Research Spotlight

Posted August 15th 2016

Recommendations for the diagnosis and initial evaluation of patients with waldenstrom macroglobulinaemia: A task force from the 8th international workshop on waldenstrom macroglobulinaemia.

Joseph W. Fay M.D.

Joseph W. Fay M.D.

Castillo, J. J., R. Garcia-Sanz, E. Hatjiharissi, R. A. Kyle, X. Leleu, M. McMaster, G. Merlini, M. C. Minnema, E. Morra, R. G. Owen, S. Poulain, M. J. Stone, C. Tam, M. Varettoni, M. A. Dimopoulos, S. P. Treon and E. Kastritis (2016). “Recommendations for the diagnosis and initial evaluation of patients with waldenstrom macroglobulinaemia: A task force from the 8th international workshop on waldenstrom macroglobulinaemia.” Br J Haematol: 2016 Jul [Epub ahead of print].

Full text of this article.

The diagnosis of Waldenstrom macroglobulinaemia (WM) can be challenging given the variety of signs and symptoms patients can present. Furthermore, once the diagnosis of WM is established, the initial evaluation should be thorough as well as appropriately directed. During the 8th International Workshop for WM in London, United Kingdom, a multi-institutional task force was formed to develop consensus recommendations for the diagnosis and initial evaluation of patients with WM. In this document, we present the results of the deliberations that took place to address these issues. We provide recommendations for history-taking and physical examination, laboratory studies, bone marrow aspiration and biopsy analysis and imaging studies. We also provide guidance on the initial evaluation of special situations, such as anaemia, hyperviscosity, neuropathy, Bing-Neel syndrome and amyloidosis. We hope these recommendations serve as a practical guidance to clinicians taking care of patients with a suspected or an established diagnosis of WM.


Posted August 15th 2016

Synthesis and immunostimulatory activity of substituted tlr7 agonists.

SangKon Oh Ph.D.

SangKon Oh Ph.D.

Akinbobuyi, B., L. Wang, K. C. Upchurch, M. R. Byrd, C. A. Chang, J. M. Quintana, R. E. Petersen, Z. J. Seifert, J. R. Boquin, S. Oh and R. R. Kane (2016). “Synthesis and immunostimulatory activity of substituted tlr7 agonists.” Bioorg Med Chem Lett: 2016 Jul [Epub ahead of print].

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Fifteen new substituted adenines were synthesized as potential TLR7 agonists. These compounds, along with 9 previously reported compounds, were analyzed for TLR7 activity and for the selective stimulation of B cell proliferation. Several functionalized derivatives exhibit significant activity, suggesting their potential for use as vaccine adjuvants.


Posted August 15th 2016

Authors’ Response.

Ashley W. Collinsworth Sc.D.

Ashley W. Collinsworth Sc.D.

Collinsworth, A. W. and A. L. Masica (2016). “Authors’ response.” J Intensive Care Med 31(7): 494-495.

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Use of “care bundles” has been advocated as a means to accelerate the adoption of multiple care processes into routine clinical practice, benchmark performance, and improve patient outcomes. We recently implemented the Awakening and Breathing Coordination, Delirium Monitoring, and Early Mobility (ABCDE) bundle in 12 Baylor Scott and White Health ICUs and found that bundling these care processes was associated with improved adherence to the individual care processes for delirium prevention and mitigation within the bundle and improved patient outcomes. Although some sites participated in structured educational workshops during the early phases of bundle implementation, we found that the greatest improvement in bundle uptake occurred after we modified the electronic health record (EHR) to facilitate clinical workflow around bundle delivery and documentation.3 This finding suggests that establishing tools that facilitate integration of delirium prevention measures into clinical workflow, such as structured forms for documentation of bundle elements within the EHR, should be the first step in the implementation process followed by educational sessions on the importance of delirium prevention and use of the tools.


Posted August 15th 2016

Safety and tolerability of etirinotecan pegol in advanced breast cancer: Analysis of the randomized, phase 3 beacon trial.

Joyce O'Shaughnessy M.D.

Joyce O’Shaughnessy M.D.

Cortes, J., H. S. Rugo, C. Twelves, A. Awada, E. A. Perez, S. A. Im, C. Zhao, U. Hoch, D. Tomkinson, J. Buchanan, M. Tagliaferri, A. Hannah and J. O’Shaughnessy (2016). “Safety and tolerability of etirinotecan pegol in advanced breast cancer: Analysis of the randomized, phase 3 beacon trial.” Springerplus 5(1): 1033.

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PURPOSE: New treatments with novel mechanisms of action and non-overlapping toxicities are needed for patients with metastatic breast cancer. Etirinotecan pegol (EP) is a long-acting topoisomerase-I inhibitor with a unique toxicity profile. The randomized phase 3 BEACON study that compared EP to treatment of physician’s choice (TPC) demonstrated its clinical activity. We now present detailed safety data from the BEACON trial. METHODS: Patients with locally recurrent or metastatic breast cancer who had received at least two prior cytotoxic regimens for advanced disease were randomized to EP or TPC. Prior treatment with an anthracycline, a taxane and capecitabine was required. The frequencies of treatment-emergent AEs (TEAEs) and serious TEAEs were evaluated for the safety population, comprising all patients who received at least one dose of assigned treatment. RESULTS: A total of 831 patients were evaluated (n = 425, EP; n = 406, TPC). Compared with TPC, EP was associated with a slightly higher median relative dose intensity (98.3 vs. 92.8 %, respectively) and significantly fewer grade >/=3 toxicities (48.0 vs. 63.1 %, P < 0.0001). The most commonly reported grade >/=3 toxicities in the EP arm were diarrhea (9.6 %) and neutropenia (9.6 %) and in the TPC arm, neutropenia (30.8 %). Median time to onset of grade >/=3 diarrhea was delayed with EP relative to TPC (43 vs. 7 days, respectively). CONCLUSIONS: The differentiated mechanism of action of EP resulted in a safety profile that is substantially distinguished from that of current widely used therapies for the treatment of women with advanced breast cancer.


Posted August 15th 2016

Influence of sacubitril/valsartan (lcz696) on 30-day readmission after heart failure hospitalization.

Milton Packer M.D.

Milton Packer M.D.

Desai, A. S., B. L. Claggett, M. Packer, M. R. Zile, J. L. Rouleau, K. Swedberg, V. Shi, M. Lefkowitz, R. Starling, J. Teerlink, J. J. McMurray and S. D. Solomon (2016). “Influence of sacubitril/valsartan (lcz696) on 30-day readmission after heart failure hospitalization.” J Am Coll Cardiol 68(3): 241-248.

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BACKGROUND: Patients with heart failure (HF) are at high risk for hospital readmission in the first 30 days following HF hospitalization. OBJECTIVES: This study sought to determine if treatment with sacubitril/valsartan (LCZ696) reduces rates of hospital readmission at 30-days following HF hospitalization compared with enalapril. METHODS: We assessed the risk of 30-day readmission for any cause following investigator-reported hospitalizations for HF in the PARADIGM-HF trial, which randomized 8,399 participants with HF and reduced ejection fraction to treatment with LCZ696 or enalapril. RESULTS: Accounting for multiple hospitalizations per patient, there were 2,383 investigator-reported HF hospitalizations, of which 1,076 (45.2%) occurred in subjects assigned to LCZ696 and 1,307 (54.8%) occurred in subjects assigned to enalapril. Rates of readmission for any cause at 30 days were 17.8% in LCZ696-assigned subjects and 21.0% in enalapril-assigned subjects (odds ratio: 0.74; 95% confidence interval: 0.56 to 0.97; p = 0.031). Rates of readmission for HF at 30-days were also lower in subjects assigned to LCZ696 (9.7% vs. 13.4%; odds ratio: 0.62; 95% confidence interval: 0.45 to 0.87; p = 0.006). The reduction in both all-cause and HF readmissions with LCZ696 was maintained when the time window from discharge was extended to 60 days and in sensitivity analyses restricted to adjudicated HF hospitalizations. CONCLUSIONS: Compared with enalapril, treatment with LCZ696 reduces 30-day readmissions for any cause following discharge from HF hospitalization.