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PubMed2026

The impact of acute sleep fragmentation on muscle blood flow responses to handgrip exercise.

Sleep fragmentation is reported to impair resting vascular function. The aim of this study was to test the hypothesis that acute sleep fragmentation would impair muscle blood flow during exercise. Twenty adults (10 females and 10 males) participated in a randomized crossover study that included one night of habitual sleep and one night of fragmented sleep. Sleep was assessed at home using wrist actigraphy. Arousals from sleep were increased by an audio alarm sounding every 30 min. The morning following each sleep condition, participants performed single handgrip contractions and rhythmic handgrip exercise at 15%, 30%, and 45% MVC. Forearm blood flow (FBF) was measured using Doppler ultrasound. Nightly awakenings and wake after sleep onset significantly increased by 18% and 43%, respectively, after fragmented sleep, leading to lower sleep duration (P < 0.001). Peak FBF and total hyperemic responses following single contractions were similar between sleep conditions (all P > 0.05). During rhythmic handgrip exercise, brachial artery dilation was reduced after fragmented sleep (main effect: 5.5 ± 4.8 vs. 3.3 ± 3.7%; P = 0.01), leading to a lower FBF response to rhythmic exercise (main effect: 122 ± 58 vs. 110 ± 56 mL/min; P = 0.04). Endothelial sensitivity to shear rate was similar between sleep conditions (habitual vs. fragmented: 0.039 ± 0.024 vs. 0.042 ± 0.031%/s-1; P = 0.77). In summary, acute sleep fragmentation decreases skeletal muscle blood flow during exercise. This finding suggests that blunted oxygen delivery may be a contributing factor for exercise performance deficits after disturbed sleep.NEW & NOTEWORTHY We demonstrate that one night of fragmented sleep decreases steady-state blood flow and vascular conductance during low- to moderate-intensity handgrip exercise. This impairment was not due to an impaired rapid vasodilation to single contractions nor altered endothelial sensitivity to shear rate as these variables were unchanged after acute sleep fragmentation. These results reveal a negative impact of disrupted sleep on the steady-state muscle vasodilatory response to rhythmic contractions.

Humans↗

PubMed2026

Effects of single-injection vs. continuous brachial plexus blocks for shoulder surgeries on patient-reported outcomes: a systematic review and meta-analysis with trial sequential analysis of randomised controlled trials.

INTRODUCTION: Single-injection and continuous brachial plexus block techniques are used widely for postoperative analgesia in patients undergoing shoulder surgery. Although patient-reported outcomes are described in individual studies, their effects have not been synthesised comprehensively using a patient-centred framework. We sought to compare the effects of single-injection vs. continuous brachial plexus block techniques on patient-reported outcomes in adult patients following elective shoulder surgery. METHODS: Databases were searched from inception to October 2025 and randomised controlled trials reporting patient-reported outcomes were included. Co-primary outcomes were postoperative patient-reported pain intensity at rest and during movement at 12 h, 24 h and 48 h post-surgery. Secondary outcomes included nausea and vomiting; sleep quality; patient satisfaction; opioid requests; and functional scores. Random-effects meta-analysis and trial sequential analysis were performed, with risk of bias and quality of patient-reported outcome reporting assessed. RESULTS: Twenty randomised controlled trials that included 1198 patients were analysed. Continuous brachial plexus blocks were associated with lower pain at rest at 12 h, 24 h and 48 h, with mean differences (MD) of -1.96 (95%CI -2.81 to -1.11, p < 0.001), -1.66 (95%CI -2.27 to -1.05, p < 0.001) and - 1.18 (95%CI -1.84 to -0.53, p < 0.001), respectively. Pain on movement could only be pooled at 24 h and 48 h and showed MD -2.04 (95%CI -4.26-0.19, p = 0.07) and - 1.30 (95%CI -3.67-1.07, p = 0.28) respectively. The co-primary outcomes approached or exceeded the predefined minimal clinically important difference for pain scores after shoulder surgery, in favour of continuous techniques. DISCUSSION: Continuous brachial plexus blocks are associated with better pain at rest and other patient-centred outcomes following shoulder surgery, while effects on dynamic pain and long-term functional recovery remain uncertain.

Humans↗

PubMed2026

Exploring the Diagnostic Utility of Ferumoxytol for Brachial Plexus MR Neurography.

Background Ferumoxytol has been described as an alternative contrast agent for vascular suppression in MR neurography (MRN), but its diagnostic utility in patients has yet to be evaluated. Purpose To evaluate the impact of ferumoxytol on vascular suppression, nerve conspicuity, and evaluation of nerve abnormalities at three-dimensional (3D) brachial plexus MRN, compared with noncontrast and gadolinium-enhanced MRN, in participants with suspected Parsonage-Turner syndrome (PTS) or thoracic outlet syndrome (TOS). Materials and Methods This prospective study included participants who underwent 3D MRN with and/or without gadolinium chelate for clinical suspicion of PTS or TOS and subsequently underwent 3D MRN with ferumoxytol (within 3 months of the clinical examination). Two musculoskeletal radiologists qualitatively evaluated 3D short-tau inversion-recovery fast spin-echo scans for the degree of vascular suppression, nerve conspicuity, and presence of nerve abnormalities. Wilcoxon signed-rank or McNemar tests were used for comparing noncontrast and gadolinium-enhanced scans with ferumoxytol-enhanced scans. Results This study included 18 participants (mean age, 42 years ± 15.2 [SD]; 10 men). Ferumoxytol-enhanced scans demonstrated improved vascular suppression compared with both noncontrast scans (both raters, P < .001) and gadolinium-enhanced scans (both P = .04). For rater 2, ferumoxytol-enhanced acquisitions demonstrated improved conspicuity of several nerve segments relative to the noncontrast scan, including segments of the suprascapular (P = .01), axillary (P = .02), and long thoracic nerves (P = .004). The distribution of scores for these nerve segments for rater 1 also favored ferumoxytol-enhanced versus noncontrast scans, but the differences were not statistically significant (all P ≥ .06). There was no evidence of a difference in nerve conspicuity between ferumoxytol-enhanced and gadolinium-enhanced scans (P ≥ .17 for all nerve segments) and also no evidence of discrepancies in abnormal nerve findings between the acquisitions (all P ≥ .48). Conclusion Ferumoxytol improved vascular suppression compared with noncontrast and gadolinium-enhanced 3D short-tau inversion-recovery fast spin-echo sequences in brachial plexus MRN, enhancing the conspicuity of several nerve branches versus noncontrast scans, with similar detection of abnormal nerve findings. © RSNA, 2026 Supplemental material is available for this article.

Humans↗

PubMed2026

Targeted Nrf2 activation improves vascular endothelial function with aging and prevents vascular dysfunction following disuse in younger and older adults.

Aging and physical inactivity/disuse contribute to cardiovascular disease, which is attributable, in part, to vascular endothelial dysfunction associated with impaired nuclear-factor erythroid 2-related factor 2 (Nrf2) signaling. However, the ability to augment Nrf2 activation and its effects on age- and disuse-related vascular dysfunction in humans remains limited. In a double-blind, randomized, placebo-controlled study design 20 younger adults (8M/12F, age 27 ± 7 y) and 24 older adults (12M/12F, age 67 ± 8 y) were randomized to receive either placebo or PB125 (200 mg/day, Nrf2 activator) across three visits: baseline, 2 weeks of supplementation, and following either 5 days of bed rest (old) or 2 weeks of limb immobilization (young). Brachial and popliteal artery flow-mediated dilation (FMD), passive leg movement-induced (PLM) leg blood flow (LBF) and vascular conductance (LVC) and serum antioxidant status (superoxide dismutase, SOD) were assessed at each timepoint. Compared to placebo, 2 weeks of PB125 increased brachial (PB125: 2.8 ± 1.5 to 3.8 ± 1.3%, p < 0.0001) and popliteal FMD (PB125: 1.5 ± 1.5 to 2.3 ± 1.4%, p = 0.033) in older, but not younger adults (both, p > 0.27). During bed rest, PB125 preserved brachial (3.8 ± 1.3 to 3.6 ± 1.4%, p = 0.543) and popliteal FMD (2.3 ± 1.4 to 2.7 ± 1.4%, p = 0.269), LVC (1.1 ± 0.8 to 1.1 ± 1.5 AUC, p = 0.530) and circulating SOD concentrations (28.3 ± 7.2 to 28.6 ± 8.6 U/mL, p = 0.888) in older adults compared to placebo (all, p < 0.05). Following limb immobilization, PB125 preserved popliteal FMD (4.4 ± 2.8 to 3.4 ± 1.8%, p = 0.302) in younger adults compared to placebo (p < 0.05). These findings demonstrate targeted Nrf2 activation with PB125 improves age-related vascular endothelial dysfunction while preserving vascular function and antioxidant capacity following periods of disuse.

Humans↗

PubMed2026

Low-Dose Perineural Dexamethasone Enhances Analgesia After Pediatric Hand Surgery Without Elevating Systemic Stress Markers: A Randomized Controlled Trial.

BACKGROUND: Supraclavicular brachial plexus block is a widely used technique for upper limb surgery in children. Although perineural dexamethasone has demonstrated efficacy in prolonging analgesia in adults, data on its optimal dosing and systemic safety in pediatric patients are limited. This study aimed to evaluate whether low-dose perineural dexamethasone can prolong postoperative analgesia without increasing systemic stress markers in young children undergoing hand or wrist surgery. METHODS: In this triple-blinded, randomized controlled trial (ClinicalTrials.gov Identifier: NCT06086392), 90 children aged 3 months to 6 years undergoing elective upper extremity surgery were assigned to receive supraclavicular brachial plexus block with 0.2% ropivacaine combined with either normal saline (control), dexamethasone 0.05 mg/kg, or dexamethasone 0.1 mg/kg. The primary outcome was time from arrival in the postanesthesia care unit to first administration of rescue opioid analgesia. Secondary outcomes included total opioid consumption, postoperative pain intensity using the FLACC scale, blood glucose levels, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and time to motor recovery. RESULTS: Both dexamethasone groups demonstrated significantly prolonged time to first opioid use compared with the control group (mean±SD: 19.4±2.2 h in the 0.1 mg/kg group, 16.0±1.9 h in the 0.05 mg/kg group, and 8.5±1.3 h in controls; P <0.0001). Total opioid consumption was significantly reduced in the dexamethasone groups. Postoperative pain scores were lower in both intervention groups, especially during the first 12 hours. No significant differences were found among groups in blood glucose, inflammatory markers, or incidence of nerve deficits. Motor recovery was delayed in the dexamethasone groups but did not interfere with early mobilization. CONCLUSIONS: Low-dose perineural dexamethasone (0.05 to 0.1 mg/kg) safely and effectively prolongs postoperative analgesia and reduces opioid needs in children undergoing upper limb surgery, without causing systemic metabolic or inflammatory disturbances. The 0.05 mg/kg dose may offer a more favorable balance between analgesic efficacy and motor recovery time. LEVEL OF EVIDENCE: Level I-randomized controlled trial.

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

The Association Between NT-Pro BNP, Nephropathy and Endothelial Dysfunction in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-Pro BNP) is an established biomarker of heart failure and has been recommended for cardiovascular risk stratification in type 2 diabetes mellitus (T2DM). However, its relationship with diabetic nephropathy and endothelial dysfunction across varying stages of kidney impairment remains unclear. This study examined the associations of NT-Pro BNP, renal impairment, albuminuria and endothelial dysfunction in patients with T2DM without overt heart failure. METHODS: A comparative cross-sectional study was conducted among 192 adults with T2DM. Participants were stratified by KDIGO eGFR groups (≥ 90, 60-89, 30-59 mL/min/1.73m2). NT-Pro BNP was considered abnormal at a cut-off of ≥ 125 pg/mL. Albuminuria was categorized using the urinary albumin-to-creatinine ratio (uACR). Endothelial function was assessed by brachial artery flow-mediated dilatation (FMD). Logistic regression analysis was performed to identify independent factors of elevated NT-Pro BNP, with p-values < 0.05 considered statistically significant. RESULTS: NT-Pro BNP levels were significantly higher in the lower eGFR groups compared with normal eGFR (204.3 vs. 96.8 vs. 62.2 pg/mL, p < 0001). A weak but significant positive correlation was observed between NT-Pro BNP and uACR (r = 0.31, p < 0.001). However, no significant association was found between NT-Pro BNP and FMD (p = 0.388). Following multivariable adjustments, older age (adjusted OR 1.14, 95% CI: 1.06-1.23, p < 0.001), higher systolic blood pressure (adjusted OR 1.05, 95% CI: 1.02-1.08, p = 0.010), lower eGFR (adjusted OR 0.97, 95% CI: 0.95-0.99, p = 0.003) and beta-blocker use (adjusted OR 4.65, 95% CI: 1.61-13.45, p < 0.001) were independently associated with elevated NT-Pro BNP. CONCLUSION: In patients with T2DM without overt heart failure, elevated NT-Pro BNP showed a statistically significant association with lower eGFR and higher albuminuria. Moderate to severe albuminuria becomes an independent factor for elevated NT-Pro BNP after adjustment excluding eGFR. The lack of association with endothelial dysfunction suggests that NT-Pro BNP may reflect different pathophysiological pathways. NT-Pro BNP may serve as a useful biomarker for early cardiovascular risk stratification and identification of individuals at risk of pre-heart failure in diabetic kidney disease.

NT‐Pro BNP↗

PubMed2026

Safety and efficacy of distal versus conventional radial artery cannulation for invasive blood pressure monitoring: a systematic review and meta-analysis.

To compare the safety and effectiveness of distal radial artery (DRA) versus conventional radial artery (CRA) catheterization for invasive arterial blood pressure monitoring. This meta-analysis followed PRISMA guidelines. Randomized controlled trials published up to December 30, 2025 were systematically searched in PubMed, Embase, Web of Science, the Cochrane Library, CINAHL, CNKI, Wanfang, VIP, and SinoMed. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Meta-analyses were conducted using Review Manager 5.4 and Stata 18.0, and evidence quality was evaluated with the GRADE system. 12 randomized controlled trials (RCTs) involving 1,790 participants were included. For the primary outcomes, compared with CRA, DRA was associated with lower incidences of haematoma (RR = 0.42, 95% CI: 0.24-0.73), catheter blockage (RR = 0.33, 95% CI: 0.14-0.81), and bleeding (RR = 0.25, 95% CI: 0.11-0.59), but a longer catheter insertion time (MD = 26.89, 95% CI: 5.28-48.50). For the secondary outcomes, DRA was associated with a shorter haemostasis time and reduced waveform instability, with no significant differences in first-attempt success rate or pain scores. Subgroup analysis showed a higher first-attempt success rate in patients aged ≤ 65 years (RR = 1.14, 95% CI: 1.02-1.28). DRA catheterization for invasive arterial blood pressure monitoring appears to be associated with fewer complications and more stable arterial waveform acquisition than CRA catheterization, despite a longer insertion time. DRA may represent a feasible alternative in surgical and intensive care settings; however, further high-quality studies are needed to confirm its long-term safety and generalizability.

Humans↗

PubMed2026

Safety and Stability of a Combined C2 Screw Placement Strategy With Vertebral Artery Mobilization.

BACKGROUND: Although C2 pedicle screws are considered the gold standard for atlantoaxial fixation, the optimal fixation strategy for patients with high-riding vertebral arteries (HRVA) or narrow C2 pedicles (NC2P) remains controversial because of the increased risk of vertebral artery injury and the limitations of alternative fixation techniques. OBJECTIVE: To evaluate the safety, stability, and clinical efficacy of an individualized C2 screw fixation strategy incorporating vertebral artery mobilization for complex upper cervical anatomy. METHODS: A retrospective study was conducted in 312 patients who underwent C2 fixation between 2017 and 2025. Patients were categorized according to fusion method, screw laterality, and VA transposition requirement. Bone fusion rates and screw accuracy (Gertzbein-Robbins grading) were compared across groups using χ2, Fisher's exact, and multivariate logistic regression analyses to control confounders. RESULTS: All procedures were successfully completed without permanent neurovascular injury. At 6 months, the fusion rate with an atlantoaxial fusion cage was significantly higher than with interlaminar bone grafting (92.3% vs. 51.0%, p < 0.001). Unilateral C2 pedicle screw fixation combined with a contralateral alternative screw achieved comparable stability to bilateral fixation (p > 0.05). Screw placement accuracy was 100% clinically acceptable in normal anatomy and 60% in cases requiring VA mobilization, with no VA injury or blood flow compromise. CONCLUSION: The proposed multi-strategy C2 screw placement protocol-integrating fusion cage support and VA mobilization-achieves superior fusion, reliable fixation, and high safety, even in anatomically challenging conditions. This approach provides a reproducible and versatile solution for C2 instrumentation in complex craniovertebral junction surgery.

Humans↗

PubMed2026

Occlusion site and outcomes in intra-arterial tenecteplase after successful endovascular therapy: a secondary analysis of the ANGEL-TNK trial.

BACKGROUND: Endovascular thrombectomy achieves macroreperfusion in large vessel occlusion (LVO) stroke, but only one-quarter of patients had excellent functional outcome. Adjunct intra-arterial (IA) tenecteplase could further improve the treatment effect, yet its efficacy across internal carotid artery (ICA) versus middle cerebral artery (MCA) M1/M2 occlusion remains unclear. OBJECTIVE: To evaluate whether IA tenecteplase improves 90-day functional outcomes in LVO patients stratified by occlusion site (ICA, MCA M1, MCA M2). METHODS: Prespecified secondary analysis of the ANGEL-TNK trial (multicenter, randomized, open-label, blinded endpoint) in 19 Chinese stroke centers. Participants were enrolled who had anterior circulation LVO, 4.5-24 hours from symptom onset, and CT angiography (CTA)/magnetic resonance angiography (MRA)-proven ICA, M1, or M2 occlusion. INTERVENTION: Randomization (1:1) to IA tenecteplase (0.125 mg/kg) or standard medical management after expanded Thrombolysis in Cerebral Infarction (eTICI) 2b50-3 reperfusion. MAIN OUTCOME MEASURE: The primary outcome was the rate of 90-day modified Rankin Scale (mRS) 0-1. RESULTS: There were 256 patients in the trial, including 71 (27.7%) ICA, 122 (47.6%) MCA M1, and 62 (24.2%) MCA M2. ICA occlusion patients treated with IA tenecteplase had higher rates of 90-day mRS 0-1 (39.4% vs 13.2%; relative risk (RR) 2.99; 95% CI 1.51 to 5.96; p=0.002) and mRS 0-3 (54.5% vs 42.1%; RR 1.30; p=0.048) versus controls, with a significant shift toward better mRS scores (median 3 (IQR 1-4) vs 4 (2-6); odds ratio (OR) 2.26; p<0.001). Post hoc analysis showed higher eTICI progression in ICA patients (51.5%) versus MCA M1 (37.9%) and M2 (25.7%). IA tenecteplase had a lower any intracranial hemorrhage within 48 hours in ICA patients (15.2% vs 39.5%; RR 0.38; p<0.001) compared with standard medical management. No significant benefits were observed in the MCA M1/M2 subgroups, and interaction effects were significant between ICA and MCA segments for functional outcomes and safety. CONCLUSIONS AND RELEVANCE: IA tenecteplase had a better functional outcome and lower hemorrhage risk in ICA occlusion compared with standard medical management but not in MCA M1/M2. Occlusion site is a critical determinant of response to IA tenecteplase. A pooled analysis of IA tenecteplase stratified by occlusion site strata is warranted.

Humans↗

PubMed2024

Proteomic serum profiles before and after lipoprotein apheresis in patients with peripheral artery disease with ulceration.

INTRODUCTION: The efficacy of lipoprotein apheresis (LA) in peripheral arterial disease (PAD) has been primarily attributed to its anti-atherosclerotic effects through the adsorption of lipoproteins. However, the other potential effects of LA remain unknown. We evaluated changes in serum profiles before and after LA using a comprehensive analysis to explore the underlying mechanism. METHODS: Ten patients with leg ulcers were included from the LETS-PAD study, in which patients with lipoprotein-controlled PAD underwent LA. Serum samples collected at baseline and 1 month after LA were analyzed for proteomic changes. RESULTS: Six patients exhibited ulcer epithelialization and skin perfusion pressure improvement. Proteomic analysis identified 2033 proteins. Fifty-five proteins showed significant differences. B-cell lymphoma protein-2 associated X (BAX) and C-X-C motif chemokine 10 (CXCL10) were downregulated. CONCLUSION: Serum BAX and CXCL10 levels significantly decreased after LA, which may be involved in the ulcer epithelialization mechanism of LA, which potentially acts through angiogenesis promotion.

Humans↗

PubMed2026

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 < 0.001), although substantial heterogeneity was present (I 2 = 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 ≥ 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↗

PubMed2026

Mechanistic Insights Into the Association Between Gut Microbiota Diversity and Atherosclerosis, Acute Coronary Syndrome, and Peripheral Arterial Disease Progression.

BACKGROUND: The gut microbiome has emerged as a potential contributor to cardiovascular diseases (CVDs), including atherosclerosis, acute coronary syndrome (ACS), and peripheral arterial disease (PAD). While observational studies link dysbiosis to CVD, causal relationships remain uncertain. METHODS: This narrative review synthesizes evidence from human observational studies, clinical interventions, and experimental models to distinguish association from mechanistic plausibility and clinical causality. Literature was searched through July 2026 in PubMed/MEDLINE, Web of Science, and Scopus. RESULTS: Microbial metabolites-including trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids, and lipopolysaccharide (LPS)-modulate endothelial function, immune cell programming, platelet activity, and plaque stability through receptor-mediated signaling and epigenetic regulation. SCFAs demonstrate potentially protective effects via GPCR and HDAC pathways, while TMAO is associated with atherothrombotic risk. However, much mechanistic evidence derives from preclinical studies. Heterogeneity from diet, geography, host characteristics, renal function, and medications substantially influences microbiota-CVD associations. CONCLUSION: The gut-vascular connection is biologically plausible, but definitive clinical causality remains unproven. Microbiome-directed therapies (dietary modulation, pre/pro/synbiotics, targeted metabolite inhibition) are investigational. Prospective, standardized, adequately powered human studies with clinically meaningful outcomes are essential before routine cardiovascular application.

Gastrointestinal Microbiome↗

PubMed2026

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

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

Humans↗

PubMed2026

Adaptive proteomic remodeling and eNOS upregulation in luminal endothelium and perivascular adipose tissue of patent saphenous vein grafts after CABG.

OBJECTIVE: Long-term patency of saphenous vein grafts (SVGs) remains a significant challenge in coronary artery bypass grafting (CABG). The biological factors underlying successful human grafts are poorly understood. We aimed to characterize the structural and molecular features associated with successful graft function. METHODS: Patent and occluded SVG and internal thoracic artery (ITA) grafts were obtained from explanted hearts of CABG patients undergoing heart transplantation for end-stage heart failure not attributable to graft failure, along with freshly harvested ITA and SVG controls. Samples underwent histomorphological analysis, immunohistochemistry (IHC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics. RESULTS: Patent ITA (ITA-P) showed minimal intimal hyperplasia with medial reinforcement, whereas patent SVGs (SVG-P) had organized, α-smooth muscle actin (αSMA)-positive myofibroblast-rich neointima. Endothelial nitric oxide synthase (eNOS) was markedly upregulated in patent grafts at two sites-the luminal endothelium and adventitial microvessels within perivascular adipose tissue (PVAT)-and lost at both sites in occluded SVG (SVG-O). Adventitial CD31-positive microvessels were significantly increased in patent grafts. Proteomically, ITA-P and SVG-P shared a largely common adaptive proteome enriched in translation, RNA processing, and extracellular matrix (ECM) organization, with shared upstream activation of NR4A3, EGFR, and STAT1, and conduit-specific signatures (IGF-1/RUNX2 in ITA-P; RETN/SRC/PTGES in SVG-P). PTGES was strongly expressed in the adventitia of SVG-P. CONCLUSIONS: Patent arterial and venous bypass grafts exhibited a shared adaptive phenotype characterized by dual-site upregulation of eNOS in both the luminal endothelium and the perivascular microvessels/PVAT. In SVG-P, PTGES was co-upregulated alongside eNOS, indicating a mechanistic link between the proteomic and IHC findings. These findings highlight the perivascular compartment as a site of adaptive, eNOS-associated changes in patent vein grafts.

Humans↗

PubMed2026

Transpulmonary proteomic gradient analysis in women with pulmonary arterial hypertension associated with systemic sclerosis.

This study investigated proteomic alterations in the pulmonary circulation of patients with pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) by analyzing the transpulmonary protein gradient and comparing the proteomic profiles with systemic sclerosis (SSc) without PAH. Twenty women were included (10 PAH-SSc, 64.6 ± 10.8 years; 10 SSc, 62.8 ± 11.5 years). The transpulmonary gradient was defined as the difference in biomarker concentrations between wedge-position and pulmonary artery blood samples. Peptides were analysed using liquid chromatography-mass spectrometry, and differentially abundant proteins were identified with Proteome Discoverer. Protein-protein interaction networks were generated with STRING and visualized in Cytoscape. A total of 270 proteins were detected, with no significant transpulmonary gradient alterations. However, patients with PAH-SSc showed distinct proteomic profiles compared to SSc. Multivariate analysis identified 48 differentially abundant proteins in pulmonary artery plasma, with 15 overrepresented and 33 downregulated in PAH-SSc. Among these, the downregulation of transforming growth factor-beta-induced protein ig-h3 (TGFβI/ig-h3) points to a potential involvement of the TGF-β-related extracellular matrix remodelling pathway in PAH-SSc. However, further validation in larger and independent cohorts is required before its relevance as a biomarker or therapeutic target can be established. In conclusion, while no transpulmonary proteomic gradient was observed, the proteomic profiles of PAH-SSc and SSc were different. The profile in PAH-SSc was characterized by differences in immune response, lipid metabolism, and hemostatic proteins. SIGNIFICANCE: This study offers the first proteomic characterization of the transpulmonary gradient in PAH-SSc and SSc. Although no differences in the gradient were found, the pulmonary artery plasma proteome of PAH-SSc patients showed a distinct pattern compared to SSc. Several proteins associated with immune function, haemostasis, and cellular processes were altered, which may indicate specific pathophysiological features of PAH-SSc or suggest how lung dysfunction develops in SSc. Targeting dysregulated proteins like TGFβI/ig-h3 or addressing immune-coagulation imbalances may support future research studies. Overall, these findings refine the molecular profile of PAH-SSc and provide a basis for future large-scale studies aimed at clarifying disease mechanisms and identifying clinically relevant molecular signatures.

Humans↗

PubMed2026

Risk factors for leg wound infection after conventional and no-touch vein harvesting: insights from a multicentre randomised trial.

ClinicalTrials.gov: ID NCT03501303.

Humans↗

PubMed2026

Pulmonary artery catheters or central venous catheters for cardiac surgery: the PUMA Pilot randomised clinical trial.

INTRODUCTION: Pulmonary artery catheters are used widely in cardiac surgery despite observed associations with worse outcomes and guidelines that recommend against their routine use. No adequately powered randomised trials are available. METHODS: The PUMA Pilot was a multicentre, randomised, parallel assignment, open-label, pilot and feasibility trial conducted at three tertiary cardiac surgery centres. Eligible patients were adults undergoing coronary artery bypass grafting, aortic valve replacement or surgery on the aortic root or ascending aorta with or without aortic valve replacement, with a predicted surgical mortality of < 2%. Patients were allocated randomly to receive a pulmonary artery catheter or a central venous catheter inserted immediately before surgery. The primary feasibility outcome was protocol compliance, defined as receiving the assigned intervention without crossover. Secondary feasibility outcomes were eligibility rate; recruitment proportion and rate; data completeness; and rate of clinician refusal. RESULTS: We screened 480 patients and 206 (43%) were eligible; 150/203 (74%) approached provided informed consent. Three of 206 (1%) eligible patients were not included due to clinician refusal. Of 149 patients who were randomised, 76 were assigned to the pulmonary artery catheter group and 73 to the central venous catheter group. For the primary feasibility outcome, 147 patients (99%) received the allocated intervention. Data were complete for 144 (97%) patients. Median (IQR [range]) days alive and at home at 30 days was 23.7 (21.9-24.7 [7.0-26.0]) in the pulmonary artery catheter group and 22.9 (20.8-23.9 [8.6-25.8]) in the central venous catheter group. Acute kidney injury occurred in 26/76 (34%) patients in the pulmonary artery catheter group and 14/73 (19%) in the central venous catheter group. DISCUSSION: A randomised trial of pulmonary artery catheters compared with central venous catheters in low-risk cardiac surgery is feasible. Such a trial would address significant practice variability and inform international guidelines.

Humans↗