Search Results (11,510)

Background/Objectives: The purpose of this study was to evaluate the reliability and diagnostic accuracy of smartphone-based photogrammetry for the assessment of pes planus and to determine its agreement with standard radiographic measurements. Methods: This prospective diagnostic study included 100 skeletally mature patients (50 males, 50 females; mean age 43.4 years) who underwent standardized lateral weight-bearing foot radiographs and smartphone-based foot photography. The calcaneal pitch angle (CPA) was measured on radiographs, and a corresponding photographic arch pitch angle (P-APA) was measured from standardized smartphone photographs using digital software (Angle Meter iOS v1.9.8). Three independent observers performed each measurement twice. Inter- and intra-observer reliability was assessed using intraclass correlation coefficients (ICC). Agreement between methods was evaluated with Pearson correlation, Lin’s concordance correlation coefficient (CCC), Bland–Altman analysis, and Deming regression. Receiver operating characteristic (ROC) analysis was performed to determine the diagnostic accuracy of calibrated P-APA, with the radiographic threshold of 18° serving as the reference standard for pes planus classification. Results: All measurements demonstrated excellent intra- and inter-observer reliability (ICC ≥ 0.900). P-APA values were systematically higher than radiographic values (31.8° ± 4.3 vs. 21.8° ± 5.5; p < 0.001). A strong correlation was observed between the two methods (r = 0.799, p < 0.001), but concordance was poor (CCC = 0.222). Bland–Altman analysis revealed a mean bias of +10.1° with wide limits of agreement (3.8° to 16.4°). Deming regression yielded the calibration equation Radiographic CPA = (P-APA × 1.371) − 21.883. ROC analysis of calibrated values yielded an AUC of 0.885 (95% CI, 0.820–0.951), with an optimal cutoff of 22.8° (sensitivity, 100%; specificity, 61.1%), corresponding to 32.6° on the uncalibrated photographic scale. Conclusions: Conventional weight-bearing radiography remains the reference standard for diagnosis and clinical decision-making in pes planus. The smartphone-derived photographic arch pitch angle is a non-equivalent surrogate measure that shows substantial systematic bias and limited agreement with radiographic calcaneal pitch, and therefore cannot replace weight-bearing radiographs. Smartphone photogrammetry may be used only as a complementary tool for preliminary screening or telemedicine support; any positive or equivocal findings require radiographic confirmation. Full article

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

Purpose: Timeliness of systemic therapy initiation for advanced lung cancer is highly dependent on pathology and molecular pathology laboratory services. Here, we aimed to prospectively evaluate liquid biopsy as a potential strategy to expedite systemic therapy decision-making in lung cancer management. Patients and Methods: This prospective cohort study included consecutive patients with suspected lung cancer seen at the time of initial specialist consultation who underwent both liquid and solid tumour biopsy (group A) and patients with confirmed lung malignancy who underwent solid tumour biopsy alone (group B), between 1 February 2022 and 31 May 2023. Due to laboratory factors, liquid biopsies were processed in batches of 13, whereas solid tumour biopsies were processed individually upon receipt, as per standard practices. Co-primary endpoints included the time from solid versus liquid biopsies to biomarker reporting and palliative systemic therapy initiation. Results: A total of 324 patients were included in the study. The median time from date of blood draw to date of liquid biopsy result was 78 days. For group A (n = 50), the median time from date of solid tumour biopsy to biomarker reporting was 22 days, and the median time from date of solid tumour biopsy to palliative systemic therapy was 42 days. The median time from date of liquid biopsy blood draw to palliative systemic therapy initiation was 56 days. For group B (n = 274), the median times from date of biopsy to biomarker reporting and to palliative systemic therapy initiation in all patients were 22 and 47 days, respectively. Conclusions: While we did not demonstrate improvement in timeliness of biomarker reporting or systemic therapy initiation with liquid biopsy, several barriers leading to delay in liquid biopsy reporting were identified due to unexpected COVID-19-related supply chain disruption and the cost-limiting need to batch sample analysis. Further studies that address the identified barriers are warranted to assess the potential improvement in timeliness of care, should liquid biopsy analysis be implemented in real-time. Full article

Background and Objectives: Psychomotor developmental delay is a frequent comorbidity in children with congenital heart defects (CHD), especially after surgical correction of the CHD and exposure to risk factors such as anesthesia, cardiopulmonary bypass and postoperative complications. Yet psychomotor delay is present in these patients before surgical correction but is under-recognized. Evidence focusing solely on unrepaired CHD remains limited. Materials and Methods: This prospective cross-sectional study evaluated 153 and included 77 children under 6 years of age with unrepaired CHD, stratified into cyanotic (n = 31) and non-cyanotic (n = 46) CHD, admitted to a pediatric cardiology department over a period of 5 years. Psychomotor development was assessed using the Denver Developmental Screening Test II (DDST-II), standardized for pediatric population. Associations with clinical, perinatal, and demographic factors were analyzed using univariate and multivariate methods. Results: Developmental delay was identified in 97% of cyanotic and 54% of non-cyanotic patients. Compared to healthy norms, CHD patients had significantly lower global developmental scores (p = 0.03). Gross motor and personal-social domains were most frequently affected. Prenatal CHD diagnosis correlated with better global developmental scores (p = 0.012), and breastfeeding was associated with improved outcomes compared with formula or mixed feeding (p = 0.008). Conclusions: Infants and young children with CHD are at increased risk of early psychomotor developmental delay, particularly in the gross motor and personal–social domains, even before exposure to surgical or intensive care damaging factors. Systematic psychomotor surveillance, integration of protective factors such as prenatal diagnosis and breastfeeding, and timely access to multidisciplinary interventions are essential to optimize long-term outcomes in this vulnerable population. Full article

Background/Objectives: Hepatocellular carcinoma remains a major cause of death from cancer globally. While ¹⁸F-FDG PET/CT is commonly used for tumor imaging, its sensitivity is limited, especially due to high liver background uptake. Recently, ⁶⁸Ga-FAPI PET/CT, which targets fibroblast activation protein in tumor stroma, has emerged as a promising diagnostic tool. In this study, we aimed to assess the diagnostic performance of ⁶⁸Ga-FAPI-04 PET/CT in HCC patients with and without liver cirrhosis and to explore the relationship between PET metrics, tumor size, and PIVKA-II serum marker. Methods: In this prospective single-center study, 59 patients with confirmed HCC (37 with cirrhosis, 22 without) underwent ⁶⁸Ga-FAPI-04 PET/CT. The standard dose (1.5–2.0 MBq/kg) was administered intravenously, and imaging was carried out 60 min post-injection. Semi-quantitative parameters including SUVmax, SUVmean, and tumor-to-background ratio were calculated. Diagnostic performance was assessed using histopathology and multimodal imaging. Statistical analyses included the Mann–Whitney U test and Spearman correlation. Results: The overall sensitivity for HCC detection was 89.8%, with a specificity of 60% and accuracy of 87%. Sensitivity and specificity showed a tendency to be lower in cirrhotic compared with non-cirrhotic patients, with a notably higher background liver uptake in cirrhosis (SUVmax 3.60 vs. 1.3, p < 0.001), resulting in lower TBR values (3.7 vs. 7.0, p < 0.001). A strong correlation between SUVmax and tumor size was seen in non-cirrhotic HCC, while a moderate association between SUVmax and PIVKA-II levels was observed in cirrhotic patients. Conclusions:⁶⁸Ga-FAPI-04 PET/CT demonstrates high sensitivity for HCC detection and may serve as a complementary imaging modality, particularly when interpreted through conventional cross-sectional imaging. Image interpretation in cirrhotic livers may be challenging due to increased background uptake and reduced TBR. Associations between PET-derived parameters, tumor size, and serum PIVKA-II levels should be considered hypothesis-generating and require validation in larger, multicenter studies with clinical outcome data. Full article

Background/Objectives: Healthcare workers at the frontline of managing pandemics are at increased risk for adverse physical and mental health outcomes, which has been shown to result in burnout. The relationship between personal resilience and burnout among clinical and non-clinical healthcare staff working in an acute care setting was assessed at the start of the COVID-19 pandemic. Methods: A prospective cross-sectional survey design with electronic questionnaires was used to measure resilience (Connor-Davidson Resilience Scale,) and burnout (Maslach Burnout Inventory—Human Services Survey). Linear regression analyses were conducted to examine the relationship between resilience and emotional exhaustion, depersonalization, and personal accomplishment. Results: A significant inverse relationship between resilience and both emotional exhaustion and depersonalization, and a positive relationship between resilience and personal accomplishment were identified. Higher resilience scores were significantly associated with lower emotional exhaustion and depersonalization and higher personal accomplishment under pandemic conditions. Conclusions: Strategies to boost resilience organization-wide amongst healthcare staff providing patient care are critical for providing skills to reduce the onset of burnout and support employee mental health. From a pandemic preparedness lens, organizational-level emergency management should consider the importance of resilience-building among staff to proactively prevent burnout and its subsequent effects on patient-care and general hospital functioning. Full article

Background: Serum C–C motif chemokine ligand 18 (seCCL18) in systemic sclerosis (SSc) has been primarily associated with progressive interstitial lung disease (SSc-ILD) and mortality. However, its relationship with non-pulmonary organ involvement, disease activity, and long-term outcome has not been comprehensively evaluated. We therefore examined the clinical relevance of seCCL18 in a single-center SSc cohort. Methods: A total of 151 patients with SSc (83 diffuse cutaneous (dcSSc), 68 limited cutaneous SSc (lcSSc); median (IQR) disease duration: 9 (4;16) years) and 47 age- and sex-matched healthy controls (HCs) were enrolled. Serum CCL18 concentrations were measured by enzyme-linked immunosorbent assay. Elevated seCCL18 was defined as >130 ng/mL (mean + 2 SD of the healthy control group). Organ involvement and disease activity (EUSTAR Activity Index, EUSTAR-AI) were assessed at baseline, while survival was analysed longitudinally. Results: Patients with SSc had significantly higher seCCL18 levels than HCs (mean ± SD: 99.9 ± 43.2 vs. 75.0 ± 27.5 ng/mL, p < 0.01). Elevated seCCL18 was associated with SSc-ILD (81.1% vs. 60.5%, p = 0.022), reduced forced vital capacity (FVC < 70%: 16.2% vs. 3.5%, p = 0.006), and reduced diffusing capacity for carbon monoxide (DLCO < 70%: 80.6% vs. 54.4%, p = 0.005). Higher seCCL18 levels were observed in patients with myocardial disease (104.8 ± 41.8 vs. 83.8 ± 44.2 ng/mL, p = 0.008), left ventricular diastolic dysfunction (107.1 ± 40.5 vs. 84.5 ± 45.0 ng/mL, p < 0.001), and oesophageal involvement (110.7 ± 38.3 vs. 93.3 ± 43.1 ng/mL, p = 0.009). SeCCL18 levels above the cut-off were more frequently associated with tendon friction rubs (51.4% vs. 27.4%, p = 0.007), active disease (EUSTAR-AI ≥ 2.5: 73% vs. 44%, p = 0.002), and elevated inflammatory markers (CRP > 5 mg/L: 51.4% vs. 19.3%, p < 0.001; ESR > 28 mm/h: 37.8% vs. 18.4%, p = 0.015). During a median follow-up of 87 months, 22 patients (15%) died. Elevated baseline seCCL18 predicted poorer survival in univariate analysis (log-rank p = 0.013) and remained an independent predictor of mortality in multivariable Cox regression (HR 1.789; 95% CI 1.133–2.824; p = 0.013), together with declining DLCO and reduced six-minute walk test performance. Conclusions: Elevated seCCL18 may identify patients with systemic sclerosis who exhibit a more severe multisystem phenotype, including cardiopulmonary, gastrointestinal, and musculoskeletal involvement, increased inflammatory activity, and reduced long-term survival. These findings suggest that seCCL18 may have some clinical utility as a prognostic biomarker reflecting widespread disease involvement beyond the lungs, even in patients with long-standing disease; however, the lack of an established cut-off value requires further validation in prospective, multicentre studies. Full article

Hyaluronic acid (HA)-based fillers are widely used in aesthetic dermatology for their biocompatibility, reversibility, and safety; however, adverse events (AEs) may occur. This review evaluated the safety profile, focusing on short- and long-term AEs, of HA fillers manufactured with MACRO (MAtrix CROsslinking) Core Technology, encompassing both current saypha and former Princess products. A systematic PubMed search identified prospective clinical trials assessing safety outcomes following facial aesthetic use of these fillers. Eleven studies including 947 patients met the inclusion criteria. The most common short-term AEs were transient swelling, injection site pain, and bruising, which were predominantly mild to moderate and resolved within two weeks. Severe or serious treatment-related events were rare, with only one reported across all studies. Long-term AEs, such as delayed-onset nodules or inflammatory reactions, were infrequent and mild, with no granulomas, hypersensitivity responses, or vascular complications observed. Safety outcomes were consistent across formulations and between the legacy Princess and current saypha products. Overall, the saypha HA filler portfolio demonstrates a predictable and strong safety profile within the expected range reported in the broader literature, noting the limitations of cross-study comparisons. Most AEs were related to injection trauma rather than the filler itself, supporting its continued use in clinical aesthetic practice. Full article

Objectives: This study aimed to define the learning curve required for cardiac surgery residents to acquire basic technical and interpretive skills in transit-time flow measurement (TTFM) and high-resolution epicardial ultrasonography (HRUS) during coronary artery bypass grafting (CABG). Methods: Prospective, observational, single-center study evaluating performance using a novel scoring system combining functional (TTFM) and anatomical (HRUS) assessment criteria. This study was registered on ClinicalTrials.gov (Identifier: NCT06589323). Nine cardiac surgery residents without prior hands-on experience in TTFM or HRUS were enrolled. Twenty-seven elective CABG patients (67 grafts) were analyzed. Each measurement was compared with those obtained by an expert benchmark surgeon (N.T.) under standardized hemodynamic conditions. Results: Residents achieved the predefined primary endpoint (combined TTFM + HRUS score/number of grafts ≥ 11) after a median of 3 cases (IQR 2–4) and 7 anastomoses (IQR 7–10). Kaplan–Meier analysis showed a progressive increase in the probability of success, with a sharp rise after the seventh anastomosis. A shorter interval between attempts (<30 days) was significantly associated with earlier achievement of the endpoint (p < 0.05). Median acquisition time for TTFM was 25 s, with <10% inter-observer variability across all flow parameters. HRUS images of adequate quality were obtained within 60 s in >90% of cases, though slightly lower success rates were observed for lateral and inferior wall targets. No resident- or procedure-related variable was independently associated with performance improvement. Conclusions: Mastery of basic TTFM and HRUS skills requires only a few cases and anastomoses, demonstrating a short and attainable learning curve. These findings challenge the perception of a steep learning process and support the routine use of intraoperative graft verification techniques in all CABG procedures. Full article

Background: Cardiac amyloidosis (CA) is characterized by progressive myocardial infiltration leading to restrictive cardiomyopathy and heart failure. While left ventricular assessment has traditionally dominated prognostic evaluation, right ventricular (RV) dysfunction and RV–pulmonary artery (PA) coupling have emerged as critical determinants of outcomes. Objectives: This review synthesizes current evidence on RV–PA coupling as a prognostic marker in cardiac amyloidosis, examining measurement methodologies, prognostic significance, pathophysiological mechanisms, and clinical applications. Methods: We comprehensively reviewed the recent literature on RV–PA coupling in CA, focusing on studies published from 2020 to 2025, including both AL and ATTR subtypes. We analyzed data from multicenter cohorts, prospective registries, and validation studies examining the relationship between RV–PA coupling indices and clinical outcomes. Results: RV–PA coupling, most commonly assessed using the tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) ratio, consistently demonstrates strong independent prognostic value for mortality and heart failure outcomes in CA patients. Impaired coupling (TAPSE/PASP < 0.45 mm/mmHg) identifies high-risk patients with hazard ratios ranging from 1.98 to 4.17 for adverse outcomes. In a multicenter cohort of 283 patients, TAPSE/PASP < 0.45 mm/mmHg was independently associated with death or heart failure hospitalization (HR 1.98, 95% CI 1.32–2.96, p = 0.001) and significantly improved risk reclassification (NRI 0.46–0.49). In ATTR-specific populations receiving disease-modifying therapy, impaired coupling (TAPSE/PASP ≤ 0.382 mm/mmHg) predicted three-year mortality with an adjusted HR of 2.99. The coupling index provides incremental value over individual RV parameters by accounting for afterload conditions and demonstrates consistent prognostic performance across both AL and ATTR subtypes. Conclusions: RV–PA coupling represents a robust, easily obtainable prognostic marker that should be routinely assessed in CA patients for risk stratification and clinical decision-making. The TAPSE/PASP ratio can be calculated from standard echocardiographic examinations without additional cost or time, making it practical for widespread implementation. Future research should focus on standardizing measurement protocols, establishing disease-specific thresholds, evaluating coupling trajectories with novel therapies, and integrating coupling assessment into staging systems and management algorithms. The strong prognostic signal, pathophysiological relevance, and ease of measurement position RV–PA coupling as an essential component of comprehensive cardiac amyloidosis evaluation. Full article

Background: Stage B heart failure (SBHF) increases the risk of symptomatic HF. Current guideline criteria for SBHF lack sex and ethnic thresholding and cardiac magnetic resonance (CMR) imaging cut-offs. We aimed to assess the prevalence of SBHF in a large cohort of people with type 2 diabetes (T2D) and healthy controls and propose a refined CMR definition for SBHF. Methods: Sex- and ethnic-specific thresholds for imaging criteria were derived from 373 healthy controls, who underwent CMR cine imaging. The current definition for SBHF and refined criteria was applied to our prospectively recruited and intensively phenotyped cohort of asymptomatic people with T2D and no evidence of cardiovascular disease. The prevalence of SBHF by different definitions was calculated and patient characteristics, including exercise capacity, were compared between those classified as Stage A vs. B HF. Finally, the refined criteria were also applied to the following two historical cohorts with symptomatic cardiovascular disease: severe aortic stenosis (AS n = 70) and HF with preserved ejection fraction (HFpEF n = 136). Results: A total of 423 people with T2D and a subset of 102 healthy controls who underwent echocardiography were prospectively recruited. Current guideline criteria classified 91% of those with T2D and 69% of the healthy controls as SBHF, suggesting a lack of specificity. Applying derived sex- and ethnicity-specific thresholds, combining echo and CMR measures, the prevalence of SBHF was reduced to 30% in those with T2D. Using the refined definition, those with Stage B HF had lower exercise capacity than those with Stage A HF (percentage predicted maximal oxygen consumption 81 ± 16% vs. 91 ± 20%, p < 0.001). Applying the refined definition to symptomatic AS and HFpEF participants classified 89% and 85% with abnormal cardiac remodelling. Conclusion: Current guideline criteria for SBHF are non-specific and likely of limited value in clinical practice. Refining these criteria with sex- and ethnic-specific thresholds may improve identification of those at risk of developing symptomatic disease. Further research is required to validate these criteria. Full article

Background: Patients with dental phobia frequently require intravenous sedation (IVS) to undergo dental treatment; however, some can gradually discontinue IVS through repeated clinical experiences. The physiological and psychological factors influencing successful IVS withdrawal remain unclear. This study aimed to compare physiological (sAA, HR) and subjective (VAS) measures between patients who discontinued IVS and those who remained dependent on IVS. Methods: This prospective cohort study included 51 patients with dental phobia treated under IVS. Participants were classified into a Non-Sedation Group (NSG; n = 25) and a Sedation-Dependent Group (SDG; n = 26) based on their ability to discontinue IVS during the course of treatment. Salivary alpha-amylase (sAA), heart rate (HR), and visual analog scale (VAS) scores for fear, tension, and anxiety were assessed at predefined time points from the waiting room to venous cannulation. Treatment satisfaction and expectations for future treatment were also evaluated. Results: sAA activity was significantly higher in the SDG than in the NSG at T0 and T1 (p < 0.05), indicating higher levels of selected physiological measures during anticipatory phases; however, the difference at T2 was not significant. HR differed significantly only in the waiting room, whereas no between-group differences were observed in self-reported VAS scores for fear, tension, or anxiety at any time point, indicating a dissociation between physiological and subjective stress measures. Treatment satisfaction and expectations for future treatment were significantly higher in the SDG. Conclusions: Patients who remained dependent on IVS showed higher levels in selected physiological measures at the group level during anticipatory stages, whereas no corresponding differences were observed in self-reported subjective measures. These findings are exploratory and descriptive in nature and do not imply predictive or causal relationships. Full article

Background: Tooth loss reflects cumulative oral inflammation and has been associated with adverse cardiovascular outcomes. This study evaluated the relationship between the number of missing permanent teeth and the angiographic severity of coronary artery disease (CAD) in patients with acute myocardial infarction (AMI). Methods: In this prospective cross-sectional study, 200 consecutive AMI patients underwent coronary angiography and standardized dental assessment during hospitalization. Tooth loss was categorized as 1–10, 11–20, or 21–32 missing teeth. CAD severity was defined by the number of major epicardial arteries with significant stenosis. Multivariate logistic regression adjusted for age, sex, smoking status, diabetes, obesity, dyslipidemia, and hypertension. Results: Increasing tooth loss was associated with more extensive CAD. The mean number of affected vessels rose from 1.58 ± 0.79 in the 1–10 tooth-loss group to 2.06 ± 0.99 in the 21–32 group (p = 0.014). Tooth loss correlated with CAD severity (r = 0.19, p = 0.007). After adjustment, >20 missing teeth remained an independent predictor of multivessel disease (OR = 1.84; 95% CI: 1.01–3.34; p = 0.047). ROC analysis showed modest discrimination (AUC = 0.61). Conclusions: Extensive tooth loss independently correlates with greater angiographic CAD severity in AMI patients. Dental status may serve as a simple, non-invasive clinical marker of cardiovascular disease burden. Full article

Background: In melanoma diagnostics key molecular markers, such as BRAF, NRAS, and KIT mutations also paved the way for targeted therapies. Immunotherapies, including immune checkpoint inhibitors like anti-CTLA-4 and anti-PD-1/PD-L1, have revolutionized treatment, improving survival outcomes for advanced-stage melanoma patients. Despite these advances, challenges such as resistance to targeted therapies and variability in patient responses to immunotherapy remain critical issues. The purpose of the project is to characterize the molecular landscape of a set of 28 malignant melanomas using next-generation sequencing, identify the prevalence and nature of class 3–5 variants (e.g., NRAS, BRAF, KIT, TP53), assess the genetic complexity and molecular patterns, and use these insights to inform personalized therapies and optimize patient stratification for potential combination strategies (targeted therapy followed by immunotherapy). Methods: We analyzed a set of malignant melanoma of the skin of 17 women (61%) and 11 men (39%) at the age of 23 to 85 years (median: 63 years) by tumor-only next generation sequencing. Results: 22/28 cases (79%) present a pathogenic or likely pathogenic variant with an allelic frequency of ≥5%. In total 42 distinct somatic pathogenic or likely pathogenic variants with an allelic frequency of ≥5% could be detected. The most frequent pathogenic molecular alteration in these melanomas were found in NRAS (25%) and BRAF (25%). The most frequent molecular alteration of unknown significance was found in FANDC2 (46%), NOTCH3 (39%), ARID1A (32%), PMS2 (32%), POLE (29%), NOTCH1 (29%), TSC2 (25%), SMARCA4 (25%), ATR (25%) and TERT (21%). Conclusions: While NRAS and BRAF were the most frequent actionable alterations (each 25%), a broad spectrum of variants of unknown significance (e.g., FANDC2, NOTCH3, ARID1A, PMS2, POLE, NOTCH1, TSC2, SMARCA4, ATR and TERT) also predominates, underscoring the genetic complexity of melanoma. These variants complicate clinical decision-making because their contribution to tumorigenesis, therapeutic response, and prognosis remains uncertain. Nevertheless, these variants also offer a valuable resource for future research, as they may uncover novel pathogenic mechanisms or therapeutic targets once their significance is elucidated. Integrating comprehensive genetic profiling with immunologic markers can enhance patient stratification and support rational, potentially synergistic strategies, such as combining targeted therapies with immunotherapy, to optimize clinical outcomes. This study is limited due to a small cohort and limited available clinical data. Larger cohort studies and prospective clinical trials are necessary to validate and explore the interplay between molecular and immune biomarkers as well as general biological mechanism in paving therapeutic way in melanoma. Full article

Background/Objectives: Recessive dystrophic epidermolysis bullosa (RDEB) is a severe congenital genodermatosis characterized by skin and mucosa fragility, chronic inflammation, recurrent infections and high nutritional demands due to increased metabolism and epithelial barrier-related losses, placing patients at risk of zinc deficiency. We aimed to investigate the clinical relevance and biochemical determinants of zinc deficiency as a potentially modifiable contributor to disease burden in RDEB. Methods: In this cross-sectional study (n = 84), serum zinc levels were analyzed in association with sex, age, disease severity, percentage of body surface area (BSA) affected, inflammatory markers, infection burden, and common clinical complications including anemia and growth impairment. Results: Zinc deficiency, defined as levels below 670 µg/L, was identified in 35% of patients and became more frequent after age 5 and during adulthood, particularly among those with more severe disease. Deficiency was strongly associated with anemia, inflammation, infection burden, growth impairment, and extensive skin involvement. A revised cutoff of 780 µg/L is proposed, showing improved diagnostic performance for identifying patients at risk of systemic complications, and offering a more suitable threshold for starting preventive supplementation. Multivariate logistic modeling confirmed that low serum zinc independently predicted anemia risk, alongside transferrin saturation and C- reactive protein levels. Serum albumin was identified as the strongest determinant of zinc levels, partially mediating the effects of inflammation and skin involvement. Conclusions: These findings identify serum zinc as a clinically relevant marker of nutritional status and complication burden in RDEB. While no causal or therapeutic effects can be inferred from this cross-sectional study, the strong and biologically plausible associations observed suggest a rationale for systematic monitoring and correction of zinc deficiency as part of comprehensive supportive care, and warrant prospective studies to assess clinical benefit. Full article