Microglial depletion after brain injury prolongs inflammation and impairs brain repair, adult neurogenesis and pro-regenerative signaling.

The adult zebrafish brain, unlike mammals, has a remarkable regenerative capacity. Although inflammation in part hinders regeneration in mammals, it is necessary for zebrafish brain repair. Microglia are resident brain immune cells that regulate the inflammatory response. To explore the microglial role in repair, we used liposomal clodronate or colony stimulating factor-1 receptor (csf1r) inhibitor to suppress microglia after brain injury, and also examined regeneration in two genetic mutant lines that lack microglia. We found that microglial ablation impaired telencephalic regeneration after injury. Microglial suppression attenuated cell proliferation at the intermediate progenitor cell amplification stage of neurogenesis. Notably, the loss of microglia impaired phospho-Stat3 (signal transducer and activator of transcription 3) and ß-Catenin signaling after injury. Furthermore, the ectopic activation of Stat3 and ß-Catenin rescued neurogenesis defects caused by microglial loss. Microglial suppression also prolonged the post-injury inflammatory phase characterized by neutrophil accumulation, likely hindering the resolution of inflammation. These findings reveal specific roles of microglia and inflammatory signaling during zebrafish telencephalic regeneration that should advance strategies to improve mammalian brain repair.

Clinical Outcomes of Robotic Assisted Partial Nephrectomy for Pathologic T3a Renal Masses With Venous Tumor Thrombus.

OBJECTIVE: To evaluate the safety, efficacy, and early oncologic outcomes of pathologic T3a (pT3a) renal cell carcinoma with venous involvement treated with robotic partial nephrectomy (RPN), given that experience and outcomes in this group is limited. METHODS: A retrospective chart review of patients undergoing RPN from September 2009 to July 2020 was performed. Outcomes were captured from patients with pT3a disease with vein involvement. Clinical characteristics were analyzed using SPSS (IBM, Armonk, NY). Local recurrence-free survival and metastasis-free survival at 2 years were calculated from Kaplan-Meier survival curves. RESULTS: For 45 included patients, mean operative and warm ischemia times were 199.6 ± 47.3 minutes and 30.5 ± 10.5 minutes, with mean estimated blood loss of 324.9 ± 209.5 cc. Rates of transfusion, embolization, re-admission, and re-operation at 30 days were 8.9% (4/45), 2.2% (1/45), 11.1% (5/45), and 6.7% (3/45; cystoscopic stent placement), respectively. All tumors were malignant on pathology, with clear cell renal cell carcinoma being the most common (91.0%, n = 41). The positive margin rate was 6.7% (n = 3). Local recurrence occurred in 4.4% (n = 2) at a mean time of 5.2 ± 2.3 months. Four patients (8.9%) progressed to metastatic disease at a mean of 22.2 ± 23.0 months. At 2 years, local recurrence-free survival was 95.4% and metastasis-free survival was 95.3%. CONCLUSION: We present the largest known series of patients RPN for pT3a renal masses with venous tumor involvement. We found it both feasible and safe in the appropriate hands. Short term oncologic outcomes for these patients appear more favorable than historic literature suggested.

Use of Pre-operative Pharmacologic Venous Thromboembolism Prophylaxis for Robotic Partial Nephrectomy.

OBJECTIVE: To determine whether a single dose of preoperative enoxaparin for venous thromboembolism (VTE) prophylaxis impacts rates of thrombotic and bleeding events after robotic partial nephrectomy (RPNx). METHODS: A retrospective cohort study of RPNx patients from 2009 to 2020 was performed. Clinical characteristics and perioperative outcomes were compared between patients receiving a single dose of preoperative enoxaparin and those who did not. The primary outcome was 30-day hemorrhagic complications (transfusion ≥2 units, embolization, or reoperation for bleeding). Secondary outcomes were 30-day VTE events. Multivariable logistic regression was performed to control for significant differences between groups and to identify predictors of hemorrhagic complications among patients. RESULTS: Among 945 RPNx procedures, 794 (84%) received preoperative enoxaparin (PPx) and 151 (16%) did not (NPPx). The PPx cohort was older (P = .004), had lower BMI (P = .03), lower ASA class (P = .049), and fewer smokers (P = .03). Warm ischemia time was longer for PPx patients (P < .001). 4.9% and 2.6% of the PPx and NPPx cohorts, respectively, developed postoperative hemorrhagic complications (P = .29). After adjustment for potential covariates, pharmacologic prophylaxis was not associated with 30-day hemorrhagic complications (P = .39). On multivariable regression, longer warm ischemia time (OR 1.05, 95% CI 1.01-1.10, P = .02) and greater tumor size (OR 1.27, 95% CI 1.03-1.56, P = .02) were predictors of hemorrhagic complications. 30-day readmissions, VTE events, and mortality were similar between groups (all P> 0.05). CONCLUSION: Similar rates of thrombotic and bleeding events occurred between patients receiving pharmacologic prophylaxis and those who did not. Single dose of preoperative enoxaparin did not significantly alter perioperative outcomes after RPNx.