Inhibition of hypoxia-inducible factor-prolyl hydroxylation protects from cyclophosphamide-induced bladder injury and urinary dysfunction.

Disruption of the blood-urine barrier can result in acute or chronic inflammatory bladder injury. Activation of the oxygen-regulated hypoxia-inducible factor (HIF) pathway has been shown to protect mucosal membranes by increasing the expression of cytoprotective genes and by suppressing inflammation. The activity of HIF is controlled by prolyl hydroxylase domain (PHD) dioxygenases, which have been exploited as therapeutic targets for the treatment of anemia of chronic kidney disease. Here, we established a mouse model of acute cyclophosphamide (CYP)-induced blood-urine barrier disruption associated with inflammation and severe urinary dysfunction to investigate the HIF-PHD axis in inflammatory bladder injury. We found that systemic administration of dimethyloxalylglycine or molidustat, two small-molecule inhibitors of HIF-prolyl hydroxylases, profoundly mitigated CYP-induced bladder injury and inflammation as assessed by morphological analysis of transmural edema and urothelial integrity and by measuring tissue cytokine expression. Void spot analysis to examine bladder function quantitatively demonstrated that HIF-prolyl hydroxylase inhibitor administration normalized micturition patterns and protected against CYP-induced alteration of urinary frequency and micturition patterns. Our study highlights the therapeutic potential of HIF-activating small-molecule compounds for the prevention or therapy of bladder injury and urinary dysfunction due to blood-urine barrier disruption.NEW & NOTEWORTHY Disruption of the blood-urine barrier can result in acute or chronic inflammatory bladder injury. Here, we demonstrate that pharmacological inhibition of hypoxia-inducible factor (HIF)-prolyl hydroxylation prevented bladder injury and protected from urinary dysfunction in a mouse model of cyclophosphamide-induced disruption of the blood-urine barrier. Our study highlights a potential role for HIF-activating small-molecule compounds in the prevention or therapy of bladder injury and urinary dysfunction and provides a rationale for future clinical studies.

A qualitative interview study on successful pregnancies in women with spina bifida.

BACKGROUND: Improvements in antenatal medicine and surgical management for conditions associated with spina bifida such as hydrocephalus have extended the lifespan for individuals with spina bifida (SB) into adulthood. Decisions and education regarding reproductive care and pregnancies for patients with spina bifida are increasingly important. Pregnancy in these patients can be particularly challenging due to physical limitations, previous abdominal surgery for urinary or bowel management and presence of a ventriculoperitoneal shunt. To date, little research has examined the unique challenges that women with spina bifida face during pregnancy. OBJECTIVE: The purpose of this descriptive study is to characterize the successful pregnancy histories of SB women and describe how pregnancy affected their mobility as well as bladder and bowel management. STUDY DESIGN: We conducted semi-structured interviews with women followed in our adult multidisciplinary SB clinic who previously had successful pregnancies. Questions regarding perinatal issues, obstetrical complications, urinary tract infections (UTI) and neurological changes were asked. Baseline mobility, bladder and bowel management were compared with changes during and after pregnancy. RESULTS: 121 women of childbearing age were followed per year by our adult multidisciplinary spina bifida clinic between 2009 and 2016. We identified 6 women who successfully carried 8 pregnancies to term. There were no miscarriages. Four women had ventriculoperitoneal (VP) shunts. No children were born with neural tube defects. Mean age at first pregnancy was 23.5 years. Average gestational age at delivery was 37 weeks. 50% of the women had a spontaneous vaginal delivery. Five of six women intended to get pregnant; only one patient consumed folic acid regularly prior to pregnancy. Two of six women had bladder augmentation surgery, one of whom had urologic changes during pregnancy that persisted after childbirth. The other patient had a concomitant bladder neck sling procedure and did not have urologic issues during pregnancy. 50% of the patients experienced bladder-bowel dysfunction during their pregnancy. While 67% patients had full baseline ambulatory function, 4 patients had decreased mobility and required additional assistance during pregnancy. All returned to their baseline functionality afterwards. CONCLUSION: Six of our patients had eight successful pregnancies, with no children born with neural tube defects. New changes to mobility, bladder and bowel management were experienced by over half of the women during their pregnancies. Future studies should focus on the role of multidisciplinary teams in reproductive health education and perinatal management of changes to activities of daily living during pregnancy in this population.

A Rare, Unusual Presentation of Newberyite Urolithiasis in Adolescent Female -A Case Report and Review of Literature.

We report a rare case of newberyite (magnesium monohydrate phosphate trihydrate) urolithiasis in a young female with a past medical history significant for longstanding autoimmune hepatitis. She presented to the emergency department with newly diagnosed nephrolithiasis. Over the next 2 years, she had recurrent renal calculi and 3 urologic procedures. Notably, she did not have any history of urinary tract infections or genitourinary abnormalities. Her last stone analysis revealed the unusual combination of newberyite and ammonium acid urate. The pathophysiology of ammonium acid urate and newberyite stone formation as well as risk factors of development are discussed in this report.

Let's Talk About Sex: Special Considerations in Reproductive Care and Sexual Education in Young Women With Spina Bifida.

Medical advances in the last several decades have allowed an increasing number of children with spina bifida to reach adolescence and adulthood. As they reach puberty, girls with spina bifida face unique social and health challenges to their sexuality, such as orthopedic restrictions, continence, and pelvic floor disorders. Recent research efforts have focused on better understanding female sexual desires, dysfunctions, and activity and the role of the physician in educating this vulnerable population. This article aims to summarize current literature on sexual function, knowledge gaps, and the importance of tailored sexual education from providers in women with spina bifida.

Data highlighting phenotypic diversity of urine-associated Escherichia coli isolates.

This article provides a reusable dataset describing detailed phenotypic and associated clinical parameters in n=303 clinical isolates of urinary Escherichia coli collected at Vanderbilt University Medical Center. De-identified clinical data collected with each isolate are detailed here and correlated to biofilm abundance and metabolomics data. Biofilm-abundance data were collected for each isolate under different in vitro conditions along with datasets quantifying biofilm abundance of each isolate under different conditions. Metabolomics data were collected from a subset of bacterial strains isolated from uncomplicated cases of cystitis or cases with no apparent symptoms accompanying colonization. For more insight, please see "Defining a Molecular Signature for Uropathogenic versus Urocolonizing Escherichia coli: The Status of the Field and New Clinical Opportunities" [1].

Novel Multi-Modal Analgesia Protocol Significantly Decreases Opioid Requirements in Inflatable Penile Prosthesis Patients.

BACKGROUND: Inflatable penile prosthesis (IPP) surgery is associated with significant perioperative pain that may reduce patient satisfaction. Though various pain management strategies have been proposed, most implanters manage postoperative patients with only prescription opioids. No protocol to date has been implemented and reported for pain management in IPP patients throughout the entire recovery process following surgery. AIM: Develop a multimodal analgesic (MMA) regimen consisting of perioperative administration of acetaminophen, meloxicam, and gabapentin with intraoperative local anesthetic injections, and compare post-operative pain control to a matched cohort of patients managed with an opioid-based (OB) regimen. METHODS: We retrospectively analyzed our prospectively maintained IPP database from November 2015-January 2018. The MMA protocol was instituted for all patients beginning June 2017, and these patients were matched in a 1:2 ratio to a cohort of eligible IPP patients managed through an OB protocol. Only patients receiving a 3-piece IPP were included; those with a history of narcotic dependence, neuropathy, or chronic non-steroidal anti-inflammatory drug use were excluded. Postoperative pain scores (visual analog scale) and opioid usage (total morphine equivalents [TME] in milligrams) were compared temporally in the post-anesthesia care unit, postoperative day (POD) 0, POD 1, and following discharge. OUTCOMES: The primary outcomes of the study are postoperative pain scores and narcotic usage. RESULTS: 57 patients were eligible for analysis: 19 (33%) and 38 (66%) in the MMA and OB groups, respectively. Groups were similar in demographics. MMA patients had significantly lower visual analog scale scores in post-anesthesia care unit, POD 0, or POD 1 (mean 0.84 vs 2.97, P = .01; 2.62 vs 4.73, P = .003; and 2.26 vs 4.0, P = .01, respectively) and used fewer narcotics on POD 0 (mean 4.08 vs 13.8 mg TME, P < .001) and POD 1 (mean 5.05 vs 25.1 mg TME, P < .001). MMA patients were discharged home with fewer narcotics (mean 12.7 vs 51.3 tabs, P < .001), and despite this, the MMA group needed less narcotic medication refills (11% vs 49%, P = .007). Neither group experienced a medication-related postoperative adverse event. CLINICAL IMPLICATIONS: Multimodal pain management allows for effective pain control with minimal side effects, enhancing recovery. STRENGTHS & LIMITATIONS: This is the first report to assess use of a multi-modal pain regimen on IPP recipients with demonstration of tangible benefit throughout the recovery process. Limitations include a single-surgeon and retrospective study design. CONCLUSION: In our rigorous assessment of IPP patients, implementation of a novel MMA protocol achieved equivalent and effective pain control, while resulting in substantially fewer narcotics throughout the entire post-operative period following IPP implantation. Tong CMC, Lucas J, Shah A, et al. Novel Multi-Modal Analgesia Protocol Significantly Decreases Opioid Requirements in Inflatable Penile Prosthesis Patients. J Sex Med 2018;15:1187-1194.