Citations

AbstractObjectivesThis study sought to compare the clinical outcomes of percutaneous coronary interventions (PCIs) performed by sleep deprived and non‐sleep deprived operators.BackgroundInterventional cardiologists are at risk for sleep deprivation as they often have to perform emergent procedures at night, but the effects of sleep deprivation on clinical outcomes have received limited study.MethodsWe examined the frequency, clinical characteristics, and outcomes of daytime PCIs performed by sleep deprived and non‐sleep deprived operators at a tertiary medical center. Operators were considered sleep deprived when performing a daytime (7 am–11:59 pm) procedure preceded by a nighttime (12 am–6:59 am) procedure on the same date.ResultsOf the 12,680 daytime PCIs performed from 6/29/09 to 12/30/2016, 367 (2.9%) were performed by sleep deprived operators. Patients undergoing PCI performed by a sleep deprived operator were more likely to be younger, white, and to present with ST‐elevation acute myocardial infarction (STEMI). The incidence of in‐hospital death (1.1% vs. 1.3%, P = 1.0) and bleeding within 72 hr (3.9% vs. 2.9%, P = 0.29) were similar for procedures performed by sleep‐deprived and non‐sleep deprived operators. When the sleep deprived group was further stratified based on degree of sleep deprivation or length of sleep interruption, differences in mortality and total bleeding remained non‐significant.ConclusionsIn this large single center study, operator sleep deprivation did not appear to adversely impact PCI outcomes.

We sought to examine further the potential role of nitric oxide (NO) in the neurally mediated cutaneous vasodilation in nonacral skin during body heating in humans. Six subjects were heated with a water-perfused suit while cutaneous blood flow was measured by using laser-Doppler flowmeters placed on both forearms. The NO synthase inhibitor NG-monomethyl-l-arginine (l-NMMA) was given selectively to one forearm via a brachial artery catheter after marked cutaneous vasodilation had been established. During body heating, oral temperature increased by 1.1 ± 0.1°C while heart rate increased by 30 ± 6 beats/min. Mean arterial pressure stayed constant at 84 ± 2 mmHg. In the experimental forearm, cutaneous vascular conductance (CVC; laser-Doppler) decreased to 86 ± 5% of the peak response to heating ( P < 0.05 vs. pre-l-NMMA values) afterl-NMMA infusion. In some subjects, l-NMMA caused CVC to fall by ∼30%; in others, it had little impact on the cutaneous circulation. CVC in the control arm showed a similar increase with heating, then stayed constant whilel-NMMA was given to the contralateral side. These results demonstrate that NO contributes modestly, but not consistently, to cutaneous vasodilation during body heating in humans. They also indicate that NO is not the only factor responsible for the dilation.

AbstractLoss of major histocompatibility Class II expression (MHCII) in diffuse large B‐cell lymphoma (DLBCL) correlates with decreased survival. MHCII transcription is in part regulated by histone acetylation. We tested the hypothesis that combination of histone deacetylase inhibitor (HDACI) with standard chemotherapy would improve outcomes in DLBCL in part through increased MHCII expression. S0806 was a single arm phase I/II trial of vorinostat given at 400 mg po daily on days 1‐9 (subsequently amended to days 1‐5 due to toxicity), combined with R‐CHOP given on day 3 of a 21‐day cycle for 8 cycles, with primary phase II endpoint of 2‐year progression free survival (PFS). With 72 evaluable patients, at median follow up of 3 years, 2‐year PFS estimate was 73%, and OS estimate was 86%. Considering that the regimen fell short of predefined efficacy improvement and was associated with high rates of febrile neutropenia (38%) and sepsis (19%), it cannot be recommended for general use. Consistent with our hypothesis, patients with low MCHII expression on S0806 had numerically superior outcomes compared to those from trial S0433 which did not use an HDACI, but the difference was not statistically significant. Current studies are focused on finding biomarkers of response to HDACI.

Abstract Background The American Board of Anesthesiology recently introduced the BASIC Examination, a component of its new staged examinations for primary certification, typically offered to residents at the end of their first year of clinical anesthesiology training. This analysis tested the hypothesis that the introduction of the BASIC Examination was associated with an acceleration of knowledge acquisition during the residency training period, as measured by increments in annual In-Training Examination scores. Methods In-Training Examination performance was compared longitudinally among four resident cohorts (n = 6,488) before and after the introduction of the staged system using mixed-effects models that accounted for possible covariates. Results Compared with previous cohorts in the traditional examination system, the first resident cohort in the staged system had a greater improvement in In-Training Examination scores between the first and second years of clinical anesthesiology training (by an estimated 2.0 points in scaled score on a scale of 1 to 50 [95% CI, 1.7 to 2.3]). By their second year, they had achieved a score similar to that of third-year clinical anesthesiology residents in previous cohorts. The second cohort to enter the staged system had a greater improvement of the scores between the clinical base year and the first clinical anesthesiology year, compared with the previous cohorts. Conclusions These results support the hypothesis that the introduction of the BASIC Examination is associated with accelerated knowledge acquisition in residency training and provides evidence for the value of the new staged system in promoting desired educational outcomes of anesthesiology training.

Background and aimsRoutine serologic testing for celiac disease (CD) may be useful in irritable bowel syndrome (IBS) patients, but this is controversial. We aimed to compare the prevalence of unrecognized CD in a large cohort of patients with and without IBS.Participants and methodsThis is a family case–control IBS study conducted at a single US academic medical center. Stored serum and DNA were available. Tissue transglutaminase (TTg) immunoglobulin A was performed, followed by indirect immunofluorescence testing for endomysial antibodies with positive or weakly positive TTg results. Individuals were considered to have CD if both results were positive.χ2and Fisher’s exact tests were used to compare prevalence between the two groups.ResultsSerum samples were studied from 533 cases and 531 controls. In all, 80% of participants were female, with a median age of 50 years; 65% of cases and 0% controls met the Rome criteria for IBS. Previous serological testing for CD had occurred in 142 (27%) cases and 13 (2%) controls, but none had CD on subsequent testing. Six (1.1%) cases versus five (0.9%) controls had positive or weakly positive TTg test. Six cases (1.1%) versus three (0.6%) controls were confirmed to have CD by endomysial antibody (P=0.51).ConclusionNo difference in the prevalence of CD between patients with IBS and patients without IBS at a tertiary medical center was observed. Our findings do not support routine celiac serologic or genetic testing in patients with IBS in all US populations.

Key Points BV and Nivo were well-tolerated in patients with R/R HL, with less than 10% of patients treated with systemic steroids for immune-related AEs. The complete response rate was 61% (82% objective response rate), and patients were able to undergo stem cell transplant without adverse impact.

Background: A shorter sleep duration has been identified as a risk factor for cardiovascular diseases and increased mortality. It has been hypothesized that a short sleep duration may be linked to changes in ghrelin and leptin production, leading to an alteration of stress hormone production. Here, we conducted a systematic review and meta-analysis to investigate the potential relationship between a sleep duration and cardiovascular disease mortality. Methods: We conducted a comprehensive search of Ovid Medline In-Process and other non-indexed citations, Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, and Scopus from database inception to March 2017. Observational studies were included if the studies reported hazard ratios or odds ratios of the associations between sleep durations (short and long) and cardiovascular disease mortality. Data were extracted by a reviewer and then reviewed by two separate reviewers. Conflicts were resolved through consensus. Using the DerSimonian and Laird random effects models, we calculated pooled hazard ratios and pooled odds ratios with 95% confidence intervals (CI). Subgroup analyses were performed to explore potential sources of heterogeneity. The quality of the included studies and publication bias were assessed. Results: In total, our meta-analysis included 19 studies (31 cohorts) with a total of 816,995 individuals with 42,870 cardiovascular disease mortality cases. In pooled analyses, both short (risk ratio 1.19; 95% CI 1.13 to 1.26, P<0.001, I2=30.7, Pheterogeneity=0.034), and long (risk ratio 1.37; 95% CI 1.23 to 1.52, P<0.001, I2=79.75, Pheterogeneity<0.001) sleep durations were associated with a greater risk of cardiovascular disease mortality. Conclusions: Both short (<7 hours) and long sleep durations (>9 hours) can increase the risk of overall cardiovascular disease mortality, particularly in Asian populations and elderly individuals. Future epidemiological studies would ideally include objective sleep measurements, rather than self-report measures, and all potential confounders, such as genetic variants.

ProblemPregnancy requires balance between tolerance to the haploidentical fetus and the mother's ability to mount immune responses. There are parallels to this phenomenon that occur in metastatic cancer. We assessed soluble program death ligand‐1 soluble PD‐L1 (sPD‐L1) and galectin‐9 in the blood of pregnant women during gestation as these molecules are highly involved in immune suppression during cancer.Method of studyMaternal blood was collected from 30 primigravida women at monthly intervals during pregnancy, delivery and 6‐week post‐partum. Blood was analyzed for sPD‐L1 and galectin‐9 concentrations by ELISA. Term placentas were collected in formalin and IHC was completed for PD‐L1 and galectin‐9 expression.ResultsMaternal blood levels of sPD‐L1 (0.438 ng/mL) and galectin‐9 (1976 pg/mL) were elevated early in normal pregnancies compared to non‐pregnant controls (0.242 ng/mL and 773 pg/mL, respectively). sPD‐L1 increased throughout gestation, whereas galectin‐9 remained elevated until parturition; both proteins returned to control levels post‐partum. Women carrying male fetuses had significantly higher galectin‐9 levels, but not sPD‐L1, than those carrying females (2263 pg/mL vs 1874 pg/mL; P = .0005). Trophoblast cells of the term placenta coexpress galectin‐9 and PD‐L1.ConclusionImmune‐regulatory molecules galectin‐9 and sPD‐L1 increased during pregnancy and may play a role in immune tolerance that is critical for the fetus.