Research Spotlight

Posted April 15th 2019

Non-invasive assessment of liver fibrosis and prognosis: an update on serum and elastography markers.

Sumeet K. Asrani M.D.

Sumeet K. Asrani M.D.

Agbim, U. and S. K. Asrani (2019). “Non-invasive assessment of liver fibrosis and prognosis: an update on serum and elastography markers.” Expert Rev Gastroenterol Hepatol 13(4): 361-374.

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INTRODUCTION: Non-invasive assessment of fibrosis is increasingly utilized in clinical practice to diagnose hepatic fibrosis. Non-invasive assessment of liver fibrosis relies on biologic and/or physical properties to assess tissue fibrosis. Serum markers estimate fibrosis by incorporating markers reflecting hepatic function (indirect markers) and/or markers measuring extracellular matrix degradation/fibrogenesis (direct markers). Radiology based techniques relay the mechanical properties and stiffness of a tissue, with increased stiffness associated with more advanced fibrosis. Areas covered: In this comprehensive review, the recent literature discussing serum markers and elastography-based techniques will be covered. These modalities are also explored in the setting of various liver diseases. Expert opinion: The etiology of liver disease and clinical context should be taken into consideration when non-invasive markers are incorporated in clinical practice. Non-invasive assessment of fibrosis has been most extensively utilized in hepatitis C, followed by hepatitis B and nonalcoholic fatty liver disease, but its role remains less developed in other etiologies of liver disease such as alcohol-associated liver disease and autoimmune liver disease. The role of non-invasive markers in predicting progression or regression of fibrosis, development of liver-related events and survival needs to be further explored.


Posted April 15th 2019

Tremfya (Guselkumab).

William Abramovits M.D.

William Abramovits M.D.

Abramovits, W., A. Wiqas, K. D. Vincent, S. G. Versteeg and A. K. Gupta (2019). “Tremfya (Guselkumab).” Skinmed 17(1): 36-38.

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Tremfya™ is the first biologic in the class of anti-IL-23 antibodies to be marketed. There are two other promising options pending for approval and about to enter the market. Being first to market has afforded guselkumab uncontested prescription competitiveness when a biologic of this class is desired. Theoretical superiority of this and other anti-IL-23 biologics over anti-IL-17, anti-IL-12/23, or anti-TNF¬ biologics is being contested with head-to-head studies. Some studies have proved the superiority of anti-IL-23 antibodies in some parameters. Clinicians have the opportunity to choose the best performing and safest treatment, individualizing the needs and risks, which sometimes depend on comorbidities, like inflammatory bowel disease, for their patients with psoriasis and psoriatic arthritis. (Excerpt from text, p. 38; no abstract available.)


Posted March 25th 2019

Usefulness of Atherectomy in Chronic Total Occlusion Interventions (from the PROGRESS-CTO Registry).

James W. Choi M.D.

James W. Choi M.D.

Xenogiannis, I., D. Karmpaliotis, K. Alaswad, F. A. Jaffer, R. W. Yeh, M. Patel, E. Mahmud, J. W. Choi, M. N. Burke, A. H. Doing, P. Dattilo, C. Toma, A. J. C. Smith, B. Uretsky, O. Krestyaninov, D. Khelimskii, E. Holper, S. Potluri, R. M. Wyman, D. E. Kandzari, S. Garcia, M. Koutouzis, I. Tsiafoutis, J. J. Khatri, W. Jaber, H. Samady, B. K. Jefferson, T. Patel, J. W. Moses, N. J. Lembo, M. Parikh, A. J. Kirtane, Z. A. Ali, D. Doshi, P. Tajti, B. V. Rangan, S. Abdullah, S. Banerjee and E. S. Brilakis (2019). “Usefulness of Atherectomy in Chronic Total Occlusion Interventions (from the PROGRESS-CTO Registry).” Am J Cardiol Feb 11. [Epub ahead of print].

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There is limited data on the use of atherectomy during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We compared the clinical and procedural characteristics and outcomes of CTO PCIs performed with or without atherectomy in a contemporary multicenter CTO PCI registry. Between 2012 and 2018, 3,607 CTO PCIs were performed at 21 participating centers. Atherectomy was used in 117 (3.2%) cases: rotational atherectomy in 105 cases, orbital atherectomy in 8, and both in 4 cases. Patients in whom atherectomy was used, were older (68 +/- 8 vs 64 +/- 10 years, p <0.0001) and had higher Japan-chronic total occlusion score (3.0 +/- 1.2 vs 2.4 +/- 1.3, p <0.0001). CTO PCI cases in which atherectomy was used had similar technical (91% vs 87%, p=0.240) and procedural (90% vs 85%, p=0.159) success and in-hospital major adverse cardiac event (4% vs 3%, p=0.382) rates. However, atherectomy cases were associated with higher rates of donor vessel injury (4% vs 1%, p=0.031), tamponade requiring pericardiocentesis (2.6% vs 0.4%, p=0.012) and more often required use of a left ventricular assist device (9% vs 5%, p=0.031). Atherectomy cases were associated with longer procedural duration (196 [141, 247] vs 119 [76, 180] minutes, p <0.0001), and higher patient air kerma radiation dose (3.6 [2.5, 5.6] vs 2.8 [1.6, 4.7] Gray, p=0.001). In conclusion, atherectomy is currently performed in approximately 3% of CTO PCI cases and is associated with similar technical and procedural success and overall major adverse cardiac event rates, but higher risk for donor vessel injury and tamponade.


Posted March 15th 2019

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer.

Joyce O'Shaughnessy M.D.

Joyce O’Shaughnessy M.D.

Bardia, A., I. A. Mayer, L. T. Vahdat, S. M. Tolaney, S. J. Isakoff, J. R. Diamond, J. O’Shaughnessy, R. L. Moroose, A. D. Santin, V. G. Abramson, N. C. Shah, H. S. Rugo, D. M. Goldenberg, A. M. Sweidan, R. Iannone, S. Washkowitz, R. M. Sharkey, W. A. Wegener and K. Kalinsky (2019). “Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer.” N Engl J Med 380(8): 741-751.

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BACKGROUND: Standard chemotherapy is associated with low response rates and short progression-free survival among patients with pretreated metastatic triple-negative breast cancer. Sacituzumab govitecan-hziy is an antibody-drug conjugate that combines a humanized monoclonal antibody, which targets the human trophoblast cell-surface antigen 2 (Trop-2), with SN-38, which is conjugated to the antibody by a cleavable linker. Sacituzumab govitecan-hziy enables delivery of high concentrations of SN-38 to tumors. METHODS: We conducted a phase 1/2 single-group, multicenter trial involving patients with advanced epithelial cancers who received sacituzumab govitecan-hziy intravenously on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxic effects. A total of 108 patients received sacituzumab govitecan-hziy at a dose of 10 mg per kilogram of body weight after receiving at least two previous anticancer therapies for metastatic triple-negative breast cancer. The end points included safety; the objective response rate (according to Response Evaluation Criteria in Solid Tumors, version 1.1), which was assessed locally; the duration of response; the clinical benefit rate (defined as a complete or partial response or stable disease for at least 6 months); progression-free survival; and overall survival. Post hoc analyses determined the response rate and duration, which were assessed by blinded independent central review. RESULTS: The 108 patients with triple-negative breast cancer had received a median of 3 previous therapies (range, 2 to 10). Four deaths occurred during treatment; 3 patients (2.8%) discontinued treatment because of adverse events. Grade 3 or 4 adverse events (in >/=10% of the patients) included anemia and neutropenia; 10 patients (9.3%) had febrile neutropenia. The response rate (3 complete and 33 partial responses) was 33.3% (95% confidence interval [CI], 24.6 to 43.1), and the median duration of response was 7.7 months (95% CI, 4.9 to 10.8); as assessed by independent central review, these values were 34.3% and 9.1 months, respectively. The clinical benefit rate was 45.4%. Median progression-free survival was 5.5 months (95% CI, 4.1 to 6.3), and overall survival was 13.0 months (95% CI, 11.2 to 13.7). CONCLUSIONS: Sacituzumab govitecan-hziy was associated with durable objective responses in patients with heavily pretreated metastatic triple-negative breast cancer. Myelotoxic effects were the main adverse reactions. (Funded by Immunomedics; IMMU-132-01 ClinicalTrials.gov number, NCT01631552.).


Posted March 15th 2019

Two-Year Outcomes After Transcatheter Aortic Valve Replacement With Mechanical vs Self-expanding Valves: The REPRISE III Randomized Clinical Trial.

Robert C. Stoler M.D.

Robert C. Stoler M.D.

Reardon, M. J., T. E. Feldman, C. U. Meduri, R. R. Makkar, D. O’Hair, A. Linke, D. J. Kereiakes, R. Waksman, V. Babliaros, R. C. Stoler, G. J. Mishkel, D. G. Rizik, V. S. Iyer, T. G. Gleason, D. Tchetche, J. D. Rovin, T. Lhermusier, D. Carrie, R. W. Hodson, D. J. Allocco and I. T. Meredith (2019). “Two-Year Outcomes After Transcatheter Aortic Valve Replacement With Mechanical vs Self-expanding Valves: The REPRISE III Randomized Clinical Trial.” JAMA Cardiol Feb 27. [Epub ahead of print].

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Importance: To our knowledge, REPRISE III is the first large randomized comparison of 2 different transcatheter aortic valve replacement platforms: the mechanically expanded Lotus valve (Boston Scientific) and self-expanding CoreValve (Medtronic). Objective: To evaluate outcomes of Lotus vs CoreValve after 2 years. Design, Setting, and Participants: A total of 912 patients with high/extreme risk and severe, symptomatic aortic stenosis enrolled between September 22, 2014, and December 24, 2015, were randomized 2:1 to receive Lotus (607 [66.6%]) or CoreValve (305 [33.4%] at 55 centers in North America, Europe, and Australia. The first 2-year visit occurred on October 17, 2016, and the last was conducted on April 12, 2018. Clinical and echocardiographic assessments are complete through 2 years and will continue annually through 5 years. Main Outcomes and Measures: All-cause mortality and all-cause mortality or disabling stroke at 2 years. Other clinical factors included overall stroke, disabling stroke, repeated procedures, rehospitalization, valve thrombosis, and pacemaker implantation. Echocardiographic analyses included effective orifice area, mean gradient, and paravalvular leaks (PVLs). Results: Of 912 participants, the mean (SD) age was 82.8 (7.3) years, 465 (51%) were women, and the mean (SD) Society of Thoracic Surgeons predicted risk of mortality was 6.8% (4.0%). At 2 years, all-cause death was 21.3% with Lotus vs 22.5% with CoreValve (hazard ratio [HR], 0.94; 95% CI, 0.69-1.26; P = .67) and all-cause mortality or disabling stroke was 22.8% with Lotus and 27.0% with CoreValve (HR, 0.81; 95% CI, 0.61-1.07; P = .14). Overall stroke was 8.4% vs 11.4% (HR, 0.75; 95% CI, 0.48-1.17; P = .21); disabling stroke was more frequent with CoreValve vs Lotus (4.7% Lotus vs 8.6% CoreValve; HR, 0.53; 95% CI, 0.31-0.93; P = .02). More Lotus patients received a new permanent pacemaker (41.7% vs 26.1%; HR, 1.87; 95% CI, 1.41-2.49; P < .01) or had a valve thrombosis (3.0% vs 0.0%; P < .01) compared with CoreValve. More patients who received CoreValve experienced a repeated procedure (0.6% Lotus vs 2.9% CoreValve; HR, 0.19; 95% CI, 0.05-0.70; P < .01), valve migration (0.0% vs 0.7%; P = .05), or embolization (0.0% vs 2.0%; P < .01) than Lotus. Valve areas remained significantly larger and the mean gradient was lower with CoreValve than Lotus (valve area, mean [SD]: Lotus, 1.53 [0.49] cm2 vs CoreValve, 1.76 [0.51] cm2; P < .01; valve gradient, mean [SD]: Lotus, 13.0 [6.7] mm Hg vs 8.1 [3.7] mm Hg; P < .01). Moderate or greater PVL was more frequent with CoreValve (0.3% Lotus vs 3.8% CoreValve; P < .01) at 2 years. Larger improvements in New York Heart Association (NYHA) functional class were observed with Lotus compared with CoreValve (improved by >/=1 NYHA class: Lotus, 338 of 402 [84.1%] vs CoreValve, 143 of 189 [75.7%]; P = .01; improved by >/=2 NYHA classes: 122 of 402 [37.3%] vs 65 of 305 [21.3%]). Conclusions and Relevance: After 2 years, all-cause mortality rates, mortality or disabling stroke were similar between Lotus and CoreValve. Disabling stroke, functional class, valve migration, and PVL favored the Lotus arm whereas valve hemodynamics, thrombosis, and new pacemaker implantation favored the CoreValve arm. Trial Registration: clinicaltrials.gov Identifier: NCT02202434.