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PubMed2026

Marine air promotes structural compaction and coating growth of soot aerosols after long-range transport from East Asia.

Soot aerosol, a key global warming contributor, undergoes morphological and chemical transformations during atmospheric transport, particularly in humidified marine environments. This study investigates morphology, mixing state, and aging mechanisms of soot particles collected in the Bohai Sea and Yellow Sea. Transmission electron microscopy analyses reveal that coated soot particles dominate the marine atmosphere, accounting for over 98 % of soot-containing particles, with a mean mixing state index (χ) of 0.83. The fractal dimension (Df) of soot particles is 1.84 ± 0.05 in the Northern Yellow Sea, 1.90 ± 0.08 in the Bohai Sea, and 1.96 ± 0.07 in the Southern Yellow Sea, indicating structural compaction during long-range transport. Correspondingly, the average Dp/Dcore ratios (particle to core size ratio) are 5.3 in the Bohai Sea, 4.2 in the Northern Yellow Sea, and 3.9 in the Southern Yellow Sea. Notably, those ratios are higher in marine environments compared to those observed during continental regional transport from northern to southern China (3.54), suggesting enhanced coating growth in humid marine air. The results highlight the important role of marine atmospheres in accelerating soot aging, which in turn leads to significantly stronger light absorption compared to soot in continental air. Our results highlight the necessity of incorporating compact morphologies, uniform mixing states, and thick coatings into optical models for accurate radiative forcing simulations.

Aerosols↗

PubMed2026

A systematic review and network meta-analysis of single nucleotide polymorphisms associated with oral submucous fibrosis risk.

BACKGROUND: Oral submucous fibrosis (OSF) is a chronic and insidious oral disease characterized by hyalinization of the subepithelial connective tissue and progressive fibrosis of the oral submucosa. It is a precancerous condition of oral squamous cell carcinoma. Studies have demonstrated that single nucleotide polymorphisms (SNPs) are closely associated with susceptibility to OSF. This study aims to comprehensively evaluate the association between SNPs and OSF risk and to rank the strength of the association between different genetic models and OSF susceptibility. METHODS: Literature related to OSF was comprehensively searched from PubMed, Web of Science, Embase, Cochrane Library, CNKI, and Wangfang databases up to July 2025. Full-text case-control studies with patients diagnosed with OSF were included. Quality assessment was performed to evaluate the risk of bias. RevMan 5.4, GeMTC 0.14.3, and STATA 17.0 were used for the pairwise and Bayesian network meta-analysis. RESULTS: A total of 24 studies with 2545 cases and 3772 controls, covering 13 SNPs in 11 genes, were included in our meta-analysis. We found that CYP1A1 rs4646903:T>C, CYP1A1 rs1048943:A>G, GSTT1 null genotype, GSTM1 null genotype, and XRCC3 rs861539:C>T were associated with an increased risk of OSF, while MMP2 rs243865:C>T and MMP3 rs3025058: 5A>6A were associated with a decreased risk of OSF. Further Bayesian network meta-analysis indicated the top 5 genetic models with the highest association with OSF risk in network group 1 were the dominant model, homozygous model, allelic model, and recessive model of CYP1A1 rs1048943:A>G (ranked 1-4), and the heterozygous/dominant model of CYP1A1 rs4646903:T>C (both ranked 5). While the allelic models of XRCC3 rs861539:C>T and MMP3 rs3025058: 5A>6A ranked first for predicting OSF in group 2 and group 3, respectively. CONCLUSION: Some specific SNPs are significantly related to the risk of OSF. Among them, the dominant model of CYP1A1 rs1048943:A>G may be the most strongly associated genetic model with OSF risk. Future large-sample, well-designed studies with detailed genotype data are needed to validate the roles of these SNPs in OSF risk.

Humans↗

PubMed2026

Clinical Outcomes and Genomic Epidemiology of Multidrug-Resistant Methicillin-Resistant Staphylococcus aureus Keratitis.

PURPOSE: To characterize the clinical features, management, antimicrobial resistance patterns, and genomic epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) keratitis at two North American centers. DESIGN: Retrospective interventional case series combined with laboratory investigation PARTICIPANTS: Seventy eyes of 67 patients presenting laboratory-confirmed MRSA keratitis were included METHODS: We performed a multicenter retrospective case series of patients with culture-proven MRSA keratitis treated between 2005 and 2022. Demographic and clinical data were collected. Antimicrobial susceptibility testing was conducted, and multidrug resistance (MDR) was defined as resistance to ≥3 antibiotic classes. A subset of isolates underwent whole-genome sequencing with core genome multilocus sequence typing. Vancomycin susceptibility, heteroresistance screening, and tolerance testing were performed on available isolates. MAIN OUTCOME MEASURES: Antimicrobial susceptibility and multidrug resistance rates, vancomycin phenotypic profiles, MRSA genotypic distribution, and final best-corrected visual acuity RESULTS: Median age was 63.5 years, and 61.4% were female. Ocular surface disease (67.7%) and prior ocular surgery (65.2%) were common. Only 25.4% had significant healthcare exposure in the preceding year. Most isolates (85.7%) were MDR. Fluoroquinolone susceptibility was low (moxifloxacin 19.7%). All isolates were susceptible to vancomycin (MIC₉₀ 2 µg/mL), and no vancomycin-intermediate, heteroresistant, or tolerant phenotypes were identified. Whole genome sequencing (n = 41) demonstrated predominance of clonal complexes 5 (68.3%) and 8 (29.2%). Visual outcomes were poor, with most patients (85.2%) having a final visual acuity worse than 20/60 among those with follow-up. CONCLUSIONS: MRSA keratitis is associated with high rates of multidrug resistance and poor visual outcomes despite guideline-based therapy. Infections were predominantly caused by CC5 MDR strains despite limited recent healthcare exposure. These findings highlight the persistence of highly resistant MRSA lineages in community-associated corneal infection and underscore the need for ongoing antimicrobial surveillance and optimized treatment strategies.

Humans↗

PubMed2026

GLP-1 Receptor Agonists and Musculoskeletal Outcomes: A Systematic Literature Review and Meta-Analysis.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the treatment of type 2 diabetes and obesity, but their effects on musculoskeletal health remain completely misunderstood. OBJECTIVE: This systematic review/meta-analysis aims to synthesise clinical data on the effects of GLP-1 RAs on key relevant bone, muscle, and joint outcomes. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) (both via Ovid® platform) and Embase were searched from inception to March 2025 to identify relevant randomised controlled trials (RCTs) or real-world evidence (RWE) studies to be included. This bibliographic search was completed manually. A random-effect model meta-analysis was performed for any outcome reported in at least 2 studies. Subgroup analyses were performed on the type of GLP-1 RAs, type of comparator used and study design. Sensitivity analyses (i.e., leave-out sensitivity analyses and analyses restricted to the most adjusted effect estimate) were performed to test the robustness of the data. The strength of evidence was assessed using GRADE. This work has been performed in adherence with PRISMA statement. (PROSPERO Record ID: CRD420251024082). RESULTS: From 1148 potentially relevant references, 60 articles (46 RCTs, 13 RWE studies and 1 pharmacovigilance study, comprising 1,250,717 individuals) met our inclusion criteria. Different GLP-1 RAs were represented across the panel of studies, i.e., semaglutide, liraglutide, exenatide, dulaglutide, tirzepatide (dual agonist gastric inhibitory polypeptide [GIP]/GLP-1) and others. No effect on bone outcomes (i.e., bone mineral density [all sites] and fractures [all sites]) were observed when the meta-analytical models included the most adjusted effect size. Regarding muscle outcomes, a significant decrease of lean body mass/fat-free mass was consistently observed with GLP-1 RAs in the global model (k = 28, standardised mean difference [SMD] 0.52, 95% confidence interval [CI] -0.8; -0.23, I2 88%, p-value for heterogeneity <0.0001), which remained robust in all sensitivity analyses. Subgroup analyses showed that the effect was mainly driven by liraglutide and semaglutide, with a decrease in lean body mass/fat-free mass observed when GLP-1 RAs were compared with placebo. No publication bias was found. Regarding joint outcome, models revealed no significant change in The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, physical function and stiffness. CONCLUSIONS: This meta-analysis is the first to investigate the effects of GLP-1 RAs on a large panel of musculoskeletal health outcomes. While no significant effects were observed on bone- or joint-related outcomes, GLP-1 RAs were associated with reductions in lean body mass/fat-free mass, although the certainty of evidence was low and these changes appeared largely related to weight loss. Whether these changes translate into clinically meaningful impairments in muscle function or physical performance remains uncertain. Further studies in this field, including those looking at muscle function, strength or performance and using multivariate models considering confounding are needed to better reinforce the models and final findings.

Journal Article↗

PubMed2026

Pharmacokinetics and safety of TBAJ-587, a novel antimycobacterial diarylquinoline, in healthy participants.

TBAJ-587 is a second-generation diarylquinoline with greater antimycobacterial activity and a potentially better safety profile than the first-generation bedaquiline. It is currently under development for the treatment of drug-susceptible and drug-resistant tuberculosis. A first-in-human trial of TBAJ-587, including single and multiple ascending oral doses and a dedicated food-effect cohort, was conducted in 92 healthy adults. Plasma exposures of TBAJ-587 were generally linear for AUCtau and slightly subproportional for Cmax, with the major circulating active metabolite, M3, remaining low relative to the parent. A high-fat meal increased the mean Cmax and AUClast 3.46- and 2.26-fold, respectively. TBAJ-587 accumulated with multiple dosing over the 28-day period, with mean accumulation ratios across the three tested doses ranging from 1.69 to 2.32 for Cmax and from 2.74 to 3.73 for AUCtau. However, steady-state conditions were not yet reached on day 28. Mean terminal half-lives after 28-day dosing of TBAJ-587 ranged from approximately 80 to 111 days. There were no deaths or serious adverse events, and TBAJ-587 was generally safe and well tolerated at single doses of 25-800 mg under fasting conditions and multiple doses of 50-200 mg once daily for 28 days after a standard breakfast. In addition, no dose- or time-dependent effects were noted for any of the other safety and tolerability parameters, including no clinically significant effects on the QTc interval. These results support further investigation of TBAJ-587 for the treatment of tuberculosis.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04890535.

Humans↗

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

Pain outcomes of pediatric circumcision patients following administration of pre-operative ketorolac: A randomized clinical trial.

INTRODUCTION: Circumcision is a common surgical intervention, and pain is the most common complaint. Poorly managed pain can increase morbidity and reduce patient and parent satisfaction. Ketorolac, a non-steroidal anti-inflammatory drug (NSAID), provides analgesia and may be effective in reducing pain after circumcision in pediatric patients. STUDY OBJECTIVES: The primary objective was to determine the effect of pre-operative intravenous ketorolac versus normal saline placebo on parental perception of postoperative pain at 24 h. We also explored the effect of ketorolac on postoperative pain scores, incidence of bleeding, incidence of vomiting, and analgesic use. MATERIALS AND METHODS: A prospective, randomized, single-blinded trial was conducted at a single tertiary children's hospital. Patients aged 1-17 presenting for circumcision were included and randomized to either normal saline injectate or ketorolac (0.5 mg/kg, maximum 30 mg). Postoperative delirium and pain scores were recorded in the post-anesthetic care unit. Parents completed the parents' postoperative pain measure (PPPM) at 24 h. The CONSORT criteria and checklist were used to guide reporting of this randomized controlled trial. RESULTS: A total of 100 participants were included. 50 participants were in each group. Mean (SD) PPPM score 24 h after normal saline and ketorolac was 6.1 (3.4) and 5.5 (3.3), respectively for a mean difference of -0.55 points [95% CI: -1.9 to 0.83; p = 0.427]. The mean (95% CI) fixed effect size of ketorolac on post anesthetic care unit reported Face, Leg, Activity, Cry, Consolability score was -0.17 (-0.77 to 0.43, p = 0.585) points, while the mean (95% CI) effect size of ketorolac on numerical rating scale was -1.2 (-2.2 to -0.18, p = 0.026) points. DISCUSSION: Pre-operative intravenous ketorolac, compared to normal saline placebo, did not result in a difference in parental perception of postoperative pain at 24 h after circumcision surgery. As part of exploratory analyses, those receiving ketorolac had modestly lower mean immediate postoperative pain scores, likely not of clinical importance. Ketorolac has often been avoided due to concerns of increased bleeding risk, however it is important to consider that there is no substantial evidence to support this. This is the first study to our knowledge evaluating the effect of ketorolac in pediatric circumcision patients. While the PPPM score is a family centered outcome, it is an indirect measurement of pediatric pain. CONCLUSIONS: Pre-operative intravenous ketorolac was not associated with lower parental reported pain scores at 24 h compared to normal saline placebo after pediatric circumcision surgery. CLINICAL TRIAL REGISTRATION: NCT02973958.

Humans↗

PubMed2026

Utility of Dynamic MRI in Surgical Outcome of Patients With Degenerative Cervical Myelopathy: A Single-Center, Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: The utility of dynamic MRI (dMRI) in surgical planning and outcomes for degenerative cervical myelopathy (DCM) has not been validated in any prospective randomized trials. METHODS: In this hospital-based randomized controlled trial conducted between February 2023 and December 2024, patients with DCM were randomized into 2 groups: the Static MRI Group, where surgery was guided by conventional static MRI alone, and the dMRI Group, in which dMRI was performed, with the potential to alter the surgical approach. The primary outcome was recovery rate (RR) at 3 months. Secondary outcomes included postoperative changes in modified Japanese Orthopaedic Association scores and Nurick grades, surgical plan alterations, comparison of surgical approaches, and complication rates. RESULTS: Seventy-four patients were analyzed at a 3-month follow-up. The dMRI group had a significantly higher mean RR (55.42% ± 29.05%) than the Static group (46.76% ± 29.51%) ( P = .044). A RR of ≥50% was observed in 91.9% of patients in the dMRI group, compared with 59.4% in the static MRI group ( P = .002). Modified Japanese Orthopaedic Association scores improved more in the dMRI group (15.47 ± 2.62 vs 13.77 ± 2.66, P = .007). While Nurick grades improved in both groups, the intergroup difference was not statistically significant ( P = .151). dMRI altered the surgical plan in 59.5% of cases. Anterior approaches yielded better RR but had more complications. By contrast, posterior approaches had fewer but more severe complications including mortality. CONCLUSION: dMRI enhances the detection of clinically significant cord compression and may aid in surgical decision-making, potentially contributing to superior functional outcomes in DCM. Further studies are required to determine its impact on long-term functional outcomes.

Humans↗

PubMed2026

Viscoelastic-Assisted Patient Interface Docking: A Technical Optimization in LenSx Femtosecond Laser-Assisted Cataract Surgery.

PURPOSE: To evaluate the efficacy of viscoelastic-assisted patient interface docking in LenSx (Alcon Laboratories, Inc) femtosecond laser-assisted cataract surgery (FLACS). METHODS: This was a randomized controlled trial. Patients undergoing FLACS from January to August 2025 at Aier Eye Hospital of Wuhan University were randomized via a random number table to receive balanced salt solution (BSS) or visoeleastic as the patient interface docking medium. The primary outcome was docking efficiency, measured by one-time docking success rate, the number of docking attempts, and mean docking time. Secondary outcomes included surgical safety (subconjunctival hemorrhage, capsulotomy completeness/tear rate), laser treatment duration (anterior capsulotomy time, nucleus pretreatment time, total laser emission time), and patient comfort (post-laser pain sensation). RESULTS: A total of 100 patients were enrolled, 50 in each group. Suction loss occurred in 7 patients (14%) in the BSS group and 1 patient (2%) in the viscoelastic group; the one-time docking success rate was significantly higher in the viscoelastic group (98%) than in the BSS group (86%) (chi-square = 3.93, P < .05). The viscoelastic group also had fewer mean docking attempts (1.02 ± 0.14) than the BSS group (1.16 ± 0.42), showing a significant difference (t = 2.23, P < .05). The viscoelastic group exhibited significantly shorter mean docking time (44.66 ± 4.47 seconds) compared to the BSS group (48.62 ± 3.11 seconds) (t = 2.17, P < .05). No significant differences were observed between the groups in subconjunctival hemorrhage, capsulotomy completeness/tear rate, anterior capsulotomy time, nucleus pretreatment time, total femtosecond laser emission time, or patient-reported pain sensation (all P > .05). CONCLUSIONS: Viscoelastic-assisted patient interface docking in FLACS effectively elevates one-time docking success rate, reduces docking attempts, and shortens docking time.

Humans↗

PubMed2026

Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock.

BACKGROUND: Whether treatment with balanced crystalloid fluid leads to better outcomes than 0.9% saline in children treated for septic shock is debated. METHODS: In this pragmatic clinical trial conducted at 47 emergency departments in five countries, patients (2 months to <18 years of age) with suspected septic shock and abnormal perfusion were randomly assigned to receive fluid resuscitation with either balanced fluid or 0.9% saline for up to 48 hours. The primary outcome was a major adverse kidney event (a composite of death, new renal-replacement therapy, or persistent kidney dysfunction) at 30 days after enrollment or hospital discharge, whichever occurred first. RESULTS: Of 9041 enrolled patients, 277 (6.1%) in the balanced-fluid group and 282 (6.2%) in the 0.9%-saline group withdrew from the trial, leaving 4235 and 4247 patients, respectively, for analysis. A primary-outcome event occurred in 137 patients (3.4%) in the balanced-fluid group and in 124 (3.0%) in the 0.9%-saline group (difference, 0.4 percentage points; 95% confidence interval [CI], -0.5 to 1.3; risk ratio, 1.10; 95% CI, 0.88 to 1.40; P = 0.85). The median number of hospital-free days during 28 days after enrollment was 23 (interquartile range, 19 to 25) in both groups. Hyperchloremia occurred in 868 patients (31.4%) in the balanced-fluid group and in 1383 (49.0%) in the 0.9%-saline group; hypernatremia in 52 (1.8%) and 89 (3.1%), respectively; and hyperlactatemia in 260 (19.8%) and 228 (16.7%). No differences in other safety outcomes or adverse events were seen. CONCLUSIONS: Among children treated for septic shock, no significant difference was seen in the incidence of death, new renal-replacement therapy, or persistent kidney dysfunction when fluid resuscitation was administered with balanced fluid as compared with 0.9% saline. (Funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; PRoMPT BOLUS ClinicalTrials.gov number, NCT04102371.).

Adolescent↗

PubMed2026

Assessment of Surgical Salvage Outcomes for Exposed Cranial Neuromodulating Devices.

OBJECTIVES: Implanted neuromodulating devices (NMDs) such as cochlear implants (CIs) and deep brain stimulators (DBSs) are commonly used in modern medicine. Rarely, complications arise post-operatively, including hardware exposure. Traditional teaching suggests that these devices require removal if exposed; however, surgical salvage is a high risk, high reward alternative. We review our single institution experience managing NMD exposure with surgical salvage. METHODS: Retrospective chart review was performed on individuals who had a NMD implanted and underwent an attempt at surgical salvage for exposure during the study period (January 01, 2021 through December 31, 2023). Study outcome success was defined as maintaining a functional NMD 1 year after salvage was attempted. Surgical techniques associated with successful salvage were compared. RESULTS: Nine of 729 patients (1.2%) implanted with NMDs experienced hardware exposure during this 2-year study period. Nine subjects were referred for NMD salvage; however, only 6 of 9 subjects (66.7%, CI = 3; DBS = 3) underwent NMD salvage attempts. Four of the subjects had successful salvage demonstrated successful salvage with a functioning NMD and without wound healing concerns 1 year after their salvage procedure. CONCLUSIONS: Classic teaching states that exposed NMDs require explantation. However, this approach necessarily imposes time without benefit from the NMD between explantation and reimplantation. Our experience demonstrates that surgical salvage can be a successful alternative for the majority (66.7%) of individuals.

Humans↗

PubMed2026

Effects of Moderate-Frequency Resistance Training on Cardiometabolic Risk Factors in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis.

BACKGROUND: Resistance training (RT) effectively manages cardiometabolic risk factors in adults, but the specific effects of moderate-frequency RT (2-3 sessions/week) in adults with overweight or obesity are understudied. OBJECTIVE: This study aimed to evaluate moderate-frequency RT's effects on cardiometabolic risk factors in this population and quantify effect sizes. DATA SOURCES: PubMed, Web of Science, EMBASE, and Cochrane Library searched up to July 2025. ELIGIBILITY: English randomized controlled trials (RCTs) comparing RT (≥ 7 weeks) to nonexercise control; nonathletic adults ≥ 18 years with BMI ≥ 25 kg/m2. PARTICIPANTS: 454 participants across 12 RCTs (mean age 58.93 ± 12.87 years; mean BMI 31.2 ± 3.5 kg/m2; ~50% female). RESULTS: RT significantly reduced diastolic blood pressure (MD = -1.53 mmHg; 95% CI: -2.16 to -0.91; p < 0.01), LDL-C (MD = -0.25 mmol/L; 95% CI: -0.41 to -0.08; p < 0.01), and triglycerides (MD = -0.17 mmol/L; 95% CI: -0.30 to -0.04; p = 0.01). No significant effects on systolic blood pressure, mean arterial pressure, waist circumference, glycemic markers, total cholesterol, or HDL-C. Subgroup analyses showed larger LDL-C/triglyceride improvements with concurrent dietary control. CONCLUSION: Moderate-frequency RT inconsistently improves cardiometabolic risk factors, benefiting diastolic blood pressure, LDL-C, and triglycerides but not glycemic or other parameters. Combining with dietary control may enhance benefits, supporting RT as a complementary strategy in multimodal lifestyle interventions. TRIAL REGISTRATION PROSPERO: CRD42022343167.

Humans↗

PubMed2026

Physician-Modified Fenestrated Stent-Grafts Planned Using Three-Dimensional Techniques for Complex Aortic Pathology: A Systematic Review and Meta-Analysis.

BACKGROUND: Complex aortic pathology involving the visceral arteries remains a significant therapeutic challenge. Open repair is associated with considerable perioperative risk, particularly in patients with multiple comorbidities, while standard endovascular aneurysm repair (EVAR) is often not feasible because of inadequate proximal sealing zones. Fenestrated and branched endovascular repair (F/BEVAR) represents an established treatment strategy; however, the use of custom-made devices is limited by manufacturing time and availability. Physician-modified stent grafts (PMSGs) have therefore emerged as a pragmatic alternative. Three-dimensional planning techniques have been increasingly used to facilitate accurate graft modification. The aim of this systematic review and meta-analysis was to evaluate the effectiveness and safety of PMSG procedures planned with three-dimensional techniques. Technical success, target vessel patency, early mortality, endoleak occurrence, and reintervention rates were analyzed. METHODS: A systematic search was conducted in the PubMed/MEDLINE and Embase databases. Studies describing the use of physician-modified fenestrated stent grafts planned with three-dimensional tools were included. Meta-analyses were performed using a random-effects model with restricted maximum likelihood estimation. A logit transformation was used for the analysis of proportions. RESULTS: The analysis included five studies involving 172 patients. The estimated weighted mean follow-up duration was 14.9 months. The overall technical success rate was 92.9% (95% confidence interval [CI]: 84.5-96.9%), with low-to-moderate heterogeneity. Target vessel patency was 96.9% (95% CI: 93.6-98.5%). Early mortality was 5.5% (95% CI: 2.1-13.3%). The incidence of endoleaks was 13.3% (95% CI: 5.8-27.4%), with significant heterogeneity among studies. Reinterventions were reported in 6.6% of patients (95% CI: 2.3-17.5%). CONCLUSION: The results indicate that PMSG procedures planned with three-dimensional techniques are associated with a high rate of technical success and preserved patency of target vessels in patients with complex aortic pathology. The observed variability in endoleak and reintervention rates likely reflects differences in anatomical complexity and patient selection among studies. Further prospective studies are needed to confirm long-term outcomes.

Humans↗

PubMed2026

Nerve injury in revision total elbow arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Revision total elbow arthroplasty (TEA) is technically demanding and carries a substantial risk of postoperative neurological complications because of scarring, altered anatomy, implant removal, and repeated humeral and ulnar exposure. The incidence, nerve distribution, and recovery profile of nerve injury after revision TEA remain incompletely defined. This study aimed to systematically review the literature to define the incidence, recovery profile, and risk factors for nerve injury after revision TEA. METHODS: A systematic review of the literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. Thirteen retrospective case series were included, comprising 282 revision TEAs in 271 patients. Random-effects meta-analysis of proportions was undertaken where the data permitted. The primary outcome was postoperative nerve injury following revision TEA. Secondary outcomes included nerve type, recovery, secondary nerve-related procedures, infection, triceps insufficiency, metallosis, periprosthetic fracture, and re-revision. RESULTS: The pooled incidence of postoperative nerve injury was 22.3% (95% confidence interval [CI] 16.3 to 29.6; I2 = 34.6%). The crude incidence was 60 of 282 revisions (21.3%, 95% CI 16.6 to 26.5). The ulnar nerve was involved in 66.7% of all nerve injuries, the radial nerve in 31.7%, and the median nerve in 1.7%. No significant difference in pooled nerve-injury incidence was identified between studies published before 2010 and those published from 2010 onwards (22.9% vs. 21.4%, P = .837). Recovery reporting was heterogeneous; among injuries with numerically extractable outcomes, 85.4% improved partially or completely (95% CI 72.2 to 93.9). Secondary nerve-related procedures were reported in 7 studies. Pooled complication estimates were 10.2% for infection, 13.6% for triceps insufficiency, 25.5% for metallosis, 15.9% for periprosthetic fracture, and 14.0% for re-revision. CONCLUSIONS: Postoperative nerve injury is a common and clinically important complication of revision TEA, affecting approximately 1 in 5 cases. The ulnar nerve is most frequently involved, although radial nerve injury accounts for a substantial proportion of cases. Many neuropathies improve during follow-up, but persistent deficits and the need for secondary nerve-related procedures are not uncommon. Future studies should adopt standardized neurological definitions and reporting to improve comparability and guide preventive surgical strategies.

Humans↗

PubMed2026

Cardiovascular risks in psychiatric disorders and psychiatric risks in cardiovascular disorders: implications for prevention and clinical management - a large-scale umbrella review encompassing 76 meta-analyses.

OBJECTIVE: Psychiatric and cardiovascular disorders often co-occur, complicating their assessment and management. No umbrella review(UR) has summarized the meta-analytic evidence on the co-occurrence of psychiatric and cardiovascular disorders and assessed its credibility. METHODS: Meta-analytic systematic reviews of observational studies documenting the prevalence, risk factors, and outcomes associated with the co-occurrence of cardiovascular and psychiatric disorders, indexed from inception through March.16.2026, and meeting established diagnostic criteria, were included. Meta-analytic association and prevalence estimates were recalculated and graded based on established or adapted criteria. The AMSTAR-2 assessed the quality of the meta-analyses, while several subgroup analyses and meta-regressions aimed to explain the heterogeneity. RESULTS: We included 76 meta-analyses yielding 131 meta-analytic estimates. Based on pre-existing meta-analytic evidence, 22/24 prevalence estimates (91.7%) met moderate/strong credibility criteria. Strong credibility emerged for: orthostatic hypotension in Lewy body(58%;95%C.I. = 50-66%) and Alzheimer's dementias(28.0% = 95%C.I. = 17.0-40.0%); pericardial effusion in anorexia nervosa(25.0%;95%C.I. = 17.0-34.0%); in heart failure(HF): major depressive disorder(MDD)(41.9%;95%C.I. = 36.7-47.1%), mild cognitive impairment(MCI)(41.4%;95%C.I. = 38.3-45.6%), anxiety(32.0%;95%C.I. = 26.5-37.6%), MDD + anxiety(24.7%;95%C.I. = 17.9-34.3%), and dementia(19.8%;95%C.I. = 12.9-27.8%); in atrial fibrillation(AF): MCI(26.0%;95%C.I. = 21.0-30.0%), anxiety in patients undergoing pulmonary vein isolation(PVI)(25.0%;95%C.I. = 12.0-46.0%), MDD in PVI patients (20.0%;95%C.I. = 13.0-29.0%); in coronary artery disease: MDD + anxiety(19.8%;95%C.I. = 16.0-24.6%): in schizophrenia spectrum disorders: clozapine-associated-cardiomyopathy(0.6%;95%C.I. = 0.2-2.3%); clozapine-associated-cardiomyopathy absolute death rates (0.0003;95%C.I. = 0.0001-0.0012); clozapine-associated-cardiomyopathy case fatality rate (0.078;95%C.I. = 0.018-0.285). Several additional disorders were multimorbid in>5% of people, yet with a lower credibility rating. No re-pooled risk factors/outcomes reached strong credibility criteria. CONCLUSIONS: The present study provides an atlas of cardiovascular and psychiatric multimorbidity across varying levels of credibility, reinforcing the need for an integrated, multidisciplinary approach to patient care and for more research on actionable risk/protective factors and outcomes.

Humans↗

PubMed2026

Genetic regulation of CPEB3-mediated alternative polyadenylation associated with survival of patients with hepatocellular carcinoma.

BACKGROUND: Alternative polyadenylation (APA) is a key post-transcriptional mechanism that regulates gene expression by modulating 3'UTR length, its dysregulation has been implicated in carcinogenesis. How genetic variants influence APA to affect hepatocellular carcinoma (HCC) prognosis remains unclear. METHODS: Prognosis-APA quantitative trait loci (apaQTL) were performed using genotype and APA profiling from TCGA data. A two-stage survival analysis in 848 Chinese and 369 TCGA LIHC patients and functional validation were used to identify prognostic apaQTL in HCC progression. RESULTS: A total of 2,025 and 817 significant APA events were identified in Chinese and TCGA cohort, respectively. Besides, 859 events were associated with poor prognosis in HCC and enriched in RNA splicing / metabolism pathways. We detected 32,034 significant apaQTLs, predominantly enriched in 3'UTRs and RBP-binding regions. CPEB3 was prioritized as a key APA regulator RBP; its low expression correlated with poor patient survival and promoted proliferation, migration, and invasion in HCC cells. Notably, a functional apaQTL variant rs2037547, located in GSK3B and mediated by CPEB3, demonstrated a poor survival of HCC patients in both cohort (pooled HR=1.29, p=0.016). Mechanistically, rs2037547 promoted aberrant APA at proximal poly(A) sites of GSK3B through CPEB3, leading to increased expression of short 3'UTR isoform. This regulatory alteration enhanced HCC cell proliferation, invasion, and migration, and contributed to HCC progression. CONCLUSION: These findings elucidated the distinct role of apaQTL-mediated APA dysregulation in HCC prognosis, providing insights for prognostic stratification and potential targets for personalized therapy in HCC.

RNA-binding proteins↗

PubMed2026

Methylation profiling in CNS tumor diagnostics: a single-centre real-world experience from Central Europe.

Genome-wide DNA methylation profiling has transformed neuro-oncology by providing an objective, machine learning-based taxonomy that mitigates interobserver variability and refines the histo-molecular criteria of the current WHO classification. We evaluate the real-world diagnostic performance and clinical utility of this modality in a prospective, consecutively accrued three-year cohort of 291 central nervous system (CNS) tumors across a mixed adult-pediatric population. Successful profiling was completed in 95.9% of cases. Using the Epignostix classifier, a high-confidence diagnostic match (calibrated score [CS] ≥ 0.84) was achieved in 70.3% of analyzable samples, while 26.5% returned lower-confidence scores (≥ 0.3 to < 0.84) and only 3.2% remained completely unclassifiable (CS < 0.3). When integrated into a comprehensive diagnostic framework, methylation profiling provided clinically useful results in 81.1% of cases, establishing diagnoses in 70 cases submitted for molecular subclassification and resolving diagnostic uncertainty or prompting major revisions in 149 histologically challenging tumors. Within truly ambiguous lesions, integration of methylome data dictated tumor grade modifications in 38.8% of cases (upgrading in 29.4% and downgrading in 9.4%), shifting patient risk stratification. Crucially, over half (52.7%) of the lower-confidence cases yielded meaningful clinical integration when supported by histomorphology and ancillary genetic or immunohistochemical markers, demonstrating that rigid score cutoffs should not dictate assay failure. Discrepant or misleading classifications occurred in 1.9%. Updating bioinformatic pipelines from version 11b4 to 12.8 rescued multiple ambiguous entries, increasing overall clinical utility to 84.1%. These findings demonstrate that integrating computational epigenomics with classical neuropathology enhances diagnostic precision, while highlighting the ongoing need for careful clinical-pathological correlation.

Central nervous system tumors↗

PubMed2026

Bipolar circumcision with mucocutaneous plane separation: A safe, precise, blood-sparing, dressing-free approach.

Conventional circumcision techniques may result in bleeding, limited control of the mucosal collar, and the need for dressings. We describe a modified bipolar technique enabling near-bloodless dissection with precise mucosal trimming. Following bipolar division of the preputial skin, the inner mucosa is separated using two forceps and retracted proximally, creating a protective plane for safe skin adjustment. The mucosal collar is trimmed with scissors. The wound is closed with sutures and 2-octyl cyanoacrylate, avoiding dressings. This technique has been performed in 55 consecutive cases (median age: 2 years and 2 months; range: 0 days-17 years and 5 months) with no reported complications over a median follow-up of 2 years and 7 months (range: 3 months-4 years and 1 month).

Humans↗