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PubMed2026

Real-World Efficacy and Safety of Standard-of-Care Chimeric Antigen Receptor T-Cell (CART) and Bispecific T-Cell Engager (TCE) Therapies in Relapsed/Refractory Multiple Myeloma (RRMM).

We aimed to evaluate the real-world (RW) efficacy and safety of standard-of-care CART versus TCE therapies in relapsed/refractory myeloma (RRMM), to assess utilization, outcomes, and tolerability of these therapies in a RW oncology in the US. Data were derived from the US-based, electronic health record-derived deidentified Flatiron Health Research Database, 2021-2024. A total of 419 patients (CART n = 220; TCE n = 199) with a confirmed diagnosis of myeloma who received CART or TCE as a standard-of-care treatment after at least 2 prior lines of therapy were included. Patients in the CART cohort were younger, had better ECOG PS, and a higher receipt of a prior autologous stem cell transplant versus bispecific TCE cohort. In CART versus TCE cohort, the overall response rates (ORR) were 83.3% versus 66.3%, median duration of response 7.9 months versus 4.3 months, progression free survival (PFS) 13.6 months versus 10.5 months, and overall survival (OS) of 29.8 months versus 21.9 months, respectively. A higher percentage of hematologic toxicity, infections, and cytokine release syndrome (CRS) were noted in the CART versus TCE cohort. This study provides insights on the RW effectiveness of CART versus TCE in the treatment of RRMM; highlights the differences in patient selection, clinical responses, treatment duration, and toxicity profiles.

CART↗
PubMed2026

Novel non-contrast computed tomography parameters for predicting spontaneous stone passage and surgical requirement in ureteral stones: The role of ureteral wall thickness and dilatation ratio.

We investigated the predictive value of standard non-contrast computed tomography (NCCT) measurements, the ureteral dilatation ratio (DDR) and intraluminal urine stasis markers, for spontaneous stone passage (SSP) versus surgical intervention in patients with ureteral stones. We also evaluated ureteral wall thickness (UWT) as a practical clinical marker. This retrospective study included 461 patients diagnosed with ureteral stones via NCCT. Patients were categorised into two groups based on clinical outcomes: the spontaneous passage group (MET; n&#x2009;=&#x2009;229) and the endoscopic surgery group (URS; n&#x2009;=&#x2009;232). Stone volume, stone density (HU), UWT, DDR and intraluminal urine attenuation values were measured for all patients. Independent risk factors were identified using a multivariate logistic regression model and clinical cut-off values were determined via ROC curve analysis. Stone volume, density, UWT and hydronephrosis grade were all significantly higher in the URS group. Multivariate regression analysis revealed that increased UWT (OR: 5.03, 95% CI: 3.66-6.90; p&#x2009;<&#x2009;0.001) was the strongest independent predictor of surgery. Higher DDR (OR: 1.88; p&#x2009;=&#x2009;0.003), advanced hydronephrosis, stone volume, and density also increased surgical risk. A UWT cut-off &#x2265;&#x2009;2.97&#xa0;mm predicted surgery with 84.8% sensitivity and 84.3% specificity (AUC: 0.872). A DDR cut-off >&#x2009;1.79 yielded 81.7% specificity and 40.4% sensitivity. UWT weakly correlated with stone volume (r&#x2009;=&#x2009;0.145), indicating wall thickening reflects an inflammatory response rather than a mere mechanical consequence. UWT is a superior predictor of SSP failure, supported by increased DDR as a highly specific complementary risk factor. These parameters could help clinicians to identify patients who would benefit from early surgical counselling and intervention rather than prolonged conservative management.

Humans↗
PubMed2026

Unraveling a Diagnostic Enigma: A TECPR2 Case Solved Through Multi-Omic Genomics.

TECPR2 is a key regulator of autophagy, encoded by the TECPR2 gene. Pathogenic variants in this gene have been linked to a rare hereditary sensory and autonomic neuropathy with intellectual disability (HSAN9). We report a teenage female with a syndromic intellectual disability disorder associated with neuromuscular abnormalities. Multi-omics analysis including genomics, transcriptomics, and proteomics, together with muscle biopsy from the affected individual, were used in this clinical case. Through trio exome sequencing we identified two heterozygous variants in the TECPR2 gene, NM_014844.4: c.480G>A; p.(Gln160=) and c.2846C>A; p.(Ala949Glu). Both were classified as variants of uncertain significance due to the lack of supporting evidence for pathogenicity. Subsequent long-read sequencing phased the variants and confirmed they were in trans. Additional functional studies using RNAseq and proteomics analyses verified the pathogenicity of the variants. This case study demonstrated the value of a multi-omics assisted analysis, which complemented the traditional phenotype-first approach in reaching a definitive clinical diagnosis.

Humans↗
PubMed2026

ATF4-histone 2-hydroxyisobutyrylation feedback loop drives sepsis-induced inflammation.

BACKGROUND AND PURPOSE: The role and mechanisms of lysine 2-hydroxyisobutyrylation (Khib) in the acute inflammatory phase of sepsis remain unclear. We investigated the function and underlying mechanisms of histone H4 lysine 5 2-hydroxyisobutyrylation (H4K5-hib) in sepsis-induced inflammation in vivo and in vitro. EXPERIMENTAL APPROACH: Acute sepsis was induced by caecal ligation and puncture (CLP) in mice, and inflammatory responses were modelled in lipopolysaccharide (LPS)-stimulated macrophages. CUT&Tag-seq was used to identify genomic targets associated with H4K5-hib and activating transcription factor 4 (ATF4). Immunofluorescence, Western blotting, qPCR, dual-luciferase assays, and ELISA were performed to investigate the underlying mechanisms. KEY RESULTS: H4K5-hib levels were increased in macrophages during the acute inflammatory phase of sepsis. LPS stimulation enhanced H4K5-hib enrichment at the ATF4 promoter, thereby promoting ATF4 transcription. Inhibition of EP300-mediated 2-hydroxyisobutyrylation or mutation of H4K5 abolished ATF4 activation. Increased H4K5-hib activated the ATF4/NLRP3 signalling axis, promoting inflammasome assembly and amplifying inflammatory responses. ATF4 directly bound to the EP300 promoter and enhanced its transcription, forming a positive feedback loop that further increased H4K5-hib levels. In CLP-induced sepsis, pharmacological inhibition of EP300 or ATF4 reduced H4K5-hib levels and suppressed NLRP3 inflammasome activation. CONCLUSION AND IMPLICATIONS: These findings reveal a previously unrecognized epigenetic mechanism underlying sepsis-induced inflammation and identify the EP300/ATF4/H4K5-hib positive feedback loop as a potential therapeutic target for sepsis.

Animals↗
PubMed2026

Transabdominal lumbar approach (TALA) versus retroperitoneal approach for robot-assisted renal surgery: a prospective randomised controlled trial.

PURPOSE: Common robotic nephrectomy approaches access the kidney via transperitoneal (TP) or retroperitoneal (RP) routes, each with distinct trade-offs. We developed the transabdominal lumbar approach (TALA), combining advantages of both accesses with improved visualisation and strategic trocar placement, and compared it with conventional RP in a prospective randomised controlled trial using technique-oriented intraoperative endpoints. METHODS: In this single-centre, prospective, open-label RCT, 40 patients were randomised to TALA (n&#x2009;=&#x2009;18) or conventional RP (n&#x2009;=&#x2009;22). Eligible patients were &#x2265;&#x2009;18 years with a renal tumour or non-functional kidney requiring robot-assisted total or partial nephrectomy. Exclusions included prior surgery on the affected kidney, renal vein tumour thrombus, and pregnancy. Both groups were followed for 30 days. The primary endpoint was time from first skin incision to renal artery identification. RESULTS: TALA achieved a median time saving of 16&#xa0;min compared to conventional RP (38 vs. 54&#xa0;min, p&#x2009;=&#x2009;0.001). Perioperative safety was comparable between groups, with three patients (7.5%) experiencing Clavien-Dindo grade III-IV complications. CONCLUSIONS: TALA met its primary endpoint with a significantly shorter time to renal artery identification than conventional RP access, and improving perceived surgical exposure and instrument handling.

Humans↗
PubMed2026

ReMeDy: A Flexible Statistical Framework for Region-Based Detection of DNA Methylation Dysregulation.

Region-based epigenome-wide association studies have demonstrated improved statistical power and biological interpretability compared with probe-wise analyses of DNA methylation data. However, most existing region-based methods characterize methylation dysregulation primarily through changes in mean methylation levels associated with a phenotype of interest. Substantial evidence indicates that phenotype-associated methylation alterations may also manifest through changes in methylation variability or through joint shifts in mean and variability. Despite this, no existing statistical framework jointly models mean-variance methylation changes in a region-based manner. We propose ReMeDy, a flexible statistical framework that uses a hierarchical likelihood approach within a generalized linear model setting to identify differentially methylated regions, variably methylated regions, and regions exhibiting joint differential and variable methylation at a genome-wide scale. Unlike existing models, ReMeDy operates directly on biologically defined co-methylated regions, allowing it to naturally capture spatial correlation inherent in DNA methylation array data, while avoiding reliance on heuristic, user-defined tuning parameters such as smoothing spans and kernel bandwidths that can substantially influence results and introduce subjectivity. Through extensive simulation studies and comprehensive benchmarking against popular models, we demonstrate that ReMeDy maintains false discovery and Type-I error rates at nominal levels while achieving consistently higher statistical power across a wide range of realistic scenarios. Application to population-level DNA methylation data further shows that ReMeDy identifies biologically meaningful regions and pathways implicated in complex human diseases that are not captured by conventional mean-based analyses alone. ReMeDy is implemented as an open-source R package and is freely available at https://github.com/SChatLab/ReMeDy.

DNA Methylation↗
PubMed2026

Effects of Family-Based Intervention for Childhood Obesity on Parental and Offspring Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Childhood obesity is a global public health issue with strong familial and intergenerational transmission. However, existing syntheses often overlook the active role of parents and fail to assess outcomes beyond the child. This systematic review and meta-analysis specifically investigate the effects of family-based interventions, which position parents as active co-agents of change, on health outcomes for both children with obesity and their parents. METHODS: A systematic review and meta-analysis were conducted. Six databases were searched for randomized controlled trials (RCTs) targeting children with obesity and at least one family member. Primary outcomes were children's BMI z-score and parental BMI; secondary outcomes included other adiposity measures and dietary behaviors. Outcomes for both children and parents were synthesized. Subgroup analyses were conducted based on intervention characteristics. Risk of bias was assessed using RoB 2, and evidence certainty was evaluated using GRADE. RESULTS: Twenty RCTs with 1740 participants were included in the meta-analysis. The interventions demonstrated a significant reduction in children's BMI z-score. Additional benefits were observed for long-term BMI z-score and percentage of total body fat. The most effective interventions commonly integrate health education, behavioral strategies, and motivational support. Subgroup analyses indicated that interventions positioning parents as active co-participants, rather than mere supporters, yielded larger effects. However, no significant effects were found on parental BMI. CONCLUSION: This study demonstrates that family-based interventions can confer significant benefits for children with obesity. Their success hinges on strategically framing parents as active co-agents and integrating motivational strategies.

Humans↗
PubMed2026

A stent-plus-irrigation protocol after adolescent hypospadias repair: a multicentre randomised controlled trial.

OBJECTIVES: To evaluate whether a stent-plus-irrigation protocol reduces complication rates following hypospadias repair in adolescents compared with catheter drainage alone. PATIENTS AND METHODS: In this multicentre randomised controlled trial, adolescents (Tanner Stage II-V) undergoing hypospadias repair were randomly assigned to either a stent-plus-irrigation group or a catheter-drainage group. The catheter-drainage group received standard urethral catheter drainage alone, whereas the stent-plus-irrigation group received an additional small-calibre urethral stent positioned within the reconstructed urethra and twice-daily saline irrigation. The primary outcome was the overall postoperative complication rate; secondary outcomes included urinary function and cosmetic outcomes. RESULTS: A total of 172 adolescents were assessed for eligibility, with 150 participants (75 in the stent-plus-irrigation group and 75 in the catheter-drainage group) included in the final analysis. Compared with the catheter-drainage group, the stent-plus-irrigation group demonstrated a significantly lower overall complication rate (risk ratio [RR] 0.33, 95% confidence interval [CI] 0.20-0.56; P&#x2009;<&#x2009;0.001), urethral fistula rate (RR 0.27, 95% CI 0.14-0.51; P&#x2009;<&#x2009;0.001), and surgical site infection (SSI) rate (RR 0.43, 95% CI 0.21-0.87; P&#x2009;=&#x2009;0.020). CONCLUSIONS: A postoperative stent-plus-irrigation protocol was associated with lower rates of postoperative complications, particularly urethral fistula and SSI, compared with catheter drainage alone after adolescent hypospadias repair. Because the intervention included both an additional urethral stent and saline irrigation, the independent contribution of irrigation cannot be determined in this two-arm trial.

Humans↗
PubMed2026

Oliceridine used for patient-controlled analgesia on postoperative quality of recovery in patients undergoing laparoscopic gynecological tumour resection: a randomized clinical trial.

BACKGROUND: Oliceridine, a novel biased &#x3bc;-opioid receptor agonist, is widely used perioperatively, yet limited data exists regarding its impact on postoperative quality of recovery. This study investigated the effect of oliceridine-based&#xa0;patient-controlled intravenous analgesia (PCIA) on postoperative quality of recovery among patients undergoing laparoscopic gynecological tumour resection. METHODS: Ninety&#x2011;four female patients scheduled for elective laparoscopic gynecological tumour resection were included. Patients were randomized to two groups: oliceridine group (loading dose 1.5&#x2009;mg, PCIA 0.55&#x2009;mg/kg) or sufentanil group (loading dose 10&#x2009;&#x3bc;g, PCIA 3&#x2009;&#x3bc;g/kg). The primary outcome was the Quality of Recovery-40 (QoR-40) score on postoperative day 1. The secondary outcomes included the QoR-40 score, the numeric rating scale (NRS) pain score, the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) score, the Fatigue, Resistance, Ambulation, Illness and Loss of weight (FRAIL) index and adverse events within 3 postoperative days. RESULTS: Higher QoR-40 scores were found in the oliceridine group on postoperative day 1 (182.9&#x2009;&#xb1;&#x2009;3.1 versus 177.5&#x2009;&#xb1;&#x2009;3.9, p&#x2009;<&#x2009;0.001). Compared with the sufentanil group, the oliceridine group showed better QoR-40 scores within 3&#x2009;days after operation. No significant differences were observed in NRS pain scores or HADS-A scores between the two groups (all p&#x2009;>&#x2009;0.05). However, the median FRAIL score in the oliceridine group was lower on postoperative day 2 (p&#x2009;=&#x2009;0.018). CONCLUSION: Oliceridine used in PCIA improves early postoperative recovery quality of patients undergoing laparoscopic gynecological tumour resection. It provides analgesic effect comparable to sufentanil and lowers incidences of postoperative frailty, nausea and vomiting. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR.org.cn, identifier: ChiCTR2400094271.

Humans↗
PubMed2026

Low Carbohydrate Availability in Energy Balance Alters Bone Turnover and Muscle Proteomic Response With Limited Endocrine Disruption.

Training with low carbohydrate availability (LCA) has been proposed as an independent determinant of physiological perturbations commonly attributed to low energy availability (LEA) and to increase skeletal muscle oxidative machinery, yet the effects of LCA in isolation from LEA remain unclear. We examined whether short-term carbohydrate restriction under energy balance alters endocrine and metabolic markers associated with LEA and skeletal muscle proteomic response. In a randomized crossover design, eight trained males completed 4&#x2009;days of either a low-carbohydrate high-fat diet (LOW; 12% carbohydrate, 69% fat, 19% protein) or a normal-carbohydrate diet (NORM; 62% carbohydrate, 19% fat, 19% protein), while undertaking daily cycloergometer exercise (15&#x2009;kcal kg FFM-1 day-1) and maintaining energy availability at 45&#x2009;kcal kg FFM-1 day-1. LOW induced a clear metabolic shift consistent with LCA, evidenced by elevated circulating free fatty acids, glycerol and &#x3b2;-hydroxybutyrate, in fasting conditions and fat oxidation at rest and during exercise, alongside reduced exercise glucose concentrations. Despite these responses, LOW did not alter insulin, testosterone, triiodothyronine, leptin, hepcidin, or P1NP. In contrast, &#x3b2;-CTX increased and IGF-1 decreased relative to NORM. Muscle glycogen concentration decreased only in LOW (40%&#x2009;&#xb1;&#x2009;14%). Proteomic analysis identified 671 proteins; 57 differentially expressed in LOW relative to NORM were limited to fatty acid metabolism pathways and suppression of ribosomal, sarcomeric, and extracellular matrix proteins. These findings indicate that isolated LCA exerts limited endocrine disruption but may selectively compromise bone turnover and muscle anabolic response, suggesting that without acute LEA, LCA has limited influence on muscle oxidative phenotype.

Male↗
PubMed2026

Accelerated Diagnostic Pathways for Suspected Acute Coronary Syndrome in Practice: A Randomized Trial of 0/1-Hour vs 0/3-Hour Troponin Testing.

BACKGROUND: For suspected acute coronary syndrome (ACS), guidelines recommend using high-sensitivity troponins (hs-cTn) in accelerated diagnostic pathways (ADPs) with 0/1-hour recommended over 0/3-hour ADP. However, implementation of these ADPs, with universal use of hs-cTns, has not been directly compared in randomized trials OBJECTIVES: This study sought to compare the efficiency and safety of the European Society of Cardiology (ESC) 0/1-hour and a 0/3-hour ADP when implemented in real-world clinical practice. METHODS: This pragmatic, randomized, noninferiority implementation trial compared the safety and efficiency of clinician decision making using these 2 pathways. To prevent incorporation bias, an independent hs-cTnI was used for formal adjudication using the fourth universal definition of myocardial infarction (MI). Efficiency was judged by the proportion of patients discharged within 4 hours. The safety endpoint was major adverse cardiac events (MACE) within 30 days (adjudicated index or representation type 1 MI, cardiovascular death, and urgent coronary revascularization) for those who were considered not to have ACS and discharged. The noninferiority margin, for absolute difference in sensitivity, between the ESC 0/1-hour and the 0/3-hour ADP was set at 3%, assessed with a 1-sided 97.5% CI. RESULTS: From December 2021 to July 2024, of 13,983 screened 3,543 individual patients with suspected ACS were recruited and consented from 2 major emergency departments in North-West England, with 100% follow-up achieved for all representations to any national hospital. The median age was 60 years (IQR: 49.5-70.5 years), 53% were men, 6.7%, and 7.6% had adjudicated index type 1 MI and MACE within 30 days, respectively. The turnaround time from sample to result for central laboratory hs-cTnT was 81 minutes (IQR: 69-101 minutes). The proportion of patients discharged within 4 hours was relatively low and did not differ substantially (21.8% vs 19.2%, P = 0.07). In addition, the 0/1-hour pathway was noninferior for safety, in patients discharged, compared with the 0/3-hour pathway, absolute difference in sensitivity was +4.2% (1-sided 97.5% CI: -2.5) in favor of the 0/1-hour pathway. The calculated sensitivities were 93.7% (95% CI: 88.4%-97.1%) vs 89.5% (95% CI: 82.7%-94.3%), respectively. CONCLUSIONS: Implementation of the ESC 0/1-hour pathway failed to discharge significantly more patients within 4 hours of presentation compared with the 0/3-hour ADP. In addition, The ESC 0/1-hour was noninferior to the 0/3-hour hs-cTn pathway for safety of discharge, although safety for both pathways was less than that imputed by observational studies. This trial demonstrates that perceived benefits to emergency department efficiency of a reduced sampling interval are mitigated by central laboratory turnaround times as well as system constraints. (Pragmatic Randomised Trial of the ESC 0/&#x200b;1 Versus 0/&#x200b;3 Hour Troponin Pathway [MACROS2]; NCT05322395).

Acute Coronary Syndrome↗
PubMed2026

Efficacy and Safety of Mechanical Insufflation-Exsufflation in Invasively Ventilated Critically Ill Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Mechanical insufflation-exsufflation (MI-E) is increasingly used in invasively ventilated adults in the intensive care unit (ICU), yet its therapeutic efficacy and safety remain uncertain due to inconsistent evidence. AIM: To synthesize evidence on the clinical efficacy and safety of MI-E in this population and to examine methodological and clinical heterogeneity underlying reported outcomes. STUDY DESIGN: A systematic review and meta-analysis of randomized studies (including RCTs and randomized crossover trials), conducted following PRISMA guidelines, with risk of bias assessed using the Cochrane risk-of-bias tool. RESULTS: Five randomized controlled trials involving 310 patients were included. Meta-analysis showed that mechanical insufflation-exsufflation (MI-E) significantly increased sputum clearance (SMD&#x2009;=&#x2009;0.63, 95% CI, 0.32-0.93; p&#x2009;<&#x2009;0.00011; I2&#x2009;=&#x2009;38%) without affecting oxygenation (MD&#x2009;=&#x2009;0.28, 95% CI, -0.53 to 1.09; p&#x2009;=&#x2009;0.50; I2&#x2009;=&#x2009;9%). Data on respiratory mechanics, ventilation duration and ICU stay could not be pooled. No serious adverse events were reported. CONCLUSIONS: MI-E significantly improves sputum clearance in invasively ventilated critically ill adults, with no severe adverse events reported in the included studies. Its effects on other outcomes remain inconclusive due to limited data and heterogeneity. Standardized protocols and larger trials are needed. RELEVANCE TO CLINICAL PRACTICE: Clinicians may consider MI-E as an adjunct for respiratory secretion management. Application should be guided by structured patient assessment and individualized parameter adjustment. Future research should standardize interventions and target well-defined patient subgroups to inform clear practice guidelines. TRIAL REGISTRATION: The review protocol was registered in the International Prospective Register of Systematic Reviews, with registration number CRD42023403299.

Humans↗
PubMed2026

Vancomycin Effectiveness in Reducing Surgical Site Infection in Posterior Spinal Fusion Surgery: A Retrospective Data Analysis of the STRIVE Trial.

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVE: To re-evaluate vancomycin as a preventive measure for surgical site infection (SSI). SUMMARY OF BACKGROUND DATA: Intrawound vancomycin powder is used to prevent SSIs in spinal surgery. Prior studies, often limited to single institutions or small samples, have shown mixed efficacy and potential increases in non- S. aureus and Gram-negative infections. We hypothesized that SSIs rates would be similar with and without intrawound vancomycin in posterior spinal fusion (PSF) surgery. METHODS: Prospectively collected data from the 3595 patients in the STaphylococcus aureus suRgical Inpatient Vaccine Efficacy (STRIVE) trial were stratified by intrawound antibiotic usage. Multivariate logistic regression assessed the effect of vancomycin use on SSI, adjusting for patient demographics and SSI-associated risk factors. Secondary outcomes included critical care stay, reoperation, sepsis, and hospital readmission. RESULTS: Of 3311 patients who underwent surgery, 847 (26%) received only intrawound vancomycin and 1534 (46%) received no intrawound antibiotics. Sixty (8%) patients developed postoperative SSI, of whom 20 (33%) had received intrawound vancomycin. Receiving intrawound vancomycin was not associated with SSI incidence versus no intrawound antibiotics [odds ratio (OR): 0.77; 95% CI: 0.42-1.42], critical care stay (OR: 0.94; 95% CI: 0.78-1.12), or sepsis (OR: 2.04; 95% CI: 0.62-6.73). However, intrawound vancomycin was associated with increased odds of hospital readmission (OR: 1.82; 95% CI: 1.28-2.6; P < 0.001) and reoperation (OR: 1.75; 95% CI: 1.18-2.6; P = 0.005). Factors significantly associated with intrawound vancomycin use included intraoperative antibiotic readministration (OR: 2.97; 95% CI: 1.36-6.5; P =0.006) and hospital location, lower odds in Europe (OR: 0.13; 95% CI: 0.06-0.29; P < 0.001) or Asia (OR: 0.02; 95% CI: 0-0.08; P < 0.001) versus North America. CONCLUSIONS: Intraoperative vancomycin use was not associated with reduced SSI incidence compared with no intrawound antibiotics after PSF surgery. LEVEL OF EVIDENCE: Level II.

Humans↗
PubMed2026

Extended Venous Thromboembolism Prophylaxis After One-Anastomosis Gastric Bypass: A Three-Arm Randomized Trial of Enoxaparin Duration and Rivaroxaban.

BACKGROUND: Venous thromboembolism (VTE) is a serious but preventable complication after bariatric surgery, most of them after hospital discharge. The optimal regimen and duration of post-discharge prophylaxis, particularly the role of direct oral anticoagulants, remain uncertain. OBJECTIVES: To estimate 30-day VTE and bleeding event rates in high-risk patients undergoing one-anastomosis gastric bypass who received 15-day enoxaparin, 30-day enoxaparin, or 30-day rivaroxaban prophylaxis, and to perform exploratory comparisons among the regimens. METHODS: In this randomized, open-label, three-arm clinical trial, high-risk adults undergoing laparoscopic OAGB were randomized before discharge (1:1:1) to enoxaparin 40&#xa0;mg subcutaneously twice daily for 15 days, enoxaparin 40&#xa0;mg twice daily for 30 days, or rivaroxaban 10&#xa0;mg orally once daily for 30 days, after standardized in-hospital enoxaparin and early ambulation. Participants underwent clinical assessment and duplex ultrasonography of the lower-limb and porto-mesenteric veins on postoperative days 15 and 30. The primary outcome was objectively confirmed VTE within 30 days. Bleeding was classified as International Society on Thrombosis and Haemostasis (ISTH) major bleeding or clinically relevant non-major bleeding (CRNMB). Because the expected event rate was low and no non-inferiority or equivalence margin was prespecified, comparisons were interpreted as exploratory. RESULTS: A total of 288 patients were randomized to 15-day enoxaparin (n&#x2009;=&#x2009;97), 30-day enoxaparin (n&#x2009;=&#x2009;97), or 30-day rivaroxaban (n&#x2009;=&#x2009;94). One symptomatic lower-limb deep vein thrombosis occurred in the 15-day enoxaparin group (1.0%; 95% CI, 0.03%-5.6%); no VTE events occurred in the 30-day enoxaparin group (0%; 95% CI, 0%-3.7%) or the rivaroxaban group (0%; 95% CI, 0%-3.8%). Total bleeding occurred in 4/97 patients (4.1%) in each enoxaparin group and 8/94 patients (8.5%) in the rivaroxaban group. The absolute difference in total bleeding between rivaroxaban and 30-day enoxaparin was 4.4% points (95% CI, -&#x2009;2.9 to 12.2), indicating substantial imprecision. No porto-mesenteric venous thrombosis was detected. CONCLUSION: Only one VTE event occurred, precluding reliable conclusions regarding comparative efficacy or prophylaxis duration. Bleeding estimates were also imprecise and do not establish comparative safety or equivalence between rivaroxaban and enoxaparin. The trial adds descriptive event-rate data from a standardized OAGB pathway, but larger multicenter studies with prespecified comparative hypotheses and assessment of adherence, oral tolerance, and drug exposure are required. The study was approved by the Research Ethics Committee and registered at ClinicalTrials.gov.

Humans↗
PubMed2026

Predictors of Efficacy Maintenance After Vunakizumab Discontinuation in Patients With Moderate-to-Severe Plaque Psoriasis: A Post Hoc Analysis of a Randomized Controlled Trial.

BACKGROUND: Efficacy cannot be maintained in some psoriasis patients after biological discontinuation. This study aimed to explore predictors of efficacy maintenance after vunakizumab discontinuation in patients with moderate-to-severe plaque psoriasis. METHODS: This post hoc analysis used data from a phase III trial (NCT04839016); 291 patients with moderate-to-severe plaque psoriasis who achieved 100% improvement in Psoriasis Area and Severity Index (PASI) score at Week 52 were enrolled. Efficacy maintenance was defined as patients who maintained PASI 90 or PASI 100 after 20&#x2009;weeks of vunakizumab discontinuation. RESULTS: There were 44.7% and 72.5% of patients with PASI 100 and PASI 90 maintenance, respectively. In the multivariate logistic regression model, body mass index (BMI) (odds ratio [OR]&#x2009;=&#x2009;0.922, p&#x2009;=&#x2009;0.024) and treatment interruption (OR&#x2009;=&#x2009;0.550, p&#x2009;=&#x2009;0.020) were independently associated with a lower possibility of PASI 100 maintenance; however, the association of family history of psoriasis and the first time of PASI 100 achievement with PASI 100 maintenance did not achieve statistical significance. Duration of psoriasis (OR&#x2009;=&#x2009;0.972, p&#x2009;=&#x2009;0.049) and treatment interruption (OR&#x2009;=&#x2009;0.257, p&#x2009;<&#x2009;0.001) were independently associated with a lower possibility of PASI 90 maintenance. Two nomograms for predicting PASI 90 and PASI 100 maintenance were constructed based on the multivariate models, which disclosed good calibration performance. CONCLUSIONS: PASI 90 and PASI 100 maintenance rates are 72.5% and 44.7% after 20&#x2009;weeks of vunakizumab discontinuation in patients with moderate-to-severe plaque psoriasis. BMI, treatment interruption, and duration of psoriasis predict a lower possibility of efficacy maintenance after vunakizumab discontinuation.

Humans↗
PubMed2026

Percutaneous left ventricular assist device in cardiogenic shock associated with and without acute myocardial infarction: a real-world retrospective cohort study.

BACKGROUND: Percutaneous left ventricular assist devices (pLVAD, such as Impella), are increasingly used for cardiogenic shock (CS). Outcomes may differ between acute myocardial infarction-related CS (AMI-CS) and non-AMI CS due to differing pathophysiology and trajectories. METHODS: Using the USA TriNetX Network (2016-2024), we identified adults with CS treated withpLVAD. AMI-CS was defined by MI within seven days of implantation; non-AMI CS included all patients with CS not attributable to acute MI, representing heterogeneous etiologies such as decompensated cardiomyopathy, myocarditis, valvular failure, pulmonary vascular causes, and arrhythmic shock. Patients with recent coronary artery bypass graft (CABG) were excluded. Propensity matching produced two balanced cohorts (n&#x2009;=&#x2009;2,026 each). RESULTS: Among 6,873 AMI-CS and 4,521 non-AMI CS patients, matched groups were similar (mean age 63&#x2009;years, 26% female). AMI-CS had higher mortality at 30&#x2009;days (hazard ratio [HR] 1.19, p&#x2009;=&#x2009;0.002), 90&#x2009;days (HR 1.13, p&#x2009;=&#x2009;0.02), and 180&#x2009;days (HR 1.14, p&#x2009;=&#x2009;0.007). Heart failure (HF) exacerbations (HR 1.21, p&#x2009;<&#x2009;0.001) and pulmonary edema (HR 1.23, p&#x2009;=&#x2009;0.005) were also more common in AMI-CS. Stroke, ventricular arrhythmias, cardiac arrest, acute kidney injury, major bleeding, vascular complications, and hemodialysis were comparable. CONCLUSION: AMI-CS patients supported with pLVAD experienced higher mortality and greater HF-related morbidity than non-AMI CS.

Humans↗
PubMed2026

Nasopharyngeal Carriage Rate, Risk Factors, and Co-Resistance Patterns of Methicillin-Resistant Staphylococcus aureus in Ethiopia: Systematic Review and Meta-Analysis.

Methicillin-resistant Staphylococcus aureus (MRSA) nasopharyngeal carriage is a major global health concern linked to severe infections and transmission. However, comprehensive evidence on the burden of MRSA carriage, antimicrobial resistance, and associated risk factors in Ethiopia remains limited. This study aimed to estimate pooled prevalence, resistance pattern, and determinants of nasopharyngeal MRSA carriage. PubMed, ScienceDirect, Scopus, Web of Science, Google Scholar, and gray literature were searched for cross-sectional studies published between January 2015 and December 2025. Two groups of reviewers screened studies based on predefined criteria. The risk of bias was assessed using the Joanna Briggs Institute tool. Pooled prevalence and resistance proportions were estimated using a random-effects model, and pooled odds ratios (ORs) were calculated using the Mantel-Haenszel method. Heterogeneity and publication bias were assessed, and a sensitivity analysis was conducted. A total of 1040 records were identified, and 20 studies (6869 participants) were included. The pooled carriage prevalence was 7.3% (95% CI, 5.0-10.8), with substantial heterogeneity (I2&#x2009;=&#x2009;95.5%). Resistance was highest to tetracycline (55.75%) and lowest to clindamycin (12.66%). Increased odds of carriage were associated with prior hospitalization (OR, 3.49) and antibiotic use (OR, 2.35). Inconsistent variable coding across included studies limited the inclusion of other potential risk factors. Evidence of publication bias was detected, suggesting that the pooled prevalence should be interpreted with appropriate caution. The findings indicate a considerable burden of MRSA and highlight the need for strengthened antimicrobial stewardship, improved surveillance, and targeted prevention efforts in higher-risk populations. This review was registered in PROSPERO (CRD420251047192).

Ethiopia↗