Faculty Bibliography

Combating plasmid-mediated carbapenem resistance is essential to control and prevent the dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Here we conducted a proof-of-concept study to demonstrate CRISPR/Cas9-mediated resistance gene and plasmid curing can effectively re-sensitize CRE to carbapenems. A novel CRISPR/Cas9-mediated plasmid-curing system (pCasCure) was developed and electrotransferred into various clinical CRE isolates. The results showed that pCasCure can effectively cure bla_KPC, bla_NDM and bla_OXA-48 in various Enterobacteriaceae species of Klebsiella pneumoniae, Escherichia coli, Enterobacter hormaechei, E. xiangfangensis and Serratia marcescens clinical isolates, with > 94% curing efficiency. In addition, we also demonstrated that pCasCure can efficiently eliminate several epidemic carbapenem-resistant plasmids, including the bla_KPC-harboring IncFIIK-pKpQIL and IncN pKp58_N, bla_OXA-48-harboring pOXA-48-like, bla_NDM-harboring IncX3 plasmids, by targeting their replication and partitioning (parA in pKpQIL) genes. However, curing bla_OXA-48 gene failed to eliminate its corresponding pOXA-48-like plasmid in a clinical K. pneumoniae isolate 49210, while further next generation sequencing revealed that it was due to IS1R mediated recombination outside the CRISPR/Cas9 cleavage site, resulting in bla_OXA-48 truncation and therefor escaped plasmid curing. Nevertheless, the curing of carbapenemase genes or plasmids, including the truncation of bla_OXA-48 in 49210, successfully restore their susceptibility to carbapenems, with > 8-fold reduction of minimum inhibitory concentration (MIC) values in all tested isolates. Taken together, our study confirmed the concept of using CRISPR/Cas9-mediated carbapenemase genes and plasmids curing to re-sensitize CRE to carbapenems. Further work is needed to integrate pCasCure in an optimal delivery system to make it applicable for clinical intervention.

Cholangiocarcinoma is a highly lethal biliary epithelial tumor that is rare in the general population but has increased rates in patients with primary sclerosing cholangitis (PSC). It is heterogenous, and management varies by location. No effective prevention exists, and screening is likely only feasible in PSC. Patients often present in an advanced state with jaundice, weight loss, and cholestatic liver enzymes. Diagnosis requires imaging with magnetic resonance cholangiopancreatography, laboratory testing, and endoscopic retrograde cholangiopancreatography. Potentially curative options include resection and liver transplant with neoadjuvant or adjuvant chemoradiation. Chemotherapy, radiation, and locoregional therapy provide some survival benefit in unresectable disease.

BACKGROUND:The Home Delivered Meals Program (HDMP) serves a vulnerable population of adults aged 60 and older who may benefit from technological services to improve health and social connectedness. OBJECTIVE:The objectives of this study are (a) to better understand the needs of HDMP participants, and (b) to characterize the technology-readiness and the utility of delivering information via the computer. DESIGN/METHODS:We analyzed data from the 2017 NSOAAP to assess the health and functional status and demographic characteristics of HDMP participants. We also conducted a telephone survey to assess technology use and educational interests among NYC HDMP participants. MEASUREMENTS/METHODS:Functional measures of the national sample included comorbidities, recent hospitalizations, and ADL/IADL limitations. Participants from our local NYC sample completed a modified version of the validated Computer Proficiency Questionnaire. Technology readiness was assessed by levels of technology use, desired methods for receiving health information, and interest in learning more about virtual senior centers. RESULTS:About one-third (32.4%) of national survey HDMP participants (n=902) reported insufficient resources to buy food and 17.1% chose between food or medications. Within the NYC HDMP participant survey sample (n=33), over half reported having access to the internet (54.5%), 48.5% used a desktop or laptop, and 30.3% used a tablet, iPad, or smartphone. CONCLUSION/CONCLUSIONS:The HDMP provides an opportunity to reach vulnerable older adults and offer additional resources that can enhance social support and improve nutrition and health outcomes. Research is warranted to compare technological readiness of HDMP participants across urban and rural areas in the United States.

BACKGROUND:Medical Education research suffers from several methodological limitations including too many single institution, small sample-sized studies, limited access to quality data, and insufficient institutional support. Increasing calls for medical education outcome data and quality improvement research have highlighted a critical need for uniformly clean and easily accessible data. Research registries may fill this gap. In 2006, the Research on Medical Education Outcomes (ROMEO) unit of the Program for Medical Innovations and Research (PrMEIR) at New York University's (NYU) Robert I. Grossman School of Medicine established the Database for Research on Academic Medicine (DREAM). DREAM is a database of routinely collected, de-identified undergraduate (UME, medical school leading up to the Medical Doctor degree) and graduate medical education (GME, residency also known as post graduate education leading to eligibility for specialty board certification) outcomes data available, through application, to researchers. Learners are added to our database through annual consent sessions conducted at the start of educational training. Based on experience, we describe our methods in creating and maintaining DREAM to serve as a guide for institutions looking to build a new or scale up their medical education registry. RESULTS:At present, our UME and GME registries have consent rates of 90% (n = 1438/1598) and 76% (n = 1988/2627), respectively, with a combined rate of 81% (n = 3426/4225). 7% (n = 250/3426) of these learners completed both medical school and residency at our institution. DREAM has yielded a total of 61 individual studies conducted by medical education researchers and a total of 45 academic journal publications. CONCLUSION/CONCLUSIONS:We have built a community of practice through the building of DREAM and hope, by persisting in this work the full potential of this tool and the community will be realized. While researchers with access to the registry have focused primarily on curricular/ program evaluation, learner competency assessment, and measure validation, we hope to expand the output of the registry to include patient outcomes by linking learner educational and clinical performance across the UME-GME continuum and into independent practice. Future publications will reflect our efforts in reaching this goal and will highlight the long-term impact of our collaborative work.

Today's health care journalists work in a very different environment than those of yesterday. The demand for stories and broadcasts has grown exponentially, and the resources available have shrunk dramatically. While it may therefore be difficult to see how improvements in health care journalism are possible, let alone a way to improve health care literacy, there is an important connection that, if illuminated, could help both fields. To understand the literature on the quality of health care journalism, it is critical to understand the backgrounds of today's health care journalists and the challenges they face. That literature also goes hand in hand with studies of the effects that news coverage has on the public's understanding of health care issues. There are training and educational programs designed to help health care journalists do their jobs better, and this chapter concludes with a discussion of how cooperation between health journalists, physicians, and other stakeholders can lift all boats.

The objective of this study was to utilize a co-culture hollow-fiber infection model (HFIM) to characterize the interplay between a small, difficult-to-detect, New Delhi metallo-β-lactamase-producing Klebsiella pneumoniae (NDM-Kp) minor population and a larger K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae population in the presence of KPC-directed antibacterial therapy. Selective plating onto agar with ceftazidime-avibactam was used to track the density of the NDM-Kp population. Susceptibility testing and the Verigene System failed to identify the small initial NDM-Kp population. However, a ceftazidime-avibactam Etest detected resistant colonies that were confirmed to be NDM-Kp. In the HFIM, all of the investigated drug regimens caused regrowth within 24 h and resulted in >10⁹ CFU/mL of NDM-Kp. Our study demonstrates that the HFIM is a powerful tool for studying the population dynamics of multiple pathogens during antimicrobial exposure and also highlights that difficult-to-detect minor populations of drug-resistant bacteria may cause treatment failure without appropriate antibacterial therapy.