Student Abstract Competition

Articlehttp://deepblue.lib.umich.edu/bitstream/2027.42/97000/1/UMURJ-Issue07_2010-StudentAbstractCompetition.pd

University of Michigan Undergraduate Research Journal, Issue 7, Winter 2010

Articlehttp://deepblue.lib.umich.edu/bitstream/2027.42/97002/1/UMURJ-Issue07_2010.pd

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Crash Characteristics for Classic/Historic Vehicles and Comparisons to Newer Vehicles

Introduction: Older vehicles, commonly referred to as “classic,” “vintage,” or “historic” vehicles (CVH), share the roadways with newer vehicles. Older vehicles lacking safety systems likely come with an increased risk of fatality, however there is no study examining the typical conditions for crashes involving CVH. Method: This study utilized information from crashes occurring in 2012 to 2019 to estimate fatal crash rates for vehicles grouped by model year deciles. Data from crashes documented in the National Highway Traffic Safety Administration’s (NHTSA) FARS and GES/CRSS data sets were utilized to examine roadway, temporal, and crash types for passenger vehicles produced in 1970 or earlier (CVH). Results: These data show CVH crashes are rare (\u3c1% of crashes), but carry a relative risk of fatality from 6.70 (95th CI: 5.44–8.26) for impacts with other vehicles, which was the most common crash, to 9.53 (7.28–12.47) for rollovers. Most crashes occurred in dry weather, typically during summer, in rural areas, most frequently on two lane roads, and in areas with speed limits between 30 and 55 mph. Factors associated with fatality for occupants in CVH included alcohol use, lack of seat belt use, and older age. Conclusions and Practical Applications: Crashes involving a CVH are a rare event but have catastrophic consequences when they do occur. Regulations that limit driving to daylight hours may lower the risk of crash involvement, and safety messaging to promote belt use and sober driving may also help. Additionally, as new “smart” vehicles are developed, engineers should keep in mind that older vehicles remain on the roadway. New driving technologies will need to safely interact with these older, less safe vehicles

Why Do Patients Choose Skilled Nursing Facilities After Total Hip and Knee Arthroplasty?

Background Current research indicates that total joint arthroplasty patients who are discharged to skilled nursing facilities (SNFs) have higher complication rates as compared to home. Many factors like age, sex, race, Medicare status, and past medical history have been shown to influence discharge destination. The present study sought to gather patient-indicated reasons for SNF discharge and identify potentially modifiable factors influencing the decision. Methods Primary total joint arthroplasty patients were asked to complete surveys at their presurgical and 2-week postsurgical follow-up appointments. The surveys included home access and social support questions as well as patient-reported outcome measures: Patient-Reported Outcomes Measurement and Information System, Risk Assessment and Prediction Tool, Knee injury and Osteoarthritis Outcome Score for Joint Replacement, or Hip dysfunction and Osteoarthritis Outcome Score for Joint Replacement. Results Of 765 patients who met inclusion criteria, 3.9% were discharged to an SNF and these were more frequently post-THA, women, older, Black, and persons living alone. Regression analyses indicated that lower Risk Assessment and Prediction Tool score, higher age, no caregiver presence, and Black race were significantly associated with SNF discharge. Patients discharged to an SNF most commonly reported social concerns rather than medical or home access concerns as the main factor for SNF discharge. Conclusions While age and sex are nonmodifiable factors, the availability of a caregiver and social support represents an important modifiable factor in regard to discharge destination. Dedicated attention during the preoperative planning period may help augment social support and avoid unnecessary discharges to SNFs

SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers

We identify a gene, SLC5A8, and show it is a candidate tumor suppressor gene whose silencing by aberrant methylation is a common and early event in human colon neoplasia. Aberrant DNA methylation has been implicated as a component of an epigenetic mechanism that silences genes in human cancers. Using restriction landmark genome scanning, we performed a global search to identify genes that would be aberrantly methylated at high frequency in human colon cancer. From among 1,231 genomic NotI sites assayed, site 3D41 was identified as methylated in 11 of 12 colon cancers profiled. Site 3D41 mapped to exon 1 of SLC5A8, a transcript that we assembled. In normal colon mucosa we found that SLC5A8 exon 1 is unmethylated and SLC5A8 transcript is expressed. In contrast, SLC5A8 exon 1 proved to be aberrantly methylated in 59% of primary colon cancers and 52% of colon cancer cell lines. SLC5A8 exon 1 methylated cells were uniformly silenced for SLC5A8 expression, but reactivated expression on treatment with a demethylating drug, 5-azacytidine. Transfection of SLC5A8 suppressed colony growth in each of three SLC5A8-deficient cell lines, but showed no suppressive effect in any of three SLC5A8-proficient cell lines. SLC5A8 exon 1 methylation is an early event, detectable in colon adenomas, and in even earlier microscopic colonic aberrant crypt foci. Structural homology and functional testing demonstrated that SLC5A8 is a member of the family of sodium solute symporters, which are now added as a class of candidate colon cancer suppressor genes

Detection in fecal DNA of colon cancer-specific methylation of the nonexpressed vimentin gene

Increased DNA methylation is an epigenetic alteration that is common in human cancers and is often associated with transcriptional silencing. Aberrantly methylated DNA has also been proposed as a potential tumor marker. However, genes such as vimentin, which are transcriptionally silent in normal epithelium, have not until now been considered as targets for cancer-associated aberrant methylation and for use as cancer markers. We applied methylation-specific polymerase chain reaction to the vimentin gene, which is transcriptionally silent in normal colonocytes, and compared methylation of vimentin exon 1 in cancer tissues and in fecal DNA from colon cancer patients versus control samples from healthy subjects. Vimentin exon-1 sequences were unmethylated in 45 of 46 normal colon tissues. In contrast, vimentin exon-1 sequences were methylated in 83% (38 of 46) and 53% (57 of 107) of tumors from two independently collected groups of colon cancer patients. When evaluated as a marker for colon cancer detection in fecal DNA from another set of colon cancer patients, aberrant vimentin methylation was detected in fecal DNA from 43 of 94 patients, for a sensitivity of 46% (95% confidence interval [CI] = 35% to 56%). The sensitivity for detecting stage I and II cancers was 43% (26 of 60 case patients) (95% CI = 31% to 57%). Only 10% (20 of 198 case patients) of control fecal DNA samples from cancer-free individuals tested positive for vimentin methylation, for a specificity of 90% (95% CI = 85% to 94%). Aberrant methylation of exon-1 sequences within the nontranscribed vimentin gene is a novel molecular biomarker of colon cancer and can be successfully detected in fecal DNA to identify nearly half of individuals with colon cancer