Faculty Bibliography

Introduction Neuroendocrine tumors (NETs), once considered a rare malignancy, has started to become a more common cancer within the United States (US). Given the limited data available on the incidence of NETs in the entire US population, our goal in this study was to investigate the incidence of NETs in at-risk populations in all 50 states. Methods The United States Cancer Statistics (USCS) was used to obtain data for NETs from 2001 to 2015. An incidence analysis was done for sex, race, stage, primary location within the gastrointestinal (GI) tract, and US regional location. Results The overall incidence of NETs from 2001 to 2015 was 2.89 per 100,000 people per year. The overall incidence rates were the greatest for each stratification of males, blacks, localized disease, primary location in the small intestine, and in the Northeast. The incidence in males between 2013 and 2015 increased with an annual percent change (APC) of 8.44. Between 2006 and 2015, the incidence in blacks increased with an APC of 1.89. Between 2013 and 2015, the incidence of localized disease and a primary location in the small intestine increased with an APC of 16.89 and 14.37, respectively. In the Northeast, between 2013 and 2015, the incidence increased with an APC of 11.09. Conclusion In this study, we investigated the incidence of NETs using data obtained from the USCS database, which covers all 50 states. We found that there is a rising incidence in most subpopulations possibly related to improved compliance with surveillance colonoscopies and improved endoscopic and radiographic techniques. Further studies are needed to ultimately determine the exact causes of our findings. However, our study will serve as an important first step to determine the exact etiology for the rising incidence of NETs in all 50 states.

BACKGROUND:Gastrointestinal endoscopies are safe and follow guidelines that emphasize patient care. Although adverse outcomes are rare, high-risk patients may be predisposed to certain events. CASE PRESENTATION/METHODS:We report a unique case of a Caucasian woman with takotsubo cardiomyopathy following an upper and lower endoscopy. CONCLUSIONS:Our report suggests the importance of understanding possible endoscopic complications in patients who may experience stress cardiomyopathy.

BACKGROUND:Heart failure (HF) is a syndrome associated with exercise intolerance, and its symptoms are more common in patients with low skeletal muscle mass (SMM). Estimation of muscle mass can be cumbersome and unreliable, particularly in patients with varying body weight. The psoas muscle area (PMA) can be used as a surrogate of sarcopenia and has been associated with poor outcomes in other populations. OBJECTIVES/OBJECTIVE:The aim of this study was to assess if sarcopenia is associated with the survival of patients with HF after an acute hospitalization. METHOD/METHODS:We retrospectively studied a cohort of 160 patients with HF who had abdominopelvic computed tomography during an acute hospitalization. We obtained standardized measurements of their PMA and defined sarcopenia as the lowest gender-based tertile of the said area. The patients were followed until death or discontinuation of care. We used Kaplan-Meier estimates and Cox regression analysis to assess the relationship between sarcopenia and all-cause mortality. RESULTS:We found that the 52 patients with sarcopenia had 4.5 times the risk of all-cause mortality at 1 year compared to the rest of the cohort (CI 1.784-11.765; p = 0.0016) after adjusting for significant covariates. Stratification by age and sex revealed that this association could be limited to males and patients < 75 years old. CONCLUSION/CONCLUSIONS:The PMA, used as a surrogate of low SMM, is independently associated with an increased risk of late mortality after an acute hospitalization in patients with HF.

Background/UNASSIGNED:Clostridium difficile infection (CDI) is common in patients with inflammatory bowel disease (IBD), often leading to diagnostic confusion and delays in IBD therapy escalation. This study sought to assess outcomes after CDI in IBD patients exposed to new or escalated immunosuppressive therapy. Methods/UNASSIGNED:This multicenter retrospective cohort study included IBD patients with documented CDI at 4 academic medical centers. Data were abstracted from clinical databases at each institution. Outcomes at 30 and 90 days were compared between patients undergoing new or intensified immunosuppressive therapy and those without therapy escalation. Continuous variables were compared using t tests, and proportions using chi-square tests. Multivariable logistic regression was used to determine the association of individual variables with severe outcomes (including death, sepsis, and/or colectomy) within 90 days. Secondary outcomes included CDI recurrence, rehospitalization, worsening of IBD, and severe outcomes within 30 days. Results/UNASSIGNED:A total of 207 adult patients with IBD and CDI were included, of whom 62 underwent escalation to biologic or corticosteroid therapy (median time to escalation, 13 days). Severe outcomes within 90 days occurred in 21 (15.6%) nonescalated and 1 (1.8%) therapy-escalated patients. Serum albumin <2.5 mg/dL, lactate >2.2 mg/dL, intensive care unit admission, hypotension, and comorbid disease were associated with severe outcomes. Likelihood of severe outcomes was decreased in patients undergoing escalation of IBD therapy after CDI (adjusted odds ratio [aOR], 0.12) and increased among patients aged >65 years (aOR, 4.55). Conclusions/UNASSIGNED:Therapy escalation for IBD within 90 days of CDI was not associated with worse clinical outcomes. Initiation of immunosuppression for active IBD may therefore be appropriate in carefully selected patients after treatment of CDI.

A diverse, antibiotic-naive microbiota prevents highly antibiotic-resistant microbes, including carbapenem-resistant Klebsiella pneumoniae (CR-Kp), from achieving dense colonization of the intestinal lumen. Antibiotic-mediated destruction of the microbiota leads to expansion of CR-Kp in the gut, markedly increasing the risk of bacteremia in vulnerable patients. While preventing dense colonization represents a rational approach to reduce intra- and interpatient dissemination of CR-Kp, little is known about pathogen-associated factors that enable dense growth and persistence in the intestinal lumen. To identify genetic factors essential for dense colonization of the gut by CR-Kp, we constructed a highly saturated transposon mutant library with >150,000 unique mutations in an ST258 strain of CR-Kp and screened for in vitro growth and in vivo intestinal colonization in antibiotic-treated mice. Stochastic and partially reversible fluctuations in the representation of different mutations during dense colonization revealed the dynamic nature of intestinal microbial populations. We identified genes that are crucial for early and late stages of dense gut colonization and confirmed their role by testing isogenic mutants in in vivo competition assays with wild-type CR-Kp Screening of the transposon library also identified mutations that enhanced in vivo CR-Kp growth. These newly identified colonization factors may provide novel therapeutic opportunities to reduce intestinal colonization by CR-KpIMPORTANCEKlebsiella pneumoniae is a common cause of bloodstream infections in immunocompromised and hospitalized patients, and over the last 2 decades, some strains have acquired resistance to nearly all available antibiotics, including broad-spectrum carbapenems. The U.S. Centers for Disease Control and Prevention has listed carbapenem-resistant K. pneumoniae (CR-Kp) as an urgent public health threat. Dense colonization of the intestine by CR-Kp and other antibiotic-resistant bacteria is associated with an increased risk of bacteremia. Reducing the density of gut colonization by CR-Kp is likely to reduce their transmission from patient to patient in health care facilities as well as systemic infections. How CR-Kp expands and persists in the gut lumen, however, is poorly understood. Herein, we generated a highly saturated mutant library in a multidrug-resistant K. pneumoniae strain and identified genetic factors that are associated with dense gut colonization by K. pneumoniae This study sheds light on host colonization by K. pneumoniae and identifies potential colonization factors that contribute to high-density persistence of K. pneumoniae in the intestine.

Multidrug-resistant (MDR) Acinetobacter spp. poses a significant therapeutic challenge in part due to the presence of chromosomally encoded β-lactamases, including class C Acinetobacter-derived cephalosporinases (ADC) and class D oxacillinases (OXA), as well as plasmid-mediated class A β-lactamases. Importantly, OXA-like β-lactamases represent a gap in the spectrum of inhibition by recently approved β-lactamase inhibitors such as avibactam and vaborbactam. ETX2514 is a novel, rationally designed, diazabicyclooctenone inhibitor that effectively targets class A, C, and D β-lactamases. We show that addition of ETX2514 significantly increased the susceptibility of clinical Acinetobacterbaumannii isolates to sulbactam. AdeB and AdeJ were identified to be key efflux constituents for ETX2514 in A. baumannii The combination of sulbactam and ETX2514 was efficacious against A. baumannii carrying bla_TEM-1, bla_ADC-82, bla_OXA-23, and bla_OXA-66 in a neutropenic murine thigh infection model. We also show that, in vitro, ETX2514 inhibited ADC-7 (k₂/K_i 1.0 ± 0.1 × 10⁶ M^-1 s^-1) and OXA-58 (k₂/K_i 2.5 ± 0.3 × 10⁵ M^-1 s^-1). Cocrystallization of ETX2514 with OXA-24/40 revealed hydrogen bonding interactions between ETX2514 and residues R261, S219, and S128 of OXA-24/40 in addition to a chloride ion occupied in the active site. Further, the C3 methyl group of ETX2514 shifts the position of M223. In conclusion, the sulbactam-ETX2514 combination possesses a broadened inhibitory range to include class D β-lactamases as well as class A and C β-lactamases and is a promising therapeutic candidate for infections caused by MDR Acinetobacter spp.IMPORTANCE The number and diversity of β-lactamases are steadily increasing. The emergence of β-lactamases that hydrolyze carbapenems poses a significant threat to our antibiotic armamentarium. The explosion of OXA enzymes that are carbapenem hydrolyzers is a major challenge (carbapenem-hydrolyzing class D [CHD]). An urgent need exists to discover β-lactamase inhibitors with class D activity. The sulbactam-ETX2514 combination demonstrates the potential to become a treatment regimen of choice for Acinetobacter spp. producing class D β-lactamases.

Background: To foster patient engagement and trust, cardiovascular procedural informed consent (IC) discussions must go beyond the routine of risks vs benefits and incorporate shared decision making (SDM). Most trainees report learning the IC process through peer observation with little emphasis on skills that enable SDM. Experiential learning with immediate faculty feedback may make it more likely that fellows incorporate these critical advanced skills into their IC practice. Method(s): We developed 3 observed structured clinical examination (OSCE) cases designed to highlight all aspects of the IC discussion for invasive cardiac procedures. We adapted validated standardized patient checklists and created a faculty observation and feedback tool. After the program, fellows completed a survey assessing the likelihood they would incorporate SDM skills into their practice. Result(s): 28 cardiology fellows successfully completed the IC OSCE. Figure 1 demonstrates that while the majority of fellows reported already routinely discussing risks and alternatives a minority reported using patient engagement skills. The majority reported they are very likely to incorporate these assessments into practice. Conclusion(s): Cardiology fellows participating in this formative IC OSCE identified SDM skills they intend to incorporate into their IC discussion practice. The clinical impact of teaching high level learners important patient engagement skills via this approach should be further studied. [Figure presented]2019 American College of Cardiology Foundation. All rights reserved