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Colchicine to prevent cardiovascular events in thoracic surgery patients with or without coronary artery disease: a secondary analysis.

OBJECTIVES: This exploratory post hoc secondary analysis of the Colchicine for the Prevention of Perioperative Atrial Fibrillation (COP-AF) randomised controlled trial evaluated the association between coronary artery disease (CAD) and postoperative ischaemic outcomes after non-cardiac thoracic surgery and assessed whether colchicine had differential effects by CAD status. METHODS: Patients were randomised to colchicine 0.5&#x2009;mg or placebo two times per day for 10 days. Follow-up was 14 days. The primary outcome was myocardial injury after non-cardiac surgery (MINS). A key secondary outcome was the composite of death, MINS and stroke. Cox proportional hazards models assessed the association between CAD and outcomes, with interaction terms to explore whether colchicine had differential effects by CAD status. RESULTS: Of 3209 patients enrolled, 331 (10.3%) had CAD. MINS occurred in 29.3% (n=97) and 18.2% (n=523) of patients with and without CAD, adjusted HR (aHR) 1.53 (95% CI 1.22 to 1.92; p<0.001). For colchicine versus placebo, the HR for MINS was 0.82 (95% CI 0.55 to 1.22) in CAD versus 0.91 (95% CI 0.77 to 1.08) in non-CAD patients (p for interaction=0.61). Death, stroke or MINS occurred in 30.2% (n=100) vs 18.6% (n=535), respectively (aHR 1.53, 95% CI 1.22 to 1.91; p<0.001). Colchicine HRs were 0.77 (95% CI 0.52 to 1.14)&#x2009;vs 0.91 (95% CI 0.76 to 1.07; p for interaction=0.45). CONCLUSIONS: Patients with CAD undergoing thoracic surgery had a higher risk of MINS and other ischaemic outcomes than non-CAD patients. There was no evidence that the effect of colchicine differed between patients with and without CAD; however, these analyses were limited by sample size and do not exclude modest differences between subgroups.

Humans

Pairwise Comparative Safety and Effectiveness of Anti-TNF Blockers, Vedolizumab, and Ustekinumab During Pregnancy: A Systematic Review and Meta-Analysis.

PURPOSE: Biologic therapies, including tumor necrosis factor (TNF) blockers, vedolizumab (VDZ), and ustekinumab (UST), are generally considered safe during pregnancy in patients with inflammatory bowel disease (IBD), though comparative data remain limited. This meta-analysis examines their safety and effectiveness. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, Cochrane, and Web of Science was conducted through July 2025. Eligible studies reported maternal or neonatal outcomes in pregnant IBD patients treated with biologics. Studies were pooled using a random-effects model to calculate risk ratios (RRs) with 95% confidence intervals. Heterogeneity was assessed using I2. Primary outcomes were preterm birth and disease activity; secondary outcomes included pregnancy and neonatal outcomes. RESULTS: Nine observational studies (n&#x2009;=&#x2009;6,054) were included. Compared to TNF blockers, VDZ was associated with a higher risk of preterm delivery (RR&#x2009;=&#x2009;1.35, 95% CI 1.04-1.75, I2&#x2009;=&#x2009;0%) and active disease (RR&#x2009;=&#x2009;1.55, 95% CI 1.01-2.40, I2&#x2009;=&#x2009;50%). UST was associated with a higher risk of active disease (RR&#x2009;=&#x2009;1.30, 95% CI 1.06-1.60, I2&#x2009;=&#x2009;0%) and congenital anomalies (RR&#x2009;=&#x2009;2.08, 95% CI 1.30-3.32, I2&#x2009;=&#x2009;0%) compared to TNF blockers. Compared to UST, VDZ was linked to increased risks of preterm birth (RR&#x2009;=&#x2009;2.60, 95% CI 1.03-6.57, I2&#x2009;=&#x2009;0%) and low birth weight (RR&#x2009;=&#x2009;2.38, 95% CI 1.01-5.60, I2&#x2009;=&#x2009;0%). No significant differences were observed for live births, abortions, hospitalizations, or neonatal infections. CONCLUSION: TNF blockers showed a favorable safety and effectiveness profile, VDZ and UST performed broadly similar, and all three biological classes appeared compatible with safe use in pregnancy to maintain effective disease control. Observed differences reflect that VDZ and UST cohorts likely had longer disease duration, prior biologic exposure, and more active disease. The results of this meta-analysis support the continuation of biologic therapy for disease control in pregnant patients with IBD. Treatment decisions should be individualized and tailored to each patient's clinical context.

Female

Cost-Effectiveness and the Economics of Genomic Testing and Molecularly Matched Therapies.

Cost-effectiveness analysis of precision oncology can help guide value-driven care. Next-generation sequencing is increasingly cost-efficient over single gene testing because diagnostic algorithms require multiple individual gene tests to determine biomarker status. Matched targeted therapy is often not cost-effective due to the high cost associated with drug treatment. However, genomic profiling can promote cost-effective care by identifying patients who are unlikely to benefit from therapy. Additional applications of genomic profiling such as universal testing for hereditary cancer syndromes and germline testing in patients with cancer may represent cost-effective approaches compared with traditional history-based diagnostic methods.

Humans

Hypertension in a Randomized Trial of Dolutegravir- Versus Efavirenz-Based Antiretroviral Therapy in Pregnant and Postpartum Women with HIV.

INTRODUCTION: We performed an analysis of incident hypertension in a randomized trial comparing dolutegravir (DTG) + emtricitabine (F)/tenofovir alafenamide (TAF) versus DTG + F/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/F/TDF in pregnant and postpartum women with HIV. METHODS: Women were randomized at 14-28 weeks gestational age (GA) to start DTG + F/TAF, DTG + F/TDF, or EFV/F/TDF and followed through 50 weeks postpartum. The composite incident hypertension outcome was defined as initiation of antihypertensive medication or &#x2265;2 elevated blood pressures categorized as elevated (130-139 and/or 80-89 mmHg), mild (140-159 and/or 90-99 mmHg), moderate (&#x2265;160-179 and/or &#x2265;100-109 mmHg), and severe (&#x2265;180 and/or &#x2265;110 mmHg). Incident gestational hypertension was defined by initiation of antihypertensive medication or &#x2265;2 blood pressures &#x2265; 140 and/or &#x2265;90 mmHg at &#x2265;20 weeks GA with resolution by 12 weeks postpartum. Cox proportional hazard models were used for by-arm comparisons of the composite outcome and to look for the effect of weight change within arm. RESULTS: Of 626 women without baseline hypertension (median age 26.6 years), the composite incident outcome occurred in 49% (n = 308), predominantly due to the incident elevated category of elevated blood pressure, with no significant differences by arm, although hypertension was numerically more likely in the DTG arms. Each additional 5 kg of weight was associated with an 8%-17% higher hazard of the composite hypertension outcome. Twenty-seven participants (4.3%) had gestational hypertension with no apparent differences between arms. CONCLUSIONS: Our data contribute information regarding the safety of DTG-based ART and TAF in pregnant and postpartum women and highlight the importance of monitoring weight and performing hypertension screening as part of maternal health care for young women with HIV.

Humans

Surgical management of jugular foramen meningiomas: a function-prioritized perioperative workflow.

OBJECTIVE: Jugular foramen meningiomas are challenging because of their deep, neurovascularly crowded location and multicompartment extension; hyperostosis and rigid dural attachment further narrow the corridor and increase the risk of lower cranial nerve morbidity, causing dysphagia and airway complications that may rarely require tracheostomy. This study aimed to describe a contemporary function-first workflow integrating compartment-based anatomy, venous sinus status, preoperative embolization, and continuous vagus nerve monitoring and its relation to clinically actionable recovery endpoints. METHODS: The authors retrospectively reviewed 26 consecutive patients who underwent primary surgery for jugular foramen meningiomas (2014-2025). Tumors were classified as intradural + intrajugular (IJ) or intradural + intrajugular + extracranial extension (IJE). Retrosigmoid, suprajugular, or transjugular approaches were selected by tumor extension and sigmoid-jugular venous status. Selective embolization and continuous vagus nerve monitoring were used when feasible. Outcomes included extubation timing, time to oral intake, 1-year swallowing/voice severity, extent of resection, and salvage stereotactic radiosurgery (SRS) for progression/regrowth. RESULTS: Twenty tumors were IJ and 6 were IJE. Selective embolization was performed in 16 patients (62%) without complications. Continuous vagus nerve monitoring was implemented in 16 patients (62%); lower preservation rates showed an exploratory association with worse 1-year swallowing. All patients were extubated immediately after surgery. Oral intake began by postoperative day &#x2264; 7 in 20 patients (77%); only 1 required > 14 days before resuming oral intake. At 1 year, swallowing and hoarseness remained worse in 54% and 46% of patients, respectively, but almost all cases were mild; the same patient had moderate dysphagia/hoarseness, and none required tracheostomy, gastrostomy, long-term tube feeding, or phonosurgery. Simpson grade IV comprised 69% of cases but predominantly reflected intrajugular/extracranial residual rather than persistent intradural disease. No patient without preoperative facial nerve palsy developed new palsy; serviceable hearing was preserved in 70%, and 38% with preoperative nonserviceable hearing improved to serviceable hearing. During a median 55.6-month follow-up, 3 patients (12%) underwent salvage SRS for regrowth; none required reoperation. CONCLUSIONS: A function-first workflow guided by anatomical compartment extension and intraoperative monitoring can support rapid recovery and durable functional independence in jugular foramen meningiomas. The IJE phenotype identifies a higher-risk subgroup for delayed oral intake and postoperative subjective dysphagia/hoarseness, while continuous vagus nerve monitoring may provide actionable insights to calibrate surgical aggressiveness and support function-prioritized acceptance of intrajugular/extracranial residual with close surveillance and salvage SRS when needed.

Humans

Height variation independent of known genetic variants and health in later life: a cohort study.

BACKGROUND: Adult-attained height is associated with later-life health, but it reflects both genetic and nongenetic influences. The health implications of height variation not explained by known common height-associated genetic variants remain unclear. OBJECTIVES: This study aimed to examine associations of residual height (height variation independent of known genetic variants) with multiple disease incidence and all-cause mortality in later life. METHODS: In this cohort study of 407,366 adults of European ancestry (aged 40-70 y) in the United Kingdom Biobank (2006-2010), sex- and age-specific genetically predicted height was estimated from 9863 height-associated variants, adjusted for 30 principal components of ancestry. Residual height was calculated as the difference between observed and genetically predicted height. Plasma proteomics (2054 proteins; Olink Explore) were profiled. Deaths and 49 incident diseases were ascertained through national registries. Multivariable Cox models estimated associations of residual height and related proteins with disease incidence and mortality. RESULTS: Higher residual height [mean (standard deviation, SD), 0.0 (4.8)] was associated with more favorable self-reported preadulthood exposures (e.g., later birth years, no maternal smoking around birth, being breastfed as an infant, no adoption experience, and lower childhood adversity scores) and lower hazard ratios (HRs) of 32 out of 49 diseases (median follow-up = &#x223c;12.5 y). Using participants with residual height within &#xb1;0.5 SDs from the mean as reference, those with residual height < -2 SDs had higher adjusted HRs of mortality [1.61; 95% confidence interval (CI): 1.50, 1.72], multimorbidity (1.28; 95% CI: 1.12, 1.46), cardiovascular disease (1.45; 95% CI: 1.32, 1.60), psychiatric/neurological disease (1.38; 95% CI: 1.28, 1.48), and other disease categories (e.g., diabetes, digestive, and musculoskeletal diseases). In contrast, higher genetically predicted height was associated with a higher incidence of 19 diseases, including subtypes of cancer, non-atherosclerotic cardiovascular diseases, and musculoskeletal diseases, as well as higher all-cause mortality. We identified 806 plasma proteins related to inflammation, immune response, and autophagy via tumor necrosis factor, Nuclear factor-kappa B, phosphoinositide-3 kinase/protein kinase B, and Janus kinase/signal transducer and activator of transcription signaling pathways, which were associated with residual height and multiple diseases and mortality. CONCLUSIONS: Higher residual height is associated with lower disease incidence and mortality, with associations that are distinct from those for genetically predicted height.

Humans

Editorial Commentary: Stiff Patients After Rotator Cuff Repair: How Many Had Underrecognized Preoperative Adhesive Capsulitis?

Stiffness after rotator cuff repair is one of the most common sources of disability and one of the most common complications. Smoking, diabetes, Workers' compensation status, and traumatic tears are among the strongest risk factors. This is important information in setting appropriate expectations for both the patient and the surgeon preoperatively. Some of these factors are also associated with preoperative stiffness, so surgeons should maintain a high index of suspicion for concomitant adhesive capsulitis in patients presenting with limited motion, particularly in diabetic and non-English speaking populations. In cases where both a rotator cuff tear and adhesive capsulitis coexist, performing a concurrent capsular release or manipulation during the index procedure may improve functional outcomes and reduce the necessity for secondary surgical intervention.

Humans

Multidisciplinary mHealth Rehabilitation for Patients With Abdominal Cancer Who Are Receiving Chemoradiotherapy: Randomized Phase II Trial.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) for abdominal cancer frequently induces muscle loss, weight loss, and malnutrition. OBJECTIVE: This exploratory randomized phase II trial evaluated whether a multidisciplinary, mobile health (mHealth)-based multimodal rehabilitation program could preserve handgrip strength and muscle mass in patients with abdominal cancer undergoing CCRT. METHODS: In this prospective, multicenter, randomized, open-label phase II trial (NCT05325554), 111 eligible patients with abdominal malignancies scheduled for CCRT were randomly assigned (1:1) to receive either multidisciplinary mHealth rehabilitation care (MRC; n=57) or standard care (SC; n=54). The MRC program was delivered by a dedicated multidisciplinary team using the AiNST mHealth platform and wearable heart rate monitors. The primary end point was handgrip strength at the end of CCRT (analyzed with analysis of covariance adjusting for baseline). Secondary end points were exploratory and analyzed without multiplicity adjustment; sensitivity analysis using false discovery rate (FDR) correction was performed. RESULTS: Between February 2022 and April 2023, 111 patients were enrolled. Adherence was high (n=93, 83.9% achieved exercise targets). After adjusting for baseline handgrip strength, the MRC group had significantly higher handgrip strength at the end of CCRT than the SC group (adjusted mean difference 4.87 kg, 95% CI 3.36-6.38; P<.001). Exploratory analyses of secondary end points (without multiplicity adjustment) showed that the MRC group also had better preservation of body weight (P=.005), skeletal muscle mass (P<.001), serum albumin (P=.009), prealbumin (P=.02), and lower rates of hematological toxicity (P<.05), as well as improved psychological status (distress thermometer [DT] and Hospital Anxiety and Depression Scale [HADS]) and nutritional scores (Nutritional Risk Screening 2002 [NRS-2002] and Patient-Generated Subjective Global Assessment [PG-SGA]) at the end of CCRT (all P<.05). All nominally significant secondary end points remained significant after FDR correction (q<.05). These findings are preliminary and should be interpreted with caution due to the open-label design, population heterogeneity, and exploratory secondary analyses. CONCLUSIONS: In this exploratory phase II trial, a multidisciplinary, mHealth-based multimodal rehabilitation program was associated with better preservation of handgrip strength, muscle mass, and nutritional status, as well as lower rates of certain treatment toxicities, compared with SC. However, definitive conclusions are limited by the open-label design, heterogeneity of tumor types, and short follow-up. Larger, blinded phase III trials are needed to confirm these findings.

Humans

Extent of resection as an independent predictor of survival for patients with glioblastoma as defined by the new WHO 2021 classification.

OBJECTIVE: Extent of resection (EOR) has previously been demonstrated to have an impact on survival in patients with glioblastoma (GBM). However, with the World Health Organization (WHO) 2021 reclassification of GBMs based on IDH-mutation status, patients with "IDH-mutant GBMs," who typically survive long term, were reclassified as WHO grade 4 IDH-mutant astrocytomas and removed from the GBM taxonomy. Therefore, it is unknown whether the previously reported impact of resection on survival was a false-positive result due to the inclusion of the less aggressive IDH-mutant tumors in previous datasets. This study aimed to determine the extent to which EOR remains an independent predictor of survival in patients with WHO 2021 GBM after the reclassification of IDH-mutant grade 4 astrocytomas. METHODS: All cases of GBM tumors (based on the pre-2021 GBM classification) that were newly diagnosed between 2005 and 2021 were identified in our institutional database and subsequently reclassified based on the updated WHO 2021 criteria using IDH status. Multivariable statistical analyses of demographic information, survival time, and EOR based on volumetric MRI were performed to determine the independent predictors of survival for the whole group of patients and for IDH-wildtype GBM patients exclusively. Additional analyses were performed to identify an EOR threshold for improvement in survival. RESULTS: Of the 523 tumors classified as GBM based on the pre-2021 taxonomy, 52 (9.9%) cases were reclassified as WHO grade 4 IDH-mutant astrocytomas, and the median survival of patients in this group was 7.9 years, whereas median survival of the IDH-wildtype GBM patients was 1.4 years. Multivariate analyses of the whole group demonstrated that IDH-mutant astrocytomas were associated with reduced hazard of death. In both the whole group (n = 523) and in IDH-wildtype GBMs (n = 471), higher EOR of the contrast-enhancing (CE) tumor was associated with reduced hazard of death, whereas older age or male sex was associated with increased hazard of death. Because most patients (90%) had high EOR values (> 81%), a statistically meaningful EOR threshold could not be established. CONCLUSIONS: These analyses demonstrated that EOR of the CE tumor is an independent predictor of survival and that greater EOR is associated with improved survival in WHO 2021 IDH-wildtype GBMs even after excluding grade 4 IDH-mutant astrocytomas. However, an absolute EOR threshold below which resection did not improve survival could not be established, raising concerns about prior cutoff assessments.

Humans

Single-nucleus transcriptomics reveals cell type-specific remodeling and epilepsy-associated microglia.

Temporal lobe epilepsy (TLE) is the most common acquired epilepsy, causing refractory seizures and cognitive deficits. We performed single-nucleus RNA sequencing on hippocampal tissue from mice 3 and 6 weeks following pilocarpine-induced status epilepticus, a robust model of TLE. Epilepsy samples showed reductions in Cck and Lamp5-Lhx6 interneuron subclusters, alongside increases in Cajal-Retzius cells, dentate granule (DG) cell precursors, and a mature DG cell subcluster. Among glia, an astrocyte subcluster and a markedly expanded microglia sublcuster were increased. We term this microglia population epilepsy-associated microglia (EAM). The transcriptomic profile of EAM overlaps with microglia described in models of Alzheimer's disease and traumatic brain injury, including enrichment of Myo1e and Igf1. EAM display amoeboid morphology, can be found in clumps around pyramidal and granule cell body layers, and exhibit enlarged vesicles and mitochondria. Cell-cell interaction analysis predicts DG cells as their primary interaction partners. This dataset defines transcriptomic programs underlying key cellular alterations in TLE, enabling mechanistic dissection of epileptogenesis.

TLE

Structural and physicochemical characterisation of branched dextrans produced by an active &#x3b1;-(1&#x2192;2) branching sucrase from Apilactobacillus kunkeei PDER37.

Recently, branching sucrases encoded in the genomes of certain Lactic Acid Bacteria (LAB) strains have become novel enzymes to obtain branched &#x3b1;-glucans. In this study an active &#x3b1;-(1&#xa0;&#x2192;&#xa0;2) branching sucrase from Apilactobacillus kunkeei PDER37 was expressed, characterised and distinct branched dextrans was obtained with reactions under different sucrose: dextran ratio. Structural characterisation by 1H and 13C NMR analysis demonstrated the branching of the dextran with (1&#xa0;&#x2192;&#xa0;2)-linked &#x3b1;-d-glucose units with no alteration in the final structure depending on sucrose: dextran ratio (D0) but this ratio was effective for the determination of the molecular weights of the branched dextrans (D1, D2 and D3). FTIR analysis further supported the dextran structures and suggested the higher accumulation of the &#x3b1;-Glc units in the branched dextrans. Thermal characterisation of the branched dextrans obtained by TGA and DSC analysis suggested the increased hygroscopicity of the branching units. Both SEM and AFM analysis demonstrated more porous chain like structures in the branched dextrans. This study provides valuable information on the role of active &#x3b1;-(1&#xa0;&#x2192;&#xa0;2) branching sucrase (BS37) for the production of branched dextrans with potential increased physicochemical status applicable for food and other industries.

Dextrans

Targeting TP53 in triple-negative breast cancer: Molecular pathogenesis, therapeutic implications, and emerging pharmacological strategies.

Triple-negative breast cancer (TNBC) remains a highly aggressive and therapeutically challenging subtype, defined by the absence of oestrogen, progesterone, and HER2 expression. Tumour Protein 53 (TP53) mutations represent the most frequent genetic alteration, occurring in over 80% of cases and driving tumour initiation, progression, and therapeutic resistance. Mutant p53 proteins not only lose canonical tumour-suppressive functions but also often acquire gain-of-function (GOF) oncogenic properties that promote metastasis, genomic instability, and resistance to mechanisms like ferroptosis. This review examines the biological role of TP53 in TNBC pathogenesis and evaluates emerging pharmacological strategies aimed at targeting these vulnerabilities. Key approaches include the pharmacological reactivation of mutant p53 using small molecules such as APR-246, COTI-2, and the mutation-specific reactivator rezatapopt (PC14586), which has shown significant clinical tumour reduction in Y220C-mutant patients. Other strategies involve targeted protein degradation, the exploitation of synthetic lethal interactions (e.g., Chk1 or Aurora kinase B inhibition), and the use of natural products like cryptolepine or piperine derivatives. Recent clinical evidence further highlights the potential of combining epigenetic agents like decitabine with chemotherapy in TP53-mutant populations. Integrating TP53 mutation status into biomarker-driven treatment paradigms is a pivotal step toward achieving precision oncology and improving clinical outcomes for patients with TNBC.

Precision oncology

Vitamin B12 Deficiency in Sickle Cell Disease: Method-Driven Estimates and Systematic Diagnostic Misclassification.

OBJECTIVES: To determine whether the reported 0%-70% prevalence of vitamin B12 deficiency in sickle cell disease (SCD) reflects true population variation or diagnostic misclassification. METHODS: We conducted a PRISMA 2020-compliant systematic review of observational studies (January 1, 2000-May 13, 2026; PROSPERO CRD420251087800) assessing B12 status in SCD. PubMed, AJOL, and Google Scholar were searched with citation tracking and dual screening. Diagnostic validity was assessed across biomarker strategy, analytical platform, thresholds, and confounder control using a proposed context-integrated framework to classify methodological robustness and discordance. RESULTS: Fourteen studies were included (57% high-income; 43% LMIC). The evidence base was dominated by limited diagnostic approaches: 71% used immunoassays, over one-third relied on circulating B12 alone, and functional biomarkers were inconsistently applied without systematic confounder adjustment. Prevalence estimates were strongly influenced by diagnostic methods rather than underlying population biology, ranging from 0% to 70% in single-marker studies (mostly 0%-7.1%, with outliers ~50%-70%) and 6.9%-53% in multi-marker studies. Discordance was substantial and greater in LMIC settings than HIC. CONCLUSION: Current diagnostic approaches in SCD appear method-dependent, generating heterogeneous prevalence estimates with uncertain clinical validity. These findings challenge existing estimates and have implications for clinical practice, research design, and diagnostic equity. TRIAL REGISTRATION: ClinicalTrials.gov identifier: CRD420251087800.

Humans

Long-term glycemic variability and risk of peripheral artery disease: a systematic review and meta-analysis of cohort studies.

BACKGROUND: A systematic review and meta-analysis to evaluate the impact of long-term glucose variability (GV) on the risk of developing peripheral artery disease (PAD). METHODS: The protocol was prospectively registered in PROSPERO (ID: CRD420251148763). Relevant longitudinal studies were identified through comprehensive searches of PubMed, Embase, and Web of Science. The primary outcome was the risk ratio (RR) of PAD comparing participants with high versus low GV. Summary effect sizes were calculated using a random-effects model to account for between-study heterogeneity. RESULTS: Eleven cohorts were included. Higher GV showed a positive association with PAD risk (RR: 1.42; 95% CI [1.21-1.66] p&#xa0;<&#xa0;0.001), although substantial heterogeneity was present (I 2&#xa0;=&#xa0;91%). This association was consistent across subgroups defined by region (Asian vs. Western), study design, diabetic status, GV metrics, PAD diagnostic methods, and adjustment for HbA1c (all p for subgroup differences > 0.05), except for follow-up duration. Studies with follow-up < 8 years showed a stronger association than those with &#x2265; 8 years (RR: 1.64 vs. 1.19; p for subgroup difference = 0.006). CONCLUSIONS: Elevated long-term GV appears to be associated with an increased risk of PAD. However, substantial heterogeneity across studies suggests that the magnitude of this association should be interpreted with caution.

Humans

Association between packed red blood cell transfusion and clinical deterioration in neonatal necrotizing enterocolitis: a systematic review and meta-analysis.

BACKGROUND: No systematic review has evaluated the existing evidence regarding the association between packed red blood cell (pRBC) transfusion and clinical worsening of necrotizing enterocolitis (NEC) in neonates. This systematic review and meta-analysis was conducted to address this knowledge gap. MATERIALS AND METHODS: We searched the Cochrane Library, EBSCO, Embase, Web of Science, Google Scholar, and PubMed for studies on pRBC transfusion and NEC published before May 10, 2025. Relevant articles were selected through title, abstract, and full-text screening. English-language case-control studies or cohort studies, or randomized controlled trials involving newborns with NEC that compared pRBC transfusion with no transfusion and reported changes in NEC clinical status were included. Review articles, systematic reviews, case reports, editorials, animal studies, duplicate publications, and studies with incomplete data were excluded. RESULTS: Five studies involving 971 neonates with NEC were included. The pooled analysis demonstrated a potential association between pRBC transfusion and clinical deterioration of NEC in neonates (odds ratio: 6.05, 95% confidence interval: 3.02-12.14). CONCLUSIONS: pRBC transfusion was associated with an exacerbation of NEC in neonates. However, these findings should be interpreted cautiously because of the small number of eligible studies included in this meta-analysis, and future large-scale, well-designed studies are needed to confirm the observed association.

Humans

From pathobiology to prescribing in obesity-driven HFpEF: A systematic review and practical therapeutic framework.

Heart failure with preserved ejection fraction (HFpEF) is increasingly driven by obesity and cardiometabolic dysfunction. In this phenotype, the dominant biology extends beyond congestion alone and includes visceral and epicardial adiposity, systemic inflammation, impaired myocardial energetics, endothelial dysfunction, and exertional elevation in filling pressures. We performed a PRISMA-compliant systematic review with structured narrative evidence synthesis to evaluate pharmacological therapy in obesity-driven HFpEF, searching PubMed/MEDLINE, Scopus, Web of Science Core Collection, ClinicalTrials.gov, and WHO ICTRP through December 2025. Eighteen reports were included in the final qualitative synthesis. The available evidence supports sodium-glucose cotransporter 2 inhibitors as the pharmacological foundation because they provide the most mature outcome data across the preserved ejection fraction spectrum. Semaglutide improves symptoms, physical limitations, exercise capacity, and body weight in dedicated obesity-related HFpEF trials, whereas tirzepatide extends this signal by improving clinical status and reducing worsening heart failure events. Finerenone broadens the therapeutic platform in HF with mildly reduced or preserved ejection fraction, although obesity-specific data remain indirect. Conventional neurohormonal therapies retain a selective role, but they are not the principal biological match for this phenotype. Obesity-driven HFpEF should therefore be managed as a cardiometabolic syndrome with heart failure expression, using a phenotype-based sequence that links diagnosis, decongestion, SGLT2 inhibition, obesity-directed therapy, and selective adjunctive intensification.

Humans

Comparative analysis of gut microbiota in yaks under different feeding management strategies during cold seasons.

Yaks (Bos grunniens) are crucial for the livelihoods of pastoral communities in cold regions, where feed scarcity during the cold season poses challenges to their health and productivity, underscoring the necessity of understanding how dietary management influences the gut microbiota. In this study, 24 yak steers matched for body weight and health status were randomly allocated to four groups: natural grazing or indoor feeding with roughage-to-concentrate ratios of 50:50, 70:30, or 90:10. Fecal samples were collected for 16S rDNA sequencing and subsequent functional prediction of the microbiota. The results showed that Firmicutes and Bacteroidetes were the dominant phyla across all groups, and UCG-005 and Rikenellaceae_RC9_gut_group were the predominant genera. Concentrate supplementation during the cold season significantly enhanced microbial richness and diversity, with the 70:30 ratio exerting the most pronounced beneficial effects on microbiota structure and key taxa enrichment. These findings highlight the critical role of dietary management in shaping the yak gut microbiota during cold seasons and suggest that the 70:30 ratio optimally improves microbial community structure, thereby promoting yak health and productivity under harsh climatic conditions. Future research should explore the long-term implications of such dietary strategies.

Animals

Time-varying hazard rates reveal patterns of progression in HR+/HER2- metastatic breast cancer: Towards risk-adapted monitoring.

BACKGROUND: optimal imaging intervals for patients with hormone receptor-positive/HER2-negative metastatic breast cancer (MBC) remains undefined. Aim of this study was to analyze the temporal patterns of disease progression to identify high risk subgroups that may benefit from intensified monitoring. METHODS: we analyzed 149 hormone receptor-positive/HER2-negative MBC patients prospectively enrolled in the MAGNETIC.1 trial (NCT05814224) and treated with first line endocrine therapy. Hazard rates (HR) for disease progression were determined according to clinico-pathological and liquid biopsy features. RESULTS: in the overall population, two distinct progression-risk peaks emerged at 2-3 months (32.9/1000 person-months) and at 24 months (28.0/1000). Higher risk of progression was observed in lobular carcinoma (61.1) [HR 61.12 per 1000 person month (pm)], progesterone receptor-negative status (HR 39.07), fulvestrant-based treatment (HR 46.88), liver metastases (HR 59.00), and presence of &#x2265; 3 metastatic sites (HR 40.10). CONCLUSIONS: Hazard distribution in hormone receptor-positive/HER2-negative MBC is biphasic and modulated by readily available clinical variables. High-risk subgroups may benefit from intensified radiologic and liquid-biopsy surveillance during the first three months and around two years after treatment start.

Breast cancer