Safety and feasibility of urological procedures in Jehovah's Witness patients.

OBJECTIVES: To describe the safety and feasibility of urological transfusion-free surgeries in Jehovah's Witness patients. METHODS: An institutional review board-approved, retrospective review of Jehovah's Witness patients who underwent urological transfusion-free surgeries between 2003 and 2019 was carried out. Surgeries were stratified into low, intermediate and high risk based on complexity, invasiveness and bleeding potential. Patient demographics, perioperative data and clinical outcomes are reported. RESULTS: A total of 161 Jehovah's Witness patients (median age 63.4 years) underwent 171 transfusion-free surgeries, including 57 (33.3%) in low-, 82 (47.9%) in intermediate- and 32 (18.8%) in high-risk categories. The mean estimated blood loss increased with risk category at 48 mL (range 10-50 mL), 150 mL (range 50-200 mL) and 388 mL (range 137-500 mL), respectively (P < 0.001). Implementing blood augmentation and conservation techniques increased with each risk category (3.5% vs 29% vs 69%, respectively; P < 0.001). Average length of stay increased concordantly at 1.6 days (range 0-12 days), 2.9 days (range 1-13 days) and 5.6 days (range 2-12 days), respectively (P ≤ 0.001). However, there was no increase in complication rates and readmission rates attributed to bleeding among the risk categories at 30 days (P = 0.9 and 0.4, respectively) and 90 days (P = 0.7 and 0.7, respectively). CONCLUSIONS: Transfusion free urological surgery can be safely carried out on Jehovah's Witness patients using contemporary perioperative optimization. Additionally, these techniques can be expanded for use in the general patient population to avoid short- and long-term consequences of perioperative blood transfusion.

Preoperative chemotherapy in clinically node positive muscle invasive bladder cancer: Radiologic variables can predict response.

PURPOSE: To evaluate pathologic downstaging after radical cystectomy and pelvic lymph node dissection for clinically lymph node positive urothelial bladder cancer and to determine optimal preoperative imaging variables in predicting pathologic nodal status. METHODS: We identified all patients with clinically lymph node positive urothelial bladder cancer who underwent radical cystectomy and extended pelvic lymph node dissection with intent to cure at our institution. Patients were stratified based on pathologic node status to determine clinical associations and survival outcomes. Pre and post-chemotherapy CT scans were reviewed to characterize lymph node size and morphology. We also sought to determine associations between post-chemotherapy radiology variables and pathologic response. RESULTS: We identified 130 patients with clinically node positive bladder cancer, out of which 76 (58.5%) received induction chemotherapy. Thirty three (43.4%) had pathologic T downstaging following chemotherapy, compared to 7 (12.9%) patients who had surgery alone (P< 0.0001). A complete nodal response (pN0) occurred in 31 (40.8%) patients post-chemotherapy, while 6 (11.1%) of those who received cystectomy alone ended up being pN0 (P< 0.0001). Median overall survival and recurrence-free survival were shorter in patients with pN+ versus pN0 disease (1.9 years vs. 12.8 years, P= 0.016 and 1.2 years vs. 4.3 years, P= 0.013, respectively). Review of 29 post chemotherapy CT scans showed that patients with pathologic nodal involvement had a greater median number of enlarged nodes (3.5 vs. 1, P= 0.038) and a greater median size of largest node (8.5 mm vs. 6.0 mm, P= 0.021) on imaging compared to those with complete pN0. Each 1 mm increase in size of the largest node on post-chemotherapy CT scan increased the chance of having pN+ disease by 1.57 (95% CI 1.02-2.44, P= 0.043). Using a median node size of 8 mm as a cut-off to predict pN+ disease provided a sensitivity and specificity of 72% and 80%, respectively (c-index = 0.761, P= 0.014). The positive predictive value for this cut-off was 87% (95% CI 58%-98%) and negative predictive value was 62% (32%-85%). CONCLUSION: Patients with clinically node positive bladder cancer may have significant pN0 after induction chemotherapy. Our data suggest a post-chemotherapy CT scan with an 8 mm nodal size cut-off may be a better predictor of pathologic nodal status than more traditional measures.

Urinary tract infections following radical cystectomy with enhanced recovery protocol: A prospective study.

OBJECTIVES: Urinary tract infection (UTI) following radical cystectomy (RC) is a common complication associated with significant morbidity and risk of readmission. Recent literature has assessed the effect of perioperative antibiotic regimens on the rate of postoperative infections but not yet yielded with significant changes in UTI rates. Our study focused on the effect of postoperative suppressive regimens on the rate of UTI following radical cystectomy with Enhanced Recovery After Surgery (ERAS) protocol. METHODS: We retrospectively reviewed 427 patients who underwent RC with ERAS protocol between May 2012 and January 2017 at our institution. The ERAS protocol infection prevention measures included 24-hr perioperative antibiotic followed by suppressive antibiotic until removal of catheter/stents. A patient was found to have a UTI if they had a positive urine culture and documented symptoms, positive urine culture with treatment per practitioner discretion, or negative or unavailable urine culture but the clinical presumption of UTI that got treatment. Urosepsis was defined if any of UTI episodes were associated with positive blood culture. Patients' characteristics, UTI events, and urine culture sensitivities were reviewed for analysis. RESULTS: The incidence of UTI and urosepsis was 36.1% and 7.13% within 90-days following RC, respectively. The median time to the first UTI was 13 days (IQR 8-35). Candida (25.57%) and Escherichia coli (22.16%) were the most commonly identified pathogens. UTI and urosepsis were significantly lower in patients who received suppressive fluoroquinolones compared to other antibiotic regimens (32.72% vs. 45.24%, P = 0.04 for UTI and 5.25% vs. 11.90%, P = 0.04 for urosepsis). In multivariable analysis, orthotopic neobladder and perioperative transfusion were significantly associated with increased UTI rate (OR = 2.3 and 1.71, p < 0.05, respectively). CONCLUSIONS: UTI is common following RC and urinary diversion with ERAS protocol. The most common isolated pathogens are candida and Escherichia coli. Orthotopic neobladder and perioperative transfusion are independent risk factors for postoperative UTI. The use of suppressive fluoroquinolones is associated with a significant decrease in UTI rate.

Repurposing Lesogaberan to Promote Human Islet Cell Survival and ß-Cell Replication.

The activation of ß-cell's A- and B-type gamma-aminobutyric acid receptors (GABAA-Rs and GABAB-Rs) can promote their survival and replication, and the activation of α-cell GABAA-Rs promotes their conversion into ß-cells. However, GABA and the most clinically applicable GABA-R ligands may be suboptimal for the long-term treatment of diabetes due to their pharmacological properties or potential side-effects on the central nervous system (CNS). Lesogaberan (AZD3355) is a peripherally restricted high-affinity GABAB-R-specific agonist, originally developed for the treatment of gastroesophageal reflux disease (GERD) that appears to be safe for human use. This study tested the hypothesis that lesogaberan could be repurposed to promote human islet cell survival and ß-cell replication. Treatment with lesogaberan significantly enhanced replication of human islet cells in vitro, which was abrogated by a GABAB-R antagonist. Immunohistochemical analysis of human islets that were grafted into immune-deficient mice revealed that oral treatment with lesogaberan promoted human ß-cell replication and islet cell survival in vivo as effectively as GABA (which activates both GABAA-Rs and GABAB-Rs), perhaps because of its more favorable pharmacokinetics. Lesogaberan may be a promising drug candidate for clinical studies of diabetes intervention and islet transplantation.

Major histocompatibility complex class I molecules modulate embryonic neuritogenesis and neuronal polarization.

We studied cultured hippocampal neurons from embryonic wildtype, major histocompatibility complex class I (MHCI) heavy chain-deficient (K(b)D(b)-/-) and NSE-D(b) (which have elevated neuronal MHCI expression) C57BL/6 mice. K(b)D(b)-/- neurons displayed slower neuritogenesis and establishment of polarity, while NSE-D(b) neurons had faster neurite outgrowth, more primary neurites, and tended to have accelerated polarization. Additional studies with ß2M-/- neurons, exogenous ß2M, and a self-MHCI monomer suggest that free heavy chain cis interactions with other surface molecules can promote neuritogenesis while tripartite MHCI interactions with classical MHCI receptors can inhibit axon outgrowth. Together with the results of others, MHCI appears to differentially modulate neuritogenesis and synaptogenesis.