Surgery Poster - 2019

Surgery Poster - 2019https://scholarlycommons.libraryinfo.bhs.org/research_education/1016/thumbnail.jp

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Sperm donor attitudes and experiences with direct-to-consumer genetic testing

Objective: To identify factors influencing sperm donor willingness to participate in direct-to-consumer genetic testing, comfort with sharing genetically identifiable data in commercial genetic testing databases, and likelihood to donate sperm again. Design: Cross-sectional online anonymous survey. Setting: Multicenter, 2 large American sperm banks from July 1, 2020 to July10, 2021. Patient(s): Sperm donors from 1980 to 2020. Intervention(s): None. Main outcome measure(s): Associations between donor demographic characteristics, donation history, and attitudes toward direct-to-consumer genetic testing. Result(s): A total of 396 donors completed the survey. Most donations (61.5%) occurred from 2010 to 2020, and 34.3% were nonidentified donations. Nonidentified donors were less comfortable with their genetic data being shared than open-identity donors (25.4% vs. 43.8%) and were less likely than open-identity donors to donate sperm again (43.3% vs. 72.1%). Donors who donated after the inception of direct-to-consumer genetic testing in 2007 were less likely to participate in commercial genetic testing than those who donated before 2007 (25.8% vs. 37.1%). Most donors (87.4%) have disclosed their donation(s) to current partners, but fewer have disclosed them to their families (56.6%) or children (30.5%). Of the donors who had been contacted by donor-conceived persons, 79.5% were identified via direct-to-consumer genetic testing. Overall, 61.1% of donors would donate again regardless of direct-to-consumer genetic testing. Conclusion(s): Direct-to-consumer genetic testing is playing a dynamic role in sperm donor identification, but donors seem willing to donate again. Implication counseling regarding future linkage and contact from donor-conceived persons needs to be standardized for potential donors before donation

Urate Lowering Efficacy of Febuxostat Versus Allopurinol in Hyperuricemic Patients with Gout

Background: The prescribed maximum dose of allopurinol is 300 mg/day to maintain a serum uric acid (sUA) concentration of < 6.0 mg/dl. However, increasing evidence shows that 300 mg dose is ineffective in achieving the target sUA level, limiting allopurinol's use in certain subsets of patients who are intolerant to allopurinol such as patients with chronic kidney disease, with multiple comorbidities and elderly patients. Objective: To determine the efficacy and safety of febuxostat compared with allopurinol in lowering sUA level in patients with hyperuricemia in gout with a baseline sUA ≥ 8 mg/ dl. Data sources: Electronic searches through COCHRANE, EMBASE, PUBMED, and Manual Search. Search terms included the following: febuxostat, allopurinol, hyperuricemia, gout. Study Selection: Randomized, double-blinded, parallelgroup clinical trials with meta-analysis quality scale of A-B were included. Intervention included administration of febuxostat and allopurinol in determined dosages and duration in each study. Analysis: All outcomes were examined using the random effects model. Dichotomous data were analyzed by calculating the odds ratio, with 95% confidence interval and a significant p value of 0.1 was used. Results: Pooled data showed significant decrease in sUA level from baseline with febuxostat 80 mg than with allopurinol with OR 0.31 (95% CI, 0.24-0.39, p = 0.00001). The risk of developing any adverse event with allopurinol is greater compared to febuxostat with RR 0.90 (95% CI, 0.84-0.96, p = 0.002). Conclusion: Febuxostat has significant urate lowering efficacy than allopurinol, and in patients with renal impairment without requiring dose adjustment, with lower incidence of any adverse events. However, elevated liver enzymes brought about by febuxostat were noted. Keywords: Allopurinol, Febuxsostat, serum uric acid, hyperuricemia, gout Abstract Background of the Stud

Routine Assessment of Surgical Resident Wellness-Related Concerns During Biannual Review

Background: Surgery residency confers stress burdens on trainees. To monitor and mitigate areas of concerns, our education team implemented a six-item biannual survey querying potential stressors. We reviewed the initial five-year experience to assess for trends and improve efforts in maintaining well-being. Methods: Surgery residents from all postgraduate years were asked to complete a survey of common concerns, prioritizing them in order of importance. Ranked items were 1) needs of family/friends, 2) nonwork time for study, 3) financial concerns, 4) personal well-being needs, 5) concerns for clinical performance, and 6) administrative demands. Changes were trended over ten review periods. Results were analyzed using Kruskal-Wallis test. Results: 333 surveys were completed, rendering a 96.5% completion rate. Rankings changed significantly for nonwork time for study (p=0.04), personal well-being needs (p=0.03) and concerns for clinical performance (p=0.004). Nonwork time for study and concerns on clinical performance were consistently ranked as top two stressors over study period, except for Spring 2020. Personal well-being needs ranked highest in Spring 2020; 41% of residents placed this as top two rankings. A decrease in concerns for clinical performance was observed in Spring 2020, corresponding to the COVID-19 pandemic emergency declaration. Conclusion: Surgery residents generally prioritized time for study and concerns for assessment of clinical performance as highest areas of concern. With the occurrence of a pandemic, increased prioritization of personal well-being was observed. Used routinely with biannual reviews, the survey was able to identify plausible changes in resident concerns. Determination of levels of actual stress and actual association with the pandemic requires additional study

Professional Education Toolkit for Management of Cancer Survivors​

https://openworks.mdanderson.org/edwk23/1002/thumbnail.jp

Exploring the smallest terrestrial planet: Dawn at Vesta

The Dawn mission is designed to map Vesta and Ceres from polar orbit for close to one year each. The ion-propelled Dawn spacecraft is illustrated in Figure 1. Dawn carries a framing camera with clear and color filters, a visible and infrared mapping spectrometer, a gamma ray and neutron spectrometer, and obtains radiometric data on the gravity field. The camera obtains stereo imagery from which a global shape and topography model are derived. The mapping spectrometer determines the mineral composition of the surface and the gamma and neutron spectrometer determines the elemental composition. As Dawn approaches Vesta, as illustrated in Figure 2, it measures the rotational characteristics of the body to determine the orientation of the rotation axis. This in turn determines when solar illumination reaches the north pole and when mapping can be completed. As shown in Figure 3, there are three science orbits: Survey at a radial distance of 3000 km and a period of 69 hr; high-altitude mapping at a radial distance of 950 km and a period of 12.3 hr; and low-altitude mapping at a radius of 465 km and a period of 4 hours. Vesta is the ultimate source of the HED meteorites from which much has been learned about their parent body. By the time of this presentation we will have surveyed the region around Vesta for moons, determined a much more accurate mass and rotation axis for Vesta, and have preliminary information on surface features and composition from the survey orbit