Faculty Bibliography

BACKGROUND:Critically ill patients with acute kidney injury (AKI) can be divided into two subphenotypes, resolving or nonresolving, on the basis of the trajectory of serum creatinine. It is unknown if the biology underlying these two AKI recovery patterns is different. METHODS:We measured eight circulating biomarkers in plasma obtained from a cohort of patients admitted to an intensive care unit (ICU) (n = 1241) with systemic inflammatory response syndrome. The biomarkers were representative of several biologic processes: apoptosis (soluble Fas), inflammation (soluble tumor necrosis factor receptor 1, interleukin 6, interleukin 8) and endothelial dysfunction, (angiopoietin 1, angiopoietin 2, and soluble vascular cell adhesion molecule 1). We tested for associations between biomarker levels and AKI subphenotypes using relative risk regression accounting for multiple hypotheses with the Bonferroni correction. RESULTS:During the first 3 days of ICU admission, 868 (70%) subjects developed AKI; 502 (40%) had a resolving subphenotype, and 366 (29%) had a nonresolving subphenotype. Hospital mortality was 12% in the resolving subphenotype and 21% in the nonresolving subphenotype. Soluble Fas was the only biomarker associated with a nonresolving subphenotype after adjustment for age, body mass index, diabetes, and Acute Physiology and Chronic Health Evaluation III score (p = 0.005). CONCLUSIONS:Identifying modifiable targets in the Fas-mediated pathway may lead to strategies for prevention and treatment of a clinically important form of AKI.

Purpose: Bronchial and gastroenteropancreatic neuroendocrine tumors (NET) are slow-growing tumors, which frequently express somatostatin receptors on their cell membranes. These receptors are targets for therapy with Lutetium-177-labeled somatostatin analogues. We have treated over 1,200 patients with peptide receptor radionuclide therapy (PRRT) with [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate (¹⁷⁷Lu-DOTATATE) since the year 2000 and present the results on efficacy, survival, and toxicity of this therapy.Experimental Design: For safety analysis, 610 patients treated with a cumulative dose of at least 100 mCi (3.7 GBq) ¹⁷⁷Lu-DOTATATE were included. A subgroup of 443 Dutch patients who were treated with a cumulative dose of at least 600 mCi (22.2 GBq) ¹⁷⁷Lu-DOTATATE before 2013 was further analyzed for efficacy and survival.Results: The objective response rate of the total group of patients was 39%. Stable disease was reached in 43% of patients. Progression-free survival (PFS) and overall survival (OS) for all NET patients were 29 months [95% confidence interval (CI), 26-33 months] and 63 months (95% CI, 55-72 months). Long-term toxicity included acute leukemia in four patients (0.7%) and myelodysplastic syndrome in nine patients (1.5%). No therapy-related long-term renal or hepatic failure occurred.Conclusions: PRRT with ¹⁷⁷Lu-DOTATATE is a favorable therapeutic option in patients with metastatic bronchial and gastroenteropancreatic NETs that express somatostatin receptors. PRRT with ¹⁷⁷Lu-DOTATATE is safe with few side-effects and shows good response rates with PFS of 29 months and OS of 63 months. Clin Cancer Res; 23(16); 4617-24. ©2017 AACR.

Antiretroviral therapy has enabled people to live long lives with human immunodeficiency virus (HIV). As a result, most HIV-infected adults in the United States are >50 years of age. In light of this changing epidemiology, HIV providers must recognize and manage multiple comorbidities and aging-related syndromes. Geriatric principles can help meet this new challenge, as preservation of function and optimization of social and psychological health are relevant to the care of aging HIV-infected adults, even those who are not yet old. Nonetheless, the field is still in its infancy. Although other subspecialties have started to explore the role of geriatricians, little is known about their role in HIV care, and few clinics have incorporated geriatricians. This article introduces basic geriatric nomenclature and principles, examines several geriatric consultation models from other subspecialties, and describes our HIV and Aging clinical program to encourage investigation of best practices for the care of this population.

Objective/UNASSIGNED:The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to standardize measurement of clinically relevant patient-reported outcomes. This study evaluated the reliability and construct validity of select PROMIS static short-form (SF) instruments in women with fibromyalgia. Design/UNASSIGNED:Analysis of baseline data from the Fibromyalgia Activity Study with TENS (FAST), a randomized controlled trial of the efficacy of transcutaneous electrical nerve stimulation. Setting/UNASSIGNED:Dual site, university-based outpatient clinics. Subjects/UNASSIGNED:Women aged 20 to 67 years diagnosed with fibromyalgia. Methods/UNASSIGNED:Participants completed the Revised Fibromyalgia Impact Questionnaire (FIQR) and 10 PROMIS static SF instruments. Internal consistency was calculated using Cronbach alpha. Convergent validity was examined against the FIQR using Pearson correlation and multiple regression analysis. Results/UNASSIGNED:PROMIS static SF instruments had fair to high internal consistency (Cronbach α = 0.58 to 0.94, P  < 0.05). PROMIS 'physical function' domain score was highly correlated with FIQR 'function' score (r = -0.73). The PROMIS 'total' score was highly correlated with the FIQR total score (r = -0.72). Correlations with FIQR total score of each of the three PROMIS domain scores were r = -0.65 for 'physical function,' r = -0.63 for 'global,' and r = -0.57 for 'symptom' domain. PROMIS 'physical function,' 'global,' and 'symptom' scores explained 58% of the FIQR total score variance. Conclusions/UNASSIGNED:Select PROMIS static SF instruments demonstrate convergent validity with the FIQR, a legacy measure of fibromyalgia disease severity. These results highlight the potential utility of select PROMIS static SFs for assessment and tracking of patient-reported outcomes in fibromyalgia.

Nurse practitioner (NP) co-management involves an NP and physician sharing responsibility for the care of a patient. This study evaluates the impact of NP co-management for clinically complex patients in a home-based primary care program on hospitalizations, 30-day hospital readmissions, and provider satisfaction. We compared preenrollment and postenrollment hospitalization and 30-day readmission rates of home-bound patients active in the Nurse Practitioner Co-Management Program within the Mount Sinai Visiting Doctors Program (MSVD) (n = 87) between January 1, 2012, and July 1, 2013. Data were collected from electronic medical records. An anonymous online survey was administered to all physicians active in the MSVD in July 2013 (n = 13).After enrollment in co-management, patients have lower annual hospitalization rates (1.26 vs. 2.27, p = .005) and fewer patients have 30-day readmissions (5.8% vs. 17.2%, p = .004). Eight of 13 physicians feel "much" or "somewhat" less burned out by their work after implementation of co-management. The high level of provider satisfaction and reductions in annual hospitalization and readmission rates among high-risk home-bound patients associated with NP co-management may yield not only benefits for patients, caregivers, and providers but also cost savings for institutions.

BACKGROUND:Serotonin secretion occurs in approximately 1%-4% of patients with a pancreatic neuroendocrine tumour (PNET), but the incidence is not well defined. The aim of this study was to determine the incidence of serotonin secretion with and without carcinoid syndrome and the prognostic value for overall survival (OS). METHODS:Data were collected from 255 patients with a PNET if 24-hours urinary 5-hydroxyindoleacetic acid excretion (5-HIAA) was assessed. Patients were diagnosed with serotonin secretion if 24-hours urinary 5-HIAA excretion was more than 3× the upper limit of normal (ULN) of 50 μmol/24 hours during follow-up. The effect of serotonin secretion on OS was estimated with uni- and multivariate analyses using a Cox regression. RESULTS:Two (0.8%) patients were diagnosed with carcinoid syndrome, and another 20 (7.8%) had a serotonin-secreting PNET without symptoms. These patients mostly had ENETS stage IV disease with high chromogranin A (CgA). Serotonin secretion was a negative prognostic factor in univariate analysis (HR 2.2, 95% CI: 1.27-3.81), but in multivariate analysis, only CgA>10× ULN (HR: 1.81, 95% CI: 1.10-2.98) and neuron-specific enolase (NSE) >ULN (HR: 3.51, 95% CI: 2.26-5.46) were predictors for OS. Immunohistochemical staining for serotonin was positive in 28.6% of serotonin-secreting PNETs (one with carcinoid syndrome) and negative in all controls. CONCLUSION/CONCLUSIONS:Carcinoid syndrome is rare in patients with a PNET, but serotonin secretion occurs often. This is a negative prognostic factor for OS, but after correction for CgA and NSE, it is no longer a predictor and probably only a "not-so innocent bystander" in patients with high tumour burden.

This article describes the experiences of a quality improvement team that used small cycles of change to improve the emergency department (ED) of an academic medical center. The role of EDs in the provision of healthcare continues to increase in importance. ED bottlenecks contribute to long waits and diminished outcomes for ED patients as well as more system-wide issues, such as inefficiencies in inpatient admission processes. The purpose of this "ED Operational Efficiency Project" was to reduce lengths of stay (LOS) for low-acuity patients. The team used lean management techniques to both improve services and shift the ED culture to prioritize continuous quality improvement. The goal to reduce LOS by 30% was met as the result of several inter=related projects (or small cycles of change). Key lessons include monitoring metrics, communicating with teams and target populations, learning from initial failures, using small wins to increase momentum, and anchoring changes.

Here we describe the spread of colistin resistance in clinical isolates of carbapenem-resistant Klebsiella pneumoniae in Medellín, Colombia. Among 32 isolates collected between 2012 and 2014, 24 showed genetic alterations in mgrB Nineteen isolates belonged to sequence type 512 (ST512) (or its single locus variant [SLV]) and harbored an 8.1-kb hsdMSR insertion corresponding to ISKpn25, indicating a clonal expansion of the resistant strain. The insertion region showed 100% identity to several plasmids, suggesting that the colistin resistance is mediated by chromosomal integration of plasmid DNA.

There are no data comparing outcomes of patients treated with ceftazidime-avibactam versus comparators for carbapenem-resistant Enterobacteriaceae infections. At our center, ceftazidime-avibactam treatment of carbapenem-resistant Klebsiella pneumoniae bacteremia was associated with higher rates of clinical success (P = 0.006) and survival (P = 0.01) than other regimens. Across treatment groups, there were no differences in underlying diseases, severity of illness, source of bacteremia, or strain characteristics (97% produced K. pneumoniae carbapenemase). Aminoglycoside- and colistin-containing regimens were associated with increased rates of nephrotoxicity (P = 0.002).