Faculty Bibliography

Carbapenem-resistant Enterobacteriaceae (CRE) are resistant to most antibiotics, making CRE infections extremely difficult to treat with available agents. Klebsiella pneumoniae carbapenemases (KPC-2 and KPC-3) are predominant carbapenemases in CRE in the United States. Nacubactam is a bridged diazabicyclooctane (DBO) β-lactamase inhibitor that inactivates class A and C β-lactamases and exhibits intrinsic antibiotic and β-lactam "enhancer" activity against Enterobacteriaceae In this study, we examined a collection of meropenem-resistant K. pneumoniae isolates carrying bla_KPC-2 or bla_KPC-3; meropenem-nacubactam restored susceptibility. Upon testing isogenic Escherichia coli strains producing KPC-2 variants with single-residue substitutions at important Ambler class A positions (K73, S130, R164, E166, N170, D179, K234, E276, etc.), the K234R variant increased the meropenem-nacubactam MIC compared to that for the strain producing KPC-2, without increasing the meropenem MIC. Correspondingly, nacubactam inhibited KPC-2 (apparent K_i [K_i app] = 31 ± 3 μM) more efficiently than the K234R variant (K_i app = 270 ± 27 μM) and displayed a faster acylation rate (k₂/K), which was 5,815 ± 582 M^-1 s^-1 for KPC-2 versus 247 ± 25 M^-1 s^-1 for the K234R variant. Unlike avibactam, timed mass spectrometry revealed an intact sulfate on nacubactam and a novel peak (+337 Da) with the K234R variant. Molecular modeling of the K234R variant showed significant catalytic residue (i.e., S70, K73, and S130) rearrangements that likely interfere with nacubactam binding and acylation. Nacubactam's aminoethoxy tail formed unproductive interactions with the K234R variant's active site. Molecular modeling and docking observations were consistent with the results of biochemical analyses. Overall, the meropenem-nacubactam combination is effective against carbapenem-resistant K. pneumoniae Moreover, our data suggest that β-lactamase inhibition by nacubactam proceeds through an alternative mechanism compared to that for avibactam.

Objectives: To identify predictors of pulmonary hypertension (PHT) and the predictive value of PHT for rehospitalization among patients with heart failure with reduced ejection fraction (HFrEF). Methods: A retrospective study of 351 hospitalized patients with heart failure (HF). Patients 18 years and above with HFrEF secondary to non-ischemic cardiomyopathy were reviewed. Patients with coronary artery disease, preserved ejection fraction and other secondary causes of PHT apart from HF were excluded. PHT as a predictor of 30-day and six-month re-admission was assessed as well as important possible predictors of PHT. Cox regression analysis, multiple linear regression as well as other statistical tools were employed as deemed appropriate. Results: Thirty-seven (37) and 99 patients were re-hospitalized within 30 days and 6 months after discharge for decompensated HF, respectively. After Cox regression analysis, higher hemoglobin reduced the odds of rehospitalization for decompensated HF (p = 0.015) within 30 days after discharge while higher pulmonary artery systolic pressure (PASP) (p = 0.002) and blood urea nitrogen (BUN) (p = 0.041) increased the odds of rehospitalization within 6 months of discharge. The predictors of the PHT among patients with HFrEF after multiple linear regression were low BMI (p = 0.027), increasing age (p = 0.006) and increased left atrial diameter (LAD) on echocardiography (p = 0.0001). Conclusion: Patients with HFrEF have a high predisposition to developing PHT if at admission, they have low BMI, dilated left atrium or are older. Patients with one or more of these attributes may need more intensive therapy to reduce the risk of developing PHT and in turn reduce readmission rates.

This paper presents the results of the literature review conducted for the working group topic on inflammation, infection, exposure, and the human microbiome. Infection and chronic inflammation can elevate risk for cardiovascular disease and cancer. Environmental exposures common among South Asian (SA) subgroups, such as arsenic exposure among Bangladeshis and particulate matter air pollution among taxi drivers, also pose risks. This review explores the effects of exposure to arsenic and particulate matter, as well as other infections common among SAs, including human papillomavirus (HPV) and hepatitis B/C infection. Emerging research on the human microbiome, and the effect of microbiome changes on obesity and diabetes risk among SAs are also explored.

PURPOSE/UNASSIGNED:Housing status can become compromised in the wake of financial hardship for some patients with cancer and become a source of disparity. This qualitative study describes the types of housing issues experienced by patients with cancer and survivors of cancer in New York City. METHODS/UNASSIGNED:Semistructured interviews were conducted with a volunteer sample of 21 patients with cancer or survivors of cancer treated in New York City who reported housing needs in the period after diagnosis through survivorship. Nine supplemental interviews were conducted with cancer and housing key informants. Conventional content analysis was conducted on transcripts to create a codebook describing types of housing needs. RESULTS/UNASSIGNED:Patients and survivors most commonly had breast (n = 9) and blood (n = 4) cancers and ranged from recently diagnosed to many years posttreatment. Twenty-nine distinct housing-related issues were identified, which were grouped into the following six major categories: housing costs (eg, rent, mortgage), home loss, doubled up or unstable housing, housing conditions, accessibility (eg, stairs, proximity to amenities), and safety. Issues were often interrelated. Housing needs sometimes predated cancer diagnosis. Other issues newly emerged in the wake of cancer-related physical limitations and disruption to finances. Needs ranged in severity and caused patients and survivors considerable burden during a difficult period of poor health and financial strain. CONCLUSION/UNASSIGNED:This study contributes depth to current understandings of housing needs among patients with cancer and survivors by providing detailed disaggregated descriptions. We recommend increasing availability of services responsive to these needs and exploring promising options such as patient navigation and legal services. Findings also highlight the importance of creative solutions addressing ecologic-level factors such as housing affordability.

Despite improvements in the management of in-hospital cardiac arrest over the past decade, in-hospital cardiac arrest continues to be associated with poor prognosis. This has led to the development of rapid response systems, hospital-wide efforts to improve patient outcomes by centering on prompt identification of decompensating patients, expert clinical management, and continuous quality improvement of processes of care. The rapid response system may include cardiac arrest teams, which are centered on identification and treatment of patients with in-hospital cardiac arrest. However, few evidence-based guidelines exist to guide the formation of such teams, and the degree of their variation across the United States has not been well described.

BACKGROUND: Multiple studies have examined the use of lumen-apposing metal stents (LAMSs) for the drainage of peripancreatic fluid collections. Data on the use of LAMSs for postoperative fluid collections (POFCs) are scarce. POFCs may lead to severe complications without appropriate treatment. We aimed to study the outcomes (technical success, clinical success, rate/severity of adverse events, length of stay, recurrence) of the use of LAMSs for the drainage of POFCs. METHODS: This international, multicenter, retrospective study involved 19 centers between January 2012 and October 2017. The primary outcome was clinical success. Secondary outcomes included technical success and rate/severity of adverse events using the ASGE lexicon. RESULTS: A total of 62 patients were included during the study period. The most common etiology of the POFCs was distal pancreatectomy (46.8 %). The mean (standard deviation) diameter was 84.5 mm (30.7 mm). The most common indication for drainage was infection (48.4 %) and transgastric drainage was the most common approach (82.3 %). Technical success was achieved in 60/62 patients (96.8 %) and clinical success in 57/62 patients (91.9 %) during a median (interquartile range) follow-up of 231 days (90 - 300 days). Percutaneous drainage was needed in 8.1 % of patients. Adverse events occurred intraoperatively in 1/62 patients (1.6 %) and postoperatively in 7/62 (11.3 %). There was no procedure-related mortality. CONCLUSION/CONCLUSIONS: This is the largest study on the use of LAMSs for POFCs. It suggests good clinical efficacy and safety of this approach. The use of LAMSs in the management of POFCs is a feasible alternative to percutaneous and surgical drainage.