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PubMed2026

Serum Albumin on Admission: A Prognostic Marker of Morbidity and Mortality in Burns? A Systematic Review and Meta-Analysis.

Albumin is essential for maintaining oncotic pressure and vascular integrity. In burn injuries, increased capillary permeability leads to hypoalbuminemia, which is a recognized marker of poor outcomes in critical illness. However, its prognostic value in acute burn care remains underexplored. This study evaluated the prognostic value of admission serum albumin in predicting mortality, acute kidney injury (AKI), hospital and intensive care unit length of stay, ventilatory requirements, sepsis, and pulmonary infection in patients with burn injuries. A systematic search of PubMed, Scopus, Cochrane Library, Web of Science, MEDLINE, and Embase was conducted. Of 5587 studies screened, 19 were included in the systematic review and 9 in the meta-analysis. Statistical analysis was performed using RStudio, with pooled outcomes reported as odds ratios (ORs), standardized mean differences, and hierarchical summary receiver operating characteristic curves. Heterogeneity was assessed using Cochran's Q, I2, and tau2. Hypoalbuminemia on admission was significantly associated with increased mortality during admission (OR 9.51; 95% CI, 3.04-29.78; I2 49.3%). Admission hypoalbuminemia was also associated with an increased risk of AKI (OR 2.83; 95% CI, 2.49-3.22; I2 0%). Evidence for other outcomes was limited and heterogeneous. Admission serum albumin appears to be a valuable prognostic marker in patients with burn injuries, particularly for mortality and AKI. Further research is required to support its integration into burn-specific risk models, characterize albumin trends within the first 24 h postinjury, and establish optimal cut-off values.

Humans↗

PubMed2026

Associations between prescribed amphetamines and spontaneous cervical artery dissection: a matched case-control study.

AIMS: To assess whether prescribed amphetamines are associated with spontaneous cervical artery dissection (sCeAD), an important cause of stroke in young adults. METHODS: We conducted a retrospective matched case-control study within a large academic health system in Chicago, Illinois. Adults aged 18-85 years with incident sCeAD were matched 1:4 to controls without dissection on age, sex, and race/ethnicity. The primary exposure was documented amphetamine prescription. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) controlling for relevant vascular and clinical covariates. Sensitivity analyses included strict matched-strata and inverse probability-weighted models. RESULTS: Among 11,463 individuals, including 2,293 cases and 9,170 controls, amphetamine exposure was associated with higher odds of sCeAD (adjusted OR 1.70, 95% CI 1.18-2.46). Results were unchanged in strictly matched strata (OR 1.70, 95% CI 1.18-2.46) and remained directionally consistent after inverse probability weighting (OR 1.40, 95% CI 1.09-1.79). High-dose amphetamine exposure (≥30 mg/day) had the strongest association (OR 1.96, 95% CI 1.18-3.26), whereas low-dose exposure was not statistically significant. CONCLUSION: Prescribed amphetamines were associated with modestly increased odds of sCeAD. While these findings are observational and hypothesis-generating, they may support a possible association in susceptible patients.

Humans↗

PubMed2026

Psychometric Evaluation of the Breast Inflammatory Symptom Severity Index Versions 2 and 3 Among Lactating Women.

OBJECTIVE: To evaluate the psychometric properties of Versions 2 and 3 of the Breast Inflammatory Symptom Severity Index (BISSI). DESIGN: Secondary data analysis of clinical trial data. SETTING: Private physiotherapy practices, a public tertiary hospital, and a community in Melbourne, Australia. PARTICIPANTS: Women more than 7 days after birth with inflammatory conditions of the lactating breast (N = 43). METHODS: We performed confirmatory factor analysis of the BISSI Version 2 to examine item loading, which informed development of the BISSI Version 3 (V3). We assessed convergent validity by comparing total BISSI V3 scores with human milk sodium to potassium ratio (Na+:K+) at Trial Days 1, 3, and 10 using Bland-Altman plots. We compared item-level scores for size of affected area with objective receiver operating characteristic curve analysis to assess discriminant validity for symptom severity and Cronbach's alpha for internal reliability. RESULTS: After confirmatory factor analysis, we removed two items, resulting in a six-item BISSI V3. All retained items demonstrated comparable loading on the overall scale. Limits of agreement for total BISSI V3 scores and item-level scores for size of affected area were acceptable at all time points, with more than 90% of observations falling within 2 standard deviations of the mean difference, supporting convergent validity. Discriminant validity of the BISSI V3 was supported. We found high internal reliability at both time points CONCLUSION: Our findings provide evidence for the validity and reliability of the BISSI V3 and support its continued development and for clinical use of the BISSI V3 and human milk Na+:K+ analysis to enhance management of inflammatory conditions of the lactating breast.

breastfeeding↗

PubMed2026

Clinical and endocrine correlates of genetic etiologies in severe hypospadias: Study from 34 patients.

OBJECTIVE: Hypospadias is a prevalent congenital anomaly (0.3%-1.0%); however, severe hypospadias (defined as proximal cases with the meatus at the penoscrotal junction, scrotum, or perineum) is a rare and clinically challenging entity with a multifactorial etiology. This study aimed to characterize the interrelationships among the clinical, endocrine, and genetic profiles in children with severe hypospadias. MATERIALS AND METHODS: We conducted a comprehensive analysis of 34 male patients with severe hypospadias. Preoperative hormone levels were measured using two methods: chemiluminescent immunoassay for luteinizing hormone and follicle-stimulating hormone, and liquid chromatography-tandem mass spectrometry for testosterone (T), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), 17α-hydroxyprogesterone (17α-OHP), and other steroids. Genetic analysis was conducted via whole exome sequencing. RESULTS: The diagnostic yield of clinically relevant genetic variants (including pathogenic and likely pathogenic, and variants of uncertain significance) in our cohort was 41.2% (14/34) of patients. Patients carrying these variants exhibited a more complex phenotypic profile compared to non-carriers, including a significantly higher rate of patients with ≥3 associated malformations and a greater prevalence of cryptorchidism. Furthermore, the group with clinically relevant variants showed selective elevations in adrenal-derived precursors, specifically 17α-OHP and DHEA. Correlation analysis revealed significant positive associations of both 17α-OHP levels and the T/DHT ratio with the number of associated malformations. CONCLUSION: This study reveals significant genetic heterogeneity in patients with severe hypospadias. Those carrying genetic variants was associated with more severe clinical phenotypes, while certain endocrine variations, including the elevation of adrenal-derived hormones, were also observed in this cohort.

Humans↗

PubMed2026

A 20-Y Analysis of Motorcycle Trauma After Helmet Law Repeal.

INTRODUCTION: After Arkansas repealed its universal motorcycle helmet law in 1997, helmet use decreased and motorcycle-related injuries and fatalities increased. Long-term clinical and population-level impacts of this policy change remain incompletely characterized. This study integrates statewide crash and fatality data with trauma center data to evaluate trends in helmet use, injury severity, and mortality at scene and hospitalization. METHODS: We retrospectively reviewed motorcycle-related admissions and emergency department deaths at the state's only adult level I trauma center from 2004 to 2023 across three periods: 2004-2006, 2013-2015, and 2021-2023. Demographics, helmet use, injury severity, and outcomes were assessed. Logistic regression evaluated associations between helmet use, severe head injury (Abbreviated Injury Scale ≥3), and inhospital mortality. Fatality data were obtained from the National Highway Traffic Safety Administration, and crash-level data (2015-2023) were obtained from the State Department of Transportation. RESULTS: Among 1104 trauma admissions, annual admissions nearly tripled over time, with nonhelmeted riders representing 64%-72%. Helmet use was independently associated with lower odds of severe head injury (odds ratio 0.48, P < 0.001). Nonhelmeted riders had higher on-scene fatality risk (relative risk 1.21). Severe head injuries increased and were strong predictors of inhospital mortality. Population-adjusted motorcycle fatality rates rose from 2.34 to 3.18 per 100,000 residents by 2021-2023. CONCLUSIONS: Motorcycle fatalities and severe head injuries increased during the postrepeal period and were associated with helmet nonuse and severe head trauma. Clinical and statewide data show consistent associations among helmet nonuse, severe head injury, and prehospital and in-hospital mortality, highlighting helmet use as a target for injury prevention policy.

Acute brain injury↗

PubMed2026

Desert-derived Ensifer sp. SA403 enhances potato salt tolerance by reshaping rhizosphere microbiome functions and host responses.

Soil salinization increasingly threatens global food security, and potato (Solanum tuberosum L.), a moderately salt-sensitive crop, is particularly vulnerable to saline soils. Plant growth-promoting rhizobacteria (PGPR) offer a promising strategy to improve crop performance, yet how PGPR interact with native microorganisms to enhance potato salt tolerance remains poorly understood. In this study, we identified a desert-derived PGPR strain, Ensifer sp. SA403, which substantially enhanced potato performance under high salinity across sterile, non-sterile and field conditions. Physiologically, inoculation with SA403 reduced shoot Na⁺ accumulation and increased the K⁺/Na⁺ ratio; notably, these effects were markedly stronger in non-sterile substrates than under sterile conditions, indicating that SA403-mediated ion homeostasis relies on cooperation with the resident microbiota rather than on the strain acting alone. Metagenomic profiling indicated that SA403 strain reshaped rhizosphere communities, significantly enriching beneficial taxa such as Priestia and Bradyrhizobium, and upregulated functional pathways involved in glutathione and sulfur metabolism. Furthermore, host transcriptomic analyses showed that SA403 modulated plant responses to salt stress, with differentially expressed genes enriched in jasmonic acid signaling, ethanolamine metabolism and amino-acid biosynthesis pathways. Field trials on saline soils confirmed that SA403 significantly increased seedling emergence and tuber weight. Together, our results demonstrate that SA403 functions as a biological mediator that optimizes rhizosphere microecology and coordinates ion balance and host signaling to enhance potato salt tolerance. These findings support the potential of SA403 as a robust PGPR-based tool for sustainable potato production on saline soils.

Rhizosphere↗

PubMed2026

Effect of Bariatric Surgery on Improvement of Retinal Microvasculature in Patients With Obesity: A Systematic Review and Meta-Analysis.

Obesity is associated with adverse retinal microvascular changes, including narrower central retinal arteriolar equivalent (CRAE), wider central retinal venular equivalent (CRVE) and lower arteriovenous ratio (AVR). Although bariatric surgery improves cardiometabolic risk, its effect on retinal microvascular calibre remains uncertain. We systematically searched the Cochrane Library, PubMed, ScienceDirect and Scopus up to June 2026. Prospective cohort studies reporting CRAE, CRVE or AVR before and after bariatric surgery in patients with obesity were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. Pooled mean differences (MD) with 95% confidence intervals (CI) were calculated using a random-effects model. Eight prospective cohort studies including 283 patients were included. Seven studies contributed to the CRAE and CRVE analyses, and seven contributed to the AVR analysis. Bariatric surgery was associated with a significant increase in CRAE (MD = +4.02 μm, CI [0.26-7.78], p = 0.04). Sensitivity analysis excluding one study showed a stronger and more consistent effect (MD = +5.41 μm, CI [4.59-6.22], p < 0.01). CRVE significantly decreased after surgery (MD = -6.75 μm, CI [-7.42 to -6.07], p < 0.01), while AVR significantly increased (MD = +0.03, CI [0.02-0.05], p < 0.01). Sensitivity analyses suggested that the direction of effect was generally robust, although between-study heterogeneity was present. Bariatric surgery may be associated with favourable retinal microvascular changes in patients with obesity, reflected by increased CRAE and AVR and decreased CRVE.

Humans↗

PubMed2026

Fused Deposition Modeling (FDM) of polyether-ether-ketone (PEEK) dental implants: A systematic review of the effect of printing parameters on mechanical behaviour and surface quality.

PURPOSE: This systematic review evaluated how FDM printing parameters influence mechanical behaviour and surface characteristics of 3D-printed PEEK and identified parameter combinations linked to the most favourable mechanical performance and surface quality. MATERIALS AND METHODS: An electronic search was conducted in: MEDLINE (Ovid), PubMed, Embase, Web of Science, Scopus, and Compendex (last update: January 2025). Studies that evaluated the effect of FDM printing parameters on mechanical and surface properties of PEEK were included. Outcomes comprised compressive, tensile, and flexural strengths, elastic modulus, fracture toughness, surface hardness, roughness, and wettability. RESULTS: Of 4005 reports screened, 54 manuscripts were included. 92.6% (n = 50) of articles showed low risk-of-bias, while 7.4% (n = 4) showed medium risk-of-bias. Tensile strength was the most investigated mechanical parameter (78%), followed by elastic modulus (41%), flexural strength (30%), compressive strength (20%), and fracture toughness (6%). Surface roughness was the most evaluated surface property (30%), followed by hardness (17%) and wettability (6%). Across studies, higher printing temperatures, lower printing speed, thinner layer thickness, and maximum infill ratio in a horizontal printing orientation were associated with higher strengths, less warpage, increased accuracy, and improved surface quality. CONCLUSION: Specific combinations of FDM printing parameters can significantly improve the mechanical and surface properties of PEEK. However, it is difficult to meet all the optimal conditions simultaneously. Thus, balancing between different parameters must be considered in practical production.

Benzophenones↗

PubMed2026

Risk of stroke in SLE: a systematic review and meta-analysis.

UNLABELLED: The association between SLE and composite stroke, ischaemic stroke and haemorrhagic stroke remains incompletely understood. This meta-analysis aims to assess the risk of stroke in patients with SLE. METHODS: Data sources included PubMed, Embase, the Cochrane Library and reference lists of included studies. This meta-analysis included cohort studies evaluating whether stroke risk is associated with SLE. The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Risk ratios (RRs) with 95% CIs were pooled using a random-effects model, and publication bias was assessed with funnel plots and Egger's test. RESULTS: A total of 25 cohort studies involving 5 220 837 individuals were included in this meta-analysis, which were published between 2001 and 2026. The pooled analysis demonstrated a significantly increased risk of stroke in patients with SLE (RR of 2.60, 95% CI 2.21 to 3.05, I²=97.9%, p<0.001). The risk of composite stroke (RR of 2.83, 95% CI 2.25 to 3.57, I²=98.0%, p<0.001), ischaemic stroke (RR of 2.34, 95% CI 1.75 to 3.12, I²=97.6%, p<0.001) and haemorrhagic stroke (RR of 2.66, 95% CI 1.57 to 4.49, I²=96.2%, p<0.001) was also increased in SLE. Despite the large heterogeneity, the sensitivity analysis indicated that the results were robust, and there was little evidence of publication bias. CONCLUSION: The risk of composite stroke, ischaemic stroke and haemorrhagic stroke is increased in SLE. PROSPERO REGISTRATION NUMBER: CRD420261294082.

Humans↗

PubMed2026

Prevalence of unruptured intracranial aneurysms according to comorbidities, risk factors, country, and time period: a systematic review and meta-analysis.

BACKGROUND: The incidence of aneurysmal subarachnoid haemorrhage declined between 1980 and 2010, which coincided with a decline in smoking and prevalence of hypertension. We aimed to investigate whether the decrease in subarachnoid haemorrhage incidence is paralleled by declines in unruptured intracranial aneurysm (UIA) prevalence. METHODS: For this systematic review and meta-analysis, we searched Embase, PubMed, and Web of Science for articles published in any language from Jan 1, 2011 to Dec 31, 2025, and reassessed 68 articles published before March 1, 2011 from a 2011 systematic review and meta-analysis. Articles were eligible for inclusion if they used a cross-sectional or case-control design and provided the crude number of participants and those with UIA. We only included studies reporting numbers of UIA separately from ruptured aneurysms and with ten or more patients. Summary data were independently extracted by JD with AZ or CB and conflicts were resolved by GJER. The primary outcome was proportion of participants with UIA. Relative to a hypothetical reference population (mean age 50 years, 50% women, and no comorbidities), age and/or sex-adjusted prevalence ratios (PRs) for regions, comorbidities, and risk ratios (RRs) for female sex, smoking, and hypertension were estimated using generalised linear mixed models. A time trend analysis was done by binomial meta regression using the mid-year of data acquisition. We assessed the certainty of evidence using GRADE. The study was registered with PROSPERO, number CRD420261296728. FINDINGS: Our search screened 4708 studies. 67 reassessed and 95 newly identified articles, reporting on 316 131 participants and 11 822 people with UIAs, were included in our meta-analysis. In the reference population, the estimated prevalence of UIAs was 3·9% (95% CI 3·0-5·1). The prevalence of UIAs in individuals with atherosclerosis was 5·5% (4·7-6·4; 2229 of 40970 participants) and the adjusted PR was 1·3 (95% CI 0·8-2·0) compared with the reference population. For positive family history of aneurysmal subarachnoid haemorrhage (aSAH) or UIA, the UIA prevalence was 7·9% (5·6-11·1; 412 of 4252 participants) and the adjusted PR was 2·4 (0·5-11·2). For connective-tissue disorder, the UIA prevalence was 10·3% (6·5-16·0; 94 of 879 participants) and the adjusted PR was 3·9 (2·0-7·6). For autosomal dominant polycystic kidney disease (ADPKD), the UIA prevalence was 12·8% (9·2-17·6; 293 of 1990 participants) and the adjusted PR was 4·4 (1·5-12·6). RRs were for current smoking 1·4 (1·2-1·6; 798 of 27911 participants), for having hypertension 1·6 (1·5-1·7, 4043 of 83053 participants), and for female sex 1·9 (1·8-2·0; 3415 of 65020 women and 2122 of 76130 men). In studies on healthy individuals with MR angiography or CT angiography as imaging modality, the prevalence in 2016-2022 was 6·6% (6·3-6·8; 2904 of 41191 participants). The adjusted PR was 1·8 (1·1-2·8) for 2016-2022 versus 2002-2015. Prevalence of UIAs of 5 mm or larger was 0·7% (0·6-0·8) in 2002-2015 and 1·4% (1·0-1·9) in 2016-2022. The UIA prevalence did not differ between countries. τ2 showed significant heterogeneity between studies. The certainty of the evidence ranged from very low to moderate. INTERPRETATION: Prevalence of UIA is increasing, particularly over the past two decades. This increase is only in part explained by improved detection of small UIAs and an ageing population, and other factors-such as environmental-are likely involved. Alongside patients with ADPKD and a positive family history of aSAH, patients with connective-tissue disorders had a higher prevalence of UIA than the reference population. Our findings warrant further investigation into the potential benefit of personalised screening and management strategies in groups at high risk for having UIAs. FUNDING: None.

Humans↗

PubMed2026

Hypothalamic-Pituitary Axis Involvement in Primary Central Nervous System Lymphoma.

CONTEXT: Primary central nervous system lymphoma (PCNSL) is a rare malignancy that may involve the hypothalamic-pituitary axis (HPA), leading to underrecognized but clinically significant endocrine dysfunction. OBJECTIVE: This work aims to characterize the spectrum and patterns of HPA-related endocrine disturbances in patients with PCNSL. DATA SOURCES: A systematic search was conducted in PubMed, EMBASE, Scopus, and Web of Science, supplemented by gray literature. The search concluded in February 2025. STUDY SELECTION: We included studies reporting adult PCNSL cases with documented dysfunction of at least one hormonal axis. Exclusion criteria were preexisting hypopituitarism or lack of endocrine data. DATA EXTRACTION: Data on demographics, tumor localization, hormonal axes affected, radiological findings, treatment, and outcomes were extracted. Risk of bias was assessed using JBI tools. RESULTS: Ninety-nine cases met the inclusion criteria. Diffuse large B-cell lymphoma accounted for 84% of cases. Endocrine dysfunction included isolated adenohypophyseal involvement (46%), neurohypophyseal (8%), and combined (45%). The most affected pituitary axes were the gonadal and thyroid axes, with 89.7% and 89.2% involvement, respectively. Hypothalamic tumors were strongly associated with combined dysfunction (odds ratio = 9.47; 95% CI, 3.76-23.86; P < .001). Persistent endocrinopathy was more frequent in progressive disease. No direct association was found between endocrine dysfunction and mortality. CONCLUSION: HPA dysfunction in PCNSL is frequent and often underdiagnosed. Hypothalamic involvement is associated broader hormonal impairment. Routine hormonal screening and multidisciplinary management should be standard in PCNSL care to minimize complications and improve outcomes.

Humans↗

PubMed2026

Antiadalimumab Antibodies in Patients With Inflammatory Ocular Diseases: Incidence and Clinical Outcomes.

PURPOSE: To determine the incidence, effect on adalimumab drug levels, and clinical consequences of antiadalimumab antibody formation, and to assess potential risk factors. DESIGN: Retrospective clinical cohort study. PARTICIPANTS: One hundred twenty-eight patients treated with adalimumab who underwent antiadalimumab antibody monitoring. METHODS: Beginning October 2023, regularly scheduled antiadalimumab antibody and adalimumab level testing was begun. Using staggered entry analysis, anchored observation to treatment initiation, incidence was calculated. Time-updated models evaluated risk factors for antiadalimumab antibody formation. MAIN OUTCOME: Incidence of antiadalimumab antibodies. RESULTS: Antiadalimumab antibodies developed in 37 of 128 patients for a rate of 0.077 per person-year (PY) (95% confidence interval [CI] 0.055/PY, 0.104/PY). Median serum adalimumab concentrations were significantly lower in antiadalimumab antibody-positive blood samples (2.6 µg/mL; interquartile range 0.8, 7.0) than in antibody-negative samples (10.2 µg/mL; interquartile range 6.9, 15.1), P < .00001. In time-updated analyses, there was a suggestion that concomitant immunosuppression was associated with a reduced risk of antiadalimumab antibodies (odds ratio [OR] 0.64; 95% CI 0.37, 1.10; P = .10) and weekly adalimumab dosing was associated with a reduced risk (OR 0.62; 95% CI 0.42, 0.91; P = .01). Antiadalimumab antibodies were associated with active ocular inflammation (OR 3.68; 95% CI 1.99, 6.82; P < .00001). CONCLUSIONS: Antiadalimumab antibodies occur commonly among patients treated with long-term adalimumab, with a cumulative incidence of nearly 50% by 8 years of therapy. Antibody formation was associated with lower serum adalimumab levels and active ocular inflammation.

Humans↗

PubMed2026

Biomass burning contributions to Mexico City's atmospheric CO2 estimated using a multi-isotope approach.

Fossil fuel combustion dominates anthropogenic emissions worldwide; however, special attention should be addressed to biomass burning, since it is an increasingly important contributor under warmer, drier fire-weather conditions exacerbated by climate change. These emissions could impact the atmospheric composition of heavily urbanized environments. To assess the influence of biomass burning, along with fossil fuels combustion and soil and plant respiration on Mexico City's atmospheric composition, we conducted a year-long (December 2023-December 2024) isotopic monitoring of atmospheric CO2, combining radiocarbon (Δ14C), CO2 stable isotopes (δ13C, δ18O), and CO/CO2 ratios. Once defined the isotopic signatures and the characteristic CO/CO2 that describe the sources, we performed Monte Carlo simulations under two tracer modalities (Δ14C + CO/CO2 and Δ14C + CO2 stable isotopes) for source apportionment. Results show that during the dry season, particularly in March-April, atmospheric Δ14C values approached and overlapped background levels despite Mexico City's fossil-fuel dominance, indicating enhanced non-fossil inputs. Moreover, backward HYSPLIT trajectories supported that these elevated Δ14C values coincided with regional wildfire activity. Monte Carlo results attributed up to ∼34 %-60 % of local CO2 to biomass burning in April, followed by March with contributions of ∼31 %-49 %. Since these biomass burning figures contrast with the official emissions inventory of Mexico City metropolitan area, which assigns <1 % of total CO2 emissions to biomass burning, this study could exhibit the emissions inventory underestimation of this source, and thus, the need to reassess and incorporate top-down isotopic constraints in fire-affected urban regions.

Mexico↗

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

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

Metformin Adherence and Risk of Polyneuropathy in Type 2 Diabetes Mellitus: An International Matched Cohort Study with Independent Validation.

BACKGROUND: Metformin is a popular first-line glucose-lowering medication for type 2 diabetes mellitus (T2DM). Although metformin reduces the risks of various complications of diabetes, its potential to cause polyneuropathy by depleting vitamin B12 levels is concerning. This study investigated whether the adherence or discontinuation of metformin after adding-on a second-line antiglycemic agent increases the risk of polyneuropathy in patients with T2DM. METHODS: Data from TriNetX were obtained, and patients with T2DM who were receiving second-line antiglycemic agents were divided into metformin-adherent and metformin-nonadherent groups based on prescription claims data. Neuropathy incidence was evaluated using diagnostic claims and nerve conduction examinations. For independent confirmation and external validation of the primary findings, we used data from the National Health Insurance Research Database (NHIRD) of Taiwan. RESULTS: After matching, 58,027 patients were included in each group. Compared with metformin adherent patients, metformin nonadherent patients had a higher risk of polyneuropathy (adjusted hazard ratios [aHR] 1.26; 95% confidence interval [CI] 1.23-1.29; P < 0.001). Risks of diabetic foot ulcer, amputation, neuropathy-related medication use, and bone fracture were also higher among nonadherent patients. Sensitivity analyses confirmed the robustness of findings. In the validation NHIRD cohort (31,384 matched pairs), metformin nonadherence remained associated with increased polyneuropathy risk (aHR 1.25; 95% CI 1.10-1.42; P < 0.001). CONCLUSIONS: Metformin adherence in patients with T2DM who require second-line treatment may reduce the risk of polyneuropathy; vitamin B supplementation may enhance this benefit.

Humans↗

PubMed2026

Reproductive Intentions and Fertility Preservation Among Transgender and Nonbinary Individuals: A Cross-Sectional Study in Brazil.

PURPOSE: This study evaluated reproductive intentions, fertility-related knowledge, prior fertility counseling, and factors associated with reproductive intentions among transgender and nonbinary individuals receiving care at a Brazilian public reference center. METHODS: This cross-sectional study with a qualitative component was conducted between July and November 2025 in a specialized gender-affirming care clinic in Brazil. Quantitative data included sociodemographic characteristics, reproductive history, gender-affirming hormone therapy (GAHT), and fertility-related variables. Logistic regression was used to assess factors associated with desire for future parenthood. Responses to a single open-ended question regarding perceived effects of GAHT on fertility were analyzed using thematic content analysis. RESULTS: Eighty-two participants were included (mean age 27.5 ± 7.4 years). Most identified as transgender men (65.9%), followed by transgender women (26.8%) and nonbinary individuals (7.3%); 79.3% were receiving GAHT. Although 63.4% expressed a desire for future parenthood, only 7.3% had children. Current interest in fertility preservation was reported by 20.8% (15/72). Having children (adjusted odds ratio [aOR] = 0.03; 95% confidence interval [CI]: 0.001-0.62; p = 0.023) and each additional year of GAHT duration (aOR = 0.83; 95% CI: 0.70-0.99; p = 0.038) were associated with lower odds of desiring future parenthood. Sex assigned at birth was not independently associated with reproductive intentions. Qualitative analysis revealed misconceptions, uncertainty, and conditional beliefs regarding fertility. CONCLUSIONS: Desire for future parenthood was common among transgender and nonbinary individuals, whereas engagement with fertility preservation remained limited. These findings highlight the need for longitudinal, patient-centered reproductive counseling integrated into gender-affirming care.

fertility preservation↗

PubMed2026

RPLP0 drives diffuse large B-cell lymphoma cell proliferation through reactive oxygen species-dependent AKT/mTOR activation and inhibition of stress-induced autophagy.

Diffuse large B-cell lymphoma (DLBCL) is a common, aggressive subtype of non-Hodgkin lymphoma with poor outcomes. Identifying the primary molecular causes of DLBCL remains key. The present study examined the function of ribosomal protein lateral stalk subunit P0 (RPLP0) in DLBCL pathogenesis. The Cancer Genome Atlas-DLBCL and GSE12453 datasets overlapping differentially expressed genes were identified. Hub genes were identified via protein-protein interaction network analysis. DLBCL cells were subjected to functional tests following RPLP0 overexpression or knockdown. Reverse transcription-quantitative PCR, western blotting, flow cytometry, transmission electron microscopy, colony formation assay and biochemical analysis were among the tests performed. N-acetylcysteine (NAC), rapamycin (RAPA) and 3-MA were among the medication therapies. In the DLBCL datasets, six ribosome-associated genes were differentially expressed. RPLP0 knockdown inhibited the proliferation of DLBCL cells and caused G2-phase arrest, without impacting apoptosis. Thioredoxin, heat shock protein family A member 1A and heat shock protein family B member 1 expression was downregulated by RPLP0 knockdown, which also increased the NAD+/NADH ratio, promoted reactive oxygen species (ROS) accumulation and caused mitochondrial membrane potential depolarization. Meanwhile, 3-MA reversed the effects of RPLP0 knockdown, which encouraged LC3-II accumulation, autophagy-related gene 5 (ATG5) overexpression and an increase in autophagic vesicles. Autophagy-related indicators were decreased, and AKT/mTOR phosphorylation was increased by RPLP0 overexpression, which RAPA inhibited. NAC therapy preserved the viability of RPLP0-silenced cells, restored p-AKT/p-mTOR levels and restored normal LC3 and ATG5 expression. These findings suggest that RPLP0 regulates stress-induced autophagy through ROS-dependent AKT/mTOR signaling and may represent a potential therapeutic target for DLBCL.

AKT/mTOR signaling pathway↗