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PubMed2026

Efficacy and safety of middle meningeal artery embolization for chronic subdural hematoma: an updated systematic review and meta-analysis focusing on time of intervention.

INTRODUCTION: Chronic subdural hematoma (cSDH) is increasingly prevalent among older adults due to population aging and widespread antithrombotic use. Although burr-hole drainage remains the standard treatment, recurrence rates are substantial. Middle meningeal artery embolization (MMAE) has emerged as an adjunctive strategy to disrupt dural neovascularization and prevent rebleeding. OBJECTIVES: To assess the efficacy and safety of MMAE combined with standard therapy versus standard therapy alone, with stratification by timing of intervention. METHODS: Randomized controlled trials (RCTs) were searched in PubMed, Scopus, and Cochrane Central up to July 2025. Adults with confirmed cSDH were included. The primary outcome was hematoma recurrence or persistence. Secondary outcomes were reoperation, hematoma resorption, serious adverse events, neurological death, mortality, functional independence, and hospital stay. Risk of bias was assessed with RoB-2, and analyses followed PRISMA guidelines (PROSPERO CRD420251112841). RESULTS: Seven RCTs (1,889 patients) were included. Compared with standard therapy, MMAE significantly reduced recurrent or residual cSDH (RR 0.63; 95% CI 0.46-0.85) and reoperation (RR 0.39; 95% CI 0.28-0.56) without increasing serious adverse events (RR 0.87; 95% CI 0.72-1.06), neurological death, mortality, or poor functional outcomes. Hematoma resorption did not differ significantly. Subgroup and sensitivity analyses confirmed the robustness of the results across age, intervention timing, and follow-up duration. CONCLUSION: MMAE combined with standard therapy significantly reduces recurrence and reoperation in cSDH without increasing adverse events or mortality. Benefits appear independent of procedural timing, though larger RCTs with extended follow-up are warranted to define long-term outcomes and optimal use.

Humans↗

PubMed2026

Craniotomy versus Endoscopic Membranectomy in the Treatment of Non-Homogeneous Chronic Subdural Hematoma: A Pilot Randomized Parallel-Group Active-Controlled Trial (EMiT CSDH 2).

BACKGROUND: Chronic subdural hematoma (CSDH) is a prevalent neurosurgical condition with persistent challenges related to recurrence. Endoscopic membranectomy (EM) has shown promising results in managing symptomatic non-homogenous (SNH)-CSDH, but comparative evidence against craniotomy with membranectomy (CM) is lacking. OBJECTIVES: To compare the safety and efficacy of EM versus CM in managing SNH-CSDH. MATERIALS AND METHODS: A pilot randomized parallel-group active-controlled open- labeled superiority trial from September 2023 to November 2024 at Government Kilpauk Medical College, Chennai, India. Sixty patients with SNH-CSDH were randomized into EM and CM groups. Recurrence was the primary outcome. Secondary outcomes included operative time, complications, radiological indices, pain, hospital stay, and functional recovery. All patients were followed for six months. RESULTS: No recurrence was observed in either group at six months. Two CM patients required reoperation on postoperative day one ( P = 0.15). EM was associated with shorter operative time ( P = 0.02), lower incidence of post-operative subdural residual fluid ( P = 0.015), better early hematoma reduction/subdural space reduction index ( P = 0.008), midline shift/symmetry improvement index ( P = 0.001), and lesser surgical site swelling ( P < 0.001). All patients were ambulant and had a Glasgow coma scale (GCS) 15 at discharge and at six months (including reoperated patients). Pain scores and functional recovery were comparable. EM patients had shorter hospital stays ( P = 0.004) and no significant complications. CONCLUSION: EM demonstrated favorable early radiological outcomes, fewer complications, and comparable functional recovery and recurrence versus CM in SNH-CSDH. Independent reproduction and larger multicentric trials are needed for validity and generalizability.

Humans↗

PubMed2026

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; I² = 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↗

PubMed2026

Prognostic value of the Island sign for hematoma expansion and functional outcome after intracerebral hemorrhage: a systematic review and meta-analysis.

PURPOSE: The Island Sign (IS) is a radiological finding observed in patients with intracerebral hemorrhage (ICH). This meta-analysis aimed to evaluate the association between IS and both hematoma expansion (HE) and functional outcomes by comparing ICH patients with and without IS. METHODS: We searched PubMed, Embase and Cochrane Library for studies of intracerebral hemorrhage reporting the IS. The primary outcomes were functional status and hematoma expansion, secondary outcome was mortality. Statistical analysis was performed using RStudio, effect sizes were calculated as odds ratios (ORs) with 95% confidence interval (95% CIs), and heterogeneity was assessed with I2 statistics. In addition, meta-regression and sensitivity analyses were performed, and publication bias was assessed through funnel plots and Egger's regression test. RESULTS: We included 21 observational studies with a total of 9,459 patients with spontaneous ICH, 1,769 of them had IS, while 7,690 did not. The mean age was 63.5 ± 13.2 and 5,835 (61.7%) were male. Poor functional outcomes (OR 2.77, 95% CI: 2.14-3.58, p < 0.0001, I2 = 4.9%) and hematoma expansion (OR 2.75, 95% CI: 1.87-4.03, p < 0.0001, I2 = 77.4%) were substantially higher in patients with IS, as well as the overall mortality rate (OR 2.54, 95% CI: 1.55-4.17, p = 0.0002, I2 = 0%). Meta-regression analysis showed no statistically significant association between imaging-related timing variables and hematoma expansion. Furthermore, the leave-one-out sensitivity analyses showed that no single study exerted a disproportionate influence on the overall effect for the examined outcomes, and Egger's linear regression tests were not statistically significant for both outcomes. CONCLUSION: Patients with the Island Sign are associated with higher rates of poor functional outcomes and hematoma expansion. Thus, IS is a relevant radiological finding with potential to support early risk stratification and optimize patient management and treatment selection.

Humans↗

PubMed2026

Tranexamic acid in spontaneous intracerebral hemorrhage: an updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Tranexamic acid (TXA) is a well-established antifibrinolytic medication in the general population. However, its efficacy and safety for patients with spontaneous intracerebral hemorrhage (ICH) remain inconclusive. Consequently, we conducted a systematic review and meta-analysis to assess the effectiveness and safety of TXA for spontaneous ICH. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) following established methodological standards. Our search encompassed eight electronic databases from inception to April 25, 2024. The primary outcome was a reduction in all-cause mortality. The secondary outcomes included improvements in functional independence, neurological impairment, activities of daily living, and reduction in hematoma expansion (HE). Fixed-effects or random-effects model were performed for pooled data where eligible. RESULTS: A total of 9 RCTs that initially enrolled 3,124 patients were included. There were no significant differences observed concerning all-cause mortality (RR, 1.03; 95% CI [0.89-1.18]), hematoma expansion (RR, 0.90; 95% CI [0.80-1.00]), improvement of functional independence (RR, 1.02; 95% CI [0.92-1.12], neurological impairment (MD, -0.88 [95% CI, -2.22-0.45]), or activities in daily living (MD, -0.83 [95% CI, -29.25-12.59]). The pooled data indicated that TXA for ICH was associated with a decrease in hematoma volume from baseline (MD, -1.74; 95% CI [-2.47 to -1.02]). No significant difference in adverse events was observed between the TXA group and the control group. CONCLUSIONS: In summary, TXA does not affect all-cause mortality, functional outcomes, or neurological impairment, nor does it reduce HE, despite reducing hematoma volulume. TXA use for ICH requires careful clinical consideration.

Humans↗

PubMed2026

Orbital involvement in sickle cell disease: A systematic review.

Orbital involvement in sickle cell disease (SCD) is rare but potentially vision-threatening and is often misdiagnosed due to overlap with infectious orbital disease. We conducted a systematic review of case reports and series describing orbital complications in patients with confirmed SCD, following PRISMA and MOOSE guidelines. Across 53 studies, 76 cases were identified. Patients were predominantly male (77.6%), with an average age of 13.2 years. Orbital disease was the initial SCD manifestation in 6.6%. Presentations included periorbital edema in all, proptosis in 64.1%, restricted ocular motility in 56.5%, reduced visual acuity in 28.1%, and bilateral involvement in 38.2%. Laboratory findings commonly included leukocytosis (73%) and raised inflammatory markers (86.7%). Radiologically, orbital subperiosteal hematoma were observed in 70%, combined orbital bone infarction and hematoma in 38.2%, and orbital bone infarction alone in 19.7%. Magnetic resonance imaging is critical for accurate diagnosis. Intracranial hemorrhage was present in 9.2%. Less frequent manifestations included orbital apex syndrome, lacrimal gland disease, and nonspecific soft tissue swelling. Management was primarily conservative (82.9%), and surgery was reserved for vision-threatening or intracranial complications. Complete recovery was achieved in 93.1% of cases. While severe vision-threatening complications are uncommon, early recognition remains critical to optimising outcomes in sickle cell orbitopathy.

Humans↗

PubMed2026

Who Is the Ideal Candidate for High-Definition Liposuction? A Systematic Review and Meta-Analysis.

BACKGROUND: High-definition liposuction (HDL) enhanced muscular definition by selectively removing superficial subcutaneous fat. Despite its growing popularity and high satisfaction rates, no consensus exists regarding the ideal candidate. This systematic review evaluates demographic factors, patient selection criteria, and complication rates associated with HDL. METHODS: A systematic review and meta-analysis were conducted utilizing PRISMA-P guidelines. PubMed, Cochrane Library, Embase, and Web of Science were searched for studies published within the past 10 years. Seventeen studies met inclusion criteria, comprising 9570 patients. Study designs included randomized controlled trials, cohort studies, and observational analyses reporting demographics, procedural details, and complications. Standardized data extraction was performed. Pooled analyses were conducted for hematoma and seroma, and univariable meta-regression assessed associations between mean age, BMI, and proportion of female patients with complication rates. RESULTS: Mean age was 36.0 years and mean BMI was 25.8 kg/m 2 (range: 18 to 66); 55% of patients were female. Selection criteria varied; most studies applied BMI thresholds (≤30 to 34 kg/m 2 ) and excluded poorly controlled diabetes, heavy smoking, and thromboembolic history. The abdomen, flanks, and chest were most treated. Mean fat removal was 4268.8 mL, with an average operative time of 235 minutes. Complication rates were low; the pooled incidence of seroma was 7% and hematoma was 1%. Meta-regression showed no significant associations between complications and age, BMI, or sex. Patient satisfaction was high. CONCLUSION: HDL is safe and effective across diverse populations; however, variability in selection criteria and reporting limits evidence-based definitions of ideal candidates. Further prospective studies with standardized reporting are needed.

Humans↗

PubMed2026

Evidence-based insights into medial pedicle reduction mammaplasty: A systematic review and meta-analysis.

BACKGROUND: Breast reduction relieves the physical and psychosocial burden of macromastia. Medial pedicle reduction mammaplasty may enhance vascular reliability, preserve nipple-areola complex (NAC) sensation, and sustain upper pole fullness, even in large-volume reductions. The purpose of this study was to assess the outcomes of medial pedicle breast reduction. METHODS: A search across ScienceDirect, Cochrane, and PubMed was conducted. Included studies reported on perioperative outcomes and complications of medial pedicle breast reduction. Data on demographics, surgical variables, complications, sensory recovery, volumetric changes, and patient satisfaction were extracted. Proportion meta-analysis was performed, and odds ratios were calculated for comparison with inferior pedicle breast reduction. RESULTS: Twenty-five studies comprising 1033 patients met the inclusion criteria. Mean BMI ranged from 27 to 42 kg/m2, with mean resection weights between 412 and 3828 g. Mean surgical times ranged from 104 to 204 min. Pooled complication rates were low: infection 1%, seroma 1%, hematoma 1%, fat necrosis 2%, NAC necrosis 1%, dehiscence 8%, and reintervention 5%. Odds of complications did not differ significantly from inferior pedicle reductions. NAC sensation typically recovered by 6-12 months, with no long-term deficits. Volumetric analyses demonstrated stable breast shape after the first postoperative year, with superior upper pole tissue maintained. Patient satisfaction ranged 75-100%, with higher ratings for scar appearance and overall aesthetics in medial pedicle reductions. CONCLUSION: Medial pedicle breast reduction is a well-established and reproducible technique, preserving NAC sensation, achieving stable long-term shape, and enhancing upper pole fullness. It offers satisfactory aesthetic outcomes compared to other traditional methods, even in large-volume reductions.

Humans↗

PubMed2026

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↗

PubMed2026

Intravenous Tranexamic Acid Reduces Perioperative Blood Loss in Reduction Mammoplasty With Immediate Implant-Based Reconstruction: A Randomized, Triple-Blinded, Placebo-Controlled Trial.

BACKGROUND: Postoperative hematoma and oozing can compromise outcomes after reduction mammoplasty with immediate reconstruction. Intravenous (IV) tranexamic acid (TXA) is antifibrinolytic, but prospective evidence in this setting is limited. OBJECTIVES: The aim of this study was to determine whether a single pre-incision dose of IV TXA reduces perioperative blood loss and fibrinolytic activation vs placebo. METHODS: In this randomized, triple-blinded, placebo-controlled trial, 60 women (American Society of Anesthesiologists I/II, 18-75 years) undergoing bilateral reduction mammoplasty with immediate implant-based reconstruction received TXA 10 mg/kg in 100 mL saline or placebo 10 min before incision. The primary outcome was total blood loss within 24 h (intraoperative suction + swab plus drain output). Secondary outcomes were perioperative changes in hemoglobin, D-dimer and fibrinogen, and complications within 30 days. Intention-to-treat analyses were performed. RESULTS: All patients completed follow-up. Total blood loss was lower with TXA than with placebo (mean ± standard deviation: 221.1 ± 72.4 vs 298.1 ± 90.6 mL; mean difference -77.0 mL; 95% CI, -122.4 to -31.6; P = .001). Intraoperative loss and 24 h drain output were also reduced. Postoperative D-dimer rise was attenuated with TXA (0.31 ± 0.15 vs 0.49 ± 0.22 µg/mL; P = .002); hemoglobin decline was smaller. No thromboembolic, neurologic, or allergic events occurred; no skin-flap necrosis was observed. CONCLUSIONS: Pre-incisional IV TXA safely reduces perioperative bleeding and fibrinolytic activity after reduction mammoplasty. These findings support incorporation of IV TXA into perioperative protocols. LEVEL OF EVIDENCE: 2 (THERAPEUTIC): For image description, please refer to the figure legend and surrounding text.

Humans↗

PubMed2026

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↗

PubMed2026

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↗

PubMed2025

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↗

PubMed2026

[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↗

PubMed2026

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 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↗

PubMed2026

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] = -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 = -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] = 1.90 to 37.00). Conversely, melatonin was not associated with an increased risk (OR = 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↗

PubMed2026

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 m²): non-CKD (eGFR ≥ 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↗

PubMed2026

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↗