Medicine and Pharmacology

Abstract: Vibrio parahaemolyticus is a halophilic, Gram-negative bacterium widely distributed in marine and estuarine environments and recognized as a leading cause of seafood-associated gastroenteritis worldwide. In recent decades, its global emergence has been driven by environmental changes, particularly ocean warming, as well as the intensification of aquaculture and the globalization of seafood trade. This narrative review provides a comprehensive overview of the epidemiology, virulence factors, antimicrobial resistance, and One Health dimensions of V. parahaemolyticus. The pathogen’s ability to cause disease in humans is largely determined by key virulence determinants, including thermostable direct hemolysin (TDH), TDH-related hemolysin (TRH), and secretion systems that facilitate host colonization and cytotoxicity. From a One Health perspective, V. parahaemolyticus represents a critical interface among environmental, animal, and human health, and also causes severe diseases in aquaculture, including acute hepatopancreatic necrosis disease (AHPND) and translucent postlarval disease (TPD) in shrimp, as well as vibriosis in bivalve mollusks such as oysters, where infection may result in tissue damage and substantial larval and juvenile mortality, with important economic consequences. The increasing emergence of antimicrobial-resistant strains further complicates clinical management and highlights the role of environmental reservoirs and aquaculture practices in the dissemination of resistance. Additionally, climate-driven changes in temperature, salinity, and marine ecosystems are expanding the geographic distribution and seasonal dynamics of this pathogen. Strengthening integrated surveillance systems, improving food safety practices, and promoting interdisciplinary research, including studies of the molecular mechanisms underlying interactions between the epigenome and V. parahaemolyticus, are essential to mitigate the growing risks associated with V. parahaemolyticus. A comprehensive One Health approach is critical to address its evolving impact on global public health and food security.

Abstract: Why cancer develops remains one of the central unsolved problems of biology. The Eco-Evolutionary Ground-State Theory of Cancer proposes that malignant transformation results from the conditional reactivation of an ancient ecological survival system whose evolutionary origins extend deep into early eukaryotic evolution. The theory reconstructs approximately one billion years of cancer genome evolution. It proposes that the common ancestor of Amoebozoa, Metazoa, and Fungi (AMF) evolved adaptive regulatory programs enabling survival under fluctuating ecological conditions, particularly changing oxygen availability. Rather than disappearing during the evolution of multicellularity, these programs became integrated into the metazoan genome as an evolutionarily conserved ancestral genomic compartment that normally remains epigenetically suppressed. Malignant transformation is initiated when an irreversibly damaged self-renewing host cell escapes apoptosis, enters reparative senescence, and undergoes unicellularization through reactivation of this ancestral genomic compartment. This transition establishes the eco-evolutionary stemgermline, which functions as the primary regulatory system governing carcinogenesis, tumor progression, cellular plasticity, genome reconstruction, metastatic dissemination, and therapeutic resistance. The genomic instability and phenotypic heterogeneity of malignant tumors are interpreted as downstream consequences of this hierarchical organization rather than its primary cause. The theory further proposes that recurrent unicellularization originally evolved as an adaptive mechanism during the transition to multicellularity but subsequently became transformed through host co-evolution into a parasite-like cellular system. By integrating genome evolution, stemgermline biology, oxygen ecology, and host–parasite co-evolution, the Eco-Evolutionary Ground-State Theory provides a unified evolutionary explanation for both the origin of cancer and the remarkable biological properties that characterize malignant disease.

Abstract: Background and Objectives: Biological correlates of admission consciousness remain incompletely characterized in older adults with acute ischemic stroke treated with intravenous thrombolysis. We evaluated associations between admission Glasgow Coma Scale (GCS) and pre-thrombolysis hematologic, inflammatory, iron-status, and micronutrient parameters, while considering the oral-systemic relevance of the resulting biological pattern. Materials and Methods: This retrospective single-center cohort included 95 unique patients aged ≥65 years treated between 2020 and 2024. Spearman correlations used the original GCS scores (11–14). Proportional-odds models used ordered categories (11–12, 13, and 14), adjusted for age and sex, with additional National Institutes of Health Stroke Scale (NIHSS) adjustment; false discovery rate (FDR) correction was applied. Results: Admission GCS correlated most strongly with RDW-CV (rho = −0.843; 95% bootstrap CI, −0.892 to −0.774) and MCV (rho = 0.779; 95% CI, 0.668 to 0.866). In age- and sex-adjusted models, odds ratios per 1-SD increase were 5.15 for hemoglobin, 3.17 for log-transformed ferritin, 4.49 for serum iron, 4.90 for log-transformed vitamin B12, 0.18 for C-reactive protein, and 0.018 for RDW-CV (all FDR-adjusted p < 0.001). Directions remained consistent after NIHSS adjustment. MCV showed a nonlinear association, with a model-derived turning point at 86.6 fL. Biomarkers were associated with absolute GCS at 24 hours but not with the direction of 24-hour change after FDR correction. Conclusions: The pre-thrombolysis biological profile was associated with the restricted range of admission GCS observed in this cohort. The convergence of hematologic, micronutrient, and inflammatory associations provides an exploratory oral-systemic research perspective but does not establish oral disease or an oral source for the systemic findings.

Abstract: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide. Finding patients with early COPD is already difficult, but even those have already an advanced disease in the biological point of view with irreversible lung damage. A lot of effort is done to find the parameters for detection of patients with early pathophysiological changes before they develop airflow limitation. The importance of this stage is recently recognized and has different labels as “pre-COPD” and “early COPD”. Exhaled breath temperature (EBT) is a non-invasive method to detect and monitor inflammation in the respiratory system. Most studies on EBT have been performed in asthma and showed the utility of this approach to assess changes in airway inflammation. In the COPD patients, the number of airways and their vasculature is reduced and EBT decreases proportionally to the level of destruction, but is still increased during the COPD exacerbation. In recent studies, change in EBT after smoking a cigarette in patients without a diagnosis of COPD was significantly predictive for disease progression after 2 years. Early interventions based on these results should be tested for efficacy in prevention of the development of overt COPD.

Abstract: Background/Objectives: The development of GLP-1 receptor agonists (GLP-1RAs) and dual GLP-1/GIP receptor agonists has expanded the possibilities for multimodal obesity treatment. However, evidence regarding the integration, combination, or sequencing of these therapies with bariatric/metabolic endoscopy and bariatric/metabolic surgery has not been comprehensively synthesized. Methods: A scoping review was conducted following the methodological framework of Arksey and Levac, the recommendations of the Joanna Briggs Institute, and the PRISMA-ScR guidelines. A systematic search was performed in PubMed, Scopus, and Embase from database inception through May 16, 2026. Studies involving adults that evaluated GLP-1/GIP agonists in relation to endoscopic and/or surgical bariatric/metabolic procedures were included. Data extraction was independently performed by two reviewers, and the evidence was synthesized using descriptive and narrative analyses. Results: A total of 61 studies were included, of which 14 directly evaluated multimodal integration strategies involving pharmacotherapy, bariatric/metabolic endoscopy, and/or bariatric/metabolic surgery, encompassing approximately 6,401 participants. Retrospective cohort studies predominated (71.4%). Semaglutide and liraglutide were the most frequently investigated medications. The intragastric balloon was the most evaluated endoscopic intervention, followed by transoral outlet reduction (TORe), endoscopic sleeve gastroplasty (ESG), revisional ESG (R-ESG), and revisional procedures. Pharmacologic-endoscopic combinations were the most common strategy (42.9%), and most studies were conducted in the postoperative setting (71.4%). Overall, combined and sequential strategies achieved greater weight loss than isolated interventions, whereas revisional surgery demonstrated superior outcomes compared with pharmacotherapy in comparative studies. Conclusions: Evidence regarding multimodal strategies for obesity treatment remains limited and is predominantly observational. The integration of pharmacotherapy with endoscopic and surgical interventions shows promising results; however, high-quality prospective studies and randomized clinical trials are needed to define the optimal treatment sequence and identify the patients most likely to benefit from these multimodal approaches.

Abstract: Most patient safety events in radiation therapy originate in treatment planning, and quality assurance (QA) checklists are widely deployed to mitigate them; however, these tools are rarely subjected to formal human factors evaluation before clinical release. Building on our prior work demonstrating suboptimal usability of an institutional dosimetry QA checklist (DQC) and its participatory, theory-driven redesign, this study evaluated an enhanced DQC using Borycki and Kushniruk’s multi-phase, multi-method usability evaluation framework, which integrates cognitive and socio-technical perspectives to create a “safety net” against usability problems and technology-induced errors. Three sequential phases were conducted at an academic medical center: (1) rapid think-aloud usability testing with two cohorts of dosimetrists and physicists (n = 10) separated by an improvement cycle; (2) remote simulation-based testing with dosimetrists (n = 7) using ten high-fidelity synthetic treatment plans with embedded errors; and (3) six weeks of near-live testing with dosimetrists, physicists, and trainees (n = 15–21) with weekly iterative refinement. Reported usability, usefulness, and safety issues decreased by 49% between think-aloud cohorts, and perceived usability met recommended standards (System Usability Scale > 80). Simulation-based testing was feasible, and usability and performance differed significantly between easy and hard plans. Near-live testing surfaced predominantly deeper usefulness and safety issues (77% of 142 codes) and achieved adoption rates of 49–67%. The framework provided complementary, progressively deeper insights and readied the enhanced DQC for clinical implementation.

Abstract: Background: Conventional interrupted microvascular anastomosis can be performed by skilled surgeons, but it requires extensive experience and is time-consuming. In this study, we developed an intraluminal microtube anastomosis system (IMAS) incorporating circumferential intimal anchoring ridges that mechanically retain each arterial end during circumferential ligation. This study compared IMAS with conventional interrupted microsurgical anastomosis in a rat infrarenal abdominal aortic model. Methods: Forty male Sprague-Dawley rats were randomly allocated to IMAS (n = 20) or conventional interrupted microsurgical anastomosis (n = 20). The primary outcome variable was anastomosis time. Secondary outcome variables were patency at 1 week and 1 month, assessed using color Doppler ultrasonography and visual inspection at necropsy. Results: Mean anastomosis time was 5 min 30 s ± 60 s in the IMAS group and 20 min 32 s ± 75 s in the conventional group (P < 0.001), representing a reduction of approximately 73% in the IMAS group. One-week patency was 95% in both groups (19/20; P = 1.000). At 1 month, patency was 85% in the IMAS group (17/20) and 90% in the conventional group (18/20; P = 0.633). No gross device migration, aneurysmal dilatation, or anastomotic leakage was observed in patent IMAS-treated vessels. Conclusions: In this experimental model, IMAS significantly reduced anastomosis time while maintaining a short patency rate similar to that of conventional interrupted micro suturing. These results support the need for further evaluation of mechanical intimal fixation strategies, including future histological assessments and long-term follow-up.

Abstract: Background: Hyposmia is a common nonmotor feature of Parkinson’s disease (PD) and is typically absent or mild in essential tremor (ET). Olfactory tests are low-cost, noninvasive tools that may improve diagnostic accuracy in tremor-dominant PD (TD-PD). Methods: PubMed/MEDLINE, Embase, and Cochrane Library were systematically searched through January 2026. Studies evaluating olfactory tests in TD-PD and ET were included. Diagnostic accuracy measures were pooled using MetaDTA, and hierarchical summary receiver operating characteristic (HSROC) curves were generated. PROSPERO: CRD420261437298. Results: Seven studies met inclusion criteria, including 454 TD-PD and 239 ET patients. Two studies used the University of Pennsylvania Smell Identification Test and five used Sniffin’ Sticks. Pooled sensitivity was 78% (95% CI, 67%-86%) and specificity was 91% (95% CI, 83%-95%) for differentiating TD-PD from ET. HSROC analysis demonstrated excellent diagnostic performance (AUC=0.90). The pooled positive likelihood ratio was 8.67 and negative likelihood ratio was 0.24. Most studies reported specificity ≥90%. Sensitivity variability likely reflected differences in disease stage and diagnostic thresholds. Risk of bias was generally high because of nonconsecutive patient selection and limited blinding. Conclusion: Olfactory testing shows high specificity and moderate sensitivity for distinguishing TD-PD from ET and may serve as a practical adjunct when motor findings are equivocal.

Abstract: Childhood overweight and obesity have been associated with earlier pubertal onset most commonly in girls than boys. An ever-increasing number of factors contributing to this association have been identified, including leptin, insulin, sirtuins, epigenetic factors and gut-derived molecules, such as short-chain fatty acids. This review aims to identify all the mechanisms involved in early puberty amongst children with increased weight and possibly help early detection and reduce any long-term related risks associated with precocious puberty in overweight children. Clarifying these links is clinically important for monitoring pubertal progression and cardiometabolic risk in children with obesity, and for informing prevention and early intervention aimed at reducing long term adverse outcome.

Abstract: Background/Objectives: Expanded endoscopic endonasal approaches (EEA) provide direct ventral access to adult intradural skull base tumors; however, postoperative complications are variably defined and reported in the literature. This review aimed to synthesize the overall spectrum of adult intradural EEA complications and distinguish pathology-specific evidence from large mixed EEA complication cohorts. Methods: A PRISMA 2020 systematic review and meta-analysis searched PubMed/MEDLINE, Embase, and Web of Science from database inception through July 2026. Eligible studies included adults or adult-separable subgroups undergoing expanded EEA for intradural skull base tumors. The primary outcomes were CSF leak, meningitis or intracranial infection, new neurological deficit or vascular injury/stroke, hydrocephalus, mortality, and postoperative seizures. Pathology-specific adult intradural series with exact counts were quantitatively synthesized when appropriate, and large mixed EEA cohorts were summarized separately when the eligible subgroup was not separable. Results: The full-text screening set included 48 reports. Five exact-count reports, including one mixed-age contextual report, contributed to the CSF leak meta-analysis and yielded a random-effects incidence of 21.1% (95% CI, 12.2%-33.8%; I² = 69.4%). Excluding the mixed-age reports yielded 23.8% (95% CI, 14.5%-36.6%). Meningitis was reported in 6/166 patients (3.6%; 95% exact CI, 1.3%-7.7%), and new neurological deficit/vascular injury/stroke in 4/166 (2.4%; 95% exact CI, 0.7%-6.1%); these rare outcomes were summarized descriptively without continuity correction. Postoperative seizures were reported in 4/652 patients (0.6%) in two studies. Large mixed EEA cohorts have reported CSF leak rates of 1.6%-15.9% but these were not pooled because adult intradural tumor subsets were not separable. Conclusion: CSF leak was the most consistently reported complication after expanded EEA for adult intradural skull base tumors; however, its incidence varied substantially across pathologies and centers. Meningitis, neurological/vascular events, and seizures were uncommon in the extractable data and were better interpreted descriptively than as precise pooled rates. Large mixed EEA cohorts provide important safety context but cannot substitute standardized adult intradural, pathology-specific reporting.

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. The Lambre is a plug occluder for left atrial appendage closure (LAAC) in patients with atrial fibrillation (AF), but direct comparisons of the most used Watchman FLX and Lambre devices are lacking. Objectives. To compare the safety and efficacy of Lambre and the well-established Watchman FLX occluder for left atrial appendage (LAA) closure Methods. Between January 2023 and April 2025, a cohort of 253 consecutive patients who underwent LAAC with Lambre or Watchman FLX at Umberto I Hospital of Siracusa were included. The primary safety endpoint included major peri-procedural complications while the primary efficacy endpoint included all cause stroke, cardiovascular/unexplained death, systemic embolism and bleedings at a mean follow up of 12 months. 1:1 propensity score matching (PSM) was performed. Results. After PSM, 152 patients were included: Lambre group (n=76) and Watchman FLX group (n=76). The mean CHA2DS2-VASc score was 4.5 ± 1.3 (Lambre) vs. 4.5 ± 1.4( Watchman FLX), p=0.97; and the HAS-BLED score was 2.7 ± 0.9 vs. 2.7± 0.8, p=0.97. At a mean follow-up of 12 months, the primary efficacy endpoint (14.9% vs. 12.5%; HR, 1.57; 95% CI, 0.52–4.72; P = 0.77) and the primary safety endpoint (3.9% vs. 2.6%; HR, 1.51; CI 0.25-9.03; P=1) were similar between groups. Conclusions. LAAC with the Lambre device has demonstrated similar efficacy and safety to the Watchman devices. In a high-volume center, experienced operators, using both singleand double-element devices, can adopt a customized strategy based on each patient’s anatomy and achieve 100% successful left atrial closure.

Abstract: The rapid proliferation of digital pathology has created an urgent need for integrated, scalable, and secure platforms capable of supporting the full lifecycle of whole-slide image (WSI) analysis — from quality assessment through collaborative annotation to AI model deployment. Existing tools address these requirements in isolation, creating fragmented workflows that impede clinical adoption and AI development. Here we present A!Path, a modular ecosystem comprising three synergistic components: (1) A!magQC, a fully automated AI-assisted quality control pipeline assessing five image quality metrics across H&E and multiplex fluorescence modalities; (2) A!HistoClouds, a unified annotation and inference platform that combines cloud-based scalability with local server flexibility, implementing a three-phase closed-loop pathologist-AI interaction workflows, Segment Anything Model (SAM)-based annotation, multi-user collaborative workflows, integrated AI inference (A!Prostate), and project analytics on a deployable backend (A!Server); and (3) A!Secure, a cryptographic security layer for WSI protection, providing application-layer encryption, policy-based access control, streaming tile decryption, and format-aware protection of compressed, pyramid-structured pathology images. A!HistoClouds is deployable on both cloud infrastructure and institutional local servers, enabling organizations to select the deployment model best suited to their data governance requirements without sacrificing platform capability. Validation across a cohort of 302 prostate tissue specimens demonstrated that A!magQC achieved greater than 95% agreement with expert visual quality assessment, while A!Secure-protected WSI regions yielded a low PSNR of 7.42 dB and SSIM of 0.0289 relative to the original images, indicating strong visual obfuscation of diagnostically relevant content. A!Path provides a coherent, deployment-flexible foundation for clinical diagnostic AI development and multi-centre digital pathology collaboration. Conceived as a coordinated data-infrastructure ecosystem rather than a set of isolated tools, A!Path reframes pathology data as an actively governed asset — standardised, clinically annotated, and securely shareable — providing the foundation for trusted multi-institution collaboration under initiatives such as the AI in Digital Pathology (AiDP) programme.

Abstract:

Background: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, with lymph node metastasis (LNM) being a key predictor of recurrence and poor prognosis. Preoperative detection of LNM remains challenging due to the limitations of imaging modalities, leading to inadequate surgical resection in 20-30% of patients. While immune checkpoint molecules have been implicated in PTC progression, the heterogeneity of CD8+ T cell exhaustion subsets and their specific association with LNM remain poorly defined. Herein, we aimed to characterize the distinct immune landscape of PTC prone to LNM, with a focus on terminal immune exhaustion, to improve risk stratification and therapeutic strategies. Methods: Fresh PTC tissues from 40 patients (22 LNM-positive, 18 LNM-negative) were analyzed by flow cytometry (FCM) to quantify immune cell subsets, inflammatory cytokines, and chemokines. Immunohistochemistry (IHC) validated CD45+ immune cell infiltration. Transcriptomic and clinical data from 448 PTC patients in The Cancer Genome Atlas (TCGA-PTC) cohort were used for bioinformatic validation, including Gene Set Variation Analysis (GSVA) of terminal exhaustion gene signatures. Results: LNM-positive PTC exhibited a unique inflammatory milieu with significantly elevated IL-6, IL-1ra, CCL5, and IL-9 levels (all p<0.05) in tumor interstitial fluid. FCM analysis revealed that LNM-positive PTC had increased infiltration of total CD45+ immune cells, CD3+ T cells, and CD3+CD8+ T cells (all p<0.05). Critically, terminally exhausted PD-1^hiTIM-3⁺ CD8+ T cells were significantly enriched in LNM-positive PTC (p=0.022) and positively correlated with extrathyroidal extension (p=0.044). Additionally, LNM risk was associated with increased CD4+ regulatory T (Treg) cell frequency (p=0.023) and elevated CTLA-4 expression on CD4+ T cells (p=0.047). In TCGA-PTC validation, the terminal exhaustion gene signature was predominantly enriched in LNM-positive (p<0.0001) and advanced-stage PTC (p<0.001), and strongly correlated with BRAF V600E mutation (p<0.0001)—the most common oncogenic driver in aggressive PTC. Conclusion: Our findings identify a terminal immune exhaustion phenotype (characterized by PD-1^hiTIM-3⁺ CD8+ T cells and Treg enrichment) as a key feature of LNM-prone PTC. This phenotype is conserved across clinical samples and TCGA datasets, linking BRAF V600E mutation to immune suppression and metastatic potential. These insights provide a novel immune-based biomarker for LNM risk stratification and support the potential of combining anti-PD-1/TIM-3 therapy with BRAF inhibitors for high-risk PTC.

Abstract: Asthma exacerbation, frequently triggered by viral infections, is a leading cause of hospitalization, respiratory failure, and death. COVID-19 and asthma share a bidirectional relationship, with each potentially worsening the other. We compared outcomes in hospitalized asthma exacerbation patients with and without COVID-19 using the National Inpatient Sample (2020–2022), adjusting for confounders via multivariable logistic regression. Among 603,219 hospitalizations for asthma exacerbation, 69,600 (11.5%) had concomitant COVID-19. The COVID-19 group had significantly higher in-hospital mortality (6.7% vs. 1.4%; aOR 6.16; 95% CI 5.61-6.76) and greater need for invasive mechanical ventilation (10.1% vs. 4.9%; aOR 2.30; 95% CI 2.15-2.45), despite lower non-invasive ventilation use. Mean length of stay (7.7 vs. 4.6 days) and total hospital charges ($97,133 vs. $58,547) were also higher. These patients were more critically ill, with higher rates of respiratory failure, ARDS, acute kidney injury, and pulmonary embolism, and greater use of ECMO, renal replacement therapy, tracheostomy, and vasopressors. COVID-19 was independently associated with worse clinical outcomes among hospitalized asthma exacerbation patients. Early recognition of COVID-19 in asthma exacerbation is warranted to guide risk stratification and timely management.

Abstract: Background:Telomeres are repetitive DNA sequences at chromosome ends that maintain genomic stability and shorten with age. Mutations in genes such as DKC1, TERC, TERT, NOP10, TINF2 and NHP2 cause Telomere Spectrum Disorders (TSD), leading to shortened telomeres. Acquired TSDs arise from environmental or occupational exposures and commonly affect veterans, truck drivers, and industrial workers (10). These exposures generate reactive oxygen species associated with cancer, liver disease, pulmonary disease, and bone marrow complications. Idiopathic Pulmonary Fibrosis (IPF) is most common pulmonary manifestation, followed by hepatic fibrosis / cirrhosis, hematologic disorders (e.g., aplastic anemia, MDS), and rarely gastrointestinal findings. This case describes a Gulf War veteran with suspected acquired short telomeres and multisystem involvement (idiopathic cirrhosis, pulmonary fibrosis, cytopenias) and uniquely found to have gastrointestinal (Gastric Antral Vascular Ectasia, GAVE)), a potential unsuspected manifestation of TSD. Methods/ Case: A 76-year-old male with atrial fibrillation (post-Watchman), cryptogenic cirrhosis, COPD, IPF, diabetes, and anemia presented with severe shortness of breath and hypoxia. Admitted for Sepsis and Acute Hypoxic Respiratory Failure. Treated with AVAPS, IV Zosyn, IV Lasix, steroids, bronchodilators, and diuretics. His condition improved, and he was discharged on baseline 3L O2. His Gl history included GAVE, an unsuspected bleeding complication causing chronic iron-deficiency anemia. Hematologic findings included chronic anemia, thrombocytopenia, and a hypocellular bone marrow with 12% atypical NK cells. Discussion/ Results: The patient's Gulf War exposure to oil fire pollutants (benzene, toluene, PAHs, lead, cadmium, and particulate matter) likely contributed to telomere shortening and TSD-related multisystem disease (10). Given his shortened telomeres, testing for TERC and TERT mutations is warranted. GAVE ("watermelon stomach") is a rare cause of GI bleeding characterized by dilated gastric vessels and chronic anemia and has been linked to TSD but no current reports have documented this association. Its occurrence in this patient suggests an unrecognized gastrointestinal manifestation of TSD as the patient does not have known history of portal hypertension. Conclusion: This represents an potentially underreported manifestation of acquired TSD presenting with combined hepatic, pulmonary, hematologic, and gastrointestinal (GAVE) involvement.

Abstract: Background: Nutritional deterioration is a common consequence of gastrectomy for gastric cancer and may persist despite standardized perioperative care. However, prospective longitudinal evidence describing the early course of postoperative nutritional recovery remains limited. This study aimed to characterize nutritional recovery trajectories follo-wing curative gastrectomy and to evaluate the influence of the extent of gastric resection on postoperative recovery. Methods: We conducted a prospective longitudinal cohort stu-dy including 217 consecutive patients who underwent curative-intent subtotal or total gastrectomy for gastric adenocarcinoma between January 2022 and December 2025. Nutri-tional status was assessed preoperatively (T0), at hospital discharge (T1), and three mon-ths after surgery (T3) using serum albumin, total cholesterol, absolute lymphocyte count, and the Controlling Nutritional Status (CONUT) score. Longitudinal changes were evalu-ated using linear mixed-effects models with patient-specific random intercepts. Results: All nutritional parameters deteriorated significantly after surgery, reaching their lowest values at hospital discharge (all p < 0.001), followed by partial recovery at three months. Nevertheless, none returned to preoperative baseline values. Recovery between discharge and three months represented 65.6% of the initial decline for serum albumin, 50.5% for absolute lymphocyte count, 51.7% for total cholesterol, and 70.1% for the CONUT score. Longitudinal mixed-effects analyses demonstrated significantly less favorable recovery trajectories after total compared with subtotal gastrectomy for serum albumin (p = 0.025), lymphocyte count (p < 0.001), and CONUT score (p < 0.001), whereas cholesterol recovery did not differ significantly between procedures (p = 0.267). Conclusions: Nutritional reco-very following gastrectomy is a dynamic and prolonged process characterized by marked early deterioration and incomplete restoration during the first three postoperative months. Patients undergoing total gastrectomy experience slower recovery trajectories, supporting the implementation of risk-adapted postoperative nutritional surveillance and individua-lized nutritional interventions extending beyond hospital discharge

Abstract: Enterocytozoon bieneusi is a major zoonotic pathogen causing human microsporidiosis, with small ruminants serving as crucial reservoir hosts. Hu sheep and local goats are pillar livestock breeds in Zhejiang Province, yet no parallel comparative epidemiological data on E. bieneusi exist for sympatric small ruminants in southern Zhejiang, and the infection status in Hu sheep remains entirely uncharacterized. Here, a total of 297 fecal samples (159 Hu sheep, 138 goats) were collected from four administrative regions in southern Zhejiang from 2021 to 2023 and screened via nested PCR targeting the ribosomal internal transcribed spacer (ITS) region of the E. bieneusi genome. Overall, the total E. bieneusi prevalence reached 18.18%, and Hu sheep exhibited a significantly higher infection rate (24.53%, 39/159) than sympatric goats (10.87%, 15/138; χ² = 9.27, P = 0.002). Obvious geographical and age-dependent disparities were observed in Hu sheep, with pre-weaning lambs (< 3 months) showing the highest prevalence (60.42%), while adult sheep (> 1 year) had the lowest rate (4.48%). No significant age or regional differences were detected in goats. Five genotypes were identified from Hu sheep: CM7 (n = 25), BEB6 (n = 10), CHG1 (n = 2), Type IV (n = 1), and CHG5 (n = 1). Five genotypes were detected from goats: CHG1 (n = 9), BEB6 (n = 3), Type IV (n = 1), CHG3 (n = 1), and CYG-2 (n = 1). BEB6, Type IV, and CHG1 were shared by both hosts. All genotypes belonged to zoonotic Group 1 and Group 2. This study represents the first systematic parallel survey of E. bieneusi in cohabiting Hu sheep and goats in eastern China, identifies distinct host-specific infection patterns linked to divergent rearing systems, provides molecular evidence for potential cross-species transmission, and underscores the need for breed-tailored biosecurity strategies under a One Health framework.

Abstract: Manual sinus magnetic resonance imaging (MRI) annotations are valuable but difficult to scale. We evaluated PARASIDE, an nnU-Net-based framework for automated sinus compartment segmentation on T1-weighted MRI, against independent manual and radiological assessments from the Study of Health in Pomerania. We linked 12,867 sinus sides from 3,217 participants. Analyses defined before outcome modelling evaluated soft-tissue fraction for healthy versus abnormal sides, inferior soft-tissue centroid position for basal versus apical maxillary opacification, and total frontal volume for aplasia/hypoplasia. Soft-tissue fraction discriminated abnormal sides in frontal (area under the receiver operating characteristic curve [AUC] 0.850, 95% confidence interval [CI] 0.834–0.866) and maxillary sinuses (AUC 0.828, 95% CI 0.818–0.839). The topographic marker discriminated basal from apical opacification (AUC 0.746 left; 0.782 right). Total frontal volume discriminated historical aplasia/hypoplasia ratings (AUC 0.988); a previously established near-absence threshold was highly specific but insensitive. Historical maxillary volumetric masks showed strong overlap and volume association for total and aerated compartments, whereas frontal comparisons reflected a predefined caudal boundary. The historical polyposis rating category remained weakly separable, and surgery-related features corresponded more closely to visible postoperative morphology than to self-reported surgery. PARASIDE reproduced anatomically measurable MRI phenotypes, whereas morphology-specific constructs required dedicated reference standards.

Abstract: The intestinal microbiome has emerged as a clinically significant modulator of outcomes across multiple domains of cancer care. In hematopoietic stem cell transplantation (HSCT), loss of microbial diversity and depletion of short-chain fatty acid–producing commensals are independently associated with graft-versus-host disease (GvHD), bloodstream infections, transplant-related mortality, and overall survival. Mechanistic studies have identified interconnected pathways — including butyrate-mediated epithelial protection, tryptophan-derived aryl hydrocarbon receptor signaling, bile acid metabolism, and Paneth cell–intestinal stem cell interactions — through which microbial communities regulate intestinal barrier integrity and immune homeostasis. These insights have provided the biological rationale for therapeutic strategies aimed at restoring microbial ecology. Fecal microbiota transplantation (FMT) has demonstrated promising clinical activity in steroid-refractory acute GvHD, with pooled remission rates exceeding 60% in meta-analyses, and proprietary live biotherapeutic products (LBPs) such as MaaT013 have advanced to phase III testing. In parallel, the gut microbiome has been established as a determinant of immune checkpoint inhibitor (ICI) efficacy, with FMT shown to overcome anti-PD-1 resistance in refractory melanoma and enhance response rates in treatment-naive patients with melanoma and non-small cell lung cancer. Defined single-strain approaches, notably Clostridium butyricum CBM588, have demonstrated significant improvements in progression-free survival when combined with ICI in metastatic renal cell carcinoma. Emerging evidence further links antibiotic-induced dysbiosis to impaired chimeric antigen receptor T-cell (CAR-T) therapy outcomes, while short-chain fatty acids have been identified as direct enhancers of CAR-T cell effector function. This review synthesizes the current evidence for microbiome-based therapeutics across HSCT, GvHD, ICI therapy, CAR-T cell therapy, and infection prevention, and addresses cross-cutting translational challenges including antibiotic stewardship, donor selection, safety in immunocompromised populations, and pharmacomicrobiomics. While randomized controlled trial data remain limited and many approaches are investigational, the convergence of mechanistic, observational, and early interventional evidence positions microbiome restoration as a promising frontier in precision oncology.