Research Spotlight

Hamid, O., C. L. Cowey, M. Offner, M. Faries and R. D. Carvajal (2019). “Efficacy, Safety, and Tolerability of Approved Combination BRAF and MEK Inhibitor Regimens for BRAF-Mutant Melanoma.” Cancers (Basel) Oct 24. [Epub ahead of print].

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No head-to-head studies exist comparing BRAF inhibitor/MEK inhibitor (BRAFi/MEKi) combination treatments for BRAF-mutant melanoma. A side-by-side analysis of randomized phase III trials is presented that evaluated dabrafenib/trametinib, vemurafenib/cobimetinib, and encorafenib/binimetinib. The baseline characteristics, efficacy, and safety were compared: COMBI-v (dabrafenib/trametinib versus vemurafenib); coBRIM (vemurafenib/cobimetinib versus vemurafenib); and COLUMBUS (encorafenib/binimetinib versus encorafenib and vemurafenib). Vemurafenib was the control arm in all studies. The data sources included literature databases, European public assessment reports, U.S. Food and Drug Administration review documents, and prescribing information. The baseline characteristics were similar, except for coBRIM, which had a higher proportion of patients with elevated lactate dehydrogenase (LDH) levels. The median progression-free survival (PFS) and overall response rate (ORR) were similar across the trials, although numerically higher values were observed with encorafenib/binimetinib. In contrast, the median overall survival (OS) was numerically longer with encorafenib/binimetinib (33.6 months) compared to dabrafenib/trametinib (25.6 months) and vemurafenib/cobimetinib (22.3 months). Among vemurafenib arms, PFS, ORR, and OS were similar, despite variations in the baseline LDH. Each combination displayed a unique safety profile, with higher incidences of pyrexia with dabrafenib/trametinib and photosensitivity reactions with vemurafenib/cobimetinib. This analysis of BRAFi/MEKi combinations for BRAF-mutant melanoma, while limited as not a direct head-to-head clinical trial, highlights the differences in tolerability and efficacy that may be useful for therapeutic decision making.

Garg, S. K., S. Sarvepalli, D. Singh, I. Obaitan, T. Peeraphatdit, L. Jophlin, S. K. Asrani, V. H. Shah and M. D. Leise (2019). “Incidence and Risk Factors Associated With 30-Day Readmission for Alcoholic Hepatitis.” J Clin Gastroenterol 53(10): 759-764.

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BACKGROUND: Alcohol abuse and liver disease are associated with high rates of 30-day hospital readmission, but factors linking alcoholic hepatitis (AH) to readmission are not well understood. We aimed to determine the incidence rate of 30-day readmission for patients with AH and to evaluate potential predictors of readmission. METHODS: We used the Nationwide Readmissions Database to determine the 30-day readmission rate for recurrent AH between 2010 and 2014 and examined trends in readmissions during the study period. We also identified the 20 most frequent reasons for readmission. Multivariate survey logistic regression analysis was used to identify factors associated with 30-day readmission. RESULTS: Of the 61,750 index admissions for AH, 23.9% were readmitted within 30-days. The rate of readmission did not change significantly during the study period. AH, alcoholic cirrhosis, and hepatic encephalopathy were the most frequent reasons for readmission. In multivariate analysis female sex, leaving against medical advice, higher Charlson comorbidity index, ascites, and history of bariatric surgery were associated with earlier readmissions, whereas older age, payer type (private or self-pay/other), and discharge to skilled nursing-facility reduced this risk. CONCLUSIONS: The 30-day readmission rate in patients with AH was high and stable during the study period. Factors associated with readmission may be helpful for development of consensus-based expert guidelines, treatment algorithms, and policy changes to help decrease readmission in AH.

Garbarino, G. M., U. Marchese, R. Tobome, M. A. Ward, E. Vibert, B. Gayet, D. Cherqui and D. Fuks (2019). “Laparoscopic versus open unisegmentectomy in two specialized centers. Feasibility and short-term results.” HPB (Oxford) Oct 28. [Epub ahead of print].

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BACKGROUND: Anatomical segmentectomy is defined as the complete removal of the Couinaud’s segment. The aim of this study was to compare the perioperative outcomes of laparoscopic (LS) versus open (OS) unisegmentectomy in two high volume centers. METHODS: A retrospective review of all consecutive unisegmentectomies from 2007 to 2017 was performed at the Institut Mutualiste Montsouris and at the Hepatobiliary Center of Paul Brousse Hospital. RESULTS: A total of 177 patients underwent unisegmentectomy: 58 LS vs 52 OS in the anterolateral segments, 33 LS vs 34 OS in the posterosuperior segments. HCC were more frequent in the OS group, whereas colorectal liver metastases were more frequently treated with LS. Blood loss (200 vs. 400 ml, p = 0.006), operative time (238 vs. 267 min, p = 0.048) and median length of stay (6 vs. 8 days, p = 0.036) were significantly lower in the LS group. The resection margins (4 mm vs. 2 mm, p = 0.763) and the overall morbidity did not differ between the two groups. In the posterosuperior segment, OS group had more pulmonary complications (9 vs. 29%, p = 0.035). CONCLUSION: Laparoscopic anatomical unisegmentectomies for selected patients, even with postero-superior based tumors, in specialized centers seems to be safe and feasible.

Flannery, B., R. J. G. Kondor, J. R. Chung, M. Gaglani, M. Reis, R. K. Zimmerman, M. P. Nowalk, M. L. Jackson, L. A. Jackson, A. S. Monto, E. T. Martin, E. A. Belongia, H. Q. McLean, S. S. Kim, L. Blanton, K. Kniss, A. P. Budd, L. Brammer, T. J. Stark, J. R. Barnes, D. E. Wentworth, A. M. Fry and M. Patel (2019). “Spread of antigenically drifted influenza A(H3N2) viruses and vaccine effectiveness in the United States during the 2018-2019 season.” J Infect Dis Oct 30. [Epub ahead of print].

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BACKGROUND: Increased illness due to antigenically drifted A(H3N2) clade 3C.3a influenza viruses prompted concerns about vaccine effectiveness and vaccine strain selection. We used U.S. virologic surveillance and Influenza Vaccine Effectiveness (VE) Network data to evaluate consequences of this clade. METHODS: Distribution of influenza viruses was described using virologic surveillance data. The VE Network enrolled ambulatory patients aged >/=6 months with acute respiratory illness at five sites. Respiratory specimens were tested by RT-PCR for influenza and sequenced. Using a test-negative design, we estimated VE comparing odds of influenza among vaccinated versus unvaccinated participants. RESULTS: During the 2018-2019 influenza season, A(H3N2) clade 3C.3a viruses caused an increasing proportion of influenza cases. Among 2,763 VE Network case patients, 1,325 (48%) were infected with A(H1N1)pdm09 and 1,350 (49%) with A(H3N2); clade 3C.3a accounted for 977 (93%) of 1,054 sequenced A(H3N2) viruses. VE was 44% (95% confidence interval [CI], 37 to 51%) against A(H1N1)pdm09 and 9% (95% CI, -4 to 20%) against A(H3N2); effectiveness was 5% (95% CI, -10 to 19%) against A(H3N2) clade 3C.3a viruses. CONCLUSIONS: Predominance of A(H3N2) clade 3C.3a viruses during the latter part of the 2018-2019 season was associated with decreased vaccine effectiveness, supporting the A(H3N2) vaccine component update for 2019-2020 northern hemisphere influenza vaccines.

Fitzgerald, S. T., S. Wang, D. Dai, A. Douglas, R. Kadirvel, M. J. Gounis, J. Chueh, A. S. Puri, K. F. Layton, I. C. Thacker, R. A. Hanel, E. Sauvageau, A. Aghaebrahim, M. A. Almekhlafi, A. M. Demchuk, R. G. Nogueira, V. M. Pereira, P. Kvamme, Y. Kayan, J. E. Delgado Almandoz, A. J. Yoo, D. F. Kallmes, K. M. Doyle and W. Brinjikji (2019). “Platelet-rich clots as identified by Martius Scarlet Blue staining are isodense on NCCT.” J Neurointerv Surg 11(11): 1145-1149.

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BACKGROUND: Current studies on clot characterization in acute ischemic stroke focus on fibrin and red blood cell composition. Few studies have examined platelet composition in acute ischemic stroke clots. We characterize clot composition using the Martius Scarlet Blue stain and assess associations between platelet density and CT density. MATERIALS AND METHOD: Histopathological analysis of the clots collected as part of the multi-institutional STRIP registry was performed using Martius Scarlet Blue stain and the composition of the clots was quantified using Orbit Image Analysis (www.orbit.bio) machine learning software. Prior to endovascular treatment, each patient underwent non-contrast CT (NCCT) and the CT density of each clot was measured. Correlations between clot components and clinical information were assessed using the chi(2) test. RESULTS: Eighty-five patients were included in the study. The mean platelet density of the clots was 15.7% (2.5-72.5%). There was a significant correlation between platelet-rich clots and the absence of hyperdensity on NCCT, (rho=0.321, p=0.003*, n=85). Similarly, there was a significant inverse correlation between the percentage of platelets and the mean Hounsfield Units on NCCT (rho=-0.243, p=0.025*, n=85). CONCLUSION: Martius Scarlet Blue stain can identify patients who have platelet-rich clots. Platelet-rich clots are isodense on NCCT.