Faculty Bibliography

IDH1/2 mutations are early drivers present in diverse human cancer types arising in various tissue sites. IDH1/2 mutation is known to induce a global hypermethylator phenotype. However, the effects on DNA methylation across IDH mutant cancers and functionally different genome regions, remain unknown. We analyzed DNA methylation data from IDH1/2 mutant acute myeloid leukemia, oligodendroglioma, astrocytoma, solid papillary breast carcinoma with reverse polarity, sinonasal undifferentiated carcinoma and cholangiocarcinoma, which clustered by their embryonal origin. Hypermethylated common probes affect predominantly gene bodies while promoters in IDH1/2 mutant cancers remain unmethylated. Enhancers showed global hypermethylation, however commonly hypomethylated enhancers were associated with tissue differentiation and cell fate determination. We demonstrate that some chromosomes, chromosomal arms and chromosomal regions are more affected by IDH1/2 mutations while others remain resistant to IDH1/2 mutation induced methylation changes. Therefore IDH1/2 mutations have different methylation effect on different parts of the genome, which may be regulated by different mechanisms.

Antimicrobial-resistant (AMR) infections pose a major threat to global public health. Similar to other AMR pathogens, both historical and ongoing drug-resistant tuberculosis (TB) epidemics are characterized by transmission of a limited number of predominant Mycobacterium tuberculosis (Mtb) strains. Understanding how these predominant strains achieve sustained transmission, particularly during the critical period before they are detected via clinical or public health surveillance, can inform strategies for prevention and containment. In this study, we employ whole-genome sequence (WGS) data from TB clinical isolates collected in KwaZulu-Natal, South Africa to examine the pre-detection history of a successful strain of extensively drug-resistant (XDR) TB known as LAM4/KZN, first identified in a widely reported cluster of cases in 2005. We identify marked expansion of this strain concurrent with the onset of the generalized HIV epidemic 12 y prior to 2005, localize its geographic origin to a location in northeastern KwaZulu-Natal ∼400 km away from the site of the 2005 outbreak, and use protein structural modeling to propose a mechanism for how strain-specific rpoB mutations offset fitness costs associated with rifampin resistance in LAM4/KZN. Our findings highlight the importance of HIV coinfection, high preexisting rates of drug-resistant TB, human migration, and pathoadaptive evolution in the emergence and dispersal of this critical public health threat. We propose that integrating whole-genome sequencing into routine public health surveillance can enable the early detection and local containment of AMR pathogens before they achieve widespread dispersal.

BACKGROUND:While Medicare is a federal health insurance program, managed Medicare limits access to healthcare services to networks within states or territories. However, if a natural disaster requires evacuation, displaced patients are at risk of losing coverage for their benefits. Previous literature has discussed the quality of managed Medicare plans within Puerto Rico but has not addressed the adequacy of this coverage if residents are displaced to the continental United States. We explore Hurricane Maria's impact on a resident of Puerto Rico with chronic health problems, and the challenges he faces seeking healthcare in New York. CASE PRESENTATION/METHODS:A 59-year-old male with a history of diabetes mellitus type II, coronary artery disease, peripheral vascular disease status post right foot amputation, and end-stage kidney disease on hemodialysis was admitted in October of 2017 for chest pain and swelling of legs for 5 days. The patient had missed his last three dialysis sessions after Hurricane Maria forced him to leave Puerto Rico. In examining this patient's treatment, we observe the effect of Hurricane Maria on the medical management of Puerto Rican residents and identify challenges managed Medicare may pose to patients who cross state or territory lines. CONCLUSIONS:We employ this patient's narrative to frame a larger discussion of Puerto Rican managed Medicare and provide additional recommendations for healthcare providers. Moreover, we consider this case in the context of disaster-related continuity of care for patients with complex medical conditions or treatment regimens. To address the gaps in the care of these patients, this article proposes (1) developing system-based approaches for screening displaced patients, (2) increasing the awareness of Special Enrollment Periods related to Medicare among healthcare providers, and (3) creating policy solutions to assure access to care for patients with complex medical conditions.

To meet the United Nations Sustainable Development Goals (SDGs) in the United States, research by nurses and midwives has a real opportunity to make a significant impact. This paper identifies opportunities to strengthen research capacity in the United States amongst nurses and midwives in ways that will help meet the SDGs and ensure its sustainability. Research capacity means that in a country, there are individuals and teams capable of defining problems, setting priorities, establishing objectives for the goals of the research study, and following rigorous scientific procedures. By strengthening U.S. research capacity by addressing critical weaknesses in content expertise, nursing and midwifery's voices in policy dialogues, and global research initiatives will be have greater assurance of being included.

OBJECTIVES/OBJECTIVE:To determine whether biomarkers of endothelial activation and inflammation provide added value for prediction of in-hospital mortality within 28 days when combined with physician judgment in critically ill emergency department patients. DESIGN/METHODS:Prospective, observational study. SETTING/METHODS:Two urban, academic emergency departments, with ≈80,000 combined annual visits, between June 2016 and December 2017. PATIENTS/METHODS:Admitted patients, greater than 17 years old, with two systemic inflammatory response syndrome criteria and organ dysfunction, systolic blood pressure less than 90 mm Hg, or lactate greater than 4.0 mmol/L. Patients with trauma, intracranial hemorrhage known prior to arrival, or without available blood samples were excluded. INTERVENTIONS/METHODS:Emergency department physicians reported likelihood of in-hospital mortality (0-100%) by survey at hospital admission. Remnant EDTA blood samples, drawn during the emergency department stay, were used to measure angiopoietin-1, angiopoietin-2, tumor necrosis factor receptor-1, interleukin-6, and interleukin-8. MEASUREMENTS AND MAIN RESULTS/RESULTS:We screened 421 patients and enrolled 314. The primary outcome of in-hospital mortality within 28 days occurred in 31 (9.9%). When predicting the primary outcome, the best biomarker model included angiopoietin-2 and interleukin-6 and performed moderately well (area under the curve, 0.72; 95% CI, 0.69-0.75), as did physician judgment (area under the curve, 0.78; 95% CI, 0.74-0.82). Combining physician judgment and biomarker models improved performance (area under the curve, 0.85; 95% CI, 0.82-0.87), with area under the curve change of 0.06 (95% CI, 0.04-0.09; p < 0.01) compared with physician judgment alone. CONCLUSIONS:Predicting in-hospital mortality within 28 days among critically ill emergency department patients may be improved by including biomarkers of endothelial activation and inflammation in combination with emergency department physician judgment.

PURPOSE/OBJECTIVE:To develop natural language processing (NLP) to identify incidental lung nodules (ILNs) in radiology reports for assessment of management recommendations. METHOD AND MATERIALS/METHODS:We searched the electronic health records for patients who underwent chest CT during 2014 and 2017, before and after implementation of a department-wide dictation macro of the Fleischner Society recommendations. We randomly selected 950 unstructured chest CT reports and reviewed manually for ILNs. An NLP tool was trained and validated against the manually reviewed set, for the task of automated detection of ILNs with exclusion of previously known or definitively benign nodules. For ILNs found in the training and validation sets, we assessed whether reported management recommendations agreed with Fleischner Society guidelines. The guideline concordance of management recommendations was compared between 2014 and 2017. RESULTS:The NLP tool identified ILNs with sensitivity and specificity of 91.1% and 82.2%, respectively, in the validation set. Positive and negative predictive values were 59.7% and 97.0%. In reports of ILNs in the training and validation sets before versus after introduction of a Fleischner reporting macro, there was no difference in the proportion of reports with ILNs (108 of 500 [21.6%] versus 101 of 450 [22.4%]; P = .8), or in the proportion of reports with ILNs containing follow-up recommendations (75 of 108 [69.4%] versus 80 of 101 [79.2%]; P = .2]. Rates of recommendation guideline concordance were not significantly different before and after implementation of the standardized macro (52 of 75 [69.3%] versus 60 of 80 [75.0%]; P = .43). CONCLUSION/CONCLUSIONS:NLP reliably automates identification of ILNs in unstructured reports, pertinent to quality improvement efforts for ILN management.

Serum amylase testing is not recommended for the workup of acute pancreatitis; yet it is commonly ordered in acute care settings. METHODS: This was a student-led quality improvement initiative with application of a pre-post study design at two urban hospitals: Mount Sinai Hospital, a 1,134-bed academic hospital, and Mount Sinai Queens, a 235-bed community hospital. The multifaceted intervention combined a targeted educational and awareness campaign with the decoupling of amylase from electronic order sets (at the academic hospital only), as well as a nonintrusive electronic medical record (EMR) advisory statement (at both hospitals). Monthly amylase orders were tracked for all emergency department visits and hospital admissions between January 2016 and May 2018 for both hospitals RESULTS: There was a significant and sustained decrease in amylase ordering at both the academic hospital (from 3,214 orders per month to 2,348 orders per month; p = 0.011) and the community hospital (from 100 orders per month to 23 orders per month; p = 0.001). Specifically, the nonintrusive EMR order advisory statement was independently associated with a significant reduction in serum amylase ordering. There was an estimated net annual cost reduction of $44,999. CONCLUSIONS: This student-led initiative was successful in reducing unnecessary amylase ordering across two diverse institutions through a combination of education, publicity, and EMR changes.