Faculty Bibliography

OBJECTIVE:Autoimmune disease is an emerging condition among persons exposed to the September 11, 2001, attack on the World Trade Center (WTC). Components of the dust cloud resulting from the collapse of the WTC have been associated with systemic autoimmune diseases (SAID), as has posttraumatic stress disorder (PTSD). We sought to determine whether dust exposure and PTSD were associated with an increased risk of SAID in a 9/11-exposed cohort. METHODS:Among 43,133 WTC Health Registry enrollees, 2,786 self-reported a post-9/11 SAID. We obtained consent to review medical records to validate SAID diagnoses for 1,041. SAIDs were confirmed by classification criteria, rheumatologist diagnosis, or having been prescribed SAID medication. Controls were enrollees who denied an autoimmune disease diagnosis (n=37,017). We used multivariable log-binomial regression to examine the association between multiple 9/11 exposures and risk of post-9/11 SAID, stratifying by responders and community members. RESULTS:We identified 118 persons with SAID. Rheumatoid arthritis was most frequent (n=71), followed by SjÓ§gren's syndrome (n=22), systemic lupus erythematosus (n=20), myositis (n=9), mixed connective tissue disease (n=7), and scleroderma (n=4). Among 9/11 responders, those with intense dust cloud exposure had almost twice the risk of SAID (adjusted risk ratio =1.86, 95% CI=1.02-3.40). Community members with PTSD had a nearly three-fold increased risk of SAID. CONCLUSION/CONCLUSIONS:Intense dust cloud exposure among responders and PTSD among community members were associated with a statistically significant increased risk of new-onset SAID. Clinicians treating 9/11 survivors should be aware of the potential increased risk of SAID in this population.

Twenty patients with carbapenem-resistant Enterobacteriaceae (CRE) infections were treated with meropenem-vaborbactam. Thirty-day clinical success and survival rates were 65% (13/20) and 90% (18/20), respectively. Thirty-five percent of patients had microbiologic failures within 90 days. One patient developed a recurrent infection due to meropenem-vaborbactam non-susceptible, ompK36 porin mutant Klebsiellapneumoniae.

PURPOSE OF REVIEW/OBJECTIVE:Plant-based diets have been used with growing popularity for the treatment of a wide range of lifestyle-related diseases, including diabetes, hypertension, and obesity. With the reinvigoration of the conservative and dietary management of chronic kidney disease (CKD) and the use of low protein diets for secondary prevention of CKD to delay or prevent dialysis therapy, there is an increasing interest in the potential role of plant-based diets for these patients. RECENT FINDINGS/RESULTS:Recently, a body of evidence related to the role of plant-based diet in preventing CKD has reemerged. Several observational studies have shown that red and processed meat have been associated with increased risk of CKD as well as faster progressing in those with preexisting CKD. In several substitution analyses, replacement of one serving of red and/or processed meat has been linked with sizable reductions in CKD risk as primary prevention. Although limited, experimental trials for the treatment of metabolic acidosis in CKD with fruits and vegetables show outcomes comparable to oral bicarbonate. The use of plant-based diets in CKD may have other benefits in the areas of hypertension, weight, hyperphosphatemia, reductions in hyperfiltration, and, possibly, mortality. The risk of potassium overload from plant-based diets appears overstated, mostly opinion-based, and not supported the evidence. Plant-based diets are generally well tolerated and provide adequate protein intake, including essential amino acids as long as the is correctly implemented. SUMMARY/CONCLUSIONS:Plant-based diets should be recommended for both primary and secondary prevention of CKD. Concerns of hyperkalemia and protein inadequacy related to plant-based diets may be outdated and unsupported by the current body of literature. Healthcare providers in general medicine and nephrology can consider plant-based diets as an important tool for prevention and management of CKD.

OBJECTIVES/OBJECTIVE:To examine the in vitro selection of aztreonam/avibactam resistance among MBL-producing Klebsiella pneumoniae and to understand the mechanism of increased resistance. METHODS:The MICs of aztreonam were determined with and without avibactam (4 mg/L) using a broth microdilution method. Single-step and multi-step mutant selection was conducted on five MBL-producing K. pneumoniae strains, including two dual carbapenemase producers. Genomic sequencing and gene cloning were performed to investigate the mechanism of increased resistance. RESULTS:We examined the MICs for 68 MBL-producing K. pneumoniae isolates, including 13 dual carbapenemase producers. Compared with aztreonam alone, the addition of avibactam (4 mg/L) reduced the MICs for all isolates by >128-fold, with MIC50 and MIC90 values of 0.25 and 1 mg/L, respectively. One NDM-1-, OXA-48-, CTX-M-15- and CMY-16-positive ST101 K. pneumoniae strain was selected to be resistant to aztreonam/avibactam, with a >16-fold increase in MIC (>128 mg/L). WGS revealed that the resistant mutants lost the blaNDM-1 gene, but acquired amino acid substitutions in CMY-16 (Tyr150Ser and Asn346His). Construction of blaCMY-16 mutants confirmed that the substitutions (Tyr150Ser and Asn346His) were primarily responsible for the decreased susceptibility to aztreonam/avibactam. In addition, transfer of blaCMY-16 mutant (Tyr150Ser and Asn346His) plasmid constructs into certain clinical carbapenemase-producing isolates demonstrated >64-fold increased MICs of aztreonam/avibactam and aztreonam/avibactam/ceftazidime. CONCLUSIONS:Aztreonam in combination with avibactam showed potent in vitro activity against MBL-producing K. pneumoniae. However, our study suggested the likelihood of aztreonam/avibactam resistance among MBL- and AmpC-co-producing strains and clinical practice should beware of the possibility of the emerging resistance.

This white paper presents principles for validating proarrhythmia risk prediction models for regulatory use as discussed at the In Silico Breakout Session of a Cardiac Safety Research Consortium/Health and Environmental Sciences Institute/US Food and Drug Administration-sponsored Think Tank Meeting on May 22, 2018. The meeting was convened to evaluate the progress in the development of a new cardiac safety paradigm, the Comprehensive in Vitro Proarrhythmia Assay (CiPA). The opinions regarding these principles reflect the collective views of those who participated in the discussion of this topic both at and after the breakout session. Although primarily discussed in the context of in silico models, these principles describe the interface between experimental input and model-based interpretation and are intended to be general enough to be applied to other types of nonclinical models for proarrhythmia assessment. This document was developed with the intention of providing a foundation for more consistency and harmonization in developing and validating different models for proarrhythmia risk prediction using the example of the CiPA paradigm.

Internet-facilitated self-diagnosis and treatment is becoming more prevalent, putting individuals at risk of toxicity when drugs are acquired without medical oversight. We report a patient with delusional parasitosis who consumed veterinary albendazole purchased on the Internet, leading to pancytopenia, transaminase elevation, and alopecia. A 53-year-old man was sent to the emergency department (ED) by his gastroenterologist because of abnormal laboratory results. The patient had chronic abdominal pain and believed he was infected with parasites. He purchased two bottles of veterinary-grade albendazole on the Internet, and over the 3 weeks before his ED visit, he consumed 113.6 g of albendazole (a normal maximal daily dose is 800 mg). Five days before admission, he noticed hair loss and a rash on his face. His examination was notable for significant scalp hair loss and hyperpigmentation along the jaw line. Laboratory studies were remarkable for pancytopenia (most notably a WBC of 0.4 × 10³ cells/mm³, with an absolute neutrophil count (ANC) of 0 × 10³ cells/mm³) and transaminase elevation (AST 268 IU/L, ALT 89 IU/L). He developed a fever and was treated with antibiotics and colony-stimulating factors for presumed neutropenic bacteremia. Over the course of 1 week, his hepatic function normalized and his ANC increased to 3,000 × 10³ cells/mm³. Serial albendazole and albendazole sulfoxide concentrations were measured in serum and urine by liquid chromatography-quadruple time-of-flight mass spectrometry. On day 2, his serum concentrations were 20.7 ng/mL and 4,257.7 ng/mL for albendazole and albendazole sulfoxide, respectively. A typical peak therapeutic concentration for albendazole sulfoxide occuring at 2-5 hours post-ingestion is 220-1,580 ng/mL. Known adverse effects of albendazole include alopecia, transaminase elevation, and neutropenia. Pancytopenia leading to death from septic shock is reported. In our patient, prolonged use of high-dose albendazole resulted in a significant body burden of albendazole and albendazole sulfoxide, leading to pancytopenia, transaminase elevation, and alopecia. He recovered with supportive therapy.

INTRODUCTION/BACKGROUND:Smoking is a key determinant of mortality among people living with HIV (PLWH). METHODS:To better understand the effects of smoking cessation interventions in PLWH, we conducted a pooled analysis of four randomized controlled trials of hospital-initiated smoking interventions conducted through the Consortium of Hospitals Advancing Research on Tobacco (CHART). In each study, cigarette smokers were randomly assigned to usual care or a smoking cessation intervention. The primary outcome was self-reported past 30-day tobacco abstinence at 6-month follow-up. Abstinence rates were compared between PLWH and participants without HIV and by treatment arm, using both complete-case and intention-to-treat analyses. Multivariable logistic regression was used to determine the effect of HIV status on 6-month tobacco abstinence and to determine predictors of smoking cessation within PLWH. RESULTS:Among 5550 hospitalized smokers, there were 202 (3.6%) PLWH. PLWH smoked fewer cigarettes per day and were less likely to be planning to quit than smokers without HIV. At 6 months, cessation rates did not differ between intervention and control groups among PLWH (28.9% vs. 30.5%) or smokers without HIV (36.1% vs. 34.1%). In multivariable regression analysis, HIV status was not significantly associated with smoking cessation at 6 months. Among PLWH, confidence in quitting was the only clinical factor independently associated with smoking cessation (OR 2.0, 95% CI = 1.4 to 2.8, p < .01). CONCLUSIONS:HIV status did not alter likelihood of quitting smoking after hospital discharge, whether or not the smoker was offered a tobacco cessation intervention, but power was limited to identify potentially important differences. IMPLICATIONS/CONCLUSIONS:PLWH had similar quit rates to participants without HIV following a hospital-initiated smoking cessation intervention. The findings suggest that factors specific to HIV infection may not influence response to smoking cessation interventions and that all PLWH would benefit from efforts to assist in quitting smoking. TRIAL REGISTRATION/BACKGROUND:(1) Using "warm handoffs" to link hospitalized smokers with tobacco treatment after discharge: study protocol of a randomized controlled trial: NCT01305928. (2) Web-based smoking cessation intervention that transitions from inpatient to outpatient: NCT01277250. (3) Effectiveness of smoking-cessation interventions for urban hospital patients: NCT01363245. (4) Effectiveness of Post-Discharge Strategies for Hospitalized Smokers (HelpingHAND2): NCT01714323.

To examine nutrition benefit under-enrollment in Latinx American immigrant families, we administered a survey to 100 adults attending a NY Latinx American community serving organization. We used a logistic regression approach to analyze misinformation impact on enrollment, and examined non-enrollment explanations, among participants in whose families a child or pregnant or breastfeeding woman appeared SNAP- or WIC-eligible. Among households (N = 51) with ≥ 1 SNAP-eligible child, 49% had no child enrolled. Reasons included repercussion fears (e.g. payback obligation, military conscription, college aid ineligibility, child removal, non-citizen family member penalties), and logistical barriers. In multivariable regression models, having heard the rumor that SNAP/WIC participation makes unauthorized status family members vulnerable to being reported to the government was associated with an 85% lower enrollment rate (OR 0.15, CI 0.03, 0.94). Misinformation impedes nutrition benefit participation. A multi-level intervention is necessary to inform potential applicants and providers regarding eligibility criteria and erroneous rumors, along with an informed discussion of the risks versus benefits of using resources, especially as public charge criteria change.

Mother-to-child transmission (MTCT) is responsible for the majority of chronic hepatitis B virus (HBV) infections worldwide. Despite timely HBV immunoprophylaxis of neonates, MTCT can occur in infants born to mothers with high levels of HBV viremia. We performed a retrospective cross-sectional analysis of Asian American women with chronic HBV evaluated with HBV DNA during prenatal care at two community health sites in New York City from 2007 to 2017. We described patient's demographic and clinical characteristics, categorized their HBV disease phase, and analyzed for variables associated with high MTCT risk (defined by HBV DNA level > 200,000 IU/mL) using multivariable logistic regression. A total of 1298 pregnancies among 1012 mostly China-born (97.6%) women with chronic HBV were included in the study. Of the 1241 pregnancies among women not on antiviral treatment, 22.4 % were considered high-risk for MTCT and of these, 255 (91.7%) were HBV e antigen (HBeAg)-positive and 19 (6.8%) were HBeAg-negative. HBeAg-positive status and ALT levels between 26 to 50 U/L were associated with higher likelihood for being high-risk for MTCT. Only 0.8% of pregnancies low-risk for MTCT were in the immune active phase while the majority (58.4%) were in the inactive chronic HBV phase of infection. Approximately one in five (22.4%) pregnancies among Asian American women with chronic HBV was considered high-risk for MTCT and met criteria for antiviral therapy. Full assessment of HBV pregnant women and early coordinated care is needed to deliver interventions to prevent MTCT during critical windows of time.