Faculty Bibliography

Fatty acids derived from fish oil are long chain omega-3 (n-3) polyunsaturated fatty acids. The important polyunsaturated fatty acids of fish oil are eicosapentaenoic acid, and docosahexaenoic acid. For decades, there has been a debate about the use of omega-3 fatty acid supplements and their benefits on cardiovascular health. The more recent trials including the JELIS, REDUCE-IT, VITAL, STRENGTH, and the ASCEND trials addressed the paucity of data of omega-3 Fatty acids on primary as well as secondary prevention of cardiovascular events and risk-benefit balance of these supplements. Prior to these studies, many large randomized controlled trials have shown conflicting results on the effect of polyunsaturated fatty acids in patients with prior coronary artery disease, stroke or major vascular events. These inconsistent results warrant a better understanding of the effects of omega-3 fatty acids on the subtypes of cardiovascular diseases, and their use in primary and secondary prevention. More recently, the REDUCE-IT study showed a possible protective benefit of fish oil supplements (in purified form and higher than normal doses) in the reduction of Triglyceride levels. It is also noteworthy that omega-3 fatty acids have found their mention in the most recent American College of Cardiology guidelines for the management of hypertriglyceridemia as an adjunct to statins and fibrates. The aim of this review is to discuss these recent updates on use of fish oil in cardiometabolic diseases, and their surrounding controversies.

PURPOSE/OBJECTIVE:To evaluate the relationship of lipocalin-2 to inflammation and cardiac injury with increased aldosterone in HIV. METHODS:A standardized 6-day low sodium diet was used to stimulate RAAS activation, and serum lipocalin-2 and biomarkers of inflammation and cardiac stretch were assessed among persons with and without HIV. RESULTS:Lipocalin-2 (71.3[59.2,99.7] vs. 67.0[51.8,86.3]ng/mL, P=.01) increased with RAAS activation vs. suppression in the HIV group. During RAAS activation, lipocalin-2 was related to biomarkers of inflammation[TNFα(P=.007)], monocyte/macrophage activation[sCD163(P=.005), CcL-2(P=.03)], and markers of cardiac stretch[BNP(P=.0008), NTproBNP(P=.001)] in HIV. CONCLUSION/CONCLUSIONS:Lipocalin-2 may be important in modulating aldosterone-induced inflammation, monocyte activation, and cardiac stretch during RAAS activation in HIV.

A positive association between mental health conditions and poor asthma control has been documented in the World Trade Center-exposed population. Whether factors such as medication adherence mediate this association is unknown. The study population was drawn from adult participants of the World Trade Center Health Registry Cohort who self-reported as asthmatic after the disaster and who were currently prescribed a long-term control medication (LTCM). Multivariable linear regression was used to estimate the associations between mental health condition (PTSD, depression, or anxiety) and continuous adherence and Asthma Control Test (ACT) scores. In the study sample of 1,293, 49% were not adherent to their LTCM and two thirds reported poorly or very poorly controlled asthma. Presence of any mental health condition was associated with a 2-point decline in ACT and half a point decrease in adherence scores. However, in the multivariable model, better adherence was statistically significantly associated with slightly worse control. The total effect of mental health on asthma control was opposite in sign from the product of the paths between mental health and adherence and adherence and asthma control; we therefore found no evidence to support the hypothesis that adherence mediated the negative association between poor mental health and adequate asthma control. More research is needed to understand the complex causal mechanisms that underlie the association between mental and respiratory health.

BACKGROUND:Driven in part by Medicare's Hospital Readmissions Reduction Program, hospitals are focusing on improving the transition from inpatient to outpatient care with particular emphasis on early follow-up with a primary care physician (PCP). OBJECTIVE:To assess whether the implementation of a scheduling assistance program changes rates of PCP follow-up or readmissions. DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:An urban tertiary care center PATIENTS: A total of 20,918 adult patients hospitalized and discharged home between September 2008 and October 2015. INTERVENTION/METHODS:A postdischarge appointment service to facilitate early PCP follow-up. MAIN MEASURES/METHODS:Primary outcomes were rates of follow-up visits with a PCP within seven days of discharge and hospital readmission within 30 days of discharge. Our first analysis assessed differences in outcomes among patients with and without the use of the service. In a second analysis, we exploited the fact that the service was not available on weekends and conducted an instrumental variable analysis that used the interaction between the intervention and day of the week of admission. RESULTS:In our multivariable analysis, use of the appointment service was associated with much higher rates of PCP follow-up (+31.9 percentage points, 95% CI: 30.2, 33.6; P < .01) and a decrease in readmission (-3.8 percentage points, 95% CI: -5.2, -2.4; P < .01). In the instrumental variable analysis, use of the service also increased the likelihood of a PCP follow-up visit (33.4 percentage points, 95% CI: 7.9, 58.9; P = .01) but had no significant impact on readmissions (-2.5 percentage points, 95% CI: -22.0, 17.0; P = .80). CONCLUSIONS:The postdischarge appointment service resulted in a substantial increase in timely PCP followup, but its impact on the readmission rate was less clear.

Rationale: Serial measurements of alveolar macrophage (AM) transcriptional changes in patients with acute respiratory distress syndrome (ARDS) could identify cell-specific biological programs that are associated with clinical outcomes.Objectives: To determine whether AM transcriptional programs are associated with prolonged mechanical ventilation and 28-day mortality in individuals with ARDS.Methods: We performed genome-wide transcriptional profiling of AMs purified from BAL fluid collected from 35 subjects with ARDS. Cells were obtained at baseline (Day 1), Day 4, and Day 8 after ARDS onset (N = 68 total samples). We identified biological pathways that were enriched at each time point in subjects alive and extubated within 28 days after ARDS onset (alive/extubated_Day28) versus those dead or persistently supported on mechanical ventilation at Day 28 (dead/intubated_Day28).Measurements and Main Results: "M1-like" (classically activated) and proinflammatory gene sets such as IL-6/JAK/STAT5 (Janus kinase/signal transducer and activator of transcription 5) signaling were significantly enriched in AMs isolated on Day 1 in alive/extubated_Day28 versus dead/intubated_Day28 subjects. In contrast, by Day 8, many of these same proinflammatory gene sets were enriched in AMs collected from dead/intubated_Day28 compared with alive/extubated_Day28 subjects. Serially sampled alive/extubated_Day28 subjects were characterized by an AM temporal expression pattern of Day 1 enrichment of innate immune programs followed by prompt downregulation on Days 4 and 8. Dead/intubated_Day28 subjects exhibited an opposite pattern, characterized by progressive upregulation of proinflammatory programs over the course of ARDS. The relationship between AM expression profiles and 28-day clinical status was distinct in subjects with direct (pulmonary) versus indirect (extrapulmonary) ARDS.Conclusions: Clinical outcomes in ARDS are associated with highly distinct AM transcriptional programs.

An Enterobacter hormaechei isolate harboring bla_VIM-4 and mcr-9 was recovered from a pediatric patient in a U.S. hospital. The bla_VIM-4 and mcr-9 genes are carried on the same IncH12 plasmid, pME-1a. The isolate tested susceptible to colistin, without observed induction of colistin resistance. The mcr-9 gene is located between two insertion elements, IS903 and IS1, but lacks the downstream regulatory genes (qseC and qseB) found in other isolates that harbor mcr-9IMPORTANCE We describe the complete genome assembly and sequence of a clinical Enterobacter isolate harboring both bla_VIM-4 and mcr-9 recovered from a pediatric patient in the United States with a history of travel to Egypt. Moreover, to the best of our knowledge, this is the first report of an Enterobacter isolate harboring both bla_VIM-4 and mcr-9 from the United States. The bla_VIM-4 and mcr-9 genes are carried on the same IncH12 plasmid, pME-1a. The isolate tested susceptible to colistin, without observed induction of colistin resistance. The mcr-9 gene is located between two insertion elements, IS903 and IS1, but lacks the downstream regulatory genes (qseC and qseB) found in other isolates that harbor mcr-9.

Introduction: CT-P6 (trastuzumab-pkrb, Herzuma) is a trastuzumab biosimilar approved for use in HER2 positive breast cancer and HER2 positive gastric cancer. CT-P6 has been shown to exhibit similar safety and efficacy profiles to its reference product, trastuzumab. Preclinical and clinical studies have been performed to prove equivalence between CT-P6 and the trastuzumab originator. Areas Covered: In this review, we examine the evidence comparing CT-P6 with its reference product, trastuzumab. Both monoclonal antibodies function to target cells that overexpress HER2 on the cell surface. Preclinical pharmacologic modeling of CT-P6 shows a similar mechanism of action to trastuzumab, similar pharmacologic properties and a phase I trial in healthy volunteers showed similar pharmacokinetics. A multicenter phase III randomized clinical trial in patients with early breast cancer showed equivalent safety and efficacy between CT-P6 and trastuzumab. One-year follow-up of patients showed identical rates of cardiotoxicity. Expert Opinion: Preclinical and clinical studies showed CT-P6 pharmacologic profile, safety and efficacy are equivalent to trastuzumab. As such, it is a safe and effective alternative for use in patients with HER2 positive breast cancer and gastric cancer. Its implementation into clinical practice can potentially increase patient access and help financially alleviate overburdened health-care systems.