Medicine and Pharmacology

Abstract: Background/Objectives: Human epidermal growth factor receptor 2 (HER2) is an important biomarker in gastric cancer (GC). Histologic assessment may be limited by tissue sampling and spatial heterogeneity. We evaluated radiomics models for preoperative HER2 classification. Methods: PubMed, the Cochrane Library, Embase, and Web of Science were searched from inception to 7 November 2024 and updated through 10 August 2026. A Study_ID–Report_ID–Cohort_ID index identified overlaps. AUROC (C-statistic) values were pooled on the logit scale using random-effects models. Patient-level diagnostic accuracy was pooled using bivariate random-effects models only for directly reported 2 × 2 tables or unique integer reconstructions. Quality and reporting were assessed using RQS, PROBAST+AI, and TRIPOD+AI. Results: Twenty-three eligible reports represented 20 independent studies and three overlapping companion reports. The modeling population comprised 6,734 patients, including 1,484 with HER2-positive tumors. Pooled AUROC was 0.812 (95% CI, 0.763–0.853; I² = 78.9%) in training cohorts and 0.821 (95% CI, 0.772–0.861; I² = 46.3%) in validation cohorts. For validation CECT models, AUROC was 0.824 (95% CI, 0.772–0.866; I² = 55.5%). In the diagnostic accuracy meta-analysis, pooled sensitivity and specificity were 0.718 and 0.764 in five training cohorts and 0.714 and 0.827 in four validation cohorts. Conclusions: Radiomics models provided preoperative discrimination of HER2 status. CECT has the largest evidence base and may serve as a research adjunct to histologic testing. PET/CT, DECT, and deep learning require further prospective multicenter validation, with standardized imaging and complete reporting of calibration, decision curves, and clinical utility.

Abstract: Overview of Long COVID Long COVID, also known as Post-COVID Conditions (PCC), Post Acute Squeal of COVID PASC, or Chronic COVID, is the lingering consequence of a SARS-CoV-2 infection. While many infections like Influenza, Ebola, Malaria and Lyme Disease also carry severe post-infection risks, Long COVID emerged as a uniquely modern challenge because of the number of people who have it. The science and treatments of the condition are rapidly evolving; nonetheless, the condition remains ill-defined, and a definitive diagnostic test does not yet exist. The Global Scale While its 7% prevalence rate may seem modest, the sheer scale of the pandemic made this a global crisis. Assuming 75% of the world's population has been infected, an estimated 420 million people suffer from Long COVID. To put that in perspective, this is roughly five times the total number of people killed or injured in all 20th- and 21st-century wars combined. Risk Factors and Prevention Research suggests that inflammation, persistent viral infection, and mitochondrial dysfunction are the primary drivers of the condition. While risk fluctuates based on demographics and health, several factors reduce the likelihood of developing Long COVID: Demographics: Being younger, male, and maintaining high physical fitness. COVID Status: Recent viral variants, early use of antivirals, and-most importantly vaccination. The protective impact of vaccines is a subject of intense study. While the average reported reduction in Long COVID risk from vaccination is 50%, individual studies show a wide range of efficacy, from 10% to 100%. Data about the impact on individuals with comorbidities is similarly varied. Treatment: Seeking "Bronze BBs" There is no single curative therapy for Long COVID. “Bronze BBs” describes interventions that some studies report as providing incremental, organ-specific symptomatic relief for some patients. Reported effect sizes are heterogeneous, and many findings have not been replicated.

Abstract: Background: Pulmonary arterial hypertension (PAH) is characterized by progressive vascular remodeling and right ventricular (RV) dysfunction. ¹⁸F FDG PET/MRI may reveal metabolic altera-tions in the pulmonary parenchyma and vasculature. We investigated pulmonary FDG up-take in PAH versus healthy controls and its associations with hemodynamics, RV function, and clinical outcomes. Methods: Twenty-eight stable PAH patients and 12 age-matched healthy controls underwent ¹⁸F-FDG PET/MRI. Standardized uptake values (SUV) were measured in lung parenchyma and proxi-mal pulmonary arteries. Hemodynamic parameters were obtained via right heart cath-eterization; RV–PA coupling was assessed as stroke volume/end-systolic volume (SV/ESV). Twen-ty PAH patients underwent follow-up imaging after targeted therapy. Clinical endpoints (CEP: death, hospitalization, disease progression) were analyzed by Kaplan–Meier and Cox regression. Results: PAH patients showed markedly elevated lung parenchymal SUV (0.405 [0.338–0.533] vs. 0.225 [0.207–0.273], p< 0.001) and proximal PA SUV (3.46 [1.95–6.89] vs. 1.48 [1.15–1.65], p< 0.001). The two metrics were uncorrelated (r=+0.105, p=0.595). SUV PA Proximal correlated with mPAP (r=+0.551) and PVR (r=+0.517), while SUV Lung showed no hemodynamic correlations. After 24 months of therapy, RV–PA coupling im-proved significantly (p=0.037); lung SUV showed a non-significant trend toward reduction (Δ=−0.10, p=0.128). Sixteen CEPs occurred; impaired RV–PA coupling (HR=0.04, p=0.002), elevated mPAP (HR=1.08, p< 0.001), and reduced RVEF (HR=0.91, p< 0.001) were strong univaria-ble predictors. Neither SUV metric retained independent prognostic value in multivariable analysis. Conclusions: Pulmonary parenchymal and proximal PA FDG uptake are markedly elevated inPAH. However, neither metric independently predicts hemodynamic severity or clinical outcomes, limiting their current role as reliable prognostic surrogates.

Abstract: Burn severity alone does not fully explain differences in health-related quality of life (HRQoL) after burn injury. This secondary observational analysis evaluated whether emotional reactivity and emotion-regulation strategies were associated with HRQoL beyond conventional measures of burn severity. Data from 256 adult patients with burn injury treated at the Vietnam National Burn Hospital, Hanoi, Vietnam, from October 2024 to January 2025, were analyzed. Total body surface area (TBSA) and burn depth represented clinical severity. Emotional reactivity was assessed using the Emotion Reactivity Scale (ERS), while cognitive reappraisal and expressive suppression were assessed using the Emotion Regulation Questionnaire–Short Form. Burn-specific HRQoL was measured using the Burn-Specific Health Scale–Brief (BSHS-B), and generic HRQoL using the EQ-5D-5L. Pearson correlations and hierarchical multivariable regression were performed. TBSA was positively associated with ERS (r = 0.30, p < 0.001), whereas burn depth was not significantly associated with ERS (p = 0.18). Higher ERS was associated with poorer BSHS-B Function (r = −0.34), Affect and Relations (r = -0.39), Skin Involvement (r = -0.28), and EQ-5D-5L (r = -0.32) scores (all p < 0.001). Cognitive reappraisal showed positive, whereas expressive suppression showed negative associations with HRQoL. In hierarchical regression, psychosocial variables increased adjusted R² from 0.168 to 0.291 (Δ adjusted R² = 0.123, p < 0.001). These findings indicate that psychosocial characteristics provide additional explanatory information beyond demographic and clinical measures of burn severity and support their consideration in multidimensional assessment and individualized burn rehabilitation.

Abstract: Background: Slowing of gait and daily activities, reported by older adults or by people close to them, may identify a clinically relevant motor phenotype in population-based movement-disorder epidemiology. We examined whether this simple baseline history item predicted long-term all-cause mortality in the Neurological Disorders in Central Spain (NEDICES) cohort. Methods: NEDICES was a prospective, population-based cohort of 5,278 census-based participants aged 65 years or older. Information on the slowing item was available for 3,994 participants. Reported slowing was defined as an affirmative answer to: 'Have you noticed, or has anyone told you, that lately you walk or do things more slowly?' Vital status and date of death were obtained through linkage to the Spanish National Population Register (Instituto Nacional de Estadística; INE). Follow-up accrued from baseline assessment to death or to administrative censoring on 31 December 2017 for participants who were alive. Survival was assessed with Kaplan-Meier curves and Cox proportional-hazards models. The multivariable model adjusted for age, sex, education, hypertension, prevalent tremor, prevalent Parkinson's disease, osteoarthritis, osteoporosis, smoking, alcohol consumption, depressive symptoms and/or antidepressant use, and comorbidity using a Carey-based index. Results: At baseline, 1,516 participants (38.0%) reported slowing. Through 31 December 2017, 3,426 deaths occurred, and 568 participants were censored alive. The mean observed time to death or censoring was 12.9 years (median 12.6 years). Crude mortality was higher among participants with reported slowing than among those without it (89.4% vs. 83.6%). Kaplan-Meier survival was shorter in the reported-slowing group (median: 140 vs. 158 months; log-rank p< 0.001). In the fully adjusted Cox model (n=3,841), reported slowing was independently associated with mortality (hazard ratio 1.09; 95% confidence interval 1.02-1.18; p=0.017). Conclusions: A single self- or informant-reported item on slowing of gait and daily activities identified older adults with a modest but independent excess long-term mortality risk.

Abstract: Acute kidney injury (AKI) is a common complication of COVID-19-associated acute respiratory distress syndrome (ARDS), yet the impact of extracorporeal membrane oxygenation (ECMO) on outcomes in this high-risk population remains unclear. We performed a retrospective study using the National Inpatient Sample (NIS) database from 2020–2022 to compare outcomes among adults hospitalized with COVID-19-associated ARDS and AKI managed with invasive mechanical ventilation (IMV) alone versus IMV and ECMO. The primary outcome was in-hospital mortality, while secondary outcomes included renal replacement therapy (RRT), complications, hospital length of stay (LOS), and healthcare utilization. Among 198,395 patients with COVID-19 ARDS complicated by AKI, 4,730 received IMV and ECMO. ECMO was not associated with reduced mortality after multivariable adjustment (adjusted odds ratio [aOR] 0.96, 95% CI 0.81-1.12). However, ECMO was associated with greater odds of RRT, intracranial hemorrhage, disseminated intravascular coagulation, cardiogenic shock, vasopressor use, tracheostomy, acute liver failure, deep vein thrombosis, ischemic stroke and ICU-acquired weakness. ECMO was also associated with longer LOS and higher hospitalization costs. In conclusion, among patients with COVID-19-associated ARDS and AKI, ECMO was not associated with a clear adjusted mortality benefit but was associated with markedly higher complication burden, longer hospitalization, and substantially greater healthcare resource utilization.

Abstract: Patient-facing medical information software is typically built one disease at a time: each new condition requires a bespoke application, with its own data model, user interface, and safety scaffolding. This approach does not scale to the breadth of human disease. Orphanet, the reference catalogue of rare conditions, alone describes on the order of six to seven thousand clinically distinct rare diseases, and broader clinical terminologies enumerate tens to hundreds of thousands of codeable entities; no hand-built, per-disease portfolio can realistically span that space. This report presents the Medical App Generator, a single SwiftUI application for macOS and iOS in which the disease is not hard-coded but is instead a selectable, user-enterable parameter that re-skins the entire application from a declarative configuration object. We describe the configuration schema (disease metadata, comorbidities with etiological-driver categories and linking mechanisms, numerical metrics with field-importance metadata, symptoms, blood tests, and a treatment database), the runtime architecture that binds it to a reactive user interface, and a free-text disease-resolution layer that loads curated content for known conditions and a functional blank template for any other name entered. A central contribution is the application's safety architecture. The system is positioned as informational rather than advisory: it presents AI-assisted, literature-derived content as structured input for a licensed clinician, never as a diagnosis or a personalized prescription. Treatments are withheld behind a combined medical, safety, warranty, liability, and intellectual-property notice that the user must explicitly accept; a dosage reference is gated behind required safety fields and never computes a patient-specific dose; and a dedicated condition (Long COVID and its synonyms) is deliberately blocked and redirected. We map these design choices to the United States Food and Drug Administration's criteria for non-device clinical decision support and to the published literature on clinical decision support systems and on the reliability of large language models in medicine. We report a transparent coverage analysis: five diseases ship with curated data, one is intentionally inert, and all other names resolve to an empty but fully navigable template. We conclude that configuration-driven generation, paired with conservative, explicit safety gating, is a defensible pattern for patient information tools, and we discuss its limitations, including the gap between representative and exhaustive clinical content and the unresolved question of formal validation.

Abstract: Background/Objectives: Health literacy (HL) is the ability to obtain, understand, and use information to make health-related decisions. There is scarce information on the impact of HL on patients with rheumatologic conditions. We explored the relationship between parental HL and clinical outcomes of patients with juvenile idiopathic arthritis (JIA) in an ethnically diverse population at a large academic center. Methods: Parents of patients with JIA completed a demographic survey and the Newest Vital Sign (NVS) assessment to identify health literacy risk. Parental HL literacy was grouped by limited HL (score of 0-1) and possible limited HL plus adequate HL (score of 2-6). Clinical Juvenile Arthritis Disease Activity Score (c-JADAS) and Patient-Reported Outcomes Measurement Information System (PROMIS) were used to determine clinical outcomes. Clinical characteristics and outcomes were compared by HL score groups. Logistic regression analysis for active disease was performed using cJADAS. Results: Seventy-five parents participated, for which 15 (20%) scored limited HL. Primary language was English in 53 (71%) and Spanish in 22 (29%). The median cJADAS in polyarticular disease was significantly higher in the limited HL group (8 (3.0, 11.0) vs 2.2 (0.0, 7.0), p=0.017). For oligoarticular disease, PROMIS mobility scores were significantly lower in the limited HL group (35.3 (27.1, 45.4) vs 52.1 (52.1, 52.9), p=0.037). Limited HL had higher odds of active disease (OR=6.85, [CI 1.18-39.58], p=0.032). Conclusions: Limited parental HL was associated with significantly higher disease activity in polyarticular patients and with an overall higher odd of active disease.

Abstract: Background: This study aimed to develop a stratified diagnostic strategy for differentiating focal organizing pneumonia (FOP) from peripheral lung cancer (PLC) by integrating CT-based morphological features with ¹⁸F-FDG PET metabolic parameters. Methods: A retrospective analysis included 102 patients with FOP and 135 patients with PLC confirmed by pathology or follow-up. All patients underwent ¹⁸F-FDG PET/CT. Lesions were stratified by diameter and compared between the FOP and PLC groups based on CT morphological features and PET metabolic parameters. A quantitative CT score was developed from significant morphological features using multivariate logistic regression and its diagnostic performance was evaluated. The performance of CT score, PET metabolic parameters and combined models were evaluated using ROC and DeLong test analysis. Results: In lesions≤10 mm, CT density distribution was the key discriminator. For 10-30 mm lesions, gender, multiple CT morphological features and metabolic tumor volume (MTV) showed significant differences (all P< 0.05). The CT scoring system achieved excellent discriminatory performance (AUC=0.961), performing better than PET (AUC=0.662, P< 0.001) and comparably to the combined PET/CT model (AUC=0.963, P=0.48). In lesions>30 mm, the combined PET/CT model (AUC=0.901) outperformed the CT score alone (AUC=0.824, P=0.03). Subgroup analysis revealed that PET added additional diagnostic value for lesions with CT scores < 49.7, increasing the AUC from 0.646 to 0.892 (P=0.02); however, the benefit was minimal for lesions with CT scores≥49.7. Conclusions: We propose a lesion size-guided diagnostic strategy integrating CT scoring and ¹⁸F-FDG PET. For small lesions (≤10 mm), CT follow-up is sufficient. For medium-sized lesions (10-30 mm), CT scoring alone provides high diagnostic accuracy. For larger lesions (>30 mm), CT scoring serves as initial screening, with PET reserved for low-score cases. This integrated diagnostic strategy can reduce unnecessary PET scans while preserving diagnostic efficacy, offering significant clinical value.

Abstract: Background: Hypoalbuminemia is a common complication after burn injury, exacerbated by surgical debridement, and contributes to edema, delayed healing, infection, and mortality. NovoSorb® Biodegradable Temporizing Matrix (BTM) is a dermal substitute that may reduce protein loss from open wounds. Objective: To evaluate the effect of BTM on serum albumin levels compared with conventional split-thickness skin grafting. Method: This retrospective review included burn patients (TBSA ≥10%, length of stay >30 days) admitted between 2020–2025 who underwent debridement followed by BTM or skin grafting. Serial albumin levels were analyzed as weekly means. Result: Baseline characteristics were comparable between BTM (n=14) and non-BTM (n=16) groups. Albumin decreased in both groups at week 1. From week 3 onward, albumin levels rose only in the BTM group, with significant intergroup differences at weeks 5–7 (p < 0.05 to p < 0.01), but not at week 8. Conclusion: BTM application was associated with faster albumin recovery compared with conventional methods. This is the first study to suggest that a dermal substitute may positively influence systemic albumin dynamics in burn patients, highlighting its potential role in reducing protein loss and supporting metabolic recovery.

Abstract: Homeostasis and its interaction with gene expression in the development and maintenance of living systems is discussed in order to formulate a new method to diagnose and treat diseases on this causative level. This includes an inquiry into the unsolved homeostasis problems of: Location - where in the cell are the totality of set-points located? How are they stored? As electrical signals or something else? Type of communication? - what language is used between the set-points? Identity - how do the set-points communicate with gene expression so that each cell can know and maintain its identity? What are the computational mechanisms for each set-point to ensure cellular differentiation? As these functions require the processing of vast amounts of information which is communicated at every level of organization including the mechanisms of epigenetics, different computer models are discussed, with examples for each. This includes an analog, digital and the possibility of a quantum biological model. Each one allows certain properties and cell functions to emerge. The difference between functional homeostasis and dysfunctional homeostasis is discussed with strategies to indirectly study dysfunctional homeostasis in terms of epigenetic signatures. The concept of hormesis is introduced as a mechanism to rebuild homeostasis functions and subsequently reverse the epimutations, leading to a method of treatment for almost any chronic disease. This model is a dynamic interconnected system.

Abstract: Purpose: To evaluate the prognostic significance of pretreatment 18F-FDG PET/CT metabolic parameters in patients with esophageal cancer and to identify independent predictors of long-term overall survival (OS). Methods: This retrospective single-center study included 152 treatment-naïve patients with histopathologically confirmed esophageal cancer who underwent staging 18F-FDG PET/CT between May 2015 and August 2025. Baseline metabolic parameters, including maximum standardized uptake value (SUVmax), SUVmean, lean body mass-corrected SUV (SUL), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), were measured for the primary tumor. Overall survival was analyzed using Kaplan–Meier and Cox proportional hazards models. Receiver operating characteristic analysis was performed to determine optimal prognostic cut-off values. Results: During a median follow-up of 70 months (maximum 124 months), 106 patients (69.7%) died. Patients with higher MTV and TLG had significantly shorter OS than those with lower values (both p< 0.05), whereas SUVmax, SUVmean, and SUL did not. ROC analysis identified MTV as the best-performing PET parameter for predicting mortality (AUC = 0.647). In univariable Cox analysis, MTV, TLG, nodal positivity, distant metastasis, and male sex were associated with OS. In the multivariable model, distant metastasis (HR 2.28 (1.39–3.74), p=0.001) and high MTV (>11.4 cm³; HR 1.72 (1.14–2.61), p=0.010) remained independent predictors of death. Conclusion: In this long-term follow-up single-center cohort, volumetric 18F-FDG PET/CT parameters, particularly MTV rather than SUVmax, carried independent prognostic information for overall survival, alongside distant metastasis. This current cohort highlights the need to include volumetric PET biomarkers in routine pre-treatment risk stratification and individualized treatment planning.

Abstract: Background: Urinary tract infections (UTIs) are a major source of antibiotic use, with increasing antimicrobial resistance compromising treatment efficacy. This study evaluates local pathogen distribution and resistance patterns to support empirical therapy. Methods: We conducted a retrospective, observational study analyzing all positive urine cultures obtained in a tertiary care hospital between January 2023 and December 2025. Bacterial identification and antimicrobial susceptibility testing were performed using routine microbiological methods. Susceptibility results were interpreted according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Results: A total of 1,298 bacterial isolates recovered from positive urine cultures obtained between January 2023 and December 2025 were included in the analysis. Antimicrobial resistance was assessed using 18,079 individual antimicrobial susceptibility test (AST) results. Gram-negative bacteria predominated, with Escherichia coli (44.5%) and Klebsiella pneumoniae (20%) accounting for approximately 64.5% of all isolates. E. coli exhibited high resistance rates to ampicillin (60.4%) and trimethoprim–sulfamethoxazole (33.8%), while resistance to fluoroquinolones was considerable (25.9%). In contrast, nitrofurantoin (2.0%) retained excellent activity, and carbapenem resistance remained very low (0.4%). Klebsiella pneumoniae demonstrated extremely high resistance to beta-lactams and fluoroquinolones, with resistance to third-generation cephalosporins exceeding 60% and carbapenem resistance reaching 34.5–41.2%. Among Gram-positive pathogens, Enterococcus faecalis showed high resistance to fluoroquinolones and high-level aminoglycosides, whereas susceptibility to nitrofurantoin, linezolid, tigecycline, and glycopeptides remained largely preserved. The prevalence of vancomycin-resistant Enterococcus (VRE) was low (7.9%). Conclusions: Our findings reveal alarmingly high resistance rates among major pathogens, particularly Klebsiella pneumoniae, significantly limiting empirical therapeutic options. Nitrofurantoin remained highly active in our cohort. In accordance with current international guidelines, nitrofurantoin and fosfomycin remain recommended first-line agents for uncomplicated UTIs. Continuous local surveillance is essential to guide empirical therapy and support antibiotic stewardship efforts.

Abstract: Background and Objectives: Most current pediatric sepsis screening tools operate in the Emergency Department to detect low incidence Phoenix criteria sepsis. We sought to create an inpatient alert with broader scope and higher predictive value to identify infectious illness cases likely to progress to major physiological decompensation. Methods: Clinician reviews of cases meeting a modified pSOFA sepsis criteria within a 10,992 inpatient cohort identified 83 cases of “gold standard” infection-related decompensation (GS-IRD). Our refinement process utilized Lasso regression to create a model identifying children likely to progress to major or extreme decompensation according to 3M’s APR-DRG severity of illness (SOI) index. Prior to live implementation, a second 4,050 patient cohort was selected and 50 GS-IRD cases identified for external validation of the model and as a baseline for assessing post-implementation patient improvements. We examined the relationship between patients’ maximum alert “score” and final SOI level. We hypothesized that post-firing decreases in score represent clinical improvement, affording a measure of the alert’s efficacy through silent versus live cohort comparisons. Results: Our final model exhibited 85.0% sensitivity and 93.6% specificity for GS-IRD cases, and positive and negative predictive values of 43.6% and 83.7% for major or extreme SOI outcomes. The live epoch showed a greater average decrease in both alert scores over the 48-hour post-firing interval (p< .0001) and maximum scores at ≥48 hours post-admission (p< .0001), compared with the silent epoch. Conclusion: Our pediatric alert shows a high predictive value for progression of infectious illness to major or extreme severity. Alert implementation was associated with significant post-firing clinical improvements.

Abstract: Understanding critical transcriptomic state transitions is essential for elucidating cancer progression and therapeutic response. Although single-cell transcriptomics has transformed the study of cellular heterogeneity, existing approaches primarily characterize gene expression changes or pseudotemporal ordering rather than the underlying dynamics of cellular state transitions. Here, we present a nonlinear dynamical systems framework for the early detection and quantitative characterization of transcriptomic state transitions. The proposed framework integrates diffusion pseudotime, data-driven observable selection, Takens delay-coordinate embedding, nonlinear dynamical analysis, trajectory-aware bootstrap uncertainty estimation, and a novel Transcriptomic Dynamical Instability Score (TDIS). The framework was evaluated using the publicly available single-cell RNA-sequencing dataset GSE147405, which captures epithelial-to-mesenchymal transition (EMT) in A549 cells following EGF, TGFβ1, and TNF stimulation. The reconstructed transcriptomic state spaces exhibited distinct treatment-specific dynamics, with TGFβ1 showing the highest dynamical instability (LLE = 0.0344; TDIS = 0.700), followed by EGF (LLE = 0.0136; TDIS = 0.309) and TNF (LLE = 0.0131; TDIS = 0.188). Local TDIS preceded canonical EMT-associated transcriptional reprogramming for EGF, provided moderate evidence for TGFβ1, and showed no detectable lead for TNF, indicating that its early-warning capability is pathway dependent. Trajectory-aware bootstrap analysis confirmed the robustness and reproducibility of the nonlinear dynamical measures, while independent validation using the GSE149428 treatment-response dataset demonstrated a strong association between transcriptomic trajectory geometry and cell viability (Pearson r = 0.891, p = 0.007; Spearman ρ = 0.821, p = 0.023). These findings establish TDIS as a robust and reproducible framework for quantifying transcriptomic instability and identifying pathway-dependent early-warning signals of critical cellular state transitions, providing a new systems-level approach for investigating cancer progression, therapeutic response, and other dynamic biological processes.

Abstract: Background: Breast cancer incidence is increasing among women <50 years, a group diagnosed outside the UK screening programme. They have a distinct tumour biology, higher hereditary risk, and long-term survivorship challenges. Methods: We conducted a retrospective cohort study of 376 women aged <50 years diagnosed with invasive breast cancer at two London centres (May 2019 – February 2025). Demographic, clinicopathological, treatment, and outcome data were extracted from electronic health records. Survival was estimated using Kaplan-Meier methods. Univariable and multivariable analyses evaluated predictors of tumour characteristics and treatment response. Results: Median age at diagnosis was 44 years. Node-positive disease was present in 47.6% of patients and 43.1% had grade 3 tumours. Women aged ≤30 years had the most adverse tumour characteristics, with 75.0% grade 3 disease and higher odds of nodal involvement than women aged 41–49 years. Higher BMI was associated with grade 3 tumours and triple-negative disease. Among women undergoing germline testing, 22.1% carried a pathogenic variant; notably, 50.0% reported no family history of breast or ovarian cancer. Pathological complete response (pCR) was achieved in 48.0% of patients receiving neoadjuvant therapy (HER2+ 62.5%, triple-negative 59.3%). The estimated 5-year recurrence-free and overall survival were 91.0% and 95.1%, respectively Conclusions: Breast cancer in women <50 years demonstrates substantial biological heterogeneity, with those aged ≤30 years representing a particularly high-risk subgroup. The high prevalence of pathogenic variants despite an absent family history supports broader germline testing. Improving outcomes requires expanded genetic testing and tailored survivorship models addressing fertility, treatment-induced menopause, and quality of life.

Abstract: Background: Healthcare-associated infections (HAIs) caused by multidrug-resistant Klebsiella spp. represent a critical and escalating global public health threat. Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been designated a critical-priority pathogen by the World Health Organization, and in the 2024 WHO Bacterial Priority Pathogens List it was the top-ranked pathogen overall. The convergence of carbapenem resistance with hypervirulence in emerging strains has further complicated therapeutic decision-making. Aim: To provide a narrative synthesis of the evidence published between 2020 and 2025 on the prevalence, resistance mechanisms, molecular epidemiology, clinical outcomes and therapeutic strategies for Klebsiella spp. infections acquired in healthcare settings, with particular attention to the Eastern European and Romanian context. Approach: PubMed/MEDLINE, Embase, Web of Science and the Cochrane Library were searched for relevant publications from January 2020 to June 2025, supplemented by WHO and ECDC surveillance reports. Studies were selected narratively for their relevance to the themes addressed. No new quantitative pooling was undertaken; all summary estimates reported here are cited from the published meta-analyses and surveillance reports that generated them. Key findings: In the most recent global meta-analysis of hospital-acquired CRKP infection, which pooled 61 studies and 513,307 patients from 14 countries, the global prevalence of CRKP among nosocomial K. pneumoniae infections was 28.69% (95% CI: 26.53–30.86%), with pronounced regional variation from 14.29% in high-income North America to 66.04% in South Asia, and 42.05% in Western Europe. Pooled mortality among patients infected with CRKP has been estimated at 42.14%, compared with 21.16% among patients infected with carbapenem-susceptible strains, rising to 54.30% in bloodstream infections. Surveillance data place Romania third in Europe for carbapenem resistance among invasive K. pneumoniae isolates, at 50.30%, with a distinctive predominance of NDM plus OXA-48-like coproducers. Ceftazidime-avibactam is recommended for KPC- and OXA-48-producing strains, whereas metallo-beta-lactamase producers require aztreonam-containing combinations. Conclusions: CRKP in HAIs constitutes a global epidemiological emergency characterised by marked regional heterogeneity in carbapenemase distribution, high attributable mortality and rapidly evolving molecular profiles. Locally adapted surveillance, rapid molecular diagnostics and stewardship programmes are required, since empirical therapy cannot be standardised across regions.

Abstract: Background: Adequate bowel preparation is essential for high-quality colonoscopy, yet patients with diabetes mellitus remain particularly vulnerable to suboptimal cleansing. This study evaluated factors associated with clinically inadequate cleansing among patients with diabetes mellitus undergoing colonoscopy. Methods: This ambispective observational study included 194 adult patients with diabetes mellitus who underwent total colonoscopy at University Hospital Center Split between 1 January 2019 and 30 October 2025 and received a standard split-dose PEG/macrogol-based regimen. Bowel preparation quality was assessed using the Boston Bowel Preparation Scale (BBPS). Clinically inadequate bowel preparation was defined as total BBPS ≤5 or at least one segmental BBPS score ≤1. Multivariable logistic regression was used to evaluate associated factors. Results: Median age was 69 years, 131 participants (67.5%) were male, and 179 (92.3%) had type 2 diabetes mellitus. Clinically inadequate bowel preparation was observed in 68/194 participants (35.1%; 95% CI: 28.3–41.8%). In the main complete-case model (N = 147; events = 52), longer diabetes duration was independently associated with clinically inadequate preparation. Each 5-year increase in diabetes duration was associated with higher odds after adjustment for age, sex, outpatient status, chronic constipation, and use of tricyclic antidepressants or opioids (adjusted OR 1.27, 95% CI: 1.05–1.54; p = 0.015). Sensitivity analyses supported this association. Conclusions: Clinically inadequate bowel preparation was frequent despite standardized split-dose PEG/macrogol preparation. Longer diabetes duration may represent a clinically accessible marker of increased risk, but it should not be used as a stand-alone criterion for intensified bowel preparation without prospective validation.

Abstract: Background: Liver fibrosis staging plays a key role in the prognosis and management of chronic liver disease. Liver biopsy remains the reference standard for fibrosis assessment but is limited by its invasiveness and risk of complications, while magnetic resonance elastography, though also considered a gold standard, is constrained by cost and limited availability. Ultrasound-based elastography techniques — vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), and two-dimensional shear wave elastography (2D SWE) — have emerged as accessible non-invasive alternatives. This narrative review aimed to summarise the principles, diagnostic performance, advantages, and limitations of these three techniques across a range of aetiologies. Methods: A comprehensive literature search was conducted across Scopus, PubMed, Embase, CINAHL, the Cochrane Library, Informit, and the JBI Database of Systematic Reviews and Implementation Reports, covering January 2015 to February 2026. Search terms included “vibration-controlled transient elastography,” “point shear wave elastography,” “two-dimensional shear wave elastography,” “liver stiffness measurement,” “non-invasive assessment,” and “chronic liver disease.” International guidelines, systematic reviews and meta-analyses, large observational cohort studies, and narrative reviews were included in the synthesis. Results: VCTE, pSWE, and 2D SWE all demonstrated good diagnostic performance for detecting advanced fibrosis and cirrhosis across multiple aetiologies. VCTE was the most extensively validated technique, with standardised cut-offs endorsed by major international guidelines. pSWE and 2D SWE showed comparable diagnostic accuracy and can be integrated into conventional ultrasound systems, enabling simultaneous structural and stiffness assessment, although validated cut-off values for these two techniques are not yet established in current guidelines. Obesity, inflammation, steatosis, and recent food intake were identified as factors affecting measurement accuracy across all three techniques. Conclusions: Ultrasound-based elastography techniques offer effective, non-invasive alternatives to liver biopsy for fibrosis assessment. VCTE remains the most validated option despite cost and availability constraints, while pSWE and 2D SWE offer comparable accuracy with practical integration advantages. Future research should focus on standardising cut-off values, addressing confounding factors, and combining elastography with biomarkers and AI-driven models.

Abstract: Background: Spontaneous rupture of hepatoblastoma is uncommon but potentially fatal in children. Published cohorts often combine spontaneous, traumatic, biopsy-related, and treatment-associated events. We aimed to identify clinical risk factors for spontaneous rupture and evaluate its prognostic impact. Methods: We retrospectively reviewed 106 children with pathologically confirmed hepatoblastoma treated at a tertiary center from July 2010 to July 2020. After excluding 10 with incomplete data or follow-up, 96 were eligible. Fourteen children who presented with spontaneous rupture were included in the rupture group. Eighty-two children without rupture were eligible as controls, and 42 were selected after 1:3 propensity score matching for age, sex, height, and weight. Rupture was diagnosed by contrast-enhanced imaging and/or intraoperative findings. Logistic regression was used to identify independent risk factors. Overall survival (OS) and event-free survival (EFS) were estimated using the Kaplan-Meier analysis. Results: The rupture group had lower hemoglobin levels, larger tumors, more frequent bilobar disease, higher PRETEXT stage, and substantially more vascular invasion. In multivariable analysis, maximum tumor diameter (odds ratio 3.078, 95% confidence interval 1.62-5.55; P< 0.001) and vascular invasion (odds ratio 13.521, 95% confidence interval 1.16-148.23; P=0.037) were independently associated with rupture. The combined model incorporating maximum tumor diameter and macrovascular invasion showed an apparent area under the curve of 0.930 and an optimism-corrected area under the curve of 0.924. Children with ruptures had significantly worse OS and EFS than matched controls. Conclusions: Large tumor burden and macrovascular invasion were independently associated with spontaneous hepatoblastoma rupture. Rupture was linked to inferior survival, supporting intensified surveillance and rapid multidisciplinary management for children with these high-risk features.