SEARCH · Search PubMed

Results for “ratio-based biomarker”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

1,333 records · Page 7Linked to original sources

PubMed2026

Prevalence of Claudin 18.2 Expression in Gastric and Gastroesophageal Junction Adenocarcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Claudin 18 isoform 2 (CLDN18.2) has emerged as a clinically validated therapeutic target in gastric and gastroesophageal junction (GEJ) adenocarcinoma following the regulatory approval of zolbetuximab in combination with first-line chemotherapy. Accurate prevalence data at the clinically validated immunohistochemical threshold are essential for patient selection, healthcare resource planning, and treatment strategy. Reported prevalence estimates vary widely across studies due to differences in populations, methodologies, and immunohistochemical protocols. This systematic review and meta-analysis aimed to generate a robust pooled prevalence estimate of CLDN18.2 expression at the threshold used in pivotal phase III trials. METHODS: PubMed, Embase, and the Cochrane Library were searched from database inception through March 12th, 2026. Studies reporting CLDN18.2 expression in gastric or gastroesophageal junction adenocarcinoma using the ≥ 75% moderate-to-strong membranous staining threshold were included. Prevalence proportions were pooled using a random-effects model with logit transformation and restricted maximum-likelihood estimation of between-study variance. Heterogeneity was assessed using the I² statistic and Cochran's Q test, and a 95% prediction interval was calculated. Pre-specified subgroup analyses assessed antibody clone and geographic region, with additional exploratory analyses according to disease setting and specimen type. Sensitivity analyses were performed to assess the robustness of the pooled estimate. RESULTS: Twenty-two predominantly retrospective cohort studies comprising 12,173 patients were included. The pooled prevalence of CLDN18.2 positivity using a random-effects model was 33.99% (95% CI: 30.13%-38.07%; 95% prediction interval: approximately 18%-55%), with high between-study heterogeneity (I² = 92.4%). Subgroup analysis by antibody clone showed no statistically significant difference between studies using the 43-14 A clone (32.79%, 95% CI: 28.86%-36.97%) and those using other reported antibody clones (41.74%, 95% CI: 26.76%-58.42%; p = 0.281). One study with an unreported antibody clone was excluded from this subgroup analysis. Geographic subgroup analysis excluding the multinational Shitara et al. cohort demonstrated a non-significant trend toward higher prevalence in non-Asian populations (37.85%, 95% CI: 31.59%-44.54%) compared with Asian populations (32.10%, 95% CI: 27.28%-37.34%; p = 0.169). All three sensitivity analyses confirmed robustness of the pooled estimate. No significant evidence of publication bias was detected (Egger's test p = 0.56). CONCLUSIONS: Approximately one-third of patients with gastric and GEJ adenocarcinoma express CLDN18.2 at the clinically validated ≥ 75% threshold. However, because the included studies encompassed heterogeneous disease settings and were predominantly HER2-unselected, the pooled estimate should not be interpreted directly as the proportion of patients eligible for zolbetuximab. The estimate was robust across sensitivity analyses and provides an evidence base for understanding CLDN18.2 prevalence and biomarker-testing requirements. Standardisation of immunohistochemical assessment methods is warranted to reduce between-study heterogeneity in future research.

Humans↗

PubMed2026

Diagnostic accuracy of bronchoalveolar lavage fluid-based testing for pulmonary cryptococcosis: A systematic review and meta-analysis.

BACKGROUND: Pulmonary cryptococcosis(PC) presents diagnostic challenges because of its non-specific clinical and radiological manifestations. Bronchoalveolar lavage fluid (BALF)-based testing, which includes latex agglutination (LA) and lateral flow assay (LFA), offers a minimally invasive diagnostic method, yet its pooled diagnostic accuracy remains unclear. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Scopus from inception to May 2026. Studies evaluating BALF-based testing for PC with extractable 2 × 2 data were included. The methodological quality of relevant studies was assessed by the QUADAS-2 tool. Pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR) were estimated using a bivariate random-effects model. Subgroup analyses were performed by testing method and reference standard type. Heterogeneity was evaluated through paired forest plots, HSROC visualization, and exploratory bivariate meta-regression. RESULTS: The pooled sensitivity was 0.87 (95% CI: 0.81-0.91), and the specificity was 0.99 (95% CI: 0.982 - 0.995). The pooled positive likelihood ratio (PLR) was 88.00 (95% CI: 47.39 - 163.42), the negative likelihood ratio (NLR) was 0.13 (95% CI: 0.09 -0.20), and the DOR was 658.50 (95% CI: 285.36-1519.55). No significant threshold effect or publication bias was detected. Exploratory meta-regression suggested a possible assay-method effect in the joint model (P = 0.03), mainly driven by specificity (P = 0.01). CONCLUSIONS: The study demonstrates the high accuracy of CrAg in BALF for the diagnosis of pulmonary cryptococcosis, supporting its role as an important adjunctive diagnostic tool, particularly when tissue biopsy is not feasible or rapid results are needed. Larger prospective studies with standardized protocols are needed to validate these estimates.

Humans↗

PubMed2026

Evaluation of the clinical and mechanistic role of MCM2 expression in the prediction of meningioma recurrence after radiotherapy.

OBJECTIVE: Postoperative radiotherapy is an effective treatment for meningiomas; however, treatment response varies among patients. In addition, practical methods for predicting tumor recurrence after radiotherapy have not been well established. Minichromosome maintenance protein 2 (MCM2), a key regulator of DNA replication licensing, was recently implicated in highly proliferative molecular subtypes of meningioma. In this study, the authors evaluated whether MCM2 immunohistochemical expression predicts response to radiotherapy in patients with meningiomas. METHODS: The authors retrospectively analyzed the records of patients with WHO grade 1-3 meningiomas treated with resection followed by radiotherapy at a single institution between July 2003 and November 2023. The MCM2 labeling index was assessed immunohistochemically, and patients were stratified into MCM2-high and -low groups using a cutoff of 35%. Progression-free survival (PFS) was defined as the interval from the completion of radiation therapy to postoperative radiological tumor recurrence or regrowth. Patients who showed no progression were censored at their last follow-up. PFS was estimated using Kaplan-Meier analysis and subsequently evaluated with Cox proportional hazards models. To further investigate the biological mechanisms associated with MCM2 expression, comprehensive transcriptomic analyses, including gene set enrichment analysis, was performed to elucidate the molecular processes that occur within MCM2-high tumors. RESULTS: The study population included 15 men (42%) and 21 women (58%), with a mean age of 63 years. Ten tumors (28%) were classified as MCM2-high meningiomas and 26 (72%) as MCM2-low meningiomas. High MCM2 expression was significantly associated with WHO grades 2-3 histology and higher Ki-67 labeling indices. During a median follow-up of 2.52 years, tumor progression after radiotherapy occurred in 47% of the patients. High MCM2 expression (HR 8.34, p = 0.03) was significantly associated with shorter PFS and remained an independent predictor of recurrence after adjustment for WHO grade, tumor size, and Ki-67 labeling index. Transcriptomic analyses of MCM2-high tumors revealed upregulation of cell proliferation-related pathways, accompanied by increased signaling through the E2F8-CHEK1 axis associated with radiation resistance and suppression of the TNF-α signaling pathway implicated in radiosensitivity. CONCLUSIONS: In meningiomas, high MCM2 expression is associated with early recurrence following radiotherapy. The study findings suggest that this association is driven by diverse biological mechanisms related to cell cycle regulation and radioresistance. Immunohistochemical assessment of MCM2 expression may serve as a practical and accessible biomarker for risk stratification and may support the future development of individualized postoperative radiotherapy strategies.

Humans↗

PubMed2026

Diurnal differences in the effects of heat exposure on renal function: A randomized controlled crossover trial.

High temperature is a major risk factor for kidney injury, and population exposure to nighttime heat is increasing as the climate warms. However, whether renal responses to heat exposure differ between daytime and nighttime remains unclear. Forty-one healthy adults participated in a randomized crossover experiment conducted in a controlled laboratory setting. Participants were exposed to heat (32°C during daytime; 30°C during nighttime) and thermoneutral conditions (26°C) for 8 h. Blood and urine samples were collected before and after each exposure to examine various renal biomarkers reflecting glomerular filtration function, tubular injury, and early kidney stress. Heat exposure affected both blood and urinary biomarkers of kidney function, with notable diurnal differences in renal responses. Daytime heat exposure primarily affected blood markers of glomerular filtration, increasing creatinine by 7.67% (95% CI: 4.73%-10.61%) and cystatin C by 3.05% (95% CI: 0.17%-5.93%), while reducing estimated glomerular filtration rate by 0.05% (95% CI: 0.02%-0.08%). In contrast, nighttime heat exposure predominantly elevated urinary biomarkers of early kidney stress, including insulin-like growth factor-binding protein 7 (58.40%, 95% CI: 27.66%-89.14%), kidney injury molecule-1 (47.25%, 95% CI: 18.91%-75.59%), and tissue inhibitor of metalloproteinases-2 (51.88%, 95% CI: 22.26%-81.51%). Moreover, increases in insulin-like growth factor-binding protein 7 were significantly greater at night than during the day. Sleep-related parameters, including sleep quality, duration, and heart rate variability, partially mediated nighttime heat effects on renal responses. These results indicated that heat exposure induced different diurnal patterns in renal responses.

Humans↗

PubMed2026

Omics in hereditary optic neuropathies: A systematic review of clinical studies with an integrated point of view.

Hereditary optic neuropathies are characterized by bilateral visual loss due to the degeneration of retinal ganglion cells, resulting in optic nerve degeneration and atrophy. Although the genetic origin of the main isolated and syndromic hereditary optic neuropathies has been characterized, the clinical phenotypes exhibit significant and poorly understood variability in both penetrance and expressivity. Additionally, the genetic and environmental factors that influence the onset of these optic neuropathies remain poorly understood, with limited biomarkers to predict disease progression or as readouts for therapeutic trials. Data-driven omics strategies allow deep phenotyping to improve our understanding of pathophysiological mechanisms and to search for new biomarkers and therapeutic targets. We explore whether the omics strategies applied to patients with hereditary optic neuropathies have provided such new insights. MEDLINE, Web of Science and EMBASE databases were screened for studies with terms relating to hereditary optic neuropathies, transcriptomics, epigenomics, proteomics, metabolomics and lipidomics in clinical studies exploring patients' samples. Out of 1244 references identified, 22 articles were included after double-masked data curation. These articles focused only on the 3 main forms of hereditary optic neuropathies, namely, OPA1-related dominant optic atrophy (n = 4), Leber hereditary optic neuropathy (n = 13), and Wolfram syndrome (n = 5). While the methodological designs and results of these studies were highly heterogeneous, they revealed molecular alterations that we have attempted to discuss at the integrated multi-omics level. This data integration highlighted several common pathophysiological mechanisms such as energetic impairment, endoplasmic reticulum stress, proteotoxic and oxidative stresses, lipid remodeling and altered amino acid and purine metabolisms, while suggesting potential new biomarkers and therapeutic targets. These findings underscore the potential of integrated multi-omics approaches to deepen our understanding of the phenotypic complexity of hereditary optic neuropathies and to support the development of innovative diagnostic and therapeutic strategies.

Humans↗

PubMed2026

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

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

Humans↗

PubMed2026

Sarcomas: Research on Ultrarare Subtypes Gains Ground.

Rare cancers account for almost one fourth of all cancers. Sarcomas belong to the group of cancerous diseases with an incidence of less than 6 cases per 100,000 inhabitants. Over the past decade, activities were launched worldwide to elucidate the peculiarities of many of the more than 100 sarcoma subtypes described in the World Health Organization handbook. The major contributor to exact diagnosis is molecular pathology. The subgroup of ultrarare sarcomas (URS) poses a significant problem as each URS type has its own morphology, biology, natural history, and prognosis. In 2020, 35 international sarcoma centers agreed to standards of evaluating URS. The threshold was set to an incidence of less than 1 case per 1,000,000 inhabitants, and 77 URS subtypes were defined. Also quality criteria for centers to be selected for retrieving data to registries were consented. This issue of Cancer Epidemiology, Biomarkers & Prevention contains the first article to validate these principles of URS using the data from a nationwide cancer database. The authors from Taiwan also pointed out limitations of the approach. Combination with the national death database allowed to calculate overall survival (OS) and identified age as a significant factor for OS per URS type. These new data might foster future research on diagnosis and treatment of URS. See related article by Lee et al., p. 1654.

Humans↗

PubMed2026

Assessment of the Potential of Different Anthropometric Indices in Predicting the Risk of Diabetes and Associated Co-morbidities.

Diabetes, a chronic disorder, is showing a rapidly increasing trend globally. India holds the second position in the global diabetes epidemic. The present investigation is an assessment of different anthropometric measurements and their association with type 2 diabetes to determine their diagnostic potential for diabetes as well as its co-morbidities. In this cross-sectional study, we have measured anthropometric parameters and blood biomarkers in subjects with diabetes. We have presented the comparisons of cost- and time-effective anthropometric variable with costly and time-dependent biochemical variables in control and diabetic groups (n = 233/group). Correlations between anthropometric variables and biochemical measurements, as well as the diagnostic utility of anthropometric variables for diabetes, were evaluated. The diagnostic utility of anthropometric variables for diabetes was assessed through receiver operating characteristic (ROC) curves. Neck circumference, sagittal abdominal diameter (SAD), skinfold thickness, and body roundness index (BRI) displayed high specificity and diagnostic utility for diabetes, emphasizing their potential in predicting diabetes and the further development of metabolic syndrome. The study highlights the importance of cost- and time-effective anthropometric assessments in diabetes risk evaluation and calls for further research to elucidate this intricate relationship and develop personalized management strategies.

Humans↗

PubMed2026

Blood Bile Acids for Inflammatory Bowel Disease Diagnosis and Disease Activity Assessment: A Metabolomics Meta-Analysis.

Alterations in circulating bile acids (BAs) have been reported in inflammatory bowel disease (IBD), but the consistency of these changes across clinically relevant comparisons remains unclear. Our goal was to investigate systemic BA alterations in IBD using a metabolomics meta-analysis with an exploratory analysis of BA-related gene expression as a supporting context. A systematic review and meta-analysis of 28 metabolomics studies examined blood BA profiles associated with IBD, IBD diagnosis, and disease activity assessment. Univariate analysis and logistic regression modeling of two independent IBD cohorts explored the blood BA-related genes and IBD. Across 28 studies that comprised 5056 IBD patients, 1721 healthy controls, and 314 non-IBD patients, 131 BAs were reported. Eight predefined clinical comparisons were eligible for the meta-analysis. Lower secondary BA levels were consistently observed in IBD patients compared with controls, between UC and CD, and in active versus remission patients. Deoxycholic acid, glycodeoxycholic acid, and taurodeoxycholic acid were frequently decreased, whereas glycocholic acid was increased in certain comparisons. Transcriptomics analyses revealed differential expression of several BA-related genes in blood, including SLC51A, ABCB4, and ACOT8, across the comparisons. Our findings identify consistent circulating BA alterations in IBD and highlight the relevance of blood BA for future biomarker research in the diagnosis and disease activity assessment.

Humans↗

PubMed2026

Evaluation of pilocarpine effects on sweat proteome.

BACKGROUND: Sweat is increasingly recognized as a valuable, non-invasive biofluid for biomarker discovery, yet its composition depends on the stimulation method. This study aimed to determine how pharmacological induction with pilocarpine compares to physiologically induced sweat through exercise in shaping the sweat proteome. RESULTS: We analyzed thermoregulatory sweat from exercise, pilocarpine-induced sweat, and combined pilocarpine plus exercise sweat. Total protein concentrations were similar across conditions, but pilocarpine markedly increased proteomic diversity, with combined pilocarpine plus exercise sweat showing the highest number of identifications. The core sweat proteome remained stable, while pilocarpine selectively enriched low-abundance proteins involved in vesicular trafficking, cytoskeletal remodelling, and metabolism. Proteins linked to the canonical M3-Gq-PLC-Ca2+ pathway, including AQP5, CALML5, and CLIC1, were consistently enriched, confirming cholinergic activation. Pilocarpine-induced sweat also contained plasma-derived and immune-related proteins, reflecting enhanced secretion and reduced ductal reabsorption. CONCLUSIONS: Exercise yields a physiologically relevant but less complex proteome, pilocarpine-induced sweat produces a pharmacologically enriched yet biased profile, and combined pilocarpine plus exercise sweat maximizes protein detection at the expense of interpretability. These findings highlight the critical impact of stimulation paradigm on sweat proteomics and provide a reference framework for biomarker research. SIGNIFICANCE: This study employed LC-MS/MS to systematically characterize eccrine sweat and delineate how stimulation paradigms-exercise, pilocarpine, and their combination-shape its proteomic landscape. By demonstrating that pharmacological induction profoundly alters protein diversity and composition compared to physiologically induced sweat, these findings establish a critical benchmark for sweat-based biomarker research and highlight the need for paradigm-aware sampling strategies in clinical and translational contexts. Nonetheless, several methodological constraints warrant consideration: the limited sample size (five individuals per group), the exclusive inclusion of women under combined oral contraceptive treatment (21 active pills followed by 7 pill-free days), which restricts extrapolation to naturally cycling women, and the focus on healthy young adults (18-25 years), limiting generalizability to older or clinically heterogeneous populations. Despite these limitations, this work provides a foundational framework for optimizing sweat collection protocols and advancing precision approaches in non-invasive diagnostics.

Pilocarpine↗

PubMed2026

Effects of CPAP on endothelial activation and fibrinolytic balance in coronary artery disease with obstructive sleep apnea: The RICCADSA randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) promotes endothelial activation and a prothrombotic milieu through intermittent hypoxia, oxidative stress, and systemic inflammation, mechanisms closely linked to atherosclerosis progression. The vascular effects of continuous positive airway pressure (CPAP) therapy in patients with established coronary artery disease (CAD) remain incompletely understood. OBJECTIVE: To evaluate the longitudinal effects of CPAP treatment on endothelial adhesion molecules and fibrinolytic balance in patients with CAD and OSA. METHODS: In this randomized controlled analysis from the RICCADSA trial, 210 revascularized CAD patients with moderate-to-severe OSA were assigned to CPAP (n = 104) or no-CPAP (n = 106) and had available biomarker measurements at baseline and 12 months. Circulating intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and plasminogen activator inhibitor-1 (PAI-1) were assessed. Linear mixed-effects models were used to examine longitudinal changes and time-by-treatment interactions adjusted for cardiometabolic covariates. RESULTS: For ICAM-1, no significant time-by-treatment interaction was observed. For PAI-1, a borderline time-by-treatment interaction suggested a numerically smaller increase in the CPAP group compared with no-CPAP (p = 0.09). CPAP treatment was associated with a significantly greater reduction in VCAM-1 over time compared with no-CPAP (time-by-treatment interaction p = 0.045 in adjusted models). CONCLUSIONS: CPAP treatment was associated with selective modulation of vascular biomarkers in patients with CAD and OSA, characterized by attenuation of endothelial activation reflected by reduced VCAM-1 levels, while fibrinolytic imbalance appeared largely resistant to intervention. These findings support pathway-specific vascular responses to CPAP and provide mechanistic insight into residual atherosclerotic risk in this high-risk population.

Aged↗

PubMed2026

Investigation of ACE gene polymorphism and serum ACE activity in relation to alopecia areata among Iraqi patients.

BACKGROUND: Alopecia areata (AA) is a multifactorial disorder with immune dysregulation and genetic susceptibility, affecting 0.5-2% globally. OBJECTIVE: This study investigated angiotensin converting enzyme (ACE) gene insertion /deletion (I/D) polymorphism and serum ACE activity in Iraqi AA patients and their association with inflammatory cytokines (interleukin [IL]-17) and nutritional markers to understand disease progression. METHODS: This case-control study included 50 AA patients (Male and Female) and 35 healthy controls. ACE gene polymorphism (rs1799752) was analyzed using real-time polymerase chain reaction (qPCR) with high-resolution melting (HRM) analysis. Serum IL-17 levels were determined by enzyme-linked immunosorbent assay (ELISA), and biochemical markers were measured using an automated analyzer. RESULTS: ACE gene polymorphism (rs1799752) showed non-significant genotype distribution between patient and control groups (p > 0.05), though a trend toward DD genotype enrichment was observed in patients. Serum ACE levels were significantly higher in patients versus controls (p < 0.0001) with high diagnostic performance. ACE correlated positively with IL-17 (P < 0.0001) and negatively with vitamin D3 and zinc (P < 0.0001). Female patients had significantly higher ACE levels than males (P < 0.01). CONCLUSIONS: ACE emerges as an immunometabolic hub in AA pathogenesis, integrating inflammation with nutritional deficits, suggesting its potential as a biomarker and therapeutic target.

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

Temporal Trends and Spatial Variation in Preterm Prelabour Rupture of Membranes: A Population-Based Study.

OBJECTIVE: To describe the temporal trends in Preterm prelabour rupture of membranes (PPROM) in metropolitan France and the geographical distribution at the administrative division level. DESIGN: Exploratory population-based study using administrative data of the French National Health Data System. SETTING: Metropolitan France, 2015 to 2023. POPULATION: Pregnancy with a diagnosis of PROM before 37 SA. METHODS: Annual crude incidence of PPROM was calculated by dividing the number of pregnancies with PPROM diagnosis by the number of live births recorded during the same period. Annual trend was estimated by a binomial negative mixed model. Smoothed standardised incidence ratios were estimated based on a BYM2 model, which accounts for spatial variability between departments. MAIN OUTCOME: PPROM cases, defined as pregnancies with first hospitalizations with a diagnosis of PROM before 37 weeks. RESULTS: Over the study period, we included 150 615 PPROM cases representing 16 735 (±596) per year. Incidence of PPROM cases showed an ascending trend over time (incidence rate ratio 1.023 per year; 95% CI: 1.017-1.030) with an annual crude incidence ranging from 2.2% in 2015 to 2.7% in 2023. A decrease in the incidence was observed in 2020 relative to other years (incidence rate ratio 0.903, 95% CI: 0.887-0.920). A map of smoothed SIRs of PPROM cases at the French administrative division level revealed geographical inequalities. CONCLUSIONS: This first population-based study describing PPROM cases in metropolitan France paves the way for further studies to explore environmental hypotheses. Identifying temporal and geographical disparities in PPROM incidence is relevant to public health policy and practice as such disparities argue for the development of targeted prevention strategies in high-risk areas.

French national health data system↗

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

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

Normoalbuminuric and albuminuric diabetic kidney disease exhibit divergent renal proteomic characteristics: implications for management.

BACKGROUND: The pathogenesis of diabetic kidney disease (DKD) is complex. Normoalbuminuric diabetic kidney disease (NADKD) is a special subtype of DKD that often progresses insidiously without detectable albuminuria, posing diagnostic and therapeutic challenges. Its pathogenesis remains unclear. Proteomic analysis of renal tissues may offer insights into its pathogenesis and identify biomarkers. METHODS: Clinicopathological data from 295 biopsy-proven DKD patients were collected and classified into normoalbuminuric (UACR < 30 mg/g, n = 25), microalbuminuric (UACR 30-300 mg/g, n = 26), and macroalbuminuric (UACR > 300 mg/g, n = 244) groups. Laser microdissection combined with mass spectrometry (LMD/MS) was used to analyze glomerular and proximal tubule proteomics in 5 patients per DKD subgroup and 5 control subjects. Associations with clinical features were examined. RESULTS: Glomerular proteomic analysis revealed that oxidative stress and metabolic pathways (UQCRC1) were upregulated in NADKD group, whereas the complement and coagulation cascades (C3, C5, C6, C9, CFH, CFHR1) were significantly upregulated in the microalbuminuric and macroalbuminuric DKD groups. The proximal tubule proteomics analysis showed that oxidative phosphorylation-related proteins (SDHA, CYCS, UQCRQ) were upregulated in NADKD, and collagen I related proteins (COL1A1, COL1A2) were significantly upregulated. CONCLUSION: Oxidative stress and mitochondrial dysfunction are involved in the progression of NADKD, lesions predominantly located in the tubulointerstitium. The complement pathway participates in the pathogenesis and progression of albuminuric DKD (ADKD). These divergent molecular profiles suggest that NADKD and ADKD may reflect different pathophysiological mechanisms and have important implications for therapeutic strategies in diabetes management.

Humans↗

PubMed2026

Digital health interventions for diabetes management in the eastern mediterranean region: A systematic review of types and effectiveness.

AIM: The aim of this study was to systematically review and evaluate the types and effectiveness of digital health interventions used for diabetes management in the Eastern Mediterranean Region (EMRO). METHODS: This systematic review, conducted according to PRISMA guidelines, searched PubMed, Web of Science, and Scopus up to May 2025 to identify studies on digital interventions for diabetes management in EMRO countries. Methodological quality of the included studies was evaluated using the EPHPP tool, and findings were categorized by intervention type, outcome measures, and intervention effectiveness. RESULTS: A total of 46 studies were included, mainly from Iran and Saudi Arabia. Phone calls and SMS were the most common digital tools. Digital interventions significantly improved HbA1c, fasting blood sugar, and several behavioral outcomes such as physical activity, medication adherence, and self-efficacy, while effects on psychological outcomes were mixed. CONCLUSION: Digital health interventions, especially phone calls and SMS, effectively improve glycemic control and self-care behaviors, though their impact on psychological outcomes remains inconsistent.

Humans↗