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Bedtime tetrahydrocannabinol ingestion reduces morning orthostatic cardiovascular reactivity in adults: An exploratory study.

Acute cannabis use and its primary psychoactive constituent tetrahydrocannabinol (THC) can induce postural dizziness, indicating increased risk of orthostatic instability. However, it is unknown if vulnerabilities persist the morning after bedtime THC consumption. This study investigated the influence of bedtime THC consumption on cardiovascular variables during an orthostatic challenge. Nine individuals with no cannabis use and eight individuals who regularly use cannabis participated in a tilt table test associated with a 3-day in-laboratory stay. Participants underwent an acclimatization day, followed by a placebo dosing day, and a 10 mg THC dosing day. Placebo and THC pills were given 1 h before a participant's habitual bedtime, and the tilt table test was performed ~1 h upon awakening. Participants were instrumented with an electrocardiogram and an automated sphygmomanometer. Fluid intake and output were measured throughout the study. The morning after THC administration, individuals with no cannabis use reported a higher frequency of dizziness and exhibited a significant reduction in both diastolic blood pressure and heart rate reactivity to tilt (reactivity = tilt - baseline) compared to the morning after placebo. Our results indicate a potential increased risk for orthostatic instability the morning after cannabis consumption in individuals with no cannabis use history.

Humans

Safety and outcomes of dapagliflozin initiation in critically ill patients with acute kidney injury: A post-hoc analysis of the defender trial.

BACKGROUND: SGLT2 inhibitor use in acute kidney injury (AKI) is controversial due to concerns about hemodynamic instability. We evaluated dapagliflozin initiation in critically ill patients with AKI enrolled in the DEFENDER trial. METHODS: Among 212 patients with AKI at enrollment (100 dapagliflozin, 112 control), we compared 28-day mortality, kidney replacement therapy (KRT), and composite death/KRT. Adjusted risk differences were estimated controlling for age, sepsis, baseline vasopressor use, and creatinine. Physiological trajectories (creatinine, urine output, fluid balance, acid-base parameters) over days 1-5 were analyzed using mixed models. Likelihood ratios quantified compatibility with clinically meaningful harm or benefit. RESULTS: Event rates were similar: 28-day mortality 38% vs 40%, KRT 12% vs 18%, composite 41% vs 42% (dapagliflozin vs control). Adjusted risk differences were - 1.9% (95% CI -14.5 to 10.7) for death, -7.4% (-16.2 to 1.5) for KRT, and - 0.9% (-13.6 to 11.8) for the composite. Physiological trajectories showed no divergence suggestive of hemodynamic or metabolic instability. Likelihood ratios provided limited separation: at 5% absolute effect threshold, LR against harm was 1.47 and against benefit 1.19. CONCLUSIONS: Dapagliflozin initiation in critically ill patients with AKI was not associated with excess mortality, KRT, or physiological derangement. The near-neutral evidential profile indicates neither moderate harm nor benefit can be excluded, supporting feasibility of dedicated trials of SGLT2 inhibitors in AKI.

Humans

Nurse-Led Home-Based Mobile Health Cardiac Rehabilitation Program for Patients With Chronic Heart Failure: A Randomized Controlled Trial.

This 12-week randomized controlled trial evaluated a nurse-led mHealth intervention for patients with chronic heart failure, conceptually informed by Riegel's middle-range theory of self-care of chronic illness. The program integrated wearable activity tracking with weekly nurse-led behavioral coaching, reflecting the core self-care processes of monitoring, maintenance, and management. Compared with usual care, the intervention significantly improved daily step count, 6-minute walk distance, metabolic equivalents, and left ventricular ejection fraction. Findings highlight the effectiveness of theory-informed, nurse-delivered mHealth strategies in enhancing physical activity and cardiopulmonary function, while underscoring the critical role of advanced practice nurses in home-based chronic disease management.

Aged

Chronic postsurgical pain: risk assessment and mitigation.

PURPOSE OF THE REVIEW: Chronic postsurgical pain (CPSP) and persistent postoperative opioid use (PPOU) are two of the most common complications of a number of surgical interventions, which can cause significant personal and economic negative consequences. This review outlines known and potential risk factors for CPSP and PPOU and approaches to reduce these risk factors. RECENT FINDINGS: Modifiable risk factors for developing CPSP include psychological distress, preoperative pain intensity, and perioperative opioid exposure. Although less studied, psychological comorbidities are also risk factors for PPOU. Evidence-based mitigation strategies include psychological interventions and perioperative opioid sparing. SUMMARY: A number of perioperative risk factors for developing CPSP and PPOU have been identified, and anesthesiologists should be cognizant of these risk factors and potential risk mitigation strategies. Additional prospective studies are needed to further develop easily adoptable, evidence-based interventions to reduce the incidence of CPSP and PPOU.

Humans

A status update on the unkept promise of high-frequency spinal cord stimulation for treatment-refractory chronic migraine.

INTRODUCTION: Chronic migraine (CM) refractory to conventional pharmacotherapy (r-CM) remains a debilitating neurological condition with limited therapeutic options. High-frequency spinal cord stimulation at 10 kilohertz (HF-SCS) has recently emerged as a distinct neuromodulatory paradigm for this patient population. Unlike traditional spinal cord stimulation, HF-SCS operates above the frequency range that generates paresthesia, thereby eliminating stimulation-induced sensation while potentially engaging unique analgesic mechanisms. AREAS COVERED: This focused narrative review synthesizes the available clinical evidence, technical considerations, and mechanistic hypotheses specifically pertaining to cervical HF-SCS for refractory chronic migraine (r-CM). The authors further provide their expert perspectives on the future of this technology as a treatment option for refractory chronic migraine. EXPERT OPINION: Current data from prospective open-label studies and retrospective case series suggest that cervical HF-SCS may reduce monthly migraine days, facilitate conversion from chronic to episodic migraine patterns in some implanted patients, and may improve headache-related disability and quality of life over at least 52 weeks of follow-up. The paresthesia-free nature of HF-SCS confers a distinct advantage for both patient tolerability and future trial design, as it permits sham-controlled methodologies that have historically been impossible with conventional neurostimulation. However, these findings remain preliminary and should be considered hypothesis-generating pending confirmation in adequately powered randomized sham-controlled trials.

Humans

Psychological interventions for children with chronic physical conditions: a systematic review assessing the role of coping, emotional and cognitive processes.

OBJECTIVES: Coping, emotional and cognitive processes are crucial in child development, particularly in children with pediatric chronic physical conditions (CPC). No systematic review in pediatric psychology has investigated the effectiveness of interventions on these processes concurrently. This review addresses this gap by focusing on the effectiveness of psychological interventions on coping, emotional and cognitive processes in children with CPCs. METHODS: Five electronic databases were searched for studies assessing at least one of these processes. Only randomized-controlled trials with children (8-12 years) with a CPC (e.g. diabetes, asthma), which implemented a psychological intervention were included. This study is registered in (CRD42021233505). RESULTS: Ten intervention studies were identified. While cognitive interventions (Cogmed) showed some improvements in working memory, the effects varied across studies despite similar methodologies. Coping interventions (e.g. Coping Skills Training) showed little effect on coping strategies or psychological health variables and were no more beneficial than control groups. No study trained coping, emotional processes and cognitive processes together. CONCLUSION: This review shows current limitations in evaluating psychological interventions targeting coping, cognitive or emotional processes in children with CPCs, limiting a comprehensive understanding of the interventions' action mechanisms. Systematically including underlying processes in intervention studies could help to better adjust those interventions.

Humans

[Complex therapy of chronic bacterial prostatitis using the immunomodulatory drug sodium aminodihydrophthalazinedione].

INTRODUCTION: Chronic bacterial prostatitis (CBP) is characterized by a recurrent course caused by pathogen persistence and impaired local immunity of the prostate. AIM: To assess the effectiveness of the use of sodium aminodihydrophthalazinedione in the complex therapy of chronic bacterial prostatitis. MATERIALS AND METHODS: The prospective comparative study included 60 men aged 21-50 years with CBP (NIH category II). Patients were randomized into two groups of 30: the comparison group received levofloxacin 500 mg/day for 28 days; the main group additionally received rectal sodium aminodihydrophthalazinedione. NIH-CPSI, IPSS, QoL, uroflowmetry, leukocyte and lecithin body counts in prostatic secretion, and bacteriological examination were assessed at baseline and on day 28, and the recurrence rate over 3 months. RESULTS: By day 28, the main group showed a more pronounced decrease in the total NIH-CPSI score (8.1+/-2.1 vs 13.4+/-2.6; p<0.001), restoration of lecithin bodies (+65.1% vs +24.5%; p<0.05), normalization of uroflowmetry, and pathogen eradication in 86.7% vs 66.7% of patients (p<0.05). The 3-month recurrence rate decreased from 26.7 to 10.0% (p<0.05). No adverse events were registered. DISCUSSION: The advantage of combinationtherapy is due to the combination of anti-inflammatory,immunomodulatory,antioxidantandregenerativeeffects of the drug,which is confirmed by the restoration of the secretoryfunction of the prostateepitheliumaccording to the dynamics of lecithingrains. CONCLUSION: The inclusion of sodium aminodihydrophthalazinedione in the combination therapy of CBP increases the clinical and microbiological efficacy of treatment and reduces the recurrence rate.

Humans

ALG-020572, an Antisense Oligonucleotide for the Treatment of Chronic Hepatitis B Virus Infection Discontinued for Drug-Induced Liver Injury.

Current treatment options for chronic HBV infection are suboptimal in that they fail to suppress HBsAg levels. ALG-020572 is an antisense oligonucleotide designed to reduce viral protein synthesis through degradation of HBV mRNA. ALG-020572-401 was a double-blind, randomized, placebo-controlled trial consisting of two parts. Part 1 (single-ascending doses) evaluated the pharmacokinetics, safety and tolerability of single doses of ALG-020572 or placebo in healthy participants. In Part 2 (multiple dosing), participants with non-cirrhotic HBeAg-negative, virologically suppressed chronic HBV infection were administered up to 7 doses of ALG-020572 to evaluate safety, pharmacokinetics and antiviral activity. In Part 1, 32 participants were randomized to ALG 020572 or placebo. Single doses of ALG-020572 up to 480&#x2009;mg were well tolerated. The most common treatment-emergent adverse event reported was injection site reaction. ALG-020572 was rapidly absorbed and plasma exposures increased with dose. In Part 2, 8 participants with non-cirrhotic HBeAg-negative virologically suppressed chronic hepatitis B infection were enrolled and received up to 7 doses of ALG-020572. The study was prematurely discontinued after 4 participants experienced significant alanine aminotransferase elevations that were subsequently attributed to drug-induced liver injury. Single doses of ALG-020572 demonstrated a favourable pharmacokinetic and safety profile in healthy participants. Unexpectedly, ALG-020572 was poorly tolerated in participants with chronic HBV infection, resulting in the early termination of the study and further development of ALG-020572 due to idiosyncratic drug-induced liver injury, suggesting caution is required in the development of this class of drugs. Trial Registration: Registered at clinicaltrials.gov: NCT0500102.

Adult

Comparative effectiveness and safety of pharmacological interventions for sleep outcomes in chronic non-cancer pain: a systematic review and network meta-analysis.

Sleep disturbances are highly prevalent among individuals with chronic non-cancer pain and are associated with worse pain severity and poorer prognosis. The comparative trade-offs between the effectiveness and safety of available pharmacotherapies for sleep outcomes in this population remain poorly defined. Ninety-eight RCTs involving 28,920 participants (mean age 53.2 years, 71.2% female) were included. Moderate-certainty evidence demonstrated that melatonin significantly improved sleep quality compared with placebo (standardized mean difference [SMD]&#x202f;=&#x202f;-0.60, 95%CI: -0.98, -0.22). Ten agents (e.g., amitriptyline, oxycodone, gabapentin, pregabalin, duloxetine) also showed statistically significant improvements in subjective sleep quality (SMD&#x202f;=&#x202f;-0.24 to -1.07), but most effects were supported by low-certainty evidence and were accompanied by an increased risk of adverse events (odds ratio [OR]&#x202f;=&#x202f;1.90 to 37.00). Conversely, melatonin was not associated with an increased risk (OR&#x202f;=&#x202f;0.88, 95%CI: 0.19, 3.94). Our findings indicate that melatonin shows promise as a safe, adjunctive option for improving sleep quality in this population, but larger, condition-specific trials are warranted to confirm these effects. Other pharmacological agents are limited by lower-certainty and unfavorable safety profiles. These results should be interpreted cautiously given limited direct comparisons, heterogeneous chronic pain populations, the high proportion of trials at high risk of bias, and the predominance of subjective sleep outcomes.

Humans

Efficacy and safety of revascularization in patients with chronic limb-threatening ischemia by kidney function.

BACKGROUND: The optimal revascularization strategy for patients with chronic limb-threatening ischemia (CLTI) with chronic kidney disease (CKD) remains unknown. We evaluated whether the efficacy and safety of surgical vs endovascular revascularization differ by kidney function. METHODS: In this post hoc secondary analysis of BEST-CLI trial (NCT02060630), 1,704 patients with CLTI were stratified by baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m&#xb2;): non-CKD (eGFR &#x2265; 90), mild-moderate CKD (eGFR 45-89), advanced CKD (eGFR < 45 or dialysis). The primary outcome was a composite of major adverse limb events (MALE) or death. We estimated the difference in restricted mean time lost (RMTL, in days) adjusted for inverse probability treatment weights. RESULTS: Surgical revascularization was significantly associated with fewer days with MALE or death in non-CKD (RMTL difference: -127.8 days; 95% CI -176.1, -79.6) and mild-moderate CKD (-63.2 days; 95% CI -104.7, -21.8) but not in advanced CKD (-16.4 days; 95% CI -78.8, 46.0; P interaction = .02). This attenuation reflected a diminishing mortality benefit with more severe CKD (P interaction = .01), whereas the association with fewer days with MALE remained consistent across CKD strata (P interaction = .34). Major adverse cardiovascular events and serious adverse events were more common with more severe CKD but did not differ significantly by treatment. CONCLUSIONS: Surgical vs endovascular revascularization was consistently associated with fewer days with MALE across CKD strata. However, its association with mortality varied by kidney function, attenuating the overall benefit for the composite endpoint of MALE or death. These results support individualized revascularization strategies, but require prospective confirmation. TRIAL REGISTRATION: The BEST CLI trial is registered at ClinicalTrials.gov (NCT02060630).

Humans

Impact of creatine supplementation alone or combined with exercise on inflammatory and clinical outcomes in chronic musculoskeletal pain treated in the rheumatological field: a systematic review.

Creatine supplementation has demonstrated ergogenic and anabolic effects in healthy and clinical populations. However, its potential therapeutic role in individuals with chronic musculoskeletal pain treated in rheumatological contexts remains unclear. The aim was to evaluate the efficacy and safety of creatine supplementation on pain, physical function/disability, quality of life, muscle strength, skeletal muscle mass, and inflammatory markers in people with chronic musculoskeletal pain usually treated from the rheumatological field. A systematic review was conducted following PRISMA guidelines. Searches were performed in MEDLINE, Web of Science, CINAHL, Scopus, and EMBASE up to July 2026. Eligible studies were randomized or nonrandomized clinical trials that provided creatine supplementation alone or in combination with exercise as a treatment compared to a control or placebo group. Eight studies (n = 189) were included, encompassing fibromyalgia, osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis. Creatine dosages varied from chronic low-dose to loading protocols (20 g/d, 2-5 g/d). Combined creatine plus resistance training may improve strength, skeletal muscle mass, and quality of life beyond exercise alone in osteoarthritis. Trials on fibromyalgia suggest an increase in muscle strength, but inconsistent effects on pain. Rheumatoid arthritis studies suggest gains in skeletal muscle mass and, in pilot studies, reduced disease activity. No major adverse events were reported. In conclusion, creatine supplementation alone may be insufficient to obtain clinical benefits, while combined with resistance exercise it could offer potential benefits for muscle strength, skeletal muscle mass and certain aspects of quality of life in these clinical conditions. However, evidence on pain and inflammation remains limited; Furthermore, the response across different clinical conditions is heterogeneous, highlighting the need for larger, high-quality trials.

Humans

Effects of Sacubitril Valsartan Combined With Vericiguat on NT-proBNP and CK-MB Levels in Patients With Chronic Heart Failure.

This study aims to probe the influence of sacubitril valsartan sodium tablets combined with vericiguat on N-terminal pro-B-type natriuretic peptide (NT-proBNP) and creatine kinase isoenzyme (CK-MB) levels in patients with chronic heart failure (CHF). One hundred and twenty CHF patients were enrolled and stratified into a control group (sacubitril valsartan sodium tablets) and a combination group (sacubitril valsartan sodium tablets&#x2009;+&#x2009;vericiguat). Outcome measures included New York Heart Association (NYHA) functional class shifts, echocardiographic indices, cardiac injury markers, 6-min walk distance (6MWD), endothelial function parameters, inflammatory mediator levels, and adverse clinical events. Following a 6-month treatment period, patients in the combination group exhibited superior functional improvement, as reflected by greater advancement in NYHA class. Echocardiographic evaluation revealed more favorable ventricular remodeling in this group, with reduced left ventricular end-diastolic and end-systolic diameters and an elevated ejection fraction. The combination group had a higher 6MWD. Biomarker analysis showed lower NT-proBNP and CK-MB levels in the combination group. Furthermore, improvements in endothelial function were noted, with decreased endothelin and elevated NO, NOS, and CGRP levels in the combination group. Markers of systemic inflammation, including CRP and IL-6, were also attenuated in the combination group. The incidence of adverse reactions and cardiovascular events did not differ significantly between the groups. Co-administration of sacubitril/valsartan and vericiguat enhances cardiac performance, optimizes vascular endothelial responsiveness, modulates heart failure-related biomarkers, and mitigates inflammatory activity in patients with CHF without increasing the risk of adverse events.

Humans

Effects of Vacuum Compression Therapy on Healing of Chronic Lower Limb Ulcers: A Randomised Controlled Study.

Chronic lower limb ulcers remain difficult to manage when unresponsive to conventional treatment. This study evaluated the clinical and physiological effects of vacuum compression therapy on wound healing and quality of life. Fifty patients with chronic lower limb ulcers were randomised to receive 12 sessions of vacuum compression therapy plus standard care or standard care alone over 4&#x2009;weeks. Wound dimensions, exudate, pain intensity and quality of life were assessed at baseline and post-treatment. Estimated wound volume was calculated as length&#x2009;&#xd7;&#x2009;width&#x2009;&#xd7;&#x2009;depth. Tissue oxygenation was measured at the dorsum of the foot in the experimental group. The vacuum compression therapy group showed greater improvements in wound width, depth, volume and quality of life. Estimated wound volume decreased by 61% in the intervention group, whereas no statistically significant volume reduction was observed in controls. Local tissue oxygenation in the experimental group increased by 43%. Baseline wound size was associated with poorer quality of life. Vacuum compression therapy may enhance wound healing and quality of life in patients with chronic lower limb ulcers. Observed increases in local tissue oxygenation represent exploratory physiological findings within the treated cohort that warrant controlled comparative evaluation. Trial Registration: ClinicalTrials.gov identifier: NCT07737184.

Humans

Yoga MAT: A factorial randomized study using the Multiphase Optimization Strategy to develop a multicomponent yoga intervention for people with chronic pain taking medications for opioid use disorder.

BACKGROUND: People taking medications for opioid use disorder (MOUD) commonly experience chronic pain. Yoga interventions show promise for decreasing pain-related disability in other populations. More time spent in yoga practice may improve pain-related outcomes. METHODS: The Multiphase Optimization Strategy (MOST) provided the framework for developing an optimized yoga intervention package. In a 2x2x2x2 factorial experiment, we evaluated four candidate intervention components which, when added to a weekly yoga class, might increase yoga engagement. The primary outcome was minutes per week of yoga practice (classes and other yoga practice) over the 12-week intervention period. We sought to determine which combination of intervention components was associated with the most yoga practice for people with chronic pain taking buprenorphine or methadone as MOUD. RESULTS: We enrolled 192 adults. There was a significant main effect for Component "B" (having two private sessions with a yoga teachers; IRR = 1.10, 90%CI 1.02; 1.18), and a synergistic interaction between Components "B" and "D" (D was financial incentives for attending class; IRR = 1.11, 90%CI 1.02; 1.19). This combination of these two components (without other potential components) was associated with the second highest model-predicted mean minutes of yoga per week (157.1min; 90% CI = 120.1-194.0) which was only 4min less than the combination including all four components. CONCLUSIONS: We identified a combination of intervention components as the optimized intervention. A next step will be to test the effect of this optimized intervention on pain and substance use outcomes in a randomized controlled clinical trial.

Humans

The Effect of Pain Catastrophizing on Acupuncture Treatment for Chronic Pain in Cancer Survivors.

CONTEXT: Pain catastrophizing (PC) predicts worse pain outcomes in cancer survivors. However, little is known whether PC influences pain outcomes of nonpharmacological treatments such as acupuncture. OBJECTIVES: This study aimed to assess the impact of PC on acupuncture efficacy for chronic pain in cancer survivors. METHODS: This secondary analysis of PEACE trial used two-sample t-test and Pearson's chi-squared test to analyze the pain outcomes of cancer survivors who received electroacupuncture (EA) or battlefield acupuncture (BFA). PC was measured using Pain Catastrophizing Scale (PCS). The Brief Pain Inventory (BPI) was used to measure pain severity and interference at the primary endpoint (week 12). RESULTS: Among 266 participants, 41 (15.41%) had a high baseline PC. Among those receiving EA, high PC patients had greater reductions in pain severity (-3.9 vs. -2.1, P = 0.006) and pain interference (-3.8 vs. -2.6, P = 0.04) than low PC. PC was not associated with pain outcomes in BFA group (P > 0.05 for both severity and interference). Among patients with high PC, a greater proportion were responders in the EA group than those in BFA group (83.3% vs. 43.5%, P = 0.009). Among low PC patients, there was no significant difference in the proportion of responders between the EA and BFA groups (66.1% vs. 64.5%, P = 0.8). CONCLUSION: We found that cancer survivors with high baseline PC had greater pain reductions with EA than BFA and compared to low PC patients. These findings suggest that EA may serve as a targeted treatment option for vulnerable patients with high PC and further support precision pain management.

Humans

Effects of Progressive Inspiratory Muscle Training on Lung Volume and Respiratory Strength in Patients With Pre-Dialysis Chronic Kidney Disease.

INTRODUCTION: Chronic kidney disease can present changes in thoracic cavity volume and respiratory muscle weakness, even in the pre-dialysis stage. However, there is little evidence on the effects of inspiratory muscle training in these patients. METHODS: This was a randomized clinical trial which comprised patients with Chronic Kidney Disease in stages 3, 4, and 5 undergoing conservative treatment, allocated experimental group (EG) with progressive loading (up to 50% of maximal inspiratory pressure [MIP]) and control group (CG) with a fixed load (5 cmH2O) and no load progression performed daily for 8&#xa0;weeks. The outcomes assessed were thoracic cavity volumes, as measured by optoelectronic plethysmography, and inspiratory and expiratory respiratory muscle strength. RESULTS: A total of 30 patients completed the study. All volumes significantly increased at the end of the protocol with a large effect size, but only the pulmonary thoracic cavity volume showed a significant interaction (F&#xa0;=&#xa0;3.698; p&#xa0;=&#xa0;0.042). There was an increase in inspiratory muscle strength in the EG (73.88-90.35&#xa0;cmH2O; p&#xa0;<&#xa0;0.001) and in the CG (70.85-86.92&#xa0;cmH2O; p&#xa0;=&#xa0;0.001), as well as in expiratory muscle strength in the EG (97.71-108.53&#xa0;cmH2O; p&#xa0;=&#xa0;0.001) and in the CG (80.69-94.77&#xa0;cmH2O; p&#xa0;=&#xa0;0.004). CONCLUSION: Daily IMT increased thoracoabdominal volumes, particularly pulmonary rib cage volume in the progressive-load group, as well as respiratory muscle strength in patients with pre-dialysis CKD. However, progressive-load IMT was not superior to minimal-load training.

Humans

Assay-dependent variability in peptide biomarker quantification: experimental evidence from renalase in chronic kidney disease.

BACKGROUND: Renalase is a promising biomarker for kidney disease, but published levels vary widely between studies. We hypothesised that variability in commercial enzyme-linked immunosorbent assays (ELISAs) kits and matrix effects (serum vs plasma) drive these inconsistencies. METHODS: Paired serum and plasma samples from 56 participants (28 chronic kidney disease (CKD) stages 2-5, 28 healthy controls) were tested using three commercial renalase ELISAs (BTLAB, Cloud-Clone, EIAab). We assessed intra-assay precision, inter-assay agreement (Spearman's rank correlation and Bland-Altman analysis on log10-transformed values), matrix effects, and associations with estimated glomerular filtration rate (eGFR). Diagnostic performance was evaluated by Receiver operating characteristic (ROC) analysis. RESULTS: Inter-assay renalase concentrations differed markedly (up to orders of magnitude), with weak inter-assay correlations (r&#x2009;&#x2264;&#x2009;0.25). Bland-Altman analyses revealed large, systematic biases between kits. Only the BTLAB assay showed consistent serum/plasma agreement, a significant correlation with eGFR (&#x3c1;&#x2009;&#x2248;&#x2009;0.32-0.42, p&#x2009;<&#x2009;0.05), and moderate discriminatory performance for CKD in serum (AUC = 0.70) and plasma (AUC = 0.68). Cloud-Clone and EIAab produced divergent results and strong matrix-dependent biases. CONCLUSIONS: Observed variability among commercial ELISA platforms may compromise comparability between studies. Harmonisation, standardised reference materials, and cross-validation are necessary before renalase assays can be used reliably in clinical practice.

Humans

Adjunctive middle meningeal artery embolization for chronic subdural hematoma: A systematic review and meta-analysis of eight randomized trials.

BACKGROUND: Randomized trials suggest that adjunctive middle meningeal artery embolization (MMAE) may reduce recurrence in chronic subdural hematoma (CSDH), but potential sources of variability in treatment effects across studies remain poorly understood. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of MMAE and to explore potential study-level sources of between-study heterogeneity. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing MMAE plus surgery versus surgery alone, following PRISMA guidelines. Trial sequential analysis (TSA) was prespecified to assess the robustness of pooled findings. Exploratory mixed-effects meta-regression was performed to examine whether aggregate study-level mean age and anticoagulation use were associated with variability in recurrence outcomes. RESULTS: Eight trials including 1961 patients were analyzed. MMAE plus surgery was associated with a reduction in recurrence compared with surgery alone (RR 0.63, 95% CI 0.46-0.85; I&#xb2; = 0%), and TSA supported this finding. Although conventional meta-analysis suggested a reduction in reoperation, the TSA findings were more sensitive to analytical assumptions and less robust. Exploratory study-level meta-regression analyses suggested possible associations between recurrence outcomes and mean age or anticoagulation use, although these findings should be interpreted as hypothesis-generating only. Safety outcomes were comparable between groups. CONCLUSIONS: Adjunctive MMAE was associated with reduced recurrence in CSDH. Exploratory analyses evaluating aggregate study-level characteristics were limited by the small number of included trials and the use of aggregate-level data, and should be considered hypothesis-generating only. Further prospective studies are needed to better understand variability in treatment effects.

Humans