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Six weeks of isometric resistance training led to evidence of corticospinal but not reticulospinal adaptation in previously untrained adult males.

The latest hypothesis regarding the source of enhanced neural activation from resistance training is the reticulospinal rather than the corticospinal tract, based on invasive animal and emerging human data. The present study employed a six-week isometric resistance training intervention in a randomized controlled design to address this knowledge gap. Thirty-nine healthy, untrained males (age ~23 y, sustained contraction group n = 13, explosive contraction group n = 9, control group n = 17) underwent neuromuscular and electrophysiological testing and completed all study requirements. Maximal isometric torque (MVC) and rate of torque development (RTD) were measured during a familiarization session as well as before and after the six-week period. Transcranial magnetic stimulation was used to assess motor-evoked potential (MEP) area and silent period duration while subjects contracted to 10% of MVC. Loud sound (120&#xa0;dB) was used to modulate MEP area and reaction time to visual stimuli during the StartReact test. Only the intervention groups demonstrated significant improvements in MVC (27%) and RTD (60%) (both P < 0.01), along with reduced MEP area (-&#xa0;21%) and silent period duration (-&#xa0;23%) (both P < 0.01). The sustained contraction group showed reduced modulation of reaction time and increased MEP suppression due to loud sound. Short-term resistance training seemed to reduce cortical inhibition and corticospinal excitability in both training groups. The study showed conflicting changes in measures purported to evaluate reticulospinal functioning. It is recommended to examine different forms of resistance training and longer training exposure in future.

Humans

GIP contributes to postprandial regulation of splanchnic blood supply in humans with type 2 diabetes: a randomised, single-blinded, placebo-controlled, crossover study.

AIMS/HYPOTHESIS: In healthy lean humans, endogenous glucose-dependent insulinotropic polypeptide (GIP) contributes significantly to the postprandial increase in arteria mesenterica superior blood flow. The vascular biology related to activation of the GIP receptor is markedly impaired in individuals with type 2 diabetes and is sometimes absent. In this population, we investigated the role of endogenous GIP on postprandial splanchnic blood flow by using the GIP receptor antagonist, GIP(3-30)NH2. The primary outcome of this study was the changes in blood flow in arteria mesenterica superior during oral glucose with or without GIP receptor antagonist infusion. METHODS: Ten participants with type 2 diabetes (age 20-80 years, BMI 20-35 kg/m2, and HbA1c >48 mmol/mol and <75 mmol/mol) were investigated in a randomised, placebo-controlled, crossover study. On four separate occasions, participants received the following treatment: oral glucose + i.v. GIP(3-30)NH2; oral glucose + i.v. saline (154 mmol/l NaCl); oral water + i.v. GIP(3-30)NH2; oral water + i.v. saline. Participants were randomly assigned to intervention groups using (random.org). Participants were unaware of allocation, while investigators were aware. No additional allocation concealment procedures were used. During all four interventions, splanchnic blood flow was measured using phase-contrast MRI in the arteria mesenterica superior, truncus coeliacus and vena portae during oral glucose (75 g) or water ingestion. The study was conducted at Rigshospitalet, Copenhagen. Liver volume and oxygenation, as well as gallbladder volume, were assessed. Blood samples were collected and analysed for insulin, C-peptide, GIP, glucagon and glucose. RESULTS: Oral glucose alone increased mean blood flow in arteria mesenterica superior by 57% (95% CI 26, 88) and this was 15% (95% CI -2, 32) lower during concomitant GIP receptor antagonist infusion, p=0.012. Infusion of GIP receptor antagonist during oral glucose treatment did also result in lower insulin secretion, C-peptide and C-peptide/glucose ratio compared with saline infusion, whereas glucagon levels and plasma glucose were unaffected. Oral water did not affect any outcomes. CONCLUSIONS/INTERPRETATION: Endogenous GIP contributes to postprandially increased splanchnic blood flow in people with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT06426823 FUNDING: This work was supported by the Novo Nordisk Foundation.

Humans

The Impact of Oncological Treatments on Return to Work, Work Ability, and Sickness Absence in Breast Cancer Survivors: A Systematic Review.

PURPOSE: Returning to work and maintaining an adequate ability to work serve as key indicators of quality of life, psychological well-being and psychosocial adjustment. Therefore, this study aims to analyze the impact of breast cancer treatments on return to work (RTW), work ability (WA), and sick leave (SL) among breast cancer survivors. METHODS: A systematic review was conducted according to the PRISMA guidelines. The sample consisted of 26 studies published between 2016 and 2025, including prospective multicenter cohorts and national registries from fifteen countries across four continents, with more than 25,000 participants. A methodological quality assessment and a narrative synthesis were performed to synthesize the results. RESULTS: Chemotherapy is the most consistent predictor of prolonged SL, delayed RTW, and significantly reduced WA. Radical surgery and axillary lymph node dissection (ALND) are associated with a significantly delayed RTW due to physical sequelae. While outcomes showed strong relationship with clinical factors, certain psychosocial variables such as depression, anxiety, and low self-efficacy seemed to act as important secondary factors that can further complicate the process. CONCLUSION: The findings suggest that more invasive or aggressive treatments (chemotherapy, ALND, and radical surgery) were associated with poorer outcomes on RTW, WA, and SL. Furthermore, the clinical recovery associated with treatment completion did not necessarily equate to a functional recovery in WA that facilitated a successful RTW. Thus, it is necessary to explore in depth the impact of cancer treatments on WA, alongside psychosocial variables, to design multidisciplinary interventions that enable sustainable occupational reintegration. REGISTRATION: PROSPERO 2026 (CRD420261322638).

Breast cancer survivors

Macroprolactinemia as a diagnostic pitfall in hyperprolactinemia: a systematic review and quantitative synthesis.

CONTEXT: Macroprolactinemia is a well-recognized cause of hyperprolactinemia and an important diagnostic pitfall in endocrine practice. However, interpretation of published quantitative prolactin data remains sparse as studies vary in confirmation method, assay platform, polyethylene glycol (PEG) recovery cutoff, and reporting of prolactin measurement. EVIDENCE ACQUISITION: PubMed, Embase, Scopus, Web of Science, the Cochrane Library, and Google Scholar were systematically searched. Eligible studies reported macroprolactinemia-specific quantitative prolactin data in patients with confirmed macroprolactinemia defined by PEG precipitation, gel filtration chromatography (GFC), or both. Two reviewers independently performed study selection, data extraction, and quality assessment. Findings were summarized using study-level descriptive synthesis. The review was prospectively registered in PROSPERO and conducted in accordance with PRISMA 2020 guidelines. EVIDENCE SYNTHESIS: Forty-five studies encompassing 2853 macroprolactinemia cases from 21 413 screened patients with hyperprolactinemia across 22 countries were included. Among 33 studies eligible for primary quantitative analysis, the median study-level central total prolactin attributed to macroprolactinemia was 61.4 ng/mL ([IQR] 42.0-80.0; range 28.1-137.6), and the median study-level post-PEG monomeric prolactin was 11.7 ng/mL (IQR 8.3-13.2; range 4.0-17.0)). The median study-level maximum total prolactin was 264.5 ng/mL (IQR 97.0-425.5; range 81.8-663.0); extreme elevations were attributable to coexisting prolactinomas. CONCLUSION: In confirmed macroprolactinemia, total prolactin elevation is typically moderate, and post-PEG monomeric prolactin is usually within or near the normal range. The post-PEG monomeric prolactin value, rather than percent recovery alone, is the most informative parameter for distinguishing isolated macroprolactinemia from coexisting true hyperprolactinemia. These quantitative benchmarks may help clinicians to avoid unnecessary investigation or treatment.

Humans

Effect of different liposomal bupivacaine concentrations in ultrasound-guided superior trunk block on postoperative analgesia and mobility: a randomized double-blind controlled trial protocol for shoulder arthroscopy.

BACKGROUND: Shoulder arthroscopy frequently causes severe postoperative pain that may impede recovery. Liposomal bupivacaine provides prolonged analgesia, and ultrasound-guided superior trunk block (STB) offers comparable analgesia to interscalene block with a lower risk of hemidiaphragmatic paralysis. However, the optimal concentration of liposomal bupivacaine for STB remains unknown. METHODS: This randomized, double-blind, controlled trial will enrol 282 adult patients scheduled for elective arthroscopic rotator cuff repair. Patients will be randomly allocated (1:1:1) to receive ultrasound-guided STB with liposomal bupivacaine 66&#x2009;mg (Group A), 44&#x2009;mg (Group B) or 33&#x2009;mg (Group C), each diluted to 10&#x2009;mL. The co-primary outcomes are (1) rest pain Numeric Rating Scale (NRS) score at 48&#x2009;h post-surgery and (2) cumulative oral morphine milligram equivalents (MME) consumption within 0-48&#x2009;h after surgery. Secondary outcomes include rest pain NRS scores at 6, 24 and 72&#x2009;h; motor function assessed by Muscle Balance Scale, Bromage score and American Shoulder and Elbow Surgeons (ASES) score at 6, 24, 48 and 72&#x2009;h; and Quality of Recovery-15 (QoR-15) score at 24 and 48&#x2009;h. DISCUSSION: This study will provide evidence on the optimal concentration of liposomal bupivacaine for STB in arthroscopic shoulder surgery, aiming to achieve effective and prolonged analgesia without compromising shoulder mobility.

Humans

The impact of drug decriminalization policy on mental health- and substance-related service utilization among people who use drugs with prior care in British Columbia.

BACKGROUND: In 2023, British Columbia implemented a pilot illicit drug decriminalization policy aimed at addressing the high burden of illicit drug toxicity deaths, creating a need to examine its health system impacts. Although research on decriminalization has largely focused only on substance-related outcomes, broader mental health service utilization, including substance-related mental health care, among people who use drugs remains an insufficiently studied domain that this study seeks to address. METHODS: In this single interrupted time series analysis of prevalent people who use drugs with prior care (PWUD-PC) in BC, we examined the proportion of people who accessed mental health and substance-related (MH-SR) services and their average monthly MH-SR visits one year before and after the decriminalization policy, stratified by physician visits, emergency department visits, and hospitalizations. RESULTS: The population prevalence of PWUD-PC remained stable at 1.8% before and after decriminalization, and no statistically significant changes were observed in the proportion of PWUD-PC accessing MH-SR physician services and hospitalizations. The early period following decriminalization did not produce large shifts in overall MH-SR service use among PWUD-PC. Some movements in trends were seen in emergency department use, while several other outcomes, particularly in hospitalizations and physician visits, continued pre-existing trends. CONCLUSION: Overall, we found stable patterns of MH-SR service engagement across the intervention period and small shifts in the post-intervention trends of average MH-SR service visits. These findings suggest that the early period following decriminalization did not lead to abrupt or large shifts in MH-SR service use among PWUD-PC.

Humans

Application of SPI-guided analgesia in laparoscopic gynecologic surgery: a randomized controlled trial evaluating the remifentanil-sparing effect and predictive value of time-weighted SPI.

This study aimed to achieve two primary objectives: (1) to evaluate the opioid-sparing effect of Surgical Pleth Index (SPI)-directed analgesia during surgery via a randomized controlled trial (RCT), and (2) to propose and preliminarily assess a novel dynamic metric, Threshold-based Time-Weighted SPI (Tb-TW-SPI), which integrates stimulus intensity and duration, for its predictive efficacy regarding postoperative moderate-to-severe pain. Employing an RCT combined with exploratory analysis, 61 patients undergoing elective laparoscopic gynecologic surgery were randomized into an SPI-directed analgesia group or a conventional analgesia group. The primary outcome was total intraoperative remifentanil consumption. Postoperatively, an exploratory analysis of the control group data evaluated the correlation between Tb-TW-SPI and Numeric Rating Scale (NRS) pain scores in the post-anesthesia care unit (PACU), calculating its predictive value for moderate-to-severe pain (NRS&#x2009;&#x2265;&#x2009;4). Results: The SPI-directed group required significantly less intraoperative remifentanil than the conventional group [median (IQR): 5.84(5.02,6.62)vs. 6.96(5.81,8.19)&#xb5;g/kg/h; P&#x2009;=&#x2009;0.016]. Postoperative pain scores did not differ significantly between groups (P&#x2009;>&#x2009;0.05). Exploratory analysis of the conventional analgesia group revealed that Tb-TW-SPI values were significantly higher in patients with moderate-to-severe postoperative pain (NRS&#x2009;&#x2265;&#x2009;4) compared to those without (P&#x2009;=&#x2009;0.0417).The area under the ROC curve for Tb-TW-SPI predicting this pain was 0.74 (95% CI: 0.52-0.96), with 67% sensitivity and 76% specificity at an optimal cutoff of 1210. This RCT suggests that SPI-directed analgesia can safely and moderately reduce intraoperative remifentanil consumption. Furthermore, the proposed Tb-TW-SPI metric, in this exploratory analysis, suggests potential for predicting postoperative pain, though this finding requires validation in larger cohorts with higher-frequency SPI sampling, offering a new direction for SPI interpretation. Large-scale, multicenter trials are warranted to validate the predictive utility of Tb-TW-SPI. Clinical Trial Registration, China Clinical Trial Registry: ChiCTR2400088444.

Humans

Risk factors for loss of skeletal muscle mass in patients with chronic kidney disease on a low-protein diet.

OBJECTIVES: A low-protein diet (LPD) is recommended for patients with chronic kidney disease (CKD) to prevent a further decline in renal function. However, its impact on muscle mass in these patients remains unclear. This study investigated the risk factors for loss of muscle mass in patients with CKD on an LPD. METHODS: Eighty-four patients with predialysis CKD (59 men, mean age 61.9 &#xb1; 11.5 y) who participated in a multicenter randomized controlled trial initiated in 2014 were retrospectively reviewed. We collected data on baseline blood and urine tests, body composition, and dietary records at the start and end of the observation period. We evaluated muscle mass using the skeletal muscle index (SMI) and analyzed risk factors for a decrease in SMI during the 24-wk observation period, using logistic regression analysis. Variables with an association (P < 0.1) in univariate analysis, as well as age, sex, use of low-protein rice, and changes in protein intake, were subjected to multivariate analysis. RESULTS: SMI decreased in 50 patients (59.5%) during the observation period. Multivariate analysis identified significant associations of the SMI with serum albumin at baseline (odds ratio 0.11, 95% confidence interval 0.02-0.52, P = 0.004) and changes in energy intake while on the LPD (odds ratio 3.39, 95% confidence interval 1.00-11.43, P = 0.049). CONCLUSIONS: Risk factors for reduced SMI in patients with CKD on an LPD were malnutrition when initiating the LPD and reduced energy intake during its implementation. Clinicians should optimize nutritional status before initiation of an LPD and ensure adequate energy intake throughout treatment.

Humans

Acceptability of alcohol-based hand rub during neonatal care in rural Ugandan households: a qualitative study nested within the BabyGel trial.

BACKGROUND: Poor access to water, sanitation and hygiene exacerbates the spread of infections among newborns. The BabyGel cluster randomised trial assessed the effectiveness of a community-level alcohol-based hand rub with a training component in reducing infection or death rates among newborns in Uganda. OBJECTIVE: Nested in the BabyGel trial, this study investigated the acceptability of the BabyGel intervention among mothers and household members in Eastern Uganda, using the Theoretical Framework of Acceptability. METHODS: In 2022, we conducted individual semistructured interviews with mothers, and group interviews with mothers and other household members, all recruited from intervention-arm clusters. Thematic analysis combined inductive and deductive coding, structured by the framework's seven constructs: affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness and self-efficacy. RESULTS: Twenty mothers and 14&#xa0;household members participated in 10 individual and 10 small group interviews. Participants found the intervention generally acceptable, appreciating its convenience and perceived protection against infection. Many described hand hygiene changes that persisted beyond the intervention period. However, concerns related to its harmful effects, spiritual beliefs and social tensions with visitors occasionally influenced its use. CONCLUSION: Alcohol-based hand rub combined with a training component was generally well accepted, driven by perceived health and practical benefits, although concerns related to safety, belief systems and social dynamics remained. Because data collection coincided with the COVID-19 pandemic, a period of heightened hygiene awareness, the acceptability observed could differ in nonpandemic periods. Culturally adapted education, community engagement and reinforcement of correct use may enhance acceptability and sustainability in similar settings.

Humans

Comparative efficacy of percutaneous vertebroplasty combined with minimally invasive pedicle screw fixation versus percutaneous vertebroplasty alone in the treatment of elderly osteoporotic vertebral compression fractures.

The study aimed to assess the comparative efficacy of percutaneous vertebroplasty (PVP) combined with minimally invasive pedicle screw fixation versus PVP alone in elderly patients with osteoporotic vertebral compression fractures (OVCF). Ninety-four elderly patients with OVCF were randomly classified into the control (47 patients) and combined (47 patients) groups. The control group received PVP, while the combined group received PVP combined with minimally invasive pedicle screw fixation. Perioperative indicators such as intraoperative blood lose, operative time, and hospitalization time were recorded. Pain was assessed using the VAS before and at baseline and 1, 3, and 7 days postoperatively. At 1 and 3 days postoperatively, Serum CRP levels, WBC, and neutrophil counts were measured postoperatively. Radiographic outcomes (vertebral height ratio and Cobb angle), ADL scores, JOA scores, and ODI were evaluated preoperatively and at 3 months post-operation. Postoperative complications were documented. Baseline characteristics were comparable. The combined group showed superior pain relief, vertebral height restoration, Cobb angle correction, functional recovery, and reduced inflammatory markers (CRP, WBC, neutrophils) postoperatively (all P&#x2009;<&#x2009;0.05). Blood loss and hospital stay were shorter in the combined group, though operative time was longer (P&#x2009;<&#x2009;0.05). Complication rates did not differ significantly (P&#x2009;>&#x2009;0.05). PVP combined with minimally invasive pedicle screw fixation yields better outcomes in elderly OVCF patients by enhancing pain control, vertebral height, and functional recovery without increasing perioperative risk.

Humans

Insulin, Semaglutide and Dapagliflozin in Adults With Type 1 Diabetes: Design and Methods of Triple Therapy for Type 1 Diabetes (TTT1)-An International Phase 3 Clinical Trial.

AIMS: Attaining target glycaemia can be a challenge in Type 1 Diabetes (T1D) due to insulin-induced weight gain. Adjunct therapy with modern glucose-lowering agents developed for type 2 diabetes (T2D) has great potential but may be insufficiently efficacious and carries risks of hypoglycaemia and ketosis. We designed the first Phase 3 clinical trial to assess the efficacy and safety of adding a Glucagon-Like Peptide 1 receptor agonist (GLP-1RA) and a Sodium-Glucose Co-transporter (SGLT2) Inhibitor to insulin therapy in overweight and obese adults with T1D and glycaemia above target (HbA1c 7.5%-11.0% inclusive) (NCT03899402). MATERIALS AND METHODS: In Period 1, participants are randomized 2:1 (open label) for 26&#x2009;weeks to semaglutide and insulin (uptitrated to 1.0&#x2009;mg weekly) or standard insulin therapy. In Period 2, those randomized to semaglutide and insulin in Period 1 are further randomized (double-blind) for 26&#x2009;weeks to dapagliflozin (10&#x2009;mg daily) or placebo, in addition to semaglutide. The primary objective is to compare change in HbA1c on 'triple therapy' (dapagliflozin, semaglutide and insulin) with 'dual therapy' (placebo, semaglutide and insulin). Secondary objectives include comparisons of triple therapy with standard insulin therapy and dual therapy (semaglutide and insulin) with standard insulin therapy. Safety outcomes include hypoglycaemia and ketosis. A sample size recalculation during the trial based on analysis of masked data revised the original recruitment target from 114 to 82 participants. CONCLUSION: The TTT1 trial will provide clinically useful information on combination adjunct therapy in the treatment of T1D.

Humans

Impact of Albuminuria-Lowering Treatments on Cardiovascular Predictive Ceramides in Diabetes: Post Hoc Analysis of the ROTATE Trials.

AIM: Cardiovascular disease (CVD) is the leading cause of mortality in individuals with diabetes. Diabetic kidney disease, closely related to CVD risk, is prevalent in up to 40% of this population. Emerging evidence suggests ceramide lipids as accurate biomarkers for CVD. We assessed the effect of four albuminuria-lowering drugs on CVD-related ceramides in diabetes by post hoc analysis of the ROTATE trials. MATERIALS AND METHODS: Twenty six adults with type 1 (T1D) as well as 37 with type 2 diabetes (T2D) with a urine albumin-creatinine ratio (UACR) of 30-500&#x2009;mg/g participated in a 4-week 4-time randomized crossover study with periods of telmisartan, empagliflozin, linagliptin and baricitinib treatment, each separated by a 4-week washout period. Blood samples were collected at the beginning and end of each period and ceramide lipids (Cer16, Cer18, Cer20, Cer22, Cer24 and Cer24:1) were measured. The effect of each treatment was evaluated using linear mixed-effect models. RESULTS: At baseline, individuals with T2D had greater levels of Cer22 and Cer24 compared to the individuals with T1D. Among the treatments, linagliptin was the only drug that demonstrated a reduction of Cer22, Cer24 and Cer24:1 from baseline by 22.6% (95% CI: -33.58; -9.79, p&#x2009;=&#x2009;0.001), 25.7% (95% CI: -38.94; -9.69, p&#x2009;=&#x2009;0.003) and 19.6% (95% CI: -31.34; -5.95, p&#x2009;=&#x2009;0.007), respectively. No changes in the ceramides were observed for the other drugs. CONCLUSION: Our exploratory findings suggest that certain albuminuria-lowering drugs may affect ceramide levels as a secondary effect. However, further mechanistic investigations are needed.

Humans

Effects of adjunctive bifrontal tDCS on depressive symptoms and cognitive performance in major depressive disorder: A randomized, double-blind, sham-controlled crossover pilot study.

BACKGROUND: Evidence for antidepressant effects of transcranial direct current stimulation (tDCS) in major depressive disorder (MDD) is heterogeneous, and cognitive effects remain uncertain. We compared depressive symptoms and DSST performance during active and sham bifrontal tDCS in medicated outpatients with MDD and baseline HAMD-17 &#x2265; 15. METHODS: In this randomized, double-blind, sham-controlled crossover pilot trial, adults with MDD and inadequate response to an adequate antidepressant trial were assigned to active&#x2192;sham or sham&#x2192;active tDCS sequences while continuing antidepressants. Each period comprised 10 sessions over 2 weeks. Active stimulation was delivered at 2 mA for 20 min (anode F3, cathode F4); sham used the same montage with brief ramping only. No washout interval was used. No washout interval was used. The primary outcome was HAMD-17; secondary outcomes were DSST and CGI ratings. RESULTS: Of 38 randomized participants, 32 completed both periods and were analyzed per protocol. HAMD-17 scores were lower during active than sham stimulation (mean difference -3.63, 95% CI -5.86 to -1.40; p = 0.002), but the condition-by-sequence interaction was significant (p = 0.026). No condition effect was observed for DSST (p = 0.261) or CGI-Severity (p = 1.000); CGI-Improvement was strongly sequence-dependent (p < 0.001). In an exploratory first-period analysis, adjusted T1 HAMD-17 scores were lower in the active-first group (adjusted difference -4.90, 95% CI -7.92 to -1.87; p = 0.003). Adverse effects were mild and transient. CONCLUSIONS: Active tDCS was associated with lower HAMD-17 scores, but the pooled contrast was order-dependent and cannot be interpreted as a definitive treatment effect. No DSST benefit was observed.

Humans

Development and validation of a liquid chromatography-tandem mass spectrometry method for the quantification of twenty-five steroids in equine serum.

Steroids are potential biomarkers for monitoring equine pregnancy. However, immunoassays currently used for their quantification suffer from cross-reactivity and limited specificity, thus requiring more accurate methods. This study reports the development and validation of a robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of 25 steroids covering the main biosynthetic pathways of progestogens, corticosteroids, androgens, and estrogens. Steroids were extracted by protein precipitation followed by evaporation, derivatization, and reconstitution before LC-MS/MS analysis. A surrogate matrix was used for calibration and validation to avoid endogenous interference. Validation was performed according to and partly adapted from Clinical and Laboratory Standards Institute guidelines (CLSI), including linearity, trueness, precision, limits of detection and quantification, measurement uncertainty, recovery, matrix effects, carryover, selectivity, and stability. Calibration curves were fitted using the best-performing weighted linear or quadratic regression model, yielding excellent linearity (R2&#xa0;>&#xa0;0.990), trueness between -9.0% and 2.3%, and intra- and inter-day precision <6.3%. Lower limits of quantification ranged from 2.07 to 2250&#xa0;pg/mL depending on physiological analytes concentration. Extraction recovery averaged 24.3-114.9%, matrix effects were acceptable, and accuracy ranged from 94.4% to 98.9%. No carryover or interferences were detected. Measurement uncertainty remained <15%. This study presents the first LC-MS/MS method partially validated per CLSI criteria for the quantification of 24 steroids in equine serum. The method offers a sensitive and specific alternative to immunoassays and provides a robust tool for equine steroid profiling with potential applications in pregnancy monitoring, placentitis diagnosis, and fetal sex determination.

Animals

Oil and gas well development and coccidioidomycosis risk in Kern County, CA, USA: a case-crossover study.

BACKGROUND: Coccidioidomycosis is an emerging fungal disease caused by inhaling Coccidioides spp spores. As spores reside in soil, activities that disturb soil and generate dust can aerosolise and transport the pathogen. The oil and gas industry has been extensively developed in some regions that are endemic for Coccidioides spp and has been associated with dust emissions. Although several adverse health outcomes have previously been associated with oil and gas development, its impact on coccidioidomycosis risk has not been investigated. We aimed to estimate the association between exposure to oil and gas well development (ie, wells in preproduction) and risk of coccidioidomycosis among residents living near new wells. METHODS: In this case-crossover study, we obtained information on reported coccidioidomycosis cases and oil and gas well development between 2007 and 2022 in Kern County, CA, USA. We then compared exposure to preproduction wells within 5 km of each individual's place of residence during both hazard (ie, the 49-139 days before case onset) and control periods using conditional logistic regression. FINDINGS: During the study period, 658&#x2009;108&#x2009;(72&#xb7;4%) of 909&#x2009;282 of Kern County residents lived within 5 km of at least one preproduction well, and 116&#x2009;020&#x2009;(12&#xb7;8%) lived within 5 km of 23 or more preproduction wells within a single 90-day period. We estimated that the odds of coccidiomycosis incidence were 12&#xb7;5% (95% CI 5&#xb7;8-19&#xb7;6) higher in the 90 days following exposure to at least one preproduction well within 5 km of an individual's place of residence and that the odds of infection increased by 0&#xb7;7% (0&#xb7;4-0&#xb7;9) for each additional preproduction well developed within this distance. INTERPRETATION: These findings support a previously-unrecognised association between the development of oil and gas wells and transmission of coccidioidomycosis, potentially driven by dust generation. Given the prevalence of oil and gas development in the study region, its impact on coccidioidomycosis incidence might be large. FUNDING: National Institutes of Health, National Science Foundation.

Journal Article

Thoracic paravertebral block with different doses of liposomal bupivacaine versus ropivacaine for postoperative analgesia in single-port thoracoscopic lung surgery: a randomized clinical trial.

OBJECTIVE: To evaluate the analgesic efficacy of thoracic paravertebral block (TPVB) with different doses of liposomal bupivacaine (LB) or ropivacaine in patients undergoing single-port thoracoscopic lung surgery. METHODS: A total of 105 patients scheduled for video-assisted single-port thoracoscopic lung surgery were randomized in a 1:1:1 ratio into three groups: low-dose LB group (group LL), high-dose LB group (group HL), or ropivacaine group (group R). All received ultrasound-guided TPVB at the T5/6 level preoperatively. The primary outcome was the area under the curve (AUC) of NRS of pain at activity (AUC-aNRS) from 1 to 72&#x2009;h postoperatively. Secondary outcomes included the AUC of NRS of pain at rest (AUC-rNRS) from 1 to 72&#x2009;h postoperatively, NRS of pain at rest and at activity at 1, 6, 24, 48, and 72&#x2009;h postoperatively, and the cumulative opioid consumption at 24, 48, and 72&#x2009;h postoperatively. Additionally, postoperative recovery and adverse events were assessed. RESULTS: AUC-aNRS differed significantly among groups (p = 0.0092), with high-dose LB lower than low-dose LB (p = 0.0071), but not versus ropivacaine. No significant difference was found in AUC-rNRS (p&#x2009;>&#x2009;0.05). The group-by-time interactions for NRS of pain at rest and at activity were not significant (p&#x2009;>&#x2009;0.05). Cumulative opioid consumption at 24, 48, and 72&#x202f;h was lower in group HL versus group LL (all p < 0.017), but not versus ropivacaine. Postoperative recovery and adverse events showed no differences (p&#x2009;>&#x2009;0.05). CONCLUSION: LB combined with TPVB is not superior to ropivacaine for postoperative analgesia in single-port thoracoscopic lung resection.

Humans

Awake Craniotomy for Eloquent Region Glioblastoma Classified by Tumor Location-A Retrospective and Prospective Cohort Study.

INTRODUCTION: The efficacy of awake craniotomy (AC) with intraoperative mapping for glioblastoma (GBM) in eloquent regions remains debated. This study aims to evaluate functional and survival outcomes of GBM patients undergoing AC stratified by tumor locations. METHODS: A combined retrospective (2015-2023, n&#x2009;=&#x2009;114: 43&#x2009;AC vs. 71 standard craniotomy) and prospective cohort (2023-2025, n&#x2009;=&#x2009;28: 13&#x2009;AC vs. 15 standard craniotomy) of GBM patients with motor/language-eloquent tumors was analyzed. Tumors were classified into motor subtypes (I: precentral gyrus; II: premotor/supplementary motor; III: internal capsule posterior limb; IV: other) and language subtypes (I: Broca's/precentral; II: postcentral/supramarginal gyrus; III: Wernicke's; IV: insular; V: other). Outcomes included extent of resection (EOR), postoperative motor/language recovery, overall survival (OS), and progression-free survival (PFS). RESULTS: The retrospective cohort demonstrated that AC has advantages in functional preservation across various motor/language subtypes. However, AC was associated with significantly deteriorated survival outcomes specifically in precentral gyrus GBMs. A prospective cohort study, enrolling only precentral gyrus GBMs for validation, yielded results consistent with the retrospective findings: worsened OS and PFS (OS: HR&#x2009;=&#x2009;3.223, p&#x2009;=&#x2009;0.0450; PFS: HR&#x2009;=&#x2009;2.374, p&#x2009;=&#x2009;0.0476); reduced EOR (AC:&#xa0;74.3%&#x2009;&#xb1;&#x2009;5.3%; standard craniotomy: 86.9%&#x2009;&#xb1;&#x2009;12.3%, p&#x2009;=&#x2009;0.0470); and better motor recovery. CONCLUSIONS: Functional preservation and survival outcomes of AC in GBM exhibited subtype-specific correlations with tumor locations. AC with intraoperative mapping effectively preserves neurological function in GBM patients. However, for tumors involving the precentral gyrus, the AC approach carries greater risks than benefits and should be considered with caution. TRIAL REGISTRATION: Strategic Intervention on Preserving Motor Function During Awake Craniotomy: NCT05143788. Strategic Intervention on Preserving Language Function During Awake Craniotomy: NCT05143775.

Adult

Safety and Effectiveness of Direct Oral Anticoagulants Versus Low-Molecular-Weight Heparin for Cancer-Associated Thrombosis: A Systematic Review and Meta-analysis.

BACKGROUND: Cancer-associated thrombosis is a condition associated with high mortality rates, yet limited evidence exists regarding the safety and effectiveness of low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs), focusing on a fixed follow-up period based on clinical practice guideline recommendations. OBJECTIVE: This study aimed to compare the safety and effectiveness of DOACs versus LMWH in patients with cancer-associated thrombosis over a 6-month follow-up period. METHODS: PubMed, Embase, and Cochrane Library databases were systematically searched up to 30 June, 2025. Recurrent venous thromboembolism, major bleeding, and all-cause mortality were pooled using a random-effects meta-analysis. RESULTS: Seven randomized controlled trials and 28 cohort studies were included in our systematic review. After applying the criteria for a 6-month follow-up period, five randomized controlled trials and 16 cohort studies with 49,824 patients were analyzed in the meta-analysis. In randomized controlled trials, DOACs showed a lower incidence of venous thromboembolism recurrence (relative risk [RR] 0.66, 95% confidence interval [CI] 0.49-0.87) compared with LMWH, with a non-significant increase in major bleeding (RR 1.28, 95% CI 0.87-1.88) and no significant difference in all-cause mortality (RR 1.00, 95% CI 0.86-1.18). Cohort studies demonstrated a lower incidence of venous thromboembolism recurrence (RR 0.69, 95% CI 0.62-0.76) with DOACs, a non-significant reduction in major bleeding (RR 0.85, 95% CI 0.68-1.07), and a lower risk of all-cause mortality (RR 0.47, 95% CI 0.31-0.72). CONCLUSIONS: In patients with cancer-associated thrombosis, DOACs demonstrated a decrease in recurrent venous thromboembolism without increasing the risk of all-cause mortality. A non-significant increase in the risk of major bleeding was recorded in randomized controlled trials, but not in cohort studies. DOACs may provide greater effectiveness for cancer-associated thrombosis compared with LMWH.

Humans