Medicina, Volume 62, Issue 8 (August 2026) – 189 articles

Background and Objectives: Inborn errors of immunity (IEI), also referred to as primary immunodeficiencies, are chronic conditions characterized by recurrent infections and long-term treatment requirements that may adversely affect psychological well-being. Although mental health outcomes in patients with IEI have been increasingly recognized, data regarding the psychological impact on family members remain limited. This study aimed to evaluate anxiety and depressive symptoms in patients with IEI and their family members compared with healthy controls and to examine the association of sociodemographic and clinical factors with anxiety and depressive symptom scores. Materials and Methods: A total of 375 participants were included, comprising 34 patients with IEI, 102 family members, and 239 healthy controls. Anxiety and depressive symptoms were assessed using the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI). Group comparisons were performed using non-parametric statistical tests. Multivariable linear regression analyses were conducted to identify independent predictors of anxiety and depressive symptoms. The internal consistency of the scales was evaluated using Cronbach’s alpha, McDonald’s omega, and Guttman’s lambda-2 coefficients. Results: Both patients with IEI and their family members demonstrated significantly higher BAI and BDI scores than healthy volunteers in the unadjusted comparisons (all p < 0.001), with no statistically significant differences between patients and relatives. After multivariable adjustment using HC3 robust standard errors, healthy volunteers had significantly lower BAI and BDI scores than patients with IEI. Patient relatives had significantly lower BDI scores, but their adjusted BAI scores did not differ significantly from those of patients. Female sex remained independently associated only with higher BAI scores. The BAI and BDI showed excellent internal consistency, with all reliability coefficients exceeding 0.90. Conclusions: Patients with IEI and their family members had higher anxiety and depressive symptom scores than healthy volunteers. Although patients and relatives had comparable BAI and BDI scores in the unadjusted comparisons, adjusted analyses showed significantly lower BDI scores among relatives, whereas the adjusted BAI difference was not statistically significant. Healthy volunteers had significantly lower adjusted BAI and BDI scores than patients, and female sex was independently associated with higher BAI scores. These findings support consideration of psychological well-being at both the patient and family levels in IEI, although the cross-sectional design precludes causal inference. Full article

Background and Objectives: Olfactory dysfunction is an early non-cognitive feature of Alzheimer’s disease (AD). The volumetric behavior of olfactory and related frontal structures and their link to eating disturbances remains unclear; we therefore compared olfactory bulb (OB) and gyrus rectus (GR) volumes between patients with AD and controls and examined their relationship with eating disturbances and their diagnostic value. Materials and Methods: In this single-center, retrospective, case–control study, 135 patients with AD and 49 age-matched controls underwent 3-Tesla MRI. Right, left, and total OB and GR volumes were measured. Groups were compared using the Mann–Whitney U test; age- and sex-adjusted logistic regression and receiver operating characteristic (ROC) analyses were performed; and OB and GR volumes were compared according to eating disturbance status in patients with AD, with adjustment for age and sex. p-Values were corrected for multiple comparisons using the Benjamini–Hochberg false discovery rate procedure. Results: All OB and GR volumes were significantly lower in patients with AD compared to controls (all p < 0.001), with the total OB volume nearly half that of the controls. Among patients with AD, all OB volumes were significantly lower in those with eating disturbances (all p < 0.001) and remained independently associated after adjustment for age and sex, whereas none of the GR volumes was significantly associated with eating disturbance status after adjustment. In adjusted models, every volumetric measure was independently associated with AD (all p < 0.001). The total OB volume showed the best diagnostic performance (AUC 0.940; sensitivity 0.82; specificity 0.98), while GR volumes performed less well (AUC 0.78–0.84). Conclusions: AD is associated with marked OB and GR atrophy. OB volume was associated with eating disturbances and discriminated AD from controls with high accuracy, supporting OB volumetry as an accessible candidate imaging marker that warrants prospective validation. Full article

Background and Objectives: Facial nerve palsy (FNP) remains a clinically relevant complication after vestibular schwannoma (VS) resection. Recovery trajectories vary according to the severity of neural injury and early postoperative facial function. This study aimed to characterize the temporal pattern of facial nerve recovery during the first postoperative year and to explore factors associated with favorable long-term function. Materials and Methods: We retrospectively analyzed 51 adult patients who developed FNP after VS surgery between 2020 and 2023. Facial nerve function was assessed using the House–Brackmann (HB) grading system and the Sunnybrook Facial Grading System (SBFGS) at discharge and at 1, 3, 6, and 12 months postoperatively. Longitudinal changes were analyzed using non-parametric repeated-measures methods with effect-size estimation. Favorable 12-month facial nerve function was defined as HB grade I–II. Given the limited number of unfavorable outcomes, associations with 12-month recovery were explored using parsimonious Firth-penalized logistic regression models. Results: At discharge, 45.1% of patients had HB II, 29.4% HB III–IV, and 25.5% HB V–VI. Facial function improved significantly during follow-up. Median SBFGS total score increased from 58.0 at discharge to 99.0 at 12 months (Friedman χ² = 118.78, df = 4, p < 0.001; Kendall’s W = 0.58), while HB grade also improved significantly (χ² = 107.48, df = 4, p < 0.001; W = 0.53). At 12 months, 37/51 patients (72.5%) achieved HB I–II and none remained in the HB V–VI category. Synkinesis, defined as an SBFGS synkinesis subscore > 0, was observed in 10/51 patients (19.6%) at 6 months and 19/51 (37.3%) at 12 months. HB grade and SBFGS score at discharge were strongly inversely correlated (Spearman ρ = −0.943, p < 0.001) and were therefore evaluated in separate models. After adjustment for age and tumor size, each one-grade increase in discharge HB was associated with lower odds of favorable 12-month function (OR 0.30, 95% CI 0.11–0.58; p < 0.001), whereas each 10-point increase in discharge SBFGS was associated with higher odds of favorable function (OR 1.90, 95% CI 1.32–3.53; p < 0.001). Conclusions: Facial nerve function showed substantial longitudinal improvement during the first year after VS surgery. Early postoperative facial function was independently associated with 12-month outcome in exploratory penalized regression analyses. Recovery may continue over several months, supporting prolonged functional surveillance, while the independent contribution of rehabilitation and the effect of nerve grafting require evaluation in larger prospective cohorts. Full article

Background and Objectives: Ovarian cancer remains the most lethal gynecologic malignancy, largely due to late diagnosis and the limitations of currently available diagnostic tools. Systemic inflammatory markers derived from routine blood tests have emerged as potential low-cost biomarkers, reflecting the interaction between tumor biology and the host immune response. This study aimed to evaluate the association and diagnostic value of preoperative inflammatory markers in distinguishing malignant from non-malignant ovarian tumors. Materials and Methods: This retrospective, single-center observational study included 780 adult female patients diagnosed with ovarian tumors and treated surgically between January 2020 and December 2025. Preoperative hematological parameters were obtained from complete blood count analyses performed before any therapeutic intervention. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were calculated. Comparisons were performed among benign, borderline, and malignant tumors. To avoid collinearity between mathematically interrelated inflammatory indices, three separate multivariable logistic regression models were constructed, each including age, CA-125, and one inflammatory index. Diagnostic performance of the individual inflammatory indices was assessed using receiver operating characteristic (ROC) curve analysis. Results: Patients with malignant tumors were significantly older and exhibited higher NLR and PLR values and lower LMR values than patients with non-malignant tumors (all p < 0.001). In separate multivariable models adjusted for age and CA-125, higher NLR (OR = 1.79, 95% CI: 1.41–2.27, p < 0.001) and PLR (OR = 1.43, 95% CI: 1.17–1.75, p = 0.001) remained significantly associated with malignant ovarian tumors, whereas higher LMR was inversely associated with malignancy (OR = 0.66, 95% CI: 0.52–0.85, p = 0.001). ROC analysis demonstrated moderate discriminative ability for NLR and PLR (AUC = 0.72 for both), whereas LMR showed lower discriminative performance (AUC = 0.64). Conclusions: Preoperative systemic inflammatory indices are significantly associated with ovarian tumor malignancy. NLR and PLR were positively associated with malignant disease, whereas LMR showed an inverse association, and these relationships remained significant after adjustment for age and CA-125. However, their individual discriminative performance was modest, suggesting that these readily available inflammatory indices should be considered complementary rather than standalone biomarkers for preoperative risk assessment. Full article

Background and Objectives: Evidence regarding predictors of pathological response and long-term outcomes in older patients receiving perioperative FLOT chemotherapy for resectable gastric or gastroesophageal junction cancer remains limited. We aimed to identify factors associated with pathological response and survival in patients aged ≥65 years treated with neoadjuvant FLOT. Materials and Methods: This retrospective single-center study included 86 consecutive patients (median age, 69 years; 72.1% male) aged ≥65 years with resectable gastric or gastroesophageal junction adenocarcinoma who underwent neoadjuvant FLOT chemotherapy followed by curative-intent gastrectomy. Major pathological response was defined as College of American Pathologists tumor regression grade (CAP TRG) 0–1. Logistic regression analyses were performed to identify predictors of pathological response. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan–Meier method and Cox proportional hazards regression analyses. Results: Overall, 14 patients (16.3%) achieved a major pathological response. Body mass index (BMI) ≥ 25 kg/m² (OR 5.13, p = 0.04) was independently associated with a major pathological response. During a median follow-up of 29.2 months, 39 patients (45.3%) developed recurrence and 35 (40.7%) died. ECOG performance status (ECOG PS) ≥ 1 was independently associated with both inferior DFS (HR = 2.76, p = 0.02) and OS (HR = 2.52, p = 0.045). In addition, ypN stage 2–3 (HR = 2.58, p = 0.008) was independently associated with worse DFS, whereas positive surgical margins were independently associated with worse OS (HR = 2.62, p = 0.02). Conclusions: In older patients with resectable gastric or gastroesophageal junction adenocarcinoma treated with perioperative FLOT chemotherapy, baseline BMI was independently associated with major pathological response, whereas ECOG PS and postoperative pathological factors were independently associated with survival. These findings highlight the importance of careful patient selection and individualized multimodal treatment in this population. Full article

Background and Objectives: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterised by recurrent nodules, abscesses, sinus tract formation, and tissue remodelling. Increasing evidence suggests that oxidative stress contributes to HS pathogenesis; however, the role of the Nrf2–Keap1–Sestrin-2 axis and its interaction with matrix remodelling pathways remains poorly understood. This study aimed to evaluate serum levels of Nrf2, Keap1, Sestrin-2, asprosin, MMP-1, and TIMP-1 in patients with HS and to investigate their potential roles in disease pathophysiology. Materials and Methods: A total of 26 patients with hidradenitis suppurativa and 20 healthy volunteers were enrolled in the study. Serum biomarkers were measured in patients with HS and healthy controls. In addition to conventional statistical analyses, multivariate analyses, including PCA, PLS-DA, VIP scoring, correlation mapping, ROC analysis, heatmap visualisation, and biplot assessment, were performed to characterise biomarker interactions and discriminatory performance. Results: HS patients exhibited significantly increased serum asprosin, Keap1, and MMP-1 levels, whereas Nrf2, Sestrin-2, and TIMP-1 levels were significantly reduced compared with controls. Multivariate analyses demonstrated clear separation between patient and control groups within the cohort, indicating a distinct biochemical signature associated with HS. VIP analysis identified Nrf2, Sestrin-2, and TIMP-1 as the most influential variables contributing to group discrimination. Within the HS group, none of the pairwise biomarker correlations remained statistically significant after Benjamini–Hochberg false discovery rate (FDR) correction. ROC analysis showed diagnostic performance for Nrf2 and Sestrin-2. Conclusions: These findings suggest that alterations in serum markers related to the Nrf2–Keap1–Sestrin-2 axis and the MMP-1/TIMP-1 balance are associated with oxidative stress, inflammation, and tissue remodelling in HS. Nrf2 and Sestrin-2 may represent candidate biomarkers; however, given the modest sample size and single-centre design, their discriminatory performance should be considered exploratory and requires confirmation in larger independent cohorts. Full article

Background and Objectives: Artificial intelligence (AI) is increasingly used in clinical dentistry, but its diagnostic accuracy for oral mucosal lesions based on clinical photographs remains insufficiently validated. This prospective observational study compared the Top-1 diagnostic accuracy of ChatGPT-4o and ChatGPT-5 in identifying normal anatomical variants and pathological oral mucosal lesions and evaluated their performance across anatomical sites. Materials and Methods: Seventy adults with either normal anatomical variants (n = 21) or pathological oral mucosal lesions (n = 49) were consecutively recruited at the Department of Dental Medicine, University Hospital of Split, Croatia. One standardized clinical photograph per patient was analyzed by ChatGPT-4o and ChatGPT-5 under image-only and image-plus-text conditions using identical prompts. The reference diagnosis was established by an oral medicine specialist, with histopathological examination (HPE) performed when clinically indicated. Diagnostic performance was assessed using Top-1 accuracy and McNemar’s test. Results: Both models showed low accuracy with image-only input, but performance improved significantly after clinical information was added (p < 0.001). Overall Top-1 accuracy increased from 19.0% to 69.0% for ChatGPT-4o and from 9.0% to 51.0% for ChatGPT-5. For normal anatomical variants, accuracy increased from 14.3% to 81.0% and from 14.3% to 76.2%, respectively. For pathological oral mucosal lesions, accuracy increased from 20.4% to 63.3% and from 6.1% to 40.8%, respectively. ChatGPT-4o showed numerically higher accuracy than ChatGPT-5, particularly for pathological oral mucosal lesions, but no statistically significant difference was found between the models in the corresponding paired comparisons. Conclusions: Diagnostic performance was limited with image-only input but improved substantially when standardized clinical information accompanied the images. The numerical differences between models, particularly for pathological oral mucosal lesions, may be clinically relevant but do not establish superiority or equivalence. Neither model can currently replace conventional clinical diagnosis, and AI should be regarded as a clinical decision-support tool for evaluating oral mucosal lesions. Full article

Background and Objectives: Radical cystectomy (RC) is standard treatment for muscle-invasive bladder cancer, but the role of gynecologic organ preservation in women remains uncertain. We primarily evaluated the prevalence and predictors of pathological gynecologic organ involvement and secondarily assessed survival and developed a prediction model. Materials and Methods: This multicenter retrospective study included 232 women undergoing RC at 13 tertiary centers. Of the 232 women, 182 had clinical T2 disease and 50 had BCG-unresponsive or very-high-risk Ta/T1 non-muscle-invasive bladder cancer. Overall survival (OS) was the primary endpoint; CSS and RFS were secondary outcomes. Multivariable logistic regression was used to identify predictors and develop preoperative prediction models. Results: Pathological gynecologic organ involvement was identified in 26 patients (11.2%): uterine in 15 (6.5%), vaginal in 11 (4.7%), ovarian in five (2.2%), and adnexal in 21 (9.1%). The median OS was shorter in patients with involvement than in those without (19.0 vs. 48.0 months; p = 0.048). Vaginal and ovarian involvement were associated with shorter OS (both p < 0.001), whereas uterine and adnexal involvement were not. Pathological T stage was associated with organ involvement (p = 0.001), with the highest frequency in pT4 disease. Model 2 showed an AUC of 0.898 and an optimism-corrected AUC of 0.872. A risk score of 0 classified 31.0% as low risk, with an NPV of 97.2% and a sensitivity of 92.3%. Conclusions: Pathological gynecologic organ involvement was uncommon but associated with poorer survival. These findings may support preoperative risk stratification, although the oncologic safety of organ-preserving surgery cannot be established from pathological involvement data alone. Full article

Background and Objectives: Identification of obstructive coronary artery disease (CAD) in patients presenting with a dilated cardiomyopathy phenotype is clinically important because it may influence etiologic classification, prognosis, and subsequent management. However, real-world angiography-based data on the prevalence and angiographic severity of obstructive CAD in this setting remain limited, particularly in regional single-center cohorts. Materials and Methods: This retrospective single-center cohort study included consecutive patients presenting with a newly diagnosed dilated cardiomyopathy (DCM) phenotype of initially unknown etiology who underwent first-time diagnostic invasive coronary angiography at St. Marina University Hospital, Varna, Bulgaria, between January 2010 and December 2025. Obstructive CAD was defined as stenosis >70% in a major epicardial coronary artery with a reference vessel diameter >2.5 mm. Patients were categorized as having non-obstructive or no significant coronary stenoses, single-vessel disease, two-vessel disease, or three-vessel disease. Additional descriptive analysis assessed severe occlusive coronary lesions, defined as chronic total occlusions or subtotal stenoses. The primary endpoint was the prevalence of obstructive CAD. Secondary analyses included angiographic disease extent, vessel-level coronary involvement, severe occlusive lesions, and coronary revascularization. Results: A total of 107 patients were included. Mean age was 55.4 ± 10.9 years, and 97 patients (90.7%) were male. Obstructive CAD was identified in 19 patients (17.8%; 95% confidence interval [CI], 11.7–26.1%), whereas 88 patients (82.2%) had non-obstructive or no significant coronary stenoses. Among patients with obstructive CAD, 3 (15.8%) had single-vessel disease, 4 (21.1%) had two-vessel disease, and 12 (63.2%) had three-vessel disease. Severe occlusive coronary lesions were present in 10 of 19 patients (52.6%); 8 (42.1%) had at least one chronic total occlusion and 5 (26.3%) had at least one subtotal stenosis. Conclusions: In this retrospective single-center cohort of patients presenting with a dilated cardiomyopathy phenotype and referred for coronary angiography, obstructive CAD was present in fewer than one in five patients. In contrast, most had non-obstructive or no significant epicardial coronary stenoses. However, when obstructive CAD was present, three-vessel disease and severe occlusive lesions were frequent. These findings indicate that obstructive epicardial CAD was uncommon in this selected angiography-referred cohort while underscoring the clinical role of coronary angiography when an ischemic or mixed etiology is clinically suspected. Full article

Background and Objectives: Wearable health technologies have become increasingly important in the remote management of cardiovascular diseases (CVDs); however, their successful implementation depends not only on technical performance but also on patient usability and technology acceptance. This study aimed to evaluate the perceived usability and technology acceptance of a wearable monitoring system among patients with CVDs and to investigate whether demographic and clinical characteristics influenced these outcomes. Materials and Methods: A cross-sectional observational study was conducted among 60 patients with CVDs enrolled in a six-month wearable monitoring program at the Medical Rehabilitation Outpatient Clinic of the Avram Iancu Clinical Hospital, Oradea, Romania. Participants used a Garmin vívosmart^® 5 fitness tracker to continuously monitor physiological and behavioral parameters. At the end of the monitoring period, perceived ease of use (PEU) was assessed using the System Usability Scale (SUS), while technology acceptance was evaluated using a Technology Acceptance Model (TAM)-based questionnaire. Descriptive statistics, reliability analysis, Spearman’s rank correlation, and multiple linear regression analyses were performed. Results: The wearable monitoring system demonstrated high PEU, with a median SUS score of 82.5 (IQR = 23.1) and a mean score of 75.5 ± 17.6. Overall, 75.0% of participants rated the system as having good or excellent usability. The SUS questionnaire demonstrated acceptable internal consistency (Cronbach’s α = 0.730; McDonald’s ω = 0.741). Technology acceptance was generally favorable, with an overall median TAM-based score of 1.33 (IQR = 0.78). Age and comorbidity burden were not associated with PEU, and no participant characteristics independently predicted SUS scores. Although the overall regression model was not statistically significant, age showed a statistically significant association with the overall TAM-based score (β = 0.328, p = 0.037). Significant positive correlations were observed between PU, self-efficacy (SE), and reverse-scored technology anxiety (TA) measure (p < 0.001). Conclusions: Patients with CVDs reported high PEU and favorable acceptance of wearable monitoring technology. While usability appeared independent of demographic and clinical characteristics, technology acceptance showed an exploratory association with age, although the overall regression model was not statistically significant. These findings support the integration of wearable monitoring systems into routine cardiovascular care and highlight the importance of patient-centered implementation strategies to promote long-term engagement. Full article

Background and Objectives: Topical diclofenac is recommended over oral non-steroidal anti-inflammatory drugs (NSAIDs) for osteoarthritis, particularly in older adults and those with comorbidities, on the assumption that low systemic absorption limits renal effects. Whether this presumed safety extends to patients already at increased risk of kidney injury has not been systematically evaluated. This review assessed the evidence on renal outcomes of topical diclofenac in adults. Materials and Methods: We conducted a systematic review (PROSPERO CRD420261393454) of studies reporting renal outcomes after topical diclofenac exposure. PubMed, Embase, Web of Science, and Scopus were searched from inception to 19 April 2026. Studies were stratified a priori into increased-renal-risk and general populations and synthesised separately, without pooling. Risk of bias was assessed with RoB 2, ROBINS-I, and JBI tools, certainty with GRADE, and synthesis followed the SWiM framework. Results: Eighteen studies, contributing data from more than 500,000 participants, were included; 14 underwent primary risk-of-bias appraisal (three at low, three at serious or high risk). In general populations, topical diclofenac produced little to no change in serum creatinine or creatinine clearance and smaller renal effects than oral diclofenac, providing high-certainty evidence of a favourable profile. In increased-renal-risk populations, one adjusted cohort reported higher acute kidney injury (AKI) risk among topical NSAID users, although exposure was predominantly to non-diclofenac agents; within the same cohort, topical NSAIDs carried lower risk than systemic NSAIDs. No study evaluated early renal injury biomarkers; certainty was moderate owing to indirectness. Conclusions: Relative to oral diclofenac, topical diclofenac shows a favourable renal safety profile, with high-certainty evidence in general populations. In adults at increased renal risk, moderate-certainty evidence derived from predominantly non-diclofenac exposure over short observation windows cannot exclude a modest excess of any-stage AKI; renal risk therefore appears reduced rather than absent. Diclofenac-specific studies in chronic kidney disease using sensitive biomarkers and longer follow-up are needed. Full article

Background and Objectives: Presurgical infant orthopedics aims to reduce cleft severity and facilitate primary surgical repair during the early neonatal period, when increased tissue plasticity enhances molding. Nasoalveolar molding is widely used but requires intraoral appliances, laboratory support, specialized training, and frequent follow-up visits, which may limit accessibility and adherence. This case series reports the clinical application of presurgical lip–alveolus–nose approximation (PLANA), an extraoral technique for early presurgical cleft management, and describes the clinical changes observed during treatment in four infants. Materials and Methods: A prospective case series conducted in neonates with non-syndromic unilateral or bilateral cleft lip and/or palate referred within the first 10 days of life to the Alabama Cleft Center. Treatment consisted of a prefabricated silicone nasal aligner combined with hydrocolloid lip adhesive taping. No intraoral plates or dental impressions were used. Devices were worn 20 to 22 h daily. Follow up occurred every 2 to 4 weeks, with remote monitoring used when appropriate. Qualitative clinical observations focused on apparent changes in nasal symmetry, columellar length, septal alignment, nasal tip projection, premaxillary position, nostril dimensions, alar base width, cleft width, and lip approximation, as well as feeding tolerance, skin tolerance, and treatment adherence. These observations were assessed qualitatively through serial clinical examinations and clinical photographs; no standardized quantitative morphometric measurements were performed. Results: Four infants with complete unilateral or bilateral cleft lip and palate received PLANA treatment. Serial clinical examinations and photographs documented qualitative changes in nasolabial morphology over the course of treatment in all four patients. Qualitative clinical assessment of serial photographs and examinations suggested greater apparent nasal symmetry, apparent columellar elongation, more central-appearing nasal alignment, increased apparent nasal tip projection, apparent cleft-width reduction, and progressive lip approximation. In unilateral clefts, changes were observed in both the cleft and non-cleft nasal sides, while bilateral clefts demonstrated changes in nasal morphology bilaterally. No device-related complications or clinically significant skin intolerance were documented during the reported treatment periods. Parent-reported device wear was approximately 20–22 h per day. Conclusions: In this four-patient prospective descriptive case series, PLANA was applied clinically, with no clinically significant treatment-related complications documented during the reported treatment periods. Serial clinical observations suggested changes in nasolabial morphology during treatment. Given the small sample size, absence of a contemporaneous control group, and qualitative nature of the assessments, these findings should be interpreted as preliminary and hypothesis-generating rather than as evidence of treatment efficacy or comparative effectiveness. Larger prospective, multicenter comparative studies incorporating standardized quantitative measurements, objective adherence assessment, and long-term surgical and aesthetic outcomes are needed to evaluate the effectiveness, reproducibility, and clinical applicability of the PLANA approach. Full article

Background and Objectives: The 2024 Korean medical–political conflict caused the mass resignation of trainee physicians, raising concerns about the quality of care for time-critical emergencies. This study aimed to assess the impact of workforce disruptions on the management and outcomes of adults presenting to the emergency department (ED) with septic shock. Materials and Methods: This retrospective single-center cohort study was conducted at a tertiary care ED and included adults with septic shock between September 2022 and August 2025. This study compared the pre-conflict period, operating under a resident-supported model, with the conflict period characterized by a specialist-led staffing model. The primary outcome was the all-cause in-hospital mortality. The secondary outcomes included process-related time intervals and clinical course measurements. Multivariate logistic regression was used to identify the independent predictors of mortality. Results: Altogether, 343 patients were included (159 pre-conflict, 184 conflict). During the conflict, ED crowding significantly decreased (average concurrent ED patients: 14.9 vs. 7.6, p < 0.001). Key diagnostic process metrics, including time to blood gas analysis, blood sampling, blood culture, computed tomography, and total ED length of stay, were significantly shortened. Time-critical therapeutic intervals, such as time to empirical antibiotics, remained unchanged. In-hospital mortality did not differ significantly between the pre- and conflict periods. Multivariate analysis demonstrated that the conflict period was not independently associated with mortality; only initial serum lactate levels and Acute Physiology and Chronic Health Evaluation II scores remained significant predictors. Conclusions: The 2024 Korean medical–political conflict was not associated with increased in-hospital mortality among patients with septic shock. Process-related metrics improved, while key therapeutic intervals and overall clinical outcomes remained stable. These findings may reflect reduced ED crowding, organizational adaptation, and continued adherence to established septic shock management practices. Reduced ED volume likely contributed substantially to improvements in diagnostic and throughput-related processes. Full article

Backgroundand Objectives: Retinal microcirculation may serve as a surrogate marker of systemic vascular status and can be non-invasively assessed using optical coherence tomography angiography (OCTA). Emerging evidence suggests that retinal and choroidal microvascular alterations may occur following coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C), potentially reflecting systemic vascular and inflammatory processes. This review summarizes the current evidence regarding retinal and choroidal microvascular changes detected by OCTA in pediatric patients with COVID-19 and MIS-C. Materials and Methods: A structured literature search of the National Center for Biotechnology Information (NCBI) PubMed database was conducted from inception until April 2026. Original English-language studies evaluating retinal and choroidal microcirculation using OCTA in pediatric patients with COVID-19 or MIS-C were identified and reviewed. Results: Available studies suggest variable retinal and choroidal microvascular alterations following COVID-19 and MIS-C, including changes in vessel density, perfusion, and foveal avascular zone parameters. Several investigations reported reduced vessel density, particularly within the deep capillary plexus, whereas others demonstrated increased peripapillary vascular parameters or no significant differences during the observation period. Differences in patient characteristics, disease severity, timing of imaging, OCTA protocols, and study design likely contribute to the heterogeneity of the reported findings. Conclusions: OCTA represents a promising research tool for investigating retinal and choroidal microvascular alterations associated with pediatric COVID-19 and MIS-C. However, the available evidence remains limited by small observational studies, methodological heterogeneity and inconsistent findings. Larger prospective longitudinal studies using standardized imaging protocols are needed to determine the clinical significance and reproducibility of OCTA-derived parameters and to establish whether they may have potential as biomarkers of ocular or systemic vascular involvement. Full article

Background and Objectives: Chronic non-specific neck pain (CNNP) is common among desk-based workers exposed to increased ergonomic risk and is accompanied by functional impairments. This study examined associations between exercise participation and pain intensity, upper-extremity disability, body awareness, and perceived sagittal trunk appearance in this population. Materials and Methods: This cross-sectional study included 250 of 512 screened desk-based workers with CNNP, pain severity ≥4/10, and a Rapid Upper Limb Assessment (RULA) score ≥ 3/7. Physical activity, upper-extremity disability, body awareness, perceived sagittal trunk appearance, and ergonomic risk were assessed using the IPAQ-SF, QuickDASH, Body Awareness Rating Questionnaire (BARQ), KyphoTAPS, and a video-call-based RULA. Results: Participants reporting exercise participation had lower QuickDASH scores (p = 0.003, d = −0.42) and higher BARQ total scores (p = 0.023, d = 0.33) than non-exercisers. BARQ function and awareness scores were higher in this group (p = 0.004 and p = 0.033), while pain severity, perceived sagittal trunk appearance, and ergonomic risk were similar between groups. QuickDASH scores were positively correlated with pain severity (rho = 0.636–0.727) and negatively correlated with BARQ total scores (rho = −0.477). RULA scores showed a weak positive correlation with general neck pain (rho = 0.288) (FDR-adjusted p < 0.002). Exploratory adjusted analyses showed that participants reporting regular exercise participation had lower QuickDASH and higher BARQ total scores than non-exercisers in all models. Participants reporting low-frequency exercise participation had lower QuickDASH scores than non-exercisers only in Model 4. Conclusions: Self-reported exercise participation may be associated with lower QuickDASH scores and higher BARQ total scores in desk-based workers with CNNP and increased ergonomic risk. Because maintaining consistent exercise participation can be challenging in occupational settings, future studies should investigate feasible exercise strategies to address pain-related, functional, and perceptual outcomes among occupational populations exposed to prolonged ergonomic loading. Full article

Background and Objectives: Transfusion-related immunomodulation (TRIM) is a recognized immunosuppressive phenomenon whose interaction with immune checkpoint blockade remains poorly defined. We evaluated the impact of erythrocyte suspension transfusion on survival and immune-related toxicity in patients with metastatic non-small cell lung cancer (NSCLC) treated with nivolumab. Materials and Methods: This retrospective, multicenter study included 253 patients with metastatic NSCLC treated with nivolumab across five centers between April 2018 and March 2025. Patients who received a transfusion within three months before or during nivolumab therapy were compared with non-transfused patients. Survival was assessed using Kaplan–Meier and Cox regression analyses. Results: Forty-two patients (16.6%) received transfusion. Transfused patients had significantly shorter progression-free survival (PFS) (median 3.6 vs. 9.3 months; HR = 2.28, 95% CI 1.47–3.56, p < 0.001) and overall survival (OS) (median 5.8 vs. 16.3 months; HR = 2.76, 95% CI 1.86–4.11, p < 0.001). In multivariable analysis, transfusion was an independent predictor of both shorter PFS (HR = 2.288, 95% CI 1.470–3.561, p < 0.001) and shorter OS (HR = 2.351, 95% CI 1.565–3.533, p < 0.001), independent of transfusion volume. No statistically significant association was detected between transfusion status and the incidence of nivolumab-related toxicity (p = 0.585), although this analysis was likely underpowered, whereas nivolumab-related toxicity was an independent favorable prognostic factor. Conclusions: Erythrocyte transfusion independently predicted poorer survival but not immune-related toxicity in nivolumab-treated metastatic NSCLC, supporting more judicious transfusion practices during immunotherapy. Full article

Background: Multisystem inflammatory syndrome in children (MIS-C) was recognized in 2020 as a post-infectious hyperinflammatory condition occurring 2–6 weeks after SARS-CoV-2 infection. While large studies from Europe and North America have described its clinical spectrum and outcomes, evidence from the Middle East remains limited. MIS-C shares features with Kawasaki disease (KD), including persistent fever, mucocutaneous manifestations, and cardiac involvement, but differs in age distribution, gastrointestinal involvement, and patterns of cardiac injury. Objective: To map the reported Middle Eastern evidence on the clinical and laboratory phenotype, Kawasaki-like manifestations, cardiovascular involvement, management, short-term outcomes, and evidence gaps in children with MIS-C. Methods: A scoping review was conducted using the Arksey and O’Malley framework, guided by Joanna Briggs Institute methodology and reported according to PRISMA-ScR. PubMed/MEDLINE, Scopus, Web of Science, and the WHO COVID-19 database were searched for studies published from 1 December 2020 through 30 September 2025. Two reviewers independently screened records in Rayyan and charted data using standardized forms. Findings were synthesized descriptively; numerical ranges reflect values reported across selected contributing studies and are not pooled regional estimates. Results: Twenty-seven original clinical studies met the eligibility criteria, including case reports, case series, and observational cohorts from the UAE, Saudi Arabia, Qatar, Jordan, and multinational Middle Eastern collaborations. Across the included reports, affected children were generally older than the typical classic Kawasaki disease population. Gastrointestinal symptoms were commonly reported, and myocardial dysfunction was reported more frequently than coronary artery abnormalities. Most patients received intravenous immunoglobulin, often combined with corticosteroids. Short-term outcomes were generally favorable, but the evidence was heterogeneous and follow-up was limited. No meta-analysis was performed. Conclusions: The available Middle Eastern literature suggests that MIS-C commonly presents in school-aged children with gastrointestinal, mucocutaneous, and myocardial involvement. These patterns are descriptive rather than definitive because the evidence is predominantly retrospective, geographically uneven, and methodologically heterogeneous. The principal contribution of this review is to map the regional literature and identify priorities for prospective, standardized, multicenter studies and long-term follow-up. Full article

Nanomaterials are increasingly used in manufacturing, medicine, consumer products, and environmental technologies due to their unique physicochemical properties. Although these materials offer substantial technological and societal benefits, their widespread use has raised concerns about potential health risks. Of particular importance is exposure during pregnancy, as certain nanoparticles can cross the placental barrier and reach the developing embryo. Fetal tissues are highly sensitive to environmental insults, so maternal exposure to nanoparticles may disrupt normal development and increase the risk of abnormal pregnancy outcomes. This review examines the current understanding of nanoparticle-induced developmental toxicity, with a focus on the vulnerability of the maternal–fetal unit. We discuss the structure and function of the placental barrier and the mechanisms that enable nanoparticle transfer from mother to fetus. Particular attention is given to how nanoparticle characteristics, including size, shape, composition, and surface chemistry, influence biodistribution, placental transport, tissue accumulation, and toxicity. We summarize the major molecular and cellular mechanisms implicated in fetotoxicity, highlighting oxidative stress, apoptosis, autophagy, and DNA damage as recurring pathways identified across experimental studies. These interconnected processes contribute to placental dysfunction, impaired fetal growth, developmental abnormalities, and adverse pregnancy outcomes. We also compare findings across different classes of nanoparticles, including metal, metal oxide, carbon-based, and polymeric nanomaterials, identifying both shared toxicological mechanisms and material-specific effects. Evidence from animal models demonstrates that susceptibility varies according to nanoparticle properties, exposure conditions, and species, underscoring the complexity of nanoparticle–biological interactions and the limitations of extrapolating experimental findings directly to humans. Overall, the available evidence indicates that nanoparticle exposure during pregnancy represents a potential risk to fetal health, although important knowledge gaps remain regarding human exposure and long-term developmental outcomes. A better understanding of the mechanisms underlying nanoparticle-induced fetotoxicity is essential for improving human health risk assessment, refining experimental models, informing regulatory policies, and supporting the safe-by-design development of nanomaterials. Such knowledge will help ensure the responsible application of nanotechnology while minimizing potential risks during pregnancy. Finally, this review is distinguished by its integrated analysis of how the chemical characteristics of nanoparticles govern placental transfer and the mechanistic pathways of fetotoxicity across multiple nanomaterial classes, providing a unified framework that connects material properties with their potential for abnormal fetal development and adverse pregnancy outcomes. Full article

Background and Objectives: Adolescent pregnancy is associated with biological, behavioral, and healthcare-related vulnerabilities that are incompletely captured by structured datasets. This study aimed to characterize selected maternal vulnerability indicators derived from narrative clinical documentation and to examine their exploratory associations with documented prenatal care deficiency and neonatal outcomes. Materials and Methods: We conducted a retrospective cohort study including 759 singleton adolescent pregnancies managed at a Romanian secondary obstetric center between 2020 and 2024. Narrative clinical observations were reviewed to extract maternal vulnerability indicators, including smoking, anemia, infection, hypertensive disorders, obesity, Rh incompatibility, and documented prenatal care deficiency. Associations between extracted variables, documented prenatal care deficiency, and neonatal outcomes were evaluated using contingency analyses, Kendall’s tau-b correlations, and multivariable logistic regression models. Results: Among pregnancies with available narrative observations, documented prenatal care deficiency was identified in 612/692 (88.4%), maternal anemia in 207/692 (29.9%), and smoking during pregnancy in 186/692 (26.9%). Validation performance differed across categories, with a sensitivity of 57.1% (95% CI 18.4–90.1%) for hypertensive disorders and wide confidence intervals for rare categories. Correlations between extracted variables were weak, indicating limited clustering of maternal risk factors. Hypertensive disorders (aOR 0.31, 95% CI 0.10–0.95, p = 0.038) and maternal obesity (aOR 0.39, 95% CI 0.16–0.98, p = 0.044) were associated with lower odds of documented prenatal care deficiency. Significant neonatal associations were observed primarily for low birth weight. Hypertensive disorders were independently associated with increased odds of low birth weight (aOR 3.56, 95% CI 1.33–9.54, p = 0.011), whereas documented maternal anemia was associated with lower observed odds of LBW (aOR 0.45, 95% CI 0.24–0.82, p = 0.009). No significant associations were identified for preterm birth or Apgar score < 7 at 5 min. Conclusions: Narrative clinical documentation allowed the identification of heterogeneous maternal vulnerability indicators that showed weak interrelationships and selective associations with prenatal surveillance patterns and low birth weight. These exploratory findings should be interpreted in the context of healthcare engagement and documentation practices. Full article

Postoperative atrial fibrillation (POAF) after cardiac surgery is often managed as a transient inpatient arrhythmia, yet recurrent or silent atrial fibrillation (AF) after discharge may identify persistent atrial vulnerability. This issue is particularly relevant in cancer survivors, whose thrombotic and bleeding risks vary according to cancer activity, treatment exposure, thrombocytopenia, frailty and planned procedures. For this narrative review, PubMed/MEDLINE and Scopus were searched from inception to 16 June 2026, with Google Scholar used for supplementary citation tracking. A total of 50 publications were included in the final narrative synthesis. Direct evidence at the intersection of cancer, cardiac surgery, POAF and digital monitoring remains limited. Accordingly, the proposed “Digital Cancer-POAF Survivorship Pathway” is presented as a conceptual, hypothesis-generating framework, rather than a validated clinical algorithm. Its distinctive contribution is to connect cancer-state phenotyping and treatment-specific arrhythmic risk with post-discharge rhythm surveillance, electrocardiogram (ECG) confirmation, multidisciplinary interpretation, data governance and outcomes for prospective validation. Digital monitoring may increase AF detection; however, whether it reduces stroke, bleeding, readmission, or healthcare utilisation in this population is unknown. Neither a low detected AF burden nor the absence of AF during finite monitoring has been validated as an independent basis for anticoagulation decisions. Full article

Background and Objectives: This retrospective cohort study aimed to evaluate the association between sagittal tibial tunnel angle and radiological and clinical outcomes following transtibial pull-out repair of medial meniscus posterior root tears. Materials and Methods: A total of 81 patients who underwent arthroscopic transtibial pull-out repair between January 2022 and October 2025 and had a minimum follow-up of 6 months were retrospectively evaluated. Demographic, clinical, radiological, and functional data were analyzed. Meniscal extrusion, hip–knee–ankle angle, mechanical axis deviation, sagittal and coronal tunnel angles, International Knee Documentation Committee (IKDC) score, and Numeric Pain Rating Scale (NPRS) score were assessed preoperatively and at 6 months postoperatively. Receiver operating characteristic (ROC) analysis was performed to explore the ability of sagittal tibial tunnel angle to discriminate achievement of the patient acceptable symptom state (PASS) based on the postoperative IKDC score. The ROC-derived 51.5° value was considered an exploratory, cohort-specific threshold. For secondary between-group comparisons, patients were classified into two groups according to sagittal tibial tunnel angle: ≤51.5° and >51.5°. Results: The cohort included 56 female patients, and the mean age was 50.0 ± 9.97 years. Receiver operating characteristic analysis identified 51.5° as the exploratory cohort-specific threshold, with an area under the curve of 0.754, sensitivity of 77.8%, and specificity of 68.9%. Patients with a sagittal tunnel angle >51.5° had lower postoperative meniscal extrusion than those with an angle ≤51.5° (3.0 mm versus 4.0 mm, p < 0.001), greater reduction in meniscal extrusion (1.10 mm versus 0.3 mm, p < 0.001), higher postoperative IKDC (71.62 ± 10.69 versus 53.0 ± 15.44, p < 0.001), and lower postoperative NPRS scores (1 versus 4, p < 0.001). Achievement of the patient acceptable symptom state was also more frequent in the >51.5° group (66.7% vs. 17.9%, p < 0.001). Conclusions: A greater sagittal tibial tunnel angle measured on 6-month postoperative MRI was associated with lower concurrent meniscal extrusion, higher functional scores, and lower pain scores following transtibial pull-out repair. However, the retrospective design and short follow-up period limit causal and long-term interpretation. The cohort-derived 51.5° threshold should be considered exploratory and requires external validation before clinical application. Full article

Background and Objectives: Urinary tract infections are common in clinical practice, but in hospital settings, especially among older and catheterized patients, the microbial ecology and resistance burden may differ substantially from community-acquired infections. Local surveillance is therefore essential to support appropriate empirical treatment and antimicrobial stewardship. The objective is to describe the microbiological epidemiology of urinary isolates in a tertiary hospital and evaluate temporal trends in antimicrobial resistance among the most frequently isolated microorganisms. Materials and Methods: This retrospective observational study analyzed microbiology laboratory data from Tor Vergata University Hospital, Rome, Italy, collected from January 2022 to June 2025. After WHONET-based deduplication using a 30-day repeat-isolate rule, 5788 deduplicated urinary isolates and 85,888 microorganism–drug associations were included. Descriptive analyses, cumulative antibiograms/antimycograms, and quarterly resistance trends were assessed using univariable and multivariable regression analyses. Results: The population was predominantly elderly, inpatient, and catheter-exposed. Gram-negative organisms predominated, followed by Gram-positive bacteria and fungi. The most frequent isolates were E. coli, K. pneumoniae, E. faecalis, and C. albicans. Although microorganism distribution remained broadly stable over time, resistance increased in several clinically relevant organism–drug combinations, especially among major Enterobacterales. Conclusions: In this high-complexity hospital population, urinary isolates showed a relatively stable microorganism distribution but progressive changes in susceptibility among selected urinary isolates. These findings support setting-specific microbiological surveillance and stewardship-informed empirical treatment strategies. Full article

Background and Objectives: The aim of this study was to evaluate the volume of dental tissue removed during conventional versus microscope-assisted coronal access cavity preparation by an undergraduate student in extracted mandibular incisors, and to compare the volumetric assessment capabilities of cone beam computed tomography (CBCT) and intraoral scanner (IOS) for this application. Materials and Methods: Thirty extracted mandibular incisors were randomly allocated to two equal groups: Group 1 (G1), access cavity preparation without magnification; and Group 2 (G2), access cavity preparation with the aid of an operating microscope. Volumetric analysis was performed using CBCT (RAYSCAN^® Alpha Plus 130) and an intraoral scanner (3Shape TRIOS^® 3) before and after access cavity preparation. Volume loss was calculated for each group. Differences in groups were assessed using the independent-samples Student’s t-test for CBCT data and the Mann–Whitney U test for IOS data. Reproducibility between methods was evaluated using the intraclass correlation coefficient (ICC). Results: The CBCT analysis revealed significantly greater tissue loss in G1 (mean 14.93 mm³, SD 4.42) than in G2 (mean 7.64 mm³, SD 2.72) (mean difference 7.29 mm³, 95% CI, 4.54–10.04; p < 0.001; Cohen’s d = 1.99, 95% CI, 1.10–2.88). The IOS analysis did not detect a statistically significant between-group difference (G1: mean 5.37 mm³ vs. G2: mean 4.55 mm³; p = 0.436). The ICC for volume loss between methods was 0.011 (95% CI: −0.150 to 0.237), below the threshold conventionally used to indicate acceptable reliability; because CBCT and IOS did not sample identical anatomical extents, this should be interpreted as limited agreement specific to the present protocols rather than general evidence of poor concordance between the two imaging methods. Conclusions: Within the limitations of this exploratory, single-operator in vitro study, microscope-assisted access cavity preparation resulted in significantly less CBCT-measured volumetric tissue loss than conventional access in mandibular incisors. Full article

Background and Objectives: Residual filling material may persist on the walls of oval root canals after mechanical retreatment, and the influence of sodium hypochlorite (NaOCl) concentration and supplementary irrigation procedures on its removal remains unclear. This laboratory study used scanning electron microscopy (SEM) to evaluate the effects of three NaOCl concentrations and five final irrigation protocols on residual filling material in retreated oval canals of mandibular premolars. The protocols tested were conventional needle irrigation (CNI), EDDY, passive ultrasonic irrigation (PUI), XP-endo Finisher R (XPFR), and Shock Wave Enhanced Emission Photoacoustic Streaming (SWEEPS). Materials and Methods: One hundred twenty extracted mandibular premolars with a single root and an oval canal were instrumented with Reciproc R25 and filled with CeraSeal and a matching gutta-percha cone using the single-cone technique. Root canal retreatment was performed using ProTaper Universal Retreatment instruments followed by Reciproc R40. The teeth were then distributed among 15 experimental subgroups according to the final irrigation protocol and NaOCl concentration used: 2.5%, 5.25%, or 8.25% (n = 8). After irrigation, each root was divided longitudinally, and one undamaged canal half was randomly chosen for SEM evaluation. Residual filling material was scored in the coronal, middle, and apical regions using an ordinal scale ranging from 1 to 5. Examiner agreement was determined with quadratically weighted Cohen’s kappa, while treatment effects were examined using a cumulative link mixed model (CLMM). Results: Residual filling material scores differed significantly according to the final irrigation protocol (p < 0.001) and root canal region (p = 0.007), but not according to NaOCl concentration (p = 0.236). The interaction between protocol and canal region was also significant (p = 0.036). In the overall comparisons, CNI produced the highest scores, whereas SWEEPS produced the lowest, and EDDY, PUI, and XPFR did not differ significantly from one another. Apical scores were higher than coronal and middle scores in the EDDY, PUI, and SWEEPS protocols, while XPFR showed no significant variation among canal regions. Conclusions: Residual filling material scores after retreatment were influenced by the final irrigation protocol and root canal region, whereas NaOCl concentration had no significant main effect. SWEEPS resulted in the lowest overall residual filling material scores and CNI in the highest, while EDDY, PUI, and XPFR showed comparable overall performance, although protocol performance varied across root canal regions. Full article

Background and Objectives: Dual-mobility cups are commonly used to reduce instability after total hip arthroplasty (THA) for femoral neck fracture (FNF), but their advantage over contemporary large-head standard cups remains uncertain. This registry study compared revision-related survival estimates up to 10 years among monoblock dual-mobility cups, modular dual-mobility constructs, and standard cups with femoral heads ≥ 36 mm in cementless THA for FNF. Materials and Methods: We retrospectively analyzed regional residents undergoing cementless, non-metal-on-metal primary THA for FNF. The cohort included 4827 THAs: 1220 monoblock dual-mobility cups, 408 modular dual-mobility constructs, and 3199 standard cups with ≥36 mm heads. Groups differed in age and sex distribution, with modular dual mobility used in older patients and both dual-mobility constructs used more often in women. Kaplan–Meier analysis estimated survival up to 10 years using aseptic failure and revision for dislocation/instability as endpoints. Cox models estimated adjusted hazard ratios, and cumulative incidence of aseptic failure was assessed with death as a competing event. Results: Kaplan–Meier-estimated 10-year aseptic failure-free survival was 94.4% for monoblock dual mobility, 96.8% for modular dual mobility, and 95.4% for standard cups (p = 0.815). Cup construct was not independently associated with aseptic failure: compared with standard cups, the HR was 1.12 for monoblock dual mobility (95% CI, 0.75–1.67) and 1.34 for modular dual mobility (95% CI, 0.71–2.52). Kaplan–Meier-estimated 10-year survival free from revision for dislocation/instability was 99.6%, 99.2%, and 99.3%, respectively (p = 0.620), with no independent effect of cup construct. Male sex increased the risk of both aseptic failure and revision for dislocation/instability. Periprosthetic fracture was the leading cause of aseptic revision in both dual-mobility groups, whereas failures were more evenly distributed in the standard cup group. Death-adjusted cumulative incidence of aseptic failure was similar across constructs (p = 0.919). Conclusions: Neither monoblock nor modular dual mobility improved revision-related outcomes compared with standard cups using femoral heads ≥ 36 mm. Late survival estimates, particularly for modular dual mobility, should be interpreted cautiously because of the limited number of patients remaining at risk. Full article

Background and Objectives: Critically ill surgical patients frequently fail to achieve prescribed enteral nutrition targets because of feeding interruptions and variability in conventional physician-directed feeding practices. Although volume-based feeding (VBF) has been proposed to improve nutritional delivery, concerns remain regarding refeeding syndrome and gastrointestinal intolerance. The aim of this study was to evaluate whether a Volume-Based Plus (VBF+) protocol integrating volume-targeted feeding with mandatory refeeding risk stratification and a standardized semi-elemental enteral formula improves nutritional delivery without increasing gastrointestinal or metabolic complications. Materials and Methods: We conducted an ambispective before-and-after implementation study (retrospective control phase, prospective intervention phase) in the surgical intensive care unit of a tertiary care center between January 2023 and March 2026. Ninety-six patients requiring enteral nutrition for ≥3 days were enrolled (48 control and 48 intervention). Both groups underwent the same refeeding risk stratification to guide feeding strategy, while the intervention group additionally received the standardized VBF+ protocol with risk-stratified caloric advancement and volume-based compensation for feeding interruptions, and a standardized semi-elemental enteral formula. The primary outcomes were median daily caloric delivery (% of target) and mean daily protein delivery (g/kg/day). Multivariable regression analyses adjusted for Nutritional Assessment Form (NAF), APACHE II score, and Charlson Comorbidity Index (CCI) were performed. Results: The VBF+ protocol was independently associated with higher caloric delivery (β = 31.2 percentage points, 95% CI 17.6 to 44.8; p < 0.001) and higher protein delivery (β = 0.168 g/kg/day, 95% CI 0.040–0.297; p = 0.011). Longitudinal analysis showed a significantly faster increase in protein delivery in the intervention group (p < 0.001), while the group-by-time interaction for caloric delivery did not reach statistical significance (p = 0.073). Rates of gastrointestinal intolerance and metabolic complications were comparable between groups; as VBF+ bundled the compensatory algorithm with a semi-elemental formula, this gastrointestinal benefit is hypothesis-generating. Conclusions: In this before-and-after study, the VBF+ bundle protocol was associated with improved caloric and protein delivery and reduced gastrointestinal intolerance; because the algorithm and formula were not evaluated independently, the gastrointestinal benefit remains hypothesis-generating and requires confirmation in randomized trials. Full article

Background and Objectives: Few cases of spontaneous evisceration through umbilical hernia (UH) in adult patients have been reported in the literature. Although uncommon, it is a potentially life-threatening surgical emergency. This scoping review aimed to map the published cases and summarize the reported clinical settings, precipitating factors, pathophysiologic mechanisms, management strategies, and outcomes. Materials and Methods: A scoping review was conducted in accordance with the PRISMA-ScR guidelines. The search was conducted through PubMed/MEDLINE and Scopus using the strings (“spontaneous evisceration” OR “spontaneous bowel evisceration” OR “umbilical hernia rupture” OR “umbilical hernia evisceration” OR “bowel evisceration umbilical” OR “umbilical evisceration” OR “bowel evisceration” OR “umbilical eventration”). Reports describing spontaneous evisceration of abdominal content through an UH in adult patients were included, whereas pediatric cases, non-umbilical eviscerations, traumatic eviscerations, animal studies, duplicates, and reports without extractable clinical data were excluded. Results: From the initial 2623 records identified, after thorough screening and reference tracking of the selected publications, 47 relevant reports for a total of 49 patients were identified. Cirrhosis was reported in 26 patients (53%), umbilical skin changes before the evisceration in 33 (67%), and death in 10 (20%). Conclusions: The available evidence suggests that spontaneous evisceration through UH is a surgical emergency that should be viewed not merely as a local mechanical event, but as the result of a multistep process involving chronic pressure overload, tissue fragility, and systemic decompensation, frequently in the setting of cirrhosis with ascites. Urgent repair is usually required, but the role of mesh reinforcement remains unclear and should be individualized according to contamination, defect size, patient condition, and ascites control. Full article

Background and Objectives: Severe traumatic limb injuries, particularly those involving extensive soft tissue damage, present significant challenges in clinical management. Thus, we aimed to critically assess the effectiveness of hyperbaric oxygen therapy (HBOT) as an adjunctive treatment for severe traumatic limb injuries. Materials and Methods: For this systematic review and meta-analysis, we conducted a systematic search of MEDLINE/PubMed, Embase, and the Cochrane Library for studies published up to 7 March 2026. We included studies evaluating the effectiveness of adjunctive HBOT in patients with severe limb injuries. The prespecified primary outcome was complete wound healing, while secondary outcomes included time to wound healing, wound necrosis, length of hospital stay (LOS), and wound infection. Risk of bias was assessed using the ROBINS-I tool for observational studies and the Cochrane RoB 2.0 for randomized controlled trials (RCTs). Results: Seven studies (three RCTs and four observational) were included. A high risk of bias was identified in two RCTs, and a serious risk of bias was noted across all four observational studies. Complete wound healing was reported in one randomized trial and favored HBOT, but the certainty of evidence was very low. The time to wound healing did not differ between the HBOT and control groups (MD, −1.44; 95% CI, −6.70 to 3.82, I² = 0%). The LOS did not differ between the HBOT and control groups (MD, −3.39; 95% CI, −14.74 to 7.79, I² = 94%). However, wound infection rates were lower in the HBOT group compared to the control group (OR, 0.31; 95% CI, 0.22–0.45, I² = 20%). Similarly, wound necrosis rates were reduced in the HBOT group (OR, 0.23; 95% CI, 0.12–0.45, I² = 41%). Conclusions: Evidence is insufficient to determine whether HBOT improves complete wound healing. Although HBOT may reduce wound infection and necrosis, the certainty of evidence was low to very low. Full article

Background: The interaction between COVID-19 vaccination and immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (NSCLC) remains incompletely characterized. Methods: Retrospective cohort study of 139 patients with stage IV NSCLC treated with first-line ICI-based therapy, stratified by vaccination status and total doses received (0–1 vs. ≥2). Progression-free (PFS) and overall survival (OS) were analyzed by Kaplan–Meier and Cox regression; logistic regression explored factors associated with treatment-related toxicity. Results: Vaccinated patients had longer median PFS (13.0 vs. 11.0 months) and OS (29.0 vs. 24.0 months; both p < 0.001). In multivariable models these associations were attenuated and of borderline significance (OS HR = 0.83, 95% CI 0.69–0.99; PFS HR = 0.79, 95% CI 0.62–0.99). Outcomes were also more favorable with ≥2 doses (median PFS 14.0 vs. 12.0 months, p = 0.001; median OS 30.0 vs. 24.0 months, p < 0.001), and tumor mutational status was the strongest independent predictor of survival. In an exploratory model, ≥2 doses were associated with higher odds of any-grade toxicity (OR = 2.47, p = 0.037); events were predominantly low grade, with no Grade 4 or 5 toxicity. Conclusions: COVID-19 vaccination was associated with improved PFS and OS in stage IV NSCLC receiving first-line ICI therapy, with a dose-related pattern. The association was attenuated after adjustment for tumor biology and is hypothesis-generating. These findings support the safety and potential clinical relevance of vaccination in this population and underline the need for structured monitoring during immunotherapy. Prospective validation is required. Full article

Background and Objectives: Laboratory parameters associated with nutritional and metabolic status may be substantially influenced by inflammatory activity, complicating their interpretation in patients with advanced neurological diseases. This study aimed to characterize within-patient changes in inflammatory biomarkers and laboratory parameters related to nutritional and metabolic status in multimorbid patients receiving long-term enteral nutrition, with particular emphasis on differences between infectious and clinically non-infectious periods. A secondary objective was to propose a conceptual framework for interpreting these laboratory parameters in the context of inflammatory activity. Materials and Methods: A prospective longitudinal observational case series was conducted in an inpatient palliative care facility. Of 23 patients who entered prospective follow-up, five completed the predefined nine-month observation period and were included in the final longitudinal analysis. Twenty-three predefined assessment time points were evaluated for each participant. Inflammatory parameters, serum proteins, micronutrient-related measurements, and vitamin concentrations were analyzed descriptively in relation to the clinical course of each patient. Results: Patients with recurrent infectious episodes demonstrated pronounced increases in inflammatory biomarkers accompanied by decreases in serum proteins, particularly albumin, transferrin, and total protein, as well as changes in serum iron (Fe) and zinc (Zn). The greatest fluctuations were observed in patients with the highest inflammatory burden, whereas patients without recurrent infections showed comparatively stable laboratory profiles. Vitamin A, vitamin D, and folate concentrations showed relatively limited fluctuations. Importantly, all five patients received continued enteral nutritional support, with daily energy intake ranging from 1450 to 1800 kcal, and body weight increased by 1.0–3.0 kg during follow-up. Based on these case-based observations and current evidence, a conceptual framework for interpreting laboratory parameters in the context of inflammatory activity was proposed. Conclusions: In patients with advanced neurological diseases, laboratory parameters associated with nutritional and metabolic status should be interpreted in the context of inflammatory activity and should not be used independently to determine nutritional status. The proposed conceptual framework is intended as an interpretative aid for laboratory findings rather than as an alternative diagnostic system for malnutrition and requires validation in larger prospective studies. Full article