Faculty Bibliography

BACKGROUND: Testing for venous thromboembolism (VTE) is associated with cost and risk to patients (e.g. radiation). To assess the appropriateness of imaging utilization at the provider level, it is important to know that provider's diagnostic yield (percentage of tests positive for the diagnostic entity of interest). However, determining diagnostic yield typically requires either time-consuming, manual review of radiology reports or the use of complex and/or proprietary natural language processing software. OBJECTIVES: The objectives of this study were twofold: 1) to develop and implement a simple, user-configurable, and open-source natural language processing tool to classify radiology reports with high accuracy and 2) to use the results of the tool to design a provider-specific VTE imaging dashboard, consisting of both utilization rate and diagnostic yield. METHODS: Two physicians reviewed a training set of 400 lower extremity ultrasound (UTZ) and computed tomography pulmonary angiogram (CTPA) reports to understand the language used in VTE-positive and VTE-negative reports. The insights from this review informed the arguments to the five modifiable parameters of the NLP tool. A validation set of 2,000 studies was then independently classified by the reviewers and by the tool; the classifications were compared and the performance of the tool was calculated. RESULTS: The tool was highly accurate in classifying the presence and absence of VTE for both the UTZ (sensitivity 95.7%; 95% CI 91.5-99.8, specificity 100%; 95% CI 100-100) and CTPA reports (sensitivity 97.1%; 95% CI 94.3-99.9, specificity 98.6%; 95% CI 97.8-99.4). The diagnostic yield was then calculated at the individual provider level and the imaging dashboard was created. CONCLUSIONS: We have created a novel NLP tool designed for users without a background in computer programming, which has been used to classify venous thromboembolism reports with a high degree of accuracy. The tool is open-source and available for download at http://iturrate.com/simpleNLP. Results obtained using this tool can be applied to enhance quality by presenting information about utilization and yield to providers via an imaging dashboard.

The cancer community understands the value of blood profiling measurements in assessing and monitoring cancer. We describe an effort among academic, government, biotechnology, diagnostic, and pharmaceutical companies called the Blood Profiling Atlas in Cancer (BloodPAC) Project. BloodPAC will aggregate, make freely available, and harmonize for further analyses, raw datasets, relevant associated clinical data (e.g., clinical diagnosis, treatment history, and outcomes), and sample preparation and handling protocols to accelerate the development of blood profiling assays.

OBJECTIVE:To evaluate which tests are performed to diagnose hypercortisolism in patients included in the European Registry on Cushing's syndrome (ERCUSYN), and to examine if their use differs from the current guidelines. PATIENTS AND METHODS:We analyzed data on the diagnostic tests performed in 1341 patients with Cushing's syndrome (CS) who have been entered into the ERCUSYN database between January 1, 2000 and January 31, 2016 from 57 centers in 26 European countries. Sixty-seven percent had pituitary-dependent CS (PIT-CS), 24% had adrenal-dependent CS (ADR-CS), 6% had CS from an ectopic source (ECT-CS) and 3% were classified as having CS from other causes (OTH-CS). RESULTS: < 0.05). CONCLUSIONS:Use of diagnostic tests for CS varies across Europe and partly differs from the currently available guidelines. It would seem pertinent that a European consensus be established to determine the best diagnostic approach to CS, taking into account specific inter-country differences with regard to the availability of diagnostic tools.

Peptide receptor radionuclide therapy (PRRT) with [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate (¹⁷⁷Lu-DOTATATE) is a treatment with good results in patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEPNETs). However, there are some pitfalls that should be taken into consideration when evaluating the treatment response after PRRT. 354 Dutch patients with GEPNETs who were treated with ¹⁷⁷Lu-DOTATATE between March 2000 and December 2011 were retrospectively selected. Liver function parameters and chromogranin A were measured before each therapy and in follow-up. Anatomical imaging was performed before therapy and in follow-up. An increase in aminotransferases by ≥20% compared to baseline was observed in 83 of 351 patients (24%). In patients with an objective response (OR) and stable disease (SD) this increase was observed in 71/297 (24%) and in patients with progressive disease (PD) it was observed in 12/54 patients (22%). An increase in chromogranin A by ≥20% compared to baseline was observed in 76 patients (29%). This was present in 34% of patients who eventually had PD and 27% of patients who had OR/SD. In 70% of patients this tumour marker returned to baseline levels after therapy. An increase in liver enzymes and chromogranin A is not uncommon after PRRT. In the vast majority of patients this will resolve in follow-up. Clinicians should be aware that these changes may occur due to radiation-induced inflammation or disease progression and that repeated measurements over time are necessary to differentiate between the two.

The number of new HIV infections continues to be on the rise in many high-income countries, most notably among men who have sex with men (MSM). Despite recent attention to the use of antiretroviral medications as pre-exposure prophylaxis (PrEP) among MSM, considerably less research has been devoted to examining the awareness and use of post-exposure prophylaxis (PEP). Based on a convenience sample of 179 self-reported HIV-uninfected MSM using a geosocial-networking smartphone application, this study is among the first to examine the awareness and use of PEP and their demographic and behavioral correlates among MSM in London. Most respondents (88.3%) had heard of PEP, where 27.4% reported having used it. In multivariable models, the disclosure of one's sexual orientation to their general practitioner (Prevalence ratio [PR]: 3.49; 95% confidence interval (CI): 1.14, 10.70; p = .029) and reporting one's HIV status as negative (rather than unknown) (PR: 11.49; 95% CI: 1.68, 76.92; p = .013) were associated with having heard of PEP; while the recent use of club drugs (PR: 3.02; 95% CI: 1.42, 6.43; p = .004) was associated with having ever used PEP. High awareness and use in this sample suggest that PEP is a valuable risk-reduction strategy that should be capitalized on, be it in addition to or in the absence of PrEP.

The subtle signs and symptoms of substance use disorder (SUD) often go unrecognized by physicians in training. Many times, this is because primary care physicians are not trained to recognize SUDs as free-standing medical illnesses that can be successfully treated, and require primary care interventions. Physicians-in-training at the residency level may not know what these disorders looks like in their early and active phases, nor in phases of recovery. Most young physicians have never had the opportunity to speak with patients who are actively working to recover or in long-term recovery. In 2008, a major NYC teaching hospital (Lenox Hill Hospital) began to require all first-year primary care internal medical residents to attend a 12-hour Physician Alcohol and Addiction Training Program (PAAT). This innovative program utilizes patients as teachers. Each physician is paired with an alcoholic or addicted patient in recovery and actively involved in AA. In a powerful reversal of the traditional doctor-patient relationship, the patients, or "buddies" act as 1:1 teachers and mentors for the resident physicians, providing a profound and personal window into the experience of alcoholism and addiction, and modeling positive treatment outcomes and recovery. This work with buddies is integrated, in real time, with the training provided by physician faculty. Buddies accompany their resident physicians to an AA meeting and provide them with an understanding of 12-step sober support meetings as a powerful treatment modality. Each Buddy-Resident pair processes their AA experience, dispelling common myths about sober support meetings and dire prognosis of alcoholism and addiction. Residents get to know their buddies as people with expertise to offer them, and not simply as patients. They administer several screening tools (MAST, CAGE, and AUDIT) to their buddies, who are asked to answer both as they would have when actively using, and as they would now, looking backward from their current perches in recovery. This provides residents insight into the defensiveness, minimization and denial that they will face when screening for SUDs, and the critical need for cultivating longitudinal primary care relationships. Residents then take full biopsychosocial histories, and are encouraged to follow their curiosity and ask the questions that they would never ask if their buddies were their patients. The program concludes with resident presentations of their buddies' histories of use and recovery, getting feedback from both faculty and peers. Data about resident ratings of the program, utilizing the Wilcoxon matched-pairs signed-ranks pre-and post-tests, will be presented, as well as results demonstrating robust changes in students' perceptions after buddy mentoring, with the emergence of an understanding that substance use is a chronic relapsing medical disease that can be successfully treated, rather than an irreparable deficiency in moral character

BACKGROUND Electrocardiographic presentations of left ventricle aneurysms are diverse; however, a persistent ST segment elevation post myocardial infarction is most commonly reported. CASE REPORT The authors present a case of a 67-year-old man who presented to the emergency department after three days of chest pain and was found to have an acute myocardial infarction with an incidental finding of a left ventricular aneurysm. His surface electrocardiogram, however, demonstrated only inverted T waves in the precordial leads. He had a very elevated serum troponin I consistent with an acute myocardial injury which prompted a cardiac catheterization with angioplasty. Post angioplasty, he had persistent T wave inversions in the precordial leads. CONCLUSIONS It is important for clinicians to appreciate that the presence of newly inverted T waves in patients with a late presentation post myocardial infarction should raise a concern for a possible left ventricular aneurysm.

Genome-wide association studies (GWAS) have highlighted a large number of genetic variants with potential disease association, but functional analysis remains a challenge. Here we describe an approach to functionally validate identified variants through differentiation of induced pluripotent stem cells (iPSCs) to study cellular pathophysiology. We collected peripheral blood cells from Framingham Heart Study participants and reprogrammed them to iPSCs. We then differentiated 68 iPSC lines into hepatocytes and adipocytes to investigate the effect of the 1p13 rs12740374 variant on cardiometabolic disease phenotypes via transcriptomics and metabolomic signatures. We observed a clear association between rs12740374 and lipid accumulation and gene expression in differentiated hepatocytes, in particular, expression of SORT1, CELSR2, and PSRC1, consistent with previous analyses of this variant using other approaches. Initial investigation of additional SNPs also highlighted correlations with gene expression. These findings suggest that iPSC-based population studies hold promise as tools for the functional validation of GWAS variants.