Faculty Bibliography

BACKGROUND:Cardiovascular disease (CVD) rates are increased in HIV. The degree to which myocyte injury, strain, and fibrosis occur prior to clinical disease and relate to coronary plaque in HIV is unknown. OBJECTIVE:To investigate newer cardiac biomarkers of subclinical myocyte injury [high-sensitivity troponin T (hs-cTnT)], strain (amino terminal proB-type natriutretic peptide), fibrosis (soluble ST2, Galectin-3), and vascular inflammation (oxidized LDL, lipoprotein-associated phospholipase A2) in HIV-infected individuals and non-HIV controls and relate these to coronary plaque by cardiac computed tomography angiography. DESIGN/METHODS:Observational. METHODS:Markers were investigated in 155 HIV-infected and 70 non-HIV-infected participants without known CVD and with low traditional CVD risk and related to cardiac computed tomography angiography data. RESULTS:Age, sex, and race did not differ between the groups. Hs-cTnT [3.1 (3.0, 6.4) vs. 3.0 (3.0, 4.0) ng/l, P = 0.03], Galectin-3 [13.5 (10.6, 18.1) vs. 11.6 (9.9, 14.5) ng/ml, P = 0.002], and soluble ST2 [31.5 (24.5, 41.5) vs. 28.3 (20.2, 33.5) ng/ml, P = 0.01] were significantly higher in HIV-infected participants vs. CONTROLS/METHODS:Detectable hs-cTnT (seen in 50% of HIV participants) related to the overall presence of plaque [odds ratio (OR) 2.3, P = 0.01] and particularly to coronary calcium (OR for Agatston calcium score > 0, 3.3, P = 0.0008 and OR for calcified plaque 7.4, P = 0.01) in HIV, but not in non-HIV. CONCLUSION/CONCLUSIONS:Subclinical myocyte injury is observed among young, asymptomatic HIV-infected individuals with low traditional cardiac risk factors. In the setting of HIV infection, the presence of detectable cardiac troponin is strongly associated with coronary plaque, particularly calcified plaque among an asymptomatic group. Future studies are needed to assess if early subclinical injury marked by hs-cTnT predicts plaque progression and cardiac events in HIV.

BACKGROUND: Type 2 myocardial infarction (MI) is defined as myocardial necrosis (myonecrosis) due to an imbalance in supply and demand with clinical evidence of ischemia. Some clinical scenarios of supply-demand mismatch predispose to myonecrosis but limit the identification of symptoms and ECG changes referable to ischemia; therefore, the MI definition may not be met. Factors that predispose to type 2 MI and myonecrosis without definite MI, approaches to treatment, and outcomes remain poorly characterized. METHODS: Patients admitted to an academic medical center with an ICD-9 diagnosis of secondary myocardial ischemia or non-primary diagnosis of non-ST-elevation MI were retrospectively reviewed. Cases were classified as either MI (n=255) or myonecrosis without definite MI (n=220) based on reported symptoms, ischemic ECG changes, and new wall motion abnormalities. RESULTS: Conditions associated with type 2 MI or myonecrosis included non-cardiac surgery (38%), anemia or bleeding requiring transfusion (32%), sepsis (31%), tachyarrhythmia (23%), hypotension (22%), respiratory failure (23%), and severe hypertension (8%). Inpatient mortality was 5%, with no difference between patients with MI and those with myonecrosis (6% vs. 5%, p=0.41). At discharge, only 43% of patients received aspirin and statin therapy. CONCLUSIONS: Type 2 MI and myonecrosis occur frequently in the setting of supply-demand mismatch due to non-cardiac surgery, sepsis, or anemia. Myonecrosis without definite MI is associated with similar in-hospital mortality as type 2 MI; both groups warrant further workup for cardiovascular disease. Antiplatelet and statin prescriptions were infrequent at discharge, reflecting physician uncertainty about the role of secondary prevention in these patients.

BACKGROUND: The development of molecular diagnostics that detect both the presence of Mycobacterium tuberculosis in clinical samples and drug resistance-conferring mutations promises to revolutionize patient care and interrupt transmission by ensuring early diagnosis. However, these tools require the identification of genetic determinants of resistance to the full range of anti-tuberculosis drugs. OBJECTIVES: To determine the optimal molecular approach needed, we sought to create a comprehensive catalogue of resistance mutations and assess their sensitivity and specificity in diagnosing drug resistance. METHODS: We developed and validated molecular inversion probes for DNA capture and deep sequencing of 28 drug resistance loci in M.tuberculosis. We used the probes for targeted sequencing of a geographically diverse set of 1397 clinical M.tuberculosis isolates with known drug resistance phenotypes. We identified a minimal set of mutations to predict resistance to first- and second-line anti-tuberculosis drugs and validated our predictions in an independent dataset. We constructed and piloted a web-based database that provides public access to the sequence data and prediction tool. RESULTS: The predicted resistance to rifampicin and isoniazid exceeded 90% sensitivity and specificity, but was lower for other drugs. The number of mutations needed to diagnose resistance is large and for the 13 drugs studied it was 238 across 18 genetic loci. CONCLUSION: These data suggest that a comprehensive M.tuberculosis drug resistance diagnostic will need to allow for a high dimension of mutation detection. They also support the hypothesis that currently unknown genetic determinants, potentially discoverable by whole genome sequencing, encode resistance to second-line TB drugs.

IMPORTANCE/OBJECTIVE:The in vivo effect of pilocarpine hydrochloride on the Schlemm canal may help explain its pharmacologic mechanism of action and better indicate its clinical use. OBJECTIVE:To investigate the effect of pilocarpine on the structure of the Schlemm canal in vivo in healthy eyes and eyes with glaucoma. DESIGN, SETTING, AND PARTICIPANTS/METHODS:In this case-control study, healthy individuals and patients with open-angle glaucoma were prospectively enrolled between September 1, 2013, and June 30, 2014, after a complete ophthalmologic examination at a tertiary glaucoma referral practice. Eighty-one serial, horizontal, enhanced depth imaging optical coherence tomographic B-scans (interval between B-scans, approximately 35 µm) of the nasal corneoscleral limbus were performed before and 1 hour after topical administration of pilocarpine, 1%, in 1 eye of healthy volunteers and pilocarpine, 2%, in 1 eye of patients with glaucoma. Fifty B-scans in the overlapping area (circumferential length, approximately 1.7 mm) between the 2 sets of serial scans (before and after pilocarpine administration) were selected for analysis based on the structures of aqueous and blood vessels as landmarks. The cross-sectional area of the Schlemm canal was measured in each selected B-scan. Volume of the Schlemm canal was calculated using commercially available 3-dimensional reconstruction software. MAIN OUTCOMES AND MEASURES/METHODS:Mean cross-sectional area of the Schlemm canal. RESULTS:Enhanced depth imaging optical coherence tomographic scans of the Schlemm canal were performed successfully before and after administration of pilocarpine, 1%, in 9 healthy eyes (9 individuals) and pilocarpine, 2%, in 10 eyes with glaucoma (10 patients) (mean [SD] age, 31.9 [7.8] and 68.7 [13.2] years, respectively). Following pilocarpine administration, mean (SD) intraocular pressure decreased from 14.3 (1.3) to 13.7 (1.1) mm Hg in healthy eyes (P = .004) and from 17.5 (6.0) to 16.6 (6.1) mm Hg in eyes with glaucoma (P = .01). The mean (SD) cross-sectional area of the Schlemm canal increased by 21% (4667 [1704] to 5647 [1911] µm2) in healthy eyes (P < .001) and by 24% (3737 [679] to 4619 [692] µm2) in eyes with glaucoma (P < .001) (mean difference in percent increase, 2.2%; 95% CI, -8.5% to 12.9%). The mean (SD) volume of the Schlemm canal in the overlapping area increased from 8 004 000 (2 923 000) to 9 685 000 (3 277 000) µm3 in healthy eyes (P < .001) and from 6 468 000 (1 170 000) to 7 970 000 (1 199 000) µm3 in eyes with glaucoma (P < .001). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:These data suggest that pilocarpine expands the Schlemm canal in eyes with and without glaucoma. No differences in the effect were identified between the 2 groups. Enhanced depth imaging optical coherence tomography may be useful in investigating the effect of pharmacologic agents on the Schlemm canal.

BACKGROUND:Expense, efficiency of use, learning curves, workflow integration and an increased prevalence of serious incidents can all be barriers to adoption. We explored an observational approach and initial diagnostics to enhance total system performance in robotic surgery. METHODS:Eighty-nine robotic surgical cases were observed in multiple operating rooms using two different surgical robots (the S and Si), across several specialties (Urology, Gynecology, and Cardiac Surgery). The main measures were operative duration and rate of flow disruptions-described as 'deviations from the natural progression of an operation thereby potentially compromising safety or efficiency.' Contextual parameters collected were surgeon experience level and training, type of surgery, the model of robot and patient factors. Observations were conducted across four operative phases (operating room pre-incision; robot docking; main surgical intervention; post-console). RESULTS:A mean of 9.62 flow disruptions per hour (95 % CI 8.78-10.46) were predominantly caused by coordination, communication, equipment and training problems. Operative duration and flow disruption rate varied with surgeon experience (p = 0.039; p < 0.001, respectively), training cases (p = 0.012; p = 0.007) and surgical type (both p < 0.001). Flow disruption rates in some phases were also sensitive to the robot model and patient characteristics. CONCLUSIONS:Flow disruption rate is sensitive to system context and generates improvement diagnostics. Complex surgical robotic equipment increases opportunities for technological failures, increases communication requirements for the whole team, and can reduce the ability to maintain vision in the operative field. These data suggest specific opportunities to reduce the training costs and the learning curve.

Background. High volumes of hepatitis C (HCV)-infected detainees pass through US jails. However, short lengths of stay and competing priorities upon release complicate linkage to HCV care. We investigated linkage rates for patients with HCV following release from New York City (NYC) jails and describe a care coordination program (CCP) we initiated in June 2015 to improve linkage rates. Methods. We conducted a pre- and post-intervention study to assess rates of linkage related to the CCP. We used NYC Department of Health surveillance data to assess pre-intervention linkage rates for patients with chronic HCV seen in a correctional health clinic at Bellevue Hospital Center from January 2014 to June 2015. Linkage was defined as an HCV viral load or genotype <90 days in the community after release from an index incarceration. The CCP consists of a needs assessment, HCV education, and appointment scheduling for detainees, followed by reminder calls and appointment escort by a community patient navigator after re-entry. Statistical significance was determined using x2 tests. Results. Of 52 patients in the pre-intervention group, 24 (46.2%) were released from their index jail stay. Of those released, 10 of 24 (42%) were reincarcerated within a median of 247 days (IQR 129-318). The remaining 28 individuals were not released from their index incarceration and transferred to state prison. Of the 26 enrolled in the CCP as of April 2016, 13 (50%) have been released (6 linked, 4 pending linkage, and 3 not linked), 9 (34.6%) have not yet been released, and 4 (15.4%) have been transferred to state prison. Criteria for linkage to care within <90 days in the pre-intervention and intervention groups, respectively, were met by 3 of 24 (12.5%) versus 5 of 9 thus far (55.6%) (p = 0.01) and overall by 11 of 24 (45.8%) versus 6 of 9 thus far (66.7%) (p = 0.29). Conclusion. Pre-intervention linkage rates were low among HCV-infected detainees. While this study is ongoing, linkage in <90 days was significantly higher in the intervention group though not overall. These data provide early evidence that an integrated community-based CCP with jail-based transitional care coordinators may be effective in improving timely linkage to HCV care following release from jail

BACKGROUND:Cancer incidence in exposed rescue/recovery workers (RRWs) and civilians (non-RRWs) was previously reported through 2008. METHODS:We studied occurrence of first primary cancer among World Trade Center Health Registry enrollees through 2011 using adjusted standardized incidence ratios (SIRs), and the WTC-exposure-cancer association, using Cox proportional hazards models. RESULTS:All-cancer SIR was 1.11 (95% confidence interval (CI) 1.03-1.20) in RRWs, and 1.08 (95% CI 1.02-1.15) in non-RRWs. Prostate cancer and skin melanoma were significantly elevated in both populations. Thyroid cancer was significantly elevated only in RRWs while breast cancer and non-Hodgkin's lymphoma were significantly elevated only in non-RRWs. There was a significant exposure dose-response for bladder cancer among RRWs, and for skin melanoma among non-RRWs. CONCLUSIONS:We observed excesses of total and specific cancers in both populations, although the strength of the evidence for causal relationships to WTC exposures is somewhat limited. Continued monitoring of this population is indicated. Am. J. Ind. Med. 59:709-721, 2016. © 2016 Wiley Periodicals, Inc.

BACKGROUND: Although metabolic surgery was originally performed to treat hypercholesterolemia, the effects of contemporary bariatric surgery on serum lipids have not been systematically characterized. METHODS AND RESULTS: MEDLINE, EMBASE and Cochrane databases were searched for studies with >/=20 obese adults undergoing bariatric surgery [Roux-en-Y Gastric Bypass (RYGBP), Adjustable Gastric Banding, Bilio-Pancreatic Diversion (BPD), or Sleeve Gastrectomy]. The primary outcome was change in lipids from baseline to one-year after surgery. The search yielded 178 studies with 25,189 subjects (pre-operative BMI 45.5+/-4.8kg/m2) and 47,779 patient-years of follow-up. In patients undergoing any bariatric surgery, compared to baseline, there were significant reductions in total cholesterol (TC; -28.5mg/dL), low density lipoprotein cholesterol (LDL-C; -22.0mg/dL), triglycerides (-61.6mg/dL) and a significant increase in high density lipoprotein cholesterol (6.9mg/dL) at one year (P<0.00001 for all). The magnitude of this change was significantly greater than that seen in non-surgical control patients (eg LDL-C; -22.0mg/dL vs -4.3mg/dL). When assessed separately, the magnitude of changes varied greatly by surgical type (Pinteraction<0.00001; eg LDL-C: BPD -42.5mg/dL, RYGBP -24.7mg/dL, Adjustable Gastric Banding -8.8mg/dL, Sleeve Gastrectomy -7.9mg/dL). In the cases of Adjustable Gastric Banding (TC and LDL-C) and Sleeve Gastrectomy (LDL-C), the response at one year following surgery was not significantly different from non-surgical control patients. CONCLUSIONS: Contemporary bariatric surgical techniques produce significant improvements in serum lipids, but changes vary widely, likely due to anatomic alterations unique to each procedure. These differences may be relevant in deciding the most appropriate technique for a given patient.

OBJECTIVES: Professionalism education is a vital component of surgical training. This research attempts to determine whether an annual, year-long professionalism curriculum in a large surgical residency can effectively change professionalism attitudes. SUMMARY OF BACKGROUND DATA: The ACGME mandated 6 competencies in 2003. The competencies of Professionalism and Interpersonal/Professional Communication Skills had never been formally addressed in surgical resident education in the past. METHODS: A professionalism curriculum was developed focusing on specific resident professionalism challenges: admitting mistakes, effective communication with colleagues at all levels, delivering the news of an unexpected death, interdisciplinary challenges of working as a team, the cultural challenge of obtaining informed consent through an interpreter, and the stress of surgical practice on you and your family. These professionalism skills were then evaluated with a 6-station Objective Structured Clinical Examination (OSCE). Identical OSCE scenarios were administered to 2 cohorts of surgical residents: in 2007 (before instituting the professionalism curriculum in 2008) and again in 2014. Surgical residents were rated by trained Standardized Patients according to a behaviorally anchored professionalism criteria checklist. RESULTS: An analysis of variance was conducted of overall OSCE professionalism scores (% well done) as the dependent variable for the 2 resident cohorts (2007 vs 2014). The 2007 residents received a mean score of 38% of professionalism items "well done" (SD 9%) and the 2014 residents received a mean 59% "well done" (SD 8%). This difference is significant (F = 49.01, P < .001). CONCLUSIONS: Professionalism education has improved surgical resident understanding, awareness, and practice of professionalism in a statistically significant manner from 2007 to 2014. This documented improvement in OSCE performance reflects the value of a professionalism curriculum in the care of the patients we seek to serve.