Faculty Bibliography

Minimal residual disease (MRD) tracking by next generation sequencing of immunoglobulin sequences is moving towards clinical implementation in multiple myeloma. However, there is only sparse information available to address whether clonal sequences remain stable for tracking over time, and to what extent light chain sequences are sufficiently unique for tracking. Here, we analyzed immunoglobulin repertoires from 905 plasma cell myeloma and healthy control samples, focusing on the third complementarity determining region (CDR3). Clonal heavy and/or light chain expression was identified in all patients at baseline, with one or more subclones related to the main clone in 3.2 %. In 45 patients with 101 sequential samples, the dominant clonal CDR3 sequences remained identical over time despite differential clonal evolution by whole exome sequencing in 49 % of patients. The low frequency of subclonal CDR3 variants and absence of evolution over time in active multiple myeloma indicates that tumor cells at this stage are not under selective pressure to undergo antibody affinity maturation. Next, we establish somatic hypermutation and non-templated insertions as the most important determinants of light chain clonal uniqueness, identifying a potentially trackable sequence in the majority of patients. Taken together, we show that dominant clonal sequences identified at baseline are reliable biomarkers for long-term tracking of the malignant clone, including both IGH and the majority of light chain clones. This article is protected by copyright. All rights reserved.

Curricular revision efforts have resulted in learner-centered programs that value content integration and active learning. Yet, less attention has been placed on assessment methods that are learner-centered and promote assessment for learning. The use of context rich short answer question (CR-SAQ) exams in the preclinical years of medical school was evaluated to determine if this format aligns with the criteria for assessment for learning. Medical students and preclinical faculty members were sent a survey comprised of closed and open-ended questions about their experience using CR-SAQ exams. Data were analyzed using a mixed-method design. Open-ended responses were evaluated using thematic analysis within the framework of criteria for assessment for learning. A total of 274 students (94%) and 24 faculty (75%) completed the survey. Fifty four percent of students reported preferring a CR-SAQ exam format over multiple choice questions (MCQ) format. Quantitative data and qualitative comments by students supported that CR-SAQ exams aligned with criteria for assessment for learning, including acceptability, authenticity, educational effect, and the cueing effect. Student concerns included preparation for USMLE Step 1 exam, as well as the validity and reproducibility of CR-SAQ assessments. Faculty largely agreed with the benefits of the CR-SAQ, but were concerned about feasibility, acceptability and reproducibility. The CR-SAQ exam format assessment strategy supports assessment for learning in an undergraduate medical education setting. Both benefits and drawbacks of this method are presented, however students and faculty describe a broader impact that this assessment method has on their development as a physician.

OBJECTIVE:To determine if World Trade Center (WTC) exposure is associated with hearing loss. METHODS:Logistic regression to evaluate the immediate impact of WTC exposure and parametric survival analysis to assess longitudinal outcomes. RESULTS:Those arriving on the morning of 9/11/2001 had elevated odds of low-frequency (odds ratio [OR]: 1.24;95%CI:1.04-1.47) and high-frequency (OR:1.16;95%CI:1.02-1.31) hearing loss at their first post-9/11/2001 exam. Longitudinally, participants arriving before 9/13/2001 and spending ≥6 months at the WTC-site had greater risk of hearing loss in the low frequencies (risk ratio [RR]:1.31;95%CI:1.05-1.60) and high frequencies (RR:1.37;95%CI:1.22-1.54). By 2016, 3,194 (37%) had abnormal hearing sensitivity in either ear and 1,751 (20%) in both ears. CONCLUSIONS:More heavily WTC-exposed workers were at increased risk of hearing loss, and group differences persisted for at least 15 years. Those with abnormal hearing sensitivity may benefit from interventions such as hearing aids and other rehabilitation.

The phase of entrainment (chronotype) is known to be associated with time perspective (TP), suggesting that the state of circadian system is involved in the long-term planning of human life. However, little is known regarding the influence of circadian misalignment on long-term planning ability. The aim of this study was to investigate the association between social jetlag (SJL) and TP. A total of 1064 schoolchildren and university students (mean age ± standard deviation, 19.2 ± 2.9 years; range, 15-25 years; females, 71.7%) from four cities in the Russian Federation located between 56.9 and 61.7 degrees North completed the Munich ChronoType Questionnaire, the Pittsburgh Sleep Quality Index, the Seasonal Pattern Assessment Questionnaire, and Zimbardo Time Perspective Inventory. Study participants also indicated personal data (age, sex, height weight, place of residence, and achievements). A multiple regression analysis with stepwise inclusion of predictors in the model was performed to evaluate associations between time perspective characteristics (dependent variables) and predictor variables. The change in R² was used as the measure of effect size. Chronotype was found to be a moderate predictor of future TP (B = 0.034; ΔR²Â = 0.037). In addition, sleep quality was found to be a moderate predictor of past negative (B = 0.043; ΔR²Â = 0.074), present fatalistic (B = 0.021; ΔR²Â = 0.035), and deviation from balanced TP (B = 0.034; ΔR²Â = 0.066). Mood seasonality was a moderate predictor of present hedonistic TP (B = 0.016; ΔR²Â = 0.038), and social jetlag was a weak predictor of present fatalistic (B = 0.052; ΔR²Â = 0.019), future (B = -0.033; ΔR²Â = 0.004), and deviation from balanced TP (B = 0.047; ΔR²Â = 0.012). In conclusion, this study found a weak but significant association between social jetlag and TP in adolescents and young adults.

BACKGROUND:Visceral infarctions appear to be more common in patients with embolic stroke subtypes, but their relation to troponin elevation remains uncertain. METHODS:Among patients with acute ischemic stroke enrolled in the Cornell AcutE Stroke Academic Registry (CAESAR) from 2011 to 2016, we included those with troponin measured within 24 hours from stroke onset and a contrast-enhanced abdominal computed tomographic scan within 1 year of admission. A troponin elevation was defined as a value exceeding our laboratory's upper limit of normal (.04 ng/ mL) in the absence of a clinically recognized acute ST-segment elevation myocardial infarction. Visceral infarction was defined as a renal or splenic infarction as ascertained by a single radiologist blinded to patients' other characteristics. Multivariable logistic regression was used to evaluate the association between elevated troponin and visceral infarction. RESULTS:Among 2116 patients registered in CAESAR from 2011 to 2016, 153 patients had both a troponin assay and a contrast-enhanced abdominal computed tomographic scan, of whom 33 (21%) had an elevated troponin and 22 (14%) had a visceral infarction. The prevalence of visceral infarction was higher among patients with an elevated troponin (30%; 95% confidence interval [CI], 16%-49%) than among patients without an elevated troponin (10%; 95% CI, 5%-17%) (P = .003). After adjustment for demographics and comorbidities, we found a significant association between elevated troponin and visceral infarction (odds ratio, 3.9; 95% CI, 1.5-10.4). CONCLUSIONS:Among patients with acute ischemic stroke, elevated troponin was associated with visceral infarction. Our results demonstrate that poststroke troponin elevation may indicate the presence of underlying embolic sources.

OBJECTIVES/OBJECTIVE:Assess Staphylococcus aureus (S. aureus) colonization in healthy Australian adults receiving an investigational S. aureus 3-antigen vaccine (SA3Ag). METHODS:In this phase 1, double-blind, sponsor-unblinded study, participants were randomized to receive a single dose (1 of 3 dose levels) of SA3Ag or placebo and a booster dose or placebo at 6 months. S. aureus isolates from nasal, perineal, and oropharyngeal swabs before and through 12 months post-vaccination were identified. RESULTS:Baseline S. aureus colonization prevalence was 30.6% (any site), with nasal carriage (27.0%) more common than oropharyngeal/perineal (3.2% each). Following initial vaccination (low-dose:102; mid-dose:101; high-dose:101; placebo:102) and booster (low-dose:45; mid-dose:44; high-dose:27; placebo:181), placebo and SA3Ag groups showed similar S. aureus carriage through 12 months. Most colonized participants (74.0%) were colonized by single spa types. Placebo and SA3Ag groups had similar persistence of colonization, with 19.6-30.7% due to single spa types. Acquisition was observed in mid- and high-dose recipients (∼20%) and low-dose and placebo recipients (∼12%). Vaccination resulted in substantial increases in antibodies to all 3 antigens, irrespective of carriage status. CONCLUSIONS:Based on descriptive analyses of this small study, SA3Ag vaccination did not impact S. aureus acquisition or carriage. Carriage status did not impact antibody responses to SA3Ag.

BACKGROUND:Gastrointestinal symptoms are prevalent in patients with cirrhosis. Cirrhotic patients have a known predilection to delayed gastric emptying compared to those without cirrhosis. However, the contributing factors have not been fully elucidated. Retained gastric food on esophagogastroduodenoscopy (EGD) has been used as a surrogate marker for delayed gastric emptying with reasonably high specificity. Therefore, we hypothesize that the frequency of retained gastric food contents at EGD will be higher in a cirrhotic population compared to a control population without liver disease. Additionally, we hypothesize that increased frequency of gastric food contents will be associated with increased severity of cirrhosis. AIM/OBJECTIVE:To determine the relative frequency of delayed gastric emptying among cirrhotics as compared to non-cirrhotics and to identify associated factors. METHODS:We performed a retrospective case-control study of cirrhotic subjects who underwent EGD at an academic medical center between 2000 and 2015. Three hundred sixty-four patients with confirmed cirrhosis, who underwent a total of 1044 EGDs for the indication of esophageal variceal screening or surveillance, were identified. During the same period, 519 control patients without liver disease, who underwent a total of 881 EGDs for the indication of anemia, were identified. The presence of retained food on EGD was used as a surrogate for delayed gastric emptying. The relative frequency of delayed gastric emptying among cirrhotics was compared to non-cirrhotics. Characteristics of patients with and without retained food on EGD were compared using univariable and multivariable logistic regression analysis to identify associated factors. RESULTS:0.01) were also associated with a higher likelihood of food retention on EGD. CONCLUSION/CONCLUSIONS:Cirrhotics have a higher frequency of retained food at EGD than non-cirrhotics. Decompensated cirrhosis, defined by Child-Pugh class C, is associated with a higher likelihood of delayed gastric emptying.