major cardiovascular comorbidities, and ESKD-related factors, including anemia parameters and CKD–mineral and bone disorder (CKD-MBD) markers. Results: A total of 679 haemodialysis patients were included (mean age 57.2 ± 12.9 years; 59.1% male); 52.7% were normal weight, 28.9% overweight, and 18.4% obese. During follow-up, 360 patients (53.0%) died, with similar crude mortality across BMI groups (normal weight 51.7%, overweight 55.1%, obese 53.6%; p > 0.05). In univariate Cox analyses, older age, obesity, hypoalbuminaemia, elevated CRP, hyperphosphataemia, peripheral and cerebrovascular disease, diabetes, low dialysis adequacy (eKt/V < 1.2), and lower ultrafiltration were associated with higher mortality, whereas preserved LVEF (≥50%) was protective. In multivariable analyses, independent predictors of mortality included older age (HR 1.042 per year, p < 0.001), obesity (HR 1.411, p = 0.045), elevated CRP (HR 1.781, p < 0.001), diabetes (HR 1.775, p < 0.001), inadequate dialysis dose (eKt/V < 1.2; HR 1.343, p = 0.029), and preserved LVEF remained protective (HR 0.665, p = 0.013). The Kaplan–Meier analysis showed significantly lower survival with increasing BMI: median survival was 7.56 years in normal-weight patients, 4.56 years in overweight patients, and 3.92 years in obese individuals (log-rank p < 0.05). Conclusions: In this Romanian cohort of multicenter hemodialysis patients, obesity as measured by BMI was associated with an increased incidence of all-cause mortality, while overweight did not confer a clear survival advantage over normal weight. These findings call into question the classic hemodialysis obesity paradox and support a more cautious interpretation of the increased BMI. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: From Diagnosis to Treatment)
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14 pages, 658 KB  
Article
Examining the Unanswered Questions in TSW: A Case Series of 16 Patients and Review of the Literature
by Max Y. Lu, Anna Erickson, Aditi Vijendra, Grace Ratley, Ashleigh A. Sun, Ian A. Myles and Nadia Shobnam
J. Clin. Med. 2026, 15(1), 361; https://doi.org/10.3390/jcm15010361 - 3 Jan 2026
Cited by 1 | Viewed by 1636
Abstract
Background/Objectives: Topical steroid withdrawal syndrome is an underrecognized (and at times controversial) diagnosis, predominantly seen in individuals with a history of prolonged medium- to high-potency steroid use with sudden cessation. We aim to present topical steroid withdrawal clinical cases along with a narrative [...] Read more.
Background/Objectives: Topical steroid withdrawal syndrome is an underrecognized (and at times controversial) diagnosis, predominantly seen in individuals with a history of prolonged medium- to high-potency steroid use with sudden cessation. We aim to present topical steroid withdrawal clinical cases along with a narrative review of the literature to better characterize this understudied phenomenon. Methods: A total of 16 patients with a history of topical steroid withdrawal were enrolled in an IRB-approved clinical trial (NCT04864886). Participants underwent clinical assessments at the National Institutes of Health, including a history and physical examination, photography, genome sequencing, and comprehensive blood work. A follow-up survey assessed symptom activity and functional impact. Results: All patients reported severe itch, heat and photosensitivity, erythema, skin dryness, and pain. A total of 11 patients exhibited elevated IgE levels, 9 patients noted metallic-smelling skin, and 4 had peripheral blood eosinophilia. Symptomatic relief was observed with dupilumab, berberine, naltrexone, and various home remedies including topical ointments, vitamins, and probiotics, though effectiveness varied and often required trial and error. At follow-up, most respondents reported partial but ongoing symptoms, with several describing residual itch and intermittent interference with daily activities. Some participants continued therapeutic interventions, such as berberine, over two years after their initial evaluation. Conclusions: Our findings report improvement in patient symptoms such as itch and detail emerging management strategies that have not been discussed before. Improved recognition, physician consensus, and systemic evaluation of therapeutic options are needed to guide care and enhance quality of life for affected patients. Full article
(This article belongs to the Section Dermatology)
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21 pages, 544 KB  
Review
Carbon Dioxide Inhalation—Risks for Health or Opportunity for Physical Fitness Development?
by Natalia Danek
J. Clin. Med. 2026, 15(1), 364; https://doi.org/10.3390/jcm15010364 - 3 Jan 2026
Cited by 2 | Viewed by 1779
Abstract
Background: Carbon dioxide (CO2) is traditionally regarded as a metabolic by-product; however, growing evidence indicates that it plays an active regulatory role across multiple physiological systems. Acute hypercapnia elicits respiratory, cardiovascular, metabolic, immune, and neurocognitive responses, some of which may [...] Read more.
Background: Carbon dioxide (CO2) is traditionally regarded as a metabolic by-product; however, growing evidence indicates that it plays an active regulatory role across multiple physiological systems. Acute hypercapnia elicits respiratory, cardiovascular, metabolic, immune, and neurocognitive responses, some of which may transiently influence exercise performance. This narrative review summarizes current evidence on CO2 inhalation in healthy individuals and critically evaluates whether controlled hypercapnia may serve as a targeted stimulus in sport and exercise contexts. Methods: A narrative review of peer-reviewed English-language articles indexed in PubMed and Web of Science was conducted. A narrative approach was chosen due to the marked heterogeneity of study designs, hypercapnia-induction methods (e.g., CO2 inhalation, voluntary hypoventilation, increased respiratory dead space), participant characteristics, and outcome measures, which precluded systematic synthesis. The review focused on studies involving healthy or physically active individuals and examined acute or short-term hypercapnic exposure. No strict publication date limits were applied. Studies conducted exclusively in clinical populations were excluded. Results: Short-term, controlled hypercapnia reliably increases ventilation, sympathetic activation, cerebral and muscular blood flow, and metabolic stress. Certain hypercapnia-based interventions—such as voluntary hypoventilation or added respiratory dead space—may enhance buffering capacity, reduce lactate accumulation and improve maximal oxygen uptake (VO2max) during submaximal efforts and repeated-sprint performance during high-intensity, short-duration exercise. However, CO2 inhalation frequently induces dyspnea, anxiety, and cognitive disruption, and higher concentrations pose clear safety risks. Current evidence does not support long-term improvements in VO2max or long-duration endurance performance following hypercapnia-based interventions. Conclusions: Controlled, intermittent hypercapnia may provide a targeted metabolic and ventilatory stimulus that enhances tolerance to high-intensity exercise, yet its application remains experimental and context-dependent. The risks associated with CO2 inhalation in healthy individuals currently outweigh its potential benefits, and safe, effective training protocols have not been fully established. Further research is needed to clarify the mechanisms, long-term adaptations, and practical utility of hypercapnia-based training strategies. Full article
(This article belongs to the Special Issue Insights and Innovations in Sports Cardiology)
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13 pages, 358 KB  
Article
Cross-Sectional Study on Electrocardiographic Disorders in Patients with Ankylosing Spondylitis in Real-World Conditions
by Carlos Rodríguez-López, Bárbara Soler Bonafont, Álvaro Gamarra, Pablo Díez-Villanueva, Luis Jesús Jiménez-Borreguero, Miren Uriarte-Ecenarro, Esther F. Vicente-Rabaneda, Miguel A. González-Gay, Fernando Alfonso and Santos Castañeda
J. Clin. Med. 2026, 15(1), 362; https://doi.org/10.3390/jcm15010362 - 3 Jan 2026
Cited by 1 | Viewed by 638
Abstract
Background/Objectives: Ankylosing spondylitis (AS) has been associated with various comorbidities, including cardiovascular morbidity. Recent studies suggest that certain arrhythmias may be more frequent in AS patients than in the general population. The aim of this study was to analyze the prevalence of [...] Read more.
Background/Objectives: Ankylosing spondylitis (AS) has been associated with various comorbidities, including cardiovascular morbidity. Recent studies suggest that certain arrhythmias may be more frequent in AS patients than in the general population. The aim of this study was to analyze the prevalence of electric heart disorders (EHD) in patients with AS in real-world conditions and compare them with those reported in the general population. Methods: Descriptive cross-sectional study aiming to determine the prevalence of EHD in AS in pre-COVID-19 period. EHD were analyzed in a resting ECG and 24 h Holter monitoring. Additionally, the association between clinical and demographic variables was analyzed. Results: Among 121 patients with AS (62% men; mean ± SD age 54.6 ± 15.6 years; median [IQR] disease duration 14 (8–20) years), 18.2% presented any EHD, including 9.1% with supraventricular tachyarrhythmias (SVT) (5% atrial fibrillation [AF]) and 7.4% with atrioventricular block (AVB). Clinically relevant disorders (≥2nd-degree AVB or SVT) were observed in 9.9% of patients. In adjusted analyses, SVT was independently associated with older age and higher BMI, while any conduction delay and clinically relevant EHD were associated with age, hypertension, and disease-modifying antirheumatic-drug treatment duration. Comparisons with previous population-based studies showed similar data, with a non-significant trend toward higher AF prevalence in AS patients. Conclusions: There appears to be a trend toward a higher prevalence of arrhythmias in patients with AS in real-world conditions, which could have clinical and therapeutic implications. An association between EHD and pro-inflammatory conditions such as age and BMI was observed, supporting the hypothesis that underlying inflammation might contribute to increased arrhythmogenicity. Full article
(This article belongs to the Section Immunology & Rheumatology)
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11 pages, 6097 KB  
Article
Optimizing Ki-67 and E-Cadherin Thresholds for Improved Grade and Stage Classification in Urothelial Bladder Cancer
by Stefan Harsanyi, Zuzana Varchulova Novakova, Lucia Neuschlova, Stefan Galbavy, Lubos Danisovic, Stanislav Ziaran and Katarina Bevizova
J. Clin. Med. 2026, 15(1), 338; https://doi.org/10.3390/jcm15010338 - 2 Jan 2026
Cited by 1 | Viewed by 600
Abstract
Background: Bladder cancer exhibits substantial heterogeneity, and accurate discrimination between non-muscle-invasive (NMIBC) and muscle-invasive disease (MIBC), as well as between low-grade (LG) and high-grade (HG) tumors, remains essential for appropriate clinical management. Established immunohistochemical (IHC) markers, such as p53, Ki-67, and E-cadherin, could [...] Read more.
Background: Bladder cancer exhibits substantial heterogeneity, and accurate discrimination between non-muscle-invasive (NMIBC) and muscle-invasive disease (MIBC), as well as between low-grade (LG) and high-grade (HG) tumors, remains essential for appropriate clinical management. Established immunohistochemical (IHC) markers, such as p53, Ki-67, and E-cadherin, could be used in a new setting, but standardized cut-off values and their combined predictive value remain unclear. This study aimed to identify optimal cut-offs for these markers and to evaluate whether biomarker combinations enhance the discrimination of tumor grade and stage. Methods: A retrospective dataset of 568 cases of bladder cancer was analyzed. For each case, the expression of p53, Ki-67, and E-cadherin was quantified, and tumors were classified as NMIBC or MIBC, and as LG or HG. ROC-based cut-off selection was performed using Youden’s J criterion with 10-fold stratified cross-validation. E-cadherin was modelled using an inverted scale to reflect biological loss. Logistic regression models were used to evaluate the discriminatory performance of single markers, two-marker combinations, and a three-marker model. Cross-validated AUC values and optimal thresholds were reported. Results: Ki-67 showed the strongest single-marker performance for predicting both MIBC (AUC 0.842) and HG disease (AUC 0.813), with optimal cut-offs of ≥40% and ≥30%, respectively. p53 demonstrated moderate discrimination (AUC 0.778 for MIBC and 0.776 for HG), while E-cadherin, evaluated on an inverted scale, showed acceptable performance (AUC 0.746 for MIBC; 0.780 for HG). Combining markers yielded modest improvements, with the best performance observed for Ki-67 + E-cadherin (AUCs of 0.851 for MIBC and 0.838 for HG). Conclusions: Ki-67 is the most effective single biomarker for distinguishing invasive and HG bladder cancer, while E-cadherin provides complementary value. A two-marker panel combining Ki-67 and E-cadherin, using appropriate cut-offs, offers the highest overall performance and may serve as a practical tool for enhanced pathological stratification. Full article
(This article belongs to the Special Issue Bladder Cancer: Diagnosis and Treatments)
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15 pages, 1261 KB  
Article
Clinical, Endoscopic, and Histological Characteristics of Severe Immune Checkpoint Inhibitor-Induced Colitis
by Diego Casas Deza, Cristina Polo Cuadro, Marta Gascón Ruiz, Manuel Barreiro-de Acosta, Míriam Mañosa, Francisco Rodríguez-Moranta, Yamile Zabana, Elena Céspedes Martínez, Ingrid Ordás, José Miranda Bautista, María José García, Irene García de la Filia Molina, Cristina Roig Ramos, Alexandra Ruiz Cerulla, José Xavier Segarra-Ortega, Virginia Matallana Royo, Esther Rodríguez González, Fernando Martínez de Juan, Noemí Manceñido Marcos, Lucía Madero Velázquez, Elena Betoré Glaría, Begoña Álvarez Herrero, Gerard Suris, Alejandro Garrido Marín, Eduard Brunet Mas, Inmaculada Alonso Abreu, Javier Santos Fernández, María Vaamonde Lorenzo, Cristina Almingol Crespo, Carla Folguera, Patricia Sanz Segura, Óscar Moralejo Lozano, Laura López Couceiro, Coral Tejido Sandoval, Raquel Mena Sánchez, Empar Sainz, Miquel Marquès-Camí, Rocío Ferreiro-Iglesias, Silvia Patricia Ortega Moya, Pablo Miles Wolfe García, Pere Borras Garriga, Belén Herreros Martínez, María Calvo Iñiguez, Santiago Frago Larramona, Pablo Ladrón Abia, Xavier Serra-Ruiz, Luis Menchén, Coral Rivas Rivas, Francisco Mesonero Gismero, Raquel Vicente Lidón, Ana Gutierrez and Santiago García Lópezadd Show full author list remove Hide full author list
J. Clin. Med. 2026, 15(1), 353; https://doi.org/10.3390/jcm15010353 - 2 Jan 2026
Cited by 1 | Viewed by 1138
Abstract
Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. They can cause immune-mediated colitis (IMC), a potentially severe adverse event. Current data on severe IMC (grade 3–4) are limited, particularly regarding clinical, endoscopic, and histological features. Methods: We conducted a multicenter, retrospective observational [...] Read more.
Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. They can cause immune-mediated colitis (IMC), a potentially severe adverse event. Current data on severe IMC (grade 3–4) are limited, particularly regarding clinical, endoscopic, and histological features. Methods: We conducted a multicenter, retrospective observational study promoted by GETECCU, including adults with solid tumors who developed grade 3–4 IMC requiring hospitalization and systemic therapy. Clinical symptoms, endoscopic findings (Mayo and UCEIS indices), and histological features were systematically collected and analyzed. Results: A total of 196 patients were included. Diarrhea was universal (median 8 bowel movements/day), with 76% reporting abdominal pain and 39% rectal bleeding. Endoscopy (n = 139) revealed vascular pattern loss (80%), mucosal lesions (69%), and Mayo scores ≥2 in 69%. Histopathology (n = 141) showed abnormalities in 85%, including cryptitis (50%), lymphocytic infiltration (48%), and crypt abscesses (37%). Notably, 72% of patients with normal endoscopy had histological inflammation. Endoscopic severity correlated with bleeding and impaired general condition but not with stool frequency or pain intensity. Histological and endoscopic severity were modestly associated. Conclusions: Severe IMC presents with heterogeneous clinical, endoscopic, and histological features, with limited correlation between these domains. Endoscopic findings were often ulcerative and inflammatory, yet histological abnormalities were frequently present even in endoscopically inactive disease. These findings highlight the importance of biopsy in all suspected IMC cases and underscore the need for validated multidimensional assessment tools for accurate diagnosis and management of severe IMC. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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