Faculty Bibliography
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department:Medicine. General Internal Medicine
recentyears:2
school:SOM
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14441
How long will you live? That depends on your zip code [Newspaper Article]
ORIGINAL:0012713
ISSN: 0261-3077
CID: 3158762
Comprehensive Genome Analysis of Carbapenemase-Producing Enterobacter spp.: New Insights into Phylogeny, Population Structure, and Resistance Mechanisms
Knowledge regarding the genomic structure of Enterobacter spp., the second most prevalent carbapenemase-producing Enterobacteriaceae, remains limited. Here we sequenced 97 clinical Enterobacter species isolates that were both carbapenem susceptible and resistant from various geographic regions to decipher the molecular origins of carbapenem resistance and to understand the changing phylogeny of these emerging and drug-resistant pathogens. Of the carbapenem-resistant isolates, 30 possessed blaKPC-2, 40 had blaKPC-3, 2 had blaKPC-4, and 2 had blaNDM-1 Twenty-three isolates were carbapenem susceptible. Six genomes were sequenced to completion, and their sizes ranged from 4.6 to 5.1 Mbp. Phylogenomic analysis placed 96 of these genomes, 351 additional Enterobacter genomes downloaded from NCBI GenBank, and six newly sequenced type strains into 19 phylogenomic groups-18 groups (A to R) in the Enterobacter cloacae complex and Enterobacter aerogenes Diverse mechanisms underlying the molecular evolutionary trajectory of these drug-resistant Enterobacter spp. were revealed, including the acquisition of an antibiotic resistance plasmid, followed by clonal spread, horizontal transfer of blaKPC-harboring plasmids between different phylogenomic groups, and repeated transposition of the blaKPC gene among different plasmid backbones. Group A, which comprises multilocus sequence type 171 (ST171), was the most commonly identified (23% of isolates). Genomic analysis showed that ST171 isolates evolved from a common ancestor and formed two different major clusters; each acquiring unique blaKPC-harboring plasmids, followed by clonal expansion. The data presented here represent the first comprehensive study of phylogenomic interrogation and the relationship between antibiotic resistance and plasmid discrimination among carbapenem-resistant Enterobacter spp., demonstrating the genetic diversity and complexity of the molecular mechanisms driving antibiotic resistance in this genus. IMPORTANCE: Enterobacter spp., especially carbapenemase-producing Enterobacter spp., have emerged as a clinically significant cause of nosocomial infections. However, only limited information is available on the distribution of carbapenem resistance across this genus. Augmenting this problem is an erroneous identification of Enterobacter strains because of ambiguous typing methods and imprecise taxonomy. In this study, we used a whole-genome-based comparative phylogenetic approach to (i) revisit and redefine the genus Enterobacter and (ii) unravel the emergence and evolution of the Klebsiella pneumoniae carbapenemase-harboring Enterobacter spp. Using genomic analysis of 447 sequenced strains, we developed an improved understanding of the species designations within this complex genus and identified the diverse mechanisms driving the molecular evolution of carbapenem resistance. The findings in this study provide a solid genomic framework that will serve as an important resource in the future development of molecular diagnostics and in supporting drug discovery programs.
PMCID:5156309
PMID: 27965456
ISSN: 2150-7511
CID: 2372092
Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease
BACKGROUND:Patients with obstructive left main coronary artery disease are usually treated with coronary-artery bypass grafting (CABG). Randomized trials have suggested that drug-eluting stents may be an acceptable alternative to CABG in selected patients with left main coronary disease. METHODS:We randomly assigned 1905 eligible patients with left main coronary artery disease of low or intermediate anatomical complexity to undergo either percutaneous coronary intervention (PCI) with fluoropolymer-based cobalt-chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). Anatomic complexity was assessed at the sites and defined by a Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score of 32 or lower (the SYNTAX score reflects a comprehensive angiographic assessment of the coronary vasculature, with 0 as the lowest score and higher scores [no upper limit] indicating more complex coronary anatomy). The primary end point was the rate of a composite of death from any cause, stroke, or myocardial infarction at 3 years, and the trial was powered for noninferiority testing of the primary end point (noninferiority margin, 4.2 percentage points). Major secondary end points included the rate of a composite of death from any cause, stroke, or myocardial infarction at 30 days and the rate of a composite of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years. Event rates were based on Kaplan-Meier estimates in time-to-first-event analyses. RESULTS:At 3 years, a primary end-point event had occurred in 15.4% of the patients in the PCI group and in 14.7% of the patients in the CABG group (difference, 0.7 percentage points; upper 97.5% confidence limit, 4.0 percentage points; P=0.02 for noninferiority; hazard ratio, 1.00; 95% confidence interval, 0.79 to 1.26; P=0.98 for superiority). The secondary end-point event of death, stroke, or myocardial infarction at 30 days occurred in 4.9% of the patients in the PCI group and in 7.9% in the CABG group (P<0.001 for noninferiority, P=0.008 for superiority). The secondary end-point event of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years occurred in 23.1% of the patients in the PCI group and in 19.1% in the CABG group (P=0.01 for noninferiority, P=0.10 for superiority). CONCLUSIONS:In patients with left main coronary artery disease and low or intermediate SYNTAX scores by site assessment, PCI with everolimus-eluting stents was noninferior to CABG with respect to the rate of the composite end point of death, stroke, or myocardial infarction at 3 years. (Funded by Abbott Vascular; EXCEL ClinicalTrials.gov number, NCT01205776 .).
PMID: 27797291
ISSN: 1533-4406
CID: 5451162
Association Between End-of-Rotation Resident Transition in Care and Mortality Among Hospitalized Patients
Importance: Shift-to-shift transitions in care among house staff are associated with adverse events. However, the association between end-of-rotation transition (in which care of the patient is transferred) and adverse events is uncertain. Objective: To examine the association of end-of-rotation house staff transitions with mortality among hospitalized patients. Design, Setting, and Participants: Retrospective multicenter cohort study of patients admitted to internal medicine services (N = 230701) at 10 university-affiliated US Veterans Health Administration hospitals (2008-2014). Exposures: Transition patients (defined as those admitted prior to an end-of-rotation transition who died or were discharged within 7 days following transition) were stratified by type of transition (intern only, resident only, or intern + resident) and compared with all other discharges (control). An alternative analysis comparing admissions within 2 days before transition with admissions on the same 2 days 2 weeks later was also conducted. Main Outcomes and Measures: The primary outcome was in-hospital mortality. Secondary outcomes included 30-day and 90-day mortality and readmission rates. A difference-in-difference analysis assessed whether outcomes changed after the 2011 Accreditation Council for Graduate Medical Education (ACGME) duty hour regulations. Adjustments included age, sex, race/ethnicity, month, year, length of stay, comorbidities, and hospital. Results: Among 230701 patient discharges (mean age, 65.6 years; men, 95.8%; median length of stay, 3.0 days), 25938 intern-only, 26456 resident-only, and 11517 intern + resident end-of-rotation transitions occurred. Overall mortality was 2.18% in-hospital, 9.45% at 30 days, and 14.43% at 90 days. Adjusted hospital mortality was significantly greater in transition vs control patients for the intern-only group (3.5% vs 2.0%; odds ratio [OR], 1.12 [95% CI, 1.03-1.21]) and the intern + resident group (4.0% vs 2.1%; OR, 1.18 [95% CI, 1.06-1.33]), but not for the resident-only group (3.3% vs 2.0%; OR, 1.07 [95% CI, 0.99-1.16]). Adjusted 30-day and 90-day mortality rates were greater in all transition vs control comparisons (30-day mortality: intern-only group, 14.5% vs 8.8%, OR, 1.17 [95% CI, 1.13-1.22]; resident-only group, 13.8% vs 8.9%, OR, 1.11 [95% CI, 1.04-1.18]; intern + resident group, 15.5% vs 9.1%, OR, 1.21 [95% CI, 1.12-1.31]; 90-day mortality: intern-only group, 21.5% vs 13.5%, OR, 1.14 [95% CI, 1.10-1.19]; resident-only group, 20.9% vs 13.6%, OR, 1.10 [95% CI, 1.05-1.16]; intern + resident group, 22.8% vs 14.0%, OR, 1.17 [95% CI, 1.11-1.23]). Duty hour changes were associated with greater adjusted hospital mortality for transition patients in the intern-only group and intern + resident group than for controls (intern-only: OR, 1.11 [95% CI, 1.02-1.21]; intern + resident: OR, 1.17 [95% CI, 1.02-1.34]). The alternative analyses did not demonstrate any significant differences in mortality between transition and control groups. Conclusions and Relevance: Among patients admitted to internal medicine services in 10 Veterans Affairs hospitals, end-of-rotation transition in care was associated with significantly higher in-hospital mortality in an unrestricted analysis that included most patients, but not in an alternative restricted analysis. The association was stronger following institution of ACGME duty hour regulations.
PMID: 27923090
ISSN: 1538-3598
CID: 2353482
Platelet-Rich Plasma (PRP): The Whole or Sum of Parts by Proteomics and Molecular Assays [Meeting Abstract]
ISI:000390569200146
ISSN: 1937-335x
CID: 2782382
Coding and billing issues in hospital neurology compensation
Background/UNASSIGNED:Accurate coding and billing are critical for the financial health of hospitals. Neurologic inpatient services have specific, complex documentation requirements, which can result in inadequate billing. Methods/UNASSIGNED:We retrospectively compared coding practices from July 2013 to June 2014 (FY2014) using evaluation and management codes for initial inpatient encounters (CPT 99221-3) of a neurohospitalist group (NHG) to a hospital medicine group (HMG) and to national benchmarks. We further examined a sample of the lowest level encounters (CPT 99221) from the 4th quarter of FY2014 for specific deficiencies and compared these among groups. Results/UNASSIGNED:= 1.0) were common in both groups. In the NHG group, documentation did not reflect the acuity of patients' medical conditions. Conclusions/UNASSIGNED:Neurologists should pay close attention to documentation requirements-especially the neurologic examination-in order to allow for accurate coding and billing.
PMCID:5964816
PMID: 29849210
ISSN: 2163-0402
CID: 3166002
Treatment of high-risk smoldering myeloma [Case Report]
Multiple myeloma (MM) is a hematologic malignancy of the plasma cell that causes symptoms of bone pain, renal failure, and anemia. It is usually preceded by a precursor disease state, such as smoldering multiple myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS), and traditional dogma dictates that treatment should be initiated on frank MM symptom development. Emerging evidence suggests that a defined group of "high-risk SMM" may benefit from early treatment, before organ damage and symptoms actually occur. The following article frames the evidence for treatment of high-risk SMM by defining risk categories, reviewing existing therapeutic trial data, and exploring the long-term biologic implications of early treatment.
PMID: 28061988
ISSN: 1532-8708
CID: 3015362
Does the saline load test still have a role in the orthopaedic world? A systematic review of the literature
INTRODUCTION/BACKGROUND:The aim of this systematic review was to assess the efficacy of Saline load tests (SLTs) to evaluate extension of periarticular wounds into capsule in emergent settings. METHODS:We systematically reviewed the literature to evaluate the accuracy of the SLT in diagnosing penetrating joint injuries in the elbow, wrist, shoulder, knee, or ankle. RESULTS:The SLT values to determine knee arthrotomies vary from 73.8Â mL to 194Â mL with sensitivities ranging between 91% and 99% depending on the size of the laceration. A SLT of 30Â mLÂ in the ankle yields sensitivities ranging from 95% to 99% in assessing joint penetration. A SLT of 45Â mL in the elbow yields a sensitivity of 95% in assessing joint penetration. The addition of methylene blue does not change the sensitivity of the SLT. CONCLUSION/CONCLUSIONS:Several studies have demonstrated the utility of the SLT as a diagnostic modality for penetrating joint injuries. However, the literature analyzed in this study was inconclusive and more studies are required to make definitive recommendations. In addition, more studies will be needed on joints other than the knee, pediatric patients, and the use of methylene blue dye in conjunction with SLT. LEVEL OF EVIDENCE/METHODS:Level II, Diagnostic study.
PMCID:6197556
PMID: 27979366
ISSN: 2589-1294
CID: 4851532
Loss of CD30 expression after treatment with brentuximab vedotin in a patient with anaplastic large cell lymphoma: a novel finding [Case Report]
Anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma characterized by strong and uniform expression of CD30. Brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate has been approved by the U.S. FDA for relapsed/refractory systemic ALCL and achieves improved outcomes. We report a 44-year-old African-American man who presented with lymphadenopathy, lip and chest nodules diagnosed as CD30+, ALK-negative ALCL. The patient was treated with BV upon recurrence. While on treatment, the patient developed new-onset nodules on the chest and back. Skin biopsy showed a diffuse dermal infiltrate of medium-to-large atypical lymphocytes with frequent mitosis and scattered eosinophils. Immunohistochemically, the atypical cells displayed the same immunophenotype as previous specimens (CD3+, CD4-/CD8-, CD56-, ALK- and TCR γ-), except for lack of CD30 expression which was attributed to BV treatment effect. The diagnosis was thought to be consistent with ALK-negative ALCL and the patient was continued on BV along with total skin electron beam radiation and the lesions cleared. The patient relapsed 2 months later with extensive disease and expired. In summary, this is the first report in the literature of loss of CD30 expression in ALCL after BV therapy. Awareness of this may prevent a mistaken diagnosis of a CD30-negative secondary T-cell lymphoma.
PMID: 27531242
ISSN: 1600-0560
CID: 3707212
Biomarker-predicted sugars intake compared with self-reported measures in US Hispanics/Latinos: results from the HCHS/SOL SOLNAS study
OBJECTIVE: Measurement error in self-reported total sugars intake may obscure associations between sugars consumption and health outcomes, and the sum of 24 h urinary sucrose and fructose may serve as a predictive biomarker of total sugars intake. DESIGN: The Study of Latinos: Nutrition & Physical Activity Assessment Study (SOLNAS) was an ancillary study to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) cohort. Doubly labelled water and 24 h urinary sucrose and fructose were used as biomarkers of energy and sugars intake, respectively. Participants' diets were assessed by up to three 24 h recalls (88 % had two or more recalls). Procedures were repeated approximately 6 months after the initial visit among a subset of ninety-six participants. SETTING: Four centres (Bronx, NY; Chicago, IL; Miami, FL; San Diego, CA) across the USA. SUBJECTS: Men and women (n 477) aged 18-74 years. RESULTS: The geometric mean of total sugars was 167.5 (95 % CI 154.4, 181.7) g/d for the biomarker-predicted and 90.6 (95 % CI 87.6, 93.6) g/d for the self-reported total sugars intake. Self-reported total sugars intake was not correlated with biomarker-predicted sugars intake (r=-0.06, P=0.20, n 450). Among the reliability sample (n 90), the reproducibility coefficient was 0.59 for biomarker-predicted and 0.20 for self-reported total sugars intake. CONCLUSIONS: Possible explanations for the lack of association between biomarker-predicted and self-reported sugars intake include measurement error in self-reported diet, high intra-individual variability in sugars intake, and/or urinary sucrose and fructose may not be a suitable proxy for total sugars intake in this study population.
PMCID:5348247
PMID: 27339078
ISSN: 1475-2727
CID: 2370732
