Imaging characteristics predicting elevated detrusor pressures in patients with spina bifida.

PURPOSE: Patients with spina bifida require urologic follow up with assessments of bladder and renal function. The ideal screening protocol for bladder compliance remains controversial. This study assessed associations between bladder end filling pressure (EFP) and detrusor leak point pressure (DLPP) on urodynamic studies (UDS) and findings from renal bladder ultrasounds (RBUS) and voiding cystourethrograms (VCUG). METHODS: Pediatric spina bifida patients who underwent RBUS and/or VCUG within six months of UDS at a single institution from 2015 to 2021 were retrospectively reviewed. Demographics, VCUG and RBUS results, and UDS EFP and DLPP were recorded. Multiple linear regression analyses and Pearson chi-square tests were conducted to correlate RBUS and VCUG findings with DLPP/EFP. RESULTS: 129 patients were included. In adjusted analyses, moderate to severe hydronephrosis on RBUS was significantly associated with elevations in mean DLPP/EFP (p = 0.006). Patients with round bladders had significantly lower mean DLPP/EFP than patients with elongated or conical bladders (p < 0.0001). The presence of trabeculations was associated with increased mean DLPP/EFP (p < 0.0001) and increases in severity of trabeculations were associated with higher DLPP/EFP (p < 0.0001). The presence of vesicoureteral reflux (VUR) on VCUG was not associated with significant differences in mean DLPP/EFP (p = 0.20). CONCLUSIONS: Abnormal bladder shape and trabeculations on VCUGs in spina bifida patients had significant associations with increased mean bladder pressures on UDS. Assessment of bladder shape and contour by VCUG may be a valuable screening tool in conjunction with routine RBUS in determining the need for further assessment of bladder pressures in patients with spina bifida.

Nephrolithiasis management and outcomes in pediatric patients with limited mobility.

INTRODUCTION AND OBJECTIVES: Pediatric patients with limited lower extremity mobility may be at increased risk of developing nephrolithiasis due to bone mineral metabolic derangements. This study sought to assess whether nephrolithiasis management and related outcomes differ between ambulatory versus non-ambulatory pediatric patients. METHODS: This was a retrospective review of ambulatory and non-ambulatory pediatric patients with nephrolithiasis from 2010 to 2021 from a single tertiary care center. Demographics, surgical history, stone compositions, and 24-h urine data were reviewed. Adjusted logistic and linear regression models were utilized to assess whether mobility status was associated with nephrolithiasis-related management and outcomes, including: age at first stone; requiring surgical intervention for stones; number of surgeries; stone compositions; urine culture results; and completion of 24-h urine studies. RESULTS: Among 339 pediatric patients with nephrolithiasis, 67 (19.8%) were non-ambulatory. In adjusted analyses, non-ambulatory patients had 3.24 times greater odds of requiring surgical intervention for stones (95% CI: 1.93-6.84; p < 0.0001); among those who required surgery, non-ambulatory patients required an average of 0.82 more surgical interventions (95% CI: 0.35-1.30; p = 0.0008) than ambulatory patients. Additionally, non-ambulatory patients had 5.28 times greater odds of having a positive urine culture at the time of surgery (95% CI: 2.35-14.08; p = 0.0001) and were significantly less likely to undergo 24-h urine studies (OR: 0.35; 95% CI: 0.15-0.83; p = 0.02). Stone composition significantly varied by mobility status, with non-ambulatory patients being significantly more likely to form calcium apatite (OR: 5.1; 95% CI: 2.18-11.93; p = 0.0002) or struvite (OR 3.72; 95% CI: 1.18-11.74; p = 0.03) stones, and significantly less likely to form calcium oxalate stones (OR: 0.19; 95 CI: 0.08-0.47; p = 0.0003). Among all patients, age at first stone occurred at a median age of 13.4 years (IQR: 8.2-16.4) and did not significantly differ by mobility status (p = 0.92). CONCLUSIONS: Patients with limited mobility required surgery for nephrolithiasis at significantly higher rates and had different stone compositions than ambulatory patients. Obtaining a 24-h urine study in patients with comorbidities affecting ambulation was uncommon, compared to ambulatory patients. Similarly to ambulatory patients, pediatric patients with limited mobility who develop nephrolithiasis tend to first present with stones in early adolescence.

Three cases utilizing the Hidden Incision Endoscopic Surgery approach to port placement during penile inversion vaginoplasty utilizing a peritoneal flap.

INTRODUCTION: Younger transgender patients undergoing penile inversion vaginoplasty (PIV) after pubertal suppression often require modified techniques to augment neovaginal tissue. Peritoneal flap vaginoplasty (PFV) is a well-established technique for improving neovaginal depth. Utilizing a Hidden Incision Endoscopic Surgery (HIdES) approach to port placement improves cosmetic outcomes of this identity-affirming procedure. OBJECTIVE: This video shows the efficacy of the HIdES port placement configuration on the daVinci robot for peritoneal flap creation and closure during PIV using the modified laparoscopic Davydov procedure. MATERIALS AND METHODS: Three young adult transgender females who had not undergone laser hair removal/epilation underwent PIV with robotic PFV utilizing HIdES port placement. The anterior superior iliac spine (ASIS) was demarcated bilaterally, and ports were placed at or below these lines. Two surgical teams, external genitoplasty and internal peritoneal flap closure via daVinci Xi robot, worked simultaneously. RESULTS: All patients underwent successful robotic assisted PIV with HIdES port placement. All patients had similar postoperative courses of return of bowel function with flatus on postoperative day (POD) 2, vaginal dressing, urethral catheter removal, and initiation of vaginal dilation on POD 5-6, and hospital discharge between POD 5-8. CONCLUSION: We present our initial experience with robotic/laparoscopic PFV using a hidden incision approach. This technique allows for excellent neovaginal depth with improved abdominal wound aesthetics.

Physical Function in Kidney Transplantation: Current Knowledge and Future Directions.

PURPOSE OF REVIEW: Low physical function (PF) is common among individuals with end-stage kidney disease. In this review, we explore data on the impacts of PF on access to kidney transplantation (KT) and KT outcomes. We also discuss the latest interventions to improve PF in pre- and post-KT settings. RECENT FINDINGS: Many US KT programs measure PF or related constructs when assessing KT candidacy. Although carefully selected KT candidates with low PF can benefit from KT with respect to survival and quality of life, low PF decreases the likelihood of being listed for KT and increases the risk of adverse post-KT outcomes. Recent trials suggest that exercise is a promising strategy to improve PF among KT candidates and recipients. SUMMARY: PF is a potentially modifiable risk factor for adverse pre- and post-KT outcomes. Research is needed to determine the ideal PF metric for use in KT evaluations and interventions to improve PF.

Association Between Weight Loss Before Deceased Donor Kidney Transplantation and Posttransplantation Outcomes.

RATIONALE & OBJECTIVE: There is debate on whether weight loss, a hallmark of frailty, signals higher risk for adverse outcomes among recipients of deceased donor kidney transplantation (DDKT). STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Using national Organ Procurement and Transplantation Network data, we included all DDKT recipients in the United States between December 4, 2004, and December 3, 2014, who were adults (aged ≥ 18 years) when listed for DDKT. EXPOSURES: Relative pre-DDKT weight change as a continuous predictor and categorized as <5% weight change from listing to DDKT, ≥5% to <10% weight loss, ≥10% weight loss, ≥5% to <10% weight gain, and ≥10% weight gain. OUTCOMES: We examined 3 post-DDKT outcomes: (1) transplant hospitalization length of stay (LOS) in days, (2) all-cause graft failure, and (3) mortality. ANALYTIC APPROACH: Unadjusted fractional polynomial methods, multivariable log-gamma models, and multivariable Cox proportional hazards models. RESULTS: Among 94,465 recipients of DDKT, median pre-DDKT weight change was 0 (interquartile range, -3.5 to +3.9) kg. There were nonlinear unadjusted associations between relative pre-DDKT weight loss and longer transplant hospitalization LOS, higher all-cause graft loss, and higher mortality. Compared with recipients with <5% pre-DDKT weight change (n = 49,366; 52%), recipients who lost ≥10% of their listing weight (n = 10,614; 11%) had 0.66 (95% CI, 0.23-1.09) days longer average transplant hospitalization LOS (P = 0.003), 1.11-fold higher graft loss (adjusted HR [aHR], 1.11; 95% CI, 1.06-1.17; P < 0.001), and 1.18-fold higher mortality (aHR, 1.18; 95% CI, 1.11-1.25; P < 0.001) independent of recipient, donor, and transplant factors. Pre-DDKT dialysis exposure, listing body mass index category, and waiting time modified the association of pre-DDKT weight change with hospital LOS (interaction P < 0.10), but not with all-cause graft loss and mortality. LIMITATIONS: Unmeasured confounders and inability to identify volitional weight change. Also, the higher significance level set to increase the power of detecting interactions with the fixed sample size may have resulted in increased risk for type 1 error. CONCLUSIONS: DDKT recipients with ≥10% pre-DDKT weight loss are at increased risk for adverse outcomes and may benefit from augmented support post-DDKT.

Metal Binding Properties of the N-Terminus of the Functional Amyloid Orb2.

The cytoplasmic polyadenylation element binding protein (CPEB) homologue Orb2 is a functional amyloid that plays a key regulatory role for long-term memory in Drosophila. Orb2 has a glutamine, histidine-rich (Q/H-rich) domain that resembles the Q/H-rich, metal binding domain of the Hpn-like protein (Hpnl) found in Helicobacter pylori. In the present study, we used chromatography and isothermal titration calorimetry (ITC) to show that the Q/H-rich domain of Orb2 binds Ni2+ and other transition metals ions with µM affinity. Using site directed mutagenesis, we show that several histidine residues are important for binding. In particular, the H61Y mutation, which was previously shown to affect the aggregation of Orb2 in cell culture, completely inhibited metal binding of Orb2. Finally, we used thioflavin T fluorescence and electron microscopy images to show that Ni2+ binding induces the aggregating of Orb2 into structures that are distinct from the amyloid fibrils formed in the absence of Ni2+. These data suggest that transition metal binding might be important for the function of Orb2 and potentially long-term memory in Drosophila.

The Functional Amyloid Orb2A Binds to Lipid Membranes.

Lipid membranes interact with and influence the aggregation of many amyloid-forming proteins. Orb2 is a cytoplasmic polyadenylation element-binding protein homolog in Drosophila melanogaster that forms functional amyloids necessary for long-term memory. One isoform, Orb2A, has a unique N-terminus that has been shown to be important for the formation of amyloid-like aggregates and long-term memory in vivo. Orb2A is also found enriched in the synaptic membrane fraction. Our sequence and hydropathy analysis suggests that it can form an amphipathic helix, which is ideal for lipid membrane interaction. We used circular dichroism and site-directed spin labeling coupled with electron paramagnetic resonance to test the first 88 amino acids of Orb2A for lipid interaction. We show that Orb2A1-88 interacts with anionic lipid membranes using an amphipathic helix at its unique N-terminus. This interaction depends on the charge of the lipid membrane and the degree of membrane curvature. We used transmission electron microscopy and electron paramagnetic resonance to show that the presence of anionic small unilamellar vesicles inhibits amyloid fibril formation by Orb2A. This inhibition by anionic membranes could be a potential mechanism regulating Orb2A amyloid formation in vivo.

Identification and Structural Characterization of the N-terminal Amyloid Core of Orb2 isoform A.

Orb2 is a functional amyloid that plays a key role in Drosophila long-term memory formation. Orb2 has two isoforms that differ in their N-termini. The N-terminus of the A isoform (Orb2A) that precedes its Q-rich prion-like domain has been shown to be important for Orb2 aggregation and long-term memory. However, besides the fact that it forms fibrillar aggregates, structural information of Orb2 is largely absent. To understand the importance of the N-terminus of Orb2A and its relation to the fibril core, we recorded solid-state NMR and EPR data on fibrils formed by the first 88 residues of Orb2A (Orb2A88). These data show that the N-terminus of Orb2A not only promotes the formation of fibrils, but also forms the fibril core of Orb2A88. This fibril core has an in-register parallel ß-sheet structure and does not include the Q-rich, prion-like domain of Orb2. The Q-rich domain is part of the unstructured region, which becomes increasingly dynamic towards the C-terminus.