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PubMed2026

Corticosteroids as adjunctive therapy to standard treatment in Kawasaki disease: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

UNLABELLED: Kawasaki disease (KD) is an acute systemic vasculitis and the leading cause of acquired heart disease in children in developed countries. While IVIG plus aspirin remains standard treatment, 10-20% of patients are IVIG-resistant and face an elevated risk of coronary artery abnormalities. Corticosteroids have been explored as adjunctive therapy, though evidence on their benefit remains inconsistent. To assess the efficacy and safety of adjunctive corticosteroids in Kawasaki disease across key clinical outcomes. This PRISMA 2020-compliant systematic review and meta-analysis included RCTs identified through database searches up to April 2026. Risk of bias was assessed using Cochrane RoB 2.0. Data were pooled using random-effects models to estimate risk ratios (RRs) and mean differences (MDs) with 95% CIs. Subgroup analyses, leave-one-out sensitivity analyses, and GRADE certainty appraisal were also performed. Eight studies (n = 4106) were included. No significant differences were found in coronary artery abnormalities (CAA) within 1 month (RR 0.49, 95% CI 0.17-1.42), after 1 month (RR 0.81, 95% CI 0.43-1.55), fever duration (MD - 1.75, 95% CI - 3.71 to 0.21), or adverse events (RR 1.08, 95% CI 0.57-2.07). Hospital stay was modestly shorter with corticosteroids (MD - 0.99, 95% CI - 1.86 to - 0.11). Exploratory subgroup analyses suggested potential benefits with prednisolone-based and prolonged corticosteroid regimens for selected outcomes; however, these findings should be interpreted cautiously given multiple subgroup comparisons. Overall certainty of evidence was very low. CONCLUSION:  Adjunctive corticosteroids did not significantly improve major outcomes in KD. Prednisolone-based regimens showed some promise, but high-quality trials are still needed before any firm conclusions can be drawn. WHAT IS KNOWN: • Corticosteroids have been studied as adjunctive therapy for Kawasaki disease, but their effects on coronary outcomes and other clinical outcomes remain inconsistent. WHAT IS NEW: • This meta-analysis found no significant improvement in major outcomes with adjunctive corticosteroids, although prednisolone-based and prolonged regimens may provide benefits for selected outcomes.

Humans↗

PubMed2026

Efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with active psoriatic arthritis: 52-week results from the randomised, double-blind, placebo-controlled phase 3 POETYK PsA-1 trial.

OBJECTIVES: The randomised, double-blind, placebo-controlled, phase 3 Program fOr Evaluation of TYK2 inhibitor Psoriatic Arthritis-1 (POETYK PsA-1) trial evaluated the efficacy, safety, and tolerability of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with PsA naïve to biologic disease-modifying antirheumatic drugs. METHODS: Adults with active PsA, high-sensitivity C-reactive protein concentration ≥ 3 mg/L, and ≥ 1 PsA-related hand and/or foot erosion detectable via radiograph were randomised 1:1 to oral deucravacitinib 6 mg once daily or placebo through week (W) 16. At W16, patients continued receiving deucravacitinib or switched from placebo to deucravacitinib through W52. The primary endpoint was American College of Rheumatology 20% improvement in response (ACR20) at W16. Nonresponder imputation was used for missing data. Efficacy and safety were evaluated through W52. Post hoc rank analysis of covariance was used to evaluate structural damage with no missing data imputation. RESULTS: In 670 patients, a significantly greater proportion of those receiving deucravacitinib vs placebo achieved ACR20 at W16 (54.2% vs 34.1%, P < .001). Responses with deucravacitinib were increased at W52. Patients who switched from placebo to deucravacitinib achieved improvements similar to those in patients who received continuous deucravacitinib. Inhibition of structural damage was observed at W16 and W52. At W16, incidences of serious adverse events (AEs) (deucravacitinib, 1.8%; placebo, 2.4%) and discontinuations due to AEs (2.4%; 1.8%) were low and remained low through W52, without imbalances in cardiovascular events, malignancies, or opportunistic infections. No new safety signals were detected; no deaths occurred. CONCLUSIONS: Deucravacitinib demonstrated superiority vs placebo for clinical responses, patient-reported outcomes, and structural damage inhibition in patients with PsA, with favourable tolerability and safety.

Humans↗

PubMed2026

Qualitative evidence of service user experiences and perspectives on long-acting injectable buprenorphine for opioid treatment - a scoping review.

BACKGROUND: There is substantial literature on opioid treatment program (OTP) formulations and how they relate to the pharmacotherapy service user experience. As a newer formulation, less is known about service user experiences of long-acting injectable buprenorphine (LAIB). The aim of this scoping review is to map the qualitative evidence and gaps in the literature on service user experiences and perspectives of LAIB. METHODS: Our search strategy included Medline, Embase, PsycINFO, CINAHL, Scopus and Web Science, and citation chaining, from January 2016 to June 2025. Studies were included if reporting qualitative descriptions of LAIB service user experiences of treatment for opioid dependence, inclusive of qualitative, mixed methods (description of qualitative data only), case reports and English language. Articles were screened by two reviewers. A living experience first author led the analysis using inductive coding and thematic analysis, to produce a descriptive summary of synthesised findings alongside key study characteristics and quality appraisal, adhering to the Systematic reviews and Meta-Analysis for Scoping Reviews (PRISMA-ScR) checklist. RESULTS: After screening 838 titles/abstracts and reviewing 150 full texts, 40 studies met the eligibility criteria. All were conducted in high income countries, principally the US (n=12); Australia (n=10); and England and Wales (n=9). We identified five themes: Navigating LAIB treatment; Embodied and relational effects of LAIB; Impact and role of the service provider; Narratives of harm reduction and recovery; Stigma and criminalisation. LAIB was commonly experienced as increasing convenience, stability and freedom from daily supervised dosing, enabling improved work, travel, privacy and social participation. Reduced clinic/dosing contact often lessened enacted stigma and treatment burden. However, experiences were heterogenous. Some participants described injection-site discomfort, uncertainty about dose adequacy, reduced flexibility once injected, and ambivalence about LAIB effects. There was inconsistency in LAIB service user reports on service connection, isolation and psychosocial support. Treatment experiences were strongly shaped by provider practices. CONCLUSIONS: Findings underscore the need for integrated, flexible, harm-reduction oriented and person-centred LAIB treatment models that prioritise choice, autonomy and therapeutic relationships to maximise benefit for service users. However, evidence of LAIB service user experiences is concentrated in high-income countries, and the absence of perspectives from low- and middle-income country settings represents a substantial gap in the evidence base.

LAIB↗

PubMed2026

Effectiveness of the DASH diet versus alternative dietary interventions for hypertension management: A systematic review and meta-analysis.

BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet is widely recommended for blood pressure control; however, its comparative effectiveness relative to other structured dietary interventions remains uncertain. OBJECTIVE: To evaluate the comparative effectiveness of the DASH diet versus alternative dietary interventions on blood pressure and cardiometabolic outcomes in adults. METHODS: A systematic review and meta-analysis of randomized controlled trials was conducted in accordance with PRISMA guidelines. Multiple databases were searched from inception to February 2026. Eligible studies included adults with elevated blood pressure or hypertension comparing the DASH diet with other dietary interventions or usual care. Continuous outcomes were pooled using random-effects models and expressed as mean differences (MD) or standardized mean differences (SMD). Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated using the GRADE approach. RESULTS: A total of 22 randomized controlled trials were included in the qualitative synthesis, of which 10 were included in the meta-analysis. The DASH diet did not demonstrate a statistically significant advantage over comparator diets in reducing systolic blood pressure (MD = 1.30; 95% CI: -1.54 to 4.14) or diastolic blood pressure (MD = 0.21; 95% CI: -3.72 to 4.14), with substantial heterogeneity observed across studies. Significant effects were identified for selected cardiometabolic outcomes, including reductions in urinary sodium excretion (MD = -32.89; 95% CI: -62.76 to -3.01), LDL cholesterol (MD = -8.59; 95% CI: -14.64 to -2.54), and glycated hemoglobin (HbA1c) (MD = -0.49; 95% CI: -0.52 to -0.46), as well as an increase in urinary potassium excretion (MD = 11.76; 95% CI: 4.08 to 19.44). The certainty of evidence ranged from moderate to very low across outcomes. CONCLUSIONS: The DASH diet was not superior to other dietary interventions in reducing blood pressure; however, it demonstrated consistent benefits in selected cardiometabolic parameters. Given the overall low certainty of evidence and substantial heterogeneity, these findings should be interpreted cautiously. Future research should focus on well-designed trials with standardized outcomes and longer follow-up to clarify comparative effectiveness.

Humans↗

PubMed2026

Transpulmonary proteomic gradient analysis in women with pulmonary arterial hypertension associated with systemic sclerosis.

This study investigated proteomic alterations in the pulmonary circulation of patients with pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) by analyzing the transpulmonary protein gradient and comparing the proteomic profiles with systemic sclerosis (SSc) without PAH. Twenty women were included (10 PAH-SSc, 64.6 ± 10.8 years; 10 SSc, 62.8 ± 11.5 years). The transpulmonary gradient was defined as the difference in biomarker concentrations between wedge-position and pulmonary artery blood samples. Peptides were analysed using liquid chromatography-mass spectrometry, and differentially abundant proteins were identified with Proteome Discoverer. Protein-protein interaction networks were generated with STRING and visualized in Cytoscape. A total of 270 proteins were detected, with no significant transpulmonary gradient alterations. However, patients with PAH-SSc showed distinct proteomic profiles compared to SSc. Multivariate analysis identified 48 differentially abundant proteins in pulmonary artery plasma, with 15 overrepresented and 33 downregulated in PAH-SSc. Among these, the downregulation of transforming growth factor-beta-induced protein ig-h3 (TGFβI/ig-h3) points to a potential involvement of the TGF-β-related extracellular matrix remodelling pathway in PAH-SSc. However, further validation in larger and independent cohorts is required before its relevance as a biomarker or therapeutic target can be established. In conclusion, while no transpulmonary proteomic gradient was observed, the proteomic profiles of PAH-SSc and SSc were different. The profile in PAH-SSc was characterized by differences in immune response, lipid metabolism, and hemostatic proteins. SIGNIFICANCE: This study offers the first proteomic characterization of the transpulmonary gradient in PAH-SSc and SSc. Although no differences in the gradient were found, the pulmonary artery plasma proteome of PAH-SSc patients showed a distinct pattern compared to SSc. Several proteins associated with immune function, haemostasis, and cellular processes were altered, which may indicate specific pathophysiological features of PAH-SSc or suggest how lung dysfunction develops in SSc. Targeting dysregulated proteins like TGFβI/ig-h3 or addressing immune-coagulation imbalances may support future research studies. Overall, these findings refine the molecular profile of PAH-SSc and provide a basis for future large-scale studies aimed at clarifying disease mechanisms and identifying clinically relevant molecular signatures.

Humans↗

PubMed2026

Risk Factors and Predictive Model for Postoperative High Myopia in Children Undergoing Congenital Cataract Surgery With Intraocular Lens Implantation.

PURPOSE: To identify risk factors associated with the development of high myopia following congenital cataract surgery and to establish a robust predictive model. DESIGN: Retrospective clinical cohort study. SUBJECTS: This retrospective study included 106 pediatric patients who underwent congenital cataract surgery with primary IOL implantation (mean follow-up 8.19 years). The model was externally validated in an independent cohort of 72 patients with a mean follow-up of 7.83 years. METHODS: Preoperative and postoperative ocular biometric parameters were collected. Risk factors for postoperative high myopia were analyzed using Cox proportional hazards regression, which served as the basis for model construction. The predictive performance of the model was rigorously evaluated for discrimination and calibration. Discriminative ability was quantified using Harrell's C-index and the area under the receiver operating characteristic curve (AUC). Model calibration was assessed via calibration plots by comparing predicted probabilities with actual observed outcomes. Internal validation was performed using a bootstrapping method (500 iterations) to ensure model stability and adjust for potential overfitting. RESULTS: An initial postoperative refraction of <+0.75D, and a higher IOL Power to Axial length Ratio (IOL/AL ratio) were identified as significant risk factors for the development of postoperative high myopia. Shorter preoperative axial length was associated with a greater magnitude of postoperative myopic shift. The predictive model demonstrated robust performance, achieving a C-index of 0.711 (internal validation C-index: 0.713). The area under the receiver operating characteristic curve (AUC) values for predicting high myopia at 5 and 10 years were 0.858 and 0.745, respectively. Furthermore, calibration curves demonstrated excellent agreement between the predicted and observed outcomes throughout the follow-up period. In external validation, the model achieved a C-index of 0.825, 5-year AUC of 0.833, and 10-year AUC of 0.713. CONCLUSIONS: Our analysis established that initial postoperative refraction <+0.75D, and an elevated IOL/AL ratio are key determinants of high myopia risk following surgery. Shorter preoperative axial length was associated with a greater magnitude of postoperative myopic shift. This predictive framework provides clinicians with a practical tool to optimize preoperative IOL selection and identify high-risk infants who require vigilant myopia prevention and balanced amblyopia management.

Humans↗

PubMed2026

Characteristics of post-exercise responders versus non-responders following aerobic or isometric exercise in physically inactive adults of African and South Asian descent with high-normal blood pressure or grade I hypertension.

OBJECTIVE: To investigate interindividual variability in post-exercise hypotension (PEH) and to characterise cardiovascular and autonomic differences between responders and non-responders following aerobic and isometric exercise in adults of African and South Asian descent with elevated blood pressure (BP). METHODS: Physically inactive adults of African and South Asian descent living in Suriname (18-65 years) with high-normal BP or grade I hypertension participated in a randomised controlled crossover trial. In this randomised cross-over trial, 47 adults (50.1 ± 10.8 years; 38% male) with high-normal blood pressure or grade I hypertension completed three conditions: aerobic exercise (30 min at 40-60% heart rate reserve), isometric handgrip exercise, and a non-exercise control. Ambulatory BP was assessed over 24 h. PEH was defined as the net effect: (post-exercise - pre-exercise) - (post-control - pre-control). Participants were classified as responders if daytime BP decreased ≥5 mmHg. Arterial stiffness, cardiac, and autonomic parameters were assessed. RESULTS: Following aerobic exercise, 46% of participants were classified as systolic responders compared with 28% after isometric exercise. No baseline differences were observed in demographic or clinical characteristics between responders and non-responders, suggesting that PEH variability may reflect underlying physiological rather than clinical differences. Aerobic responders demonstrated greater reductions in aortic augmentation index (-19.4% vs. -10.9%, p = 0.05), larger increases in stroke volume (+8.1 vs. -5.3 mL, p = 0.05) and cardiac output (+1.54 ± 1.89 vs. +0.58 ± 1.60 L/min, p = 0.009), and more favourable autonomic recovery. Among all variables, only the change in cardiac output was associated with PEH magnitude (r = -0.46, p = 0.006). No consistent physiological differences were observed following isometric exercise. CONCLUSION: PEH following aerobic exercise is characterised by a distinct responder phenotype associated with greater reductions in aortic augmentation index and favourable cardiac adaptations. These findings highlight substantial interindividual variability in BP responses and support the need for individualised exercise strategies in hypertension management.

Adolescent↗

PubMed2026

[Study of a patient with azoospermia due to variant of MOV10L1 gene].

OBJECTIVE: To explore the clinical and genotypic characteristics of a patient with Sertoli cell-only syndrome (SCOS) due to variants of MOV10L1 gene. METHODS: A 27-year-old patient with Non-obstructive azoospermia (NOA) underwent routine semen analysis. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), prolactin (PRL), and testosterone (T) were determined by chemiluminescence assays. Peripheral blood samples were collected for G-banded karyotyping analysis. Multiplex PCR fluorescence detection was used to screen for AZF gene microdeletions. Whole exome sequencing (WES) and Sanger sequencing were performed simultaneously. Testicular biopsy tissues were subjected to Hematoxylin-Eosin (HE) staining to assess seminiferous tubule cell composition, and MOV10L1 protein expression was detected by immunohistochemical staining. Bioinformatics tools were employed to predict the pathogenicity of variants and their impact on protein structure and function. This study was approved by the Medical Ethics Committee of the Guangdong Institute of Reproductive Sciences [Ethics No.: 2023(01)]. RESULTS: The patient's two semen analyses had failed to detect any sperm. Hormone tests indicated elevated FSH (22.32 mIU/mL) and PRL (397.6 mIU/mL), while T (3.68 nmol/L) and E2 (38.32 pmol/L) were reduced. Chromosomal karyotyping revealed 46,XY, and no AZF gene deletion was detected. WES and Sanger sequencing detected compound heterozygous variants of the MOV10L1 gene, including a c.345C>A (p.C115X) nonsense variant and a c.3323C>T (p.T1108I) missense variant, with the former being unreported previously. HE staining showed only Sertoli cells in the seminiferous tubules, confirming the diagnosis of SCOS. Immunohistochemical staining revealed absent MOV10L1 protein expression in the testicular tissue. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the c.345C>A (p.C115X) was classified as a pathogenic variant (PVS1+PM2_Supporting+PP4), while the c.3323C>T (p.T1108I) was deemed variant of uncertain significance (PM2_Supporting+PP3_Supporting+PP4). Bioinformatics analysis demonstrated that c.345C>A (p.C115X) may cause premature termination of protein translation, while c.3323C>T (p.T1108I) may disrupt the hydrophobicity of the RNA helicase domain, reducing the active pocket volume and decreasing its affinity for MILI protein. CONCLUSION: This study has diagnosed a case of SCOS due to compound heterozygous variants of the MOV10L1 gene, which also enriched its mutational spectrum.

Humans↗

PubMed2026

Prevalence of Slowly Expanding Lesions in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Chronic active lesions (CALs) reflect chronic inflammation in multiple sclerosis (MS). Slowly expanding lesions (SELs) are CALs identified on conventional MRI by linear, concentric expansion over time, while paramagnetic rim lesions (PRLs) are CALs characterized by a paramagnetic rim on susceptibility-sensitive MRI. However, the prevalence of SELs and their overlap with PRLs remain unclear. The aims of this study were to (1) estimate the proportion of SELs among all T2 lesions and the proportion of patients with at least 1 SEL and (2) assess the proportion of SELs overlapping with PRLs. METHODS: We systematically searched PubMed, Scopus, Web of Science, and Embase on February 1, 2026, for studies evaluating SELs in MS. At least 2 authors independently assessed study eligibility. Primary outcomes were the pooled proportion of SELs among T2 lesions and the proportion of patients with at least 1 SEL. We estimated mean per-patient volumes of SELs and total T2 lesions and the proportion of SELs overlapping with PRLs. Random-effects generalized linear mixed-effects models and inverse-variance methods were used, with between-study heterogeneity assessed using τ2 and I2 and robustness using sensitivity analyses. Univariable meta-regression explored heterogeneity. PROSPERO: CRD42024603778. RESULTS: Of 5,980 records, 20 studies comprising 4,786 patients with MS were included (mean age: 43.6 ± 6.3 years; 63.7% female). Sample sizes varied by outcome. SELs accounted for 14% (95% CI 10-21) of all T2 lesions, and 78% (67-85) of patients had at least 1 SEL. After sensitivity analysis, per-patient mean volumes were 1.42 mL (0.79-2.06) for SELs and 10.6 mL (8.53-12.67) for total T2 lesions. In total, 11% (6-20) of SELs overlapped with PRLs. In subgroup analyses, proportions of SELs were similar in relapsing-remitting and progressive MS (15%), but the proportion of patients with at least 1 SEL was higher in progressive MS. Between-study heterogeneity was high across analyses with no significant sources identified. DISCUSSION: Although SELs represent a minority of T2 lesions, most patients have at least 1 SEL and a subset overlaps with PRLs, suggesting a partial correspondence between these 2 imaging markers of chronic inflammatory activity. Limitations include possible publication bias, high unexplained heterogeneity, differences in SEL identification methods, and differences in MRI time point number/timing.

Humans↗

PubMed2026

Application of 13C MRS demonstrates carbohydrate feeding spares muscle but not liver glycogen utilization during high-intensity interval exercise.

We examined liver and muscle glycogen utilization during high-intensity interval cycling, and the impact of carbohydrate (CHO) feeding, using noninvasive 13C magnetic resonance spectroscopy (MRS). Following 24 h of standardized dietary intake, nine male cyclists completed 8 × 5-min intervals (1-min recovery), ingesting either placebo (PLA), 60 g maltodextrin (CHO), or 60 g maltodextrin plus caffeine, taurine, l-theanine, l-citrulline, and citicoline (CHO+) in a randomized crossover design. 13C MRS and 1H imaging were performed pre- and postexercise to determine liver and muscle glycogen and liver volume, respectively. Liver glycogen utilization was not significantly different between trials (P = 0.101) despite lower postexercise plasma glucagon concentrations in CHO and CHO+ (P = 0.001). In contrast, muscle glycogen utilization was significantly lower (∼40%) with CHO feeding compared with PLA (P = 0.006), yet this sparing effect was not evident with CHO+ (P = 0.073) in accordance with a higher mean power output during the late intervals (+2.8%, P = 0.046). Plasma glucose was comparable between trials (P = 0.175), whereas plasma lactate was higher in CHO+ versus CHO (P = 0.003), alongside lower blood bicarbonate (P = 0.005), base excess (P < 0.001), and total CO2 (P = 0.004). These findings demonstrate preferential use of skeletal muscle glycogen during high-intensity interval training (HIIT), which is attenuated under conditions of CHO feeding. This sparing effect is, however, not evident with the coingestion of a caffeine-containing multi-ingredient blend, potentially due to an increased capacity to sustain higher power outputs resulting in greater glycogen utilization.NEW & NOTEWORTHY Using 13C MRS, we provide data demonstrating preferential use of skeletal muscle glycogen during HIIT. Furthermore, data show muscle glycogen utilization is attenuated with CHO feeding, yet sparing is not evident when coingesting a caffeine-containing formulation, potentially reflecting increased capacity to perform more total work rather than a direct metabolic effect of caffeine. In contrast, liver glycogen utilization was not significantly different with CHO feeding despite a modest reduction of ∼5 g versus placebo.

Male↗

PubMed2026

Hyper-oncotic albumin administration reduces mortality in acute Respiratory Distress Syndrome compared to crystalloid: a systematic review and meta-analysis.

BACKGROUND: To evaluate the association between albumin administration as volume replacement and mortality in adult ARDS patients, we performed this meta-analysis and trial sequential analysis (TSA). METHODS: We searched databases including PubMed, Science Direct, Scopus, Web of Science databases and Cochrane Central Register of Controlled Trials up to 12 December 2024. We screened trials that included adult ARDS patients and compared albumin with crystalloid. The 28-day mortality served as the primary endpoint, while the oxygenation change, the length of ICU stay and the length of hospital stay were designated as secondary outcomes. To clarify the differing concentrations of albumin, we formed two distinct subgroups: the hyper-oncotic albumin subgroup (≥20%) and the iso-oncotic albumin subgroup (4%∼5%). Statistical synthesis was performed with Cochrane Review Manager 5.4.1, employing random-effects models. To mitigate random errors, TSA was implemented with α = 0.05 and β = 0.20 parameters. RESULTS: The analysis incorporated 5 publications: 3 randomized controlled trials (RCTs) and 2 non-randomized studies (NRSs). Overall mortality was lower in the albumin group (33.2%, 97/292) than in the crystalloid group (44.9%, 133/296) (OR = 0.61, 95%CI 0.43-0.85, p = 0.004). RCTs (n = 204) showed no benefit (OR = 0.83, p = 0.54), but NRSs (n = 384) demonstrated reduced mortality (OR = 0.52, p = 0.002). Hyper-oncotic albumin was associated with lower mortality in NRSs (OR = 0.40, p = 0.02) but not in RCTs (OR = 0.74, p = 0.57). Iso-oncotic albumin showed no benefit (OR = 0.88, p = 0.72). Regarding the impact of albumin on oxygenation, significant improvements in oxygenation were observed only on the first (p = 0.05) and second days (p < 0.0001). The TSA indicated a continued need for high-quality RCTs. CONCLUSIONS: Our analysis suggests that hyper-oncotic albumin may reduce mortality and improve early oxygenation in ARDS patients compared to crystalloids. Larger RCTs are urgently needed to validate these findings and define their potential role in clinical management.

Humans↗

PubMed2026

Access to palliative care in rural settings: A mixed-methods systematic review.

BACKGROUND: Rural populations experience persistent inequities in access to palliative care. Existing evidence often describes individual barriers separately, with less attention to how access breaks down across the care pathway or how different service configurations shape access. OBJECTIVES: To synthesise evidence on access to palliative care in rural settings and examine how access barriers, service models, and implementation conditions interact across the care pathway. METHODS: A mixed-methods systematic review using a convergent integrated approach searched nine databases (PubMed, Embase, CINAHL, Web of Science, Scopus, PsycINFO, CNKI, WanFang, SinoMed) from inception to 15 March 2026, supplemented by hand-searching. Eligible studies were primary qualitative, quantitative, and mixed-methods studies on access to palliative care for adults in rural or non-urban settings. Two reviewers independently screened studies, extracted data, and assessed quality using the Mixed Methods Appraisal Tool. Findings were mapped to the Levesque access framework, analysed using the updated Consolidated Framework for Implementation Research, and integrated through mixed-methods synthesis, with additional coding of service models. RESULTS: Thirty-four studies were included, of which 26 were conducted in high-income countries and eight in low- and middle-income countries. Service configurations included specialist or hospice-oriented care, generalist or primary-care-oriented care, mixed specialist-generalist models, home-based and caregiver-centred care, nurse-coordinated services, telehealth-supported care, and community or implementation-oriented approaches. Access broke down cumulatively across four interdependent stages: recognition, entry, reach, and use and continuity, with affordability constraining every stage. Recognition was limited by low awareness, poor service visibility, and delayed identification of need. Entry was shaped by stigma, trust, family expectations, and unclear referral processes. Reach was constrained by distance, transport, workforce shortages, limited specialist capacity, and weak infrastructure. Use and continuity were affected by fragmented coordination, weak transitions, unstable follow-up, and reliance on family caregivers. Access problems varied across service configurations. Evidence on service innovations was methodologically less certain, and the overall evidence base remained concentrated in high-income countries. CONCLUSIONS: Access to palliative care in rural settings is best understood as a pathway and service-configuration problem rather than simply a deficit in service availability. Improving access requires earlier recognition, clearer referral routes, stronger specialist-generalist and nursing links, better support for family caregivers, and greater attention to affordability, continuity, and rural settings with limited resources. REGISTRATION: International Prospective Register of Systematic Reviews: CRD420261340783.

Health Services Accessibility↗

PubMed2026

Naltrexone Is Superior to Placebo for Abstinence and Craving Reduction in Alcohol-Associated Cirrhosis: NAL-CI Trial.

BACKGROUND AND AIMS: Alcohol use disorder (AUD) coexisting with cirrhosis carries high morbidity and mortality, with no approved pharmacotherapy for AUD. We evaluated the safety and efficacy of naltrexone, an opioid receptor antagonist, in patients with compensated alcohol-associated cirrhosis (AaC) and AUD. METHODS: One hundred patients with compensated AaC and DSM-5 AUD were randomised 1:1 to naltrexone (50 mg/day) or placebo for 12 weeks. The primary endpoint was point-prevalence abstinence at 12 weeks, defined as no alcohol use in the four preceding weeks. Secondary endpoints included craving (Obsessive Compulsive Drinking Scale [OCDS]-Obsessive and Compulsive subscales), lapses, relapses, and hepatic safety. Standardised psychosocial support was provided to both arms. RESULTS: Baseline characteristics were well matched between groups (mean MELD 12.6 vs. 12.7; CTP score 5.9 vs. 6.2; age 42.9 vs. 44.3 years). AUDIT and OCDS scores were comparable between groups. Abstinence at 12 weeks was significantly higher with naltrexone: 64% (32/50) versus 22% (11/50), p < 0.001; OR 10.86 (95% CI: 1.89-62.2). Naltrexone significantly reduced lapses at 3 months (28% vs. 54%, p = 0.008) and showed a trend toward fewer heavy-drinking relapses (12% vs. 28%, p = 0.07). Maintenance of abstinence at 6 months favoured naltrexone (22% vs. 8%, p = 0.09). No patient developed hepatic decompensation attributable to study medication, and no AST/ALT elevation exceeding 5× ULN was observed in either group. Mean craving scores were lower with naltrexone by week 12 than with placebo: OCDS-O score (6.63 ± 1.16 vs. 9.29 ± 1.78, p < 0.01) and OCDS-C score (6.35 ± 1.23 vs. 9.02 ± 1.86, p < 0.01). Adverse events were comparable between the groups. CONCLUSION: Naltrexone is safe and effective in patients with compensated alcohol-associated cirrhosis, achieving a threefold higher abstinence rate and significantly reducing craving compared with placebo. These findings support the use of naltrexone as a pharmacological option in patients with compensated AaC and AUD. TRIAL REGISTRATION: NCT04391764.

Humans↗

PubMed2026

Diagnostic performance of intraoperative in vivo hyperspectral imaging for meningioma grading and molecular alterations: results from a prospective feasibility study.

OBJECTIVE: Hyperspectral imaging (HSI) is an emerging intraoperative, noninvasive, contrast agent-free imaging modality that enables quantitative assessment of tissue composition. The present study aimed to investigate whether HSI-derived tissue parameters correlate with WHO grade and molecular markers of aggressiveness in cranial meningiomas. METHODS: In this prospective study, intraoperative in vivo HSI was performed using the TIVITA tissue system, capturing spectral signatures between 500 and 1000 nm. Quantitative tissue parameters included tissue oxygen saturation (StO2), near-infrared perfusion index, organ hemoglobin index (OHI), and tissue water index (TWI). HSI parameters were correlated with histopathological WHO grade and molecular alterations, including CDKN2A/B deletion, TERT promoter mutation, and 1p/22q loss. Group differences were analyzed using one-way ANOVA, and diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. RESULTS: Forty-six meningiomas were included, comprising WHO grade 1 (n = 35) and WHO grade 2-3 (n = 11) tumors. TWI was significantly higher in WHO grade 2-3 meningiomas compared with WHO grade 1 tumors (mean 0.49 [SD 0.12] vs 0.38 [SD 0.17], p = 0.048). ROC analysis demonstrated an area under the ROC curve (AUC) of 0.71 (95% CI 0.56-0.86, p = 0.036) for TWI in discriminating higher-grade disease. A TWI cutoff ≥ 0.367 identified all WHO grade 2-3 meningiomas with 100% sensitivity and 100% negative predictive value. In a molecular subgroup (n = 15), OHI appeared higher in tumors with homozygous CDKN2A/B deletion than in nondeleted tumors (mean 0.77 [SD 0.04] vs 0.62 [SD 0.10]). However, only 3 CDKN2A/B-deleted cases were available, and these findings should be considered descriptive. ROC analysis yielded an AUC of 0.89 (95% CI 0.71-1.00). An OHI cutoff ≥ 0.712 identified all three CDKN2A/B-deleted tumors (100% sensitivity), with 83.3% specificity and 86.7% accuracy. CONCLUSIONS: The present investigation demonstrated that HSI-derived tissue water and hemoglobin metrics provide biologically meaningful information in meningiomas. Low tissue water content appeared to rule out higher-grade diseases in this first subset cohort, while elevated hemoglobin showed a potential association with CDKN2A/B deletion in a small exploratory subgroup. These findings support the potential of HSI as a real-time noninvasive tool for intraoperative risk stratification and should be evaluated in large-scale studies. German Clinical Trials Register no. DRKS00036771 (www.drks.de).

Humans↗

PubMed2026

PCa Detection in PI-RADS 4 and 5 Lesions: Comparison of [68Ga]Ga-PSMA-11 PET/CT-Guided Robot-Assisted Biopsy Versus mpMRI Cognitive-Fusion TRUS-Guided Prostate Biopsy.

Lesions with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 4 or greater on multiparametric MRI (mpMRI) indicate a high likelihood of prostate cancer (PCa), and guidelines recommend a targeted biopsy. We aimed to compare the diagnostic performance of robotic arm-assisted [68Ga]Ga-PSMA-11 PET/CT-guided prostate biopsy (PGPB) with mpMRI-directed cognitive-fusion transrectal ultrasound-guided biopsy (MCFB) in biopsy-naïve men with clinical findings suggestive of PCa. Methods: This prospective, single-center, randomized clinical trial (NCT05137561) enrolled biopsy-naïve men age 50-90 y with elevated levels of prostate-specific antigen (≥4 ng/mL) and abnormal digital rectal examination findings. All participants underwent mpMRI, and those with a PI-RADS score of 4 or greater were randomized into 2 arms. In arm 1, participants underwent PGPB for a [68Ga]Ga-PSMA-avid lesion, and participants in arm 2 underwent MCFB. Participants in arm 1 with PET-negative findings subsequently underwent MCFB, and participants with negative biopsy results underwent PET and PGPB. The primary outcome was the detection of PCa. Secondary outcomes included complication rates and participant-reported pain. Result: Of the 267 participants enrolled, 81.3% (217) had lesions with a PI-RADS score of 4 or greater and were randomized to either PGPB (n = 112) or MCFB (n = 105). PCa was detected in 97.1% of participants (101/104) in arm 1 and 81.0% (85/105) in arm 2 (P < 0.05). PGPB showed higher diagnostic accuracy for PI-RADS 5 lesions (100% vs. 95.1%, P = 0.09). Major complications were observed in arm 2 only (n = 5). Arm 1 had significantly fewer complications (10.8% vs. 51.4%, P < 0.01), a lower median visual analog scale score for pain (3 vs. 5), and shorter procedure times. The core positivity rate was higher in arm 1 (60% ± 20%), despite obtaining fewer cores. Conclusion: [68Ga]Ga-PSMA-11 PGPB demonstrated higher diagnostic performance, fewer complications, and better tolerability compared with MCFB. This approach enables integrated diagnosis and staging, offering a promising alternative for efficient, safe, and accurate evaluation of prostate cancer.

Humans↗

PubMed2026

Quality of life and gender identity in females with congenital adrenal hyperplasia after genital restoration surgery: A single-center experience.

BACKGROUND: Legislation restricting surgical interventions in children with differences of sex development (DSD) has intensified debate about female genital restoration surgery (FGRS) in patients with congenital adrenal hyperplasia (CAH). Long-term patient-reported outcomes are needed regarding the optimal timing of surgery. OBJECTIVE: We aimed to assess health-related quality of life (HRQoL), gender identity, and family satisfaction regarding surgical timing and outcome in females with CAH following genital restoration surgery. STUDY DESIGN: Cross-sectional survey of CAH patients who underwent surgery between January 2007 to December 2016 at our institution. Validated instruments (KINDL questionnaire for HRQoL, Utrecht Gender Dysphoria Scale, UGDS) and structured telephone interviews were employed. RESULTS: Data on HRQoL was available for 25 patients (self- and/or parent-reported) out of 56 eligible patients (45% response rate). Median age at first surgery was 6 months (range: 3-137 months). Patients' age at time of participation ranged from 2 to 28 years. All had 21-hydroxylase deficiency (92% salt-wasting form) with Prader grades ranging from II-V. Wound dehiscence requiring secondary suturing occurred in 15% of patients with primary surgery at our center, while only one (4%) patient developed vaginal stenosis after early primary vaginoplasty. Two additional patients (8%) with prior outside surgery required vaginal revision after FGRS at age 12. HRQoL scores were comparable to healthy reference populations across most age groups. Children aged 3-6 and adolescents and young adults showed no significant difference from reference values, while children aged 7-13 showed a slight elevation. None of five patients ≥14 years demonstrated gender dysphoria (all UGDS scores <40, threshold ≥40). 14 patients and families were also interviewed by telephone. All preferred early surgical timing. No family expressed regret about the decision or preferred delayed surgery. DISCUSSION: This study provides validated intermediate-term patient- and parent-reported outcomes after FGRS in CAH. Key limitations include the small sample size, single-center design, and young age of most patients. Selection bias may exist, though participating families included those who underwent revision surgery. The absence of a non-operated comparison group reflects current clinical reality, as nearly all CAH patients with urogenital sinus underwent surgical correction. CONCLUSIONS: Females with CAH reported normal HRQoL and a comfortable female gender identity after early FGRS. The patients and their families expressed a preference for early surgery. However, there is need for longer-term follow-up to assess sexual function and reproductive outcomes as well comparison of outcomes with a non-operated group.

Humans↗

PubMed2026

Increasing gut short-chain fatty acids protects intestinal barrier function but does not spare muscle glycogen or impact aerobic performance.

Animal studies suggest gut microbiota-derived short-chain fatty acids (SCFA) provide an intestinal barrier-protecting, glycogen-sparing energy source that increases aerobic endurance performance, but confirmation in humans is needed. This study aimed to determine whether increasing colonic SCFA availability impacts intestinal barrier function, substrate metabolism, muscle glycogen and aerobic performance in healthy adults. Using a randomized, double-blind, crossover design 12 active men (age 18-30 years;40.0 ± 7.1 mL/kg/min) performed prescribed exercise and consumed a provided diet supplemented with acetylated and butyrylated high-amylose maize starch engineered to deliver SCFA to the colon (HAMS-A/B) or low-amylose maize starch (LAMS) for 7 days, separated by a 2 week washout. Indirect calorimetry, stable isotopes and blood, muscle and urine biomarkers were measured on intervention day 8 while participants completed 90 min of steady-state cycle ergometry (ExSS; 60 ± 5%) followed by a 5 km treadmill time trial. HAMS-A/B, relative to LAMS, increased faecal and serum SCFA. Multiple markers of intestinal barrier damage and permeability were lower, and the respiratory exchange ratio during ExSS was higher (0.02 [95% confidence interval (CI): 0.01, 0.03], Ptreatment < 0.001) following HAMS-A/B versus LAMS. However no between-treatment difference in glucose turnover, muscle glycogen depletion (14 µmol/kg/g dry wt. [95% CI: -116, 143], Pinteractio n = 0.613) or TT performance (5 s [95%CI: -44, 54], Ptreatment = 0.816) was observed. Increasing colonic and circulating SCFA modestly altered substrate oxidation and preserved intestinal barrier function during endurance exercise. However effects were not sufficient to spare muscle glycogen or increase aerobic endurance performance, leaving the practical relevance unclear and underscoring challenges inherent in translating promising preclinical findings to humans. KEY POINTS: Animal studies suggest gut microbiota-derived short-chain fatty acids (SCFA) provide an intestinal barrier-protecting, glycogen-sparing energy source that increases aerobic endurance performance, but confirmation in humans is lacking. A gut microbiota-targeted dietary supplementation strategy was used to deliver SCFA to the colon and successfully increased colonic and systemic SCFA concentrations in healthy, physically active adults before and during an endurance exercise bout and aerobic performance test. Increasing colonic and systemic SCFA availability preserved intestinal barrier function but did not impact glucose turnover, alter protein expression in muscle or spare muscle glycogen during endurance exercise. Increasing colonic and systemic SCFA availability did not impact aerobic endurance performance.

Humans↗

PubMed2026

Selective monitoring of trace-level catechin and myricetin in herbal and aqueous matrices using magnetic MIP-DSPME: Optimization via design of experiments.

A novel dispersive solid-phase microextraction approach utilizing a magnetic molecularly imprinted polymer (MMIP) integrated with HPLC-UV detection was developed for the concurrent quantification of catechin and myricetin in herbal extracts and aqueous samples. The sorbent was engineered as a core-shell nanocomposite, consisting of a selective polymer layer deposited onto Fe3O4@SiO2-APTMS magnetic nanoparticles. Dual-template imprinting using catechin and myricetin generated complementary binding cavities within the polymer framework. Experimental variables influencing extraction were systematically screened and subsequently optimized. A Plackett-Burman design was first applied to identify the most influential factors, with pH and sorption time identified as the dominant variables. These parameters were subsequently fine-tuned using a central composite design, and the optimization process was completed in only 30 experimental runs. The sorption characteristics of the imprinted sorbent (MMIP) were compared with those of its non-imprinted counterpart (MNIP). The MMIP demonstrated markedly higher maximum binding capacities (Qmax), reaching 119.3 mg g-1 for myricetin and 112.1 mg g-1 for catechin, whereas the corresponding values for the MNIP were 32.55 and 32.08 mg g-1, respectively. Moreover, the affinity constants (KL = 0.760-0.950 L mg-1) were approximately 2.3-fold higher for the MMIP, confirming its stronger and more selective interactions with the target analytes. The selectivity coefficients for the targeted flavonoids relative to structurally related compounds, including ferulic acid, p-coumaric acid, melatonin, and curcumin, exceeded 3.5 for the MMIP, whereas the corresponding values for the MNIP were close to 1.1, demonstrating the high molecular recognition capability of the imprinted sorbent. Method validation demonstrated limits of detection (LODs) of 0.33-0.59 ng mL-1 and limits of quantification (LOQs) of 1.10-1.96 ng mL-1, and excellent linearity over the concentration range of 5.0-5500 ng mL-1 (R2 > 0.998). The method achieved recoveries of 93.96% to 105.69% with RSDs below 5.5%, while the preconcentration factors ranged from 209 to 229. Furthermore, the sorbent retained more than 95% of its extraction efficiency after four consecutive reuse cycles and more than 80% after six cycles, demonstrating excellent stability and reusability. The proposed method was successfully applied to the analysis of six medicinal plant extracts and water samples, showing negligible matrix interference and superior sensitivity, selectivity, and operational simplicity compared with conventional solid-phase extraction methods.

Flavonoids↗