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Effects of detomidine alone or combined with butorphanol on oxygenation status, F-shunt and sedation level in healthy sheep.

This study evaluated the effects of detomidine alone or combined with butorphanol on arterial oxygenation, gas exchange indices, estimated shunt fraction (F-shunt) and sedation level in healthy sheep. A prospective, randomized, blinded, experimental study was conducted on twenty-seven Merino sheep allocated to three groups (9 sheep/group): 5 μg/kg detomidine +200 μg/kg butorphanol (Deto5But), 10 μg/kg detomidine + 200 μg/kg butorphanol (Deto10But), or 10 μg/kg detomidine (Deto10) administered intravenously. Following arterial and venous catheter placement, arterial blood samples were collected to determine oxygenation status and F-shunt at baseline (fraction of inspired oxygen, FiO₂: 21%), 5 min after sedation (FiO₂: 21%), and at 5 and 30 min after propofol induction (FiO₂: 100%). Sedation was evaluated by a blinded observer at 5, 10, and 15 min after drug administration using two numerical scales. Sedation produced a significant deterioration in oxygenation parameters, gas exchange indices, and F-shunt (15.36%: 95% CI 10.07-20.65; p = 0.001) compared with baseline, without significant differences between treatment groups. However, five minutes after induction of anaesthesia, the Deto5But group presented better oxygenation, gas exchange efficency, and F-shunt values compared with Deto10But (10.30%: 95% CI 0.86-19.76; p = 0.029) and Deto10 (13.93%: 95% CI 2.94-24.92%; p = 0.008). Sedation scores did not differ significantly between treatment groups or across time points. Combination of detomidine at 5 μg/kg with 200 μg/kg of butorphanol provided adequate sedation and was associated with a milder impact on oxygenation and F-shunt at 5 min post-induction.

Animals

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 (&#x2265;&#x2009;7&#x2009;weeks) to nonexercise control; nonathletic adults &#x2265;&#x2009;18&#x2009;years with BMI&#x2009;&#x2265;&#x2009;25&#x2009;kg/m2. PARTICIPANTS: 454 participants across 12 RCTs (mean age 58.93&#x2009;&#xb1;&#x2009;12.87&#x2009;years; mean BMI 31.2&#x2009;&#xb1;&#x2009;3.5&#x2009;kg/m2; ~50% female). RESULTS: RT significantly reduced diastolic blood pressure (MD&#x2009;=&#x2009;-1.53&#x2009;mmHg; 95% CI: -2.16 to -0.91; p&#x2009;<&#x2009;0.01), LDL-C (MD&#x2009;=&#x2009;-0.25&#x2009;mmol/L; 95% CI: -0.41 to -0.08; p&#x2009;<&#x2009;0.01), and triglycerides (MD&#x2009;=&#x2009;-0.17&#x2009;mmol/L; 95% CI: -0.30 to -0.04; p&#x2009;=&#x2009;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

Transabdominal lumbar approach (TALA) versus retroperitoneal approach for robot-assisted renal surgery: a prospective randomised controlled trial.

PURPOSE: Common robotic nephrectomy approaches access the kidney via transperitoneal (TP) or retroperitoneal (RP) routes, each with distinct trade-offs. We developed the transabdominal lumbar approach (TALA), combining advantages of both accesses with improved visualisation and strategic trocar placement, and compared it with conventional RP in a prospective randomised controlled trial using technique-oriented intraoperative endpoints. METHODS: In this single-centre, prospective, open-label RCT, 40 patients were randomised to TALA (n&#x2009;=&#x2009;18) or conventional RP (n&#x2009;=&#x2009;22). Eligible patients were &#x2265;&#x2009;18 years with a renal tumour or non-functional kidney requiring robot-assisted total or partial nephrectomy. Exclusions included prior surgery on the affected kidney, renal vein tumour thrombus, and pregnancy. Both groups were followed for 30 days. The primary endpoint was time from first skin incision to renal artery identification. RESULTS: TALA achieved a median time saving of 16&#xa0;min compared to conventional RP (38 vs. 54&#xa0;min, p&#x2009;=&#x2009;0.001). Perioperative safety was comparable between groups, with three patients (7.5%) experiencing Clavien-Dindo grade III-IV complications. CONCLUSIONS: TALA met its primary endpoint with a significantly shorter time to renal artery identification than conventional RP access, and improving perceived surgical exposure and instrument handling.

Humans

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 (&#x2265;&#x2009;90, 60-89, 30-59&#x2009;mL/min/1.73m2). NT-Pro BNP was considered abnormal at a cut-off of &#x2265;&#x2009;125&#x2009;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 <&#x2009;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&#x2009;pg/mL, p&#x2009;<&#x2009;0001). A weak but significant positive correlation was observed between NT-Pro BNP and uACR (r&#x2009;=&#x2009;0.31, p&#x2009;<&#x2009;0.001). However, no significant association was found between NT-Pro BNP and FMD (p&#x2009;=&#x2009;0.388). Following multivariable adjustments, older age (adjusted OR 1.14, 95% CI: 1.06-1.23, p&#x2009;<&#x2009;0.001), higher systolic blood pressure (adjusted OR 1.05, 95% CI: 1.02-1.08, p&#x2009;=&#x2009;0.010), lower eGFR (adjusted OR 0.97, 95% CI: 0.95-0.99, p&#x2009;=&#x2009;0.003) and beta-blocker use (adjusted OR 4.65, 95% CI: 1.61-13.45, p <&#x2009;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&#x2010;Pro BNP

Association Between 24-Hour Blood Pressure and Rates of Retinal Nerve Fiber Layer Progression in Glaucoma: The Vascular Imaging in Glaucoma Study.

PURPOSE: Low systemic blood pressure (BP) has been implicated as a risk factor for glaucoma progression. The purpose of this study was to investigate the association between 24-hour BP and rates of retinal nerve fiber layer (RNFL) loss in eyes with primary open-angle glaucoma. DESIGN: Prospective cohort study. PARTICIPANTS: Seventy-nine eyes from 42 subjects with glaucoma (mean age, 68.5 &#xb1; 7.6 years) enrolled in the Vascular Imaging in Glaucoma Study at the Bascom Palmer Eye Institute. METHODS: Participants underwent 24-hour ambulatory BP monitoring at baseline. Follow-up evaluations were conducted at 4-month intervals and included ophthalmic examination, BP measurement, and peripapillary RNFL thickness measurement with spectral-domain optical coherence tomography. The association between BP and RNFL loss over time was assessed using linear mixed-effects models adjusted for age, sex, race, baseline RNFL thickness, central corneal thickness, and intraocular pressure. MAIN OUTCOME MEASURES: The effect of baseline 24-hour mean arterial pressure (MAP), systolic BP (SBP), and diastolic BP (DBP) on the rate of average RNFL loss over time. RESULTS: Eyes underwent an average of 13 &#xb1; 3 optical coherence tomography exams over 43 &#xb1; 10 months of follow-up. The mean rate of RNFL loss was -0.34 &#xb1; 0.64 &#xb5;m/y (median: -0.32; interquartile range: -0.66 to -0.04 &#xb5;m/y). After adjusting for confounding factors, every 10 mm Hg lower in 24-hour minimum MAP, SBP, and DBP was associated with -0.542 &#xb5;m/y (P < .001), -0.360 &#xb5;m/y (P = .003), and -0.458 &#xb5;m/y (P = .008) faster RNFL loss, respectively. Eyes in the lowest quartile of average 24-hour MAP (81-90 mm Hg) and minimum 24-hour DBP (35-47 mm Hg) experienced significantly faster progression compared to those in the highest quartile, with differences of -0.68 &#xb5;m/y (P = .017) and -0.63 &#xb5;m/y (P = .030), respectively. CONCLUSIONS: Lower systemic BP, especially minimum MAP, SBP, and DBP measured by 24-hour ambulatory BP monitoring, is associated with faster rates of RNFL loss in primary open-angle glaucoma eyes. 24-hour BP monitoring may help predict glaucoma patients at greater risk of progression.

Humans

IgA Vasculitis with necrotizing arteritis: a multicenter retrospective study from the French Vasculitis Study Group and systematic review of the literature.

IgA vasculitis (IgAV) primarily affects small vessels, but rare cases with necrotizing arteritis (NA) raise questions about overlap with polyarteritis nodosa (PAN). To characterize IgAV with necrotizing arteritis (IgAV-NA) and compare its phenotype with classical IgAV and PAN. We performed a multicenter retrospective study combined with a systematic literature review (1990-2025). Patients fulfilled EULAR/PRINTO/PRES IgAV criteria, had pathological or imaging evidence of NA in small or medium arteries, and were ANCA-negative. Thirty patients were included (7 from databases, 23 from the literature). NA was confirmed by biopsy (n&#x2009;=&#x2009;16) or vascular imaging (n&#x2009;=&#x2009;14). Clinical features, treatments, remission, and mortality were compared with 257 adult IgAV and 196 PAN patients. Median age was 54.5 years. IgAV-NA was characterized by severe manifestations, including gastrointestinal bleeding, perforation, surgical abdomen, neuropathy, pancreatitis, and livedo. Compared with classical IgAV, IgAV-NA showed significantly higher rates of multi-organ involvement and mortality. Compared with PAN, IgAV-NA shared vascular complications but had less fever and neuropathy. Despite arterial involvement, patients did not fulfil PAN criteria. IgAV-NA represents a rare, severe IgAV phenotype with life-threatening complications rather than an IgAV-PAN overlap. Severe or atypical IgAV presentations should prompt vascular imaging and intensified immunosuppression.

Humans

The Efficacy of Erector Spinae Plane Block Versus Subcostal Transversus Abdominis Plane Block in Laparoscopic Nephrectomy: A Randomized Clinical Trial.

OBJECTIVES: This study compared the efficacy and safety of erector spinae plane block (ESPB) versus subcostal transversus abdominis plane (TAP) block in reducing postoperative pain among patients undergoing laparoscopic nephrectomy. METHODS: This randomized clinical trial enrolled 70 adult patients, ASA physical status I or II, who underwent total (radical) laparoscopic nephrectomy under general anesthesia. Patients were randomly assigned to 2 groups. Group ESPB received an ultrasound-guided ESPB at the T7 transverse process level, while group TAP received an ultrasound-guided subcostal TAP block. The primary outcome was the total amount of morphine consumed at 6 and 24 hours postoperatively. Secondary outcomes included the incidence of patients requiring opioid analgesia, time to rescue analgesia, visual analog scale of pain intensity, time to postoperative ambulation, intraoperative and postoperative hemodynamics, arterial partial pressure of oxygen to fraction of inspired oxygen (PaO 2 /FiO 2 or P /F) ratio, and incidence of complications. RESULTS: Compared with the TAP group, the ESPB group exhibited significantly lower median morphine consumption at 24 hours ( P =0.032), prolonged time to first analgesic rescue ( P =0.049), and lower incidence of rescue morphine requirement (OR=0.23; 95% CI=0.06-0.94; P =0.031), with lower visual analog scale pain scores at 12, 18, and 24 hours postoperatively ( P <0.001). The mean arterial blood pressure and heart rates were comparable between groups. No significant adverse effects from either approach. DISCUSSION: In laparoscopic nephrectomy, ultrasound-guided ESPB may safely and effectively be used to improve pain management and reduce pain intensity, with stable hemodynamics and a comparable risk of postoperative complications to the ultrasound-guided subcostal TAP block.

Humans

Treatment of OSA using mandibular advancement versus CPAP in improving cardiovascular health.

BACKGROUND: Obstructive sleep apnea is a significant risk factor for hypertension. We assessed the relative effectiveness of mandibular advancement device (MAD) versus continuous positive airway pressure (CPAP) in reducing 24 h ambulatory blood pressure (BP) and other health-related outcomes over 12 months. METHODS: In a randomized, non-inferiority trial, 321 participants with hypertension and increased cardiovascular risk were recruited for polysomnography. Of these, 220 with moderate-to-severe OSA (apnea-hypopnea index (AHI) &#x2265;15 events/hour) were randomized to MAD or CPAP (1:1). We report the final outcomes at the 12-month follow-up. RESULTS: A total of 180 participants (MAD: 89; CPAP: 91) completed the 12-month follow-up. Median usage for MAD and CPAP was 5.5 and 4.9 h per night, respectively. Compared to baseline, the 24 h mean arterial BP at 12 months decreased by 2.3 mmHg (P = 0.200) in the MAD group and by 1.0 mmHg (P = 0.999) in the CPAP group. The difference between-groups was -0.6 mmHg (95% confidence interval: -2.53 to 1.39, non-inferiority P < 0.019). The MAD group demonstrated a larger reduction in asleep BP compared to the CPAP group. The prevalence of excessive daytime sleepiness in the MAD group decreased from 30.3% at baseline to 10.1% at 12-month follow-up (P = 0.001), and from 38.5% to 7.7% in the CPAP group (P < 0.001). The between-group difference was 10.6% (P = 0.097). No significant within-group or between-group differences were observed in the prevalence of arrhythmias and plasma levels of cardiac biomarkers. CONCLUSION: At 12-month, MAD is non-inferior to CPAP for reducing 24 h mean arterial BP in participants with hypertension and increased cardiovascular risk. TRIAL REGISTRATION: NCT04119999.

Humans

Human iPSC-EV-loaded nanofiber stent coatings accelerate vascular repair by enhancing EGFR/HIF-1&#x3b1; signaling and suppressing ROCK1-mediated remodeling.

Arterial disease management is shifting from antiproliferative drug-eluting stents toward approaches that restore endothelial function and modulate smooth muscle cell (SMC) behavior. Stem cell-derived extracellular vesicles (EVs) carry miRNAs that promote endothelial proliferation and migration while restraining aberrant SMC growth and inflammation. Here, human induced pluripotent stem cell (iPSC)-derived EVs were collected by ultracentrifugation and incorporated into 50:50 poly (lactic-co-glycolic acid) (PLGA 503) core-shell nanofibrous membranes, which were fabricated as stent coatings for sustained release to overcome rapid clearance and poor tissue retention. EVs derived from three independent iPSC lines all enhanced tube formation in human umbilical vein endothelial cells (HUVECs) under hypoxic and serum-starved conditions and revealed a trend toward reduced platelet-derived growth factor-BB (PDGF-BB)-induced smooth muscle cell (SMC) migration. The fabricated core-shell nanofibers enabled sustained EV release, maintaining therapeutic efficacy for 28 days. Small RNA sequencing (NGS) analysis demonstrated that EVs from these independent iPSC lines shared miR-148a-3p and members of the miR-92 family, which collectively accounted for more than 75% of the reads within the 25 top-expressed miRNA set. In vitro, iPSC-EVs enhanced HUVEC proliferation and survival signaling by downregulating the negative regulators ERRFI1 and VHL, which are specific targets of miR-148a-3p and the miR-92 family, thereby activating the EGFR and HIF-1&#x3b1; axes and driving downstream ERK1/2 and VEGF expression under hypoxic and serum starvation stress conditions. Concurrently, iPSC-EVs prevented PDGF-BB-induced SMC phenotypic switching by downregulating ROCK1, a target of miR-148a-3p, thereby inhibiting downstream AKT and ERK signaling and preserving contractile markers while suppressing the synthetic phenotype. In vivo, the iPSC-EV-functionalized scaffolds significantly accelerated re-endothelialization and inhibited neointimal hyperplasia, evidenced by the upregulation of angiogenic factors (VEGF, CD31) and the concurrent suppression of pathological remodeling markers (&#x3b1;-SMA, MMPs) and inflammatory cytokines (IL-6, TGF-&#x3b2;1). Therefore, iPSC-EVs enriched with specific miRNAs and delivered via PLGA 503 core-shell nanofibers promote endothelial repair while suppressing SMC overgrowth, providing a promising strategy for vascular healing.

Core-shell nanofibers

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&#x202f;&#xb1;&#x202f;7&#x202f;y) and 24 older adults (12M/12F, age 67&#x202f;&#xb1;&#x202f;8&#x202f;y) were randomized to receive either placebo or PB125 (200&#x202f;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&#x202f;&#xb1;&#x202f;1.5 to 3.8&#x202f;&#xb1;&#x202f;1.3%, p&#x202f;<&#x202f;0.0001) and popliteal FMD (PB125: 1.5&#x202f;&#xb1;&#x202f;1.5 to 2.3&#x202f;&#xb1;&#x202f;1.4%, p&#x202f;=&#x202f;0.033) in older, but not younger adults (both, p&#x202f;>&#x202f;0.27). During bed rest, PB125 preserved brachial (3.8&#x202f;&#xb1;&#x202f;1.3 to 3.6&#x202f;&#xb1;&#x202f;1.4%, p&#x202f;=&#x202f;0.543) and popliteal FMD (2.3&#x202f;&#xb1;&#x202f;1.4 to 2.7&#x202f;&#xb1;&#x202f;1.4%, p&#x202f;=&#x202f;0.269), LVC (1.1&#x202f;&#xb1;&#x202f;0.8 to 1.1&#x202f;&#xb1;&#x202f;1.5 AUC, p&#x202f;=&#x202f;0.530) and circulating SOD concentrations (28.3&#x202f;&#xb1;&#x202f;7.2 to 28.6&#x202f;&#xb1;&#x202f;8.6 U/mL, p&#x202f;=&#x202f;0.888) in older adults compared to placebo (all, p&#x202f;<&#x202f;0.05). Following limb immobilization, PB125 preserved popliteal FMD (4.4&#x202f;&#xb1;&#x202f;2.8 to 3.4&#x202f;&#xb1;&#x202f;1.8%, p&#x202f;=&#x202f;0.302) in younger adults compared to placebo (p&#x202f;<&#x202f;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

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&#xa0;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&#x2009;min (T1), and during OLV at 15&#x2009;min (T2) and 45&#x2009;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&#x2009;<&#x2009;0.05), with no significant differences between Groups N and C (all p&#x2009;>&#x2009;0.05). Compared to T1, Groups N and C showed significantly lower PaO2 and higher Qs/Qt at T2 and T3 (all p&#x2009;<&#x2009;0.05), with no significant differences in PaO2 and Qs/Qt at T3 compared with T2 (all p&#x2009;>&#x2009;0.05). Group P patients had lower PaO2 and higher Qs/Qt at T2 and T3 compared to T1 (all p&#x2009;<&#x2009;0.05), but at T3, PaO2 increased and Qs/Qt decreased compared to T2 (all p&#x2009;<&#x2009;0.05). Lung tissue levels of endothelin and COX-2 were significantly elevated in group P compared to groups N and C (all p&#x2009;<&#x2009;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

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&#x2009;=&#x2009;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

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&#x2009;>&#x2009;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&#x2009;000/&#x3bc;L. HITT rate was 190/352 (53.9%; 8% had arterial thrombosis). Mean follow-up was 7.6&#x2009;months. TR was 20/352 (Pooled proportion&#x2009;=&#x2009;0.064 [95% CI&#x2009;=&#x2009;0.042-0.092]) (30% of them were new thromboses without initial thrombosis), and BR was 9/352 (Pooled proportion&#x2009;=&#x2009;0.039 [95% CI&#x2009;=&#x2009;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

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

Dosimetric Parameters of the Heart and Its Substructures in Predicting Cardiac Events or Survival in Patients With Lung Cancer After Radiation Therapy: A Systematic Review and Meta-analysis.

The predictive value of radiation dose to the whole heart (WH) and cardiac substructures (CS) for cardiac events (CEs) and survival in patients with lung cancer remains uncertain. The goal of this study was to conduct a systematic review and meta-analysis to provide an evidence-based estimate of the relationship between these associations. A systematic meta-analysis was performed following PRISMA guidelines. Risk of bias was assessed using the JBI Critical Appraisal Checklist for Case Series. Outcomes were classified into major adverse cardiac events (MACE), arrhythmias, pericardial effusion, and survival. Depending on heterogeneity, random- or fixed-effects models were applied to calculate pooled hazard ratios (HRs) for univariable and multivariable analyses. A total of 80 studies, including 21,645 patients, were analyzed. Of these, 25 studies reported CEs, and 69 reported survival outcomes. Among 91 WH and 215 CS parameters evaluated, several showed significant associations. Key findings from our meta-analysis include: (1) left anterior descending (LAD) V15 was significantly associated with MACE. The mean heart dose (MHD), as well as ventricle and LAD doses, were significantly associated with ischemic events. (2) Multiple CS parameters were associated with different arrhythmia subtypes. (3) MHD, heart V5/V35/V55 and pericardial doses were significantly associated with pericardial effusion. (4) MHD was significantly associated with survival; CS parameters also showed predictive value, and especially, heart base dose being the most significant. (5) We also identified several thresholds with potential predictive values, such as LAD V15 <10% for MACE, left pulmonary vein (LPV) V55 <2%, and right pulmonary vein (RPV) V10 <54% for atrial fibrillation (AF), right atrium (RA) V60 <0.03 cc for non-AF supraventricular tachyarrhythmia, and left main artery (LMA) V10 &#x2265;1 cc for bradyarrhythmia. This study identified 130 WH and CS dosimetric parameters associated with CEs and 131 with survival outcomes. These findings enhance our understanding of radiation-induced heart injury mechanisms and provide guidance for potential protective and intervention strategies.

Humans

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 (&#xb1;2&#x2009;hours). Participants completed 3&#x2009;&#xd7;&#x2009;25 maximal, unilateral, isokinetic (60&#xb0;&#xb7;s-1), concentric-eccentric leg extensions on both legs. Each leg was randomly assigned to receive pBFR (80% arterial occlusion pressure) or sham (20&#x2009;mmHg) at 0, 24, 48, 72, and 96&#x2009;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&#x2009;hours (mean difference [meandiff] = 4.9 au; p&#x2009;<&#x2009;0.001) and recovered by 96&#x2009;hours (p&#x2009;=&#x2009;0.482), with no differences between conditions (p&#x2009;=&#x2009;0.450). ROM (meandiff&#x2009;=&#x2009;-3.1&#xb0;; p&#x2009;=&#x2009;0.040), PPT (meandiff&#x2009;=&#x2009;-1.63 kgf; p&#x2009;<&#x2009;0.001), CPT (meandiff&#x2009;=&#x2009;-27.7&#x2009;Nm; p&#x2009;<&#x2009;0.001), and MVIC torque (meandiff&#x2009;=&#x2009;-30.8&#x2009;Nm; p&#x2009;<&#x2009;0.001) decreased at 24&#x2009;hours, with recovery occurring between 48-96&#x2009;hours. Condition-specific differences were observed for ROM (meandiff&#x2009;=&#x2009;2.5&#xb0;; p&#x2009;<&#x2009;0.001), PPT (meandiff&#x2009;=&#x2009;0.49 kgf; p&#x2009;=&#x2009;0.005), CPT (meandiff&#x2009;=&#x2009;6.2&#x2009;Nm; p&#x2009;=&#x2009;0.020), and MVIC torque (meandiff&#x2009;=&#x2009;7.1&#x2009;Nm; p&#x2009;=&#x2009;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

Comparison of a Modified Regimen of Prophylactic Phenylephrine Boluses Versus Variable Rate Infusion During Elective Cesarean Delivery Under Spinal Anesthesia: A Noninferiority Randomized Double-Blind Study.

BACKGROUND: Prophylactic phenylephrine boluses have been found to be as effective as variable rate infusions during elective cesarean delivery but require a higher number of physician interventions to maintain blood pressure near baseline values. Therefore, there is a need to find a feasible regimen of bolus administration that is equally efficacious to the infusion regimen while at the same time requires a comparable number of physician interventions and is thus non-inferior to the infusion regimen. METHODS: Healthy pregnant women with term, uncomplicated, singleton pregnancies undergoing elective cesarean delivery under spinal anesthesia were randomly divided into two groups. The Bolus group received a phenylephrine bolus 100 &#x3bc;g immediately after spinal anesthesia and then at every systolic blood pressure value <90% of the baseline. The infusion group received a prophylactic variable-rate infusion of phenylephrine beginning at 50 &#x3bc;g/min and titrated to maintain systolic blood pressure at 90-99% of baseline. The primary outcome was the number of physician interventions needed to maintain the target systolic blood pressure; the secondary outcomes included phenylephrine requirements, incidence of hypotension/hypertension/bradycardia, umbilical arterial and venous blood gas analysis, Apgar scores, and maternal complications. The primary outcome was analyzed in terms of non-inferiority using a non-inferiority margin of two interventions. RESULTS: Eighty patients were included in the study. The median (interquartile range [IQR]) number of physician interventions was 6 (5-8) in the infusion group and 3 (2-4) in the bolus group (P < .001). The difference of medians (95% confidence interval [CI]) between the two groups was -3 (-4 to -2). Phenylephrine requirements were higher in the infusion group (630 [426-765] &#x3bc;g) compared to the bolus group (300 [200-400] &#x3bc;g; P < .001). Blood pressure was higher at certain time points in the infusion group, but overall accuracy of blood pressure control was not different between the groups. Incidence of hypotension, hypertension, and bradycardia, neonatal outcomes, and maternal complications did not differ between the groups. CONCLUSIONS: The modified regimen of prophylactic boluses is non-inferior to variable rate prophylactic phenylephrine infusion in terms of physician interventions needed to maintain systolic blood pressure within the target range and maternal and neonatal outcomes.

Humans

Physician-Modified Fenestrated Stent-Grafts Planned Using Three-Dimensional Techniques for Complex Aortic Pathology: A Systematic Review and Meta-Analysis.

BACKGROUND: Complex aortic pathology involving the visceral arteries remains a significant therapeutic challenge. Open repair is associated with considerable perioperative risk, particularly in patients with multiple comorbidities, while standard endovascular aneurysm repair (EVAR) is often not feasible because of inadequate proximal sealing zones. Fenestrated and branched endovascular repair (F/BEVAR) represents an established treatment strategy; however, the use of custom-made devices is limited by manufacturing time and availability. Physician-modified stent grafts (PMSGs) have therefore emerged as a pragmatic alternative. Three-dimensional planning techniques have been increasingly used to facilitate accurate graft modification. The aim of this systematic review and meta-analysis was to evaluate the effectiveness and safety of PMSG procedures planned with three-dimensional techniques. Technical success, target vessel patency, early mortality, endoleak occurrence, and reintervention rates were analyzed. METHODS: A systematic search was conducted in the PubMed/MEDLINE and Embase databases. Studies describing the use of physician-modified fenestrated stent grafts planned with three-dimensional tools were included. Meta-analyses were performed using a random-effects model with restricted maximum likelihood estimation. A logit transformation was used for the analysis of proportions. RESULTS: The analysis included five studies involving 172 patients. The estimated weighted mean follow-up duration was 14.9 months. The overall technical success rate was 92.9% (95% confidence interval [CI]: 84.5-96.9%), with low-to-moderate heterogeneity. Target vessel patency was 96.9% (95% CI: 93.6-98.5%). Early mortality was 5.5% (95% CI: 2.1-13.3%). The incidence of endoleaks was 13.3% (95% CI: 5.8-27.4%), with significant heterogeneity among studies. Reinterventions were reported in 6.6% of patients (95% CI: 2.3-17.5%). CONCLUSION: The results indicate that PMSG procedures planned with three-dimensional techniques are associated with a high rate of technical success and preserved patency of target vessels in patients with complex aortic pathology. The observed variability in endoleak and reintervention rates likely reflects differences in anatomical complexity and patient selection among studies. Further prospective studies are needed to confirm long-term outcomes.

Humans