Faculty Bibliography

A colonic perineurioma is often considered a benign cousin to a colonic polyp. However, in the submucosal type of perineurioma, it is important to rule out the malignant gastrointestinal stromal tumor (GIST). Alternatively, in the BRAF-positive serrated types of perineuriomas, surveillance is equivalent to intervals designated to serrated polyps due to a similar malignant potential. These versions serve as reminders that colonic perineuriomas are not to be disregarded.

Glioblastoma (GBM), representing WHO grade IV astrocytoma, is a relatively common primary brain tumor in adults with an exceptionally dismal prognosis. With an incidence rate of over 10 000 cases in the United States annually, the median survival rate ranges from 10-15 months in IDH1/2-wildtype tumors and 24-31 months in IDH1/2-mutant tumors, with further variation depending on factors such as age, MGMT methylation status, and treatment regimen. We present a cohort of 4 patients, aged 37-60 at initial diagnosis, with IDH1-mutant GBMs that were associated with unusually long survival intervals after the initial diagnosis, currently ranging from 90 to 154 months (all still alive). We applied genome-wide profiling with a methylation array (Illumina EPIC Array 850k) and a next-generation sequencing panel to screen for genetic and epigenetic alterations in these tumors. All 4 tumors demonstrated methylation patterns and genomic alterations consistent with GBM. Three out of four cases showed focal amplification of the CCND2 gene or gain of the region on 12p that included CCND2, suggesting that this may be a favorable prognostic factor in GBM. As this study has a limited sample size, further evaluation of patients with similar favorable outcome is warranted to validate these findings.

BACKGROUND:Topical retinoids are a first-line treatment for acne vulgaris. OBJECTIVE:This systematic review aims to evaluate the efficacy, safety, and tolerability of topical retinoids approved in the United States for the treatment of acne vulgaris. METHODS:A PubMed and Embase search was conducted using the search terms 'adapalene,' 'tretinoin,' 'tazarotene,' and 'acne vulgaris.' Selection of articles fit the following inclusion criteria: clinical trials evaluating both efficacy and safety/tolerability of topical retinoids approved in the United States for the treatment of acne vulgaris and published between January 1, 2008 and September 1, 2018. Exclusion criteria included clinical trials involving 20 subjects or fewer, subjects under 12 years of age, and topical retinoid combination therapies with moisturizers or aloe vera. Of 424 search results found, a total of 54 clinical trials were chosen based on selection criteria. RESULTS:Topical retinoids are superior to vehicle in improving Investigator Global Assessment and Investigator's Static Global Assessment (24.1-28.8% and 13.3-17.3%, respectively; p < 0.001). A topical retinoid combined with benzoyl peroxide led to IGA improvement compared with vehicle (26.1-34.9% vs 7-11.8%; p < 0.001) at Week 12. Topical retinoid plus an oral antibiotic was superior to vehicle in reducing lesion counts (64-78.9% vs 41-56.8%, p < 0.001). There was no significant difference in efficacy between tretinoin and tazarotene. Tretinoin 0.05% resulted in 62% of patients experiencing AEs compared with adapalene 0.1% (19%) and adapalene 0.3% (40%). More patients receiving adapalene were tolerant of the AEs compared with tazarotene (55.4% vs 24.4%; p < 0.0012). CONCLUSIONS:Topical retinoids are safe and efficacious for the treatment of acne vulgaris. They should be used in combination with benzoyl peroxide to optimize results in patients. The differences in efficacy of topical retinoids appears minor; therefore, the type of topical retinoid is not as important as choosing a particular strength of topical retinoid and combining it with an antimicrobial agent. Adapalene has a superior tolerability profile amongst topical retinoids.

BACKGROUND AND PURPOSE/OBJECTIVE:Cardiac biomarkers may help identify stroke mechanisms and may aid in improving stroke prevention strategies. There is limited data on the association between these biomarkers and acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). We hypothesized that cardiac biomarkers (cardiac troponin and left atrial diameter [LAD]) would be associated with the presence of LVO. METHODS:Data were abstracted from a single center prospective AIS database over 18 months and included all patients with AIS with CT angiography of the head and neck. The presence of LVO was defined as proximal LVO of the internal carotid artery terminus, middle cerebral artery (M1 or proximal M2), or basilar artery. Univariate analyses and predefined multivariable models were performed to determine the association between cardiac biomarkers (positive troponin [troponin ≥0.1 ng/mL] and LAD on transthoracic echocardiogram) and LVO adjusting for demographic factors (age and sex), risk factors (hypertension, diabetes, hyperlipidemia, history of stroke, congestive heart failure, coronary heart disease, and smoking), and atrial fibrillation (AF). RESULTS:We identified 1234 patients admitted with AIS; 886 patients (71.8%) had vascular imaging to detect LVO. Of those with imaging available, 374 patients (42.2%) had LVO and 207 patients (23.4%) underwent thrombectomy. There was an association between positive troponin and LVO after adjusting for age, sex and other risk factors (adjusted OR 1.69 [1.08-2.63], P = .022) and this association persisted after including AF in the model (adjusted OR 1.60 [1.02-2.53], P = 0.043). There was an association between LAD and LVO after adjusting for age, sex, and risk factors (adjusted OR per mm 1.03 [1.01-1.05], P = 0.013) but this association was not present when AF was added to the model (adjusted OR 1.01 [0.99-1.04], P = .346). Sensitivity analyses using thrombectomy as an outcome yielded similar findings. CONCLUSIONS:Cardiac biomarkers, particularly serum troponin levels, are associated with acute LVO in patients with ischemic stroke. Prospective studies are ongoing to confirm this association and to test whether anticoagulation reduces the risk of recurrent embolism in this patient population.

Aim: Naltrexone is first-line pharmacotherapy for alcohol use disorders (AUD). Oral naltrexone (ONTX) is under-prescribed in primary care and possibly limited by poor adherence. Monthly injectable extended-release naltrexone (XR-NTX) may improve adherence and good clinical outcomes.
Method(s): This is a randomized, open-label, comparative effectiveness trial of 24 weeks of XR-NTX vs. O-NTX as AUD treatment in primary care at a public hospital in New York City. Adults (>18 yo) with AUD randomized to XR-NTX (380 mg/month) vs. O-NTX (50 mg/day) with Medical Management. Self-reported daily drinking recall informed the primary outcome, a Good Clinical Outcome (GCO) across weeks 5-24, defined as abstinence or moderate drinking and 0-2 days of heavy drinking per month. Data & Results: N = 237 adults randomized (n = 117 XR-NTX; n = 120 O-NTX); mean age 48.5 (SD 10.6); 71%male; 54%AA, 21% Hispanic; 41%employed. At baseline mean drinks/day were 9.6 (SD 11.6); 29% abstinent days; 61%heavy drinking days; mean Obsessive Compulsive Drinking Scale (OCDS) scores were 17.6 (SD 7.1) and mean AUDIT scores were 24.2 (SD 8.0). 64%of monthly XR-NTX injections were received and 67%ofmonthly O-NTX refills were provided. The primary GCO across weeks 5-24 was reported by 29%XR-NTX and 23%O-NTX (p = 0.29). Mean months with a GCO was 2.9 XR-NTX, 2.5 O-NTX (p = 0.21). Rates of%days abstinent (70%XRNTX vs. 71%O-NTX; p = 0.77) and %heavy drinking days (20%XR-NTX vs. 16%O-NTX; p = 0.28) were similar weeks 1-24. Mean blood pressure decreased from 127/86 mmHg at baseline to 124/83 mmHg at week 25; there was no change in mean weight (180 lb) pre/post, and there were no differences in BP or weight changes by arm. Declines in OCDS scores (17.6 to 7.6) were similar by arm.
Conclusion(s): Initiation and retention on both forms of naltrexone was robust. Overall, participants reported improved longitudinal drinking outcomes. There was insufficient evidence of any differences in primary and secondary self-reported drinking outcomes between monthly XR-NTX and daily ONTX. Additional analysis will examine CDT and LFT levels during treatment, and interactions with OPMR1 genotype status

Background/UNASSIGNED:Dynamic nutrition education strategies may help prepare physicians to provide nutrition guidance to patients. Activity/UNASSIGNED:We pilot tested a nutrition-focused iBook chapter with a group of medical students and residents (June 2017) through pre and post-test Qualtrics surveys. Results/UNASSIGNED:All 29 respondents recognized the role of nutrition in medical care. Two-thirds reported some nutrition training in their medical education; nearly 90% reported this training was inadequate. Few (17%) reported reading scholarly nutrition articles; 84% reported they would recommend the iBook to their peers. Conclusions/UNASSIGNED:An iBook is a resource that could be used to teach nutrition to medical trainees.

BACKGROUND:Reducing costs while increasing or maintaining quality is crucial to delivering high value care. OBJECTIVE:To assess the impact of a hospital value-based management programme on cost and quality. DESIGN/METHODS:Time series analysis of non-psychiatric, non-rehabilitation, non-newborn patients discharged between 1 September 2011 and 31 December 2017 from a US urban, academic medical centre. INTERVENTION/METHODS:NYU Langone Health instituted an institution-wide programme in April 2014 to increase value of healthcare, defined as health outcomes achieved per dollar spent. Key features included joint clinical and operational leadership; granular and transparent cost accounting; dedicated project support staff; information technology support; and a departmental shared savings programme. MEASUREMENTS/METHODS:Change in variable direct costs; secondary outcomes included changes in length of stay, readmission and in-hospital mortality. RESULTS:The programme chartered 74 projects targeting opportunities in supply chain management (eg, surgical trays), operational efficiency (eg, discharge optimisation), care of outlier patients (eg, those at end of life) and resource utilisation (eg, blood management). The study cohort included 160 434 hospitalisations. Adjusted variable costs decreased 7.7% over the study period. Admissions with medical diagnosis related groups (DRG) declined an average 0.20% per month relative to baseline. Admissions with surgical DRGs had an early increase in costs of 2.7% followed by 0.37% decrease in costs per month. Mean expense per hospitalisation improved from 13% above median for teaching hospitals to 2% above median. Length of stay decreased by 0.25% per month relative to prior trends (95% CI -0.34 to 0.17): approximately half a day by the end of the study period. There were no significant changes in 30-day same-hospital readmission or in-hospital mortality. Estimated institutional savings after intervention costs were approximately $53.9 million. LIMITATIONS/CONCLUSIONS:Observational analysis. CONCLUSION/CONCLUSIONS:A systematic programme to increase healthcare value by lowering the cost of care without compromising quality is achievable and sustainable over several years.

RATIONALE, AIMS, AND OBJECTIVES/UNASSIGNED:There are well-documented barriers that have limited widespread, sustained adoption of screening and brief intervention for risky substance use in health care settings. In order to better inform implementation efforts, this study evaluates whether patient characteristics, screening results, and implementation success indicators differed between two clinical setting types: primary care and emergency. METHODS:Patients presenting to an emergency or primary care setting were screened for risky substance use (n = 41 567). Patients with a positive screen were further assessed for psychosocial, health, and substance use problems (n = 1604). Differences in patient characteristics between primary care and emergency settings were examined using chi-square and t tests. Multilevel logistic regression was used to examine whether setting type predicted screening results. Site-level indicators of implementation success were calculated (percentage prescreens completed, percentage full screens completed, and percentage refused services) for all patient visits (n = 78 656). RESULTS:As compared with primary care patients, emergency patients had more severe substance use patterns and screening scores, were more likely to use a variety of illicit drugs, and reported more psychosocial issues. In logistic regression models, setting type did not predict whether patients screened positive; however, it did predict screening into a higher vs lower risk category such that emergency patients were more likely to be in a higher risk category. Emergency settings had lower indicators of implementation success (eg, 14% lower prescreen completion rate) as compared with primary care settings on some implementation measures. CONCLUSIONS:This evaluation found important differences in patient characteristics and screening and implementation results between primary care and emergency settings. Health care organizations and administrators implementing screening and brief intervention should attend to setting differences that could affect implementation and clinical care.

PURPOSE/OBJECTIVE:The IGF and mTOR-pathways are considered as potential targets for therapy in patients with adrenocortical carcinoma (ACC). This study aims to describe the IGF pathway in ACC and to explore the response to the combined treatment with the IGF1R/IR inhibitor linsitinib, and mTOR inhibitors (sirolimus and everolimus) in in vitro models of ACC. METHODS:The protein expression level of IGF2, IGF1R and IGF2R was evaluated by immunohistochemistry in 17 human ACCs and the mRNA expression level of IGF1, IGF2, IGF1R, IR isoforms A and B, IGF2R, IGF-Binding-Proteins[IGFBP]-1, 2, 3 and 6 was evaluated by RT-qPCR in 12 samples. In H295R and HAC15 ACC cell lines the combined effects of linsitinib and sirolimus or everolimus on cell survival were evaluated. RESULTS:A high protein expression of IGF2, IGF1R and IGF2R was observed in 82, 65 and 100% of samples, respectively. A high relative expression of IGF2 mRNA was found in the majority of samples. The mRNA levels of the IRA were higher than that of IRB and IGF1R in the majority of samples (75%). Linsitinib inhibits cell growth in the H295R and HAC15 cell lines and, combined with sirolimus or everolimus, linsitinib showed a significant additive effect. CONCLUSIONS:In addition to IGF2 and IGF1R, ACC express IGF2R, IRA and several IGFBPs, suggesting that the interplay between the different components of the IGF pathway in ACC could be more complex than previously considered. The addition of mTOR inhibitors to linsitinib may have stronger antiproliferative effects than linsitinib alone.