Citations

Significance This study demonstrates that underexpression of succinate dehydrogenase (SDH) subunits resulting in accumulation of oncogenic succinate is a common, adverse, epigenetic modulating feature in clear cell renal cell carcinoma (ccRCC), during pathogenesis and progression. The study sheds light on the mechanisms of down-regulation of SDH subunits in ccRCC and deciphers the consequent oncogenic effects. It shows that functional SDH deficiency is a common feature of ccRCC (∼80% of all kidney cancers), and not just limited to the 0.05 to 0.5% of kidney cancers with germline SDH mutations.

Background: Preclinical studies and pilot patient studies have shown that chronic infarctions can be detected and characterized from cardiac magnetic resonance without gadolinium-based contrast agents using native-T1 maps at 3T. We aimed to investigate the diagnostic capacity of this approach for characterizing chronic myocardial infarctions (MIs) in a multi-center setting. Methods: Patients with a prior MI (n=105) were recruited at 3 different medical centers and were imaged with native-T1 mapping and late gadolinium enhancement (LGE) at 3T. Infarct location, size, and transmurality were determined from native-T1 maps and LGE. Sensitivity, specificity, receiver-operating characteristic metrics, and inter- and intraobserver variabilities were assessed relative to LGE. Results: Across all subjects, T1 of MI territory was 1621±110 ms, and remote territory was 1225±75 ms. Sensitivity, specificity, and area under curve for detecting MI location based on native-T1 mapping relative to LGE were 88%, 92%, and 0.93, respectively. Native-T1 maps were not different for measuring infarct size (native-T1 maps: 12.1±7.5%; LGE: 11.8±7.2%, P =0.82) and were in agreement with LGE ( R 2 =0.92, bias, 0.09±2.6%). Corresponding inter- and intraobserver assessments were also highly correlated (interobserver: R 2 =0.90, bias, 0.18±2.4%; and intraobserver: R 2 =0.91, bias, 0.28±2.1%). Native T1 maps were not different for measuring MI transmurality (native-T1 maps: 49.1±15.8%; LGE: 47.2±19.0%, P =0.56) and showed agreement ( R 2 =0.71; bias, 1.32±10.2%). Corresponding inter- and intraobserver assessments were also in agreement (interobserver: R 2 =0.81, bias, 0.1±9.4%; and intraobserver: R 2 =0.91, bias, 0.28±2.1%, respectively). While the overall accuracy for detecting MI with native-T1 maps at 3T was high, logistic regression analysis showed that MI location was a prominent confounder. Conclusions: Native-T1 mapping can be used to image chronic MI with high degree of accuracy, and as such, it is a viable alternative for scar imaging in patients with chronic MI who are contraindicated for LGE. Technical advancements may be needed to overcome the imaging confounders that currently limit native-T1 mapping from reaching equivalent detection levels as LGE.

Background— The appropriate indication for coronary computed tomographic angiography (CTA) as a part of preoperative evaluation has not been defined yet. We investigated the value of coronary CTA in patients undergoing noncardiac surgery. Methods and Results— We included 844 patients (median age, 67 years; male sex, 62%) who underwent coronary CTA for screening of coronary artery disease before noncardiac surgery. Clinically determined revised cardiac risk index were compared with the extent and severity of coronary artery disease assessed by coronary CTA. Perioperative major cardiac event (PMCE), defined as cardiac death, myocardial infarction, or pulmonary edema within postoperative 30 days, developed in 25 patients (3.0%). Significant coronary CTA finding was defined as >3 any lesions with ≥1 (diameter stenosis ≥70%) stenosis based on the relationship between the severity of coronary artery disease and PMCE risk. The risk of PMCE was 14.0% in patients with significant CTA findings, whereas 2.2% of patients without significant CTA findings regardless of revised cardiac risk index score. The predictive performance of revised cardiac risk index could be improved significantly after addition of significant coronary CTA findings (c-statistics=0.631 versus 0.757; net reclassification improvement=0.923; integrated discrimination improvement=0.051). On the basis of revised cardiac risk index and coronary CTA, the risk of PMCE could be estimated with sensitivity, specificity, positive predictive value, and negative predictive value of 76%, 73%, 8%, and 99%, respectively. Conclusions— Addition of coronary CTA to clinical risk improved perioperative risk stratification. Absence of significant coronary CTA findings conferred low PMCE risk with high specificity and negative predictive value regardless of clinical risk. Coronary CTA may improve perioperative risk stratification in patients undergoing noncardiac surgery.