Faculty Bibliography

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.

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

This study reports the first assessment of published comments in the family medicine literature using structured codes, which produced commentary annotations that will be the foundation of a knowledge base of appraisals of family medicine trials. Evidence appraisal occurs in a variety of formats and serves to shed light on the quality of research. However, scientific discourse generally and evidence appraisal in particular has not itself been analyzed for insights. A search strategy was devised to identify all journal comments indexed in PubMed linked to controlled intervention studies published in a recent 15-year period in major family medicine journals. A previously developed structured representation in the form of a list of appraisal concepts was used to formally annotate and categorize the journal comments through an iterative process. Trends in family medicine evidence appraisal were then analyzed. A total of 93 comments on studies from five journals over 15 years were included in the analysis. Two thirds of extracted appraisals were negative criticisms. All appraisals of measurement instruments were negative (100%). The participants baseline characteristics, the author discussions, and the design of the interventions were also criticized (respectively 91.7%, 84.6% and 83.3% negative). In contrast, appraisals of the scientific basis of the studies were positive (81.8%). The categories with the most appraisals were, most generally, those focused on the study design, and most specifically, those focused on the scientific basis. This study provides a new data-driven approach to review scientific discourse regarding the strengths and limitations of research within academic family medicine. This methodology can potentially generalize to other medical domains. Structured appraisal data generated here will enable future clinical, scientific, and policy decision-making and broader meta-research in family medicine.

BACKGROUND:Topical corticosteroids are available in many vehicles. However, patients' preference for vehicles are variable and could be tailored to maximize patient adherence. Spray vehicles may offer, convenience, and strong efficacy. METHODS:A literature review was conducted using keywords: clobetasol, desoximetasone, betamethasone, triamcinolone, corticosteroid, topical, spray, vehicles, treatment, and clinical trial. RESULTS:For moderate-to-severe plaque psoriasis, 87% of subjects achieved an Overall Disease Severity (ODS) Score ≤2 at week two and 78% achieved an ODS ≤1 after four weeks with clobetasol propionate (CP) 0.05% spray compared to 17% and 3% in the control group, respectively (P&lt;0.001). For desoximetasone 0.25% spray, 31%-53% with moderate-to-severe psoriasis achieve Physician's Global Assessment (PGA) score ≤1 at day 28 versus 5%-18% in the vehicle spray group (P&lt;0.01). For betamethasone dipropionate 0.05% spray, 19% with mild-to-moderate plaque psoriasis achieved an Investigator's Global Assessment (IGA) score ≤1 or a 2-grade reduction in IGA versus 2.3% in vehicle group (P≤0.001). For mild-to-severe steroid responsive inflammatory dermatoses, 64% using triamcinolone acetonide 0.2% spray achieved clear or almost clear skin at day 14 (no P value reported). Adverse events including burning, irritation, and dryness were similar across all corticosteroids.

Recent scholarship suggests that the genomes of those around us affect our own phenotypes. Much of the empirical evidence for such "metagenomic" effects comes from animal studies, where the socio-genetic environment can be easily manipulated. Among humans, it is more difficult to identify such effects given the nonrandom distribution of genes and environments. Here we leverage the as-if-random distribution of grade-mates' genomes conditional on school-level variation in a nationally representative sample. Specifically, we evaluate whether one's peers' genetic propensity to smoke affects one's own smoking behavior net of one's own genotype. Results show that peer genetic propensity to smoke has a substantial effect on an individual's smoking outcome. This is true not only when the peer group includes direct friends, and therefore where the individual plays an active role in shaping the metagenomic context but also when the peer group includes all grade-mates and thus in cases where the individual does not select the metagenomic environment. We explore these effects further and show that a small minority with high genetic risk to smoke ('bad apples') can greatly affect the smoking behavior of an entire grade. The methodology used in this paper offers a potential solution to many of the challenges inherent in estimating peer effects in nonexperimental settings and can be utilized to study a wide range of outcomes with a genetic basis. On a policy level, our results suggest that efforts to reduce adolescent smoking should take into account metagenomic effects, especially bad apples, within social networks.

BACKGROUND:Mineralocorticoid receptor antagonists (MRA) are an underutilized therapy for heart failure with a reduced ejection fraction (HFrEF), but the current impact of hospitalization on MRA use is not well characterized. The objective of this study was to describe contemporary MRA prescription for heart failure patients before and after the full scope of hospitalizations and the association between MRA discharge prescription and post-hospitalization outcomes. METHODS:We conducted a retrospective cohort study at an academic hospital system in 2013-2016. Among 1500 included hospitalizations of 1009 unique patients with HFrEF and without MRA contraindication, the mean age was 71.9 ± 13.6 years and 443 (29.5%) were female. We compared MRA prescription before and after hospitalizations with McNemar's test and between patients with principal and secondary diagnoses of HFrEF with the chi-square test, and association of MRA discharge prescription with 30-day and 180-day mortality and readmissions using generalized estimating equations. RESULTS:MRA prescriptions increased from 303 (20.2%) to 375 (25.0%) at discharge (+4.8%, p < 0.0001). More patients with principal diagnosis of HFrEF compared to those hospitalized for other reasons received MRA (34.9% versus 21.3%, p < 0.0001) and had them initiated (21.8% versus 9.7%, p < 0.0001). MRA prescription at discharge was not associated with mortality or readmission at 30 and 180 days, and there was no interaction with principal/secondary diagnosis. CONCLUSIONS:Among hospitalized HFrEF patients, 75% did not receive MRA before or after hospitalization, and nearly 90% of eligible patients did not have MRA initiated. As we found no signal for short-term harm after discharge, hospitalization may represent an opportunity to initiate guideline-directed heart failure therapy.

BACKGROUND:Hepatitis C virus (HCV) is a major public health problem in correctional settings. HCV treatment is often not possible in U.S. jails due to short lengths of stay. Linkage to care is crucial in these settings, but competing priorities complicate community healthcare engagement and retention after incarceration. METHODS:We conducted a single arm clinical trial of a combined transitional care coordination (TCC) and patient navigation intervention and assessed the linkage rate and factors associated with linkage to HCV care after incarceration. RESULTS:During the intervention, 84 participants returned to the community after their index incarceration. Most participants were male and Hispanic, with a history of mental illness and a mean age of 45 years. Of those who returned to the community, 26 (31%) linked to HCV care within a median of 20.5 days; 17 (20%) initiated HCV treatment, 15 (18%) completed treatment, 9 (11%) had a follow-up lab drawn to confirm sustained virologic response (SVR), and 7 (8%) had a documented SVR. Among those with follow-up labs the known SVR rate was (7/9) 78%. Expressing a preference to be linked to the participant's existing health system, being on methadone prior to incarceration, and feeling that family or a loved one were concerned about the participant's wellbeing were associated with linkage to HCV care. Reporting drinking alcohol to intoxication prior to incarceration was negatively associated with linkage to HCV care. CONCLUSION/CONCLUSIONS:We demonstrate that an integrated strategy with combined TCC and patient navigation may be effective in achieving timely linkage to HCV care. Additional multicomponent interventions aimed at treatment of substance use disorders and increasing social support could lead to further improvement. TRIAL REGISTRATION/BACKGROUND:Clinicaltrials.gov NCT04036760 July 30th, 2019 (retrospectively registered).