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PubMed2026

Auditory brainstem response in the identification of cochlear synaptopathy in aged rodents: a systematic review with meta-analysis.

PURPOSE: This systematic review and meta-analysis evaluated the diagnostic performance of auditory brainstem response (ABR) for identifying age-related cochlear synaptopathies in rodents. METHOD: Following PRISMA guidelines, searches were conducted in PubMed/MEDLINE, Cochrane Library, Scopus, Embase, Web of Science, SciELO, LILACS, and gray literature. Studies evaluating CS in naturally aged rodents using short-latency auditory evoked potentials (AEPs) were included. Study selection, data extraction, risk-of-bias (JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies), and certainty of the evidence (GRADE® system) assessment were conducted independently by two reviewers. Meta-analyses were performed using a random-effects model, with standardized mean differences and 95% confidence intervals. ABR wave I amplitudes were analyzed for click (80 and 90 dB SPL) and tone-burst stimuli stratified by frequency. RESULTS: Among 3,008 identified records, 12 studies were included in the review and five in the meta-analysis. All included studies used ABR measures to investigate CS, with wave I amplitude being the most frequently evaluated biomarker. Meta-analysis demonstrated a significant reduction in ABR wave I amplitude in aged rodents compared with young controls for both click- and tone-burst-evoked responses. Tone-burst ABR showed no significant differences among the evaluated frequencies. These findings should be interpreted with caution due to the limited number of studies and the methodological heterogeneity, which may have reduced statistical power and comparability. CONCLUSIONS: The evidence supports ABR wave I amplitude as a sensitive electrophysiological marker of age-related CS in rodents. Nevertheless, further studies with standardized protocols are needed to strengthen its diagnostic utility and improve comparability across studies.

Animals↗

PubMed2026

Intramuscular Fat Infiltration and Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

BACKGROUND: Intramuscular fat infiltration (IMFI) is considered to be closely associated with knee osteoarthritis (KOA); however, its overall association, muscle-specific involvement, and clinical relevance remain unclear. OBJECTIVE: To quantify the association between IMFI and KOA, identify affected muscle groups, and evaluate prognostic value. METHODS: We searched PubMed, Web of Science, Scopus, and Embase up to December 2025 for observational studies. Two reviewers independently screened, extracted data, and assessed bias (NOS/JBI). Pooled standardized mean differences (SMDs) were calculated using random-effects models, with subgroup and sensitivity analyses. RESULTS: Seventeen studies were included. IMFI was significantly higher in KOA patients than controls (SMD = 0.63, 95% CI 0.41-0.85, I2 = 84.7%). Anatomically, the anterior thigh muscles (rectus femoris, vastus lateralis, vastus medialis) demonstrated a significant pooled effect (SMD = 0.96, 95% CI 0.66-1.25, I2 = 3.2%) and showed the strongest pooled association, whereas posterior, medial, and composite measures did not demonstrate significant associations. At the individual muscle level, a single study reported a notable association for the semimembranosus (SMD = 1.25, 95% CI 0.57-1.93); however, this finding is based on limited evidence and requires confirmation in future studies. Subgroup by imaging modality: CT demonstrated a significant association (SMD = 0.59, 95% CI 0.28-0.90), while MRI and ultrasound did not show significant associations. Elevated IMFI was also associated with reduced muscle strength, higher KOA incidence, structural progression, and increased knee replacement risk. CONCLUSION: A moderate positive association exists between IMFI and KOA, with notable muscle-specific heterogeneity. Anterior thigh muscles show the strongest pooled association, whereas individual muscle findings require further confirmation. These findings suggest that IMFI may represent a promising potential marker warranting further prospective investigation for risk stratification, though causality and its role in modifying disease progression remain to be established.

Humans↗

PubMed2026

Quantitative susceptibility mapping in neurodegenerative diseases: An umbrella review of iron-related biomarkers and mechanisms.

Pathological iron accumulation is a common pathophysiological hallmark across multiple neurodegenerative diseases (NDDs), motivating the need for accurate, non-invasive quantification methods. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique that enables in vivo measurement of tissue magnetic susceptibility (χ), providing a sensitive proxy for iron content. This umbrella review systematically evaluates the diagnostic accuracy, clinical correlations, and distinct iron distribution patterns of QSM in major NDDs, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and atypical Parkinsonism. We included 15 (13/15 were rated Low or Critically Low on AMSTAR 2) systematic reviews and meta-analyses (through July 15, 2026); however, the findings should be interpreted cautiously because of heterogeneity and the low methodological quality. A Corrected Covered Area (CCA) analysis demonstrated only slight overlap of primary studies across the included reviews (CCA = 5.42%). Collectively, the evidence indicates that QSM provides comparable or higher diagnostic sensitivity and reliability than conventional R2* and SWI techniques, particularly for deep gray matter structures. The findings support significant iron overload in the substantia nigra, particularly in the pars compacta, as a robust biomarker for PD that correlates with motor severity and disease duration. Furthermore, regional iron profiling in the basal ganglia is critical for differential diagnosis; specifically, elevated χ in the putamen and globus pallidus effectively distinguishes multiple system atrophy and progressive supranuclear palsy from idiopathic PD. Distinctively, AD and ALS exhibit specific χ alterations in the thalamus, motor cortex, and hippocampus, reflecting divergent iron-related pathophysiological mechanisms, which correlate with cognitive impairment and upper motor neuron signs. Overall, QSM shows diagnostic promise and offers mechanistic insights into iron-related neurodegenerative processes.

Humans↗

PubMed2026

Glymphatic dysfunction mediates inflammation-driven vascular burden and cognitive decline in cerebral small vessel disease.

BACKGROUND: Cerebral small vessel disease (CSVD) is increasingly recognized as a disorder involving microvascular dysfunction, impaired perivascular clearance, and inflammatory processes. However, how systemic inflammatory burden, neurovascular coupling (NVC), glymphatic MRI markers, vascular lesion burden, and cognition are interrelated remains unclear. MATERIALS AND METHODS: In this prospective study, 155 patients with CSVD and 70 healthy controls (HCs) underwent multimodal MRI. NVC was quantified using the cerebral blood flow/fractional amplitude of low-frequency fluctuations ratio. Glymphatic function was assessed via the diffusion tensor image analysis along the perivascular space (ALPS) index, choroid plexus volume (CPV), and perivascular space (PVS) fractions. Structural equation modeling (SEM) was employed to evaluate the direct and indirect effects of inflammatory markers on vascular burden and cognitive performance. RESULTS: Patients with CSVD exhibited significantly diminished NVC (specifically in the right median cingulate and left frontal gyri) and impaired glymphatic function (lower ALPS-index; higher CPV and PVS fractions) compared to HCs. SEM revealed that inflammatory biomarkers exerted both a direct effect on vascular burden and a substantial indirect effect (accounting for 66.3% of the total effect) mediated through two pathways: a single-mediation path via glymphatic function (42.8%) and a serial-mediation path via NVC and glymphatic function (23.5%). Increased vascular burden was significantly associated with poorer cognitive performance. CONCLUSION: Inflammation drives CSVD progression and cognitive decline primarily through the disruption of NVC and glymphatic clearance mechanisms. These findings highlight glymphatic dysfunction as a critical mediator of inflammation-related structural brain damage.

Humans↗

PubMed2026

Integrated phytochemical and bioactivity profiling of Xanthium strumarium fruits from Korea and China: Implications for origin-specific quality specification.

BACKGROUND: Geographic origin influences the phytochemical composition and biological activities of medicinal plant resources. Xanthium strumarium L. (XS) fruit is widely used in East Asian traditional medicine. However, current pharmacopeial standards primarily recognize Chinese-derived material, despite the availability and traditional use of XS in Korea. To address this gap and support origin-informed quality specification, we compared fruits from Korea (XS-K) and China (XS-C) using chloroplast genome sequencing, targeted phytochemical profiling (high-performance liquid chromatography (HPLC) for selected phenolics and gas chromatography-flame ionization detection (GC-FID) for fatty acids and phytosterols, and multivariate chemometric analysis. RESULTS: Chloroplast genome analysis revealed high overall similarity but localized divergence around the rpoC2 locus and a greater mutation burden in XS-C, supporting origin-associated genomic differentiation. Phytochemical profiling revealed distinct origin-dependent metabolic signatures. XS-K showed higher levels of phytosterols, chlorogenic acid, 4,5-dicaffeoylquinic acid (4,5-DCQ), and xanthatin was detected only in XS-K, whereas XS-C exhibited greater abundance of total fatty acids, particularly oleic acid. Unsupervised clustering and log2 fold-change ranking confirmed clear compositional separation, and variable importance in projection (VIP) analysis identified chlorogenic acid, β-sitosterol, oleic acid, 4,5-DCQ, and xanthatin as major discriminators between origins. Bioactivity assays demonstrated that XS-K exerted stronger antioxidant effects in ABTS, DPPH and FRAP assays, stronger skin-related enzyme inhibition, and greater antibacterial activity against Staphylococcus aureus, consistent with its enriched phenolic and sterol profile. CONCLUSION: Together, chloroplast sequence variation, targeted metabolite quantification, and screening bioassays consistently distinguished XS-K from XS-C. These findings support the use of candidate markers for the origin-based authentication and quality control of XS fruit-derived ingredients. © 2026 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Fruit↗

PubMed2026

Impact of Baseline Polyneuropathy Severity on Eplontersen Efficacy in the NEURO-TTRansform Clinical Trial.

BACKGROUND AND AIMS: In the NEURO-TTRansform clinical trial (NCT04136184), eplontersen improved neuropathy impairment and quality of life (QoL) through Week 66 versus the NEURO-TTR historical placebo in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). This analysis assessed the impact of baseline ATTRv-PN severity on eplontersen response in patients from NEURO-TTRansform. METHODS: This post hoc analysis grouped patients into tertiles by baseline Neuropathy Impairment Score (NIS): T1 (least baseline impairment: 3.5 to < 27.5; n = 67), T2 (27.5 to < 55.0; n = 67), and T3 (55.0 to < 127.8; n = 66). Outcomes assessed were neuropathy impairment (modified NIS+7 [mNIS+7] and NIS, Neuropathy Symptom and Change, Polyneuropathy Disability), QoL (Norfolk QoL-Diabetic Neuropathy), physical functioning (36-Item Short-Form Health Survey Physical Component Summary), nutritional status (modified body mass index), and serum transthyretin levels; these were compared with NEURO-TTR historical placebo. Autonomic dysfunction (Composite Autonomic Symptom Score-31), disability (Rasch-built Overall Disability Scale), and walking speed (10-Meter Walk Test) were also assessed. Final assessments were carried out following 65/66 or 81/85 weeks of treatment. RESULTS: Mean mNIS+7 composite scores were maintained over 85 weeks with eplontersen (changes from baseline of -4.5 [T1], -1.3 [T2], and -2.6 [T3] points). Other disease parameter scores were similarly maintained or improved with eplontersen. Patients receiving placebo experienced disease worsening across outcomes. T1 mean disease scores were typically better than in T2 and T3. INTERPRETATION: Consistent, sustained benefits of eplontersen were observed regardless of baseline ATTRv-PN severity. These findings strengthen the importance of early treatment initiation for patients with ATTRv-PN across the disease spectrum.

Humans↗

PubMed2026

Patient and Public Involvement and Engagement in Pediatric Health Research: A Systematic Review.

BACKGROUND: Patient and public involvement and engagement (PPIE) can increase the relevance and efficiency of research projects. An overview of PPIE approaches and implementation in pediatric research studies is needed to facilitate learning from others' experiences. OBJECTIVE: We aimed to systematically review practices in PPIE across all pediatric health research disciplines regarding characteristics and recruitment of PPIE participants, timepoints and methods used for PPIE, levels of involvement, benefits and barriers of PPIE. SEARCH STRATEGY: We searched Pubmed, EMBASE, Cochrane and PsycInfo using a comprehensive set of terms based on the concepts 'Patient and Public Involvement,' 'Health Research' and 'Pediatrics.' INCLUSION CRITERIA: We included original research articles describing PPIE implementation in pediatric health research published in English or German between 01/2003-10/2024. DATA EXTRACTION AND SYNTHESIS: Data was extracted using predefined categories and synthesized by narrative summary and thematic synthesis. PPIE reporting quality was assessed using the GRIPP2 short form checklist. MAIN RESULTS: Out of 1910 references, we included 37 original research articles, representing 35 studies. PPIE participants were mostly children, adolescents or caregivers involved in all research stages, especially in study design (89%) and recruitment (51%). Key positive impacts of PPIE on research included enhanced recruitment and retention rates and personal benefits for PPIE participants. Barriers to PPIE were financial and time resources required and challenges in recruiting representative PPIE participants. The level of involvement and PPIE reporting quality varied highly between studies. DISCUSSION: Common benefits and barriers of PPIE exist across pediatric research disciplines. Reporting quality varied highly between studies. CONCLUSIONS: PPIE is valuable in pediatric health research. Adherence to guidelines for conducting and reporting PPIE is important to enhance mutual learning. PATIENT OR PUBLIC CONTRIBUTION: PPIE input contributed to the understandability of the lay summary. The findings of this review, together with parent and public input, will inform guidelines for future PPIE activities at the authors' institutions.

Humans↗

PubMed2026

Secretory Phospholipase A2 in Patients With Sickle Cell Disease Hospitalized for Vaso-Occlusive Pain Episodes.

BACKGROUND: Secretory phospholipase A2 (sPLA2) is an inflammatory mediator linked to acute chest syndrome (ACS) in sickle cell disease (SCD), a serious complication that can develop during an acute vaso-occlusive pain episode (VOE). Plasma sPLA2 levels have been proposed as a potential biomarker for predicting ACS onset. OBJECTIVE: To assess serial plasma sPLA2 levels in 105 pediatric patients hospitalized for SCD-VOE and determine the effects of arginine therapy compared to placebo. PROCEDURES: This is a pharmacokinetics/pharmacodynamics and randomized controlled trial of intravenous arginine therapy. Statistical methods included t-tests, chi-square, and correlation analyses. RESULTS: Mean age was 12.7 ± 3.7 years, 48% were male, 67% had Hb-SS, and 70% were prescribed hydroxyurea. Using a previously established SCD-specific cutoff of 48 ng/mL, presenting sPLA2 levels were elevated in 33% of patients (mean sPLA2 level 85.7 ± 32.9 ng/mL). SPLA2 elevation in the emergency department was more common in patients with ACS compared to those without ACS (64% vs. 30%; p = 0.02; negative predictive value of 94%). Peak sPLA2 levels were significantly higher in febrile (n = 34) versus afebrile patients (n = 71;101.0 ± 45.3 vs. 48.7 ± 35.4 ng/mL; p < 0.0001). Among subjects with elevated baseline sPLA2, arginine therapy resulted in a significant reduction in sPLA2 levels by discharge compared to placebo (-27.8 ± 38.1 ng/mL; p = 0.002; n = 23 vs. -15.0 ± 41.2 ng/mL; p = 0.23; n = 12). CONCLUSIONS: SPLA2 is an underutilized biomarker of ACS given accumulating evidence of its role. In particular, low levels may identify patients at low risk for ACS. Arginine therapy may modulate inflammation in patients with SCD during VOE and/or ACS. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02447874; NCT02536170.

Humans↗

PubMed2026

Pembrolizumab-Chemotherapy Versus Pembrolizumab in Head and Neck Squamous Cell Carcinoma: A PD-L1 CPS-Stratified Analysis of Updated KEYNOTE-048 Data.

Based on KEYNOTE-048, pembrolizumab monotherapy and pembrolizumab-chemotherapy are established category 1 first-line treatments for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 1. We compared their efficacy using updated trial data. We analyzed 4-year progression-free survival on next-line therapy (PFS2) and 5-year overall survival (OS) data from KEYNOTE-048 by reconstructing time-to-event data using KMSubtraction. Efficacy was compared in CPS 1-19 and CPS ≥ 20 subgroups using Kaplan-Meier estimates, Cox models, restricted mean survival time (RMST), and landmark analyses. Among 499 patients with CPS ≥ 1, 240 (48.1%) had CPS 1-19 and 259 (51.9%) had CPS ≥ 20. In the CPS 1-19 subgroup, pembrolizumab-chemotherapy showed numerically longer median PFS2 (10.1 vs. 8.0 months; hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.62-1.06) and OS (12.8 vs. 10.8 months; HR: 0.87; 95% CI: 0.67-1.15) versus monotherapy, without statistical significance. For CPS ≥ 20 patients, efficacy was comparable between regimens, with similar median PFS2 (11.3 vs. 11.7 months; HR: 0.95) and OS (14.7 vs. 14.9 months; HR: 0.96). RMST and landmark analyses showed an early PFS2 benefit and a trend toward OS benefit with pembrolizumab-chemotherapy in CPS 1-19, with comparable outcomes in CPS ≥ 20. Pembrolizumab-chemotherapy showed a trend toward improved outcomes in the CPS 1-19 subgroup, with comparable efficacy in the CPS ≥ 20 subgroup, supporting a refined first-line strategy: monotherapy for CPS ≥ 20 to minimize toxicity, and combination therapy for CPS 1-19 to potentially enhance disease control.

Humans↗

PubMed2026

Efficacy and Safety of Bimagrumab in Adults With Obesity and Metabolic Dysfunction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

AIMS: This study aims to systematically evaluate the efficacy of bimagrumab on body composition and glucose parameters in adults with obesity and metabolic dysfunction and its safety profile. METHODS: We searched MEDLINE, PubMed, Embase, and the Cochrane Library on April 20, 2026, for randomized controlled trials (RCTs) assessing bimagrumab treatment in adults with obesity, insulin resistance, or type 2 diabetes mellitus (T2DM). The risk of bias was assessed using the Cochrane Risk of Bias tool (RoB 2), and meta-analyses of efficacy and safety data were conducted using R software. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system was used to assess the strength of evidence. The study was registered with PROSPERO (CRD420261377110). RESULTS: Of the 134 retrieved records, 4 RCTs (enrolling 268 participants) were included. The included population represented a broad spectrum of metabolic dysfunction, from obesity and nondiabetic insulin resistance to established T2DM. Compared with placebo, bimagrumab treatment significantly reduced total weight (mean difference [MD] -4.85 kg, 95% confidence interval [CI] -6.82 to -2.88), fat mass (-4.72 kg [-8.05 to -1.40]), and glycated haemoglobin (HbA1c) (-0.13% [-0.23 to -0.03]) and significantly increased total lean mass (1.66 kg [0.81 to 2.51]). However, bimagrumab led to an increase in low-density lipoprotein (LDL) concentrations of 0.47 mmol/L [0.03 to 0.91] and significantly increased incidences of discontinuation (risk ratio [RR] 5.75 [1.61 to 20.46]), muscle spasms (RR 10.44 [4.23 to 25.75]), and diarrhoea (RR 4.91 [2.38 to 10.11]). CONCLUSION: Bimagrumab effectively reversed adverse effects on body composition in obese individuals, resulting in significant fat reduction, increased skeletal muscle mass, and improved glycemic control, suggesting that bimagrumab is a promising new target for personalized metabolic therapy.

Humans↗

PubMed2026

Direct Oral Anticoagulants as Primary or Secondary Treatment for Heparin-Induced Thrombocytopenia (HIT) and Associated Thromboembolism (HITT)-A Meta-Analysis.

INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is associated with a high risk for thrombosis. The role of direct oral anticoagulants (DOACs) is still emerging and data are limited considering efficacy and safety among patients with HIT. The aim of this review is to evaluate current data on DOACs as primary or secondary treatment among patients with HIT. METHODS: This is a systematic review utilising Pubmed, Scopus and Embase online databases. Eligible studies were published up to December 2024 evaluating DOACs as primary or secondary treatment among patients with HIT and/or associated thrombosis (HITT). Primary outcomes included thrombosis rate (TR) and bleeding rate (BR) during follow-up. RESULTS: A total of 44 publications were included (29 case reports, 5 case studies and 10 cohort studies [n > 10 patients]). Regarding treatment, 19 articles evaluated only rivaroxaban, 7 articles only apixaban, 11 articles only dabigatran and 7 articles more than one regimen. A total of 352 patients were included. Overall, 190 patients (53.8%) were given DOAC as primary treatment whereas 162 patients were given a parenteral treatment first and continued with a DOAC. Mean nadir platelet count at diagnosis was 63 000/μL. HITT rate was 190/352 (53.9%; 8% had arterial thrombosis). Mean follow-up was 7.6 months. TR was 20/352 (Pooled proportion = 0.064 [95% CI = 0.042-0.092]) (30% of them were new thromboses without initial thrombosis), and BR was 9/352 (Pooled proportion = 0.039 [95% CI = 0.022-0.062]). Finally, there was no difference found regarding TR and BR between primary or secondary treatment, and among different regimens. CONCLUSIONS: DOACs are associated with low rates of thrombosis and major bleeding among patients treated for HIT or HITT, either as primary or secondary treatment. However, the certainty of evidence is very low because of the quality and limitations of the available studies.

Humans↗

PubMed2026

Effect of cognitive enhancement therapy for early course schizophrenia on gray matter volume: A confirmatory multisite randomized clinical trial.

BACKGROUND: Cognitive Enhancement Therapy (CET) is an evidence-based cognitive remediation intervention for early course schizophrenia with established benefits for cognition. CET may protect against broad temporolimbic gray matter volume loss associated with cognitive improvement, but this finding has yet to be replicated. This research reexamined if CET protects against temporolimbic gray matter volume loss in an independent and larger multisite early course sample, and if this neuroprotective effect predicts cognitive and social adjustment improvement. METHODS: Ninety-nine participants with early course schizophrenia completed MRI, cognitive, and social adjustment assessments at baseline, 9 (mid-treatment), and 18 (end of treatment) months. Linear mixed-effects models examined the differential impact of CET (n = 56) compared to Enriched Supportive Therapy (n = 43) on temporolimbic gray matter volume in regions-of-interest (ROIs) that previously demonstrated CET-related neuroprotection (primary ROIs), as well as frontotemporal ROIs outlined in the first trial (secondary ROIs). RESULTS: The right rostral anterior cingulate was the only primary ROI to demonstrate a significant group × time interaction, but was unrelated to cognitive and social adjustment change. No secondary ROIs exhibited a differential treatment effect. CONCLUSION: This confirmatory trial did not recapitulate the observed broad pattern of CET-related temporolimbic gray matter volume neuroprotection. Consistent with the larger literature demonstrating limited evidence of cognitive remediation effects on the brain in schizophrenia, these findings underscore the need for continued investigation of CET-related changes with other neuroimaging modalities, especially given its established cognitive benefits. Such information is critical for cognitive remediation optimization based on validated therapeutic mechanisms.

Humans↗

PubMed2026

EffectS of Lifestyle Interventions in Older PEople With Obesity (Effective SLOPE): a Systematic Review With Network Meta-Analyses.

BACKGROUND/AIM: We conducted a systematic review with network meta-analyses (NMA) summarizing the effects and safety of lifestyle interventions containing nutrition (NUT; e.g., calorie restriction), exercise (EX; e.g., aerobic/resistance exercise) and behavior change interventions (BCI; e.g., behavioral therapy) on physical function, body composition, quality of life, psychosocial outcomes, health and adverse events in community-dwelling older adults with obesity. METHODS: We used the methodology proposed by Cochrane and searched six databases and one trial registry for eligible randomized controlled trials (RCTs; intervention duration ≥ 12 weeks) up to May 2022 with a full new search in MEDLINE and a re-assessment of previously identified eligible trial registry entries in October 2025. Random-effects NMA ((standardized) mean difference ((S)MD), 95% confidence intervals) were conducted if possible. RESULTS: We included 72 RCTs (n = 6716) for descriptive summaries and 54 RCTs (n = 4249) for NMA. NUT+EX+BCI improved physical function (performance batteries) compared to control (SMD 3.37 [1.76;4.97]; high certainty of evidence). NUT+EX+BCI may reduce body (MD -8.69 [-13.14;-4.25]) and fat mass (MD -6.58 [-10.44;-2.73]) while not negatively affecting fat-free mass (MD -1.38 [-3.52;0.76]) or bone mineral density (MD -0.01 [-0.05;0.02]) (evidence very uncertain). Other interventions (single/combined) may also be effective; however, effects were often imprecise. For psychosocial outcomes, quality of life, and health events, data were insufficient or too heterogeneous to derive clear results. CONCLUSION: The evidence suggests that NUT+EX+BCI interventions are most suitable for the management of obesity in older adults. Nevertheless, further RCTs-especially in frail populations and on patient-relevant outcomes-are needed.

Humans↗

PubMed2026

Providing Feedback on Previous Pain Scores Did Not Affect Weekly Pain Variability: A Cohort-Nested Randomised Study.

BACKGROUND: Spinal pain is one of the leading causes of disability worldwide and repeated symptom monitoring is increasingly used to capture its fluctuating nature. However, repeated pain assessments may be influenced by prior responses, potentially affecting longitudinal patterns of pain reporting. This study examined whether providing feedback on prior pain scores influenced within-person variability in weekly pain intensity ratings and retention over 60 weeks. METHODS: This randomised study evaluating a methodological feature of repeated pain assessment was embedded within a cohort of adults with spinal pain referred to an outpatient hospital clinic. Participants (n = 2448) were randomised 1:1 to weekly pain intensity ratings (0-10 numerical rating scale) either with feedback ('You answered [X] last week') or without feedback. Analyses included participants with ≥ 40% valid responses (n = 1883), of whom 948 received feedback and 935 did not. The primary outcome was within-person variability in pain intensity, quantified using the root mean square of successive differences. Secondary outcomes included additional fluctuation metrics and the number of weeks with missing responses. RESULTS: No meaningful between-group differences were observed for the primary outcome (mean difference -0.04 points [95% confidence interval -0.08 to 0.01]) or secondary outcomes, including retention rates. Sensitivity analyses yielded consistent findings. CONCLUSIONS: Providing participants with feedback on their previous pain score did not meaningfully influence within-person pain variability or retention during 60 weeks of weekly monitoring. These findings aid the interpretation of repeated longitudinal pain assessments by showing that the observed variability was robust to this specific study design. SIGNIFICANCE: This randomised study showed that providing participants with feedback on prior pain scores did not meaningfully alter weekly pain variability or retention during 60 weeks of longitudinal monitoring. These findings contribute to the interpretation of repeated longitudinal pain assessments in spinal pain research and suggest that weekly pain reporting patterns are robust to prior-pain feedback during long-term symptom monitoring.

Humans↗

PubMed2026

Epigenetic Clocks of Biological Aging and Cognitively Healthy Longevity: The Women's Health Initiative Memory Study.

BACKGROUND: Little is known about whether epigenetic age acceleration (EAA) clocks are capable of predicting exceptional longevity with or without preserved cognitive function. METHODS: We examined 5844 women from the Women's Health Initiative Memory Study. Fifteen epigenetic clocks were measured at baseline (1996-1999). Longevity outcomes were defined as: 1) survival to age 90 with preserved cognition (n = 1726, 29.5%); or 2) survival to age 90 with cognitive impairment (n = 956, 16.4%); vs. 3) death before age 90 (n = 2611, 44.7%). Logistic regression models examined associations between the 15 clocks and survival to age 90 (vs. death before age 90), adjusting for covariates. Multinomial logistic regression models examined associations with survival to age 90 without cognitive impairment and survival to age 90 with cognitive impairment (each vs. death before age 90), also adjusting for covariates. RESULTS: Each standard deviation increase in EAA for the first-generation clocks was associated with 7%-18% reduced odds of survival to age 90 vs. earlier death. Stronger associations were observed for second- and third-generation clocks, including AgeAccelGrim2 (OR = 0.66; 95% CI 0.61-0.71), PCGrimAge (OR = 0.64; 95% CI 0.59-0.69), PCPhenoAge (OR = 0.73; 95% CI 0.68-0.78) and DunedinPACE (OR = 0.77; 95% CI 0.72-0.82). None of the clocks was more strongly associated with survival to age 90 with preserved cognition than with survival to age 90 with cognitive impairment, relative to death before age 90. CONCLUSION: All epigenetic clocks were associated with exceptional longevity, but none were associated with cognitive healthspan. Developing clocks that can differentiate long survival with and without preserved cognitive function is critical.

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PubMed2026

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

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

Humans↗

PubMed2026

Penpulimab and Gemcitabine With or Without Anlotinib in Metastatic Nasopharyngeal Carcinoma: A Randomized, Open-Label, Multicenter Phase 2 Study.

This prospective exploratory phase 2 study employed a three-cohort, two-phase design to evaluate the potential of anlotinib as a substitute for cisplatin in gemcitabine-penpulimab combinations for metastatic nasopharyngeal carcinoma (NPC) patients who were previously treated with cisplatin-based chemoradiotherapy. Patients enrolled in the study were randomized in a 1:1:1 ratio during the lead-in phase to one of three treatment arms: gemcitabine, cisplatin, penpulimab, and anlotinib (GP-PA, n = 8); gemcitabine, cisplatin, and penpulimab (GP-P, n = 6); or gemcitabine, penpulimab, and anlotinib (GAP, n = 6). The expansion phase enriched the optimal cohort, with stratification based on PD-L1 expression. The primary endpoints were safety and objective response rate (ORR), while the secondary endpoints included duration of response, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). In the lead-in phase, grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred in 87.5% (GP-PA), 100% (GP-P), and 66.7% (GAP) patients, predominantly hematologic toxicities. ORR/DCR were 62.5%/87.5% (GP-PA), 83.3%/100% (GP-P), and 100%/100% (GAP). At median 20.2-month follow-up, median PFS/OS were 4.1/18.4 months for GP-PA and not reached for GP-P/GAP. In the expansion phase, a total of 14 patients received GAP, with an ORR of 93.3% and grade ≥ 3 TEAEs in 71.4% of patients. At data cut-off point, the median PFS had not been reached, and the 12-month PFS and OS rates were 53.8% and 78.6%, respectively. The GAP regimen demonstrated a favorable safety and efficacy profile, compared to the GP-PA and GP-P regimens in patients with metastatic NPC. These findings suggest that substituting cisplatin with anlotinib may offer a viable therapeutic strategy for this patient population.

Humans↗

PubMed2026

Clinical Performance of Bulk-Fill Versus Incremental Composite Placement Approaches in Vital Posterior Teeth: A 24 Months Randomized Controlled Trial.

BACKGROUND: Composite resin placement technique may influence marginal integrity, polymerization stress distribution, and long-term clinical performance of posterior restorations. This randomized controlled clinical trial evaluated the 24-month clinical performance of four different placement techniques in Class I posterior composite restorations. METHODS: Fifty patients aged 20-35 years presenting with four occlusal carious lesions each were enrolled, resulting in 200 restorations. Cavities (4-5 mm depth) were prepared according to caries extension. Restorations were randomly allocated into four equal groups (n = 50) according to placement technique: stamp technique, snowplow technique, modified incremental "pizza" technique, and bulk-fill technique. All materials were applied following manufacturers' instructions. Clinical evaluation was performed at baseline and after 6, 12, and 24 months using FDI criteria. Functional (fracture/retention, marginal adaptation), esthetic (marginal staining, anatomical form), and biological (postoperative sensitivity, secondary caries) properties were assessed by two calibrated evaluators. Statistical analysis was performed at a significance level of α = 0.05. RESULTS: Thirty-eight patients with a total of 152 restorations were evaluated at the end of the 24 months in line with FDI at the end of the study with 76% recall rates. No statistically significant differences were observed among groups regarding fracture/retention or secondary caries (p > 0.05). Marginal adaptation and marginal staining demonstrated minor deterioration over time across all groups, with statistically significant intergroup differences found (p < 0.05). Postoperative sensitivity was minimal and transient in all groups with no significant difference (p = 0.181). CONCLUSIONS: Within the limitations of this 24-month follow-up, the four placement techniques demonstrated comparable clinical performance in Class I posterior composite restorations. Selection of technique may therefore be guided by clinical preference and procedural efficiency rather than differences in short-term clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT07415317.

Humans↗

Results for “disorder of gut&#x2010;brain interaction”

Results for “disorder of gut‐brain interaction”