Nedosiran Dramatically Reduces Serum Oxalate in Dialysis-Dependent Primary Hyperoxaluria 1: A Compassionate Use Case Report.

Primary hyperoxaluria 1 (PH1) is a devastating condition involving recurrent urolithiasis, early end-stage renal disease and multisystemic deposition of calcium oxalate crystals. Treatment options for PH1 are limited, inevitably requiring transplantation, usually combined kidney and liver transplant. Here we report successful compassionate use of Nedosiran, an RNA interference targeting lactate dehydrogenase, in an index patient. Monthly Nedosiran injections led to dramatically decreased plasma oxalate levels, decreased frequency of weekly hemodialysis sessions from 6 to 3, and deferral of combined kidney and liver transplant. Nedosiran represents a novel and impactful potential therapeutic for PH1 patients with end-stage renal disease

A large staghorn stone diagnosed and managed in an asymptomatic patient using the "Kidney Injury Test (Kit)" spot urine assay: A case report.

The Kidney Injury Test (KIT) Stone-Score provides an objective measure of stone burden. Unlike urinary supersaturation the KIT Stone-Scores assess underlying stone disease rather than urinary solute composition. We report a case of a 43-year-old woman with no history of nephrolithiasis who underwent an elective, voluntary KIT assay and was diagnosed with a large staghorn renal stone after an unanticipated markedly elevated score. This clinical scenario highlights the potential future use of the non-invasive urinary KIT assay as a reliable non-invasive tool to detect and monitor urinary stone disease

Bacillus subtilis Swarmer Cells Lead the Swarm, Multiply, and Generate a Trail of Quiescent Descendants

International audienceBacteria adopt social behavior to expand into new territory, led by specialized swarmers, before forming a biofilm. Such mass migration of Bacillus subtilis on a synthetic medium produces hyperbranching dendrites that transiently (equivalent to 4 to 5 generations of growth) maintain a cellular monolayer over long distances, greatly facilitating single-cell gene expression analysis. Paradoxically, while cells in the dendrites (nonswarmers) might be expected to grow exponentially, the rate of swarm expansion is constant, suggesting that some cells are not multiplying. Little attention has been paid to which cells in a swarm are actually multiplying and contributing to the overall biomass. Here, we show in situ that DNA replication, protein translation and peptidoglycan synthesis are primarily restricted to the swarmer cells at dendrite tips. Thus, these specialized cells not only lead the population forward but are apparently the source of all cells in the stems of early dendrites. We developed a simple mathematical model that supports this conclusion. IMPORTANCE: Swarming motility enables rapid coordinated surface translocation of a microbial community, preceding the formation of a biofilm. This movement occurs in thin films and involves specialized swarmer cells localized to a narrow zone at the extreme swarm edge. In the B. subtilis system, using a synthetic medium, the swarm front remains as a cellular monolayer for up to 1.5 cm. Swarmers display high-velocity whirls and vortexing and are often assumed to drive community expansion at the expense of cell growth. Surprisingly, little attention has been paid to which cells in a swarm are actually growing and contributing to the overall biomass. Here, we show that swarmers not only lead the population forward but continue to multiply as a source of all cells in the community. We present a model that explains how exponential growth of only a few cells is compatible with the linear expansion rate of the swarm

Reimagining Ambulatory Care in Urology: Conversion of the Urology Clinic into a Procedure Center Improves Patient's Experience

Introduction: The coronavirus disease 2019 (COVID-19) pandemic made it necessary to practice social distancing and limited in-person encounters in health care. These restrictions created alternative opportunities to enhance patient access to care in the ambulatory setting. We hypothesized that by transforming clinics into centers that prioritize procedures and transitioning ambulatory appointments to telehealth, we could establish a secure, streamlined, and productive method for providing patient care. Methods: Clinic templates were restructured to allow the use of the physical space to perform procedure-based clinics exclusively, while switching to virtual telemedicine for all nonprocedural encounters. Staff members were given specific roles to support one of the patient care modalities for a given day (Procedures vs. Telehealth). Performance and patient satisfaction metrics were collected between two periods of time defined as P1 (February-June 2019) and P2 Post-COVID (February-June 2020) and compared. These served as proxies of periods when the clinic workflow and templates were structured in the traditional versus the emerging way. Statistical analysis was performed using bivariate analyses. Results: The percentage of procedures performed among all in-person visits were higher in P2 compared to P1 (45% vs. 29%, p < 0.001). Although total charges and relative value units were lower in P2, the overall revenue generated was higher compared to P1 ($4,597,846 vs.$4,517,427$, respectively). This increase in revenue was mainly driven by the higher relative income generated by procedures. Patient experience, reflected through patient-reported outcomes, was more favorable in P2 where patients seemed more likely to "Recommend this provider office" (90% vs. 85.7%, p = 0.01), report improved "Access overall" (56% vs. 49%, p = 0.02), and felt they were "Moving through your visit overall" (59% vs. 51%, p = 0.007). Conclusions: Our data suggest that reorganizing urology clinics into a space that is centered around outpatient procedures can represent a model that improves the patient's access to care and clinical experience, while simultaneously improving operational financial strength. This efficient care model could be considered for many practice settings and drive high-value outpatient care

LVAD as a Bridge to Remission from Advanced Heart Failure: Current Data and Opportunities for Improvement

Left ventricular assist devices (LVADs) are an established treatment modality for advanced heart failure (HF). It has been shown that through volume and pressure unloading they can lead to significant functional and structural cardiac improvement, allowing LVAD support withdrawal in a subset of patients. In the first part of this review, we discuss the historical background, current evidence on the incidence and assessment of LVAD-mediated cardiac recovery, and out-comes including quality of life after LVAD support withdrawal. In the second part, we discuss current and future opportunities to promote LVAD-mediated reverse remodeling and improve our pathophysiological understanding of HF and recovery for the benefit of the greater HF population

Ultrasound-Only Percutaneous Nephrolithotomy Is Safe and Effective Compared to Fluoroscopy-Directed Percutaneous Nephrolithotomy.

Introduction: Outcomes after ultrasound-only percutaneous nephrolithotomy (PCNL), in which no fluoroscopy is used, are not well known. The goal of this study was to compare outcomes of ultrasound-only and fluoroscopy-directed PCNL. Materials and Methods: Prospectively collected data from the Registry for Stones of the Kidney and Ureter database were reviewed for all patients who underwent PCNL at one academic center from 2015 to 2021. Primary outcomes were complications and stone-free rates (no residual fragments ≥3 mm). Results: Of the 141 patients who underwent ultrasound-only PCNL and 147 who underwent fluoroscopy-directed PCNL, there was no difference in complication rates (15% vs 16%, p = 0.87) or stone-free status (71% vs 65%, p = 0.72), respectively. After adjusting for body mass index, American Society of Anesthesiologists (ASA), stone size, and stone complexity by Guy score, ultrasound-only PCNL was not associated with any increased odds of complications (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.3-1.6, p = 0.41) or residual stone fragments ≥3 mm (OR 1.0, 95% CI 0.5-1.9, p = 0.972) compared with fluoroscopy-directed PCNL. Ultrasound-only PCNL was associated with shorter operative time (median 99.5 vs 126 minutes, p < 0.001), and the use of ultrasound remained a significant predictor of short operative time (<100 minutes) after controlling for supine positioning, stone size, and stone complexity by Guy score (OR 2.31, 95% CI 1.01-5.29, p = 0.048). Patients in the ultrasound-only group were spared a mean radiation exposure dose of 10 mGy per procedure. Conclusions: Ultrasound-only PCNL is safe and achieves similar stone-free rates compared with fluoroscopy-directed PCNL with the added benefit of avoidance of radiation