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PurposeThe WHO 2016 update classifies glioblastomas (WHO grade IV) according to isocitrate dehydrogenase (IDH) gene mutation status. We aimed to determine MRI-based metrics for predicting IDH mutation in glioblastoma.MethodsThis retrospective study included glioblastoma cases (n = 199) with known IDH mutation status and pre-operative MRI (T1WI, T2WI, FLAIR, contrast-enhanced T1W1 at minimum). Two neuroradiologists determined the following MRI metrics: (1) primary lobe of involvement (frontal or non-frontal); (2) presence/absence of contrast-enhancement; (3) presence/absence of necrosis; (4) presence/absence of fluid attenuation in the non-contrast-enhancing tumor (nCET); (5) maximum width of peritumoral edema (cm); (6) presence/absence of multifocal disease. Inter-reader agreement was determined. After resolving discordant measurements, multivariate association between consensus MRI metrics/patient age and IDH mutation status was determined.ResultsAmong 199 glioblastomas, 16 were IDH-mutant. Inter-reader agreement was calculated for contrast-enhancement (ĸ = 0.49 [− 0.11–1.00]), necrosis (ĸ = 0.55 [0.34–0.76]), fluid attenuation in nCET (ĸ = 0.83 [0.68–0.99]), multifocal disease (ĸ = 0.55 [0.39–0.70]), and primary lobe (ĸ = 0.85 [0.80–0.91]). Mean difference for peritumoral edema width between readers was 0.3 cm [0.2–0.5], p < 0.001. Multivariate analysis uncovered significant associations between IDH-mutation and fluid attenuation in nCET (OR 82.9 [19.22, ∞], p < 0.001), younger age (OR 0.93 [0.86, 0.98], p = 0.009), frontal lobe location (OR 11.08 [1.14, 352.97], p = 0.037), and less peritumoral edema (OR 0.15 [0, 0.65], p = 0.044).ConclusionsConventional MRI metrics and patient age predict IDH-mutation status in glioblastoma. Among MRI markers, fluid attenuation in nCET represents a novel marker with high inter-reader agreement that is strongly associated with Glioblastoma, IDH-mutant.

To examine the effects of exercise intensity on acute changes in endothelial function in lean and obese adults. Sixteen lean (BMI <25, age 23 ± 3 yr) and 10 obese (BMI >30, age 26 ± 6 yr) physically inactive adults were studied during 3 randomized admissions [control (C, no exercise), moderate-intensity exercise (M, @ lactate threshold (LT)) and high-intensity exercise (H, midway between LT and VO2peak) (30 min)]. Endothelial function was assessed by flow-mediated dilation (FMD) at baseline and 1, 2, and 4 h post-exercise. RM ANCOVA revealed significant main effects for group, time, and group x condition interaction (p<0.05). A diurnal increase in FMD was observed in lean but not obese subjects. Lean subjects exhibited greater increases in FMD than obese subjects (p = 0.0005). In the obese group a trend was observed for increases in FMD at 2- and 4-hr after M (p = 0.08). For lean subjects, FMD was significantly elevated at all time points after H. The increase in FMD after H in lean subjects (3.2 ± 0.5%) was greater than after both C (1.7 ± 0.4%, p = 0.015) and M (1.4 ± 0.4%, p = 0.002). FMD responses of lean and obese subjects significantly differed after C and H, but not after M. In lean young adults, high-intensity exercise acutely enhances endothelial function, while moderate-intensity exercise has no significant effect above that seen in the absence of exercise. The FMD response of obese adults is blunted compared to lean adults. Diurnal variation should be considered when examining the effects of acute exercise on FMD.

Background Underwater endoscopic mucosal resection (UEMR) without submucosal injection is a novel endoscopic procedure. It is not known if UEMR can be easily taught and learned, and the efficacy and safety of UEMR has not been demonstrated at multiple medical centers. Our aims were to demonstrate that (1) UEMR is a technique that can be easily learned by an endoscopist trained in traditional EMR, (2) endoscopic ultrasound (EUS) may not be required before UEMR, and (3) UEMR is an efficacious and safe method for resection of large or flat neoplastic colorectal lesions. Methods An experienced interventional endoscopist began performing UEMR after observing UEMR procedures. Colorectal UEMR was performed using a pediatric colonoscope with a cap, a waterjet, and a ‘duck-bill’ snare using blended current. Submucosal injection was not used. Patient data were collected prospectively. Results A total of 21 patients (17 men, mean age 64.9 years, range 51–83) referred for polypectomy of large colorectal lesions underwent UEMR. A total of 43 colorectal lesions with a mean size of 20 mm (range 8–50) were resected by UEMR. Lesions were found in the right colon ( N  = 16), transverse colon ( N  = 5), left colon ( N  = 19), and rectum ( N  = 3). Pathology demonstrated tubular adenoma ( N  = 29), tubulovillous adenoma ( N  = 5), high-grade dysplasia ( N  = 3), serrated sessile adenoma without dysplasia ( N  = 3), and non-neoplastic tissue ( N  = 3). EUS was used in only two cases of rectal neoplasia (4.7 %). Of the UEMRs, 97.7 % were successful with complete resection of colorectal polyps. The only adverse event was one case (2.3 %) of delayed post-UEMR bleeding. Conclusions UEMR was easily learned by an endoscopist already skilled in conventional EMR. EUS may not be required prior to most UEMR procedures. UEMR appears to be an efficacious and safe alternative to traditional EMR or ESD for large or flat colorectal neoplasms.

Hypoadiponectinemia is speculated to play a key role in the relationship between obesity and COVID‐19 respiratory failure. However, only one study has examined adiponectin levels in COVID‐19 patients, and none have investigated adiponectin levels strictly in patients with acute respiratory failure. In this study, we performed a retrospective case‐control study of adipokine levels in patients with acute respiratory failure caused by either COVID‐19 or other viral/bacterial source. All patients with COVID‐19 respiratory failure in the University of Virginia Biorepository and Tissue Research database were included. We also selected patients with non‐COVID‐19 infectious respiratory failure from the same biorepository to serve as a comparison cohort. Plasma adipokine levels were measured on three occasions during the first 72 hours of hospitalization. Twelve patients with COVID‐19 respiratory failure and 17 patients with other infectious respiratory failure were studied. Adiponectin levels were significantly lower in patients with COVID‐19 respiratory failure, even after adjustment for age, sex, BMI, and other covariates. In conclusion, adiponectin levels appear to be reduced in COVID‐19 respiratory failure. Larger studies are needed to confirm this report.

Insulin increases muscle microvascular perfusion and enhances tissue insulin and nutrient delivery. Our aim was to determine phenotypic traits that foretell human muscle microvascular insulin responses. Hyperinsulinemic euglycemic clamps were performed in 97 adult humans who were lean and healthy, had class 1 obesity without comorbidities, or controlled type 1 diabetes without complications. Insulin-mediated whole-body glucose disposal rates (M-value) and insulin-induced changes in muscle microvascular blood volume (ΔMBV) were determined. Univariate and multivariate analyses were conducted to examine bivariate and multivariate relationships between outcomes, ΔMBV and M-value, and predictor variables, body mass index (BMI), total body weight (WT), percent body fat (BF), lean body mass, blood pressure, maximum consumption of oxygen (VO 2 max), plasma LDL (LDL-C) and HDL cholesterol, triglycerides (TG), and fasting insulin (INS) levels. Among all factors, only M-value (r = 0.23, p = 0.02) and VO 2 max (r = 0.20, p = 0.047) correlated with ΔMBV. Conversely, INS (r = − 0.48, p ≤ 0.0001), BF (r = − 0.54, p ≤ 0.001), VO 2 max (r = 0.5, p ≤ 0.001), BMI (r = − 0.40, p < 0.001), WT (r = − 0.33, p = 0.001), LDL-C (r = − 0.26, p = 0.009), TG (r = − 0.25, p = 0.012) correlated with M-value. While both ΔMBV (p = 0.045) and TG (p = 0.03) provided significant predictive information about M-value in the multivariate regression model, only M-value was uniquely predictive of ΔMBV (p = 0.045). Thus, both M-value and VO 2 max correlated with ΔMBV but only M-value provided unique predictive information about ΔMBV. This suggests that metabolic and microvascular insulin responses are important predictors of one another, but most metabolic insulin resistance predictors do not predict microvascular insulin responses.

Parkinson's disease psychosis (PDPsy) is associated with increased nursing home placement and mortality and is closely linked with cognitive dysfunction. Assess the clinical and cognitive features associated with PDPsy in patients without dementia. We prospectively recruited people with Parkinson's disease (PwP) without dementia for a 3-year, longitudinal study at an outpatient movement disorders clinic. Participants completed annual visits involving assessment of motor and non-motor symptoms including neuropsychological testing. PDPsy was defined as the recurring presence of visual illusions, sense of presence, hallucinations, or delusions for at least 1 month. Using generalized estimating equations, we conducted two sets of analyses to separately assess the clinical and the cognitive predictors of PDPsy. We enrolled 105 participants. At baseline, mean age was 67.8 (SD = 8.0), median disease duration was 4.9 years (IQR: 3.4-7.7), and mean MoCA was 24.8 (SD = 2.3). Prevalence of PDPsy increased over 3 years from 31% ( = 32) to 39% ( = 26). Forty-five participants (43%) experienced PDPsy. Visual illusions were most common (70%, = 84), followed by hallucinations (58.3%, = 70). In multivariate analysis, of the clinical variables, only depressive symptoms [OR 1.09, 95% CI: (1.03, 1.16), = 0.004] increased the odds of PDPsy; of the cognitive variables, only Trail Making Test B-A scores [OR 1.43, 95% CI: (1.06, 1.93), = 0.018] significantly increased the odds of PDPsy. In PwP without dementia, depressive symptoms were associated with increased risk of PDPsy. Executive/attentional dysfunction was also associated with PDPsy and may mark the transition from isolated minor hallucinations to more complex psychotic symptoms.

Renal artery fibromuscular dysplasia (FMD) may be underdiagnosed. We evaluated the prevalence of FMD in CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) renal artery stent trial participants, in which FMD was an exclusion criterion for inclusion. We also evaluated the prevalence of FMD in a relatively healthy population of patients undergoing computed tomographic angiographic (CTA) screening for renal donor evaluation. All renal donor CTAs performed at our institution from January 2003 through November 2011 were retrospectively reviewed for the presence of FMD along with patient sex and age. These results were compared to angiographic core lab (ACL) findings for the CORAL trial. The CORAL ACL database contained 997 patients (mean age 69.3 years; 50% female). Fifty-eight (5.8%) CORAL trial patients (mean age 71.8 years; 75.9% female) demonstrated incidental FMD. The renal donor cohort included 220 patients (mean age 40.5 years; 64.5% female). Five (2.3%) demonstrated FMD (mean age 48.6 years; all female). The odds of FMD in the CORAL cohort were 2.65 times that seen in the renal donor cohort (95% CI: 1.12, 7.57). In conclusion, the 5.8% prevalence of renal artery FMD in the CORAL trial population, the presence of which was biased against, suggests underdiagnosis.

Obese children frequently complain of breathlessness. Asthma and obesity can both contribute to the symptoms during exercise, and this symptom can contribute to a diagnosis of asthma in these children. Despite the high prevalence of obesity few studies have investigated the cardiopulmonary physiology of breathlessness in obese children with a diagnosis of asthma. In this case-control study, thirty adolescents between age 12 and 19 were studied with baseline spirometry and a cardiopulmonary exercise test. Ten adolescents were normal controls, ten had obesity without a diagnosis of asthma, and ten had obesity with a history of physician-diagnosed asthma. Baseline characteristics including complete blood count and spirometry were comparable between obese adolescents with and without a diagnosis of asthma. During exercise, obese asthmatic and obese non-asthmatic adolescents had significantly reduced physical fitness compared to healthy controls as evidenced by decreased peak oxygen uptake after adjusting for actual body weight (21.7 ± 4.5 vs. 21.4 ± 5.4 vs. 35.3 ± 5.8 ml/kg/min, respectively). However, pulmonary capacity at the peak of exercise was comparable among all three groups as evidenced by similar pulmonary reserve. In this study, breathlessness was primarily due to cardiopulmonary deconditioning in the majority of obese adolescents with or without a diagnosis of asthma.

Feedback facilitates the lifelong process of practice-based learning and improvement by helping to identify strengths and deficits, set goals, and provide data that allows for self-evaluation and behavioral change. Increasing evidence demonstrates that intraoperative hypotension contributes to postoperative acute kidney injury, myocardial injury after noncardiac surgery, and increased thirty-day mortality [1–3]. The Institutional Review Board at the University of Virginia waived the requirement for written informed consent.

OBJECTIVE:--Magnesium deficiency has been associated with insulin resistance (IR) and increased risk for type 2 diabetes in adults. This study was designed to determine whether obese children exhibit serum or dietary magnesium deficiency and its potential association with IR. RESEARCH DESIGN AND METHODS--We studied 24 obese nondiabetic children (BMI [>/=]85th percentile) and 24 sex- and puberty-matched lean control subjects (BMI <85th percentile). We measured serum magnesium, indexes of insulin sensitivity, dietary magnesium intake (using a food frequency questionnaire), and body composition (by air displacement plethysmography). RESULTS:--Serum magnesium was significantly lower in obese children (0.748 ± 0.015 mmol/l, means ± SE) compared with lean children (0.801 ± 0.012 mmol/l) (P = 0.009). Serum magnesium was inversely correlated with fasting insulin (r[subscript s] = -0.36 [95% CI -0.59 to -0.08]; P = 0.011) and positively correlated with quantitative insulin sensitivity check index (QUICKI) (0.35 [0.06-0.58]; P = 0.015). Dietary magnesium intake was significantly lower in obese children (obese: 0.12 ± 0.004 vs. lean: 0.14 ± 0.004 mg/kcal; P = 0.003). Dietary magnesium intake was inversely associated with fasting insulin (-0.43 [-0.64 to -0.16]; P = 0.002) and directly correlated with QUICKI (0.43 [0.16-0.64]; P = 0.002). CONCLUSIONS:--The association between magnesium deficiency and IR is present during childhood. Serum magnesium deficiency in obese children may be secondary to decreased dietary magnesium intake. Magnesium supplementation or increased intake of magnesium-rich foods may be an important tool in the prevention of type 2 diabetes in obese children.