Research Spotlight

Posted February 15th 2018

Association between triglyceride levels and cardiovascular disease in patients with acute pancreatitis.

Laurel A. Copeland Ph.D.

Laurel A. Copeland Ph.D.

Copeland, L. A., C. S. Swendsen, D. M. Sears, A. A. MacCarthy and C. J. McNeal (2018). “Association between triglyceride levels and cardiovascular disease in patients with acute pancreatitis.” PLoS One 13(1): e0179998.

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Conventional wisdom supports prescribing “fibrates before statins”, that is, prioritizing treatment of hypertriglyceridemia (hTG) to prevent pancreatitis ahead of low-density lipoprotein cholesterol to prevent coronary heart disease. The relationship between hTG and acute pancreatitis, however, may not support this approach to clinical management. This study analyzed administrative data from the Veterans Health Administration for evidence of (1) temporal association between assessed triglycerides level and days to acute pancreatitis admission; (2) association between hTG and outcomes in the year after hospitalization for acute pancreatitis; (3) relative rates of prescription of fibrates vs statins in patients with acute pancreatitis; (4) association of prescription of fibrates alone versus fibrates with statins or statins alone with rates of adverse outcomes after hospitalization for acute pancreatitis. Only modest association was found between above-normal or extremely high triglycerides and time until acute pancreatitis. CHD/MI/stroke occurred in 23% in the year following AP, supporting cardiovascular risk management. Fibrates were prescribed less often than statins, defying conventional wisdom, but the high rates of cardiovascular events in the year following AP support a clinical focus on reducing cardiovascular risk factors.


Posted February 15th 2018

Quality of Life Outcomes for Cabozantinib Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma: METEOR Phase III Randomized Trial.

Thomas Hutson D.O.

Thomas Hutson D.O.

Cella, D., B. Escudier, N. M. Tannir, T. Powles, F. Donskov, K. Peltola, M. Schmidinger, D. Y. C. Heng, P. N. Mainwaring, H. J. Hammers, J. L. Lee, B. J. Roth, F. Marteau, P. Williams, J. Baer, M. Mangeshkar, C. Scheffold, T. E. Hutson, S. Pal, R. J. Motzer and T. K. Choueiri (2018). “Quality of Life Outcomes for Cabozantinib Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma: METEOR Phase III Randomized Trial.” J Clin Oncol: Jan 29:JCO2017752170. [Epub ahead of print].

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Purpose In the phase III METEOR trial (ClinicalTrials.gov identifier: NCT01865747), 658 previously treated patients with advanced renal cell carcinoma were randomly assigned 1:1 to receive cabozantinib or everolimus. The cabozantinib arm had improved progression-free survival, overall survival, and objective response rate compared with everolimus. Changes in quality of life (QoL), an exploratory end point, are reported here. Patients and Methods Patients completed the 19-item Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI-19) and the five-level EuroQol (EQ-5D-5L) questionnaires at baseline and throughout the study. The nine-item FKSI-Disease-Related Symptoms (FKSI-DRS), a subset of FKSI-19, was also investigated. Data were summarized descriptively and by repeated-measures analysis (for which a clinically relevant difference was an effect size >/= 0.3). Time to deterioration (TTD) was defined as the earlier of date of death, radiographic progressive disease, or >/= 4-point decrease from baseline in FKSI-DRS. Results The QoL questionnaire completion rates remained >/= 75% through week 48 in each arm. There was no difference over time for FKSI-19 Total, FKSI-DRS, or EQ-5D data between the cabozantinib and everolimus arms. Among the individual FKSI-19 items, cabozantinib was associated with worse diarrhea and nausea; everolimus was associated with worse shortness of breath. These differences are consistent with the adverse event profile of each drug. Cabozantinib improved TTD overall, with a marked improvement in patients with bone metastases at baseline. Conclusion In patients with advanced renal cell carcinoma, relative to everolimus, cabozantinib generally maintained QoL to a similar extent. Compared with everolimus, cabozantinib extended TTD overall and markedly improved TTD in patients with bone metastases.


Posted February 15th 2018

Oculomotor and Vestibular Findings in Gaucher Disease Type 3 and Their Correlation with Neurological Findings.

Raphael Schiffmann M.D.

Raphael Schiffmann M.D.

Bremova-Ertl, T., R. Schiffmann, M. C. Patterson, N. Belmatoug, T. Billette de Villemeur, S. Bardins, C. Frenzel, V. Malinova, S. Naumann, J. Arndt, E. Mengel, J. Reinke, R. Strobl and M. Strupp (2017). “Oculomotor and Vestibular Findings in Gaucher Disease Type 3 and Their Correlation with Neurological Findings.” Front Neurol Jan 15; 8:711.

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Objectives: To evaluate the function of the oculomotor and vestibular systems and to correlate these findings with the clinical status of patients with Gaucher disease type 3 (GD3). The goal of this cross-sectional and longitudinal study was to find oculomotor biomarkers for future clinical trials. Methods: Twenty-six patients with GD3 were assessed for eligibility and 21 were able to perform at least one task. Horizontal and vertical reflexive saccades, smooth pursuit, gaze-holding, optokinetic nystagmus, and horizontal vestibulo-ocular reflex (VOR) were examined by video-oculography/video-head impulse test and compared concurrently with 33 healthy controls. The Scale for the Assessment and Rating of Ataxia (SARA), the modified Severity Scoring Tool (mSST), and Grooved Pegboard Test (GPT) were administered to assess overall neurological function. Eleven patients were also re-assessed after 1 year. Results: Nine out of 17 patients exhibited gaze-holding deficits. One patient had upbeat nystagmus. Three patients presented with bilateral abducens palsy in combination with central oculomotor disorders, suggesting a bilateral involvement of the abducens nucleus. Horizontal angular VOR gain was reduced in all patients (0.66 +/- 0.37) compared with controls (1.1 +/- 0.11, p < 0.001). Most strongly correlated with clinical rating scales were peak velocity of downward saccades (SARA: rho = -0.752, p < 0.0005; mSST: rho = -0.611, p = 0.003; GPT: rho = -0.649, p = 0.005) and duration of vertical saccades (SARA: rho = 0.806, p < 0.001; mSST: rho = 0.700, p < 0.0005; GPT: rho = 0.558, p = 0.02) together with the VOR gain (SARA: rho = -0.63, p = 0.016; mSST: rho = -0.725, p = 0.003; GPT: rho = -0.666, p = 0.004). Vertical smooth pursuit gain decreased significantly at follow-up. Interpretation: This study shows neuronal degeneration of the brainstem and cerebellum with combined involvement of both supranuclear and nuclear oculomotor structures and the vestibular system in GD3. We also identified oculomotor parameters that correlate with the neurological status and can be used as biomarkers in future clinical trials.


Posted February 15th 2018

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy in Early-Stage Invasive Breast Cancer.

Joanne L. Blum M.D.

Joanne L. Blum M.D.

Blum, J. L., N. Robert, J. Andersen, A. Favret, P. Ward, C. Osborne and J. Pippen (2018). “Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy in Early-Stage Invasive Breast Cancer.” J Clin Oncol 36(4): 428-429.

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Although we agree with the decision of the ASCO Guideline Panel members to update the use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer1 on the basis of the published results of the MINDACT (Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy) trial, we take exception with two issues. One is the language used in most of the detailed recommendations in the update, which state that physicians “should” or “should not” use specific tests in specific situations. We believe that the use of directive language, such as should and should not, goes beyond the concept of recommended guidelines and becomes a directive to clinicians. We note that recommendation 1.2.1 includes language that states that physicians “may” use the 70-gene signature assay and does not use the more directive should or should not language. Second, we agree that the 70-gene assay may provide some utility for decision making for patients with breast cancer with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2–negative, lymph node–positive disease with one to three positive lymph nodes. However, we note that this recommendation is based on a small prospective data set of 731 women with lymph node–positive disease with one to three positive lymph nodes and high clinical and low genomic risk who were randomly assigned to receive chemotherapy or not. Although the entire high clinical and low genomic risk group included 1,550 women randomly assigned to receive chemotherapy or not, this group included both patients with positive and patients with negative lymph nodes. The outcome data provided for the entire group as noted in Figure 2 and Table 3 of the report included one half of the patients who had lymph node–negative disease. Moreover, follow-up for this study is still short at only 5 years, and the results may change with later follow-up. (Excerpt from text.)


Posted February 15th 2018

Research priorities for the discovery of a cure for chronic hepatitis B: Report of a workshop.

Robert P. Perrillo M.D.

Robert P. Perrillo M.D.

Block, T. M., H. Alter, N. Brown, A. Brownstein, C. Brosgart, K. M. Chang, P. J. Chen, C. Cohen, H. El-Serag, J. Feld, R. Gish, J. Glenn, T. F. Greten, J. T. Guo, Y. Hoshida, K. V. Kowdley, W. Li, A. S. Lok, B. McMahon, A. Mehta, R. Perrillo, C. M. Rice, J. Rinaudo, R. F. Schinazi and K. Shetty (2018). “Research priorities for the discovery of a cure for chronic hepatitis B: Report of a workshop.” Antiviral Res 150: 93-100.

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In early 2017, the Hepatitis B Foundation invited 30 experts in the fields of hepatitis B and liver cancer research to identify projects they deemed important to the goal of finding a cure for chronic hepatitis B and D and the diseases with which these viral infections are associated. They were also asked to identify general categories of research and to prioritize sub-project topics within those areas. The experts generally agreed on broadly defined areas of research, but there was usually little difference between the highest and lowest scoring projects; for the most part, all programs described in this document were considered valuable and necessary. An executive summary of this discussion was recently published (Alter et al., Hepatology 2017). The present manuscript reports the areas of research identified by the workshop participants, provides a brief rationale for their selection, and attempts to express differences among the priorities assigned to each area of research, when such distinctions were expressed.