Double haploidentical hematopoietic stem cell transplantation results in successful engraftment of bone marrow from both donors without graft-versus-host or graft-versus-graft effects.

We established double-haploidentical (DH) hematopoietic stem cell transplantation (HSCT) murine models to explore competitive engraftment, graft-versus-graft effect and graft-versus-host disease (GVHD). T cell-depleted (TCD) bone marrow (BM) cells from B6SJF1 (donor 1 [D1]) and B6D2F1 (donor 2 [D2]) mice achieved >90% donor engraftment when transplanted into B6CBAF1 mice. B6CBAF1 recipients survived without evidence of GVHD when undergoing HSCT with TCD-BM from 2 haploidentical donors, D1 and D2. DH-HSCT recipients had significantly higher leukocyte and neutrophil counts than single-haploidentical HSCT recipients from either D1 or D2. DH recipients consistently showed successful mixed chimerism in both BM and spleen. Two other DH-HSCT models, B6D2F1 + C3D2F1→B6C3F1 and B6CBAF1 + B6SJLF1→B6D2F1, showed similar engraftment patterns. Low-dose T cell infusion from both D1 and D2 increased the degree of early engraftment of the respective donors in BM and spleen; however, this early engraftment pattern did not determine long-term engraftment dominance. In the long term, minimally engrafted D1 BM recovered and comprised >50% of all donor- derived B, T, and natural killer cells. We conclude that early BM engraftment is determined by donor T cell immunodominance, but long-term engraftment is related to the engraftment potential of stem cells after DH-HSCT.

A Rationale to Use Bladder Boari Flap Reconstruction for Late Kidney Transplant Ureteral Strictures.

OBJECTIVE: To evaluate the efficacy of Boari flap reconstruction (BFR) in the management of late-onset transplant ureteral strictures (TUS). METHODS: Between March 2007 and March 2014, there were 730 patients who underwent kidney transplant (KTx) at our institution. We identified 16 patients with TUS, occurring more than 60 days after KTx. Baseline clinical and posttransplant characteristics were reviewed and stratified upon treatment modality. Outcomes for each treatment modality were determined. RESULTS: Median time from transplant to the treatment of TUS was 703 days (range, 65-2617 days). BFR was the most common treatment modality and was used in 87.5% of patients (n = 14/16). This procedure was performed as both a primary treatment and as a salvage procedure in recurrent TUS refractory to balloon dilation and neoureterocystotomy. Incidence of BFR failure was 6.3% (n = 1/14). BFR as a primary treatment was more successful compared to other methods (P < .01). CONCLUSION: Late TUS after KTx is a difficult complication to treat. Our study suggests that BFR can provide a higher success rate of primary treatment compared to other common treatment options. BFR can be used as a primary treatment of TUS or as a salvage procedure with similar success. Additional follow-up is necessary to evaluate the long-term efficacy of BFR for the treatment of late-onset TUS.

Pioglitazone Enhances Survival and Regeneration of Pelvic Ganglion Neurons After Cavernosal Nerve Injury.

OBJECTIVE: To investigate the effects of pioglitazone on pelvic ganglion neurons in a rat model of bilateral cavernosal nerve crush injury (BCNI), thereby elucidating the actions of pioglitazone in preventing post-prostatectomy neurogenic erectile dysfunction. METHODS: Sprague-Dawley rats aged 12 weeks were divided into four groups: (a) sham procedure, (b) BCNI, (c) BCNI + postsurgical pioglitazone, and (d) BCNI + pre and postsurgical pioglitazone (preventive therapy). Preoperative injection of Fluoro-Gold (FG) fluorescent tracer into the cavernosal tissue was performed for retrograde labeling of pelvic ganglion cells. Pelvic ganglia were resected at 2 weeks in all rats and processed for real-time polymerase chain reaction, immunohistochemistry, and Western blot to examine the expression of FG, neuronal nitric oxide synthase, ß-III tubulin, neurturin, and glial cell line-derived neurotrophic factor family receptor alpha-2 (GFRα2). RESULTS: Animals treated with pre- and postsurgical pioglitazone demonstrated increased staining for FG similar to sham levels. Gene expression of neuronal nitric oxide synthase, neurturin, GFRα2, and ß-III tubulin was also upregulated in the group receiving preventive therapy. CONCLUSION: Pioglitazone provides a protective effect on pelvic ganglion neurons after BCNI.

Avanafil for erectile dysfunction in elderly and younger adults: differential pharmacology and clinical utility.

The treatment modalities of erectile dysfunction range from oral pharmacotherapy to intracavernosal injections, intraurethral pellets, vacuum erectile devices, and the surgical option of penile prosthesis insertion. Oral phosphodiesterase 5 inhibitors still remain the preferred treatment for patients since they are the least invasive, not to mention that they can be prescribed by non-urologists. Due to these factors, there has been development of newer drugs with fewer side effects. This is a review of the second generation phosphodiesterase 5 inhibitor, avanafil, looking into its pharmacology as well as its clinical utility. Avanafil's faster onset and shorter duration of action has made it preferred as compared to other PDE5 inhibitors for patients with multiple comorbidities.