Research Spotlight

Mack, M. and H. Baumgarten (2016). “Just because you get on a scale doesn’t mean you lose weight: is Meetbaar Beter really measurably better?” Eur J Cardiothorac Surg. 2016 Mar 16. [Epub ahead of print]

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The article by van Veghel et al.[First results of a national initiative to enable quality improvement of cardiovascular care by transparently reporting on patient-relevant outcomes; Eur J Cardiothorac Surg., first published online March 16, 2016] describes a national initiative in the Netherlands termed ‘Meetbaar Beter’ or in English ‘Measurably Better’. The stated goal of this multicentre effort according to its website ‘aims to improve quality and transparency of care for patients with heart diseases by measuring limited patient-relevant outcome measures’ (http://www.meetbaarbeter.com/). Those outcomes include survival, degree of health/recovery, time to recovery and return to normal activity, disutility of the care of treatment process, sustainability of health/recovery and nature of recurrences and long-term consequences of the therapy. By doing this, they are proposing to implement a ‘Value Based Healthcare Theory’ by ‘measuring patient relevant outcomes and sharing and adopting each others best practices.’ This programme that began in 2012, termed the Netherlands Joint Outcomes and Transparency Initiative is a voluntary cooperative of 14 of the 16 heart centres in the country. The initial results of that effort in 86 000 patients treated at 12 of those hospitals with one of three diseases are reported in the accompanying article. The conclusion of this study is that ‘annual data collection of patient relevant outcomes appears to be feasible’. Furthermore, the authors conclude that transparency drives quality improvement and that using a limited set of outcomes measures enables comparisons and ‘exposes the quality of decision-making’. Lastly, they conclude that transparent communication is feasible, safe, cost-effective and stimulates professional decision-making and disease management . . . While this is an ambitious national multicentre initiative that is based on achieving patient-centred healthcare value, it is not clear from this study exactly how much the ‘needle has moved’. It is also not apparent how much of any change that may have occurred is truly causation and not merely association. Don Berwick, former administrator of the Center for Medicare and Medicaid in the USA, has recently stated as the first of nine steps to improve healthcare that we must stop excessive measurement. Stated another way, just because you step on a scale does not mean you lose weight. While the goals of this programme are laudable and beyond reproach, the evidence that change is actually occurring is not evident from this report. We would encourage the leaders of this national initiative to make efforts to provide greater clarity of results actually achieved and quality improvement in patient-relevant outcomes that they can directly credit to the programme. They are stepping on the scales and weighing a lot but is any weight really being lost? (Excerpts from text; no abstract.)

Giulino-Roth, L. and S. Goldman (2016). “Recent molecular and therapeutic advances in B-cell non-Hodgkin lymphoma in children.” Br J Haematol. Mar 21. [Epub ahead of print]

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Paediatric B-cell non-Hodgkin lymphoma (B-NHL) compromises a heterogeneous group of histological entities of which Burkitt lymphoma is the most common. In resource-rich countries, the expected cure rate is in excess of 85% with application of risk-adapted short intensive chemotherapy. In recent years, large paediatric cooperative group trials have sought to improve upon outcomes by decreasing the intensity of cytotoxic treatment as well as introducing targeted therapies, such as rituximab. These efforts have resulted in excellent outcomes, however there remains a group of high-risk patients for whom novel treatment approaches are needed. In this review, we will summarize the recent paediatric clinical trials in B-NHL as well as compare treatment approaches across the major cooperative groups. We will also highlight our current understanding of the molecular biology of paediatric B-NHL with a focus on how this may help guide future rational targeted therapy.

Weir, M. R., T. C. Pearson, A. Patel, V. R. Peddi, R. Kalil, J. Scandling, L. Chan, P. Baliga, L. Melton, S. Mulgaonkar, T. Waid, H. Schaefer, N. Youssef, L. Anandagoda, D. McCollum, S. Lawson and R. Gordon (2016). “Long-term Follow-up of Kidney Transplant Recipients in the Spare-the-Nephron-Trial.” Transplantation. Mar 4. [Epub ahead of print]

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In the Spare-the-Nephron (STN) Study, kidney transplant recipients randomized about 115 days posttransplant to convert from CNI (calcineurin inhibitor)/MMF to sirolimus (SRL)/MMF had a significantly greater improvement in measured GFR (mGFR) at 12 months compared with those kept on CNI/MMF. The difference at 24 months was not statistically significant. From 14 top enrolling centers, 128 of 175 patients identified with a functioning graft at 2 years consented to enroll in an observational, noninterventional extension study to collect retrospectively and prospectively annual follow-up data for the interval since baseline (completion of the parent STN study at 24 months posttransplant). Overall, 11 patients died, including 5 (7.6%) in the SRL/MMF group and 6 (9.7%) in the CNI/MMF group. Twenty-two grafts have been lost including 10 (15.2%) in the SRL/MMF arm and 12 (19.4%) in the CNI/MMF arm. Death and chronic rejection were the most common causes of graft loss in both arms. There were modestly more cardiovascular events in the MMF/SRL group. Estimated creatinine clearance (Cockcroft-Gault) from baseline out to 6 additional years (8 years posttransplant, ITT analysis, SRL/MMF, n = 34; CNI/MMF, n = 26) was 63.2 +/- 28.5 mL/min/1.73 m in the SRL/MMF group and 59.2 +/- 27.2 mL/min/1.73 m in the CNI/MMF group and was not statistically significant, but there is a clinically meaningful trend for improved long-term renal function in the SRL/MMF group compared with the CNI/MMF group. The long-term decision for immunosuppression needs to be carefully individualized.

Gupta, A., G. B. Klintmalm and P. T. Kim (2016). “Ligating coronary vein varices: An effective treatment of “Coronary Vein Steal” to increase portal flow in liver transplantation.” Liver Transpl. Mar 30. [Epub ahead of print]

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Portal hypertension in cirrhosis leads to the formation of portosystemic shunts (PSS). These venous shunts divert portal blood from the high-resistance liver to the lower-resistance systemic veins. Although most PSS resolve after liver transplantation, some may persist. The factors that increase graft resistance, such as acute rejection, volume overload, or ischemia, as well as large varix size may result in residual shunting. Persistent PSS after liver transplantation results in diversion of portal venous flow that may be detrimental to the liver allograft. The newly transplanted liver requires adequate flow of the portal vein (PV) for its survival. The coronary vein is one potential site where physiologically significant PV flow shunting can occur, resulting in the coronary vein “steal.” This condition has been associated with PV thrombosis after liver transplantation (5); however, there are no reports of improvement in measured PV blood flow following coronary vein ligation when the steal phenomenon was suspected. Herein, we present 3 cases of coronary vein steal, all detected intraoperatively and addressed with ligation of the varix, resulting in improvements of PV flow as measured using the Cliniflow II FM701D Electromagnetic Blood Flow Meter (Carolina Medical Electronics Inc., East Bend, NC, USA).

Liu, M. C., J. Cortes and J. O’Shaughnessy (2016). “Challenges in the treatment of hormone receptor-positive, HER2-negative metastatic breast cancer with brain metastases.” Cancer Metastasis Rev. Mar 29. [Epub ahead of print]

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Brain metastases are a major cause of morbidity and mortality for women with hormone receptor (HR)-positive breast cancer, yet little is known about the optimal treatment of brain disease in this group of patients. Although these patients are at lower risk for brain metastases relative to those with HER2-positive and triple-negative disease, they comprise the majority of women diagnosed with breast cancer. Surgery and radiation continue to have a role in the treatment of brain metastases, but there is a dearth of effective systemic therapies due to the poor penetrability of many systemic drugs across the blood-brain barrier (BBB). Additionally, patients with brain metastases have long been excluded from clinical trials, and few studies have been conducted to evaluate the safety and effectiveness of systemic therapies specifically for the treatment of HER2-negative breast cancer brain metastases. New approaches are on the horizon, such as nanoparticle-based cytotoxic drugs that have the potential to cross the BBB and provide clinically meaningful benefits to patients with this life-threatening consequence of HR-positive breast cancer.