Mutant IDH1 and thrombosis in gliomas.

Mutant isocitrate dehydrogenase 1 (IDH1) is common in gliomas, and produces D-2-hydroxyglutarate (D-2-HG). The full effects of IDH1 mutations on glioma biology and tumor microenvironment are unknown. We analyzed a discovery cohort of 169 World Health Organization (WHO) grade II-IV gliomas, followed by a validation cohort of 148 cases, for IDH1 mutations, intratumoral microthrombi, and venous thromboemboli (VTE). 430 gliomas from The Cancer Genome Atlas were analyzed for mRNAs associated with coagulation, and 95 gliomas in a tissue microarray were assessed for tissue factor (TF) protein. In vitro and in vivo assays evaluated platelet aggregation and clotting time in the presence of mutant IDH1 or D-2-HG. VTE occurred in 26-30 % of patients with wild-type IDH1 gliomas, but not in patients with mutant IDH1 gliomas (0 %). IDH1 mutation status was the most powerful predictive marker for VTE, independent of variables such as GBM diagnosis and prolonged hospital stay. Microthrombi were far less common within mutant IDH1 gliomas regardless of WHO grade (85-90 % in wild-type versus 2-6 % in mutant), and were an independent predictor of IDH1 wild-type status. Among all 35 coagulation-associated genes, F3 mRNA, encoding TF, showed the strongest inverse relationship with IDH1 mutations. Mutant IDH1 gliomas had F3 gene promoter hypermethylation, with lower TF protein expression. D-2-HG rapidly inhibited platelet aggregation and blood clotting via a novel calcium-dependent, methylation-independent mechanism. Mutant IDH1 glioma engraftment in mice significantly prolonged bleeding time. Our data suggest that mutant IDH1 has potent antithrombotic activity within gliomas and throughout the peripheral circulation. These findings have implications for the pathologic evaluation of gliomas, the effect of altered isocitrate metabolism on tumor microenvironment, and risk assessment of glioma patients for VTE.

What Is the Appropriate Use of Renal Sonography in an Inner-City Population With New-Onset Acute Kidney Injury?

OBJECTIVES: We aimed to determine the prevalence of hydronephrosis in patients who underwent renal sonography for new-onset acute kidney injury (AKI) and to identify clinical factors predictive of hydronephrosis. In patients with hydronephrosis, we sought to investigate how routine renal sonography affects patient treatment, including performance of interventional procedures. METHODS: A retrospective chart review identified 274 adults with AKI who underwent renal sonography at an urban teaching hospital from January through July 2011. The prevalence of hydronephrosis was determined. Electronic medical records were reviewed for comorbidities, including risk factors for hydronephrosis such as a pelvic mass, prior renal or pelvic surgery, and neurogenic bladder, and for subsequent interventions and outcomes. RESULTS: Sonography showed hydronephrosis in 28 patients (10%); 5 (18%) had subsequent interventions. In a multivariable logistic regression model with the outcome being hydronephrosis, all considered risk factors (pelvic mass, prior renal or pelvic surgery, and neurogenic bladder) were significantly associated with hydronephrosis (odds ratio, 6.4; 95% confidence interval, 2.7-15.4; P < .001) when adjusting for age and diabetes mellitus. Diabetes had a negative predictive value for hydronephrosis. No diabetic patients younger than 85 years and without clinical risk factors had hydronephrosis. CONCLUSIONS: Hydronephrosis is infrequently seen on sonograms in hospitalized patients with AKI who lack risk factors for urinary tract obstruction. Deferral of sonography pending a trial of medical treatment is safe and will reduce medical costs. Adoption of clinical guidelines to assess patients' risk levels for hydronephrosis is critical to avoid unnecessary imaging.

Assessing the impact of an orientation week on acclimation to radiology residency.

PURPOSE: Acclimating residents to radiology residency requires attention to new responsibilities, educational material, and social cohesion. To this end, we instituted a structured orientation week for incoming residents and assessed its impact. PROCEDURES: During the first weeks of July 2016 and 2017, first year residents attended a five day orientation free of clinical duties, consisting of didactics, hands-on training sessions, and social events. After two orientation cohorts, residents who completed orientation week, and two cohorts who had not, were given a voluntary, anonymous survey using Likert scale questions (1 [worst] to 5 [best]) regarding preparedness for responsibilities, learning, and social cohesion. Residents were asked which components were or would have been helpful. Independent samples t-tests were performed to evaluate differences between the two groups (two-tailed p < 0.05). FINDINGS: 21/37 (57%) residents participated. Higher percentages of residents who participated in the orientation week gave scores ≥4 when asked about preparedness for rotations (70% vs. 36%), learning new material (80% vs. 36%), and class cohesiveness (90% vs. 70%). Mean scores on these questions were also higher for these residents with regards to: preparedness for new responsibilities (3.7 vs. 2.9), learning new material (3.8 vs. 2.9), and class cohesiveness (4.5 vs. 3.8), with differences approaching significance (p = 0.09-0.15). Individual components receiving most votes of ≥4 were social outings, resident lunches, didactic lectures, and PACS training. CONCLUSION: A weeklong orientation program free of clinical duties was valued by residents and contributed to acclimation to new responsibilities, education, and social cohesion.