Citations

Carbohydrate availability and caffeine ingestion have been shown to elicit improvements in performance independently of one another. The purpose of the study was to examine the effect of a carbohydrate + caffeine beverage on performance and perceived effort in soccer players. Forty-three collegiate women’s soccer athletes were recruited to participate during a single day of simulated match play, in which each team played once. Athletes consumed either a carbohydrate + caffeine (Experimental) beverage or a control (Control) beverage (flavored water) during half-time in a double-blind, placebo-controlled, randomized control trial design. Prior to and after each game, Ratings of Perceived Exertion (RPE) and blood glucose levels were assessed. Heart rate, training impulse (TRIMP), total distance covered, high-speed distance, and velocity were recorded. Blood glucose levels after the match simulation were positively associated with total distance (r = 0.434; p = 0.01), distance per minute (r = 0.439; p < 0.01), average velocity (r = 0.438; p = 0.01), and TRIMP (r = 0.404; p = 0.018) during the second half. There was a significant main effect for half regarding blood glucose (p < 0.001), total distance (p < 0.001), high-speed distance (p < 0.001), and TRIMP (p = 0.046). There was a significant half × condition effect for blood glucose (p = 0.05). Pairwise comparisons indicated the Experimental beverage condition resulted in a +27 mg/dL (95% CI: −3.6, 58.8) difference compared to the Control beverage following the 2nd Half. In the current study, consumption of the carbohydrate + caffeine beverage during half-time resulted in higher blood glucose levels post-game compared to placebo; however, the experimental beverage did not influence the total distance covered, average velocities, average heart rate, or TRIMP values during the second half of simulated match play.

Objective: Esophageal cancer is a leading cause of cancer-related mortality, with a 5-year survival rate of 20%. Surgical resection remains the primary treatment for early and locally advanced disease. Anastomotic leak is a major concern, which significantly increases morbidity and mortality. Impaired conduit perfusion and tissue ischemia are key risk factors. This series describes the use of ELUXEO Oxygen Saturation Endoscopic Imaging (OXEI) technology (Fujifilm Healthcare Americas Corp, Lexington, MA, USA) to assess tissue oxygen saturation during esophagectomy. Methods: OXEI was used in 6 cases to evaluate conduit perfusion during esophagectomy procedures. Real-time hemoglobin oxygen saturation imaging identified ischemic areas, with StO 2 levels ranging from 17% in poorly perfused regions to 92% in well-perfused areas. OXEI findings were congruent with indocyanine green fluorescence imaging but avoided dye-related limitations. Results: OXEI technology offered a dye-free alternative that allowed real-time assessment of tissue oxygenation, facilitating accurate perfusion quantification. Its reproducibility without dye administration and limitations of tissue saturation or washout concerns added reliability, especially during long multistage procedures. In addition, OXEI has been shown to be consistent irrespective of distances from the targeted area, providing precise tissue saturation quantification throughout critical steps of esophagectomy. These findings highlight the potential of this technology as a valuable adjunct in esophageal surgery. Conclusions: The experience with ELUXEO technology in esophagectomy is promising. It provides a reliable, dye-free method for real-time perfusion assessment, potentially reducing the incidence of anastomotic leaks, preventing dye-associated complications, and improving surgical outcomes. Further studies are warranted to validate these findings in esophagectomies.

Background and Aims: Cholangiocarcinoma (CCA) is a rare but aggressive malignancy with poorly understood genetic susceptibility. To date, genome-wide association studies (GWAS) investigating germline variants associated with CCA risk remain limited. We aimed to identify genetic risk loci for CCA and its clinical subtypes through comprehensive GWAS and post-GWAS analyses. Approach and Results: We conducted a GWAS of 2366 CCA cases and 11,750 controls of European ancestry. Genome-wide significant loci ( p <5×10 −8 ) were identified and further examined through fine-mapping, functional annotation, and HLA imputation. Subgroup analyses were conducted by CCA subtypes and primary sclerosing cholangitis (PSC) status. Cross-trait linkage disequilibrium score regression and Mendelian randomization were employed to investigate the shared genetic architecture and potential causal relationships with a diverse range of traits. We identified 1 new genome-wide significant variant, rs535777 (OR=1.44), near HLA-DRB1/DQA1 associated with CCA, and 2 variants associated with extrahepatic CCA: rs116224263 (OR=0.17) in LINC02506 at 4p15.1 and rs6914950 (OR=1.63) near HLA-DRB1/DQB1 . Stratified analyses revealed rs2395184 (OR=3.51) near HLA-DRA/DRB5 associated with PSC-related CCA, and rs142674434 (OR=2.98) in THSD7A at 7p21.3 associated with non-PSC-related CCA. HLA imputation uncovered new amino acid residues associated with disease risk. Cross-trait analyses identified shared genetic signals between CCA and anthropometric, lipidemic, lifestyle, and medical traits. Mendelian randomization supported putative causal associations for 12 traits with CCA or its subtypes. Conclusions: Our large-scale GWAS highlights new genetic variants and HLA-linked mechanisms underlying CCA susceptibility. Integrating multi-step post-GWAS approaches enhances understanding of CCA pathogenesis and may facilitate the development of risk biomarkers for early detection and precision prevention strategies.

Abstract Healthcare personnel (HCP) are at risk for occupational exposure to tuberculosis. Current guidelines for managing exposed HCP are broad and resource intensive. Based on review of our internal data, we propose a risk-based stratification approach to streamline exposure follow-up testing and optimize resource utilization.

Objective To quantitatively examine immune cell markers and spatial distribution in human diabetic kidney disease (DKD) to enhance understanding of the inflammatory landscape contributing to injury. Maladaptive inflammation is an underrecognized contributor to DKD pathogenesis and progression and remains undertreated. Patients and methods NanoString GeoMx™ Digital Spatial Profiling technology targeted antibodies labeled with unique oligonucleotide barcode in kidney biopsy [DKD (n=5), tubulointerstitial nephritis (TIN; n=4), and normal (n=2)] with regions of interest selection of compartments (glomeruli, tubules, interstitium). Inflammation-related proteins were analyzed with differential expression through linear mixed modeling. Results Compared to normal tissue, inflammatory cell surface protein markers were increased in DKD tubules and interstitium. Markers of T cells (CD4, CD44), macrophages (CD68; proinflammatory), and antigen-presenting cells (APCs; CD40 and CD11c) were increased across all DKD compartments (vs. normal). Macrophage (CD163; prorepair) marker was increased in DKD tubules and interstitium (vs. normal). Fewer differences were observed in glomeruli for normal vs. DKD or TIN vs. DKD groups. CD66b+ (granulocytes) cell marker was higher in DKD (vs. TIN). As expected, TIN had higher levels of T cell and macrophage markers in tubules and interstitium (vs. DKD). Interestingly, CD34, a hematopoietic stem cell and endothelial cell marker, was lower in DKD tubules and interstitium (vs. normal) but higher in DKD (vs. TIN). Conclusion NanoString GeoMx DSP technology may fulfil a role in enhancing the understanding the inflammatory landscape engaged in DKD pathogenesis as well as measuring response to therapy. Moreover, additional investigations of CD34 progenitor cell depletion in DKD may be warranted.

Abstract Primary liver cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), arise from the neoplastic transformation of hepatocytes and cholangiocytes, respectively. Loss or downregulation of PTEN, a tumor suppressor negatively regulating the PI3K/AKT pathway, is frequently observed in CCA and HCC. Notably, PTEN mutations are observed at nearly twice the frequency in combined CCA-HCC tumors than either HCC or CCA alone. Using lineage-specific liver-targeted PTEN-deficient mouse models, we demonstrate that PTEN loss drives cellular dedifferentiation and tumorigenesis, a process that is critically dependent on AKT2. Mechanistically, PTEN deficiency induces activation of NOTCH and upregulation of transcriptional factor SOX9, which plays a central role in tumor cell transformation. In parallel, PTEN loss increases SMAD4 expression and sensitizes the tumor cells to TGFβ signaling, with TGFβ treatment repressing SOX9 expression in tumor cells lacking PTEN. Together, our study defined a critical role for PTEN-AKT2 signaling in maintaining liver epithelial lineage fidelity and revealed how its disruption promotes the conversion of mature hepatocytes or cholangiocytes into liver cancer stem-like cells (LCSCs). Furthermore, we identify a PTEN-dependent crosstalk between NOTCH and TGFβ pathways that governs liver tumor development. Together, this work provides mechanistic insight into lineage plasticity in liver cancer with implications for pathway-directed therapy.

Background: Patients with cervical artery dissection (CAD) have a higher prevalence of cerebral aneurysms, likely due to underlying vasculopathies. Understanding risk factors and outcomes in this population may inform screening and management strategies. Methods: We conducted a post-hoc analysis of the STOP-CAD study, a multicenter international registry of patients with non-major trauma-related CAD across 63 centers. Cerebral aneurysms were identified based on medical history and intracranial vascular imaging obtained for dissection diagnosis. We compared demographic, clinical, laboratory, and imaging characteristics between patients with and without aneurysms. Variables with p<0.05 in univariate analysis were entered into a multivariable binary logistic regression to identify independent predictors. Clinical outcomes including ischemic stroke and symptomatic intracranial hemorrhage at follow-up were compared between both groups. Results: Out of 4023 patients included in the STOP-CAD study, 116 (2.9%) had at least one incidental cerebral aneurysm. In adjusted binary logistic regression, patients with cerebral aneurysm were more likely to have a history of migraine (aOR 1.78 95% CI 1.15-2.75, p=0.009), history of hypertension (aOR 1.65 95% CI 1.12-2.43, p = 0.010), known connective tissue disorder (aOR 3.47 95% CI 1.71-7.03), history of dissection (aOR 2.63 95% CI 1.31-5.28, p = 0.007), and a dissecting aneurysm at the site of the dissection (aOR 1.94 95% CI 1.25-3.01, p = 0.003). At follow-up, the presence of a cerebral aneurysm was not associated with ischemic stroke (7.8% vs. 5.6% p>0.1), but with a trend towards increased odds of symptomatic intracranial hemorrhage (3.4% vs. 1.2%, p = 0.062). Conclusions: Patients with CAD and concurrent incidental cerebral aneurysm were more likely to have a history of migraine headaches and markers of underlying vasculopathy and had a non-significantly increased risk of intracranial hemorrhage at follow-up. Further studies are needed to identify best practices for surveillance and risk stratification in this subgroup.

Background: High-grade intracranial atherosclerosis (ICAS) is associated with an elevated risk of recurrent ischemic stroke, particularly in patients with severe stenosis (70–99%). Identifying predictors of early recurrence can inform risk stratification and guide treatment strategies. Methods: The Biomarkers and Recurrence Risk in Symptomatic Intracranial Arterial Stenosis (BIORISK-ICAS) study is a multicenter, international, retrospective cohort analysis pooling data from 35 comprehensive stroke centers. We included hospitalized adult patients with symptomatic ICAS, defined as 50–99% stenosis of an intracranial artery (intracranial vertebral, basilar, distal ICA, or M1 MCA), confirmed by vascular imaging and associated with a qualifying ischemic event. Patients with only high-grade stenosis (70-99%) were included in this analysis. The primary outcome was to determine predictors of recurrent ischemic stroke in the territory of the symptomatic artery within 90 days of the index event. Baseline demographic, clinical, and imaging characteristics were recorded. Multivariable Cox proportional hazards regression with stepwise selection (p < 0.1) was used to identify independent predictors of recurrence; model discrimination was assessed using Harrell’s C-statistics. Results: Among 2,050 patients, 1,476 had high-grade (70-99%) symptomatic ICAS. The mean age was 67 ± 12.5 years, and 767 (55%) were male. Most patients were non-Hispanic (90.1%), taking dual antiplatelet therapy (77.8%), and statins (94.5%). Recurrent stroke occurred in 160 patients (10.8%) within 90 days. In multivariable Cox model, independent predictors of recurrence included atrial fibrillation (HR 2.05; 95% CI, 1.26–3.33; p = 0.004), hyperlipidemia (HR 1.57; 95% CI, 1.10–2.24; p = 0.014), diabetes mellitus (HR 1.36; 95% CI, 0.98–1.88; p = 0.064), and home use of dual antiplatelet therapy (HR 1.60; 95% CI, 1.01–2.54; p = 0.043)(Harrell’s C-statistic=0.62). In patients who underwent perfusion(n=402), mistmatch >10seconds were associated with increased recurrence (HR 1.80; 95% CI 0.95-3.38, p=0.07) and atrial fibrillation (HR 2.06: 95% CI 0.03-4.60, p=0.78) though did not reach statistical significance. Conclusion: In this population, diabetes, hyperlipidemia, atrial fibrillation, and prior use of dual antiplatelet therapy were associated with increased risk of 90-day recurrent ischemic stroke. Perfusion imaging may help identify high-risk patients who could benefit from intensified secondary prevention.

Background: Although the embolic stroke of undetermined source (ESUS) construct was proposed as a unifying concept for embolic-appearing strokes without an identified cause, it includes patients with diverse and often unrecognized underlying mechanisms. This study investigates the differential rate of recurrent stroke according to the completeness of neurodiagnostic testing in a diverse multicenter cohort. Methods: This was a retrospective analysis of a multicenter observational cohort study (n=27 sites). Patients with ESUS were categorized into three groups: (1) established mechanism after further work up (ESUS-E), (2) patients who underwent a comprehensive diagnostic workup without an identified etiology (ESUS 2.0), and (3) no advanced workup (ESUS-NAW). The primary outcome of recurrent ischemic stroke was assessed by comparing ESUS 2.0 to both ESUS-E and ESUS-NAW groups using adjusted Cox proportional hazards models. Results: Of the 2,281 patients included, 694 (30%) were classified as ESUS-E, 344 (15%) as ESUS 2.0, and 1,443 (55%) as ESUS-NAW. The ESUS 2.0 group had a significantly lower annualized recurrence rate (1.98 per 100 person-years) compared to both the ESUS-NAW group (7.7 per 100 person-years; aHR 0.27, 95% CI: 0.11–0.62; p=0.002) and the ESUS-E group (6.10 per 100 person-years; aHR = 0.35; 95% CI 0.15–0.85, p=0.020). Within the ESUS-E group, cancer (aHR 5.33; 95% CI: 2.09–13.63; p < 0.001) and non-stenosing atherosclerotic disease or arch atheroma (aHR 3.40; 95% CI: 1.18–9.83; p = 0.023) were associated with significantly increased risk of recurrence when compared to ESUS 2.0. Conclusion: These findings demonstrate a lower risk of recurrent stroke in patients classified as ESUS 2.0, diverging from the 5–6% annual recurrence rates observed in prior ESUS trials. These findings suggest that patients who receive comprehensive diagnostic evaluation without identification of a specific etiology have a lower risk of recurrent stroke, an important consideration for the design of future ESUS studies.