Faculty Bibliography

The Dietary Approaches to Stop Hypertension (DASH) diet is recommended for lowering blood pressure and preventing cardiovascular disease (CVD), but little data exist on these associations in US Hispanics/Latinos. We sought to assess associations between DASH score and prevalence of metabolic syndrome (MetS) and its components in diverse Hispanics/Latinos. We studied 10,741 adults aged 18-74 in the multicenter Hispanic Community Health Study/Study of Latinos. Dietary intake was measured using two 24-hour recalls, and MetS defined per the 2009 harmonized guidelines. We assessed cross-sectional associations of DASH score and MetS (and its dichotomized components) using survey logistic regression, and DASH and MetS continuous components using linear regression. We also stratified these models by Hispanic/Latino heritage group to explore heritage-specific associations. We found no associations between DASH and MetS prevalence. DASH was inversely associated with both measures of blood pressure (p < 0.01 for systolic and p < 0.001 for diastolic) in the overall cohort. DASH was also inversely associated with diastolic blood pressure in the Mexican (p < 0.05), Central American (p < 0.05), and South American (p < 0.01) groups; triglycerides (p < 0.05) in the Central American group; fasting glucose overall (p < 0.01) and in the Mexican group (p < 0.01); and waist circumference overall (p < 0.05) and in the South American group (p < 0.01). DASH was positively associated with HDL-cholesterol (p < 0.01) in the Central American group. DASH may better capture diet-MetS associations in Hispanic/Latino subpopulations such as Central/South Americans; this study also adds evidence that Hispanics/Latinos should be analyzed by heritage. Further research, and/or culturally tailored DASH measures will help further explain between-heritage differences.

Carbapenem-resistant Enterobacteriaceae (CRE) strains are an urgent public health threat. We evaluated the in vitro activities of 19 antimicrobial agents, including imipenem-relebactam, against (i) 106 CRE bloodstream isolates that primarily expressed Klebsiella pneumoniae carbapenemase (KPC) and (ii) 20 OXA-48-like-expressing CRE isolates. Ninety-five percent of CRE bloodstream isolates were susceptible to imipenem-relebactam. In contrast to their comparable activities against KPC-producing CRE strains, ceftazidime-avibactam was more active in vitro against OXA-48-like CRE strains than was imipenem-relebactam (90% susceptible versus 15% susceptible).

Tigecycline is one of the last-resort antibiotics to treat complicated infections caused by both multidrug-resistant Gram-negative and Gram-positive bacteria¹. Tigecycline resistance has sporadically occurred in recent years, primarily due to chromosome-encoding mechanisms, such as overexpression of efflux pumps and ribosome protection^2,3. Here, we report the emergence of the plasmid-mediated mobile tigecycline resistance mechanism Tet(X4) in Escherichia coli isolates from China, which is capable of degrading all tetracyclines, including tigecycline and the US FDA newly approved eravacycline. The tet(X4)-harbouring IncQ1 plasmid is highly transferable, and can be successfully mobilized and stabilized in recipient clinical and laboratory strains of Enterobacteriaceae bacteria. It is noteworthy that tet(X4)-positive E. coli strains, including isolates co-harbouring mcr-1, have been widely detected in pigs, chickens, soil and dust samples in China. In vivo murine models demonstrated that the presence of Tet(X4) led to tigecycline treatment failure. Consequently, the emergence of plasmid-mediated Tet(X4) challenges the clinical efficacy of the entire family of tetracycline antibiotics. Importantly, our study raises concern that the plasmid-mediated tigecycline resistance may further spread into various ecological niches and into clinical high-risk pathogens. Collective efforts are in urgent need to preserve the potency of these essential antibiotics.

PURPOSE/OBJECTIVE:There is variability in survival within IDH mutant gliomas determined by chromosomal events. Copy number variation (CNV) abundance associated with survival in low-grade and IDH mutant astrocytoma has been reported. Our purpose was to correlate the extent of genome-wide CNV abundance in IDH mutant astrocytomas with MRI features. METHODS:Presurgical MRI and CNV plots derived from Illumina 850k EPIC DNA methylation arrays of 18 cases of WHO grade II-IV IDH mutant astrocytomas were reviewed. IDH mutant astrocytomas were divided into CNV stable group (CNV-S) with ≤ 3 chromosomal gains or losses and lack of focal gene amplifications and CNV unstable group (CNV-U) with > 3 large chromosomal gains/losses and/or focal amplifications. The associations between MR features, relative cerebral blood volume (rCBV), CNV abundance, and time to progression were assessed. Tumor rCBV estimates were obtained using DSC T2* perfusion analysis. RESULTS:There were nine (50%) CNV-S and nine (50%) CNV-U IDH mutant astrocytomas. CNV-U tumors showed larger mean tumor size (P = 0.004) and maximum diameter on FLAIR (P = 0.004) and also demonstrated significantly higher median rCBV than CNV-S tumors (2.62 vs 0.78, P = 0.019). CNV-U tumors tended to have shorter time to progression although without statistical significance (P = 0.393). CONCLUSIONS:Larger size/diameter and higher rCBVs were seen associated CNV-U astrocytomas, suggesting a correlation of aggressive imaging phenotype with unstable and aggressive genotype in IDH mutant astrocytomas.

Objective: To compare morbidity and mortality of Acute Coronary Syndrome (ACS) patients, with hemoglobin level above 7g/dl in transfused or not transfused groups.
Method(s): We conducted a retrospective cohort study of patients admitted with ACS to both campuses of NYU Langone Hospital. Of 1080 patients screened in, 82 met inclusion criteria and were included in our analysis. Patients with hemoglobin less than 7 g/dL or greater than 10 g/dL during their ischemic event were excluded. The outcomes of interest were length of stay (LOS) and negative clinical events as ascertained by physician chart review. The Mann-Whitney U test, was used to compare continuous variables, and the chi-squared test compared categorical variables.
Result(s): 54 patients were transfused, and 28 were not transfused. Mean age (72.5 vs 74.4 years), and race did not differ significantly between groups. Proportion with heart failure, known anemia and mean baseline hemoglobin of anemic patients prior to admission were similar between both groups. ACS diagnosis and proportion of patients receiving medical management were similar between groups as well. However, transfused patients were more likely to be male, have Chronic Kidney Disease (51.9% vs 28.6%), have known Coronary Artery Disease (77.8 vs 42.6%) and those with Congestive Heart Failure had a lower baseline ejection fraction (34.5 vs 57.5%). For outcomes, blood transfusion was associated with a longer LOS (mean 11.48 vs 6.36 days, p=0.002). Furthermore, transfusion was associated with a higher likelihood to have a combined negative outcome which included new or worsening respiratory distress, hypoxia, volume overload, upgrade to the Intensive Care Unit and death (79% vs 24%, RR=3.29, P<0.001), driven by a significant increase in volume overload (40.7 vs 4.0% P<0.001) and a non-significant tendency towards increased mortality (16.7 vs 4.0%, p=0.12).
Conclusion(s): ACS patients who underwent blood transfusion had worse outcomes, namely longer LOS, increased risk for volume overload and a pronounced but not significant trend towards increased mortality. This effect was confounded by more severe comorbidities in the transfused group. However, given the size and significance of this harmful association, it is possible or perhaps even likely that transfusion itself was a factor in the worsened outcomes in the transfused group. Though transfusion for a hemoglobin > 7g/dl and even > 8g/dl is common in ACS patients, the harms associated with blood transfusions may outweigh the possible risk of worsened myocardial ischemia in the setting of lower oxygen carrying capacity

INTRODUCTION/BACKGROUND:Systems-based Practice 3 (SBP 3) in the orthopedic residency developmental milestones evaluates residents' knowledge, understanding, and utilization of the electronic medical record (EMR). In order to better assess SBP 3, we conducted a review of residents' clinical notes in order to quantify the current state of orthopedic residents' documentation in the EMR. The purpose of this study was to objectively evaluate orthopedic resident documentation in the EMR. METHODS:Orthopedic resident medical notes from a single orthopedic residency at one academic medical center were scored by faculty members who had directly observed the clinical encounter. These notes were then independently scored by one investigator (N.F.) using clinical contentspecific, objective criteria. Sixty-five medical records were reviewed. All 62 orthopedic residents anonymously completed an 84-question survey on the value of EMR utilization and documentation within the medical record. RESULTS:Many key elements necessary to diagnosing a patient's injury and developing a treatment plan were often omitted (e.g., "Mechanism of Injury" in 32.3% of records), and the majority of notes did not include "Decision Making and Patient Preference" (95.2%) or "Risks/Benefits of Surgery" (93.7%). However, 95.2% of residents agreed that their notes reflect their medical knowledge and 96.8% agreed that their notes reflect their clinical reasoning. DISCUSSION/CONCLUSIONS:The results of this objective review revealed significant deficits in orthopedic resident documentation not identified by faculty observers.

Increasingly, obstructive sleep apnea treatment is being recognized as amenable to a precision medicine approach. Many pathophysiologic mechanisms (endotypes) beyond anatomic compromise have now been identified and are readily determined during polysomnography, although randomized controlled trials of endotype-specific therapies are needed. Research indicates that endotypes may also be important in predicting both adherence to therapy and disease consequences (phenotypes). Biomarker discovery and Big Data approaches derived from wearable technology are areas of active investigation and may allow more robust conclusions to be drawn over time, such that patients may soon fully realize the benefits from fresh insights into sleep science.

PEGylation is a biochemical modification process of bioactive molecules with polyethylene glycol (PEG), which lends several desirable properties to proteins/peptides, antibodies, and vesicles considered to be used for therapy or genetic modification of cells. However, PEGylation of proteins is a complex process and can be carried out using more than one strategy that depends on the nature of the protein and the desired application. Proteins of interest are covalently conjugated or non-covalently complexed with inert PEG strings. Purification of PEGylated protein is another critical step, which is mainly carried out based on electrostatic interactions or molecular sizes using chromatography. Several PEGylated drugs are being used for diseases like anemia, kidney disease, multiple sclerosis, hemophilia and cancers. With the advancement and increased specificity of the PEGylation process, the world of drug therapy, and specifically cancer therapy could benefit by utilizing this technique to create more stable and non-immunogenic therapies. In this article we describe the structure and functions of PEGylation and how this chemistry helps in drug discovery. Moreover, special emphasis has been given to CCN-family proteins that can be targeted or used as therapy to prevent or block cancer progression through PEGylation technology.