Review of Advances in Uroprotective Agents for Cyclophosphamide- and Ifosfamide-induced Hemorrhagic Cystitis

© 2016 Elsevier Inc. Cyclophosphamide and ifosfamide are widely used drugs for malignancies and rheumatologic conditions. One of the most significant adverse reactions to these drugs is hemorrhagic cystitis. Mesna is the most widely used uroprotective agent that acts to neutralize the caustic metabolite, acrolein, responsible for induction of hemorrhagic cystitis. However, mesna is not a perfect alternative, and studies since its discovery have investigated the use of alternative drugs and adjuncts to increase mesna\u27s efficacy. This review details some of the recent work into novel uroprotective agents for drug-induced hemorrhagic cystitis

Review of Advances in Uroprotective Agents for Cyclophosphamide and Ifosfamide-Induced Hemorrhagic Cystitis.

© 2016 Elsevier Inc. Cyclophosphamide and ifosfamide are widely used drugs for malignancies and rheumatologic conditions. One of the most significant adverse reactions to these drugs is hemorrhagic cystitis. Mesna is the most widely used uroprotective agent that acts to neutralize the caustic metabolite, acrolein, responsible for induction of hemorrhagic cystitis. However, mesna is not a perfect alternative, and studies since its discovery have investigated the use of alternative drugs and adjuncts to increase mesna\u27s efficacy. This review details some of the recent work into novel uroprotective agents for drug-induced hemorrhagic cystitis

The authors reply: Safety and feasibility of platelet rich fibrin matrix injections for treatment of common urologic conditions

Purpose: Autologous platelet rich plasma (PRP) is used increasingly in a variety of settings. PRP injections have been used for decades to improve angiogenesis and wound healing. They have also been offered commercially in urology with little to no data on safety or efficacy. PRP could theoretically improve multiple urologic conditions, such as erectile dysfunction (ED), Peyronie's disease (PD), and stress urinary incontinence (SUI). A concern with PRP, however, is early washout, a situation potentially avoided by conversion to platelet rich fibrin matrix (PRFM). Before clinical trials can be performed, safety analysis is desirable. We reviewed an initial series of patients receiving PRFM for urologic pathology to assess safety and feasibility. Materials and Methods: Data were reviewed for patients treated with PRFM at our center from November 2012 to July 2017. Patients were observed immediately post-injection and at follow-up for complications and tolerability. Where applicable, International Index of Erectile Function (IIEF-5) scores were reviewed before and after injections for ED and/or PD. Pad use data was collected pre/post injection for SUI. Results: Seventeen patients were identified, with a mean receipt of 2.1 injections per patient. Post-procedural minor adverse events were seen in 3 men, consisting of mild pain at injection site and mild penile bruising. No patients experienced complications at follow-up. No decline was observed in men completing pre/post IIEF-5 evaluations. Conclusions: PRFM appears to be a safe and feasible treatment modality in patients with urologic disease. Further placebo-controlled trials are warranted

A Heterotopic Xenograft Model of Human Airways for Investigating Fibrosis in Asthma.

Limited in vivo models exist to investigate the lung airway epithelial role in repair, regeneration, and pathology of chronic lung diseases. Herein, we introduce a novel animal model in asthma—a xenograft system integrating a differentiating human asthmatic airway epithelium with an actively remodeling rodent mesenchyme in an immunocompromised murine host. Human asthmatic and nonasthmatic airway epithelial cells were seeded into decellularized rat tracheas. Tracheas were ligated to a sterile cassette and implanted subcutaneously in the flanks of nude mice. Grafts were harvested at 2, 4, or 6 weeks for tissue histology, fibrillar collagen, and transforming growth factor-β activation analysis. We compared immunostaining in these xenografts to human lungs. Grafted epithelial cells generated a differentiated epithelium containing basal, ciliated, and mucus-expressing cells. By 4 weeks postengraftment, asthmatic epithelia showed decreased numbers of ciliated cells and decreased E-cadherin expression compared with nonasthmatic grafts, similar to human lungs. Grafts seeded with asthmatic epithelial cells had three times more fibrillar collagen and induction of transforming growth factor-β isoforms at 6 weeks postengraftment compared with nonasthmatic grafts. Asthmatic epithelium alone is sufficient to drive aberrant mesenchymal remodeling with fibrillar collagen deposition in asthmatic xenografts. Moreover, this xenograft system represents an advance over current asthma models in that it permits direct assessment of the epithelial–mesenchymal trophic unit

Sex differences in the association between neck circumference and asthma.

INTRODUCTION: The association between obesity and asthma control/quality of life commonly relies on body mass index (BMI) as the anthropomorphic measure. Due to limitations of BMI and the existence of alternative measures, such as neck circumference (NC), we examined the association between NC and asthma control/quality of life, with particular attention to male–female differences MATERIALS AND METHODS: The AsthMaP-2 Project is an observational study of youth with physician–diagnosed asthma. NC was stratified according to age- and sex-specific cutoffs and associated with asthma control (via Asthma Control Test [ACT]) and quality of life (via Integrated Therapeutics Group [ITG]—Asthma Short Form) RESULTS: The mean±SD age was 11.9±3.6 years, and 53% were male (N=116). The mean BMI percentile was at the 71±28 percentile. Thirty-one participants (27%) met criteria for high NC. Males with high NC had significantly worse asthma control (P =0.02) and lower quality of life than those with low NC. No similar association was found for females and the proportion of variability in ACTand ITG was best explained by BMI percentile. Conversely, for males, the proportion of variability in these scores explained by NC was larger than BMI percentile alone (Cohen’s f(2) =0.04–0.09, a small to medium effect size) DISCUSSION: Among male youth with asthma, combined use of NC and BMI percentile explained asthma control and quality of life better than BMI alone. Future studies of asthma should include measurement of NC and other anthropogenic measures of regional adiposity to clarify sex differences in asthma