Prone vs supine percutaneous nephrolithotomy: does position affect renal pelvic pressures?

The purpose of this study was to measure and compare renal pelvic pressure (RPP) between prone and supine percutaneous nephrolithotomy (PCNL) in a benchtop model. Six identical silicone kidney models were placed into anatomically correct prone or supine torsos constructed from patient CT scans in the corresponding positions. A 30-Fr renal access sheath was placed in either the upper, middle, or lower pole calyx for both prone and supine positions. Two 9-mm BegoStones were placed in the respective calyx and RPPs were measured at baseline, irrigating with a rigid nephroscope, and irrigating with a flexible nephroscope. Five trials were conducted for each access in both prone and supine positions. The average baseline RPP in the prone position was significantly higher than the supine position (9.1 vs 2.7 mmHg; p < 0.001). Similarly, the average RPP in prone was significantly higher than supine when using both the rigid and flexible nephroscopes. When comparing RPPs for upper, middle, and lower pole access sites, there was no significant difference in pressures in either prone or supine positions (p > 0.05 for all). Overall, when combining all pressures at baseline and with irrigation, with all access sites and types of scopes, the mean RPP was significantly higher in the prone position compared to the supine position (14.0 vs 3.2 mmHg; p < 0.001). RPPs were significantly higher in the prone position compared to the supine position in all conditions tested. These differences in RPPs between prone and supine PCNL could in part explain the different clinical outcomes, including postoperative fever and stone-free rates.

Which Laser System Is Optimal for Cystolithotripsy of Large Bladder Calculi?

Introduction and Objective: A variety of laser sources are available to treat bladder stones. The aim of this study was to compare time and cost efficiency of the thulium fiber laser (TFL) to four holmium lasers (HLs) with different powers or technologies, including MOSES™ during simulated cystolithotripsy. Materials and Methods: In a benchtop simulation of laser cystolithotripsy, 25 identical 4-cm BegoStones (calcium oxalate monohydrate consistency) were placed on a grid within a 3D-printed bladder model. Lasers were operated at maximal energy, using a 550 µm fiber. Lasers compared were as follows: 60 W TFL, 120 W HL with MOSES, and conventional 120, 100, and 30 W HLs. Five trials were performed for each laser with endpoints of laser time, total time, number of fiber strippings, and total energy. Cost-effectiveness was modeled using laser purchase price, fiber, and operating room (OR) time cost. ANOVA with Tukey's B post hoc was performed to compare outcomes. Spearman's test was used to assess correlation between laser power and procedure time. Results: The laser and total operating times were significantly different between the five systems (p < 0.001). The 120 W HL with MOSES was the fastest with 60.9 minutes of laser and 68.3 minutes of procedure times, while the 30 W HL was the slowest with 281.2 minutes of laser and 297.5 minutes of procedure times. The 60 W TFL was faster than the 30 W HL, but slower than the higher power HLs. Higher laser power was associated with shorter procedure time (Rs = -0.98; p = 0.002). When estimating cost per procedure, the MOSES HL was the cheapest, but had the highest purchase cost. The TFL was not cost-effective for large bladder stones compared with the 100 W HL. Conclusions: When treating large bladder stones, total laser power was highly correlated with laser and procedure times and the TFL was limited by its total power. The most cost-effective laser for use will depend on the case volume.

Does renal failure worsen radiation cystitis following radical prostatectomy?

OBJECTIVE: To investigate the impact of renal function on the risk, severity, and management of radiation cystitis in patients who underwent postoperative radiation therapy for prostate cancer. METHODS: Retrospective data was assessed from patients treated with adjuvant/salvage radiation therapy at a single academic institution between 2006 and 2020. The incidence, severity, and management of radiation cystitis were compared between three groups: CKD 0-2, CKD 3-4, and CKD 5. Associations of clinicopathologic factors with radiation cystitis were assessed in univariate and multivariate Cox regression models. RESULTS: A total of 110 patients who underwent radiation therapy following robot-assisted laparoscopic radical prostatectomy were included. The incidence of radiation cystitis following postoperative radiation therapy was 17% with a median presentation time of 34 months (interquartile range 16-65 months). The incidence of radiation cystitis was 100% in CKD 5 patients compared to 15% in CKD 0-2 and 17% in CKD 3-4 patients (p < 0.001). CKD 5 patients required more treatments, emergency department visits, and longer hospitalization times than CKD 0-4 patients (all p < 0.001). Multivariate analyses identified CKD 5 as the only significant factor associated with radiation cystitis (HR = 10.39, p = 0.026). CONCLUSION: End-stage renal failure is associated with the risk and severity of radiation cystitis in patients receiving postoperative radiation therapy. Knowledge of the potential morbidity of this complication in this population could guide physicians and patients as they evaluate risks and benefits prior to selecting adjuvant or salvage radiation therapy.

TSP1 and TSP2 Have Unique and Overlapping Roles in Protecting against Noise-Induced Auditory Synaptopathy.

Thrombospondins (TSPs) are cell adhesion molecules that play an important role in the maintenance of hearing and afferent synaptic connections. Based on their reported function in restoring synaptic connections after stroke, we tested a potential role for TSP1 and TSP2 genes in repairing cochlear synapses following noise injury. We observed a tonotopic gradient in the expression of TSP1 and TSP2 mRNA in control mouse cochleae and an upregulation of these genes following noise exposure. Examining the functional sequelae of these changes revealed that afferent synaptic counts and auditory brainstem responses (ABRs) in noise-exposed TSP1 and TSP2 knockout (-/-) mice exhibited a worst recovery when compared to controls. Consistent with their tonotopic expression, TSP1-/- mice showed greater susceptibility to noise-induced hearing loss (NIHL) at 8 kHz and 16 kHz frequencies, whereas NIHL in TSP2-/- mice occurred only at mid and high frequencies. Further analysis of the ABR waveforms indicated peripheral neuronal damage in TSP2-/- but not in TSP1-/- mice. Noise trauma affecting mid to high frequencies triggered severe seizures in the TSP2-/- mice. We found that decreased susceptibility to audiogenic seizures in TSP1-/- mice was correlated with increased TSP2 protein levels in their inner ears, suggesting that TSP2 might functionally compensate for the loss of TSP1 in these mice. Our data indicate that TSP1 and TSP2 are both involved in susceptibility to NIHL, with TSP2 playing a more prominent role.

Complications of Botox and their Management.

PURPOSE OF REVIEW: Adherence to anticholinergic medications is known to be a problem in patients with overactive bladder, with only 13.2% of patients continuing anticholinergic therapy beyond 1 year D'Souza et al. (J Manag Care Pharm. 14:291-301, 2008). RECENT FINDINGS: Prior to the advent of third line therapies such as onabotulinumtoxin A, refractory overactive bladder (OAB) was managed with augmentation cystoplasty, a lengthy surgery with associated side effects including lifetime need for self-catheterization, ileus, and metabolic disturbances. The advent of onabotulinumtoxin A has drastically reduced the rates of augmentation cystoplasties being performed for refractory OAB. However, all procedures are associated with side effects which should be relayed to the patient prior to beginning therapy, as well as their management. In the current review, we summarize the common complications following onabotulinumtoxin A injection as well as their management.

A lack of immune system genes causes loss in high frequency hearing but does not disrupt cochlear synapse maturation in mice.

Early cochlear development is marked by an exuberant outgrowth of neurites that innervate multiple targets. The establishment of mature cochlear neural circuits is, however, dependent on the pruning of inappropriate axons and synaptic connections. Such refinement also occurs in the central nervous system (CNS), and recently, genes ordinarily associated with immune and inflammatory processes have been shown to play roles in synaptic pruning in the brain. These molecules include the major histocompatibility complex class I (MHCI) genes, H2-K(b) and H2-D(b), and the complement cascade gene, C1qa. Since the mechanisms involved in synaptic refinement in the cochlea are not well understood, we investigated whether these immune system genes may be involved in this process and whether they are required for normal hearing function. Here we report that these genes are not necessary for normal synapse formation and refinement in the mouse cochlea. We further demonstrate that C1qa expression is not necessary for normal hearing in mice but the lack of expression of H2-K(b) and H2-D(b) causes hearing impairment. These data underscore the importance of the highly polymorphic family of MHCI genes in hearing in mice and also suggest that factors and mechanisms regulating synaptic refinement in the cochlea may be distinct from those in the CNS.

Thrombospondins 1 and 2 are important for afferent synapse formation and function in the inner ear.

Thrombospondins (TSPs) constitute a family of secreted extracellular matrix proteins that have been shown to be involved in the formation of synapses in the central nervous system. In this study, we show that TSP1 and TSP2 are expressed in the cochlea, and offer the first description of their putative roles in afferent synapse development and function in the inner ear. We examined mice with deletions of TSP1, TSP2 and both (TSP1/TSP2) for inner ear development and function. Immunostaining for synaptic markers indicated a significant decrease in the number of formed afferent synapses in the cochleae of TSP2 and TSP1/TSP2 knockout (KO) mice at postnatal day (P)29. In functional studies, TSP2 and TSP1/TSP2 KO mice showed elevated auditory brainstem response (ABR) thresholds as compared with wild-type littermates, starting at P15, with the most severe phenotype being seen for TSP1/TSP2 KO mice. TSP1/TSP2 KO mice also showed reduced wave I amplitudes of ABRs and vestibular evoked potentials, suggesting synaptic dysfunction in both the auditory and vestibular systems. Whereas ABR thresholds in TSP1 KO mice were relatively unaffected at early ages, TSP1/TSP2 KO mice showed the most severe phenotype among all of the genotypes tested, suggesting functional redundancy between the two genes. On the basis of the above results, we propose that TSPs play an important role in afferent synapse development and function of the inner ear.

Increased lymphangiogenesis and hemangiogenesis in infant cornea.

BACKGROUND: Corneal lymphangiogenesis (LG) and hemangiogenesis (HG) accompany many diseases after inflammatory, infectious, traumatic or chemical insults. They also contribute to transplant rejection. It is known that corneal transplants in infants or children have a higher rejection rate than in adults. However, it has never been studied whether infant corneas differ from adult corneas in inflammatory LG, HG, or both, which is the focus of this study. METHODS AND RESULTS: Corneal inflammatory LG and HG were induced by a standard suture placement model in C57BL/6 mice of 3 weeks and 8 weeks of age, respectively. Corneal LG, HG, and macrophage infiltration were assessed by immunofluorescent microscopic studies using specific antibodies against CD31 (a panendothelial cell marker), LYVE-1 (a lymphatic marker), and F4/80 (a macrophage marker). Blood vessels were also examined by ophthalmic slit-lamp microscopic assays in vivo. Digital images were analyzed by NIH Image J software. It was found, for the first time, that infant corneas exhibited a higher level of LG, HG, and macrophage infiltration during inflammation. Infant lymphatic and blood vessels demonstrated greater density and invasion area but similar branching points. Additionally, infant lymphatic vessels were also of larger diameter. CONCLUSIONS: Infant and adult corneas differ greatly in their inflammatory responses of LG, HG, and macrophage infiltration. These novel findings will shed some light on our understanding of the LG and HG processes, as well as the development of new therapeutic protocols for corneal diseases, particularly, in infants or children, where an early restoration of sight is critically important in preventing amblyopia or permanent vision loss.