Research Spotlight

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.

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.

Edmonds, J. K., L. A. Campbell and R. E. Gilder (2016). “Public health nursing practice in the affordable care act era: A national survey.” Public Health Nurs: 2016 Jul [Epub ahead of print].

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OBJECTIVES: To explore public health nurses’ knowledge, perceptions, and practices under the Affordable Care Act (ACA). DESIGN AND SAMPLE: A cross-sectional, web-based survey was completed by a sample of 1,143 public health nurses (PHNs) in the United States. MEASURES: Descriptive statistics were analyzed for variables related to general knowledge and perception of the ACA and for the extent of involvement in activities related to the implementation of the ACA. Qualitative analysis was conducted on free text comments to two open-ended questions about current and future PHNs involvement in the ACA. RESULTS: Approximately 45% of PHNs reported changes in their daily work due to the ACA. PHNs reported being very or somewhat involved in these activities of the ACA: integration of primary care and public health (62%), provision of clinical preventive services (60.3%), care coordination (55.4%), patient navigation (55.3%), establishment of private-public partnerships (55.3%), population health strategies (53.6%), population health data assessment and analysis (53.8%), community health assessments (49%), involvement in medical homes (37.8%), provision of maternal and child health home visiting services (32.1%), and involvement in Accountable Care Organizations (29.2%). CONCLUSION: PHNs are making substantial contributions to implementation of the ACA.

Gandhi, S. S., J. V. Blas, S. Lee, J. F. Eidt and C. G. Carsten, 3rd (2016). “Nonoperative management of grade iii blunt thoracic aortic injuries.” J Vasc Surg: 2016 Jul 2022 [Epub ahead of print].

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OBJECTIVE: Blunt thoracic aortic injuries (BTAIs) have historically been treated with open surgery; thoracic endovascular aortic repair (TEVAR), however, is rapidly becoming the standard of care for all grades of injury. Previous studies have shown successful, conservative management of low-grade (I and II) BTAI, but limited literature exists regarding nonoperative management (NOM) for high-grade BTAI. The purpose of this study was to evaluate NOM for grade III BTAI compared with TEVAR. METHODS: There were 75 patients diagnosed with BTAI between January 2004 and June 2015. Of these, 40 were excluded for different grades of BTAI (17), death before any treatment (6), and need for urgent open repair (17). The remaining 35 patients were divided into two groups by treatment approach: NOM (n = 18) and TEVAR (n = 17). Primary end points were complications and mortality. The secondary end point was difference in pseudoaneurysm and aortic diameter measurements between groups. RESULTS: The groups of patients were similar in age, gender, Injury Severity Score, length of stay, in-hospital mortality, and hospital-associated complications. There were four TEVAR-related complications: graft involutions (2), type I endoleak (1), and distal embolization (1). All TEVAR-related complications required either an adjunctive procedure at the time of the primary procedure or an additional procedure. No patients from the NOM group required operative intervention. There were seven in-hospital mortalities: two in the TEVAR group (11.8%) and five in the NOM group (27.8%; P = .402). One death in the NOM group was related to aortic disease. Follow-up computed tomography imaging revealed similar aortic-related outcomes between groups, with a high proportion showing resolved or improved aortic injury (NOM, 87.5%; TEVAR, 92.9%; P = .674). Initial computed tomography imaging showed similar aortic diameters between groups. The average diameter of the aorta distal to the subclavian artery was 22.6 mm in the NOM group vs 22.8 mm in the TEVAR group (P = .85). The average maximum diameter of the pseudoaneurysm was 30.1 mm in the TEVAR group and 29.9 mm in the NOM group (P = .90). The average ratio of diameter of the pseudoaneurysm to diameter of the aorta distal to the subclavian artery was 1.32 for the TEVAR group and 1.33 for the NOM group (P = .85). CONCLUSIONS: The natural history of grade III BTAIs is not well described. This study suggests that observation and NOM of grade III BTAI may be a reasonable therapeutic option in selected patients. It also speaks to the need for further delineation of the natural history of this injury. Serial imaging and long-term follow-up are necessary to monitor the progression of the pseudoaneurysm.

Gayed, B. A., R. Youssef, O. Darwish, P. Kapur, A. Bagrodia, J. Brugarolas, G. Raj, J. M. DiMaio, A. Sagalowsky and V. Margulis (2016). “Multi-disciplinary surgical approach to the management of patients with renal cell carcinoma with venous tumor thrombus: 15 year experience and lessons learned.” BMC Urol 16(1): 43.

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BACKGROUND: The management of patients with renal cell carcinoma (RCC) with venous tumor thrombus (VTT) is challenging. We report our 15 year experience in the management of patients with RCC with VTT utilizing a multidisciplinary team approach, highlighting improved total and specifically Clavien III-V complication rates. METHODS: We reviewed the records of 146 consecutive patients who underwent radical nephrectomy with venous thrombectomy between 1998 and 2012. Data on patient history, staging, surgical techniques, morbidity, and survival were analyzed. Additionally, complication rates between two surgical eras, 1998-2006 and 2006-2012, were assessed. RESULTS: The study included 146 patients, 97 males (66 %), and a median age of 61 years (range, 24-83). Overall complications rate was 53 %, high grade complications (Clavien III -V) occurred in 10 % of patients. Most importantly, there was a lower incidence of overall and high grade complications (45 % and 8 %, respectively) in the last 6 years compared to the earlier surgeries included in the study (67 % and 13 % respectively) [p = .008 and .03, respectively). 30 day postoperative mortality was 2.7 %. 5 year overall survival (5Y- OS) and 5 year cancer specific survival (5Y- CSS) were 51 % and 40 %, respectively. Metastasis was the only independent predictor factor for CSS (HR 3.8, CI 1.9-7.6 and p < .001) and OS (HR 2.6, CI 1.5-4.7 and p = .001) in all patients. CONCLUSIONS: Our data suggest that patients with RCC and VTT can be treated safely utilizing a multidisciplinary team approach leading to a decrease in complication rates.