Publications

To date, no prospective randomized trials exist comparing high-dose therapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT) against conventional therapy for management of peripheral T cell lymphomas either as upfront consolidation or in the relapsed/refractory setting. Available data supporting this approach are limited to single-arm prospective or retrospective studies only. Accordingly, we performed a systematic review/meta-analysis of the published literature. Our search identified 1586 publications, but only 27 (n = 1368) met our inclusion criteria. In the front-line setting, pooled analysis of only prospective studies showed rates of progression-free survival (PFS) of 33% (95% confidence interval [CI], 14% to 56%), overall survival (OS) of 54% (95% CI, 32% to 75%), relapse/progression of 26% (95% CI, 20% to 33%), and transplantation-related mortality (TRM) of 2% (95% CI, 0% to 5%); for retrospective studies, rates of PFS, OS, relapse/progression, TRM, and secondary malignancies were 55% (95% CI, 40% to 69%), 68% (95% CI, 56% to 78%), 36% (95% CI, 24% to 48%), 6% (95% CI, 2% to 11%), and 7% (95% CI, 2% to 14%), respectively. On the other hand, pooled analysis of retrospective studies evaluating HDT/auto-HCT in the relapsed/refractory setting showed pooled rates of PFS, OS, relapse/progression, and TRM of 36% (95% CI, 32% to 40%), 47% (95% CI, 43% to 51%), 51% (95% CI, 39% to 62%), and 10% (95% CI, 5% to 17%), respectively. Among the various histologic subtypes, PFS and OS rates appear to be higher in anaplastic large cell lymphoma, regardless of disease stage. In the absence of a multicenter, randomized controlled trial comparing HDT/auto-HCT to a nontransplantation strategy, the findings of this systematic review/meta-analysis may represent the best evidence supporting the role of HDT/auto-HCT for treatment of peripheral T cell lymphomas as front-line consolidation or in the relapsed/refractory setting.

We sought to establish clinical practice recommendations to redefine the role of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with chronic lymphocytic leukemia (CLL) in an era of highly active targeted therapies. We performed a systematic review to identify prospective randomized controlled trials comparing allo-HCT against novel therapies for treatment of CLL at various disease stages. In the absence of such data, we invited physicians with expertise in allo-HCT and/or CLL to participate in developing these recommendations. We followed the Grading of Recommendations Assessment, Development and Evaluation methodology. For standard-risk CLL we recommend allo-HCT in the absence of response or if there is evidence of disease progression after B cell receptor (BCR) inhibitors. For high-risk CLL an allo-HCT is recommended after failing 2 lines of therapy and showing an objective response to BCR inhibitors or to a clinical trial. It is also recommended for patients who fail to show an objective response or progress after BCR inhibitors and receive BCL-2 inhibitors, regardless of whether an objective response is achieved. For Richter transformation, we recommend allo-HCT upon demonstration of an objective response to anthracycline-based chemotherapy. A reduced-intensity conditioning regimen is recommended whenever indicated. These recommendations highlight the rapidly changing treatment landscape of CLL. Newer therapies have disrupted prior paradigms, and allo-HCT is now relegated to later stages of relapsed or refractory CLL.

OBJECTIVES: Caffeine consumption is reported to be associated with reduced hepatic fibrosis in patients with chronic liver diseases. We performed a systematic review and meta-analysis to assess the association between caffeine consumption and prevalence or hepatic fibrosis of nonalcoholic fatty liver disease (NAFLD) in observational studies.

METHODS: We searched the literature of all languages from PubMed, EMBASE, and the Cochrane library from 1 January 1980 through 10 January 2015. Total caffeine consumption was defined as the daily intake of caffeine (mg/day) from all caffeine-containing products. Combined and subgroup analyses stratified by study designs, study locations, and type of caffeine intake were performed.

RESULTS: Four cross-sectional and two case control studies with a total of 20,064 subjects were included in the meta-analysis. Among these, three studies with 18,990 subjects were included in the analysis for prevalence of NAFLD while the other three studies with 1074 subjects were for hepatic fibrosis. Total caffeine consumption (mg/day) was not significantly associated with either the prevalence [pooled mean difference (MD) 2.36; 95% confidence interval (CI) -35.92 to 40.64] or hepatic fibrosis (higher versus lower stages; pooled MD -39.95; 95% CI -132.72 to 52.82) of NAFLD. Subgroup analyses stratified by study designs and locations were also not significant. However, after stratifying by type of caffeine intake, regular coffee caffeine intake (mg/day) was significantly associated with reduced hepatic fibrosis of NAFLD (pooled MD -91.35; 95% CI -139.42 to -43.27; n = 2 studies).

CONCLUSION: Although total caffeine intake is not associated with the prevalence or hepatic fibrosis of NAFLD, regular coffee caffeine consumption may significantly reduce hepatic fibrosis in patients with NAFLD.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is associated with significant morbidity and mortality. Bedaquiline is the first drug approved for treating MDR-TB.

OBJECTIVES: We performed a systematic review and meta-analysis to summarize the totality of all available evidence on the efficacy of bedaquiline for the management of MDR-TB.

MATERIALS AND METHODS: We searched the following PubMed and Cochrane Registry of Clinical Trials. Randomized controlled trials (RCTs) with a parallel design comparing bedaquiline versus any treatment for the management of MDR-TB in adults were eligible for inclusion. Data were pooled under a random effects model.

RESULTS: Two trials published as three manuscripts with a total of 207 patients were included. As per the Cochrane risk of bias tool, majority of parameter were labeled as high or unclear risk of bias. Bedaquiline compared with placebo was associated with a statistically significant decrease in time to conversion of positive sputum culture to negative at 8 and 24 weeks with a significant increase in mortality on long-term follow-up. There was no difference in completion rates between bedaquiline and placebo.

CONCLUSION: Bedaquiline is an effective treatment modality for MDR-TB but needs to be balanced against significant mortality. Future Phase 3 RCTs are needed to make a conclusive recommendation.

Allogeneic hematopoietic cell transplantation (allo-HCT) is the only known treatment that can offer a cure in mantle cell lymphoma, but it is unclear if regimen dose-intensity offers any advantage. We performed a systematic review/meta-analysis to assess efficacy of allo-HCT using myeloablative or reduced-intensity conditioning. We report results according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. On the basis of a relatively lower nonrelapse mortality and a slightly better progression-free survival/event-free survival and overall survival rates, reduced-intensity allo-HCT regimens appear to be the preferred choice when an allo-HCT is being considered for mantle cell lymphoma. The higher rate of relapse when offering reduced-intensity regimens cannot be ignored but certainly highlights opportunities to incorporate post-transplant strategies to mitigate this risk. A prospective comparative study is ultimately needed to generate more conclusive evidence.

BACKGROUND: Nipple-sparing mastectomy (NSM) with tissue expander reconstruction is a widely used technique that can produce aesthetically pleasing reconstruction results after mastectomy. Nipple position and healthy mastectomy flaps with good vascularity are important determinants of an adequate aesthetic final result. An initial high fill volume of the expander can produce a more natural breast mound appearance postoperatively. However, this can often lead to ischemia with loss of the nipple-areolar complex (NAC). Conversely, low intraoperative fill rates are conducive to enhanced tissue circulation and viability. But this may lead to poor skin envelope draping and nipple placement lower than desired. We have developed a new technique called "Duoderm®-bra" that brings together both mastectomy skin tissue health and aesthetic success with optimal nipple positioning. We hypothesized that with Duoderm®-bra, the NAC can be stabilized in the desired high position and ptosis can be reduced. We also hypothesized that by eliminating the need for acellular dermal matrix and intraoperative fill, "Duoderm®-bra" would decrease the rate of complications. The objective of this study was to evaluate the effects of using novel "Duoderm®-bra" technique in NSM.

METHODS: After an institutional review board approval, a retrospective chart review of 35 consecutive patients was done with 65 breasts undergoing NSM and tissue expander reconstruction by the same plastic surgeon. Patients in whom "Duoderm®-bra" was used were compared with patients without the "Duoderm®-bra." Patients with acellular dermal matrix were excluded. Age, ptosis grade, preoperative nipple to IMF ratio (R/L), tumor characteristics, mastectomy specimen weight (R/L), time from mastectomy to first fill, time from mastectomy to final fill, final fill volume (R/L), NAC and skin necrosis, and other complications requiring surgery were recorded. Postoperative photographs for NAC positioning (side view most projected point versus at a lower point) were assessed using a scoring system. Two groups were then compared.

RESULTS: Complications were higher in the non-Duoderm® group compared with Duoderm®-bra (odds ratio, 4.5; 95% confidence interval [CI], 1.35-15.04; P = 0.021). Optimum nipple positioning was significantly higher with Duoderm®-bra compared with no Duoderm®-bra (odds ratio, 50.0; 95% CI, 10.9-230.1; P < 0.0001). There was no difference in timing from mastectomy to completion of expansion in the Duoderm® group compared with no Duoderm®-bra group (mean difference, -2.35; 95% CI, -10.37 to 5.68).

CONCLUSIONS: Use of "Duoderm®-bra" without intraoperative tissue expansion in NSM is a new technique. This technique improves nipple position with less ptosis and greater elevation, decreases flap and NAC necrosis complications, and does not increase total reconstructive period in NSM patients.

To date, no prospective randomized trials exist comparing high-dose therapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT) against conventional therapy for management of peripheral T cell lymphomas either as upfront consolidation or in the relapsed/refractory setting. Available data supporting this approach are limited to single-arm prospective or retrospective studies only. Accordingly, we performed a systematic review/meta-analysis of the published literature. Our search identified 1586 publications, but only 27 (n = 1368) met our inclusion criteria. In the front-line setting, pooled analysis of only prospective studies showed rates of progression-free survival (PFS) of 33% (95% confidence interval [CI], 14% to 56%), overall survival (OS) of 54% (95% CI, 32% to 75%), relapse/progression of 26% (95% CI, 20% to 33%), and transplantation-related mortality (TRM) of 2% (95% CI, 0% to 5%); for retrospective studies, rates of PFS, OS, relapse/progression, TRM, and secondary malignancies were 55% (95% CI, 40% to 69%), 68% (95% CI, 56% to 78%), 36% (95% CI, 24% to 48%), 6% (95% CI, 2% to 11%), and 7% (95% CI, 2% to 14%), respectively. On the other hand, pooled analysis of retrospective studies evaluating HDT/auto-HCT in the relapsed/refractory setting showed pooled rates of PFS, OS, relapse/progression, and TRM of 36% (95% CI, 32% to 40%), 47% (95% CI, 43% to 51%), 51% (95% CI, 39% to 62%), and 10% (95% CI, 5% to 17%), respectively. Among the various histologic subtypes, PFS and OS rates appear to be higher in anaplastic large cell lymphoma, regardless of disease stage. In the absence of a multicenter, randomized controlled trial comparing HDT/auto-HCT to a nontransplantation strategy, the findings of this systematic review/meta-analysis may represent the best evidence supporting the role of HDT/auto-HCT for treatment of peripheral T cell lymphomas as front-line consolidation or in the relapsed/refractory setting.