Can single-stage bilateral unicompartmental knee arthroplasty be safely performed in patients over 70?

Background: For patients with bilateral, symptomatic unicompartmental knee arthritis, single-stage bilateral unicompartmental knee arthroplasty (ssBUKA) presents an attractive option. However, most studies have examined younger patient cohorts and the safety of ssBUKA remains controversial for older individuals. Therefore, the purpose of this study was to compare complication rates following ssBUKA for patients ≤70 and > 70 years old. Methods: A retrospective chart review of 238 patients having undergone ssBUKA was performed, including 134 patients ≤70 and 104 patients >70. Post-operative complications were recorded at the six-week post-operative visit, along with emergency room visits and hospital readmissions within 90 days. Results: Compared to patients ≤70, patients >70 were more frequently female (43.3% and 55.8%, respectively) (p = 0.037) and had significantly lower body mass index (30.41 ± 4.64 and 27.30 ± 3.68, respectively) (p < 0.001). Patients >70 were discharged home (50%) less commonly than patients ≤70 (73.1%) (p < 0.001). Two patients ≤70 (1.5%) and two patients >70 (1.9%) sought emergency room treatment (p = 0.589), with respiratory complications most common. There were no differences regarding any postoperative complications between patients ≤70 and > 70 years old. Conclusion: These results suggest that patients >70 can safely undergo ssBUKA, as it does not appear to increase the incidence of early post-operative complications compared to patients ≤70. However, 50% of patients >70 were not able to discharge directly home following surgery.

Exocyst inactivation in urothelial cells disrupts autophagy and activates non-canonical NF-κB signaling.

Ureter obstruction is a highly prevalent event during embryonic development and is a major cause of pediatric kidney disease. We have previously reported that ureteric bud-specific ablation of the gene expressing the exocyst subunit EXOC5 in late murine gestation results in failure of urothelial stratification, cell death and complete ureter obstruction. However, the mechanistic connection between disrupted exocyst activity, urothelial cell death and subsequent ureter obstruction was unclear. Here, we report that inhibited urothelial stratification does not drive cell death during ureter development. Instead, we demonstrate that the exocyst plays a critical role in autophagy in urothelial cells, and that disruption of autophagy activates a urothelial NF-κB stress response. Impaired autophagy first provokes canonical NF-κB activity, which is progressively followed by increasing levels of non-canonical NF-κB activity and cell death if the stress remains unresolved. Furthermore, we demonstrate that ureter obstructions can be completely rescued in Exoc5 conditional knockout mice by administering a single dose of the pan-caspase inhibitor z-VAD-FMK at embryonic day 16.5 prior to urothelial cell death. Taken together, ablation of Exoc5 disrupts autophagic stress response and activates progressive NF-κB signaling, which promotes obstructive uropathy.

The Pacific Region Indigenous Doctors Congress Medical Student Track Report.

The 2018 Pacific Region Indigenous Doctors Congress (PRIDoC) conference featured a student track curriculum that was developed by students at the John A. Burns School of Medicine. Activities were designed around the student track theme, ho'oku'ikahi, meaning "unity" or "unify," as well as the overarching conference theme 'Oi Ola Wai Honua meaning "life is better while the earth has water." Following the conference, surveys were distributed among the trainees who had participated in the student track. The survey feedback was used to evaluate the student track curriculum, as well as its execution. Learning objectives developed for the Student Track were (1) to build formal professional networks, (2) to build a knowledge economy with shared knowledge among participants, and (3) to engage in cultural experiences. Analysis of qualitative data suggest that all learning objectives were satisfactorily fulfilled through planned conference activities. The data will be used to facilitate student tracks at future PRIDoC conferences. The student track at PRIDoC aims to establish and contribute to an ever-growing international network of indigenous students that will extend into professional practice.

Fibroproliferative response to urothelial failure obliterates the ureter lumen in a mouse model of prenatal congenital obstructive nephropathy.

Congenital obstructive nephropathy (CON) is the most prevalent cause of pediatric chronic kidney disease and end-stage renal disease. The ureteropelvic junction (UPJ) region, where the renal pelvis transitions to the ureter, is the most commonly obstructed site in CON. The underlying causes of congenital UPJ obstructions remain poorly understood, especially when they occur in utero, in part due to the lack of genetic animal models. We previously showed that conditional inactivation of Sec10, a central subunit of the exocyst complex, in the epithelial cells of the ureter and renal collecting system resulted in late gestational bilateral UPJ obstructions with neonatal anuria and death. In this study, we show that without Sec10, the urothelial progenitor cells that line the ureter fail to differentiate into superficial cells, which are responsible for producing uroplakin plaques on the luminal surface. These Sec10-knockout urothelial cells undergo cell death by E17.5 and the urothelial barrier becomes leaky to luminal fluid. Also at E17.5, we measured increased expression of TGFß1 and genes associated with myofibroblast activation, with evidence of stromal remodeling. Our findings support the model that a defective urothelial barrier allows urine to induce a fibrotic wound healing mechanism, which may contribute to human prenatal UPJ obstructions.

Urothelial Defects from Targeted Inactivation of Exocyst Sec10 in Mice Cause Ureteropelvic Junction Obstructions.

Most cases of congenital obstructive nephropathy are the result of ureteropelvic junction obstructions, and despite their high prevalence, we have a poor understanding of their etiology and scarcity of genetic models. The eight-protein exocyst complex regulates polarized exocytosis of intracellular vesicles in a large variety of cell types. Here we report generation of a conditional knockout mouse for Sec10, a central component of the exocyst, which is the first conditional allele for any exocyst gene. Inactivation of Sec10 in ureteric bud-derived cells using Ksp1.3-Cre mice resulted in severe bilateral hydronephrosis and complete anuria in newborns, with death occurring 6-14 hours after birth. Sec10 FL/FL;Ksp-Cre embryos developed ureteropelvic junction obstructions between E17.5 and E18.5 as a result of degeneration of the urothelium and subsequent overgrowth by surrounding mesenchymal cells. The urothelial cell layer that lines the urinary tract must maintain a hydrophobic luminal barrier again urine while remaining highly stretchable. This barrier is largely established by production of uroplakin proteins that are transported to the apical surface to establish large plaques. By E16.5, Sec10 FL/FL;Ksp-Cre ureter and pelvic urothelium showed decreased uroplakin-3 protein at the luminal surface, and complete absence of uroplakin-3 by E17.5. Affected urothelium at the UPJ showed irregular barriers that exposed the smooth muscle layer to urine, suggesting this may trigger the surrounding mesenchymal cells to overgrow the lumen. Findings from this novel mouse model show Sec10 is critical for the development of the urothelium in ureters, and provides experimental evidence that failure of this urothelial barrier may contribute to human congenital urinary tract obstructions.