Medicine and Pharmacology

Abstract: Meta-analysis results depend on statistical assumptions that are partly determined by the software used to conduct the analysis. Meta-epidemiological studies show that Review Manager remains the most frequently reported software in published intervention meta-analyses, but software versions, estimators, interval methods, heterogeneity specifications, and other analytical outputs are often incompletely described. This methods-focused narrative tutorial provides a structured comparison of selected meta-analysis software platforms used in health-related evidence synthesis, including Review Manager, Meta-DiSc, Comprehensive Meta-Analysis, R, and Stata. The comparison focuses on how these platforms implement or restrict key modeling choices relevant to intervention/effect-size meta-analysis and diagnostic test accuracy meta-analysis, including between-study variance estimation, confidence-interval construction, prediction intervals, sparse-data handling, meta-regression, hierarchical diagnostic accuracy modeling, transparency, and reproducibility. The article also distinguishes legacy graphical interfaces, updated web-based platforms, commercial software, and script-based environments, emphasizing how differences in flexibility, auditability, and reporting can affect interpretation. The aim is to help authors, reviewers, editors, and clinical readers recognize when software choices affect model specification, uncertainty quantification, heterogeneity assessment, sparse-data handling, diagnostic accuracy modeling, and reproducibility. Software should therefore be reported as part of the statistical specification of a meta-analysis, not only as a computational detail.

Abstract: Schuurs-Hoeijmakers syndrome, caused by pathogenic variants in PACS1, is a rare neurodevelopmental disorder characterized by intellectual disability, distinctive craniofacial dysmorphism, and multisystem involvement. A 6-year-old male presented with global developmental delay, nocturnal seizures, hypotonia, and progressive craniofacial dysmorphism, including frontal hypertrichosis, synophrys, cup-shaped ears, and digital pads. Whole-exome sequencing revealed a de novo pathogenic variant in PACS1 c.607C>T (p.Arg203Trp), absent in both parents, becoming the first molecularly confirmed case of SHMS in southwestern Colombia. Interestingly, the patient fulfilled the clinical criteria for KS, but no pathogenic variants were identified in KMT2D or KDM6A, supporting the consideration of SHMS as a Kabuki-like syndrome. Brain MRI was unremarkable; however, additional findings such as stereotypic movements, photophobia, and feeding difficulties contributed to an expanded phenotypic spectrum. This case expands the genotypic and phenotypic spectrum of SHMS and reinforces its role as a phenotypic mimic of chromatinopathies like KS. We recommend that PACS1 be included in the genetic evaluation of patients with Kabuki-like features, especially when standard testing yields inconclusive results. This report also underscores the diagnostic value of exome sequencing in complex neurodevelopmental disorders.

Abstract: Background: Ketamine is used as an adjunct analgesic for cancer pain refractory to opioids, but evidence remains limited to small series, predominantly from high-income settings. Few studies include both adults and children, and data from the Middle East are sparse. Methods: We conducted a retrospective study of all patients who received intravenous ketamine for pain at King Hussein Cancer Center (KHCC), Jordan, between February 2018 and April 2026. Pain scores, medications, and vital signs were extracted from the structured EHR. Unstructured variables (pain mechanism, adverse events) were extracted using a schema-constrained large language model pipeline (GPT-4.1-mini) and validated in a 10% random sample by two investigators (AA, EK). The primary outcome was the paired within-patient change in peak pain (maximum NRS in 72 hours pre-ketamine vs maximum NRS in 24 hours post), tested by the Wilcoxon signed-rank test. Results: 433 patients received IV ketamine (183 [42%] paediatric; 72% deceased at follow-up). Among 141 patients with paired peak data, the median paired reduction in peak pain at 24 hours was 1 point (IQR 0 to 5; mean 2.5 ± 3.8; p < 0.001; matched-pairs rank-biserial r = 0.58). Among 107 patients with baseline peak pain >=3, 67 (63%) achieved a >=2-point reduction. Planned sensitivity analyses using peak-to-nadir and mean-to-mean metrics confirmed the direction of the effect. Adverse events were documented in 25 patients (5.8%); retrospective ascertainment likely underestimates true incidence. Conclusions: In the largest single-centre series to date, adjunctive IV ketamine was associated with reduced peak cancer pain in adults and children. The observational design precludes causal inference. These data support ketamine’s feasibility as a palliative analgesic adjunct across age groups in a middle-income setting. The bimodal response pattern (63% responders alongside non-responders) is a hypothesis-generating finding for future trial enrichment. A placebo-controlled randomised trial stratified by pain mechanism is a logical next step where equipoise can be established.

Abstract: Background/Objectives: Tinnitus is often a distressing and disabling condition that negatively affects individuals' emotional well-being and quality of life. The aim of this study was to evaluate the relationship between perceived tinnitus handicap and sociodemographic and clinical characteristics, personality traits, and symptoms of depression, anxiety, and stress. Methods: Tinnitus patients with hearing loss (N = 127) underwent audiologic testing and completed the Tinnitus Handicap Inventory (THI), Depression Anxiety Stress Scales (DASS), and Eysenck Personality Questionnaire-Revised Short Form (EPQ-RS). Patient sociodemographic data (age, sex, and education level) and descriptive tinnitus characteristics were collected. The control group (N = 119) comprised tinnitus-free patients with hearing loss. Results: Patients experiencing catastrophic tinnitus reported significantly higher depression, anxiety, and stress scores compared to those with slight, mild, or moderate tinnitus grades. Education level was weakly negatively associated with THI scores. Conversely, weak-to-moderate positive relationships were observed for tinnitus loudness, pure tone average, the three DASS subscales, and the neuroticism subscale. Hierarchical multiple regression identified subjective tinnitus loudness, neuroticism, and total emotional distress (the total DASS score) as statistically significant predictors of the total THI score. Patients with tinnitus showed statistically significantly higher depression, anxiety, and stress subscale scores compared to tinnitus-free controls. Conclusions: The severity of tinnitus handicap is primarily driven by subjective loudness, underlying neuroticism, and emotional distress. Patients with catastrophic tinnitus exhibit markedly higher levels of depression, anxiety, and stress. Consequently, clinical management of tinnitus must move beyond standard audiologic testing to include comprehensive psychological screening and targeted distress-reduction therapies.

Abstract: Background/Objectives: As cancer survival improves, rehabilitation has become an increasingly important component of comprehensive oncology care, addressing the growing burden of treatment-related impairments. Although electrotherapy modalities are widely used in Physical and Rehabilitation Medicine, their use in oncology remains controversial because of persistent safety concerns and potential interactions with tumor biology. This narrative review critically evaluates current evidence on the clinical applications, safety considerations, contraindications, and therapeutic potential of electrotherapy modalities in oncology rehabilitation.Methods: A structured literature search was performed in PubMed, Scopus, and Web of Science for studies published between January 2000 and March 2026. Evidence from randomized controlled trials, observational studies, systematic reviews, meta-analyses, clinical practice guidelines, consensus statements, and narrative reviews was analyzed.Results: The available evidence demonstrates considerable heterogeneity among electrotherapy modalities with respect to their mechanisms of action, biological effects, safety profiles, and clinical applicability. TENS, neuromuscular and functional electrical stimulation, and Deep Oscillation Therapy have reached a relatively mature stage of development, with growing evidence supporting their use for pain, lymphedema, cancer-related weakness, functional impairment, and selected manifestations of chemotherapy-induced peripheral neuropathy. Photobiomodulation represents a notable example in which theoretical concerns regarding tumor stimulation coexist with clinical evidence and guideline-supported indications, particularly for the prevention and management of oral mucositis. Electromagnetic field therapies constitute a rapidly evolving area of investigation, whereas evidence remains limited for interferential currents, diadynamic currents, high-intensity laser therapy, and diathermy-based interventions.Conclusions: Electrotherapy should not be regarded as a homogeneous therapeutic category in oncology rehabilitation. Current evidence supports a shift from generalized contraindications toward modality-specific, evidence-informed, and individualized clinical decision-making. Further high-quality clinical studies are required to establish optimal treatment parameters and clarify the interactions between physical agent modalities, tumor biology, and rehabilitation outcomes.

Abstract: Background: Ischemic stroke is a very uncommon serious vaccine adverse event (SVAE) after COVID-19 vaccination. Ischemic stroke is also associated with SARS-CoV-2 infection and post-COVID-19 syndrome (PCS). As an SVAE, ischemic stroke may occur alone or in association with vaccine-induced immune thrombotic thrombocytopenia. Methods: We present a 63-year-old man who developed systemic post-vaccination symptoms shortly after the first dose of ChAdOx1 nCoV-19/AZD1222, followed by clinical ischemic stroke. Neuroimaging demonstrated an acute vertebrobasilar infarct, with possible small supratentorial ischemic lesions. There was no evidence of vaccine-induced immune thrombotic thrombocytopenia, no alternative cardioembolic source, and no evidence of SARS-CoV-2 infection. We also conducted a narrative review in MEDLINE and Google Scholar, focusing on stroke following SARS-CoV-2 infection, COVID-19 vaccination, PCS, and PCVS. Results: Ischemic stroke is a recognized manifestation of SARS-CoV-2 infection (1–5% in hospitalized patients) and an extremely uncommon SVAE associated with COVID-19 vaccination. Patients with SARS-CoV-2 infection and PCS appear to have an increased risk of stroke. Across these SARS-CoV-2-related entities, proposed mechanisms include immune responses targeting the spike protein, coagulopathy, endothelial dysfunction, and microvascular injury. Conclusions: The temporal and clinical features of the presented case are compatible with an SVAE, although causality cannot be definitively established from a single case. The reviewed literature suggests that ischemic stroke after SARS-CoV-2 infection, COVID-19 vaccination, PCS, and PCVS may share overlapping pathophysiological mechanisms.

Abstract: Background/Objectives: Extracranial-intracranial (EC-IC) arterial bypass, particularly superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis, is employed in selected patients with moyamoya disease or atherosclerotic steno-occlusive disease to augment cerebral perfusion. Objective hemodynamic monitoring before and after revascularization remains essential. This study evaluated the impact of STA-MCA bypass on regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) with a semi-quantitative area-based method. Methods: Fifteen patients who underwent STA-MCA bypass between June 2018 and June 2022 with available pre- and postoperative CTA and rCBF-SPECT studies were retrospectively analyzed. A custom semi-quantitative technique using Labelme annotation, Canny edge detection, and Green’s theorem was applied to calculate the proportional perfusion area in basal ganglia and temporal regions, normalized to total brain area. Paired pre–post comparisons and subgroup analyses (left- vs. right-sided surgery; ipsilateral vs contralateral regions) were performed. Results: Mean age was 56 ± 15.7 years (40% female). Indications included moyamoya disease (20%) and arterial stenosis/occlusion (80%). All 16 anastomoses (14 unilateral, 1 bilateral) were patent postoperatively. Overall, postoperative perfusion area proportion improved significantly in basal ganglia (mean difference 0.24, 95% CI 0.13–0.35, p = 0.0003) and temporal regions (0.34, 95% CI 0.08–0.60, p = 0.0131). Improvement in basal ganglia perfusion was similar between left-sided (Δ 0.23) and right-sided (Δ 0.28) surgery groups. In unilateral cases, there was no significant difference between ipsilateral and contralateral basal ganglia improvement (p = 0.839), suggesting a global hemodynamic effect. Conclusions: STA-MCA bypass was associated with objective rCBF improvement on semi-quantitative SPECT, with consistent benefits in the basal ganglia regardless of surgical laterality. The lack of significant ipsilateral-contralateral difference supports a global hemispheric perfusion augmentation mechanism. The pragmatic semi-quantitative SPECT method is feasible for hemodynamic monitoring after revascularization.

Abstract: Background: Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterised by abnormal angiogenesis resulting from dysregulation of the BMP9/10–ALK1–ENG–SMAD signalling axis. The disease is clinically characterised by recurrent epistaxis, iron-deficiency anaemia, gastrointestinal bleeding and visceral arteriovenous malformations. Increasing knowledge of the molecular mechanisms underlying endothelial dysfunction has led to the development of targeted therapeutic approaches aimed at modulating angiogenic pathways involved in disease progression. Methods: A narrative review with a clinical and translational perspective was performed using publications identified in PubMed/MEDLINE, Scopus, Web of Science and ClinicalTrials.gov from January 2012 to May 2026. Medical Subject Headings (MeSH) and free-text terms related to HHT, angiogenesis, VEGF, FGFR, PI3K/AKT/mTOR, ANGPT2 and currently available or emerging therapies were used. Priority was given to randomised clinical trials, prospective studies, observational cohorts, systematic reviews, meta-analyses, international guidelines and consensus documents. Results: Bevacizumab remains the systemic anti-VEGF therapy with the strongest clinical evidence for severe bleeding, transfusion-dependent anaemia and symptomatic hepatic involvement. Pomalidomide has provided the most robust randomised evidence for the treatment of moderate-to-severe epistaxis and improvement of quality of life. Multikinase inhibitors such as nintedanib and pazopanib, together with tacrolimus, sirolimus and beta-blockers, have expanded the therapeutic landscape, although additional evidence is still required for several of these approaches. More recently, the AKT inhibitor engasertib demonstrated clinically meaningful reductions in epistaxis frequency and severity, providing the first direct clinical validation of AKT as a therapeutic target in HHT. Emerging strategies targeting ANGPT2/Tie2 and other vascular stabilisation pathways may further broaden future treatment options. Conclusions: The therapeutic management of HHT is moving progressively towards a precision medicine model integrating genotype, haemorrhagic phenotype, visceral involvement, angiogenic biomarkers and treatment tolerability. Bevacizumab and pomalidomide currently represent the most established systemic therapies, whereas AKT inhibition has emerged as one of the most promising developments in the field. Future progress will depend on international collaboration, standardised outcome measures, biomarker-guided patient selection and the development of personalised therapeutic strategies.

Abstract: Orthobiologic and aesthetic biostimulatory injectables hold a privileged regulatory and commercial position in the orthobiologic and aesthetic injectable markets. Most common amongst these injectable products are Platelet-Rich Plasma (PRP), Bone Marrow Aspirate Concentrate (BMAC), Calcium Hydroxylapatite (CaHA; Radiesse®), and Poly-L-Lactic Acid (PLLA; Sculptra®). Currently, PRP qualifies for Investigational New Drug (IND)-exempt Randomized Controlled Trial (RCT) access as a minimally manipulated, homologous-use autologous biologic. CaHA and PLLA have received FDA clearance for aesthetic applications largely due to mechanistic claims of neocollagenesis and fibroblast biostimulation. BMAC has widespread off-label clinical usage due to clinical literature claims of mechanistic growth-factor and mesenchymal stem cell presence. The purpose of this perspective review is to highlight a foundational mechanistic attribution error in the previous clinical literature of these four orthobiologic and aesthetic injectables. The previous in vitro findings that claimed proliferative, chondrogenic, and neocollagenic effects of these injectables incorporated Fetal Bovine Serum (FBS) or fetal calf serum into the cell culture models. FBS does not have a functional analog in human synovial fluid, bone marrow, or dermal interstitium and is not commercially available to clinicians as an injectable product. The reagent largely responsible for the mechanistic signal produced in these previously conducted clinical trials is absent from clinical practice and cannot be replicated in human patients. Burgeoning state regulatory frameworks around which new Stem Cell and Regenerative Therapy Laws are drafted should therefore anticipate and invite both comparative IRB-approved research and expanded clinical use as paired conditions of the same legislative authority.

Abstract: Background/Objectives: Oxidative stress and low-grade chronic inflammation are implicated in the early pathogenesis of non-communicable diseases (NCDs). Malondialdehyde (MDA), a stable biomarker of lipid peroxidation, may reflect subclinical oxidative stress in apparently healthy young adults. This study aimed to: (1) establish a population-specific reference interval for plasma MDA in healthy Thai undergraduate students; and (2) evaluate associations between plasma MDA levels and lifestyle risk factors. Methods: This cross-sectional study enrolled 141 Thai college students aged 18–27 years. Plasma MDA was measured using the thiobarbituric acid reactive substances (TBARS) assay. A reference interval was determined non-parametrically (P2.5–P97.5) following IFCC recommendations in a healthy reference subgroup (n = 94). The 75th percentile (P75) was used as an exploratory cutoff for elevated MDA. Binary logistic regression identified independent lifestyle predictors of elevated MDA. Results: The plasma MDA reference interval was 1.16–9.23 µmol/L, with P75 = 6.07 µmol/L. Using this cutoff, 24.8% of participants had elevated MDA. High sugar intake (&gt;24 g/day) was the only independent predictor of elevated MDA after multivariate adjustment (adjusted OR = 3.42; 95% CI: 1.08–10.87; p = 0.036). Conclusions: To our knowledge, this study established the first population-specific plasma MDA reference interval for Thai young adults using the TBARS method. High sugar intake was identified as a key modifiable lifestyle predictor of elevated lipid peroxidation, even in apparently healthy individuals. These findings support the use of plasma MDA as a practical, cost-effective screening biomarker for early oxidative stress surveillance and NCD prevention in young populations.

Abstract: Background: Type 2 diabetes mellitus is a progressive cardiometabolic disease in which many patients require treatment intensification despite lifestyle intervention and evidence-based pharmacotherapy. Oleanolic acid, a pentacyclic triterpenoid found in olives and other plants, has shown insulin-sensitizing, antioxidant, anti-inflammatory, and hepatometabolic effects in experimental models.Aim: This review evaluates oleanolic acid as a potential adjunctive intervention in type 2 diabetes, emphasizing translational evidence, formulation-dependent bioavailability, clinical endpoints, and patient relevance.Methods: We performed a narrative translational review of mechanistic, preclinical, pharmacokinetic, clinical, and trial-registry evidence on oleanolic acid, insulin resistance, prediabetes, and type 2 diabetes.Results: Preclinical studies support multiple mechanisms by which oleanolic acid may influence glucose homeostasis, including modulation of insulin signaling, hepatic glucose production, oxidative stress, inflammatory pathways, lipid metabolism, and beta-cell vulnerability. Human evidence remains limited but clinically relevant. PREDIABOLE reported reduced progression from prediabetes to type 2 diabetes after long-term intake of oleanolic acid-enriched olive oil. BIO-OLTRAD demonstrated measurable systemic exposure after a 30 mg dose delivered in functional olive oil, with transport through albumin and triglyceride-rich lipoproteins. OLTRAD is testing whether this formulation improves glycemic control as an adjunct to metformin-based therapy.Conclusion: Oleanolic acid is a plausible investigational adjunct for type 2 diabetes. Its clinical value depends on formulation-specific exposure, reproducible effects on glycemic and cardiometabolic endpoints, and long-term safety.Relevance for patients: Oleanolic acid-enriched functional foods may eventually complement, but should not replace, evidence-based diabetes treatment.

Abstract: Diagnostic laboratory tests are often judged by analytic validity, clinical validity, sensitivity, specificity, predictive values, and likelihood ratios. These quantities describe test per­formance, but they do not determine whether a result improves care. A laboratory test has clinical value when it changes a decision in a way that improves expected outcomes after accounting for uncertainty, downstream management, time, cost, patient burden, and treatment harm. This ar­ticle presents DECIDE-Lab (Decision-centered Evaluation of Clinical Information and Dynamic Evidence for Laboratory Testing), a decision-theoretic framework for diagnostic laboratory test selection. DECIDE-Lab combines value-of-information analysis with partially observable Markov decision processes to evaluate single tests, reflex testing, serial monitoring, and stopping rules. The framework links sensitivity and specificity to posterior belief updating, action thresholds, expected utility, utility elicitation, clinical utility frontiers, diagnostic dominance, implementation pathways, and subgroup-specific value. An illustrative acute coronary syndrome application shows that the value of serial troponin testing concentrates in intermediate-risk patients for whom an additional result can change disposition or treatment. A worked sepsis pathway demonstrates the POMDP mechanics step by step, including an initial belief state, Test 1, posterior updating, conditional value for Test 2, and the resulting stop-or-continue decision. Five disease-state applications–acute coronary syndrome, sepsis, prostate cancer, autoimmune disease, and tuberculosis–demonstrate how the framework can support diagnostic stewardship, adaptive ordering, and value-based labo­ratory evaluation. The central implication is that diagnostic value should be measured by action­changing utility rather than accuracy alone, while explicitly examining how conclusions change when utilities, implementation constraints, and equity goals vary.

Abstract: Background: Tuberculosis (TB) remains the leading cause of death among persons with advanced HIV disease (AHD) in high HIV-burden settings. Digital chest X-ray (dCXR) with computer-aided detection (CAD) is a promising tool to overcome human resource constraints and improve TB case detection. This study evaluates the real-world im-plementation and performance of dCXR/CAD for TB screening within a specialized AHD clinic in Maputo, Mozambique. Methods: We conducted a retrospective cohort analysis of 487 new AHD patients at Centro de Referência do Alto Maé (CRAM) from October 2023 to September 2024. Of these, 238 underwent dCXR with CAD interpreta-tion. All patients underwent systematic TB screening according to Ministry of Health (MoH) guidelines. Using the recorded diagnosis of TB (bacteriologically confirmed or clinically diagnosed) as the reference standard, we calculated the sensitivity, specifici-ty, positive predictive value (PPV), and negative predictive value (NPV) of the nation-ally adopted CAD threshold (≥0.5). Results: Among 238 AHD patients screened with CAD, 116 (49%) were diagnosed with TB. At the ≥0.5 threshold, sensitivity was 50% (58/116; 95% CI: 41–59), specificity 92% (112/122; 95% CI: 85–96), PPV 85% (58/68; 95% CI: 75–92), and NPV 65.9% (112/170; 95% CI: 58–73). TB diagnosis rates increased sharply with CAD score: 30% (43/143) in normal, 52% (15/27) in abnormal non-suggestive, and 85% (58/68) in suggestive cases. Bacteriological confirmation was low across all groups (19–26%), reflecting reliance on clinical diagnosis. Conclu-sion: Integrating dCXR/CAD into AHD care is feasible and identifies a high TB burden. However, at the adopted threshold of ≥0.5, CAD demonstrated high specificity but low sensitivity (50%) in this population, missing half of all TB cases. These findings suggest that CAD functions better as a confirmatory decision-support tool than a standalone screening test in AHD. Threshold optimization for this specific population warrants prospective evaluation. Implementation challenges — including fragmented systems and lack of dedicated human resources — must be addressed to realize CAD's full po-tential in TB programs.

Abstract: Hopkins syndrome (HS) is a rare paediatric condition characterized by acute flaccid paralysis following an asthma attack and is classically attributed to irreversible anterior horn cell damage. Despite decades of case reports, its pathophysiology remains poorly understood, and therapeutic responses to intravenous steroids or immunoglobulins are inconsistent. Nineteen paediatric cases reported over the past 30 years were reviewed, and marked heterogeneity in clinical presentation, neuroimaging findings, treatment timing, and outcomes was identified. Notably, several patients, particularly those with upper extremity involvement, showed substantial or complete recovery, suggesting that HS represents a spectrum of disorders rather than a single entity. Delayed diagnosis and treatment were frequent and likely contributed to irreversible motor neuron injury. Based on clinical patterns and emerging experimental evidence, a unified model is proposed, in which asthma-associated vascular vulnerability, microcirculatory dysfunction, and amplified neuroinflammation converge to produce region-specific injury in the spinal anterior horn. This perspective reframes HS as a potentially treatable condition when recognized early, emphasizing the importance of optimal asthma control, vigilance for neurological symptoms after asthma attacks, and timely initiation of immunomodulatory therapy. Clarifying the neurovascular and inflammatory mechanisms underlying HS may improve outcomes and guide future research on this rare but devastating disorder.

Abstract: Rotavirus infection in neonates is occasionally associated with neurological complications, including encephalopathy and white matter injury; however, the underlying mechanisms remain elusive. While direct viral invasion of the central nervous system (CNS) has been proposed, accumulating evidence suggests that indirect mechanisms may also contribute to the pathogenesis. In this review, we propose a barrier-centered, hypothesis-driven framework in which rotavirus nonstructural protein 4 (NSP4), a multifunctional viral protein known for its role in calcium dysregulation and enterotoxicity, may influence neuroimmune function through its effects on endothelial and epithelial barriers. Evidence derived primarily from intestinal and non-neural systems suggests that NSP4 may modulate inflammatory signaling pathways and barrier integrity. We hypothesize that circulating NSP4-related signals could interact with CNS interfaces without requiring widespread direct neuroinvasion. However, most supporting evidence remains indirect, and the relevance of these mechanisms to the neonatal CNS has not been directly established. This framework integrates current evidence while distinguishing between established findings and hypothesis-driven interpretations. Importantly, it also highlights key experimental questions, including whether NSP4 interacts with CNS barrier cells and whether such signaling alters barrier function in vivo. Addressing these questions may improve our understanding of rotavirus-associated neurological disease.

Abstract: Introduction: Critical care medicine in Nigeria has evolved from a single postoperative recovery unit in 1973 to a recognised subspecialty, yet it remains severely under-resourced relative to population need. This systematic review synthesises evidence on the evolution, current capacity, workforce challenges, and financing of critical care in Nigeria and proposes evidence-informed strategies for sustainable system strengthening. Methods: We systematically searched PubMed/MEDLINE, African Journals Online, Scopus, and Web of Science from inception to March 2025, supplemented by reference list screening and grey literature from Nigerian Ministry of Health and professional society sources. Studies reporting on critical care capacity, workforce training, clinical outcomes, policy development, or financing in Nigerian settings were included. Two reviewers independently screened records and extracted data. Risk of bias was assessed using the JBI critical appraisal tools. Due to heterogeneity in study designs and outcome measures, data were synthesised thematically. Certainty of evidence was evaluated using the GRADE framework. This review is reported according to the PRISMA 2020 statement. Results: Of 254 unique records screened, 40 studies were included in the thematic synthesis. Nigeria has approximately 30 intensive care units (ICUs), yielding an estimated 0.1–0.2 beds per 100,000 population. Most ICUs are in tertiary public hospitals and are led by consultant anaesthetists rather than dedicated intensivists. Mortality rates in Nigerian ICUs are reported between 38% and 74% depending on diagnosis and case mix. The National Postgraduate Medical College of Nigeria approved a fellowship and MD curriculum in Intensive Care Medicine in December 2024, formalising the specialty. Paediatric ICUs exist in only 12.1% of training institutions. Out-of-pocket payments dominate financing, and the National Health Insurance Scheme excludes critical care. The certainty of evidence was very low to low across all key outcomes, primarily due to risk of bias, inconsistency, and indirectness. Conclusion: Critical care in Nigeria has progressed from an anaesthesia-led recovery service to an independent specialty with a formal curriculum, but structural deficits persist. Targeted investment in bed capacity, workforce retention, NHIS reform, tele-ICU platforms, and national registry development are essential for building a resilient, equitable critical care system.

Abstract: The educational portfolio is in line with the principles of OBE (Outcome-Based Education) as a tool enabling the documentation and assessment of learning outcomes in a continuous, individualized manner, embedded in a real clinical context. Its use allows for a shift away from point-based assessment of achievements in favor of monitoring the progression of competencies over time, which is one of the key postulates of competency-based education (programmatic assessment). The educational portfolio is an important tool supporting the process of medical education, combining the perspectives of the teaching physician and the medical student. From the clinical teacher’s point of view, the portfolio enables systematic assessment of the student’s progress, clinical competencies, reflective skills, and professional development over time. It also facilitates the individualization of the teaching process, supports constructive feedback, and promotes the development of professional attitudes consistent with the principles of evidence-based medicine and medical ethics. For medical students, the portfolio is a space for active learning, integrating theoretical knowledge with clinical experience. It allows them to document the skills they have acquired, analyze their strengths and areas for further development, and develop self-reflection and responsibility for their own learning process. Regular portfolio maintenance promotes awareness of the role of a future physician and prepares students for lifelong learning. The joint use of the portfolio by the teacher and student strengthens the partnership model of education, increases the transparency of requirements, and improves the quality of medical education, making it more focused on the development of competencies and patient needs.

Abstract: The implementation of automated clinical decision support systems (CDSS) is essential for enhancing patient safety and optimizing public healthcare ecosystems. While advanced predictive analytics and machine learning (ML) architectures offer high diagnostic accuracy, their "black-box" nature and heavy infrastructure demands often restrict their real-time deployment at the bedside. This study introduces a translational framework designed to close this gap by converting high-dimensional predictive intelligence into an explainable, zero-overhead deployment pathway: the Surgery-Complication Risk Index (S-CRI). Using a multicenter digital health registry of 19,965 surgical records from Greek public hospitals, we subjected macroscopic parameters to target-directed combinatorial topology and to multivariate logistic regression optimization. Length of hospitality stay (Adjusted Odds Ratio [aOR] = 1.44 per day), admitting hospital department classifications, and empirically pooled entry diagnosis risk clusters were isolated as core predictive features. These continuous statistical weights were linearly aligned into an integer scorecard where 1.0 point maps directly to the independent risk contribution of a single inpatient day. Signal detection validation demonstrated excellent discriminative power, yielding an Area Under the ROC Curve (AUC) of 0.882. Operating at an optimized screening threshold of -4, the index achieved a sensitivity of 66.56% and a specificity of 89.64%, effectively minimizing alert fatigue. Continuous risk scores were stratified into five actionable digital health triage tiers ranging from Very Low (<1% complication incidence) to Very High (>75%). Rather than acting as an alternative to AI, the S-CRI functions as a transparent, explainable layer for clinical decision support. This framework democratizes predictive medical insights, providing an immediate deployment vector for resource-constrained environments within modern digitized healthcare systems.

Abstract: Background/Objectives: Gastric precancerous conditions and early gastric cancer rep-resent a heterogeneous disease spectrum with variable malignant potential and complex management pathways. Despite well-established international guidelines, discrepancies remain between recommended strategies and routine clinical practice, particularly regarding endoscopic diagnosis, risk stratification, therapeutic selection, and follow-up. This review aims to synthesize current evidence and provide practice-oriented, question-based guidance for the management of gastric precancerous lesions and early gastric cancer. Methods: A comprehensive review of the literature was conducted using PubMed and Google Scholar, focusing on endoscopic diagnosis, histological risk assessment, thera-peutic options, and surveillance strategies for gastric precancerous lesions and early gastric cancer. Key areas of clinical uncertainty and controversy were identified and translated into focused, practice-oriented clinical questions designed to reflect and possibly help to improve real-world gastroenterological practice. Results: Clinical questions were formulated to cover the entire management pathway, from endoscopic detection and characterization to therapeutic decision-making and post-treatment surveillance. Topics include high-quality endoscopic diagnosis, biopsy strategies, histological staging system, selection between endoscopic and surgical therapy, and follow-up according to individual risk profile. For each question, current evidence is summarized into concise, actionable recommendations. Conclusions: Management of gastric precancerous lesions and early gastric cancer requires a structured and individualized approach integrating high-quality endoscopy, accurate histological risk stratification, and evidence-based therapeutic and surveillance strategies. Organizing available evidence into practice-oriented clinical questions may help harmonize clinical practice, reduce unwarranted variability, and support gastroenterologists in delivering optimal patient-centered care.

Abstract: Large language models (LLMs) have advanced medical reasoning, but static question-answering performance remains insufficient for clinical workflows that require evolving patient-state tracking, evidence integration, role coordination, and accountable decisions. Medical multi-agent systems (MAS) shift AI from isolated answer generation toward workflow-level clinical intelligence by combining role specialization, memory, tool use, retrieval, communication, and orchestration. This Review maps medical MAS across diagnosis, treatment decision support, imaging, monitoring, surgery, hospital workflow automation, evidence synthesis, medical education, and safety governance. We further synthesize key architectures for collaboration, knowledge-augmented evidence chains, multimodal integration, privacy-preserving coordination, and adaptive optimization, together with evaluation strategies spanning outcomes, process quality, robustness, efficiency, human comparison, and temporal backtesting. We argue that MAS should be validated not merely as answer engines, but as auditable, controllable workflow systems. Future work should prioritize traceable evidence chains, human oversight, privacy-preserving collaboration, standardized reporting, and prospective clinical validation.