Faculty Bibliography

OBJECTIVE:The aim of this study was to identify and test whether AKI sub-phenotypes have prognostic and therapeutic implications. METHODS:First, latent class analysis methodology was applied independently in two critically ill populations (Discovery: n=794 and Replication: n=425) with AKI. Second, a parsimonious classification model was developed to identify AKI sub-phenotypes. Third, the classification model was applied to patients with AKI in the Vasopressin in Septic Shock (VASST: n=271) clinical trial and differences in treatment response were determined. In all three populations, AKI was defined using serum creatinine and urine output. RESULTS:A two-sub-phenotype LCA model had the best fit in both the Discovery (p = 0.004) and Replication (p= 0.004) AKI groups. The risk of 7-day renal non-recovery and 28-day mortality was greater with AKI sub-phenotype 2 (AKI-SP2) relative to AKI sub-phenotype 1 (AKI-SP1). The AKI sub-phenotypes discriminated risk for poor clinical outcomes better than the Kidney Disease Improving Global Outcomes (KDIGO) Stages of AKI. A three-variable model that included markers of endothelial dysfunction and inflammation accurately determined sub-phenotype membership (C-statistic 0.92). In VASST, vasopressin compared to norepinephrine was associated with improved 90-day mortality in AKI-SP1 (46% vs 27%, respectively; p=0.02), but no significant difference in AKI-SP2 (49% vs 45%, respectively; p=0.54) and the p-value for interaction was 0.05. CONCLUSION/CONCLUSIONS:This analysis identified two molecularly distinct AKI sub-phenotypes with different clinical outcomes and response to vasopressin therapy. Identification of AKI sub-phenotypes could improve risk prognostication and may be useful for predictive enrichment in clinical trials.

AIMS:Coronary artery calcium (CAC) is the strongest predictor of cardiovascular disease (CVD), yet is also associated with chronic non-CVD such as cancer. We performed this analysis in order to describe the association of CAC with CVD vs. cancer mortality. METHODS AND RESULTS:The CAC Consortium is comprised of 66 636 scans performed in asymptomatic patients without known CVD. The mean age was 54 ± 11 years and 67% of participants were men. Cause of death was ascertained from death certificates. The association of CAC with cause-specific mortality was calculated using Fine and Gray sub-distribution hazard ratio (SHR) models, which account for competing causes of death. There were 3158 deaths over a median 12 ± 4 years follow-up (37% cancer and 32% CVD). Cancer was the leading cause of death when CAC = 0 (50%) with CVD overtaking cancer when baseline CAC >300. Compared to participants with CAC = 0, the SHR for CVD mortality was 1.44 [95% confidence interval (CI) 1.14-1.81], 2.26 (95% CI 1.76-2.90), and 3.68 (95% CI 2.90-4.67) for patients with CAC 1-99, 100-299, and ≥300, and the SHR for cancer was 1.04 (95% CI 0.88-1.23), 1.19 (95% CI 0.98-1.46), and 1.30 (95% CI 1.07-1.58). CONCLUSION:Cancer was the leading cause of death for patients with baseline CAC = 0, whereas CVD overtook cancer above a threshold of CAC >300. These results argue for a focused approach for patients at the extremes of CAC scoring while suggesting that combined CVD and cancer primary prevention strategies for patients with intermediate CAC scores may significantly decrease mortality from the two leading causes of death.

PURPOSE/OBJECTIVE:Peptide receptor radionuclide therapy (PRRT) with the radiolabeled somatostatin analogue [Lutetium-177-DOTA0-Tyr3]octreotate (177Lu-DOTATATE) is widely applied for inoperable metastatic small intestinal and nonfunctioning pancreatic neuroendocrine tumors (pNETs). The aim of this study is to describe the safety and efficacy of the treatment of functioning pNETs. METHODS:Patients were treated with up to four cycles of 177Lu-DOTATATE with an intended dose of 7.4 Gbq per cycle. Radiological (Response Evaluation Criteria in Solid Tumors 1.1), symptomatic, and biochemical response were analyzed retrospectively for all patients with a functioning pNET (insulinoma, gastrinoma, VIPoma, and glucagonoma) treated with 177Lu-DOTATATE. Quality of life (QOL) was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Module questionnaire. RESULTS:Thirty-four patients with a metastatic functioning pNET (European Neuroendocrine Tumor Society grade 1 or 2) were included: 14 insulinomas, 5 VIPomas, 7 gastrinomas, and 8 glucagonomas. Subacute hematological toxicity, grade 3 or 4 occurred in 4 patients (12%) and a hormonal crisis in 3 patients (9%). PRRT resulted in partial or complete response in 59% of patients and the disease control rate was 78% in patients with baseline progression. 71% of patients with uncontrolled symptoms had a reduction of symptoms and a more than 80% decrease of circulating hormone levels was measured during follow-up. After PRRT, median progression-free survival was 18.1 months (interquartile range: 3.3 to 35.7) with a concurrent increase in QOL. CONCLUSION/CONCLUSIONS:Treatment with 177Lu-DOTATATE is a safe and effective therapy resulting in radiological, symptomatic and biochemical response in a high percentage of patients with metastatic functioning pNETs. Hormonal crises occur relatively frequent and preventive therapy should be considered before and/or during PRRT.

BACKGROUND:While an expanding armamentarium of pharmacologic therapies has contributed to improved outcomes among adults with heart failure (HF) over the past two decades, this has also been accompanied by an increase in the number of medications taken by adults with HF. The use of at least 10 medications, defined as hyperpolypharmacy, is particularly notable given its association with adverse outcomes. We aimed to assess the prevalence and identify determinants of hyperpolypharmacy among adults with HF. METHODS:We studied adults aged ≥50 years with self-reported HF from the National Health And Nutrition Examination Survey (NHANES) in 2003-2014. We calculated weighted means and percentages to describe patient characteristics. We conducted a multivariable Poisson regression analysis to identify factors independently associated with hyperpolypharmacy; we adjusted for survey sampling, socio-demographics, comorbidity, geriatric conditions, and health care utilization. We examined 947 participants, representing 4.6 million adults with HF. RESULTS:The prevalence of hyperpolypharmacy was 26%. In a multivariable regression analysis, comorbidity count, ≥10 ambulatory contacts, and ≥ 3 hospitalizations were independently associated with hyperpolypharmacy. Interestingly, functional impairment and cognitive impairment were not independently associated with hyperpolypharmacy; while low annual household income and low educational status were each associated with an almost 2-fold increase in hyperpolypharmacy. CONCLUSION:Hyperpolypharmacy is a common condition among adults with HF. We additionally found that low household income and low educational status are independently associated with hyperpolypharmacy, suggesting that non-medical factors may be contributing to this potentially harmful condition.

Background/Purpose: Despite the increasing trend toward ambulatory surgery rate in general, for cleft lip repair, 72.1% of patients in the United States are still hospitalized. Multiple centers have been studying this and with the very recent publishing of 2 large volume studies published in Plastic and Reconstructive Surgery supporting the safety of outpatient cleft lip surgery, it has become a high-profile debatable topic in cleft management. Last year at ACPA in the plastic surgery breakout session there was a heated debate on the topic between surgeons. And just this summer, one of the authors articles was featured as the PRS Journal Club article of the month via Social media, where there were 68 comments, 11 shares, and 40 likes, which placed the article in the TOP 15 most viewed article in PRS Journal's website. So this is a topic that more and more surgeons and craniofacial teams are thinking about and considering changing practice management but that deserves being brought into the spotlight to discuss all the pros and cons. The goal of the presentation are to present a literature review up to date on inpatient versus outpatient cleft lip surgery and have members of the panel share their and data behind their approach to postoperative cleft lip management. We would like to focus on what has been studied and reported versus what people practice because "that is how they were trained" or that is how they "historically" have always done it. Methods/Description: We will start with an overview of the literature surrounding inpatient versus outpatient cleft lip surgery and epidemiology about the numbers of institutions that do inpatients versus outpatient. If possible, we would like to include an audience poll to get an idea of practice patterns in the room. Then based on the recent published studies, each panelist will share different protocols that have been successful for outpatient cleft lip management and how that could be implemented if a center wants to consider outpatient cleft lip surgery. This includes: preoperative education that can be done by the team or nurse managers, perioperative management before, during, and after the operation, and postoperative care after they go home. All are very key components to a successful outpatient cleft lip management. We will also discuss the barriers to doing outpatient cleft lip surgery as well as having a panelist who consistently does inpatient cleft lip surgery to present the rationale behind their practice management and also their barriers to outpatient cleft lip surgery. I have reached out to a few people and will be discussing with them at the upcoming ASPS meeting to see who may be interested in joining the panel to discuss that. We will discuss the economic impact overall of practice changes to a predominantly outpatient surgery and also potential insurance policy impact. We think this will be a very useful topic for any team member participating in the care of a cleft lip patient

Background: Although the population of older adults is rising rapidly, the number of physicians seeking specialty training in geriat-rics is decreasing. This study of fellows in geriatrics training programs across the United States explored motivating factors that led fellows to pursue geriatrics as a career in order to inform the recruiting of more trainees to the field.
Method(s): 10-15 fellows were sought for interviews, until satu-ration was reached. 30-minute semi-structured telephone interviews were conducted by the primary investigator with fifteen geriatrics fellows from academic medical centers across the United States, 14 of whom were at Claude D. Pepper Older Americans Independence Centers. This qualitative study involved interviews that were tran-scribed and descriptively coded by two independent reviewers. A thematic analysis of the codes was summarized.
Result(s): Fifteen geriatrics fellows in seven different states partic-ipated in the study, and they revealed that mentorship and early clin-ical exposure to geriatrics were some of the most influential factors affecting career choice. Having positive attitudes and close relation-ships with older adults prior to medical school are other critical factors in influencing trainees to pursue careers in geriatrics.
Conclusion(s): The results of this study have the potential for a large impact, helping to inform best practices in encouraging trainees to enter the field, and enhancing medical student and resident exposure to geriatrics and mentorship from geriatricians. As the number of older individuals rises, we need innovative ways to draw medical students and residents to geriatrics. This study demonstrates the need for geri-atricians to serve not only as mentors to trainees but also as proactive ambassadors to the field

BACKGROUND:Awareness of disease status has been identified as a factor in the treatment decision-making process. Women with recurrent ovarian cancer are facing the challenge of making treatment decisions throughout the disease trajectory. It is not understood how women with ovarian cancer perceive their disease and subsequently make treatment decisions. PURPOSE/OBJECTIVE:The purpose of this phenomenological study was to understand the lived experience of women with recurrent ovarian cancer, how they understood their disease and made their treatment decisions. METHODS:A qualitative design with a descriptive phenomenological method was used to conduct 2 in-depth interviews with 12 women (n = 24 interviews). Each interview was ∼60 minutes and was digitally recorded and professionally transcribed. Data collection focused on patients' understanding of their disease and how patients participated in treatment decisions. A modified version of Colaizzi's method of phenomenological reduction guided data analysis. RESULTS:Three themes emerged to describe the phenomenon of being aware of disease status: (1) perceiving recurrent ovarian cancer as a chronic illness, (2) perceived inability to make treatment decisions, and (3) enduring emotional distress. CONCLUSIONS AND IMPLICATIONS/CONCLUSIONS:This study revealed how 12 women conceptualized recurrent ovarian cancer as a chronic disease and their perceived inability to make treatment decisions because of lack of information and professional qualifications, resulting in enduring emotional distress. Future research should replicate the study to confirm the persistence of the themes for racially, ethnically, and religiously diverse patient samples and to improve understanding of awareness of disease status and decision-making processes of patients.