Research Spotlight

Lima, B., A. Bansal, J. Abraham, J. D. Rich, S. S. Lee, B. Soleimani, J. N. Katz, A. Kilic, J. S. Young, C. B. Patel and S. M. Joseph (2018). “Controversies and Challenges of Ventricular Assist Device Therapy.” Am J Cardiol 121(10): 1219-1224.

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Left ventricular assist device (LVAD) therapy has emerged as an increasingly vital facet of the treatment algorithm for advanced heart failure. Growing experience with LVAD support has led to substantial improvements in outcomes, with 1-year survival rates approaching that of cardiac transplantation. These therapeutic refinements have engendered growing interests in the potential for expanding the clinical indications for LVAD therapy to patients with less advanced heart failure. The primary obstacles to this evolution of care center largely on the prevention and/or management of the adverse events associated with LVAD therapy along with patient preference. Many programs also face the mounting difficulty of balancing quality outcomes with the increased volume of implants. During the recently assembled Users Meeting organized by St. Jude Medical, heart failure clinicians from nearly 50 LVAD implanting centers discussed these and other challenges and controversies impacting the field. The present review summarizes the key insights gleaned from this meeting.

Warren, A. M., G. Testa, T. Anthony, G. J. McKenna, G. B. Klintmalm, K. Wallis, E. C. Koon, R. T. Gunby, Jr. and L. Johannesson (2018). “Live nondirected uterus donors: Psychological characteristics and motivation for donation.” Am J Transplant 18(5): 1122-1128

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Emerging research suggests that uterus transplantation is a viable option for women without a uterus who want to become pregnant and carry a child to term. Currently, no knowledge exists regarding nondirected uterus donors. This study (NCT 02656550) explored the baseline psychological characteristics of nondirected uterus donors at a single study site. Of the 62 potential donors who underwent initial screening, 6 nondirected donors were chosen and participated in uterus donation. Participants received a comprehensive evaluation, which included clinical history and psychological assessments. The mean age of the donors was 42 years; most (83%) were white/not Hispanic, and all had a college degree. Current depression was reported by 2 participants, past depression was reported in 2 participants, and past anxiety was reported in 3 participants. Based on several different psychological measures, donors had a higher general well-being than the normative sample, and none of the participants’ scores indicated psychological distress. All 6 women indicated that giving another woman an opportunity to carry her own child was a motivation for pursuing uterus donation. Further research on potential psychological motives and gains for the donor as well as long-term effects on donors is crucial for ethical practice.

Yadlapati, R., M. F. Vaezi, M. F. Vela, S. J. Spechler, N. J. Shaheen, J. Richter, B. E. Lacy, D. Katzka, P. O. Katz, P. J. Kahrilas, C. P. Gyawali, L. Gerson, R. Fass, D. O. Castell, J. Craft, L. Hillman and J. E. Pandolfino (2018). “Management options for patients with GERD and persistent symptoms on proton pump inhibitors: recommendations from an expert panel.” Am J Gastroenterol. Apr 24. [Epub ahead of print].

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BACKGROUND: The aim of this study was to assess expert gastroenterologists’ opinion on treatment for distinct gastroesophageal reflux disease (GERD) profiles characterized by proton pump inhibitor (PPI) unresponsive symptoms. METHODS: Fourteen esophagologists applied the RAND/UCLA Appropriateness Method to hypothetical scenarios with previously demonstrated GERD (positive pH-metry or endoscopy) and persistent symptoms despite double-dose PPI therapy undergoing pH-impedance monitoring on therapy. A priori thresholds included: esophageal acid exposure (EAE) time >6.0%; symptom-reflux association: symptom index >50% and symptom association probability >95%; >80 reflux events; large hiatal hernia: >3 cm. Primary outcomes were appropriateness of four invasive procedures (laparoscopic fundoplication, magnetic sphincter augmentation, transoral incisionless fundoplication, radiofrequency energy delivery) and preference for pharmacologic/behavioral therapy. RESULTS: Laparoscopic fundoplication was deemed appropriate for elevated EAE, and moderately appropriate for positive symptom-reflux association for regurgitation and a large hiatal hernia with normal EAE. Magnetic sphincter augmentation was deemed moderately appropriate for elevated EAE without a large hiatal hernia. Transoral incisionless fundoplication and radiofrequency energy delivery were not judged appropriate in any scenario. Preference for non-invasive options was as follows: H2RA for elevated EAE, transient lower esophageal sphincter relaxation inhibitors for elevated reflux episodes, and neuromodulation/behavioral therapy for positive symptom-reflux association. CONCLUSION: For treatment of PPI unresponsive symptoms in proven GERD, expert esophagologists recommend invasive therapy only in the presence of abnormal reflux burden, with or without hiatal hernia, or regurgitation with positive symptom-reflux association and a large hiatus hernia. Non-invasive pharmacologic or behavioral therapies are preferred for all other scenarios.

Wang, J., J. Y. Park, R. Huang, R. F. Souza, S. J. Spechler and E. Cheng (2018). “Obtaining adequate lamina propria for subepithelial fibrosis evaluation in pediatric eosinophilic esophagitis.” Gastrointest Endosc 87(5): 1207-1214.e1203.

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BACKGROUND AND AIMS: Subepithelial fibrosis in eosinophilic esophagitis (EoE) can be detected only in esophageal biopsy specimens with adequate amounts of lamina propria (LP). We investigated how often pediatric esophageal biopsy specimens contain adequate LP, and whether esophageal eosinophilia influences the acquisition rates. METHODS: We evaluated 284 esophageal biopsy specimens from 39 patients with EoE, and 87 biopsy specimens from 32 patients without esophageal eosinophilia or other esophageal abnormalities for the presence of adequate LP and fibrosis. RESULTS: On a per biopsy specimen basis, there was no significant difference in the rate of procuring adequate amounts of LP between patients with EoE and patients without esophageal eosinophilia (43% vs 31%, P = .14). Eighty-five percent of patients with EoE had fibrosis. Fibrosis in patients with EoE was patchy and more likely to be detected in the middle or distal esophagus (odds ratio, 19.93; 95% confidence interval, 4.12-91.52). Among patients with fibrosis, the probability of its detection reached >95% with 7 middle-distal esophageal biopsy specimens. Most children with newly diagnosed EoE already had subepithelial fibrosis despite exhibiting only inflammatory endoscopic features. CONCLUSIONS: Most individual esophageal biopsy specimens in children are inadequate for assessing subepithelial fibrosis, and the rates of procuring adequate LP per biopsy specimen are similar in patients with and without EoE. To reliably detect fibrosis in patients with EoE, at least 7 biopsy specimens should be taken from the middle-distal esophagus. The finding of fibrosis in children with newly diagnosed EoE and only inflammatory endoscopic features suggests that fibrosis can occur early in this disease.

Verma, S., J. O’Shaughnessy, H. A. Burris, M. Campone, E. Alba, D. Chandiwana, A. A. Dalal, S. Sutradhar, M. Monaco and W. Janni (2018). “Health-related quality of life of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer treated with ribociclib + letrozole: results from MONALEESA-2.” Breast Cancer Res Treat. Apr 13. [Epub ahead of print].

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PURPOSE: Evaluate patient-reported outcomes (PROs) for postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer treated with first-line ribociclib plus letrozole. METHODS: In the phase III MONALEESA-2 study (NCT01958021), 668 patients were randomized 1:1 to ribociclib (600 mg/day; 3-weeks-on/1-week-off) plus letrozole (2.5 mg/day) or placebo plus letrozole. PROs were assessed using the European Organisation for Research and Treatment of Cancer core quality-of-life (EORTC QLQ-C30) and breast cancer-specific (EORTC QLQ-BR23) questionnaires. Changes from baseline and time to deterioration in health-related quality of life (HRQoL) were analyzed using linear mixed-effect and stratified Cox regression models, respectively. Exploratory analysis of area-under-the-curve for change from baseline in pain score (AUC-pain) was performed. RESULTS: On-treatment HRQoL scores were consistently maintained from baseline and were similar between arms. A clinically meaningful (> 5 points) reduction in pain score was observed as early as Week 8 and was maintained up to Cycle 15 in the ribociclib arm. A statistically significant increase in mean AUC-pain was also observed in the ribociclib arm. Scores for all other EORTC QLQ-C30 and EORTC QLQ-BR23 domains were maintained from baseline and were similar between arms. CONCLUSIONS: HRQoL was consistently maintained from baseline in postmenopausal women with HR+, HER2- advanced breast cancer receiving ribociclib plus letrozole and was similar to that observed in the placebo plus letrozole arm. Together with the improved clinical efficacy and manageable safety profile, these PRO results provide additional support for the benefit of ribociclib plus letrozole in this patient population.