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PubMed2026

Psychological distress and incident cardiovascular disease independent of life's essential 8: a prospective cohort study.

BACKGROUND: Although psychological stress has emerged as an important determinant of cardiovascular disease (CVD) risk, it remains excluded from the recently updated cardiovascular health (CVH) metrics, known as Life's Essential 8 (LE8). This study aimed to examine the association between psychological distress and the incidence of CVD, independent of Life's Essential 8 metrics, in a large Korean adult population. METHODS: This study included 6,410 participants from the Korean Genome and Epidemiology Study Ansan-Ansung cohort, who had no history of CVD and had complete baseline data on psychological distress and Life's Essential 8 cardiovascular health (LE8 CVH) metrics. Psychological distress was assessed using the Psychosocial Wellbeing Index Short Form (PWI-SF). CVD events were identified based on participants' self-reports of physician-diagnosed conditions: myocardial infarction, stroke, coronary artery disease, and congestive heart failure. Cox proportional hazards models were used to examine the association between PWI-SF scores and incident CVD, adjusting for age, sex, residential area, educational attainment, household income, and LE8 CVH metrics. RESULTS: During a median follow-up of 13.8 years, 500 new cases of CVD were identified. Higher PWI-SF scores were independently associated with an increased risk of CVD after adjusting for LE8 CVH metrics and other potential confounders (hazard ratio: 1.321; 95% confidence interval: 1.067-1.636; p = 0.011). CONCLUSION: These findings suggest that higher levels of psychological distress are independently associated with an increased risk of CVD, even after accounting for established LE8 CVH metrics. Incorporating psychological distress into future CVH assessments may enhance risk stratification and prevention strategies.

Humans↗

PubMed2026

Genetic risk stratification of common diseases in breast cancer survivors: a population-based cohort study.

IMPORTANCE: Patients diagnosed with breast cancer (BCa) are at increased risk of multiple common diseases; however, the spectrum of these diseases and the contribution of inherited genetic susceptibility remain incompletely characterized. METHODS: We evaluated 15 common diseases and tested their associations with BCa exposure and disease-specific polygenic risk scores (PRS) in the UK Biobank (UKB; N = 254,736). Analyses were performed using cause-specific Cox proportional hazards models within a full-cohort framework, with time-updated BCa status, delayed entry at study recruitment, and age as the underlying time scale. RESULTS: After recruitment, incident BCa was diagnosed in 11,386 women (4.47%), including 2,742 (24.08%) with metastatic BCa. Patients with BCa had an increased risk of nine diseases spanning cardiovascular, metabolic, and neuropsychiatric domains (P<0.003, Bonferroni-corrected). Elevated risks were generally observed among patients with both early staged and advanced BCa. Inherited susceptibility further stratified disease risk, with the highest risks observed among patients with BCa with elevated disease-specific PRS. For example, compared with women without BCa, the hazard ratio (HR; 95% CI) for osteoporosis was 2.33 (2.15-2.52) among women with any BCa, 2.38 (2.18-2.59) among those with non-metastatic BCa, and 2.12 (1.78-2.54) among those with metastatic BCa; the HR was 4.48 (3.99-5.02) among patients with BCa in the highest quartile of osteoporosis-specific PRS (all P<0.001). In contrast, BCa was not significantly associated with risk of coronary artery disease. CONCLUSION: BCa and inherited genetic susceptibility jointly contribute to increased risk of multiple common diseases, supporting the integration of genetic risk stratification into survivorship care.

Complications↗

PubMed2026

A multi-scale fusion model based on multi-phase contrast-enhanced CT for predicting pancreatic cancer resectability.

Purpose.Develop a multi-scale fusion model (MSFM) based on multi-phase contrast-enhanced computed tomography (CECT) to predict pancreatic cancer (PC) resectability, thereby assisting expert decision-making.Methods.This retrospective study enrolled 280 patients with PC from four institutions, which were randomly divided into a training cohort (202 patients) and an independent test cohort (78 patients). Three-phase CECT images (arterial, venous, and delayed phases) were used for modeling. The MSFM comprises two sub-networks: (1) a multi-phase fusion network for extracting cross-phase shared fusion features, (2) a phase-specific branch network for capturing phase-specific features; and a post-fusion strategy to generate the final predictive score by integrating the shared fusion features and three groups of phase-specific features. Additionally, a human-machine fusion deep learning model (HMfDL) was constructed by fusing the predictive score of the MSFM with expert assessments.Results.In the independent test, the MSFM achieved an AUC (area under the receiver operating characteristic curve) of 0.8385 (95% CI: 0.7521-0.9249), accuracy of 84.62%, sensitivity of 72.00%, and specificity of 90.57%. This performance outperformed single-phase models (AUC range: 0.7638-0.7781), two-phase models (AUC range: 0.7826-0.7864), and ten states-of-the-art classifiers (AUC range: 0.7404-0.7796). The HMfDL further improved the performance, reaching an AUC of 0.8626 (95% CI: 0.7853-0.9400), accuracy of 91.03%, sensitivity of 80.00%, and specificity of 96.23%. Notably, the HMfDL corrected 58.82% of misdiagnosis made by experts.Conclusions. The MSFM effectively fuses multi-phase CECT to enable highly accurate predictions of PC resectability, and provides valuable support for expert decision-making through HMfDL.

Humans↗

PubMed2026

Tissue origins of the plasma proteomic response to glucose ingestion in humans.

AIMS/HYPOTHESIS: Circulating proteins act as important hormonal signals of nutrient intake. We aimed to systematically characterise the time-resolved proteomic response to glucose ingestion in humans, and to assess its robustness following prolonged complete caloric restriction. METHODS: We conducted oral glucose tolerance tests (OGTTs) in 11 healthy volunteers before and after 7 days of complete caloric restriction and measured the response of >2900 targets through high-resolution plasma protein profiling. RESULTS: We identified a signature of 44 proteins that changed significantly following glucose ingestion, which was reproducible after 7 days without food, and was strongly (20-fold) enriched for 'stomach-specific' proteins. We report that annexin A10 (ANXA10) shows the most significant post-glucose change observed, similar to the trajectories of secreted hormones. We present observational human evidence from multiple sources suggesting that ANXA10 is secreted upon sensing an increase in gastric pH, with the stomach as the major contributing tissue. Despite a profound metabolic shift after 7 days of complete caloric restriction, characterised by delayed insulin secretion and postprandial hyperglycaemia, only four proteins showed robust evidence for a differential trajectory during both OGTTs. This included plasma levels of tryptophanyl-tRNA synthetase 1 (WARS), for which we found a genetic association with glucose homeostasis and coronary artery disease. CONCLUSIONS/INTERPRETATION: Our exploratory study identifies the proteomic response to glucose ingestion and demonstrates its reproducibility despite major shifts in glucose homeostasis. We characterise the gastrointestinal origin of these changes, and hypothesise a hitherto under-recognised role for sensing of changes in gastric pH on the plasma proteome.

Humans↗

PubMed2026

Effects of Moderate-Frequency Resistance Training on Cardiometabolic Risk Factors in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis.

BACKGROUND: Resistance training (RT) effectively manages cardiometabolic risk factors in adults, but the specific effects of moderate-frequency RT (2-3 sessions/week) in adults with overweight or obesity are understudied. OBJECTIVE: This study aimed to evaluate moderate-frequency RT's effects on cardiometabolic risk factors in this population and quantify effect sizes. DATA SOURCES: PubMed, Web of Science, EMBASE, and Cochrane Library searched up to July 2025. ELIGIBILITY: English randomized controlled trials (RCTs) comparing RT (≥ 7 weeks) to nonexercise control; nonathletic adults ≥ 18 years with BMI ≥ 25 kg/m2. PARTICIPANTS: 454 participants across 12 RCTs (mean age 58.93 ± 12.87 years; mean BMI 31.2 ± 3.5 kg/m2; ~50% female). RESULTS: RT significantly reduced diastolic blood pressure (MD = -1.53 mmHg; 95% CI: -2.16 to -0.91; p < 0.01), LDL-C (MD = -0.25 mmol/L; 95% CI: -0.41 to -0.08; p < 0.01), and triglycerides (MD = -0.17 mmol/L; 95% CI: -0.30 to -0.04; p = 0.01). No significant effects on systolic blood pressure, mean arterial pressure, waist circumference, glycemic markers, total cholesterol, or HDL-C. Subgroup analyses showed larger LDL-C/triglyceride improvements with concurrent dietary control. CONCLUSION: Moderate-frequency RT inconsistently improves cardiometabolic risk factors, benefiting diastolic blood pressure, LDL-C, and triglycerides but not glycemic or other parameters. Combining with dietary control may enhance benefits, supporting RT as a complementary strategy in multimodal lifestyle interventions. TRIAL REGISTRATION PROSPERO: CRD42022343167.

Humans↗

PubMed2026

Effects of phenylephrine and norepinephrine with restrictive infusion on oxygenation during one-lung ventilation for lung surgery: a randomized controlled trial.

OBJECTIVE: This study compared the effects of norepinephrine or phenylephrine combined with restrictive infusion on the oxygenation during thoracoscopic one-lung ventilation (OLV). METHODS: Ninety patients were randomly divided into three groups: the norepinephrine group (Group N), the phenylephrine group (Group P), and the control group (Group C). Arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt fraction (Qs/Qt) were measured with patients in lateral positions during two-lung ventilation (TLV) at 10 min (T1), and during OLV at 15 min (T2) and 45 min (T3). Lung tissue samples were analyzed for endothelin and COX-2 levels after surgery. RESULTS: At T3, Group P had significantly higher PaO2 and lower Qs/Qt than Groups N and C (all p < 0.05), with no significant differences between Groups N and C (all p > 0.05). Compared to T1, Groups N and C showed significantly lower PaO2 and higher Qs/Qt at T2 and T3 (all p < 0.05), with no significant differences in PaO2 and Qs/Qt at T3 compared with T2 (all p > 0.05). Group P patients had lower PaO2 and higher Qs/Qt at T2 and T3 compared to T1 (all p < 0.05), but at T3, PaO2 increased and Qs/Qt decreased compared to T2 (all p < 0.05). Lung tissue levels of endothelin and COX-2 were significantly elevated in group P compared to groups N and C (all p < 0.05). CONCLUSION: Combining phenylephrine with restrictive infusion during OLV improved oxygenation by increasing PaO2, decreasing Qs/Qt, and raising endothelin and COX-2 levels in lung tissue, thereby enhancing the HPV effect.

Humans↗

PubMed2026

No association between alcohol consumption and hip osteoarthritis: a diverse national analysis of 87,585 adults from the "All of Us" research program.

INTRODUCTION: Hip osteoarthritis (OA) is estimated to affect 62.6 million individuals by 2050. A probable link exists between alcohol use and hip OA. However, the results are inconsistent, and the relationship between alcohol and hip OA remains speculative. To address these gaps, this study aimed to utilize the diverse, nationally representative All of Us Research Program dataset to explore the association between alcohol consumption and hip OA. METHODS: This retrospective case-control study utilized data from the All of Us Research Program Controlled Tier Dataset v8. 17,517 hip OA cases and 70,068 controls were identified. A 1:4 case-to-control matching ratio was applied based on age and sex. Alcohol use frequency was categorized into five levels: Never, Monthly or Less, Two to Four Times per Month, Two to Three Times per Week, and Four or More Times per Week. Multivariable logistic regression models evaluated the association between alcohol use frequency and hip OA after adjusting for demographic and clinical variables. RESULTS: Multivariable analysis found that alcohol use frequency was not significantly associated with hip OA. Compared to never users, participants with low (OR 0.98, 95% CI 0.93-1.04, P = 0.583), moderate (OR 0.99-1.01, all P > 0.05), and high (OR 1.02, 95% CI 0.95-1.09, P = 0.599) levels of alcohol consumption had no statistically significant differences in odds of hip OA. Female sex, Asian race, diabetes, hypertension, hyperlipidemia, and nicotine dependence increased the odds of hip OA. CONCLUSION: Any level of alcohol consumption was not significantly associated with the odds of hip OA. This study adds valuable insight to the current body of conflicting evidence. Further prospective studies appear warranted to shed light on the long-term effects of different alcoholic beverages on different joints. Key Points • This study found no significant association between any degree of alcohol consumption and the odds of developing hip osteoarthritis. • Utilizing data from 87,585 adults in the NIH "All of Us" Research Program, this is the first study to analyze this relationship in a large, nationally representative population. • The research provides clarity to previously conflicting literature by demonstrating that alcohol lacks a clear harmful or protective effect on the clinical course of the disease. • The analysis highlights that independent risk factors such as Asian race, nicotine dependence, and components of metabolic syndrome increase the odds of hip osteoarthritis.

Humans↗

PubMed2026

Factors associated with periprosthetic joint infection following total knee arthroplasty: an updated systematic review and meta-analysis.

BACKGROUND: This study aimed to systematically evaluate factors associated with periprosthetic joint infection (PJI) following total knee arthroplasty (TKA), and thereby to provide evidence-based references for clinical prevention and perioperative risk stratification. METHODS: Computerized searches were conducted in the following databases from their inception until May 26, 2025: PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. Two researchers independently screened the literature, extracted data, and assessed study quality. The methodological quality was assessed using the Newcastle-Ottawa Scale. Quantitative synthesis was performed when at least two studies reported comparable exposure definitions and sufficient comparator information; otherwise, narrative synthesis was used. Review Manager 5.4 software was used for the primary analysis. This study is registered on PROSPERO (CRD420251079339). RESULTS: A total of 25 observational studies were included in the qualitative synthesis, of which 24 contributed to the primary quantitative synthesis. Quantitatively pooled factors associated with PJI included male sex (OR = 1.39, 95% CI 1.27-1.51), BMI ≥30 kg/m2 (OR = 5.72, 95% CI 2.65-12.36), prolonged operative time, type 2 diabetes mellitus (OR = 2.09, 95% CI 1.45-3.01), rheumatoid arthritis (OR = 2.64, 95% CI 1.38-5.02), smoking (OR = 1.65, 95% CI 1.34-2.04), blood transfusion (OR = 2.27, 95% CI 1.59-3.25), American Society of Anesthesiologists score ≥3 (OR = 2.73, 95% CI 1.02-7.32), history of hormone therapy (OR = 4.88, 95% CI 2.90-8.22), postoperative urinary tract infection (OR = 3.59, 95% CI 1.15-11.21), intraoperative blood loss >200 ml (OR = 1.51, 95% CI 1.03-2.22), postoperative drainage tube placement duration ≥24 h (OR = 2.23, 95% CI 1.50-3.32), preoperative anemia (OR = 1.82, 95% CI 1.67-1.99), and combined pulmonary disease (OR = 5.54, 95% CI 1.93-15.96). Age was narratively summarized because its classification differed substantially across studies. CONCLUSION: Multiple demographic, comorbidity-related, and perioperative factors were associated with PJI after TKA. However, because the included studies were observational and clinically heterogeneous, these findings should be interpreted as associations rather than causal effects. Optimization of modifiable factors may help reduce the burden of PJI, but further prospective studies using standardized PJI definitions and adjusted effect estimates are required.

Humans↗

PubMed2026

Effects of semaglutide and empagliflozin on markers of endothelial function in persons with type 2 diabetes: A post hoc analysis of a randomized clinical trial.

AIMS: The endothelium maintains vascular health by regulating blood flow and protecting against inflammatory damage. In type 2 diabetes (T2DM), however, hyperglycemia, hypertension, and hyperlipidemia place a significant burden on the endothelium, potentially leading to atherosclerosis and cardiovascular disease (CVD). While semaglutide and empagliflozin have been shown to reduce CVD risk in T2DM, it remains unclear whether these benefits are mediated by improved endothelial function. This post-hoc analysis explores the effects of these agents on markers of endothelial function, i.e. the reactive hyperaemic index (RHI) and the endothelial-derived cell adhesion molecules (CAMs) E-Selectin, ICAM-1, P-Selectin, and VCAM-1. METHODS: This was a post-hoc analysis of a 32-week randomized trial evaluating the separate and combined effects of semaglutide and empagliflozin on cardio-renal organ damage. One hundred and twenty participants with type 2 diabetes, age ≥ 50 were randomized to four groups (semaglutide, empagliflozin, the combination or placebo). An increase in RHI and/or a decrease in CAMs were considered beneficial. RESULTS: RHI increased compared to baseline (0.11, 95%CI [0.008;0.21], p = 0.03) but not compared to placebo in the semaglutide group (0.11, 95%CI [-0.04;0.24], p = 0.16). There was no effect on RHI in the empagliflozin group. Compared to placebo, E-Selectin decreased significantly in the semaglutide and combination groups (-9, 95%CI [-14.1;-5.1] p < 0.01 and - 9, 95%CI [-14.3; -5.2] p < 0.01, respectively). VCAM-1 increased in the same groups, compared to placebo (12.3, 95%CI[2.8;20.8] p = 0.01 and 16.2, 95%CI [7.2;24.3], p < 0.01, respectively).P-Selectin and ICAM-1 was not significantly affected in any of the groups, compared to placebo (p ≥ 0.11 and p ≥ 0.09, respectively). CONCLUSION: Semaglutide improved endothelial function compared to baseline, but not significantly versus placebo, which likely is due to limited power. CAM responses were heterogeneous, suggesting distinct roles in endothelial dysfunction and atherosclerosis. ClinicalTrialsRegister.eu: EudraCT 2019-000781-38.

Aged↗

PubMed2026

Comparison of the Effects of Spinal Versus General Anesthesia on the Perioperative Intraocular Pressure: A prospective, randomized clinical trial.

OBJECTIVES: To evaluate the effects of spinal and general anesthesia on the intraocular pressure (IOP) in patients, who had lumbar spine and lower extremity orthopedic surgeries. METHODS: Sixty adult were randomly classified into Group spinal anesthesia (SA) and Group general anesthesia (GA). The IOP, mean systemic arterial pressure, and heart rhythm were measured at 6 pre-determined timepoints (T0: Baseline, T1: Before spinal procedure or anesthesia induction, T2: After injection with intrathecal or anesthesia induction, T3: 5th minutes (min) after spinal procedure or tracheal intubation, T4: 30th min intraoperative, T5: At the end of surgery, T6: 5th min after surgery or tracheal extubation in the operation room. RESULTS: The baseline IOP and IOP1 measurements during were not significantly different between the groups (SA = 14.28 ± 0.8 mmHg; GA = 14.62 ± 0.9 mmHg, p = 0.923; and IOP1: SA = 15.83 ± 0.9 mmHg; GA = 15.88 ± 0.9 mmHg, p = 0.929). The most significant decrease in IOP in both groups was recorded at T2 (SA: 12.37 ± 0.6. GA: 12.24 ± 0.4, p < 0.001). The decrease in IOP2 was more significant in the GA group. The IOP3 was significantly higher in GA group after intubation (GA: 19.82 ± 1.2, SA: 12.86 ± 1.0)(p < 0.05). The IOP4 and IOP5 in the SA group were lower than those in the GA group. The IOP6 in both groups was higher (SA: 15.20 ± 0.8, GA: 16.50 ± 1.0) than the baseline IOP values, albeit not significant (p > 0.05). In prone position, IOP at the T4 and T5 timepoints were significantly higher than the initial values in both the SA and the GA groups; however, the increase in the GA group was more higher than that of the SA group. CONCLUSION: In intraoperative period, intraocular pressure may increase in both management of anesthesia, but this increase is higher in the general anesthesia group.

Humans↗

PubMed2026

Physicochemical effects of bicarbonate-buffered solution versus compound sodium lactate during major abdominal surgery: A randomized, open-label, non-inferiority trial.

INTRODUCTION: Bicarbonate-buffered crystalloids avoid exogenous lactate and have physicochemical properties distinct from compound sodium lactate (CSL), but direct comparative evidence during major abdominal surgery remains limited. METHODS: This single-center, open-label, randomized non-inferiority trial enrolled high-risk adults undergoing elective major abdominal surgery. Participants received bicarbonate-buffered solution or CSL as the allocated intraoperative crystalloid. The primary estimand was the arithmetic mean difference in standard base excess (SBE) at skin closure (bicarbonate-buffered solution minus CSL). The non-inferiority margin was -1.5 mEq/L. The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619001228178). RESULTS: Fifty participants were randomized (25 per group) and received their allocated intervention. End-of-surgery arterial blood gas data were missing for two CSL participants. In the intention-to-treat analysis using multiple imputation, the estimated mean difference in end-of-surgery SBE was -0.42 mEq/L (95% confidence interval [CI], -1.92 to 1.09 mEq/L). The complete-case per-protocol estimate was -0.48 mEq/L (95% CI, -2.02 to 1.06 mEq/L). In both analyses, the lower CI bound was below the prespecified non-inferiority margin; non-inferiority was not established. Secondary outcomes were exploratory; observed end-of-surgery lactate was lower with bicarbonate-buffered solution (median 0.9 vs 1.2 mmol/L; unadjusted P = 0.031), without a corresponding difference in SBE or pH. CONCLUSIONS: In this small trial of hemodynamically stable adults undergoing elective major abdominal surgery, the primary non-inferiority result was inconclusive. The data did not establish interchangeability, equivalence, superiority, or inferiority of the two fluids. As the trial was powered for a physiologic endpoint, no comparative inference can be made about organ dysfunction, postoperative complications, recovery, or mortality. Larger trials with standardized co-interventions and patient-important outcomes are required before routine substitution for CSL can be recommended.

Humans↗

PubMed2026

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

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

Humans↗

PubMed2026

Higher versus Routine Intraoperative Blood Pressure Targets in Noncardiac Surgery: A Systematic Review and Meta-analysis with Trial Sequential Analysis of Randomized Trials.

BACKGROUND: Observational studies consistently link intraoperative hypotension to adverse postoperative outcomes, leading guidelines to recommend maintaining mean arterial pressure 60 to 65 mmHg or greater during noncardiac surgery. Whether targeting higher intraoperative blood pressure values improves clinical outcomes remains uncertain. METHODS: The authors conducted a Preferred Reporting Items for Systematic Reviews and Meta-analyses-guided search on PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Embase from inception to April 2026. Randomized trials comparing higher intraoperative blood pressure targets, either as fixed absolute thresholds or personalized to preoperative baseline, versus routine blood pressure management in adults undergoing elective noncardiac surgery with general anesthesia were included. Outcomes included in-hospital or 30-day mortality, postoperative delirium, acute kidney injury (AKI), 30-day major cardiovascular events, acute myocardial injury, stroke, length of stay, and intraoperative hypotension. RESULTS: Fifteen trials (15,603 patients) were included. Higher targets did not reduce AKI (risk ratio [RR], 0.95; 95% CI, 0.85 to 1.06; P = 0.36; I 2 = 16%) or acute myocardial injury (RR, 1.02; 95% CI, 0.94 to 1.12; P = 0.59; I 2 = 0%) compared with routine targets, with firm evidence from trial sequential analysis. Higher targets were associated with a significant reduction in postoperative delirium (RR, 0.73; 95% CI, 0.54 to 0.98; P = 0.04; I 2 = 26%), although trial sequential analysis indicated the cumulative evidence remained insufficient to draw firm conclusions. No significant effect was observed on in-hospital or 30-day mortality (RR, 1.00; 95% CI, 0.75 to 1.34; P = 1.00; I 2 = 0%); evidence on 30-day major cardiovascular events, stroke, and length of stay was similarly insufficient to draw firm conclusions. CONCLUSION: In adults undergoing elective noncardiac surgery, targeting higher intraoperative blood pressure values does not improve major postoperative outcomes compared with routine management. A potential reduction in postoperative delirium warrants confirmation in adequately powered trials.

Humans↗

PubMed2026

Design, rationale, and baseline patient characteristics for the Sickle Cell Disease and CardiovAscular Risk-Red cell Exchange (SCD-CARRE) trial.

BACKGROUND: Despite wide utilization of automated red blood cell exchange (RBCX) transfusion in adult patients with sickle cell disease (SCD), no consensus or quality efficacy data exist on its use. The Sickle Cell Disease and CardiovAscular Risk- Red cell Exchange (SCD-CARRE) trial tests the hypothesis that an automated chronic RBCX transfusion strategy reduces acute health care encounters and death while improving quality of life and end-organ function (cardiac, pulmonary and renal) in participants with SCD that are at high risk of death. METHODS: Adult patients with SCD with elevated tricuspid regurgitant jet velocity (TRV) and/or chronic kidney disease were considered to be at high risk of death and were randomly assigned to RBCX plus standard of care vs standard of care alone. Participants assigned to RBCX received 12 months of exchange transfusions to maintain target pretransfusion hemoglobin S% < 30%, post-transfusion hemoglobin S% < 20%, and post-transfusion hemoglobin concentration ≥10 g/dL. All study participants were managed according to NHLBI/ASH/ATS Expert Panel guidelines. The primary endpoint was the number of SCD acute health care encounters or death over 13 months. Secondary endpoints included measures of cardiovascular and renal function, exercise capacity, patient reported outcomes (all collected at baseline, and months 4, 8, and 12), and transfusion-related adverse events (collected monthly). RESULTS: Between 2020 and 2025, the SCD-CARRE trial randomized 173 participants at 23 sites across 3 countries. Enrolled participants had mean (SD) age of 45.8 (11.8) years and 54% were female. At baseline, participants had average TRV of 2.8 (0.5) m/s such that 45.9% had a TRV between 2.5 to 2.9 m/sec and 28.1% had a TRV ≥ 3.0 m/sec. The median (Q1, Q3) eGFR in this cohort was 60 (36, 110) mL/min/1.73 m2. The median (Q1, Q3) 6-minute walk test distance was 375 meters (309, 439), the median daily steps were 3,728 (2,187, 5,821), and participants experienced a median (Q1, Q3) of 2 (1, 5) pain episodes in the year prior to randomization. The trial results are pending. CONCLUSIONS: The SCD-CARRE trial successfully enrolled a cohort of n = 173 adults with SCD. This study highlights a rationale to evaluate the effect of automated chronic RBCX transfusion strategy plus standard of care as compared to standard of care alone in SCD patients at high risk of death with a focus on patient centered outcomes, preservation of cardiovascular function, end-organ complications and death. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT04084080, https://clinicaltrials.gov/study/NCT04084080.

Adult↗

PubMed2026

[Pathogenicity analysis and prenatal genetic counseling for five Chinese pedigrees harboring a hemizygous c.-32C>G variant of FGF13 gene].

OBJECTIVE: To explore the pathogenicity and prenatal counseling strategies for five Chinese pedigrees harboring a hemizygous c.-32C>G (NM_001139500.2) variant of fibroblast growth factor 13 (FGF13) gene. METHODS: Five Chinese pedigrees found to carry a hemizygous c.-32C>G variant of the FGF13 gene at the Prenatal Diagnosis Center of Henan Provincial People's Hospital between January 2024 and January 2025 were selected as study subjects. The pedigrees had undergone prenatal diagnosis for a family history of genetic disorders, abnormal fetal ultrasound findings, or advanced maternal age. A retrospective analysis was carried out, wherein clinical data for all members of the pedigrees were obtained through the medical records system and outpatient visit system. Peripheral blood samples were collected from all pedigree members, and amniotic fluid samples were obtained from the probands. Following extraction of genomic DNA, prenatal diagnosis was performed using chromosomal microarray analysis (CMA) and trio whole-exome sequencing (trio-WES). Sanger sequencing was used to determine the carrier status for the candidate variant, and Mini-Mental State Examination (MMSE) was used to assess the cognitive function of hemizygous individuals carrying the FGF13 gene c.-32C>G variant. Pathogenicity of candidate variant was assessed based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2021-171). RESULTS: CMA and trio-WES revealed no pathogenic variants in all probands, whilst trio-WES and Sanger sequencing had identified 11 male individuals carrying a hemizygous c.-32C>G variant of the FGF13 gene from the five pedigrees, which included six adult males, a young boy, and four fetuses. One fetus had undergone termination of pregnancy due to hydrocephalus, one was born pre-term at 34+1 weeks of gestation owing to maternal hypertension, and other two were delivered at full term. Follow-up of the survived males revealed no phenotypic manifestations related to language or intellectual impairment. Among these, three adult males underwent the MMSE assessment, all of whom showed normal cognitive function. Search of the gnomAD database suggested the carrier frequency of FGF13 c.-32C>G variant in the East Asian population to be 0.125%, with 11 hemizygous males documented. Three male patients harboring the variant showed severe intellectual disability. Both in vitro and in vivo studies suggested that it could reduce the translation levels of FGF13 protein. Based on the ACMG guidelines, it was classified as variant of uncertain significance (BS4+PS3_Supporting). CONCLUSION: There is insufficient evidence to classify the FGF13 c.-32C>G as a pathogenic variant in clinical practice, and its presence should not be considered an indication for pregnancy termination due to major birth defects.

Adult↗

PubMed2026

Effects of passive blood flow restriction on muscle function following exercise-induced muscle damage in recreationally active males.

This investigation examined the effects of passive blood flow restriction (pBFR) on indices of exercise-induced muscle damage (EIMD) in recreationally active males. Fifteen males completed six consecutive visits (±2 hours). Participants completed 3 × 25 maximal, unilateral, isokinetic (60°·s-1), concentric-eccentric leg extensions on both legs. Each leg was randomly assigned to receive pBFR (80% arterial occlusion pressure) or sham (20 mmHg) at 0, 24, 48, 72, and 96 hours post-EIMD. Perceived muscle soreness, range of motion (ROM), pain pressure threshold (PPT), concentric peak torque (CPT), and maximal voluntary isometric contraction (MVIC) torque were assessed and analyzed using separate linear mixed-effects models. Perceived muscle soreness increased at 24 hours (mean difference [meandiff] = 4.9 au; p < 0.001) and recovered by 96 hours (p = 0.482), with no differences between conditions (p = 0.450). ROM (meandiff = -3.1°; p = 0.040), PPT (meandiff = -1.63 kgf; p < 0.001), CPT (meandiff = -27.7 Nm; p < 0.001), and MVIC torque (meandiff = -30.8 Nm; p < 0.001) decreased at 24 hours, with recovery occurring between 48-96 hours. Condition-specific differences were observed for ROM (meandiff = 2.5°; p < 0.001), PPT (meandiff = 0.49 kgf; p = 0.005), CPT (meandiff = 6.2 Nm; p = 0.020), and MVIC torque (meandiff = 7.1 Nm; p = 0.044), which were greater in pBFR than sham. These findings suggested that pBFR may reduce impairments in ROM, PPT, CPT, and MVIC torque following EIMD, despite a similar recovery trajectory between conditions.

Humans↗

PubMed2026

Premeal insulin administration lowers postprandial blood glucose and increases myocardial microvascular blood flow in people with type 1 diabetes: a randomised, crossover clinical trial.

AIMS/HYPOTHESIS: We aimed to evaluate whether prandial insulin timing affects vascular function in people with type 1 diabetes. Our hypothesis was that premeal insulin administration would lead to greater myocardial microvascular blood flow (MBF) via blunting postprandial hyperglycaemia. METHODS: People with type 1 diabetes between 18 and 35 years of age with BMI <30 kg/m2 underwent two protocols with a 1:1 randomised crossover design wherein prandial insulin was injected either 15 min before or 15 min after meal intake began. To provide a physiological comparison, age-, sex- and BMI-matched control participants completed one study where they consumed the same meal but received no exogenous insulin. Glucose, insulin, vascular function (including ultrasound measures of myocardial and skeletal muscle microvascular perfusion, aortic stiffness, brachial artery endothelial function) and biomarkers of systemic inflammation and endothelial dysfunction were assessed at baseline and then 2 h after meal ingestion within each protocol. The primary outcome was change in myocardial MBF within each protocol. Study personnel assessing outcomes were masked to group assignment. RESULTS: Eighteen people with type 1 diabetes and 18 matched control participants were analysed within each protocol. Glucose area under the curve was significantly greater (p=0.015) in the postmeal insulin study compared with the premeal insulin study in participants with type 1 diabetes. Myocardial microvascular flow velocity significantly increased (p=0.031) with premeal insulin administration in people with type 1 diabetes and this consequently led to greater myocardial MBF (p=0.044). There were no changes in myocardial MBF within the other protocols. Changes in vital signs were similar between all protocols. CONCLUSIONS/INTERPRETATION: Appropriately timed premeal insulin led to lower postprandial blood glucose along with increased myocardial MBF in people with type 1 diabetes. Further work is needed to determine the underlying aetiology of these changes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04730882.

Humans↗

PubMed2026

Angiography-Based Index of Microcirculatory Resistance in Assessing the MVO and Infarct Size in STEMI Patients.

OBJECTIVES: To evaluate angiography-based index of microcirculatory resistance (angio-IMR) in assessing microvascular obstruction (MVO) and infarct size (IS) in ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The effect of thrombolysis on post-percutaneous coronary intervention (PCI) angio-IMR, and its associations with MVO and IS remains unclear. METHODS: One hundred twenty-three STEMI patients randomized to receive 5 mg intravenous bolus of recombinant staphylokinase (r-SAK) or normal saline (NS) before PCI were recruited. Angio-IMR was computed in infarct-related arteries. MVO and IS were detected by cardiac magnetic resonance imaging. RESULTS: Compared with NS group, r-SAK group exhibited numerically lower post-PCI angio-IMR (39.12 U vs. 42.57 U; p = 0.567), MVO (54.0% vs. 70.9%; p = 0.059), MVO extent (0.70% vs. 1.90%; p = 0.101) and IS (21.30% vs. 24.50%; p = 0.079). Post-PCI angio-IMR was positively correlated with MVO extent (ρ = 0.347; p < 0.001) and IS (ρ = 0.324; p < 0.001). Receiver operating characteristic analyses showed moderate diagnostic performance of angio-IMR for MVO (area under the curve [AUC] = 0.750; p < 0.001), MVO > 2.6% (AUC = 0.735; p < 0.001) and IS > 25% (AUC = 0.712; p < 0.001). The exploratory optimal cut-off values for these endpoints were approximately 40 U. CONCLUSIONS: In STEMI patients, a single bolus of r-SAK before PCI was associated with numeric reductions in post-PCI angio-IMR, MVO, MVO extent and IS. Additionally, angio-IMR exhibited a significantly positive correlation with both MVO extent and IS, demonstrating the diagnostic value of this wire-free method for assessing microvascular injury.

Humans↗