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PubMed2026

Quantitative N-glycoproteomic analysis reveals glycosylation signatures of plasma immunoglobulin G in sepsis.

INTRODUCTION: Sepsis is a life-threatening condition resulting from organ dysfunction due to a dysregulated immune response to infection. Immunoglobulin G (IgG) plays a role in modulating immune responses. However, the precise IgG subclass-specific N-glycosylation profiles in patients with sepsis remain poorly characterized. METHODS: This study aimed to define the site-specific N-glycosylation signatures of plasma IgG subclasses in sepsis patients with different prognoses using quantitative glycoproteomics. By employing our established GlycoQuant strategy, we quantified the intact N-glycopeptides (IGPs) of IgG subclasses in 40 healthy controls and 40 sepsis patients with a clear prognosis. RESULTS: We identified 12 IGPs with altered abundances between patients with sepsis and healthy controls. After Benjamini-Hochberg (BH) correction of the 31 outcome-stratified IGP comparisons, IGP24 and IGP25 remained significant and met the prespecified fold-change criterion. Global BH correction across 124 IGP-clinical parameter correlations retained positive associations of IGP19, IGP22, and IGP23 with procalcitonin (PCT). In exploratory outcome-stratified ROC analyses, candidates were selected using the original unadjusted P-value and fold-change screen; five IGPs were evaluated, with IGP25 and IGP24 yielding the highest individual AUCs. Collectively, our findings underscore the potential of IgG subclass-specific glycosylation profiling as a novel translational approach for clinical applications in sepsis management. SIGNIFICANCE: Sepsis remains a leading cause of global mortality, with patient outcomes heavily dependent on timely diagnosis and accurate prognosis. The dysregulated host immune response, particularly involving immunoglobulins, is central to its pathophysiology. This study provides a significant advance in the field of clinical glycoproteomics by applying a quantitative, site-specific strategy to delineate the plasma IgG subclass N-glycosylation landscape in sepsis. We report, for the first time, a panel of subclass-specific intact IgG N-glycopeptides (IGPs) that are significantly altered in sepsis patients compared to healthy controls. The identified IGPs not only demonstrate diagnostic and prognostic potential but also show a significant correlation with procalcitonin, a key clinical severity index. These findings bridge a critical knowledge gap by moving beyond bulk IgG glycosylation analysis to subclass-resolved profiling, offering novel molecular insights into sepsis immunopathology. The identified glycosylation signatures hold substantial translational promise as a foundation for developing innovative, glycan-based biomarker panels to improve the precision management of this heterogeneous and life-threatening syndrome.

Humans↗

PubMed2026

Hydrogen-rich water combined with traditional Chinese medicine compound in the treatment of kidney stones: a randomized controlled prospective clinical trial.

JOURNAL/mgres/04.03/01612956-202701000-00009/figure1/v/2026-09-13T085902Z/r/image-tiff The formation and development of kidney stones are related to abnormal urine metabolism, oxidative stress and inflammation. Hydrogen-rich water has clear efficacy in antioxidant and improving inflammatory status, while Ye-Shi-Shi-Lin-Formula is a clinically effective traditional Chinese medicine compound preparation for treating kidney stones. This randomized controlled prospective clinical trial from July 2025 to March 2026 at the Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine examined the effect of hydrogen-rich water and Ye-Shi-Shi-Lin-Formula on kidney stones. The included 100 patients with kidney stones were randomly divided into blank, hydrogen-rich water, hydrogen-rich water and Chinese medicine, and Chinese medicines groups. The patients received drinking hydrogen-rich water and/or Ye-Shi-Shi-Lin-Formula daily for 12 weeks. All subjects received basic treatment following the guidelines. Imaging examination, urine metabolism testing, renal function, inflammation and oxidative stress index, blood routine and liver function are used to detect the efficacy and safety of hydrogen-rich water and Ye-Shi-Shi-Lin-Formula. Results showed that the total effective rate of kidney stone treatment in blank group, Chinese medicines group, hydrogen-rich water and Chinese medicine group and hydrogen-rich water group was 28%, 76%, 80% and 32%. The Ye-Shi-Shi-Lin-Formula can partially alleviate the oxidative stress, uric acid metabolism and urinary magnesium levels of patients with kidney stone and improve the function of renal tubules. The hydrogen-rich water therapy showed only efficacy in improving glutathione reductase but the combination of hydrogen-rich water and Ye-Shi-Shi-Lin-Formula has shown superior efficacy in improving oxidative stress and related metabolic factors of blood uric acid and urine stones, as well as in renal tubular function. The results indicate that the addition of hydrogen-rich water can improve urinary metabolism and oxidative stress status in the treatment of kidney stones with Ye-Shi-Shi-Lin-Formula. The study was registered at the International Traditional Medicine Clinical Trial Registry (Registration No. ITMCTR2025001446).

Humans↗

PubMed2026

Clinical outcomes of Epstein-Barr virus infection/reactivation following CAR-T cell therapy: A systematic review.

BACKGROUND: Epstein-Barr virus (EBV) infection or reactivation is an emerging but underrecognized complication following chimeric antigen receptor T-cell (CAR-T) therapy and is likely associated with treatment-induced immune dysregulation. Data regarding its clinical impact remain limited. OBJECTIVE: To evaluate the reported occurrence, clinical manifestations, and outcomes of EBV infection or reactivation in adults undergoing CAR-T therapy. METHODS: A systematic review was conducted in accordance with the PRISMA 2020 guidelines. PubMed, Embase, and Cochrane CENTRAL were searched from inception to March 2025 for studies reporting EBV infection or reactivation after CAR-T therapy in adults. Due to limited and heterogeneous data, results were synthesized descriptively. RESULTS: Five studies comprising 80 patients were included (median age, 55 years; 52.6% male among patients with reported sex data [10/19]). Across the included studies, 11 EBV infection/reactivation events were identified among 80 described CAR-T recipients, representing 13.8% of the reported sample rather than a true incidence estimate. Among events with usable individualized timing data, the median interval from CAR-T infusion to EBV detection/reactivation was 9.8 months (approximate range, 1-44 months). Because EBV surveillance strategies and definitions were inconsistently reported across studies, this proportion should not be interpreted as a true incidence estimate. Four patients (36.4%) developed EBV-associated disease, including three cases of EBV-related lymphoproliferative disorder and one case of EBV-associated diffuse large B-cell lymphoma. Among seven patients with reported post-CAR-T treatment response, four achieved Complete Remission/ Continuous Complete Remission; treatment response should be interpreted separately from final survival status. Confirmed EBV-related mortality occurred in 2/11 patients with reported EBV infection/reactivation and in 2/4 patients with EBV-associated disease; all-cause mortality could not be reliably estimated because patient-level vital status could not be fully attributed to the EBV-reactivated subgroup. Reported toxicities predominantly consisted of low-grade cytokine-release syndrome; however, toxicity data were limited. CONCLUSION: Although infrequently reported, EBV infection or reactivation after CAR-T therapy may be associated with substantial morbidity and mortality among affected patients. However, the available evidence is limited by the small sample size, heterogeneous study designs, and inconsistent EBV surveillance practices.

Humans↗

PubMed2026

Prevalence and risk factors of red blood cell alloimmunization among sickle cell disease patients in resource-limited countries: A systematic review and meta-analysis.

BACKGROUND: Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by hemoglobin S production, in which homozygous individuals (HbSS) develop a broad range of acute and chronic complications. While disease-modifying and curative therapies are increasingly available in high-income settings, red blood cell (RBC) transfusion remains the mainstay of treatment in resource-limited countries and is associated with high rates of alloimmunization. This systematic review and meta-analysis aimed to estimate the prevalence of alloimmunization and identify associated risk factors among patients with SCD living in resource-limited settings. METHODS: Africa Journals Online (AJOL), Embase, PubMed, Scopus, and Web of Science were searched for original studies published from inception to December 15, 2025. Only studies conducted in low- and lower-middle-income countries (LMICs) were included. Eligible studies evaluated the prevalence of alloimmunization in patients with SCD receiving RBC transfusions. A random-effects meta-analysis of proportions was performed to pool quantitative data, while qualitative findings were systematically summarized in tabular form. Statistical heterogeneity was assessed using the I² statistic and further explored using Baujat plots, leave-one-out analyses, and meta-regression. RESULTS: Our analysis included 27 studies conducted in Africa (n = 23) and Asia (n = 4), predominantly from lower-middle-income countries (n = 19) and mainly employing a cross-sectional design (n = 20), comprising 3128 previously transfused patients with SCD. The pooled prevalence of RBC alloimmunization was 8.76% (95% CI: 6.71-11.37%; I² = 75%). Higher alloimmunization rates were observed in West and North Africa, particularly in Côte d'Ivoire, Egypt, and Nigeria, whereas lower rates were reported in Asia and East Africa. The most frequently identified antibodies belonged to the Rh blood group system (n = 153), followed by the Kell system (n = 65). CONCLUSION: In resource-limited settings, RBC alloimmunization is a frequent and clinically significant complication in patients with SCD, contributing to increased morbidity and potential mortality. Targeted and economically viable antigen matching may reduce alloimmunization rates and improve transfusion safety in LMICs.

Humans↗

PubMed2026

Dynamics and virulence of Enterobacteriaceae reservoirs harboring blaCTX-M group 1 in community wastewater.

UNLABELLED: Extended-spectrum beta-lactamase (ESBL)-producing bacteria are ubiquitous and can cause serious infections. Here, we examined untreated community wastewater influent as a reservoir for blaCTX-M group 1 organisms and their virulence potential. Raw influent samples (n = 268) were collected from four wastewater treatment plants (WWTPs) representing dense urban populations. We observed that blaCTX-M group 1 levels were high at all WWTPs and only ~1-2 log10 lower and not correlated to common human-specific microbiome fecal markers, Lachno3 and HF183, indicating a lack of connection to human fecal inputs. Concentrations of blaCTX-M group 1 genes and markers for presumptive host organisms Escherichia coli and Klebsiella pneumoniae were influenced by travel time and season. Amplicon sequencing revealed high diversity of blaCTX-M group 1-9 genes, with 63% belonging to group 1. Selective culture and 16S rRNA gene sequencing showed blaCTX-M group 1 isolates were 26% E. coli, 26% K. pneumoniae, 40% other Enterobacteriaceae, and 8% Aeromonas. Overall, E. coli averaged 3.6E7 cells/L, with 3% of all E. coli found to contain blaCTX-M group 1. Whole-genome sequencing of blaCTX-M group 1 E. coli from wastewater revealed resistance and virulence gene profiles similar to clinical isolates and distinct from other wastewater ESBL-resistant and non-resistant E. coli. Interpretation of wastewater data needs to consider both the existence of environmental reservoirs that contain potentially pathogenic organisms and the strong influence the dynamics of the conveyance system can have on final concentrations measured at the WWTP. IMPORTANCE: The CTX-M enzyme family is highly abundant in nosocomial, community, and environmental settings and is leading to treatment of infections with carbapenem antibiotics, a last-line therapeutic option. The progressive increase of the clinically relevant blaCTX-M group 1 resistance genes in the human population warrants investigation, particularly to understand the establishment and dynamics of environmental reservoirs. This study utilized molecular and culture methods to gain insight into the possible origin, abundance, and dynamics of blaCTX-M group 1 genes in untreated wastewater influent samples. We found extremely high levels of these genes, with Escherichia coli as a major host organism that closely resembled clinical strains, suggesting they are seeded and propagate in sewer pipe systems. The significance of our research is in developing approaches to monitor antimicrobial resistance reservoirs in community wastewater, which could shed light on global burdens and potential transmission cycles and indicate increasing inputs of clinically relevant strains originating from human populations.

E. coli↗

PubMed2026

Optimized AAV5-RPGR ORF15 Gene Therapy Rescues Photoreceptor Structure and Function in X-Linked Retinitis Pigmentosa Mouse Model.

PURPOSE: To develop and evaluate an rAAV5-based gene therapy vector expressing an optimized human RPGR ORF15 transgene (rAAV5-RPGR) for the treatment of X-linked retinitis pigmentosa caused by RPGR mutations, addressing the challenges of cloning the unstable wild-type ORF15 sequence. DESIGN: This was a prospective experimental study. SUBJECTS: This was an animal study. METHODS: An optimized RPGR ORF15 sequence was designed to eliminate problematic secondary structures and cryptic splice sites. In vitro expression was validated in HEK 293T and photoreceptor-like 661 W cells. A complete Rpgr knockout mouse model (Rpgr-knockout [KO]) was generated and characterized phenotypically. Therapeutic efficacy was assessed in Rpgr-KO mice via subretinal injection of rAAV5-RPGR at low (1 × 10⁹ vg/eye), medium (3 × 10⁹ vg/eye), or high (1 × 10¹⁰ vg/eye) doses. Structural and functional outcomes were evaluated at 12- and 14-month postinjection. Short-term safety was assessed in rabbits 1 month after subretinal injection. MAIN OUTCOME MEASURES: Level of RPGR protein expression and Protein isoform profile (elimination of truncated isoforms), Cellular localization of transgene expression and Dose-dependence of expression, outer nuclear layer thickness, and electroretinography parameters. RESULTS: (1) The optimized vector increased RPGR protein expression 3.3-fold in vitro compared to wild-type and eliminated truncated isoforms. (2) Subretinal delivery of rAAV5-RPGR in mice demonstrated dose-dependent transgene expression localized correctly to photoreceptor inner segments. (3) In Rpgr-KO mice, high-dose treatment significantly preserved outer nuclear layer thickness at the injection site (42% greater than controls at 14 months, P < .01) and central retina (P < .05), reduced aberrant rhodopsin mislocalization (P < .01), and partially restored retinal function. ERG showed significantly improved scotopic a-wave (≥100 vs <90 µV in controls at 10 cd·s/m²) and photopic b-wave amplitudes (49-66 vs 31-46 µV at 30 cd·s/m²) in treated mice. (4) No vector-related toxicity was observed in rabbits. CONCLUSIONS: rAAV5-RPGR mediated efficiently, targeted expression of optimized RPGR-ORF15, significantly preserved photoreceptor structure and function in a severe X-linked retinitis pigmentosa mouse model, and demonstrated a favorable safety profile. This study provides preclinical proof-of-concept for RPGR-targeted gene replacement therapy.

Animals↗

PubMed2026

Safety Profile of the Non-steroidal Anti-inflammatory Drug Celecoxib in the Short-Term Management of Acute Non-cancer Pain: A Systematic Review with Meta-analysis of Randomised Controlled Trials.

OBJECTIVE: To summarise the literature regarding the safety of short-term use of the non-steroidal anti-inflammatory drug (NSAID) celecoxib. STUDY DESIGN: Systematic review with meta-analysis of randomised trials. Participants comprised individuals of all ages with acute non-cancer pain. Interventions included celecoxib at 200-400 mg/day for up to 10 days. The comparators were placebo, other NSAIDs (including cyclooxygenase-2 [COX-2] inhibitors and non-selective NSAIDS [nsNSAIDS]), or opioids. DATA SOURCES: Five databases were searched from inception to April 2025: Embase, Web of Science, MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus. Additionally, a registry was searched: ClinicalTrials.gov. DATA SYNTHESIS: Meta-analyses using Mantel-Haenszel and random-effects model were used to calculate risk ratios (RRs) and 95% confidence intervals (CIs) for severe cardiovascular, respiratory, and gastrointestinal adverse events and secondary outcomes. The Cochrane Risk of Bias Tool for randomised trials (RoB-2) was used to assess bias risk. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) was conducted to assess the certainty of evidence of each reported outcome. RESULTS: Title/abstract and full text screening comprised 3976 and 273 studies, respectively. Fifty studies were included with 10,693 participants. The RRs for adverse events were no different between celecoxib and placebo for severe events (3 studies) (RR 0.44 [95% CI 0.10-2.03]), cardiovascular (3 studies) (RR 0.84 [95% CI 0.24-2.92]), respiratory (4 studies) (RR 1.23 [95% CI 0.29-5.26]), and gastrointestinal events (33 studies) (RR 0.96 [95% CI 0.64-1.43]). There was no difference between celecoxib and NSAIDS for gastrointestinal adverse events, RR 0.89 (95% CI 0.68-1.17). Celecoxib had a lower risk compared to opioids for gastrointestinal events, RR 0.34 (95% CI 0.14-0.86), and showed a lower risk of nausea compared with placebo, RR 0.75 (95% CI 0.60-0.93), and nsNSAIDS, RR 0.80 (95% CI 0.64-0.99). Most studies had some risk of bias concerns, and the overall certainty of evidence for most outcomes was very low. Celecoxib appears to be safe for acute non-cancer pain when compared to placebo, NSAIDS, and opioids. It had a lower risk compared to opioids for gastrointestinal adverse events in general, nausea and vomiting, as well as a lower risk for nausea adverse events when compared to placebo and nsNSAIDS. REGISTRATION: PROSPERO-CRD42025642152.

Journal Article↗

PubMed2026

Surgical management of jugular foramen meningiomas: a function-prioritized perioperative workflow.

OBJECTIVE: Jugular foramen meningiomas are challenging because of their deep, neurovascularly crowded location and multicompartment extension; hyperostosis and rigid dural attachment further narrow the corridor and increase the risk of lower cranial nerve morbidity, causing dysphagia and airway complications that may rarely require tracheostomy. This study aimed to describe a contemporary function-first workflow integrating compartment-based anatomy, venous sinus status, preoperative embolization, and continuous vagus nerve monitoring and its relation to clinically actionable recovery endpoints. METHODS: The authors retrospectively reviewed 26 consecutive patients who underwent primary surgery for jugular foramen meningiomas (2014-2025). Tumors were classified as intradural + intrajugular (IJ) or intradural + intrajugular + extracranial extension (IJE). Retrosigmoid, suprajugular, or transjugular approaches were selected by tumor extension and sigmoid-jugular venous status. Selective embolization and continuous vagus nerve monitoring were used when feasible. Outcomes included extubation timing, time to oral intake, 1-year swallowing/voice severity, extent of resection, and salvage stereotactic radiosurgery (SRS) for progression/regrowth. RESULTS: Twenty tumors were IJ and 6 were IJE. Selective embolization was performed in 16 patients (62%) without complications. Continuous vagus nerve monitoring was implemented in 16 patients (62%); lower preservation rates showed an exploratory association with worse 1-year swallowing. All patients were extubated immediately after surgery. Oral intake began by postoperative day ≤ 7 in 20 patients (77%); only 1 required > 14 days before resuming oral intake. At 1 year, swallowing and hoarseness remained worse in 54% and 46% of patients, respectively, but almost all cases were mild; the same patient had moderate dysphagia/hoarseness, and none required tracheostomy, gastrostomy, long-term tube feeding, or phonosurgery. Simpson grade IV comprised 69% of cases but predominantly reflected intrajugular/extracranial residual rather than persistent intradural disease. No patient without preoperative facial nerve palsy developed new palsy; serviceable hearing was preserved in 70%, and 38% with preoperative nonserviceable hearing improved to serviceable hearing. During a median 55.6-month follow-up, 3 patients (12%) underwent salvage SRS for regrowth; none required reoperation. CONCLUSIONS: A function-first workflow guided by anatomical compartment extension and intraoperative monitoring can support rapid recovery and durable functional independence in jugular foramen meningiomas. The IJE phenotype identifies a higher-risk subgroup for delayed oral intake and postoperative subjective dysphagia/hoarseness, while continuous vagus nerve monitoring may provide actionable insights to calibrate surgical aggressiveness and support function-prioritized acceptance of intrajugular/extracranial residual with close surveillance and salvage SRS when needed.

Humans↗

PubMed2026

Assessment of the role and effectiveness of nurse-led multimodal intervention in the rehabilitation of dysphagia in patients with brain tumors.

BACKGROUND: Dysphagia is a common complication in patients with brain tumors, which has a profound adverse impact on patients' health status and quality of life. However, there is a relative lack of research on the rehabilitation of dysphagia in brain tumor patients, especially regarding the role and effectiveness of nurse-led multimodal interventions in the rehabilitation of dysphagia in brain tumor patients, which lacks systematic assessment and in-depth discussion. AIM: This study aimed to evaluate the role and effectiveness of a nurse-led multimodal intervention in improving swallowing function and quality of life in brain tumor patients with dysphagia. METHODS: In this study, a randomized controlled trial (RCT) design was used to select 120 dysphagia patients among brain tumor patients admitted to our hospital during the period of January 2024 to May 2024 as the study subjects, and they were stratified and randomly divided into an intervention group (n = 60) and a control group (n = 60). While the control group received conventional nursing care and treatment protocols, the intervention group received a nurse-led multimodal intervention program, including personalized swallowing training, nutritional support, psychological care, and a family-participatory rehabilitation program, which was developed and dynamically adjusted by nurses, rehabilitation therapists, and dietitians. Differences in data before and after the intervention were analyzed using the paired t-test or Wilcoxon signed-rank test, and between-group comparisons were made using the independent samples t-test or Mann-Whitney U test. RESULTS: Both the intervention and control groups showed improvement in swallowing function among the patients. The Kubota drinking test score, Saito's swallowing function grading, and the quality of life scores for patients in the intervention group showed a significant enhancement compared to those in the control group (P < 0.05), indicating that the intervention was more effective than the control. When compared within groups, all scores in both the intervention and control groups improved gradually with the time of intervention (P < 0.05). The improvement was significantly higher in the intervention group than in the control group. CONCLUSION: This study demonstrates that a nurse-led multimodal intervention is significantly effective in improving swallowing function and quality of life in patients with brain tumors. The intervention provides comprehensive rehabilitation support for patients through multidisciplinary collaboration and personalized care and has certain clinical promotion value.

Humans↗

PubMed2026

Multi-omics reveals that burdock seed aglycone alleviates renal fibrosis by restoring mitochondrial oxidative phosphorylation function.

Renal fibrosis (RF), a common pathological process driving chronic kidney disease (CKD) progression to end-stage renal failure, is closely associated with oxidative phosphorylation (OXPHOS). Arctigenin (ATG), the main active component of burdock seed, exhibits anti-inflammatory and anti-fibrotic activities, but its mechanisms in RF treatment remain unclear. Here, we performed integrated transcriptomic and proteomic analyses to identify key targets and pathways of ATG in a unilateral ureteral obstruction-induced rat RF model. Multi-omics enrichment analysis revealed that NDUFS8 and NDUFS2 were the core targets of ATG, with the OXPHOS pathway as the central intersecting pathway. Our results suggest that ATG exerts anti-renal fibrosis effects by targeting the OXPHOS pathway to inhibit excessive reactive oxygen species production and oxidative stress. SIGNIFICANCE: Chronic kidney disease (CKD) continues to impose an escalating global health and socioeconomic burden, while renal fibrosis (RF), as the convergent pathological endpoint of virtually all progressive nephropathies, remains the principal determinant of irreversible renal failure and adverse clinical outcomes. Despite extensive efforts to develop antifibrotic therapies, effective clinical interventions remain elusive, largely due to the complex and multifactorial nature of RF pathogenesis. In this study, we employed an integrated multi-omics framework encompassing transcriptomics, proteomics, and metabolomics to systematically decipher the antifibrotic mechanism of arctigenin (ATG), a bioactive natural compound derived from traditional Chinese medicine. Our findings identify mitochondrial oxidative phosphorylation as the pivotal regulatory axis underlying the renoprotective effects of ATG and further establish key catalytic subunits of mitochondrial complex I as its direct molecular targets. Mechanistically, ATG not only restores complex I activity and reprograms mitochondrial energy metabolism but also preserves the intracellular stability and localization of these subunits, thereby preventing their aberrant release-mediated inflammatory activation and disrupting the self-perpetuating cycle linking metabolic dysfunction, inflammation, and fibrosis progression. Beyond revealing a previously unrecognized dual mechanism integrating metabolic and inflammatory regulation, this study provides compelling evidence that mitochondrial dysfunction is not merely a secondary consequence of tissue injury but a fundamental driver of fibrotic remodeling. Importantly, our work highlights the translational potential of natural product-based mitochondrial interventions for CKD treatment and supports a broader conceptual shift toward metabolism-centered therapeutic strategies for chronic fibrotic diseases. Given the central role of mitochondrial dysfunction across multiple organs, these findings may also have far-reaching implications for the treatment of systemic fibrosis-related disorders beyond the kidney.

Animals↗

PubMed2026

Comparison of Adult Tracheostomy Outcomes Before and After Implementation of a Dedicated Tracheostomy Team.

OBJECTIVE: (A) Determine patient and institutional factors associated with increased length of stay (LOS) and complications of tracheostomy, (B) Develop data-driven quality improvement in tracheostomy care. DESIGN: Mixed methods protocol used cross-sectional survey assessing institutional trends in tracheostomy-specific care. Retrospective chart review compared tracheostomy patient outcomes prior to and during implementation of a multidisciplinary tracheostomy care team and standardized guidelines. PARTICIPANTS: Patients undergoing tracheostomy from January 2019 to December 2021 at a tertiary hospital. METHODS: Patient factors, procedure type and indication, tracheostomy tube size, management timeline, insurance, and disease severity using Acute Physiology and Chronic Health Evaluation II (APACHE II) score were analyzed for associations with LOS and adverse events. Multivariate analyses controlled for APACHE II score and payer source. LOS and complications were compared between patients before and during implementation of multidisciplinary tracheostomy care team and standardized guidelines. RESULTS: Three-hundred and eighteen patients met criteria with a 21.7% complication rate, average LOS of 24 days (SD = 28.523), and median LOS post-tracheostomy of 14 days (IQR 7, 29). Departments without standardized protocols had greater LOS (F[1,316] = 28.706, P < .001]) and complication odds (OR = 2.92, P = .015, 95% CI[1.231, 6.930]). Larger tracheostomy tube size was linked to increased LOS (β = .253, t(314) = 4.741, P < .001, 95% CI[4.137, 10.081]). Delays from ventilation discontinuation to cuffless tube exchange and decannulation correlated with increased LOS (β = .406, t(184) = 6.321, P < .001, 95% CI[.928, 1.771]); (β = .554, t(129) = 7.625, P < .001, 95% CI[1.008, 1.715]). When focusing on a single department, comparing 2019 patients to 2021 patients (pre- and post-guideline and care team), overall, LOS decreased from 33.08 to 30.83 days (P = .586). When excluding patients discharged on a ventilator, the 2019 group had average LOS of 37.938 days versus 33.41 days in 2021 (P = .344). CONCLUSIONS: Standardized tracheostomy care guidelines and multidisciplinary care teams are critical to improving institutional outcomes. Data-driven approaches to quality improvement ensure efficient and targeted methods to improving patient care. LEVEL OF EVIDENCE: 4.

Humans↗

PubMed2026

Naltrexone Is Superior to Placebo for Abstinence and Craving Reduction in Alcohol-Associated Cirrhosis: NAL-CI Trial.

BACKGROUND AND AIMS: Alcohol use disorder (AUD) coexisting with cirrhosis carries high morbidity and mortality, with no approved pharmacotherapy for AUD. We evaluated the safety and efficacy of naltrexone, an opioid receptor antagonist, in patients with compensated alcohol-associated cirrhosis (AaC) and AUD. METHODS: One hundred patients with compensated AaC and DSM-5 AUD were randomised 1:1 to naltrexone (50 mg/day) or placebo for 12 weeks. The primary endpoint was point-prevalence abstinence at 12 weeks, defined as no alcohol use in the four preceding weeks. Secondary endpoints included craving (Obsessive Compulsive Drinking Scale [OCDS]-Obsessive and Compulsive subscales), lapses, relapses, and hepatic safety. Standardised psychosocial support was provided to both arms. RESULTS: Baseline characteristics were well matched between groups (mean MELD 12.6 vs. 12.7; CTP score 5.9 vs. 6.2; age 42.9 vs. 44.3 years). AUDIT and OCDS scores were comparable between groups. Abstinence at 12 weeks was significantly higher with naltrexone: 64% (32/50) versus 22% (11/50), p < 0.001; OR 10.86 (95% CI: 1.89-62.2). Naltrexone significantly reduced lapses at 3 months (28% vs. 54%, p = 0.008) and showed a trend toward fewer heavy-drinking relapses (12% vs. 28%, p = 0.07). Maintenance of abstinence at 6 months favoured naltrexone (22% vs. 8%, p = 0.09). No patient developed hepatic decompensation attributable to study medication, and no AST/ALT elevation exceeding 5× ULN was observed in either group. Mean craving scores were lower with naltrexone by week 12 than with placebo: OCDS-O score (6.63 ± 1.16 vs. 9.29 ± 1.78, p < 0.01) and OCDS-C score (6.35 ± 1.23 vs. 9.02 ± 1.86, p < 0.01). Adverse events were comparable between the groups. CONCLUSION: Naltrexone is safe and effective in patients with compensated alcohol-associated cirrhosis, achieving a threefold higher abstinence rate and significantly reducing craving compared with placebo. These findings support the use of naltrexone as a pharmacological option in patients with compensated AaC and AUD. TRIAL REGISTRATION: NCT04391764.

Humans↗

PubMed2026

Using Organoids to Unlock the Potential of Human Torpor for Spaceflight.

PURPOSE OF REVIEW: This paper reviews the current understanding of the potential for humans to enter a state of torpor/hibernation, and discusses the possibility of inducing torpor in astronauts for long-duration space travel, including some of the physiological, technological, and ethical considerations associated with its implementation. By exploring means to induce torpor in various human organoid systems, we hope such research can provides insights to comprehensive solutions to overcome some of the major hurdles that limit the potential for human to enter a state of torpor during long-duration deep-space missions, and contribute to the ongoing efforts to make such missions more feasible and safer for astronauts. RECENT FINDINGS: On future deep space missions such as NASA's planned missions to the Moon, Mars, and near-Earth asteroids, astronauts will be continuously exposed to environments that are radically different from those on Earth, each presenting multiple logistical and physiological challenges. Beyond the well-documented physiological effects of microgravity, space travelers will encounter a complex radiation environment that may contribute to significant short- and long-term adverse effects on human physiology and increase the risk of cancer and other diseases. Besides these physical challenges, life support systems must also be designed to mitigate psychological impacts of long-term isolation and confinement - all of which collectively pose formidable engineering problems. Hibernation/torpor is a state of prolonged inactivity and metabolic depression used by a wide variety of mammals to survive periods of cold temperatures and food scarcity, including some primates and perhaps even an extinct early line of hominins that lived nearly half a million years ago. Since modern humans share common ancestry with these hominins and hibernating primates, it is likely the human genome encodes the necessary genetic information to hibernate, or at least enter the similar, more transient state of torpor. The reduced body activity, lowered metabolism, and decreased energy requirements that characterize torpor suggest that developing means of inducing such a state in astronauts could address these challenges, including providing a degree of radioprotection. SUMMARY: This review explores the potential application of human torpor as a countermeasure to address the many challenges posed by long-duration spaceflight beyond low-Earth orbit (LEO), discusses various natural hibernating model systems for studying means of inducing a torpor-like state in humans, and highlights the vast potential of using human organoids to test and validate mechanisms that govern induction and maintenance of torpor to identify the means to one day safely induce this state in astronauts to provide additional protection from the myriad stressors of spaceflight.

Astronaut Health↗

PubMed2026

Evaluation of the clinical and mechanistic role of MCM2 expression in the prediction of meningioma recurrence after radiotherapy.

OBJECTIVE: Postoperative radiotherapy is an effective treatment for meningiomas; however, treatment response varies among patients. In addition, practical methods for predicting tumor recurrence after radiotherapy have not been well established. Minichromosome maintenance protein 2 (MCM2), a key regulator of DNA replication licensing, was recently implicated in highly proliferative molecular subtypes of meningioma. In this study, the authors evaluated whether MCM2 immunohistochemical expression predicts response to radiotherapy in patients with meningiomas. METHODS: The authors retrospectively analyzed the records of patients with WHO grade 1-3 meningiomas treated with resection followed by radiotherapy at a single institution between July 2003 and November 2023. The MCM2 labeling index was assessed immunohistochemically, and patients were stratified into MCM2-high and -low groups using a cutoff of 35%. Progression-free survival (PFS) was defined as the interval from the completion of radiation therapy to postoperative radiological tumor recurrence or regrowth. Patients who showed no progression were censored at their last follow-up. PFS was estimated using Kaplan-Meier analysis and subsequently evaluated with Cox proportional hazards models. To further investigate the biological mechanisms associated with MCM2 expression, comprehensive transcriptomic analyses, including gene set enrichment analysis, was performed to elucidate the molecular processes that occur within MCM2-high tumors. RESULTS: The study population included 15 men (42%) and 21 women (58%), with a mean age of 63 years. Ten tumors (28%) were classified as MCM2-high meningiomas and 26 (72%) as MCM2-low meningiomas. High MCM2 expression was significantly associated with WHO grades 2-3 histology and higher Ki-67 labeling indices. During a median follow-up of 2.52 years, tumor progression after radiotherapy occurred in 47% of the patients. High MCM2 expression (HR 8.34, p = 0.03) was significantly associated with shorter PFS and remained an independent predictor of recurrence after adjustment for WHO grade, tumor size, and Ki-67 labeling index. Transcriptomic analyses of MCM2-high tumors revealed upregulation of cell proliferation-related pathways, accompanied by increased signaling through the E2F8-CHEK1 axis associated with radiation resistance and suppression of the TNF-α signaling pathway implicated in radiosensitivity. CONCLUSIONS: In meningiomas, high MCM2 expression is associated with early recurrence following radiotherapy. The study findings suggest that this association is driven by diverse biological mechanisms related to cell cycle regulation and radioresistance. Immunohistochemical assessment of MCM2 expression may serve as a practical and accessible biomarker for risk stratification and may support the future development of individualized postoperative radiotherapy strategies.

Humans↗

PubMed2026

Navigating Social Media: Balancing Connectivity With Media Literacy to Combat Misinformation and Protect Mental Well-Being.

BACKGROUND: The pervasive use of social media has created a complex digital ecosystem where high connectivity coexists with significant challenges, including the rapid spread of misinformation, particularly regarding mental health, and documented negative impacts on psychological well-being. Platform architectures designed for engagement maximization have been identified as central factors in both issues. OBJECTIVE: This paper critically analyzes the interconnected relationships between social media use, misinformation dissemination, and mental health impacts, with particular attention to psychiatric misinformation across diagnostic categories (e.g., depression, anxiety, ADHD). A primary objective is to evaluate the potential of advanced critical digital literacy frameworks to serve as protective mechanisms against these dual threats. METHODS: A systematic search was conducted following PRISMA 2020 guidelines across APA PsycInfo, PubMed, JSTOR, and Google Scholar for literature published between January 2018 and March 2026 (updated from the original 2023 search). The search yielded 2672 records. After removing 624 duplicates, 2048 records underwent title and abstract screening, with 1802 excluded. The remaining 246 full-text articles were assessed for eligibility, resulting in 86 studies included in the final qualitative synthesis. Inter-rater reliability was established (Cohen's κ = 0.82). Quality assessment was conducted using the Joanna Briggs Institute Checklist, AXIS, and CASP tools, with findings weighted by methodological quality. A thematic analysis was undertaken to synthesize findings. RESULTS: The analysis reveals that core architectural features of social media platforms, algorithmic curation and engagement-based metrics, simultaneously foster environments ripe for misinformation spread and contribute to psychological distress, including anxiety, depression, and harmful social comparison. Psychiatric misinformation specifically (e.g., inaccurate claims about treatment effectiveness, diagnostic criteria, and medication side effects) represents a growing concern, particularly on image- and video-based platforms. The findings indicate that conventional media literacy approaches focused solely on fact-checking are insufficient. Instead, a critical digital literacy framework encompassing algorithmic awareness, data literacy, and emotional awareness is essential for building user resilience, with evidence from high-quality systematic reviews supporting this approach. CONCLUSIONS: Navigating the complexities of modern social media requires an integrated approach combining "pedagogies of play" for experiential skill development with advocacy for structural change (e.g., algorithmic transparency, well being by design principles). This dual strategy empowers individual users to critically engage with digital content while advocating for ethical platform design, thereby safeguarding both mental well-being and democratic discourse. Implications for educators, mental health professionals (including competencies for addressing patient encounters with psychiatric misinformation), policymakers, and platform designers are discussed.

Humans↗

PubMed2026

High-Flow Nasal Oxygen and the Risk of Gastric Insufflation: A Systematic Review and Meta-Analysis Supplemented by Narrative Synthesis.

High-flow nasal oxygen (HFNO) generates positive airway pressure, raising concerns about gastric insufflation and aspiration risk. Although most studies report minimal or no gastric distension, some suggest significant changes. This systematic review and meta-analysis applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to evaluate the effect of HFNO on gastric insufflation and related markers across clinical settings. We searched Medline, Embase, Emcare, and CINAHL through August 2025 for studies reporting qualitative or quantitative markers of gastric insufflation during HFNO use, including comet-tail artifacts, antral cross-sectional area, and gastric volume. Eligible designs included randomized trials, observational and volunteer studies, and case reports. Methodological quality was evaluated using the Mixed Methods Appraisal Tool, and certainty of evidence was rated with GRADE. Meta-analysis was performed for outcomes reported in two or more studies. Six randomized trials, five observational studies, two volunteer studies, one case series, and two case reports were included. Observational studies primarily assessed outcomes before and after HFNO intervention. Pooled analysis of four randomized controlled trials (RCTs; n = 375) showed HFNO significantly reduced gastric insufflation compared with face-mask ventilation during elective peri-intubation (risk ratios [RR] = 0.32; 95% confidence interval [CI], 0.19-0.52; P < .00001; I 2 = 0%), rated moderate-certainty. For antral cross-sectional area, pooled analysis of three RCTs (n = 318) found no significant difference between HFNO and face-mask ventilation (MD -0.33 cm 2 ; 95% CI, -0.72 to 0.05; P = .09; I 2 = 74%), rated moderate-certainty. Observational studies assessing pre- and post-HFNO changes showed no significant increase in antral cross-sectional area (MD 0.08 cm 2 ; 95% CI, -0.29 to 0.45; P = .67; I 2 = 0%) and no significant change in gastric liquid volume (MD -0.01 ml/kg; 95% CI, -0.07 to 0.06; P = .80; I 2 = 0%), both rated low certainty. Nonpooled data suggested possible increases in critically ill patients, but the evidence was of very low certainty. A single study assessing microaspiration found HFNO reduced gastroesophageal reflux and prevented microaspiration compared with face-mask ventilation. No clinically significant aspiration events were reported across studies. Moderate-certainty evidence supports HFNO as safe regarding gastric insufflation and antral cross-sectional area in most elective and procedural contexts. Low-certainty evidence suggests no increase in gastric volume. Caution is warranted due to limited, low-to-very-low-certainty evidence at higher flow rates and among critically ill patients. Larger multicenter trials and robust observational studies are necessary to confirm safety in these settings.

Humans↗

PubMed2026

Unraveling the Clinical Spectrum of DNASE1L3 Deficiency: Insights from Case Series and Systematic Literature Review.

BACKGROUND: DNASE1L3 deficiency is a rare monogenic cause of lupus and lupus-like autoimmunity resulting from impaired extracellular DNA clearance and sustained immune activation. Although most reported patients present with early-onset systemic lupus erythematosus (SLE), emerging evidence suggests broader phenotypic variability, including vasculitic and overlap manifestations. Whether these presentations represent distinct clinical entities or a continuum of DNASE1L3-associated immune dysregulation remains unclear. We aimed to define the clinical spectrum of DNASE1L3 deficiency and examine the relationship between recurrent pathogenic variants and disease severity. METHODS: We conducted a combined pediatric case series and systematic literature review. Four children with genetically confirmed biallelic DNASE1L3 variants followed at a tertiary pediatric rheumatology centre were retrospectively analysed for clinical, immunological, genetic, treatment, and outcome data. In parallel, a systematic search of PubMed/MEDLINE, Scopus, and Web of Science identified previously reported patients with confirmed biallelic pathogenic or likely pathogenic DNASE1L3 variants and extractable patient-level clinical data. To facilitate cross-case comparison, we applied an exploratory three-tier descriptive framework reflecting increasing disease severity: vasculitic or organ-limited disease (G1), systemic lupus or overlap phenotypes without irreversible organ damage (G2), and severe systemic organ-damaging disease (G3). The assigned grades were descriptive rather than permanent categories, as some patients may meet the criteria for a higher grade if broader systemic manifestations or irreversible organ damage develop during follow-up. FINDINGS: Fifteen reports provided extractable patient-level data, corresponding to 45 unique previously reported patients after accounting for known or probable overlapping reports. Combined with four patients from our centre, the analysis included 49 genetically confirmed individuals. SLE-dominant disease was the most frequent phenotype (27 [60%] of 45), followed by hypocomplementaemic urticarial vasculitis/HUVS-dominant disease (10 [22.2%]) and overlap phenotypes (8 [17.8%]). Renal involvement was reported in 30 (66.7%) of 45 patients, and disease onset occurred by age 3 years in 20 (44.4%). Persistent hypocomplementemia affecting C3 and C4 was frequently reported across the spectrum. Recurrent DNASE1L3 variants were observed across multiple phenotypic and severity grades. Variants such as p.Asn191Ser and p.Thr97Ilefs*2 occurred in patients spanning organ-limited vasculitic disease, lupus overlap phenotypes, and severe multisystem lupus with major organ involvement. CONCLUSION: DNASE1L3 deficiency was associated with a broad clinical spectrum of immune-mediated disease rather than a single clinicopathological entity. The occurrence of identical pathogenic variants across distinct phenotypic and severity states argues against a simple genotype-phenotype model and suggests that additional modifiers influence disease expression.

Humans↗

PubMed2026

No association between alcohol consumption and hip osteoarthritis: a diverse national analysis of 87,585 adults from the "All of Us" research program.

INTRODUCTION: Hip osteoarthritis (OA) is estimated to affect 62.6 million individuals by 2050. A probable link exists between alcohol use and hip OA. However, the results are inconsistent, and the relationship between alcohol and hip OA remains speculative. To address these gaps, this study aimed to utilize the diverse, nationally representative All of Us Research Program dataset to explore the association between alcohol consumption and hip OA. METHODS: This retrospective case-control study utilized data from the All of Us Research Program Controlled Tier Dataset v8. 17,517 hip OA cases and 70,068 controls were identified. A 1:4 case-to-control matching ratio was applied based on age and sex. Alcohol use frequency was categorized into five levels: Never, Monthly or Less, Two to Four Times per Month, Two to Three Times per Week, and Four or More Times per Week. Multivariable logistic regression models evaluated the association between alcohol use frequency and hip OA after adjusting for demographic and clinical variables. RESULTS: Multivariable analysis found that alcohol use frequency was not significantly associated with hip OA. Compared to never users, participants with low (OR 0.98, 95% CI 0.93-1.04, P = 0.583), moderate (OR 0.99-1.01, all P > 0.05), and high (OR 1.02, 95% CI 0.95-1.09, P = 0.599) levels of alcohol consumption had no statistically significant differences in odds of hip OA. Female sex, Asian race, diabetes, hypertension, hyperlipidemia, and nicotine dependence increased the odds of hip OA. CONCLUSION: Any level of alcohol consumption was not significantly associated with the odds of hip OA. This study adds valuable insight to the current body of conflicting evidence. Further prospective studies appear warranted to shed light on the long-term effects of different alcoholic beverages on different joints. Key Points • This study found no significant association between any degree of alcohol consumption and the odds of developing hip osteoarthritis. • Utilizing data from 87,585 adults in the NIH "All of Us" Research Program, this is the first study to analyze this relationship in a large, nationally representative population. • The research provides clarity to previously conflicting literature by demonstrating that alcohol lacks a clear harmful or protective effect on the clinical course of the disease. • The analysis highlights that independent risk factors such as Asian race, nicotine dependence, and components of metabolic syndrome increase the odds of hip osteoarthritis.

Humans↗