Search Results (37,988)

Background: Escherichia coli (E. coli) bacteremia is a significant cause of mortality, particularly in older adults. Limited data exists on clinical outcomes in octogenarians. This study aims to evaluate the clinical outcomes of E. coli bacteremia in octogenarians and determine whether appropriate empirical therapy leads to improved outcomes in this specific population. Methods: We conducted a retrospective cohort study of hospitalized patients with E. coli bacteremia at Beilinson Hospital from January 2012 to December 2022. Clinical characteristics, bacteremia sources, antibiotic resistance patterns, and patient outcomes were analyzed. The primary outcome was 30-day mortality. Multivariate regression was used to assess the impact of empirical antibiotic appropriateness on mortality. Results: The study included 2717 patients, of which 1042 (38%) were 80 years or older. Older patients had more comorbidities with increased rates of ischemic heart disease (20% vs. 14%, p < 0.01) and congestive heart failure (19% vs. 9%, p < 0.01). Patients with 3rd generation cephalosporin resistant strains were more likely to receive inappropriate empiric antibiotic therapy (54% vs. 23%, p < 0.01). Although appropriate empirical therapy was associated with improved survival in univariate analysis (19% vs. 28%, p < 0.01), it was not an independent predictor of 30-day mortality in multivariate analysis [adjusted OR = 1.10, 95% CI (0.64–1.81), p = 0.7]. A lower SOFA score [adjusted OR = 0.17, CI95% (0.01–0.31), p < 0.01] was associated with decreased 30-day mortality. Hypoalbuminemia was significantly associated with increased 30-day mortality [adjusted OR = 2.49, CI95% (0.1.56–3.97), p < 0.01]. Conclusions: E. coli bacteremia in octogenarians is associated with significant mortality. While timely appropriate antibiotic therapy is crucial, mortality appears to be more influenced by overall health status, comorbidities, and infection severity. Future research should focus on addressing these factors and developing personalized care strategies to improve survival in this high-risk group. Full article

Background: Breast cancer (BC) is the most common malignancy among women, and genetic predisposition plays a critical role in its development. Among DNA mismatch repair (MMR) genes, MLH1 is essential for maintaining genomic stability, and promoter variants may influence its transcriptional regulation. Variants in MMR genes, including MLH1, have been implicated in cancer susceptibility; however, evidence regarding the promoter polymorphism −93G>A (rs1800734) and its association with BC remains limited and inconsistent across populations. Methods: We conducted a case–control study of 143 breast cancer patients and 161 cancer-free controls of Azerbaijani origin. Genotyping of MLH1 −93G>A was performed using PCR-RFLP and validated by next-generation sequencing (NGS). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under different genetic models by logistic regression, followed by false discovery rate (FDR) correction for multiple testing. Results: The genotype distribution among patients was 25.9% GG, 58.7% GA, and 15.4% AA, compared with 37.9%, 46.6%, and 15.5% in controls. A significant association was observed between the GA genotype and BC risk (OR = 1.855, 95% CI: 1.104–3.085, p = 0.019). In the dominant model (GA + AA vs. GG), carriers of the A allele showed increased breast cancer risk (OR = 1.747, 95% CI: 1.069–2.856, p = 0.026). Genotype distribution was also associated with tumor grade (p = 0.047) and stage (p = 0.013). However, none of the associations remained significant after FDR adjustment. Conclusions: This pilot study provides the first evidence from Azerbaijan suggesting a potential role of the MLH1 −93G>A variant in breast cancer susceptibility. Although the associations were nominal and require validation in larger cohorts, the findings point to a biologically plausible link between MLH1 promoter variation and impaired MMR activity, which may contribute to polygenic breast cancer risk. These preliminary results emphasize the importance of evaluating MMR gene variants in underrepresented populations and support further studies integrating functional assays and broader gene coverage. Full article

Multidrug-resistant (MDR) bloodstream infections (BSIs) constitute a major challenge in intensive care units, with the COVID-19 pandemic compromising infection control and potentially increasing MDR incidence. Comparative data between COVID and non-COVID ICU populations remain limited. The MARTINI study is a retrospective observational analysis held in a tertiary hospital during the COVID-19 pandemic (2020–2022) encompassing adult patients with MDR BSIs admitted to COVID and non-COVID ICUs. Demographics, comorbidities, severity scores, microbiology, resistance patterns, and outcomes were accessed and compared. A binary logistic regression model and multivariate regression was performed to identify independent predictors of ICU mortality. Among the study’s 156 patients (106 COVID-ICU, 50 non-COVID-ICU), COVID-ICU patients were significantly older with higher comorbidity and severity scores. Gram-negative pathogens predominated in both cohorts, mainly Acinetobacter baumannii and Klebsiella pneumoniae, with comparable resistance mechanisms. Timing of bacteremia onset and initiation of appropriate therapy did not differ between groups. However, ICU mortality was markedly higher in COVID-ICU patients (74.5% vs. 38%, p < 0.001). Age, SOFA score, the presence of systemic inflammation (SIRS) and COVID-19 infection were identified as independent predictors of mortality. Although pathogen distribution and resistance were similar across groups, COVID-ICU patients experienced significantly poorer outcomes. Strengthened infection control and timely and targeted antimicrobial therapy are essential to diminish MDR bacteremia risk in critically ill populations. Full article

Objectives: We aimed to develop and validate a per-cycle prediction model for in vitro fertilization (IVF) success using only preprocedural clinical variables available at the first consultation. Methods: We retrospectively analysed 1243 IVF/ICSI cycles (University of Szeged, 21 January 2022–12 December 2023). An Extreme Gradient Boosting (XGBoost version 1.7.7.1) classifier was trained on 14 baseline predictors (e.g., female age, AMH, BMI, FSH, LH, sperm concentration/motility, and infertility duration). A parsimonious 9-variable model was derived by feature importance. Model performance was assessed on the untouched test set and, as a final step, on an independent same-centre external validation cohort (n = 92) without re-fitting or recalibration. Results: The 9-variable model achieved an AUC of 0.876 on the internal test set, with an accuracy of 81.70% (95% CI 76.30–86.30%), sensitivity of 75.60%, specificity of 84.40%, PPV of 68.60%, and NPV of 88.50%. In external validation, the model maintained strong performance with an accuracy of 78.30%, confirming consistent discrimination on an independent same-centre cohort. Female age was the dominant high-impact feature, while AMH and BMI acted as “workhorse” predictors, and male factors added incremental value. Conclusions: IVF outcome can be predicted at the first visit using routinely collected preprocedural data. The model showed consistent discrimination internally and in external validation, supporting its potential utility for early, individualized counselling and treatment planning. Full article

Introduction: Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder associated with both venous and arterial thrombosis, most notably ischemic stroke. Patients face a high risk of recurrence, and yet optimal strategies for secondary prevention remain uncertain. Methods: We conducted a narrative review of the literature on secondary prevention of ischemic stroke in APS. We performed a comprehensive literature search of PubMed for English-language articles on secondary stroke prevention in APS. Studies were included if they were original human research (e.g., randomized trials, cohort, or case–control studies) or relevant reviews addressing APS-related stroke prevention. Results: Vitamin K antagonists (VKAs) remain the standard of care for high-risk patients with arterial events. Several randomized controlled trials demonstrated higher recurrence rates, particularly of stroke, among APS patients treated with direct oral anticoagulants (DOACs). The optimal target INR remains debated; pooled analyses suggest no clear advantage of high-intensity anticoagulation (INR 3–4) over standard-intensity (INR 2–3), but individualized adjustment is warranted in select cases. In patients with recurrence despite adequate anticoagulation, adding an antiplatelet agent may be beneficial, although supporting evidence is limited. Adjunctive statin therapy shows promise in reducing endothelial dysfunction and prothrombotic markers, with observational data suggesting a possible protective effect, although randomized evidence is lacking. In addition, patent foramen ovale (PFO) closure has been proposed in selected APS patients with paradoxical embolisms, particularly when combined with anticoagulation. Non-pharmacological strategies, including structured lifestyle modification and rigorous vascular risk-factor management, are strongly recommended, as traditional cardiovascular risk factors synergistically increase recurrence risk. Conclusions: Secondary prevention of ischemic stroke in APS requires an individualized approach. VKAs remain first-line, with consideration of antiplatelet add-on, statins, lifestyle interventions, and PFO closure in appropriate settings. Future well-designed clinical trials are needed to refine INR targets, validate combination strategies, and clarify the role of adjunctive therapies in this complex patient population. Full article

Background: The intersection between oncology and intensive care has shifted from predominantly end-of-life care to a therapeutic bridge that can preserve anticancer trajectories in carefully selected patients. Yet, criteria separating benefit from futility remain fragmented. Objective: This paper seeks to map contemporary evidence (2015–2025) on outcomes after Intensive Care Unit (ICU) admission in adults with cancer and to identify clinical constellations in which ICU-level care still changes prognosis. Methods: PRISMA-ScR scoping review (PCC framework). PubMed search (2015–2025), dual screening, standardized extraction; narrative/thematic synthesis across six clusters (hematologic, solid tumors, sepsis/non-COVID-19 infection, COVID-19/viral pneumonia, novel/targeted-therapy toxicities, end-of-life/aggressive ICU) were used. No meta-analysis given heterogeneity. Results: Seventy-three studies (>170,000 ICU admissions) were included, mostly cohort designs across 27 countries. ICU mortality ranged 8–72% (weighted mean ≈ 41%); hospital ≈ 38%; 90-day ≈ 46%; 1-year ≈ 62%. About one third of ICU survivors resumed systemic therapy. Benefit concentrated in early admissions, single-organ failure, controlled/remission disease, postoperative/elective monitoring, and reversible treatment-related toxicities (e.g., ICI pneumonitis, CAR-T CRS/ICANS). Futility clustered around ≥3 organ supports, RRT > 7 days, refractory/progressive disease, and ECOG ≥ 3. Sepsis outcomes averaged 45–55% ICU mortality but improved with rapid recognition and source control; COVID-19 mortality was particularly high in hematologic malignancies early in the pandemic, with subsequent declines post-vaccination. Conclusions: In modern oncologic practice, ICU care changes prognosis when the acute physiological insult is reversible and cancer control remains plausible; conversely, high organ-support burden and refractory disease define practical futility thresholds. These signals support time-limited ICU trials, earlier ICU involvement for sepsis/irAEs, and embedded palliative care to align intensity with goals. Full article

Background/Objectives: Systemic hydrocortisone (HCS) in very low birth weight (VLBW) infants is commonly used to treat early hypotension or prevent bronchopulmonary dysplasia. This study evaluated the associations between postnatal HCS exposure and neurodevelopment in VLBW infants by comparing regional brain volume at term-equivalent age (TEA) with neurodevelopmental outcomes in early infancy. Methods: This retrospective cohort study included VLBW infants admitted to a neonatal intensive care unit (NICU) between 2013 and 2019. The cumulative HCS dose during hospitalization was recorded, and regional brain volumes were analyzed using magnetic resonance imaging at TEA. Neurodevelopmental outcomes were assessed at a corrected age for prematurity of 18–24 months. Results: Among 146 infants, 57 were classified in the high HCS group (>90 mg/kg) and 89 in the low HCS group (≤90 mg/kg HCS). Bronchopulmonary dysplasia, periventricular leukomalacia, and sepsis were more frequent in the high HCS group. Ninety-five infants underwent magnetic resonance imaging, which revealed reduced brain volumes in the high HCS group. At follow-up, cerebral palsy (35.9% vs. 9.1%, p = 0.003), neurodevelopmental impairment (54.0% vs. 23.6%, p = 0.002), and head circumference <10th percentile (64.3% vs. 19.5%, p < 0.001) were more common in the high HCS group. After adjustment, HCS > 90 mg/kg remained independently associated with cerebral palsy (adjusted odds ratio [aOR] 5.44, p = 0.016) and reduced head circumference (aOR 4.45, p = 0.016). Conclusions: High cumulative HC exposure correlated with reduced brain volume at TEA and adverse neurodevelopmental outcomes at 24 months of age. Careful monitoring of dose and treatment duration is essential to balance therapeutic benefits against potential risks. Full article

Objective: This cross-sectional survey aimed to comprehensively gather data on radial forearm free flap (RFFF) utilization and practices in head and neck reconstructive surgery. Methods: An online questionnaire was organized into seven sections: demographics, surgeon experience, harvesting techniques, microsurgical considerations, postoperative care, flap monitoring, and outcomes. It was distributed by email to 216 head and neck reconstructive surgeons who attended the International Federation of Head and Neck Oncologic Societies (IFHNOS) congress in Rome (21–25 June 2023) using the congress mailing list. Responses were collected from 54 surgeons (25% response rate), representing 15 countries across Europe, Asia, the Americas, and Oceania, underscoring the international scope of the survey between 5 February and 25 March 2024. The questionnaire was not formally piloted or validated. Missing data were managed on a per-question basis. Descriptive statistics were used, and 95% confidence intervals (CIs) were calculated for key surgical outcomes to indicate estimate precision. Associations between categorical variables were analyzed using Pearson’s χ² test with Cramér’s V as an effect size, and relationships between continuous variables were examined using Spearman’s rank correlation (ρ) with 95% confidence intervals (CIs). Given the exploratory design and limited sample size, no correction for multiple comparisons was applied, and the risk of both Type I and Type II errors was acknowledged. Results: Variations were observed in harvesting techniques, microsurgical preferences, and postoperative care protocols. Most surgeons initiated flap harvesting concurrently with tumor resection, primarily preserving superficial sensory nerves. Regarding venous outflow, 50% of respondents preferred the cephalic vein, 19% used comitant veins, and 29% utilized both systems when possible. Perioperative antibiotic use was standard practice, though anticoagulant preferences and flap monitoring methods varied. The study achieved a high success rate for RFFF procedures, exceeding 95%, with venous thrombosis identified as the main cause of flap failure. No significant correlations were found between flap failure rate and training method (p = 0.21), specialty (p = 0.37), annual number of RFFF procedures (p = 0.89), surgeon age (p = 0.42), or hospital type (p = 0.48). Effect sizes were small to moderate, indicating weak or negligible associations. Similarly, perioperative factors such as anticoagulant use (p = 0.84), preoperative antibiotics (p = 0.42), surgical instruments (p = 0.61), suture techniques (p = 0.51), and donor vein selection (p = 0.20) showed no statistically significant associations with flap loss. Patient satisfaction assessments were inconsistent, with only 39% of surgeons routinely performing them. Conclusions: The study provides valuable insights into current RFFF practices and outcomes across an international cohort of head and neck surgeons, highlighting patterns and variability in techniques, perioperative care, and monitoring strategies. Full article

Introduction: The management of symptomatic peripancreatic fluid collections (PFCs), including pancreatic pseudocysts (PPs) and walled-off necrosis (WON), remains a clinical challenge. Methods: We conducted a single-center retrospective cohort study to compare the efficacy, safety, and cost of endoscopic drainage (lumen-apposing metal stent vs. double pigtail stent) and percutaneous drainage for PFCs. From an initial cohort of 75 patients with symptomatic PFCs between 2020 and 2025, 63 underwent drainage procedures. Primary endpoints were the clinical success, defined as >50% collection size reduction, and the need for direct endoscopic necrosectomy (DEN). Secondary endpoints included adverse events, recurrence rates, length of hospital stay (LOS), and procedural costs. Results: In our study, endoscopic drainage proved high clinical efficacy for PFCs, especially PPs. Once a technique was chosen, complication rates were comparable, indicating no clear safety advantage for either approach. While percutaneous drainage relieved symptoms and reduced collection size in half of the cases, the other half had only transient or partial improvement. When comparing endoscopic drainage techniques, median costs and length of hospital stay trended higher for lumen-apposing metal stent (LAMS) than double pigtail stent (DPS), but the differences were not statistically significant. However, the “other” group proved markedly higher costs and the longest mean hospital stay. Conclusions: The choice of drainage technique impacts short-term outcomes and safety profile in managing PFCs. Our findings support a tailored, step-up approach, prioritizing endoscopic ultrasound-guided drainage based on PFC characteristics to optimize clinical outcomes. Full article

Background/Objectives: Pre-analytical variation is a major challenge in metabolomics, yet most stability studies have focused on healthy volunteers and have overlooked the impact of disease and medication. To address this gap, we conducted a pilot study in systemic lupus erythematosus (SLE) to assess serum metabolite stability under delayed centrifugation. Methods: Peripheral blood from 10 SLE patients and 5 healthy controls (HC) was stored at room temperature for 1–24 h before processing and analyzed by untargeted LC-MS-based metabolomics. This design enabled direct evaluation of the effect of pre-analytical delay within the context of clinical heterogeneity. Results: Principal component trajectories showed reproducible temporal shifts in HC but dispersed patterns in SLE, indicating disease- and treatment-related influences. Linear mixed-effects models identified metabolites with condition-specific kinetics, including glucose, choline, glycerophosphocholine, and pyroglutamic acid. Mycophenolate intake was further associated with distinct AMP dynamics. Conclusions: These findings demonstrate that both disease state and medication reshape apparent metabolite stability, highlighting the need for strictly controlled sample handling and well-characterized clinical cohorts in metabolomics studies. Full article

Objective: This study focuses on selected potential determinants of self-harm in adolescents of two age groups. The considered factors are depression, sex, and parental cohabitation. The aim of the study is to reveal the association between the mentioned factors and self-harm in younger and older adolescents. A secondary goal is to identify the prevalence of self-harm in two age groups. Self-harm is defined as the repeated occurrence of its physical forms. Methods: In the non-experimental research study, the respondents (N = 1285) were primary and secondary school pupils from Slovakia and made up two age cohorts (12–15 and 16–18 y). A battery of questionnaires consisted of the CDI, Self-Harm Inventory and a demographic questionnaire. Procedures of statistical analysis including the logistic regression were applied for data processing. Results: Depression as a risk factor for physical forms of self-harm was recognised in both age cohorts. In terms of sex as a predictor (girls), it proved to be a strong determinant of development of self-harm in the younger group. Conclusions: The results demonstrate the relevance of the need for a separate study of self-harm in boys and girls, as well as in the context of developmental peculiarities in adolescence. Full article

Hereditary breast and ovarian cancer (HBOC) syndrome accounts for 5–10% of all breast and ovarian cancers, with BRCA1 and BRCA2 pathogenic variants being the most common genetic alterations. However, additional genes such as BARD1, whose protein product interacts with BRCA1 via its N-terminal RING domain, have been implicated as low-penetrance contributors to cancer risk. This study aimed to investigate the frequency and distribution of the BARD1 variant c.1518_1519delinsCA (p.Val507Met) in a cohort of 920 patients undergoing genetic testing for hereditary cancer predisposition. Next Generation Sequencing (NGS) was performed using a 28-gene panel, and allelic frequencies of BARD1 were analyzed. Among 920 patients, 159 (17.28%) were pure heterozygous for the c.1518_1519delinsCA variant. Notably, c.1519G>A was never observed without c.1518T>C, suggesting a strong linkage between the two variants. The allele frequencies observed (34.51% for A at c.1519 and 77.88% for C at c.1518) challenge current reference genome expectations. Data from the ALFA database confirmed that these frequencies are consistent with population-level variation, not sample bias. Our findings raise the hypothesis that the reference allele at position c.1518 may not reflect the true wild-type sequence. While both c.1518T>C and c.1519G>A are individually classified as benign, their combined occurrence as a dinucleotide substitution (c.1518_1519delinsCA) warrants further investigation. These results underscore the importance of accurate variant annotation and population-specific frequency data for clinical interpretation of NGS findings. Although BARD1 remains a low-frequency contributor to HBOC compared to BRCA1/2, its inclusion in multigene panels is supported by the potential relevance of such complex variants. Full article

Background: Lower-limb fractures often require prolonged use of assistive devices, which may increase mechanical stress on the upper extremities. However, the association between lower-limb fractures and subsequent carpal tunnel syndrome (CTS) remains unclear. Methods: This nationwide population-based cohort study used Taiwan’s National Health Insurance Research Database (2011–2019) to identify 10,140 patients with lower-limb fractures and 10,140 propensity score-matched controls. Cox regression analysis estimated CTS risk after adjusting for demographics and comorbidities. Results: Patients with lower-limb fractures demonstrated increased CTS risk compared to controls (adjusted hazard ratio [HR] = 1.12, 95% confidence interval [CI]: 1.003–1.26; p = 0.044), with stronger associations in males (HR = 1.28, 95% CI: 1.05–1.55) and younger adults aged 20–65 years (HR = 1.19, 95% CI: 1.03–1.38). Conclusions: Lower-limb fractures are associated with modestly increased CTS risk, particularly in males and younger patients. Though biologically plausible, this observational study cannot establish causality. Heightened clinical awareness may be warranted, though prospective validation is needed. Full article

Background: Rotavirus (RV) continues to be the leading cause of acute gastroenteritis (AGE) globally among children under five. National RV vaccination efforts have lowered morbidity and mortality. Vaccination is a key public health tool to alleviate this substantial burden of RV in middle- and low-income countries. In Syria, RV morbidity accounts for 27% of severe GE. We conducted a cost-effectiveness analysis of introducing rotavirus vaccinations (RVV) into Syria’s National Immunization Program. Methods: A decision tree model was developed to assess the cost-saving of two-dose rotavirus vaccinations (Rotarix^®) compared to no vaccination. A birth cohort of 573,944 newborns was simulated throughout a 5-year time frame to capture the near-term health and economic effects. The analysis adopted an incremental cost-saving approach, evaluating a hypothetical 2023 birth cohort from the government’s perspective. Outcomes included the cost per disability-adjusted life year (DALY) prevented and the cost per death averted. Model inputs were derived from local data, specifically including healthcare and vaccination costs and deaths attributable to RVGE, the scientific literature, and national/international databases. The incremental cost-effectiveness ratio (ICER) measures the cost of avoiding one disability-adjusted life year (DALY) adopted. Results: Over five years, the two-dose RV strategy would avert 77,500 RVGE cases, reduce outpatient visits by 59%, and reduce severe RV hospitalizations by 41%. The vaccination program would cost $21,817,918 USD and avert $3,239,907 USD in healthcare costs, resulting in a net cost of $18,578,011 USD. The incremental cost-effectiveness ratio (ICER) was $2098 USD per DALY averted, which is below three times Syria’s GDP per capita ($753.6 USD), indicating high cost-effectiveness according to WHO benchmarks. Conclusions: Introducing rotavirus vaccination is highly cost-saving and will result in a substantial reduction in healthcare burdens and lives lost. Policy planners must ensure its inclusion in the National Immunization Programs, ensuring sustainable financing and equitable access. Full article

Traumatic spinal cord injury (SCI) is a devastating complication of trauma, causing long-term disability and significant socioeconomic burden. Beyond the primary mechanical insult, secondary injury cascades involving apoptosis, oxidative stress, and inflammation amplify tissue damage. MicroRNAs (miRNAs) regulate these processes at the post-transcriptional level, yet data on circulating miRNAs in human SCI remain scarce. This study aimed to characterize acute plasma miRNA expression patterns in isolated traumatic SCI that may indicate SCI-specific signatures. Plasma was collected from five SCI patients at admission and 48 h post-injury and five healthy controls (HCs), and next-generation sequencing (NGS) was performed on plasma RNAs. Differentially expressed miRNAs were identified, and selected candidate miRNAs were validated by droplet digital PCR (ddPCR) in an expanded cohort of SCI patients, polytrauma patients without neurotrauma (PT), and HC (each n = 8). Pathway enrichment and validated target analysis were performed to assess biological relevance of candidate miRNAs. At emergency room admission, 46 miRNAs were differentially expressed in SCI plasma (18 upregulated, 28 downregulated). By 48 h, a global downregulation was observed, with 47 miRNAs significantly decreased compared with HC. ddPCR validation revealed markedly stronger suppression of miR-182-5p, miR-190a-5p, miR-144-5p, and miR-30c-5p expression levels in SCI compared with PT. Pathway analysis indicated enrichment of mitochondrial oxidative phosphorylation pathways, and target prediction suggested that the identified miRNAs may be linked to neuroprotective and regenerative functions. Our findings demonstrate early and profound alterations in circulating miRNAs after acute SCI. The downregulation of the identified miRNAs may reflect maladaptive changes that promote neuroinflammation and hinder axonal regeneration, although the exact functional consequences remain to be clarified. These data suggest that circulating miRNAs could hold promise as diagnostic and prognostic biomarkers and, potentially, as therapeutic targets to influence secondary injury processes. However, given the exploratory nature and limited sample size of this study, the findings should be validated in larger, sufficiently powered cohorts to robustly delineate differences between patient groups. Full article