Faculty Bibliography

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.

BACKGROUND:Double pituitary adenomas are a rare occurrence. Synchronous clinical manifestation is extremely rare. CASE DESCRIPTION/METHODS:We report a case of a 51-year-old female with symptoms of both hypercortisolism and acromegaly during the past 2 years. Endocrine evaluation confirmed active acromegaly and revealed adrenocorticotropin hormone-dependent hypercortisolemia. Preoperative magnetic resonance imaging of the pituitary demonstrated separated double microadenomas with different intensity. Immunohistochemical analysis of each separate adenoma confirmed an exact diagnosis. The diagnosis of acromegaly and adrenocorticotropin hormone-dependent Cushing's disease was confirmed. CONCLUSIONS:This is the third reported case in the literature of synchronous clinical manifestation of acromegaly and Cushing's disease. Extensive surgical exploration of the sella must be performed to avoid surgical failures from residual tumor. Immunohistochemical analysis is required to confirm an exact diagnosis for each of the double pituitary adenomas.

BACKGROUND:Evidence-based therapy for heart failure remains underutilized at hospital discharge, particularly for patients with heart failure who are hospitalized for another cause. We developed clinical decision support (CDS) to recommend an angiotensin converting enzyme (ACE) inhibitor during hospitalization to promote its continuation at discharge. The CDS was designed to be implemented in both interruptive and non-interruptive versions. OBJECTIVES/OBJECTIVE:To compare the effectiveness and implementation of interruptive and non-interruptive versions of a CDS to improve care for heart failure. METHODS:Hospitalizations of patients with reduced ejection fraction were pseudo-randomized to deliver interruptive or non-interruptive CDS alerts to providers based on even or odd medical record number. We compared discharge utilization of an ACE inhibitor or angiotensin receptor blocker (ARB) for these two implementation approaches. We also assessed adoption and implementation fidelity of the CDS. RESULTS:percentile) of 14 (5,32) alerts were triggered per hospitalization. CONCLUSIONS:A CDS implemented as an interruptive alert was associated with improved quality of care for heart failure. Whether the potential benefits of CDS in improving cardiovascular care were worth the high burden of interruptive alerts deserves further consideration. CLINICALTRIALS. GOV IDENTIFIER/UNASSIGNED:NCT02858674.