Medicine and Pharmacology

Abstract: Background: Behçet’s syndrome is a chronic, relapsing, multisystem inflammatory disorder characterised by recurrent mucosal ulceration and variable ocular, vascular, neurological, gastrointestinal, articular, and cutaneous involvement. Over the past two decades, the field has moved from syndrome-based description and empiric immunosuppression towards mechanism-informed phenotyping and targeted treatment. Objectives: To provide a contemporary narrative review of Behçet’s syndrome from 2000 to the present, with particular emphasis on search methods, pathophysiological foundations, clinical expression, diagnostic and classification frameworks, and the evidence base for conventional and targeted therapies. Methods: A structured narrative review was undertaken using major bibliographic databases and guideline repositories. The search strategy combined Medical Subject Headings, Emtree terms, and free-text keywords relating to Behçet’s syndrome, pathophysiology, diagnostic criteria, and treatment, with particular attention to randomised trials, prospective cohorts, systematic reviews, and international recommendations. Results: Current evidence supports Behçet’s syndrome as a complex immunovascular disease at the interface between autoinflammation, adaptive immune dysregulation, endothelial injury, and thromboinflammation. HLA-B51 remains the strongest genetic association, while ERAP1, IL10, IL23R-IL12RB2 and related pathways broaden the mechanistic framework. Neutrophil hyper-reactivity, NETosis, Th1/Th17 polarisation, endothelial activation, and cytokine circuits involving TNF, IL-1, IL-6, IL-17 and IL-23 underpin much of the clinical spectrum. The International Criteria for Behçet’s Disease improved sensitivity over the earlier International Study Group criteria, but diagnosis remains clinical. Therapeutically, colchicine, glucocorticoids and conventional immunosuppressants retain important roles, yet anti-TNF therapy has transformed outcomes in severe ocular, vascular, neurological and intestinal disease. Apremilast is now an evidence-based option for recurrent oral ulcers, while IL-1 blockade, IL-6 inhibition, IL-17 blockade, IL-12/23 inhibition and Janus kinase inhibition remain promising but incompletely defined strategies. Conclusions: Behçet’s syndrome requires rapid organ-based risk stratification and early suppression of major organ inflammation. The contemporary therapeutic landscape is considerably broader than it was at the turn of the century, but important gaps remain in comparative trials, biomarkers, treatment sequencing, and precision phenotyping.

Abstract: Background/Objectives: Vitamin B12 (cobalamin) plays an essential role in DNA synthesis, erythropoiesis, and cellular metabolism. Its deficiency is common in the general population and may influence various biochemical markers. Tumor markers such as CA 125, CA 15-3, CA 19-9, CEA, and AFP are widely used in oncology, yet their levels can also be affected by non-malignant conditions. This study aimed to investigate the relationship between serum vitamin B12 levels and tumor marker concentrations in non-cancerous patients. Methods: This retrospective study included 250 adult participants (141 with low serum vitamin B12 < 200 ng/L and 109 with normal B12 ≥ 200 ng/L) who presented to Etlik City Hospital between June 2022 and June 2025. All participants were non-smokers and had no history of chronic kidney disease or malignancy. Hematologic, biochemical, thyroid, and iron parameters were analyzed alongside tumor markers (CA 15-3, CA 125, CA 19-9, CEA, and AFP) using standard immunoassay techniques. Statistical analyses included group comparisons, correlation testing, and logistic regression to identify factors independently associated with low vitamin B12 levels. Results: Patients with low vitamin B12 levels exhibited significantly lower hemoglobin, hematocrit, white blood cell, and neutrophil counts (p < 0.01 for all). Free T4 and serum iron were independently associated with low B12 levels in multivariable analysis (p < 0.001). Among tumor markers, CA 125 and CEA were significantly reduced in patients with vitamin B12 deficiency (p < 0.0001), while CA 15-3 showed a moderate inverse correlation with B12 concentration (r = –0.36, p < 0.0001). Conclusions: Vitamin B12 deficiency is associated with alterations in hematologic, thyroid, and iron parameters and may be associated with serum tumor marker levels even in non-cancerous individuals. Recognizing the potential association between B12 status and tumor marker variability may contribute to more cautious interpretation of tumor marker results in clinical practice.

Abstract: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is the pathogen driving the deterioration of the European antimicrobial resistance landscape, and the burden falls disproportionately on Romania and South-Eastern Europe. This narrative review synthesises evidence published between 2020 and 2025 on the epidemiology, molecular characteristics, clinical impact and pandemic-era trajectory of CRKP healthcare-associated infections across Romania, Bulgaria, Greece, Croatia, Slovenia, Serbia, Bosnia and Herzegovina, Montenegro, North Macedonia, Albania and Kosovo. The search was deliberately multilingual: alongside the international literature we interrogated national-language sources in Romanian, Bulgarian, Greek, Croatian, Slovenian and Serbian, including congress abstract books, doctoral theses, national reference-laboratory reports and agency surveillance series that are absent from PubMed. Three findings emerge. First, the region is not epidemiologically uniform: estimated incidence of carbapenem-resistant K. pneumoniae bloodstream infection in 2024 ranged from 0.62 per 100,000 population in Slovenia to 20.31 in Romania, against an EU/EEA figure of 3.46, and the steepest relative rise between 2019 and 2024 was recorded in Bulgaria (+374.1%). Second, a distinctive molecular signature has consolidated in the northern half of the region: co-production of a metallo-β-lactamase with an OXA-48-like enzyme, reported in 44.4–61.2% of characterised Romanian isolates across independent centres, which removes ceftazidime-avibactam from the therapeutic repertoire and leaves aztreonam-avibactam and cefiderocol as the principal remaining options. Third, the pandemic did not produce a single regional signal but a consistent sequence — a transient interruption of upward trends during 2020, a marked acceleration from 2021, and persistence of the elevated level after 2022 — with national-language surveillance from Croatia and Slovenia showing that the direction of the apparent pandemic effect depends on whether incidence or resistance proportion is measured. The national-language literature adds granularity unavailable in English, but the evidence base remains structurally uneven: Albania, Kosovo and North Macedonia contribute almost no primary data, and no country in the region has published a CRKP-attributable mortality estimate for the review period.

Abstract: Functional reserve is treated here as a latent physiological construct. Under controlled challenge its measurable phenotype is rate asymmetry—the ratio of restoration rate to degradation rate within a domain. The proposed estimator is ρ_d = r_g / r_l, formed only when both rates are fitted constants obtained from the same instrument in identical units. The primary quantity is the minimum of the point estimates across eligible domains; uncertainty is reported separately as a bootstrap or simultaneous interval for that minimum. Mandatory core domains (force recovery, lactate clearance, dual-task cost recovery) are required for cross-person comparison and are reported with the domain count.On the acute cycle the model predicts ρ < 1: parallel multi-factorial degradation outruns sequential, energy-constrained restoration. Net adaptation occurs later, outside the measured window. The governing domain—the eligible domain with the smallest ρ_d—identifies the recovery bottleneck under the specified challenge. Intensity is measured, volume is measured, frequency is inherited.The construct shares formal structure with a companion single-domain definition formed over weeks, but operates at a different timescale and reflects different physiology.

Abstract: Atopic dermatitis (AD) is a common inflammatory dermatosis often accompanied by itching and sleep disturbances. Various treatment options exist, including antihistamines (AHs) even though current clinical recommendations do not mention them. This prospective study measured and recorded salivary melatonin at two timepoints in three groups of participants: those not treated with AHs, those who discontinued H1-AHs, and those for whom H1-AHs were introduced. Also assessed were disease severity (Scoring Atopic Dermatitis/SCORAD and Eczema Area and Severity Index/EASI), pruritus severity (Peak Pruritus Numeric Rating Scale/NRS), and sleep quality (Pittsburgh Sleep Quality Index/PSQI). Initially, EASI scores significantly negatively, linearly correlated with salivary melatonin levels (p = 0.009). At the second measurement, SCORAD correlated with EASI, NRS, and PSQI (p < 0.001; p = 0.022, and p < 0.001; respectively). EASI correlated with NRS and PSQI (p = 0.003; p < 0.001). In those who discontinued AHs, AD severity indicators significantly increased (SCORAD, EASI, NRS) (p = 0.012; p = 0.012; p = 0.010), while in those for whom AHs were introduced, a significant decrease was observed in SCORAD, EASI, NSR (p = 0.012; p = 0.012; p = 0.010). Those who discontinued AHs showed increased AD severity indicators (SCORAD, EASI, NRS), whereas participants for whom AHs were introduced showed decreases in the same scores. The results support an association between melatonin levels and AD severity, as well as AHs' significant treatment efficacy in AD.

Abstract: Echocardiography is an important imaging modality in the assessment of cardiovascular diseases. Several echocardiographic signs have been described to aid in the diagnosis of specific clinical conditions and to help clinicians remember the key sonographic features. This review summarizes five classic signs in echocardiography, including the McConnell's Sign, the D-Sign, the 60:60 Sign, the SAM Sign, and the Swinging Heart Sign, as well as three novel signs, the Three Pipes Sign, the LTS Sign, and the LTI Sign. This review aims to provide an overview of the classic echocardiographic signs, focusing on their naming logics, definitions, and clinical implications to facilitate a better understanding of them, and to first propose three novel signs, the Three Pipes Sign, the LTS Sign, and the LTI Sign, which may aid in diagnosis and serve as teaching aids in echocardiography.

Abstract: This review proposes a new life-course nutritional hypothesis generated from Okinawa’s unique postwar history and changing longevity advantage relative to mainland Japan. After World War II, Okinawa underwent rapid socioeconomic and dietary change and experienced a nutrition transition earlier than mainland Japan. During subsequent decades, Okinawa developed a marked relative longevity advantage, which later diminished as longevity in mainland Japan continued to improve. We propose that this pattern may partly reflect differences in the timing and sequence of life-course nutritional environments. Older Okinawan cohorts experienced an initially relatively Lean nutritional environment followed by postwar nutritional enrichment, approximating a Lean-to-Rich trajectory. Comparable trajectories may have emerged later in mainland Japan, potentially contributing to national catch-up, while progressively younger Okinawan cohorts experienced the post-transition environment from earlier life stages, increasingly approximating a Rich-to-Rich trajectory. We therefore propose the Lean-to-Rich Healthy Aging Hypothesis, distinguishing three conceptual trajectories: persistent relative nutritional restraint (Lean-to-Lean), transition from an initially Lean to a subsequently Rich nutritional environment (Lean-to-Rich), and prolonged nutritional abundance (Rich-to-Rich). We hypothesize that Lean-to-Rich may be more favorable for healthy longevity than either persistent Lean-to-Lean or prolonged Rich-to-Rich. The hypothesis does not specify the optimal timing, magnitude, duration, or composition of the transition, and available ecological evidence cannot distinguish a sequence effect from cumulative Rich exposure. Rather than establishing causality, this framework generates testable predictions concerning how the sequence and duration of nutritional environments across the life course may influence healthy longevity.

Abstract: Background: The American Heart Association's cardiovascular–kidney–metabolic (CKM) syndrome framework has not previously been applied to cardiac surgery–associated acute kidney injury (CSA-AKI) risk after coronary artery bypass grafting (CABG). We used this framework to test, for the first time in this setting, whether cumulative CKM burden predicts severe CSA-AKI independently of established cardiorenal dysfunction, specifically baseline kidney function and left ventricular ejection fraction (LVEF). Methods: In this retrospective secondary analysis of the KARMA cohort, a prospectively maintained CABG registry at University Malaya Medical Centre, adults undergoing isolated CABG between January 2021 and December 2025 were classified into three CKM-CABG stages: Stage A (one or fewer metabolic risk factors, no CKD or heart failure [HF]), Stage B (two or more metabolic risk factors, no CKD or HF), and Stage C (CKD and/or HF, irrespective of metabolic burden). The primary outcome, severe CSA-AKI (KDIGO Stage 2–3), was modelled by multivariable logistic regression, with a secondary model adjusting for baseline estimated glomerular filtration rate (eGFR) and LVEF. Results: Among 517 patients, severe CSA-AKI occurred in 46 (8.9%). Stage C was associated with higher odds of severe CSA-AKI in the primary adjusted model (adjusted odds ratio [OR] 5.49, 95% confidence interval [CI] 1.72–17.50; p=0.004), but this attenuated substantially after adjustment for baseline eGFR and LVEF (adjusted OR 3.23, 95% CI 0.88–11.80; p=0.077), suggesting substantial overlap between Stage C classification and baseline cardiorenal function. Stage B did not differ significantly from Stage A (adjusted OR 2.42, 95% CI 0.73–8.01; p=0.148), though power was limited. Adding CKM-CABG stage to the clinical model modestly improved discrimination (apparent ΔAUC 0.032, 95% CI 0.005–0.065; p=0.034; bootstrap-corrected AUCs 0.776 vs 0.803) with satisfactory calibration. Conclusions: Severe CSA-AKI was more frequent among patients with established CKD and/or HF, and this association was substantially attenuated after adjustment for baseline eGFR and LVEF, indicating that its prognostic signal overlaps substantially with routinely measured cardiorenal function. Metabolic burden in the absence of established organ dysfunction was not independently associated with severe AKI. CKM-CABG staging provided only modest incremental discrimination beyond routinely measured eGFR and LVEF, and this finding requires external validation. Its potential utility may therefore be as a pragmatic framework for communicating cardiorenal–metabolic vulnerability. In elective CABG, baseline eGFR and LVEF appear to capture most of the CKM-related risk of severe AKI; metabolic burden alone should not prompt escalation of AKI risk categorization.

Abstract: Background: Medication errors (MEs) are a frequent cause of preventable harm but remain insufficiently quantified in emergency care. This study assessed the frequency, characteristics, and clinical impact of MEs among adverse drug reaction (ADR)–related emergency department (ED) admissions in Germany. Methods: We conducted a prospective multicenter study across six EDs over six years (n=7,967). ADRs and MEs were classified using standard causality (World Health Organization-Uppsala Monitoring Centre (WHO-UMC)) and preventability criteria (Schumock). Patient, drug, symptom, and outcome characteristics were compared between ADRs with and without MEs. Regression models assessed predictors of MEs and length of stay in hospital. Results: 20.1% of ADR-related cases, involved a preventable ME. Clinical presentation between groups; symptom burden, triage severity, and discharge outcomes, were similar. MEs clustered around chronic medications (pantoprazole, torasemide, metoprolol, ramipril, phenprocoumon, ibuprofen). Schumock analysis showed preventability as primarily linked to dosing errors (30%), non-adherence (28%), contraindications (26%), and monitoring (20%). Drug-specific symptom clusters mirrored expected pharmacology but were not error-specific. Multimorbidity was modestly protective (OR 0.84, 95%CI 0.71–1.00), while age, sex, polypharmacy, and number of diagnoses were not. Length of hospital stay was slightly longer in ME cases (+0.37 days; p = 0.037). Conclusion: MEs were identified in a substantial proportion of ADR-related ED admissions. Most MEs arose from routine prescribing and monitoring processes involving commonly used drugs suggesting that preventive efforts should focus on upstream safeguards, including medication reviews, electronic prescribing support, pharmacist involvement, and adherence monitoring, rather than detection at emergency presentation.

Abstract: Critical illness creates an extreme relational and regulatory environment in which patients may lose orientation, communication, and control while depending on unfamiliar people and systems. Drawing on clinical observations and an iterative ICU research program, this conceptual paper develops the Superorganismic Connection State (SCS) as a working hypothesis for how stress-related changes in cognitive and social processing may create both vulnerability and an adaptive opportunity for rapid connection to a new survival-supporting social system. Relational continuity and recurring sex-stratified findings prompted further examination of how relational qualities may shape suggestive effects. Integrating Bányai’s maternal–paternal interactional model with pacing–leading, the paper proposes a maternal–paternal regulatory spiral: maternal-mode pacing supports bodily-affective attunement, while paternal-mode leading provides orientation, meaning, roles, and direction. This process is conceptualized through in-event contextualization, scaffolded co-regulation, and supported agentic experience, including the possibility that safely delegating control can itself be agentic. These processes may also offer a possible preventive pathway against later posttraumatic stress. Critical illness is treated as a magnifying condition through which basic human regulatory needs become unusually visible, potentially clarifying relational processes relevant to hypnosis and psychotherapy more broadly.

Abstract: This contribution suggests a conceptual framework for a Basque country research institution. Over 20 years of data have been treated to assess CIC bioGUNE eligibility for Nature Index (NI). The tide of excitement swept up in the currents of this evolution, in the competitive races for fundings and staff. The characterization of liver injury research as a race, and the importance of the rankings and indicators can be calibrated by providing an insight into the practice of this middle-sized institution. Particularly acute is the issue of strategically designed by the Basque Government policies to create a bioregion in south-western Europe. CIC bioGUNE is enrolled in two ESI disciplines, ‘biochemistry & molecular biology’ and ‘cell biology’, and it belongs to top 1% worldwide ranking in this two disciplinary fields. As a research institution its academic influence has determined the creation of a network of interconnected publicly funded facilities which have a very similar internal culture. Comparisons between individual disciplines are reported here to provide a framework. Generally, it was found that the fact that provides internal cohesion to identify the driving force behind the context of this scientific race is the preeminent private and public funding relationships. Across the categories considered our results show the research impact of the work performed and the high profile of comparison for investment in science with leading institutions in the field.

Abstract: Background: The population of patients surviving previous multivalve surgery is expanding, and structural Heart Teams increasingly encounter complex, multivalvular disease requiring reintervention, for which redo surgery often carries prohibitive risk. Combined, single-session transcatheter treatment of two diseased valves is increasingly reported, but patient selection, procedural sequencing, prosthesis choice, and, in particular, pacing strategy and protection of pre-existing intracardiac hardware remain largely unstandardized. Case Presentation: We report a 73-year-old woman with a twenty-year history of rheumatic multivalvular heart disease, comprising mechanical mitral valve replacement, tricuspid annuloplasty and pacemaker implantation in 2006, redo bioprosthetic tricuspid valve replacement in 2019, and, in 2026, critical native aortic stenosis combined with severe bioprosthetic tricuspid stenosis. After multidisciplinary evaluation, the patient underwent single-stage transfemoral transcatheter aortic valve implantation (TAVI) followed immediately by tricuspid valve-in-valve implantation using a reversed balloon-expandable valve, with dedicated stiff guidewires positioned in each ventricle before device deployment and used as combined delivery-and-pacing platforms. Both procedures were successful, with no lead dysfunction, paravalvular leak, or other complications. Review: Using this case as a clinical anchor, we review contemporary evidence on simultaneous double-valve transcatheter intervention, addressing patient selection, the rationale for simultaneous versus staged treatment, valve sequencing, procedural planning, prosthesis choice, pacing strategies — including guidewire-based and leadless pacing — and management of permanent pacing leads, and propose a practical decision algorithm to guide Heart Team planning in similarly complex patients. Conclusions: Individualized, literature-informed Heart Team planning, including a dedicated biventricular guidewire strategy, can simplify combined transcatheter treatment of multivalvular disease in patients with pre-existing intracardiac hardware; this review provides a structured framework to support such planning as the evidence base for combined double-valve transcatheter intervention continues to grow.

Abstract: Background: Early systemic antibiotics are central to open-fracture care, and administration within 60 minutes is widely used as a quality benchmark. Whether 60 minutes represents a biological threshold for deep infection remains uncertain. Methods: We conducted a PRISMA 2020- and MOOSE-informed systematic review of acute open long-bone fractures in adults. The protocol and amendment history were retrospectively archived on OSF (doi:10.17605/OSF.IO/7J8QN). Injury-to-antibiotic, first-medical-contact, first-hospital-arrival, and receiving-trauma-centre intervals were analysed separately. Exact 60-, 120-, and 180-minute thresholds were prespecified. Deep infection or fracture-related infection assessed at 90 days or longer was prioritised, and adjusted estimates were preferred. Results: Twenty-four records were screened, 18 full reports were assessed, and 16 reports were retained in the evidence map; 13 provided explicitly adult-only data. No threshold-by-clock stratum contained two compatible adjusted estimates. At 60 minutes, adjusted estimates were centred near the null, including an adjusted odds ratio of 1.02 (95% CI 0.39–2.68). One 120-minute study reported an adjusted hazard ratio of 2.40. An exploratory 180-minute synthesis yielded an odds ratio of 1.15 (95% CI 0.58–2.31; I² = 0%) but combined adjusted and crude evidence. A delay beyond 12 hours was associated with fracture-related infection in one adjusted study (adjusted odds ratio 4.92, 95% CI 1.63–16.90). Certainty was very low for all threshold questions. Conclusions: Available evidence does not establish a universal 60-minute biological cutoff. This uncertainty should not be interpreted as evidence that delay is safe; antibiotics should be administered as soon as feasible.

Abstract: Background/Objectives: Shift work is an essential component of modern occupational systems but represents a major source of chronic circadian disruption associated with adverse gastrointestinal outcomes. The biological pathways underlying these associations remain incompletely integrated across circadian, neuroendocrine, immune, epithelial, and microbial domains. This narrative review aimed to synthesize current evidence linking shift work with gastrointestinal dysfunction and disease and to examine its translational implications for occupational medicine. Methods: A structured literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science, focusing primarily on studies published between January 2020 and July 2026. Recent original studies, systematic reviews, meta-analyses, and mechanistic and translational investigations were prioritized, while relevant landmark studies were retained. Evidence was synthesized within a seven-stage mechanistic framework spanning occupational exposure, circadian clock disruption, neuroendocrine misalignment, immune dysregulation, intestinal barrier dysfunction, gut microbial and metabolic alterations, and gastrointestinal disease. Results: Current evidence supports a multidirectional pathway in which chronic circadian misalignment disrupts melatonin and cortisol rhythms, autonomic regulation, and innate and adaptive immune homeostasis. Persistent inflammatory signaling and oxidative stress may subsequently impair epithelial tight junction integrity and increase intestinal permeability, thereby promoting microbial translocation and gut dysbiosis. Alterations in microbial metabolites, including short-chain fatty acids, secondary bile acids, and tryptophan derivatives, may further reinforce barrier and immune dysfunction. These interconnected mechanisms provide biological plausibility for the increased burden of disorders of gut–brain interaction, gastroesophageal reflux disease, peptic ulcer disease, and potentially inflammatory bowel disease and colorectal neoplasia among shift workers. Emerging circadian, inflammatory, intestinal barrier, microbiome, and multi-omics biomarkers may enable earlier identification of biologically susceptible individuals. Conclusions: Gastrointestinal consequences of shift work appear to arise from interacting circadian, neuroendocrine, immune, epithelial, and microbial disturbances rather than from isolated mechanisms. Integrating occupational exposure assessment with multidimensional biological profiling may support biomarker-guided surveillance, individualized prevention, and the development of Precision Occupational Medicine for shift workers. Prospective longitudinal and interventional studies are required to validate biomarkers, clarify causal pathways, and determine whether mechanism-based interventions can prevent gastrointestinal disease.

Abstract: Background and Objectives: Off-label medical narcotic use may be classified as misuse and abuse, but this classification need not coincide with judgments about how broadly medical narcotic use should be permitted. We examined the association and discordance between these judgments, as well as how each was related to three dose reduction-related responses. Materials and Methods: We analyzed cross-sectional web-based survey data from 300 physicians specializing in neurology, psychiatry, or anesthesiology and pain medicine in South Korea. Strict classification of all off-label use as misuse and abuse and a restrictive view of how broadly medical narcotic use should be permitted were entered simultaneously into logistic regression models for prior recommendation of dose reduction or discontinuation, belief that dose reduction would be helpful, and future intention to attempt dose reduction. Models were adjusted for age, sex, practice type, and specialty, with false discovery rate (FDR) adjustment across six primary associations. Results: Strict classification was selected by 42 physicians (14.0%), and a restrictive view by 107 (35.7%). The two judgments were positively associated (adjusted odds ratio [aOR], 4.99; 95% confidence interval [CI], 2.38–10.46), but 92 of 297 physicians (31.0%) gave discordant responses. After FDR adjustment, strict classification was associated with prior recommendation (aOR, 3.06; 95% CI, 1.37–6.83) and belief that dose reduction would be helpful (aOR, 4.51; 95% CI, 1.91–10.67). A restrictive view was associated with the same belief (aOR, 3.59; 95% CI, 2.12–6.10) and future intention (aOR, 2.89; 95% CI, 1.55–5.40). Conclusions: These findings indicate that physicians’ broad judgments about off-label medical narcotic use and the permitted scope of medical narcotic use are related but distinct and show different patterns of association with three dose reduction-related responses. They support the view that tapering decisions should be guided by individualized clinical assessment rather than by legal and regulatory frameworks alone.

Abstract: Clinical studies have shown that patients who had sepsis with COVID-19 infection had worse clinical outcomes, however, there is a paucity of data on the nationwide impact of COVID-19 infection in patients with sepsis. Hence, we conducted a retrospective cohort study using the National Inpatient Sample (NIS) database from 2020 through 2022 to determine the impact of COVID-19 infection on the outcomes of patients with sepsis. Adult sepsis hospitalizations were identified using ICD-10-CM codes and stratified by concurrent COVID-19 infection status. Survey weighted multivariate regression analysis was performed. Patients with sepsis with concurrent COVID-19 infection had worse outcomes with higher mortality rate (15.6% vs 5.4%; aOR 3.71; 95% CI 3.62-3.80), higher need for invasive ventilation (13.1% vs 6.5%) and NIV (non-invasive ventilation) (10.2% vs 4.9%), higher incidence of acute kidney injury (37.6% vs 36.7%), acute respiratory failure (57.5% vs 20.3%), acute liver failure (1.0% vs 1.2%), disseminated intravascular coagulation (DIC) (0.4% vs 0.3%), cardiac arrest (3.1% vs 1.5%), acute respiratory distress syndrome (ARDS) (7.9% vs 0.4%), higher need for renal replacement therapy (4.9% vs 4.5%), tracheostomy (1.6% vs 0.6%), extra corporeal membrane oxygenation (ECMO) (0.2% vs 0.04%), longer length of hospital stay (10.3 days vs 7.6 days), higher total charges ($127,632 vs $93,735 respectively). The results demonstrate that the COVID-19 infection was independently associated with worse clinical outcomes among hospitalized with sepsis. These results underscore the need for early recognition, aggressive treatment, and targeted therapy in this high-risk clinical group.

Abstract: Background: Relapsing polychondritis (RP) is a rare systemic inflammatory disorder characterised by recurrent inflammation and progressive structural damage of cartilaginous and proteoglycan-rich tissues, particularly auricular, nasal and laryngotracheobronchial cartilage. Ocular, audiovestibular, cardiovascular, cutaneous, neurological and musculoskeletal manifestations illustrate its systemic nature. Traditionally regarded as an autoimmune chondropathy, RP is increasingly recognised as a heterogeneous clinical syndrome. The discovery of somatic mutations in UBA1 causing VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome has substantially changed this conceptual framework.Objective: To provide an updated translational review of the pathophysiology, clinical phenotypes, diagnostic approach and treatment of RP, with particular emphasis on the distinction between classical immune-mediated RP and UBA1-mutated VEXAS-associated chondritis, and on the transition from empirical immunosuppression towards precision therapeutics.Methods: A narrative review of the literature was undertaken, focusing predominantly on publications between January 2000 and August 2026 while retaining seminal earlier studies defining RP and its diagnostic criteria. PubMed/MEDLINE and the reference lists of major reviews, multicentre cohorts and consensus documents were examined. Because randomised therapeutic evidence remains exceptionally limited in RP, treatment data were interpreted according to study design, number of treated patients, consistency of response and potential sources of bias.Results: Classical RP appears to involve loss of immune tolerance towards cartilage-associated extracellular matrix components, followed by interaction between adaptive and innate immune pathways. By contrast, VEXAS syndrome originates from acquired somatic UBA1 mutations in haematopoietic progenitor cells, resulting in altered ubiquitination, proteotoxic stress, clonal haematopoiesis and profound innate autoinflammation. Macrocytic anaemia, cytopenias, neutrophilic dermatosis, venous thromboembolism, persistent systemic inflammation and myelodysplastic features should prompt UBA1 testing in an appropriate RP phenotype. Airway involvement remains a major determinant of irreversible morbidity and mortality. Treatment of classical RP remains largely evidence-informed rather than evidence-based, whereas VEXAS requires a distinct strategy integrating anti-inflammatory and clone-directed therapy.Conclusions: RP should no longer be regarded exclusively as a uniform autoimmune chondropathy. The VEXAS paradigm demonstrates that a clinically similar phenotype may arise from fundamentally different pathogenic mechanisms. Contemporary management should combine clinical phenotyping, advanced imaging, haematological assessment and selective molecular testing, with therapy chosen according to organ threat, inflammatory activity, accumulated damage and underlying biology.

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.