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The Effects of Age, Gender, and Postvoid Residual Volume on Catheterization Rates After Treatment with OnabotulinumtoxinA for Overactive Bladder

BackgroundTransient increases in postvoid residual urine volume (PVR) requiring clean intermittent catheterization (CIC) have occurred with onabotulinumtoxinA treatment for overactive bladder (OAB). ObjectiveTo evaluate onabotulinumtoxinA safety and the effect of age, gender, and maximum PVR (PVRmax) on CIC initiation in adults with OAB and urinary incontinence (UI). Design, setting, and participantsThis was a pooled post hoc analysis of four placebo-controlled, multicenter randomized trials that included adults with idiopathic OAB after first onabotulinumtoxinA treatment (NCT00910845, NCT00910520, NCT01767519, NCT01945489). Patients had at least three urgency UI episodes over 3 d and at least eight micturitions per day, had inadequate management with at least one anticholinergic agent, and were willing to use CIC. Outcome measurements and statistical analysisWe measured the following outcomes: PVRmax within 12 wk after first treatment; CIC incidence; estimated functional capacity; PVR ratio (PVR/estimated functional capacity). Results and limitationsOf 1504 patients, 87.7% were women and 88.8% were White. The mean age was 60.5 yr across 10-yr age groups, baseline PVR was 13.8–35.0 ml, and estimated functional capacity was 293.5–475.7 ml. Mean baseline PVR was 21.3 ml overall versus 34.0 ml in the group that started CIC. The CIC incidence was 6.2% for women (range 1.1–8.4%) and 10.5% for men (range 0–14.6%). Higher CIC rates were observed for PVRmax >350 ml (women 91.9%, men 84.6%) in comparison to PVRmax of 201–350 ml (women 32.5%, men 17.4%) and PVRmax <200 ml (women 1.2%, men 1.6%). Overall, 2/1504 patients (both women) were unable to void spontaneously. The mean PVR ratio was highest at week 2. Some subgroups had small sample sizes. ConclusionsCIC incidence was low overall, was less frequent for women, was rare with PVRmax ≤200 ml, and did not appear to correlate with baseline PVR. Patient summaryAfter onabotulinumtoxinA treatment for OAB, patients sometimes insert a catheter to help in emptying their bladder after urinating. In this study, few patients needed a catheter, especially when less urine volume remained after urination.

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Perinatal Morbidity in Healthy Obese Pregnant Individuals Delivered by Elective Repeat Cesarean at Term.

This study aimed to compare the risks of adverse perinatal outcomes by body mass index (BMI) categories in healthy pregnant individuals delivered by term elective repeat cesarean (ERCD) to describe an optimal timing of delivery in otherwise healthy patients at the highest-risk BMI threshold. A secondary analysis of a prospective cohort of pregnant individuals undergoing ERCD at 19 centers in the Maternal-Fetal Medicine Units Network from 1999 to 2002. Nonanomalous singletons undergoing prelabor ERCD at term were included. The primary outcome was composite neonatal morbidity; secondary outcomes included composite maternal morbidity and individual components of the composites. Patients were stratified by BMI classes and to identify a BMI threshold for which morbidity was the highest. Outcomes were then examined by completed week's gestation, between BMI classes. Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI). A total of 12,755 patients were included in analysis. Patient's with BMI ≥ 40 had the highest rates of newborn sepsis, neonatal intensive care unit admissions, and wound complications. While a weight-related response was observed between BMI class and neonatal composite morbidity (p < 0.001), only those with BMI ≥ 40 had significantly higher odds of composite neonatal morbidity (aOR: 1.4, 95% CI: 1.0-1.8). In analyses of patients with BMI ≥ 40 (n = 1,848), there was no difference in the incidence of composite neonatal or maternal morbidity across weeks' gestation at delivery; however, as gestational age approached 39 to 40 weeks, rates of adverse neonatal outcomes decreased, only to increase again at 41 weeks' gestation. Of note, the odds of the primary neonatal composite were the highest at 38 weeks compared with 39 weeks (aOR: 1.5, 95% CI: 1.1-2.0). Neonatal morbidity is significantly higher in pregnant individuals with BMI ≥40 delivering by ERCD. Despite this increased perinatal morbidity, delivery prior to 39 and after 41 weeks in these patients is associated with increased neonatal risks. · Obese patients without additional comorbidities have higher rates of neonatal morbidity.. · Patients with BMI ≥ 40 carry the highest odds of poor perinatal outcomes.. · Earlier timing of delivery does not appear to reduce this risk..

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Efficacy of extracorporeal shock wave lithotripsy for post-transplant kidney stones. Hope or Disappointment?

Nephrolithiasis in a transplanted kidney is an important medical and social problem. The presence of renal calculi may not manifest clinically for a long time due to the peculiarities of the surgical intervention during organ transplantation. Development of chronic urinary tract infection and deterioration of the functional ability of the renal transplant in the presence of kidney stones can lead to graft death, which is an immediate threat to the patient’s life. Existing Russian guidelines on the treatment of urolithiasis currently lack a clear strategy for the management of kidney transplant recipients.Objective: to systematize literature data on analysis of the outcomes of extracorporeal shock wave lithotripsy (ESWL) and other methods in patients with post-transplant kidney stones.Results. Thirty-five publications on the research topic were selected. We summarized the information on various therapy options for patients with stones in transplanted kidney: endourological approach, ESWL, percutaneous nephrolithotripsy (PCNL), open surgical treatment (nephrostomy, pyelolithotomy). A modern foreign algorithm for the management of patients with post-transplant kidney stones depending on the severity of obstruction with sepsis and the size of the renal calculi is presented.Conclusion. 1. The presence of stones in a kidney graft is a clinical situation that requires surgical treatment. 2. In clinical practice, different methods of treatment can be used, such as open intervention, ESWL, PCNL, retrograde transurethral manipulations. 3. In most cases, patient management tactics depend on the clinical picture (presence/absence of obstruction) and the size of the calculi. 4. The use of ESWL, as the most frequently used method, testifies to its efficiency and low-traumatic effect.

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PSMC3 proteasome subunit variants are associated with neurodevelopmental delay and type I interferon production.

A critical step in preserving protein homeostasis is the recognition, binding, unfolding, and translocation of protein substrates by six AAA-ATPase proteasome subunits (ATPase-associated with various cellular activities) termed PSMC1-6, which are required for degradation of proteins by 26S proteasomes. Here, we identified 15 de novo missense variants in the PSMC3 gene encoding the AAA-ATPase proteasome subunit PSMC3/Rpt5 in 23 unrelated heterozygous patients with an autosomal dominant form of neurodevelopmental delay and intellectual disability. Expression of PSMC3 variants in mouse neuronal cultures led to altered dendrite development, and deletion of the PSMC3 fly ortholog Rpt5 impaired reversal learning capabilities in fruit flies. Structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune programs. The proteostatic perturbations in T cells from patients with PSMC3 variants correlated with a dysregulation in type I interferon (IFN) signaling in these T cells, which could be blocked by inhibition of the intracellular stress sensor protein kinase R (PKR). These results suggest that proteotoxic stress activated PKR in patient-derived T cells, resulting in a type I IFN response. The potential relationship among proteosome dysfunction, type I IFN production, and neurodevelopment suggests new directions in our understanding of pathogenesis in some neurodevelopmental disorders.

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