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PubMed2026

Risk factors of venous thromboembolism in ICU patients: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to identify risk factors associated with the development of VTE in patients admitted to the intensive care unit (ICU). METHODS: A systematic literature search was conducted via PubMed, Embase, Web of Science, and Cochrane databases up to 25 April 2025, to identify studies examining the association between risk factors and the occurrence of venous thromboembolism (VTE) in ICU patients. Data were pooled using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 2465 relevant studies were identified through the systematic search, of which 30 were included in the meta-analysis. The pooled data showed that the following were significant risk factors for venous thromboembolism (VTE) in ICU patients: central venous catheterization (OR = 2.67, 95% CI: 1.67-4.28; I2 = 28%), invasive mechanical ventilation (OR = 2.08, 95% CI: 1.46-2.96; I2 = 0%), advanced age (OR = 2.06, 95% CI: 1.28-3.31; I2 = 86%), length of ICU stay (OR = 4.24, 95% CI: 1.43-12.57; I2 = 98%), malignancy (OR = 2.30, 95% CI: 1.03-5.12; I2 = 67%), elevated D-dimer levels (OR = 2.46, 95% CI: 1.37-4.40; I2 = 34%), and a history of VTE (OR = 2.84, 95% CI: 1.45-5.55; I2 = 51%). According to the GRADE assessment, the quality of evidence was rated as moderate for invasive mechanical ventilation, low for central venous catheterization and D-dimer levels, and very low for the remaining factors. CONCLUSION: Invasive mechanical ventilation, central venous catheterization, and elevated D-dimer levels are associated with VTE risk, supported by relatively high-quality evidence. These findings may help identify ICU patients at higher risk of VTE, inform the development of risk assessment models for patient stratification, and ultimately contribute to improved prognosis through optimal screening and management strategies.

Humans↗

PubMed2026

Comparative safety of lipid-lowering drugs alone or in combination: insights from a systematic review and network meta-analysis.

BACKGROUND AND AIMS: Although the safety profile of lipid-lowering therapies (LLTs) is known, there are no comprehensive comparative assessments. We aimed to compare the risk of muscle-related events, diabetes, liver dysfunction, and cognitive disorders among LLTs through a network meta-analysis. METHODS AND RESULTS: Databases were searched from inception to May 2025. Eligible studies included adult patients, using statins, ezetimibe, PCSK9 monoclonal antibodies (PCSK9mAbs), inclisiran, bempedoic acid, or their combinations as intervention, reporting the information about any of the selected adverse events, a total sample size of ≥200 subjects, and had ≥1 month of intervention. Pooled estimates were assessed by fixed effects model within a frequentist setting. Pooled relative risks (RR) and their 95% confidence interval were estimated. A total of 303,397 subjects from 153 RCTs were included. Bempedoic acid ranked the lowest risk of myalgia (vs PCSK9mAbs, RR 0.80 [0.69, 0.93]). PCSK9mAbs were associated with lower incidence of creatine kinase (CK) elevation, diabetes, and liver dysfunction comparing to statins (statins vs PCSK9mAbs, RR 1.44 [1.14, 1.81], RR 1.13 [1.05, 1.22], and RR 1.38 [1.17, 1.62], respectively). In terms of muscle-related events and cognitive disorders, no significant risk differences were found among treatments and their combinations. CONCLUSIONS: PCSK9mAbs appear to have a more favourable safety profile regarding the risk of CK elevation, diabetes, and liver dysfunction. Bempedoic acid seem to be a better choice for subjects with high risk of myalgia. This information can be valuable when selecting therapy for specific patient subgroups at higher risk of certain adverse events.

Humans↗

PubMed2026

Exercise for the mitigation of cancer therapy-related cardiac dysfunction in breast cancer patients treated with anthracyclines: a systematic review and meta-analysis.

PURPOSE: Cancer therapy-related cardiac dysfunction (CTRCD) is a significant concern for breast cancer patients undergoing anthracycline-based chemotherapy. Although exercise has been proposed as a cardioprotective strategy, existing reviews have largely examined heterogeneous cancer populations receiving varied treatments, leaving a gap in the evidence base focused exclusively on anthracycline-induced CTRCD. This systematic review and meta-analysis aimed to address that gap by evaluating the effects of long-term exercise on key CTRCD markers in breast cancer patients treated exclusively with anthracyclines. METHODS: A comprehensive search of PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science was conducted for randomized controlled trials including breast cancer patients undergoing anthracycline-based chemotherapy, receiving long-term exercise interventions (≥ 12 weeks, ≥ 1 session/week) compared to usual cancer care, and reporting at least one of the following outcomes: left ventricular ejection fraction, global longitudinal strain, cardiac troponin I, cardiac troponin T, or N-terminal prohormone of brain natriuretic peptide. RESULTS: Six randomized controlled trials involving 360 participants were included. Exercise significantly attenuated cardiac troponin I elevation compared to controls (SMD = -0.50; 95% CI, -0.93 to -0.06; p = 0.02). No statistically significant between-group differences were observed for left ventricular ejection fraction, global longitudinal strain, cardiac troponin T, or N-terminal prohormone of brain natriuretic peptide. CONCLUSION: The cardioprotective role of exercise during anthracycline treatment remains uncertain, though the attenuation of cardiac troponin I elevation suggests a potential protective signal warranting further investigation through larger, standardized trials employing advanced assessment modalities and longer follow-up periods.

Humans↗

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

Altered reproductive hormone profiles in systemic lupus erythematosus - A systematic review and meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) shows a marked female predominance during reproductive years, possibly suggesting hormonal factors in its pathogenesis. However, evidence regarding reproductive hormone alterations in SLE remains inconsistent. OBJECTIVES: To systematically review studies assessing reproductive hormone levels in adult SLE patients compared with healthy controls and across disease activity states. METHODS: Following PRISMA guidelines and a pre-registered protocol (PROSPERO CRD42024544730), PubMed and Scopus were searched (May 2024). Eligible observational studies reported estradiol, testosterone, progesterone, prolactin, FSH, LH, DHEA-S, DHEA or androstenedione in SLE patients versus controls or by disease activity. Random-effects meta-analyses were conducted. RESULTS: Eighty-three studies were included (5389 individuals for SLE vs. controls; 2067 for active vs. inactive SLE). Prolactin was consistently higher in SLE (MD 8.07 ng/mL; 95% CI 4.69-11.45; p < 0.001) and even more during flare (MD 5.83 ng/mL; 95% CI 3.88-7.78; p < 0.001). Estradiol showed non-significant overall elevations but was significantly higher in women with active disease (MD 8.55 pg/mL; 95% CI 1.37-15.73; p = 0.03). DHEA-S was found to be significantly lower in SLE (MD -1.00 μg/mL; 95% CI -1.5 to -0.50; p = 0.002) but too few studies evaluated its dynamics during flares. FSH and LH were significantly higher in men with SLE. Other hormones were inconsistent. Only three small heterogeneous studies evaluated hormonal changes during flares. CONCLUSIONS: Prolactin excess and androgen deficiency are consistent features of SLE, particularly in women, while elevated gonadotropins are mainly seen in men. Estradiol is higher during active disease but other data are inconsistent. Longitudinal studies are limited, with prolactin the only hormone consistently linked to disease activity and full hormonal profiles during flares are largely unstudied.

Humans↗

PubMed2026

Bone progression in multiple myeloma: Benefit of zoledronic acid for patients achieving at least Very Good Partial Response and prognostic value of bone turnover markers.

The Magnolia study demonstrated that continuation of zoledronic acid (ZOL) beyond 2 years reduces the risk of progressive bone disease (PBD) in patients with multiple myeloma (MM). This follow-up study investigated the effects of ZOL in patients achieving very good partial response (VGPR) compared to patients who did not and whether bone turnover markers could identify patients at an increased risk of PBD following treatment cessation. Two Magnolia trial subgroups were analysed: patients with VGPR or better after 2 years of ZOL, randomized to either continued treatment or observation, and patients randomized to observation in whom serial bone markers (C-terminal cross-linked telopeptide of type I collagen [CTX], procollagen type I N-terminal propeptide [P1NP], bone-specific alkaline phosphatase [BAP], tartrate-resistant acid phosphatase isoform 5b [TRAcP]) were measured for up to 4 years. Continued monthly ZOL beyond 2 years significantly reduced the risk of PBD (hazard ratio 0.40; 95% confidence interval [CI] 0.16-0.92) in patients with VGPR or better (subgroup 1). After ZOL discontinuation, bone markers increased gradually. Elevated CTX (≥0.30 μg/L) and TRAcP (≥4 U/L) levels were associated with increased 6-month PBD risk (29% and 15% respectively) (subgroup 2). Continuation of ZOL beyond 2 years seems to reduce skeletal progression risk in patients achieving VGPR or better. Elevated CTX or TRAcP levels may help identify patients who could benefit from re-initiating ZOL.

Humans↗

PubMed2026

Norgestrel drives mitochondrial collapse and plasma membrane impairment in Pacific oyster (Crassostrea gigas) sperm by triggering premature acrosome reaction.

The toxic mechanisms of norgestrel (NGT), an emerging marine pollutant, on the sperm from externally fertilized invertebrates remain elusive. This study employed an integrated physiological and multi-omics framework to elucidate how NGT (10 and 1000 ng/L) disrupts acrosome reaction (AR) signaling machinery, thereby impairing the functional integrity of Pacific oyster (Crassostrea gigas, also known as Magallana gigas) sperm. Exposure to NGT triggered a significant, dose-dependent premature AR, characterized by elevated acrosin activity and a loss of acrosomal integrity. Multi-omics integration supports a model in which this premature exocytosis is linked to signaling disturbances, including disruption of calcium signaling and reduced transcript abundance of calmodulin (CaM) and the primary recognition protein zonadhesin (Zan). This signaling interference induced an premature AR, subsequently driving a cascade of bioenergetic and structural failures. At the mitochondrial level, NGT induced abnormal mitochondrial permeability transition pore (mPTP) opening and elevated the transcript levels of antioxidant defense genes (e.g., peroxiredoxin-5, PRDX5). These alterations indicate the occurrence of mitochondrial collapse. Concurrently, scanning electron microscopy verified localized plasma membrane wrinkling and pore formation in sperm. In addition, NGT exposure decreased the transcript abundance of cytoskeleton-related genes, including solute carrier family 26 member 6 (SLC26A6), actin (ACT), and tubulin polymerization promoting protein family member 3 (TPPP3). These molecular changes further disrupted membrane phospholipid homeostasis, as represented by altered glycerophospholipid metabolism. At the same time, cumulative cellular stress was associated with decreased transcript abundance of cytoprotective factors (e.g., baculoviral IAP repeat-containing proteins, birc2) and changes in apoptosis-related genes consistent with activation of a caspase-8-mediated apoptotic programme. In conclusion, NGT, as a representative synthetic progestin, exerts reproductive toxicity by interfering with signaling mediators to induce premature AR, which subsequently exhausts metabolic energy and triggers plasma membrane impairment. These findings provide a critical mechanistic basis for the aquatic ecological risk assessment of synthetic progestins.

Animals↗

PubMed2026

Changes in heroin-related ambulance attendances following the introduction of a medically supervised injecting room in Victoria, Australia.

BACKGROUND: Injecting drug use contributes significantly to morbidity, mortality and broader social harms globally. Supervised Injecting Facilities (SIFs) are harm reduction interventions that reduce overdose risk and facilitate access to health services for marginalised individuals. While international evidence supports the effectiveness of SIFs, Australian population-level surveillance data quantifying their impact on emergency medical service utilisation remain limited. METHODS: Using data from the National Ambulance Surveillance System, we conducted a retrospective, interrupted time series analysis of heroin-related ambulance attendances within the local catchment of the Medically Supervised Injecting Room (MSIR) between January 2015 and December 2023. Supplementary analysis included comparisons with central Melbourne suburbs and the broader state of Victoria. Key intervention timepoints, including the opening of the MSIR on 30 June 2018, expansion of its operating hours in July 2019, and the COVID-19 pandemic from April 2020 to October 2021, were examined to assess changes in heroin-related attendances over time. Segmented regression models were used to assess changes in heroin-related ambulance attendance trends over time. RESULTS: At the time the MSIR opened, the model-predicted heroin-related ambulance attendance rate within the MSIR catchment was 123 per 100,000 population per month, equivalent to approximately 48 heroin-related ambulance attendances per month. Prior to implementation, the attendance rate was increasing by an estimated 0.74 per 100,000 population per month. Following the opening of the MSIR, the previously increasing trajectory reversed, with ambulance attendance rates declining by approximately 2.3 per 100,000 population per month relative to the pre-intervention trend. By the end of the study period (December 2023), the predicted monthly heroin-related ambulance attendance rate had declined to 36 per 100,000 population (approximately 14 attendances per month), representing an overall reduction of 70.7% from the time of MSIR implementation. These reductions persisted throughout the COVID-19 lockdown period and were sustained after restrictions lifted. Supplementary analysis showed no comparable reductions in the central Melbourne region or the remainder of Victoria. CONCLUSIONS: The introduction of the MSIR in Richmond was associated with a sustained reduction in heroin-related ambulance attendances within its catchment area. These findings provide strong population-level evidence that SIFs reduce acute heroin-related harms requiring emergency ambulance response, reinforcing their role as an effective harm reduction strategy within the Australian context.

Humans↗

PubMed2026

Blood Metabolomic Signatures of 1-Hour Glucose Predict Cardiometabolic Risk.

BACKGROUND: Elevated 1-hour glucose levels during an oral glucose tolerance test strongly predict type 2 diabetes (T2D) and cardiovascular disease. We investigated whether the fasting blood metabolome predicting 1-hour glucose could be a target for improving β-cell function, long-term glycemic trajectories, and reducing the risks of T2D and coronary heart disease. We also investigated whether plasma microRNAs derived from key metabolic organs regulate changes in a metabolomic risk score (MRS) for predicting 1-hour glucose. METHODS: Untargeted blood metabolomics and a frequently sampled 75-g oral glucose tolerance test were performed in participants from the OmniCarb trial (n=162). In an independent weight-loss dietary intervention trial (POUNDS Lost [Preventing Overweight Using Novel Dietary Strategies]), temporal changes in MRS and plasma microRNAs measured by genome-wide sequencing were analyzed. In addition, associations of MRS at baseline and its 10-year changes with long-term risk of incident T2D and coronary heart disease were prospectively investigated in the NHS (Nurses' Health Study). RESULTS: We created a fasting blood MRS for predicting 1-hour glucose (Pearson r=0.8) and found significant associations with half-day (diurnal) postprandial glucose excursions and insulin secretion after 5-week controlled feeding interventions varying in carbohydrate amount and glycemic index. In the POUNDS Lost trial, diet-induced changes in MRSs were related to 2-year trajectories of glucose metabolism; circulating microRNAs regulating cardiometabolic abnormalities were pivotal factors influencing these changes. In the NHS, women in the top 20% of MRS had a multivariate-adjusted relative risk of 3.80 (95% CI, 2.22-6.51) for T2D and 1.48 (95% CI, 1.04-2.12) for coronary heart disease compared with those in the lowest 20%. In addition, 10-year increases in plasma metabolites related to 1-hour glucose were linearly associated with a higher risk of T2D. CONCLUSIONS: Our findings indicate that fasting blood metabolomic signatures predicting elevated 1-hour glucose reflect disease pathophysiology and could be targets for preventing T2D and coronary heart disease.

blood glucose↗

PubMed2026

Obesity-Related Coagulation Activation in Adolescents and Children: A Systematic Review and Meta-Analysis.

UNLABELLED: Obesity is recognized as a pro-thrombotic condition, yet the extent of coagulation activation across biomarkers remains unclear. This meta-analysis evaluates the impact of obesity on parameters-D-dimer, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF), factor VIII (FVIII), and endogenous thrombin potential (ETP)-in children and adults. METHODS: Sixty-four studies comprising 59,503 individuals were analyzed. Plasma biomarker levels were compared between non-obese and obese groups using standardized mean differences (SMDs), with subgroup analyses. RESULTS: D-dimer was significantly elevated in adults with obesity (SMD 1.36, 95% CI 0.47-2.25, p = 0.003) and children with obesity (SMD 0.77, 95% CI 0.19-1.36, p = 0.009), indicating increased fibrin turnover. Fibrinogen levels were markedly higher in both adults (SMD 1.17, 95% CI 0.14-2.20, p = 0.03) and children (SMD 1.43, 95% CI 0.93-1.92, p < 0.0001). PAI-1 showed the most pronounced increase in adults (SMD 2.30, 95% CI 0.1.51-3.09, p < 0.0001) and children (SMD 3.54, 95% CI 1.65-5.43, p = 0.0002). FVIII levels were modestly elevated (SMD 0.52, 95% CI 0.10-0.94, p = 0.02), whereas vWF levels showed inconsistent changes. ETP was significantly higher in obesity, in children (SMD 1.06, 95% CI 0.24-1.88, p = 0.01) and adults (SMD 0.71, 95% CI 0.46-0.97, p < 0.0001). Gender-stratified data indicated higher PAI-1, fibrinogen, and ETP levels in females. CONCLUSION: Obesity is associated with increased coagulation activation, suggesting a pro-thrombotic shift. These findings support the need for age- and gender-specific research into obesity-related hemostatic alterations.

Humans↗

PubMed2026

Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk. Dysregulation of programmed cell death is implicated in T2DM, MDD, and neurodegeneration, but proteomic markers of apoptosis have yet to be studied as dementia predictors in people with T2DM and/or MDD. This study examines apoptosis markers in comorbid T2DM and MDD, and their associations with cognitive, dementia, and neuroimaging outcomes. The retrospective sample (n = 15,765) consisted of UK Biobank participants (MDD only n = 1230; T2DM only n = 3644; comorbid T2DM + MDD n = 721). Individuals with T2DM + MDD comorbidity had poorer cognitive performance, and a higher 15-year dementia incidence (HR = 4.44, 95% CI = [3.23,6.11]). Among 60 apoptosis-related proteins identified by Kyoto Encyclopedia of Genes and Genomes pathway enrichment, 41 were significantly up-regulated in comorbid T2DM + MDD relative to controls, and 4 were higher in the comorbid group than both T2DM alone and MDD alone. Tumor necrosis factor ligand superfamily member 10 (TNFSF10), growth arrest and DNA damage-inducible protein GADD45 beta, tumor necrosis factor ligand superfamily member 6, and RAC-gamma serine/threonine-protein kinase were associated with dementia risk. Nine proteins (e.g. apoptosis-inducing factor 1, mitochondrial, caspase-2, mitogen-activated protein kinase kinase kinase 5, TNFSF10), were associated with white matter hyperintensity volumes in comorbid T2DM + MDD after FDR correction, but none were associated with cognitive performance, atrophy, or white matter microstructural changes. These findings identify peripheral apoptosis markers that were further elevated in comorbid T2DM + MDD compared to either alone, pointing to an important pathophysiological element underlying adverse outcomes in the context of mood and metabolic comorbidity.

Humans↗

PubMed2026

Effects of faba bean-based crisping culture on phenotypic characteristics, muscle quality, and serum metabolome in Nile tilapia: Screening biomarkers to assess the degree of crisping.

Feeding Nile tilapia (Oreochromis niloticus) a faba bean-based crisping diet enhances muscle hardness (crispness) and overall flesh quality. However, the underlying mechanisms and reliable biomarkers remain insufficiently defined. This study integrated phenotypic traits, muscle texture, collagen content, serum antioxidant enzyme activities (SOD, CAT, and GSH-Px), MDA levels, and serum metabolomics to understand the determinants of muscle crisping. Fish were assigned to a crisping diet or a control group for 90 days. Individuals in the crisping group were implanted with passive integrated transponder (PIT) tags to enable correlation analyses among phenotypic traits (body weight/length/frame changes), serum indicators (NAM, FAD, and GSH-Px) and muscle hardness. Compared with controls, the crisping diet significantly increased muscle hardness, gumminess, and chewiness, accompanied by elevated collagen content. Antioxidant profiles were altered, with higher activities of serum SOD and CAT, together with elevated MDA levels and reduced GSH-Px activity (P < 0.05). Metabolomic analysis identified 830 differential metabolites (682 upregulated and 148 downregulated), predominantly comprising carboxylic acids and derivatives, glycerophospholipids, and benzene derivatives. Enrichment analysis indicated significant involvement in general metabolic pathways, ATP-binding cassette (ABC) transporters, amino acid biosynthesis, and glycine, serine, and threonine metabolism (P < 0.05). Notably, acetylpyruvate was upregulated in glutathione metabolism, nicotinate and nicotinamide metabolism, and galactose metabolism; pantothenic acid was upregulated in glycine, serine, and threonine metabolism; whereas δ-tocotrienol was downregulated. Correlation analysis revealed weak negative associations between muscle hardness and phenotypic traits (body weight/length/frame changes D5-7, D5-10, D7-8) (P < 0.05). In contrast, serum NAM and FAD were weakly positively correlated with muscle hardness, whereas GSH-Px showed a weak negative correlation (P < 0.05). Collectively, these findings suggest that body weight, body length, frame measurements (D5-7, D5-10, and D7-8), and serum NAM, FAD, and GSH-Px are associated with the degree of muscle crispness in Nile tilapia fed a faba bean-based crisping diet and may serve as candidate biomarkers under these culture conditions.

Animals↗

PubMed2026

Occlusion site and outcomes in intra-arterial tenecteplase after successful endovascular therapy: a secondary analysis of the ANGEL-TNK trial.

BACKGROUND: Endovascular thrombectomy achieves macroreperfusion in large vessel occlusion (LVO) stroke, but only one-quarter of patients had excellent functional outcome. Adjunct intra-arterial (IA) tenecteplase could further improve the treatment effect, yet its efficacy across internal carotid artery (ICA) versus middle cerebral artery (MCA) M1/M2 occlusion remains unclear. OBJECTIVE: To evaluate whether IA tenecteplase improves 90-day functional outcomes in LVO patients stratified by occlusion site (ICA, MCA M1, MCA M2). METHODS: Prespecified secondary analysis of the ANGEL-TNK trial (multicenter, randomized, open-label, blinded endpoint) in 19 Chinese stroke centers. Participants were enrolled who had anterior circulation LVO, 4.5-24 hours from symptom onset, and CT angiography (CTA)/magnetic resonance angiography (MRA)-proven ICA, M1, or M2 occlusion. INTERVENTION: Randomization (1:1) to IA tenecteplase (0.125 mg/kg) or standard medical management after expanded Thrombolysis in Cerebral Infarction (eTICI) 2b50-3 reperfusion. MAIN OUTCOME MEASURE: The primary outcome was the rate of 90-day modified Rankin Scale (mRS) 0-1. RESULTS: There were 256 patients in the trial, including 71 (27.7%) ICA, 122 (47.6%) MCA M1, and 62 (24.2%) MCA M2. ICA occlusion patients treated with IA tenecteplase had higher rates of 90-day mRS 0-1 (39.4% vs 13.2%; relative risk (RR) 2.99; 95% CI 1.51 to 5.96; p=0.002) and mRS 0-3 (54.5% vs 42.1%; RR 1.30; p=0.048) versus controls, with a significant shift toward better mRS scores (median 3 (IQR 1-4) vs 4 (2-6); odds ratio (OR) 2.26; p<0.001). Post hoc analysis showed higher eTICI progression in ICA patients (51.5%) versus MCA M1 (37.9%) and M2 (25.7%). IA tenecteplase had a lower any intracranial hemorrhage within 48 hours in ICA patients (15.2% vs 39.5%; RR 0.38; p<0.001) compared with standard medical management. No significant benefits were observed in the MCA M1/M2 subgroups, and interaction effects were significant between ICA and MCA segments for functional outcomes and safety. CONCLUSIONS AND RELEVANCE: IA tenecteplase had a better functional outcome and lower hemorrhage risk in ICA occlusion compared with standard medical management but not in MCA M1/M2. Occlusion site is a critical determinant of response to IA tenecteplase. A pooled analysis of IA tenecteplase stratified by occlusion site strata is warranted.

Humans↗

PubMed2026

Second-Generation ELZA-sub400 Protocol: Individualized High-Fluence Cross-Linking for Ultra-Thin Keratoconus Corneas.

PURPOSE: To evaluate the safety and efficacy of a second-generation individualized corneal cross-linking (CXL) protocol (ELZA-sub400) using high-fluence UV-A irradiation in ultrathin ectatic corneas. DESIGN: Retrospective, single-center, consecutive interventional case series. METHODS: Twenty-nine eyes of 24 patients with progressive keratoconus or post-LASIK ectasia and a post-soak intraoperative thinnest stromal thickness <400 µm were included. After epithelial removal and riboflavin soaking, continuous UV-A irradiation (365 nm) at 3 or 9 mW/cm² was delivered with total fluence titrated up to 10 J/cm² based on intraoperative ultrasound pachymetry and a previously published nomogram targeting an uncross-linked stromal margin of approximately 70 µm above the endothelium. Outcomes were assessed at baseline and up to 12 months using corrected distance visual acuity (CDVA) and corneal parameters measured using Scheimpflug tomography and anterior segment OCT (AS-OCT) with Placido-based topography. The main outcome measure was the proportion of eyes without progression at 12 months, defined as <1.0 D increase in maximum keratometry (Kmax). Secondary outcomes included changes in CDVA, refraction, Kmax, stromal thickness, demarcation line depth, densitometry, and safety parameters. RESULTS: At 12 months, 22/29 eyes (76%; 95% CI, 57.9%-87.8%) met the nonprogression criterion. Mean change in Kmax was -0.77 ± 5.10 D (95% CI, -2.71 to 1.17; P = .418). Mean demarcation line-to-anterior stroma distance was 205 ± 64 µm (95% CI, 180.7-229.3), and demarcation line-to-endothelium distance was 64 µm (IQR, 49-152). All demarcation lines remained within the stromal layer; 15/29 eyes (51.7%) had a demarcation line located ≤70 µm from the endothelium. Median CDVA changed from 0.10 to 0.32 logMAR (P = .142). Minimum stromal thickness showed a median change of -4.0 µm (P = .309). No significant change was observed in densitometry, and no eye developed deep stromal haze or endothelial decompensation. CONCLUSIONS: Second-generation ELZA-sub400 CXL halted ectasia progression in 76% of ultrathin corneas at 12 months and was associated with an acceptable short-term safety profile, including stromal-confined demarcation line formation and no observed endothelial decompensation. The numerical decline in spectacle CDVA observed in this severely affected cohort did not reach statistical significance but is clinically important and warrants confirmation in larger prospective studies.

Humans↗

PubMed2026

Vestibular schwannoma associated normal pressure hydrocephalus: clinical features and shunt responsiveness compared with idiopathic NPH.

BACKGROUND: Vestibular schwannoma (VS) is commonly associated with obstructive hydrocephalus due to mass effect; however, a rarer communicating form resembling normal pressure hydrocephalus (NPH) has also been described, possibly related to impaired CSF absorption from elevated CSF protein. We aimed to characterize the clinical and imaging features of VS-associated NPH (VS-NPH) and compare them with those of an idiopathic NPH (iNPH) cohort. METHODS: We retrospectively analyzed 18 patients with VS-NPH identified between 2008 and 2024. For comparison, 41 iNPH patients were drawn from a prospective longitudinal study at our center. Variables included demographics, tumor size, VS treatment modality, CSF parameters, Radscale imaging features, and shunt responsiveness. RESULTS: VS-NPH patients had markedly higher CSF protein levels than patients with iNPH (median 100 vs. 51 mg/dL, p < 0.001). Radiological features largely overlapped; however, parasagittal sulcal narrowing was more frequent in VS-NPH (61 % vs.13 %, p = 0.002). These differences remained significant in the sensitivity analysis excluding the two patients without gait impairment. VS-NPH patients were younger in the primary analysis (66.8 vs. 72.0 years, p = 0.03), while exploratory associations between larger tumor size and both earlier NPH symptom onset (r = -0.48, p = 0.049) and smaller callosal angle (r = -0.49, p = 0.048) attenuated to non-significant trends in the sensitivity analysis. Tumor size was < 30 mm in 89 % of patients. Ventriculoperitoneal shunt (VPS) resulted in clinical improvement in both groups, although response rates were numerically lower in VS-NPH than in iNPH (63 % vs.75 %). CTT was positive in 9 of 11 VS-NPH patients who underwent testing, although improvement after shunting also occurred in patients with negative CTT results or without prior CTT. CONCLUSIONS: VS-NPH may represent a secondary subtype of NPH with distinct biochemical and subtle imaging features. Elevated CSF protein may contribute to altered CSF dynamics. These findings are exploratory and require confirmation in larger prospective studies.

Humans↗

PubMed2026

Source- and Solubility-specific Choline, Gut Microbiota, and Dyslipidemia Risk: Trimethylamine N-oxide-associated and Non-trimethylamine N-oxide-Associated Patterns in a Prospective Cohort Study.

BACKGROUND: Dietary choline, a major precursor of the gut microbial metabolite trimethylamine N-oxide (TMAO), is implicated in dyslipidemia risk; however, source- and form-specific associations and interactions with gut microbiota remain unclear. OBJECTIVES: The aim of this study was to examine longitudinal associations of source- and form-specific dietary choline with plasma TMAO and dyslipidemia and to identify gut microbiota interactions. METHODS: Using data from the China Health and Nutrition Survey (2018-2023), dietary intake was assessed via 3 consecutive 24-h recalls in this prospective cohort study. Two-level generalized linear mixed-effects models were applied in 4828 adults (mean age: 55.9 ± 12.6 y, 56.6% females) to assess choline-dyslipidemia associations. Choline-TMAO and TMAO-dyslipidemia analyses were conducted in 1091 participants free of dyslipidemia at baseline. Among 7169 adults with gut microbiome data, Least Absolute Selection and Shrinkage Operator and logistic regression identified lipid-associated gut genera; TMAO relationships were examined in a subset of 693 participants. RESULTS: Higher intakes of total [Q4 compared with Q1: odds ratio (OR) = 1.261; 95% confidence interval (CI): 1.007, 1.580], red meat-derived (OR: 1.753; 95% CI: 1.196, 2.568), and lipid-soluble choline (OR: 1.304; 95% CI: 1.047, 1.624) were associated with higher risk of elevated low-density lipoprotein cholesterol (LDL cholesterol), whereas vegetable-derived choline was inversely associated. Egg-derived and lipid-soluble choline were positively associated with plasma TMAO, which was prospectively associated with 5-y incident dyslipidemia (Q4 compared with Q1-OR: 1.620; 95% CI: 1.047, 2.509), elevated LDL cholesterol (Q3 compared with Q1-OR: 2.478; 95% CI: 1.187, 5.174), and hypertriglyceridemia (Q4 compared with Q1-OR: 1.829; 95% CI: 1.028, 3.225). Three TMAO-associated genera were identified: Lachnospiraceae and Phascolarctobacterium as pro-risk taxa and Turicibacter as protective. The adverse LDLcholesterol association of egg-derived choline was observed exclusively in Phascolarctobacterium-enriched individuals. CONCLUSIONS: Dietary choline source and solubility differentially associated with dyslipidemia risk through TMAO-associated and non-TMAO-associated patterns, with gut microbiota as key modulators.

Humans↗

PubMed2026

The efficacy of modified psychodynamic psychotherapy for patients with schizophrenia-spectrum disorders in Germany: a prospective, single-centre, assessor-blinded, parallel-group, randomised controlled trial.

BACKGROUND: People with schizophrenia-spectrum disorders have difficulties in interpersonal functioning that remain insufficiently addressed by standard care. Despite long-standing clinical use, psychodynamic psychotherapy has little empirical support compared with other psychosocial treatments for people with schizophrenia-spectrum disorders. We evaluated the efficacy of Modified Psychodynamic Psychotherapy for Schizophrenia (MPP-S), a manualised treatment tailored to the interpersonal vulnerability characteristic of this population, plus treatment as usual (TAU), compared with TAU alone. METHODS: This prospective, single-centre, assessor-blinded, parallel-group, randomised controlled trial was conducted at the Psychiatric University Hospital of the Charité at St Hedwig Hospital in Berlin, Germany. Participants were outpatients aged 18-64 years who were diagnosed with schizophrenia or schizoaffective disorder and exclusion criteria included organic brain disorder, somatic illness affecting cerebral function, and current or past alcohol or illicit drug misuse requiring addiction-specific treatment. Participants were randomly assigned 1:1 in blocks of ten to MPP-S (minimum 30 sessions) plus TAU or TAU alone. Outcome assessors were masked, but participants and therapists were not. The primary outcome was psychosocial functioning, measured using the Mini International Classification of Functioning, Disability and Health Rating for Limitations of Activities and Participation in Psychological Disorders (Mini-ICF-APP) and evaluated at baseline and prespecified post-treatment (24 months) and follow-up (36 months) assessments. Analyses followed the intention-to-treat principle. Linear mixed models were used to analyse incomplete longitudinal data under a missing-at-random assumption. People with lived experience were not formally involved in the design, conduct, or reporting of this study. This trial was preregistered at ClinicalTrials.gov (NCT02576613) and is complete. FINDINGS: From Oct 12, 2015, to Dec 7, 2021, 130 participants (57 [44%] female and 73 [56%] male) were randomly assigned to either MPP-S plus TAU (n=65) or TAU alone (n=64). One participant withdrew consent to data analysis. Regarding the primary outcome of psychosocial functioning, linear mixed models showed significant group-by-time interactions favouring the intervention: estimated marginal means indicated adjusted between-group differences in Mini-ICF-APP scores of -3·45 (95% CI -5·51 to -1·40; p=0·0011) at 24 months and -4·07 (-6·19 to -1·94; p=0·0002) at 36 months. The frequency of adverse events was similar between groups. There were three serious adverse events: two participants died by suicide (one in the MPP-S plus TAU group who did not start psychotherapy and one in the TAU alone group) and one participant in the MPP-S plus TAU group was admitted to a forensic hospital. INTERPRETATION: MPP-S added to TAU could improve psychosocial functioning compared with TAU alone. Our findings suggest efficacy and possible long-term benefits of psychodynamic psychotherapy for schizophrenia-spectrum disorders and indicate its potential role alongside other psychotherapeutic and psychosocial treatments. FUNDING: Berlin Institute of Health, Deutsche Gesellschaft für Psychoanalyse, Psychotherapie, Psychosomatik und Tiefenpsychologie, International Psychoanalytic University Berlin, and Köhler-Stiftung.

Humans↗

PubMed2026

Obesity in obstetric anesthesia: A systematic review.

Maternal obesity presents complex challenges for anesthetic management, with implications spanning neonatal, cardiovascular, airway, neuraxial, and procedural domains. This review synthesizes evidence on how elevated maternal body mass index (BMI) impacts perioperative evaluations, risks, complications, and outcomes, in addition to anesthetic modalities and efficacy in the pregnant population. Given the increasing global prevalence of maternal obesity, anesthesiologists must refine clinical practices, employing tailored, evidence-based strategies to mitigate risks and enhance patient outcomes. This review aims to provide anesthesiologists and obstetricians with key considerations and best practices for managing obstetric anesthesia patients with obesity. Clinical recommendations herein are based on current research and evaluated using Oxford Centre for Evidence-Based Medicine for level of evidence and class of recommendation.

Humans↗