Microbiota dynamics in a randomized trial of gut decontamination during allogeneic hematopoietic cell transplantation.

BACKGROUNDGut decontamination (GD) can decrease the incidence and severity of acute graft-versus-host disease (aGVHD) in murine models of allogeneic hematopoietic cell transplantation (HCT). In this pilot study, we examined the impact of GD on gut microbiome composition and the incidence of aGVHD in HCT patients.METHODSWe randomized 20 patients undergoing allogeneic HCT to receive (GD) or not receive (no-GD) oral vancomycin-polymyxin B from day -5 through neutrophil engraftment. We evaluated shotgun metagenomic sequencing of serial stool samples to compare the composition and diversity of the gut microbiome between study arms. We assessed clinical outcomes in the 2 arms and performed strain-specific analyses of pathogens that caused bloodstream infections (BSI).RESULTSThe 2 arms did not differ in the predefined primary outcome of Shannon diversity of the gut microbiome at 2 weeks post-HCT (genus, P = 0.8; species, P = 0.44) or aGVHD incidence (P = 0.58). Immune reconstitution of T cell and B cell subsets was similar between groups. Five patients in the no-GD arm had 8 BSI episodes versus 1 episode in the GD arm (P = 0.09). The BSI-causing pathogens were traceable to the gut in 7 of 8 BSI episodes in the no-GD arm, including Staphylococcus species.CONCLUSIONWhile GD did not differentially affect Shannon diversity or clinical outcomes, our findings suggest that GD may protect against gut-derived BSI in HCT patients by decreasing the prevalence or abundance of gut pathogens.TRIAL REGISTRATIONClinicalTrials.gov NCT02641236.FUNDINGNIH, Damon Runyon Cancer Research Foundation, V Foundation, Sloan Foundation, Emerson Collective, and Stanford Maternal & Child Health Research Institute.

Computational Fluid Dynamics Simulations to Predict False Lumen Enlargement After Surgical Repair of Type-A Aortic Dissection.

We aim to use computational fluid dynamics to investigate the hemodynamic conditions that may predispose to false lumen enlargement in this patient population. Nine patients who received surgical repairs of their type-A aortic dissections between 2017-2018 were retrospectively identified. Multiple contrast-enhanced post-operative CT scans were used to construct 3D models of aortic geometries. Computational fluid dynamics simulations of the models were run on a high-performance computing cluster using SimVascular - an open-source simulation package. Physiological pulsatile flow conditions (4.9 L/min) were used at the aortic true lumen inlet, and physiological vascular resistances were applied at the distal vascular ends. Exploratory analyses showed no correlation between rate of false lumen growth and blood pressure, immediate post-op aortic diameter, or the number of fenestrations (p = 0.2). 1-year post-operative CT scans showed a median false lumen growth rate of 4.31 (3.66, 14.67) mm/year Median (Interquartile range) peak systolic, mid-diastolic, and late diastolic velocity magnitudes were 0.90 (1.40); 0.10 (0.16); and 0.06 (0.06) cm/s respectively. Spearman's ranked correlations between fenestration velocity and 1-year false lumen growth rates were found to be statistically significant: Velocity magnitude at peak systolic (p = 0.025; rho = 0.75), mid diastolic (p = 0.025; rho = 0.75) and late diastolic phases of the cardiac cycle (p = 0.006; rho = 0.85). We have shown that false lumen growth is strongly correlated to fenestration flow velocity, which has potential implications for post-operative surveillance and risk stratification.

Use of patient-specific computational models for optimization of aortic insufficiency after implantation of left ventricular assist device.

OBJECTIVE: Aortic incompetence (AI) is observed to be accelerated in the continuous-flow left ventricular assist device (LVAD) population and is related to increased mortality. Using computational fluid dynamics (CFD), we investigated the hemodynamic conditions related to the orientation of the LVAD outflow in these patients. METHOD: We identified 10 patients with new aortic regurgitation, and 20 who did not, after LVAD implantation between 2009 and 2018. Three-dimensional models of patients' aortas were created from their computed tomography scans. The geometry of the LVAD outflow graft in relation to the aorta was quantified using azimuth angles (AA), polar angles (PAs), and distance from aortic root. The models were used to run CFD simulations, which calculated the pressures and wall shear stress (rWSS) exerted on the aortic root. RESULTS: The AA and PA were found to be similar. However, for combinations of high values of AA and low values of PA, there were no patients with AI. The distance from aortic root to the outflow graft was also smaller in patients who developed AI (3.39 ± 0.7 vs 4.07 ± 0.77 cm, P = .04). There was no significant difference in aortic root pressures in the 2 groups. The rWSS was greater in AI patients (4.60 ± 5.70 vs 2.37 ± 1.20 dyne/cm2, P < .001). Qualitatively, we observed a trend of greater perturbations, regions of high rWSS, and flow eddies in the AI group. CONCLUSIONS: Using CFD simulations, we demonstrated that patients who developed de novo AI have greater rWSS at the aortic root, and their outflow grafts were placed closer to the aortic roots than those patients without de novo AI.

"One day I might find myself HIV-positive like her": audience involvement and identification with role models in an entertainment-education radio drama in Botswana.

Entertainment-education programs promote health and development goals throughout the world. This study looks specifically at a radio serial drama designed to provide behavioral role models for HIV prevention and reproductive health in Botswana as part of the behavior-change strategy, Modeling and Reinforcement to Combat HIV/AIDS (MARCH). The purpose of this qualitative study is to elucidate regular listeners' involvement and identification with three different types of fictional characters in the drama. Regular listeners were interviewed using a semi-structured guide; 31 interviews were analyzed to assess respondents' reactions to three female characters. The findings suggest that characters designed to be "negative," "positive," and "transitional" (i.e., moving from negative to positive) role models were generally perceived as such and that the type of behavior modeled influenced whether a character was perceived to be transitional or positive. Audience members discussed the implications of specific behaviors by contrasting the different character types. Although characters modeled behaviors within distinct but interrelated storylines, the respondents spontaneously compared characters' ways of confronting similar dilemmas across storylines, suggesting that listeners perceived the drama as a unified whole rather than as a series of parallel stories. The use of more than one transitional character for each behavioral objective might be beneficial for improving audience identification with agents of behavior change by providing several models to which the audience can relate.