Early identification of transplant glomerulopathy in pediatric kidney transplant biopsies: A single-center experience with electron microscopy analysis.

Banff 2013 criteria recommend performing ultrastructural studies with electron microscopy (EM) in kidney transplant biopsies if the technology is available. We sought to determine the impact of EM on enhancing diagnostic findings in pediatric kidney transplant biopsies and the prognostic information gained from the additional findings. All kidney transplant biopsies since routine EM use started on June 1, 2014, until October 31, 2016, were reviewed. Primary outcome measures included the positive yield frequency of EM use defined as an upgraded diagnosis based on EM findings relative to light microscopy, and 12-month kidney allograft outcome of progression to ESRD or doubling of serum creatinine stratified by transplant glomerulopathy (TG) status on EM. Eighty unique kidney transplant biopsies were reviewed. EM studies were completed for 61 biopsies (76%). Complication rate was low (3.7%). In 61 biopsies where EM was completed, EM findings included foot process fusion (62%), endothelial cell swelling (38%), subendothelial lucencies (31%), and glomerular basement membrane duplication (41%). EM confirmed FSGS recurrence in three cases. In the remaining 58 cases, there was a positive yield of 31% where 18 biopsies were upgraded to a worse category after TG identification on EM. Kidney allograft outcome was poor regardless whether TG was detected early on EM or advanced on LM. Routine EM use in analyzing pediatric kidney transplant biopsies proved safe and provided valuable additional diagnostic information in almost one-third of cases. Additional studies are needed to determine if clinical interventions for early TG identified on EM can improve long-term outcomes.

A Ric8/synembryn homolog promotes Gpa1 and Gpa2 activation to respectively regulate cyclic AMP and pheromone signaling in Cryptococcus neoformans.

The G protein α subunits Gpa1, Gpa2, and Gpa3 mediate signal transduction and are important in the growth and virulence of Cryptococcus neoformans. To understand how Gpa1 functions without a conventional Gß subunit, we characterized a resistance to inhibitors of cholinesterase 8 (Ric8) homolog from C. neoformans, which shares amino acid sequence homology with other Ric8 proteins that exhibit guanine nucleotide exchange factor (GEF) activity toward Gα. We found that the ric8 mutant was reduced in capsule size and melanin formation, which could be suppressed by cyclic AMP (cAMP) supplementation or by introducing the activated GPA1(Q284L) allele. Consistent with the fact that Ric8 participates in cAMP signaling to regulate virulence, the ric8 mutant was attenuated in virulence toward mice. Interestingly, disruption of RIC8 also resulted in opposing effects on pheromone signaling, as the ric8 mutant showed reduced mating but an enhanced ability to induce the pheromone response in the mating partner. To identify Ric8 functional mechanisms, we examined the interactions between Ric8 and the three Gα proteins. Ric8 interacted with Gpa1 and Gpa2, but not Gpa3. The presence of Gpa1(Q284L) negatively affected its interaction with Ric8, whereas the activated Gpa2(Q203L) allele abolished the interaction. Collectively, these findings suggest that Ric8 functions as a GEF to facilitate the activation of Gpa1-cAMP signaling and to promote Gpa2, affecting mating efficiency. Our study highlights the distinct and conserved characteristics associated with G protein signaling and contributes to our overall understanding of how G protein α subunits function with or without a canonical Gß partner in C. neoformans.

Gene therapy for retinitis pigmentosa.

Rhodopsin-mediated autosomal dominant retinitis pigmentosa (RP) is the most common cause of RP in North America. There is no proven cure for the disease, and multiple approaches are being studied. Gene therapy is an evolving field in medicine and ophthalmology. In this review, we will go over the basic concept of gene therapy and the different types of gene therapy that are currently being studied to treat this disease.

Medical management and visual rehabilitation of limbal niche dysfunction.

Limbal niche dysfunction (LND) has been described as a medically reversible form of limbal stem cell deficiency. The current literature is sparse regarding therapeutic options to improve visual function after stabilization of the disease. A 61-year-old monocular woman with an extensive medical and ocular history presented with long-standing recalcitrant epitheliopathy in both eyes. History and examination findings on presentation led to a diagnosis of LND, and medical therapy was initiated. After 8 months, her ocular surface had improved and corrected distance visual acuity (CDVA) was 20/40. She was fit with a scleral contact lens because of its ability to promote ocular surface healing and improve visual acuity. She maintained symptom resolution and her CDVA improved to 20/20. LND is a distinctive and reversible epitheliopathy that responds favorably to appropriate medical therapy. To the authors' knowledge, this is the first reported case of using the scleral contact lens as an adjunctive visual rehabilitation therapy to complement medical treatment for LND.

Reducing instruments in a vitrectomy surgical tray: cost savings and results from a major academic hospital.

BACKGROUND: Unused or rarely used instruments in standard surgical trays can unnecessarily increase costs. Prior studies have demonstrated the practicality and cost savings of reduced instrument tray sizes in various subspecialties. This study describes results and estimated cost savings from a reduced instrument tray used for vitrectomy surgery at a large, tertiary academic medical center. METHODS: Common usage patterns of vitrectomy instruments by one retina surgeon were reviewed and a reduced instrument vitrectomy tray was created and implemented in successive vitrectomy surgeries. Need for opening the previously utilized larger tray was recorded. Estimated cost savings of the new trays were calculated based upon per instrument sterilization, processing, and instrument replacement costs. RESULTS: New vitrectomy trays including just 7 instruments (89% reduction compared to original trays) were created and implemented in 189 successive cases. The original tray was never opened. Estimated cost savings from saved sterilization and processing resources is approximately $9588 per year. Assuming 5- and 10-year lifespan per instrument, annual cost avoidance is projected at $7886 and $15,772, respectively. Other indirect benefits relevant to healthcare quality were also noted. CONCLUSION: A reduced instrument tray can be successfully implemented for vitrectomy surgery and can result in significant indirect benefits as well as direct cost savings from reduced sterilization costs. Our study highlights the substantial impact made by evaluating the usage pattern and making appropriate instrument tray changes for just one retina surgeon. Applying these same methods to other surgeons and specialties can have significant implications on healthcare costs and quality.