Robotic Simulation in Urologic Surgery.

Robotic surgery continues to revolutionize the field of urologic surgery, and thus it is crucial that graduating urologic surgery residents demonstrate proficiency with this technology. The large learning curve of utilizing robotic technology limits resident immediate participation in real-life robotic surgery, and skill acquisition is further challenged by variable case volume. Robotic simulation offers an invaluable opportunity for urologic trainees to cultivate strong foundational skills in a non-clinical setting, ultimately leading to both competence and operative confidence. Several different simulation technologies and robotic assessment protocols have been developed and demonstrate validity in several domains. However, despite their demonstrable utility, there is no formal robotic curricula within US urologic surgery residencies. In this article, we will review the current state of robotic simulation training in urologic surgery and highlight the importance of its widespread utilization in urologic surgery residency training programs.

Partial Component Exchange of a Non-Infected Inflatable Penile Prosthesis is Associated With a Higher Complication Rate.

OBJECTIVE: To describe the infectious and non-infectious complications in men undergoing Inflatable penile prosthesis (IPP) revision with partial and complete component exchange for mechanical malfunction. METHODS: We performed a multicenter retrospective cohort study of patients who underwent IPP revision. Men undergoing procedures for implant infection were excluded. Patients were divided into those who had complete exchange of the entire device or partial exchange of only one or 2 components. Infectious and non-infectious complications were compared between groups. RESULTS: Three hundred sixty-eight men had complete exchange of the entire device and 85 had partial component exchange. Men undergoing partial exchange had a significantly higher infection rate (7.1% vs 2.2%, P = .031). The partial exchange group also was more likely to receive antifungals (51.8 vs 16.6%, P < .001), have a modified salvage washout (77.4 vs 60.2%, P = .004), and less likely to receive vancomycin and gentamicin (63.5 vs 83.7%, P < .001). Time to revision was significantly shorter in the partial exchange group (44.9 vs 168.2 months, P < .001). Mean follow-up was slightly longer in the complete exchange group (18.3 vs 13.0 months). In multivariable analysis, partial exchange surgery, vancomycin and gentamicin prophylaxis, modified salvage washout, and antifungal prophylaxis were no longer associated with postoperative infections. The partial exchange group had greater rates of non-infectious complications (21.2% vs 9.5%, P = .005) such as pump malfunction and tubing breakage. CONCLUSION: Patients undergoing partial component revision had more infectious and non-infectious complications. These findings suggest that partial component exchange increases complications in men undergoing IPP revision.

Does the 5-item Frailty Index predict surgical complications of endoscopic surgical management for benign prostatic obstruction? An analysis of the ACS-NSQIP.

PURPOSE: To assess whether the 5-item Frailty Index (5i-FI) predicts surgical complications of endoscopic surgery for benign prostatic obstruction (BPO) and examine the rates of these complications across BPO surgical modalities adjusting for patient frailty. METHODS: The ACS-NSQIP registry was queried for patients who underwent transurethral resection of the prostate (TURP), photoselective vaporization of the prostate (PVP), and laser enucleation of the prostate (LEP) between 2009 and 2019. Patients' frailties were estimated using the 5i-FI. We assessed the association between 5i-FI and the following endpoints: all complications, major complications (Clavien-Dindo ≥ 3), length of stay (LOS) ≥ 2 days, and 30-day postoperative readmission. Inverse probability of treatment weighting (IPTW) was used to account for selection bias in treatment allocation. IPTW-adjusted rates for 30-day complications were compared between surgical modalities. RESULTS: The cohort included 38,399 (62.6%) TURP, 19,121 (31.2%) PVP, and 3797 (6.2%) LEP. Men with 5i-FI score ≥ 2 were more likely to receive TURP (22.7%) and PVP (22.5%) than LEP (18.8%). 5i-FI ≥ 2 was associated with higher odds of all complications (OR 1.50), major complications (OR 1.63), LOS ≥ 2 (OR 1.31), and readmission (OR 1.65). After IPTW, LEP had the lowest rates for all complications (6.29%; 95%CI 5.48-7.20), major complications (2.30%; 95%CI 1.83-2.89), and readmission (3.80%; 95%CI 3.18-4.53). CONCLUSION: The 5i-FI score is an independent predictor of 30-day postoperative surgical complications after endoscopic BPO surgery. After IPTW, LEP and PVP were associated with lower rates of complications than TURP. However, frail patients were less likely to undergo PVP and LEP. Preoperative frailty assessment could improve risk stratification before BPO surgery.

Mitochondrial DNA damage and vascular function in patients with diabetes mellitus and atherosclerotic cardiovascular disease.

OBJECTIVE: Prior studies demonstrate mitochondrial dysfunction with increased reactive oxygen species generation in peripheral blood mononuclear cells in diabetes mellitus. Oxidative stress-mediated damage to mitochondrial DNA promotes atherosclerosis in animal models. Thus, we evaluated the relation of mitochondrial DNA damage in peripheral blood mononuclear cells s with vascular function in patients with diabetes mellitus and with atherosclerotic cardiovascular disease. APPROACH AND RESULTS: We assessed non-invasive vascular function and mitochondrial DNA damage in 275 patients (age 57 ± 9 years, 60 % women) with atherosclerotic cardiovascular disease alone (N = 55), diabetes mellitus alone (N = 74), combined atherosclerotic cardiovascular disease and diabetes mellitus (N = 48), and controls age >45 without diabetes mellitus or atherosclerotic cardiovascular disease (N = 98). Mitochondrial DNA damage measured by quantitative PCR in peripheral blood mononuclear cells was higher with clinical atherosclerosis alone (0.55 ± 0.65), diabetes mellitus alone (0.65 ± 1.0), and combined clinical atherosclerosis and diabetes mellitus (0.89 ± 1.32) as compared to control subjects (0.23 ± 0.64, P < 0.0001). In multivariable models adjusting for age, sex, and relevant cardiovascular risk factors, clinical atherosclerosis and diabetes mellitus remained associated with higher mitochondrial DNA damage levels (ß = 0.14 ± 0.13, P = 0.04 and ß = 0.21 ± 0.13, P = 0.002, respectively). Higher mitochondrial DNA damage was associated with higher baseline pulse amplitude, a measure of arterial pulsatility, but not with flow-mediated dilation or hyperemic response, measures of vasodilator function. CONCLUSIONS: We found greater mitochondrial DNA damage in patients with diabetes mellitus and clinical atherosclerosis. The association of mitochondrial DNA damage and baseline pulse amplitude may suggest a link between mitochondrial dysfunction and excessive small artery pulsatility with potentially adverse microvascular impact.

Restoration of autophagy in endothelial cells from patients with diabetes mellitus improves nitric oxide signaling.

BACKGROUND: Endothelial dysfunction contributes to cardiovascular disease in diabetes mellitus. Autophagy is a multistep mechanism for the removal of damaged proteins and organelles from the cell. Under diabetic conditions, inadequate autophagy promotes cellular dysfunction and insulin resistance in non-vascular tissue. We hypothesized that impaired autophagy contributes to endothelial dysfunction in diabetes mellitus. METHODS AND RESULTS: We measured autophagy markers and endothelial nitric oxide synthase (eNOS) activation in freshly isolated endothelial cells from diabetic subjects (n = 45) and non-diabetic controls (n = 41). p62 levels were higher in cells from diabetics (34.2 ± 3.6 vs. 20.0 ± 1.6, P = 0.001), indicating reduced autophagic flux. Bafilomycin inhibited insulin-induced activation of eNOS (64.7 ± 22% to -47.8 ± 8%, P = 0.04) in cells from controls, confirming that intact autophagy is necessary for eNOS signaling. In endothelial cells from diabetics, activation of autophagy with spermidine restored eNOS activation, suggesting that impaired autophagy contributes to endothelial dysfunction (P = 0.01). Indicators of autophagy initiation including the number of LC3-bound puncta and beclin 1 expression were similar in diabetics and controls, whereas an autophagy terminal phase indicator, the lysosomal protein Lamp2a, was higher in diabetics. In endothelial cells under diabetic conditions, the beneficial effect of spermidine on eNOS activation was blocked by autophagy inhibitors bafilomycin or 3-methyladenine. Blocking the terminal stage of autophagy with bafilomycin increased p62 (P = 0.01) in cells from diabetics to a lesser extent than in cells from controls (P = 0.04), suggesting ongoing, but inadequate autophagic clearance. CONCLUSION: Inadequate autophagy contributes to endothelial dysfunction in patients with diabetes and may be a target for therapy of diabetic vascular disease.

Intravenous Lipid Infusion Induces Endoplasmic Reticulum Stress in Endothelial Cells and Blood Mononuclear Cells of Healthy Adults.

BACKGROUND: Endoplasmic reticulum (ER) stress and the subsequent unfolded protein response may initially be protective, but when prolonged, have been implicated in atherogenesis in diabetic conditions. Triglycerides and free fatty acids (FFAs) are elevated in patients with diabetes and may contribute to ER stress. We sought to evaluate the effect of acute FFA elevation on ER stress in endothelial and circulating white cells. METHODS AND RESULTS: Twenty-one healthy subjects were treated with intralipid (20%; 45 mL/h) plus heparin (12 U/kg/h) infusion for 5 hours. Along with increased triglyceride and FFA levels, intralipid/heparin infusion reduced the calf reactive hyperemic response without a change in conduit artery flow-mediated dilation consistent with microvascular dysfunction. To investigate the short-term effects of elevated triglycerides and FFA, we measured markers of ER stress in peripheral blood mononuclear cells (PBMCs) and vascular endothelial cells (VECs). In VECs, activating transcription factor 6 (ATF6) and phospho-inositol requiring kinase 1 (pIRE1) proteins were elevated after infusion (both P<0.05). In PBMCs, ATF6 and spliced X-box-binding protein 1 (XBP-1) gene expression increased by 2.0- and 2.5-fold, respectively (both P<0.05), whereas CHOP and GADD34 decreased by ≈67% and 74%, respectively (both P<0.01). ATF6 and pIRE1 protein levels also increased (both P<0.05), and confocal microscopy revealed the nuclear localization of ATF6 after infusion, suggesting activation. CONCLUSIONS: Along with microvascular dysfunction, intralipid infusion induced an early protective ER stress response evidenced by activation of ATF6 and IRE1 in both leukocytes and endothelial cells. Our results suggest a potential link between metabolic disturbances and ER stress that may be relevant to vascular disease.

Endothelial Dysfunction in Human Diabetes Is Mediated by Wnt5a-JNK Signaling.

OBJECTIVE: Endothelial dysfunction is linked to insulin resistance, inflammatory activation, and increased cardiovascular risk in diabetes mellitus; however, the mechanisms remain incompletely understood. Recent studies have identified proinflammatory signaling of wingless-type family member (Wnt) 5a through c-jun N-terminal kinase (JNK) as a regulator of metabolic dysfunction with potential relevance to vascular function. We sought to gain evidence that increased activation of Wnt5a-JNK signaling contributes to impaired endothelial function in patients with diabetes mellitus. APPROACH AND RESULTS: We measured flow-mediated dilation of the brachial artery and characterized freshly isolated endothelial cells by protein expression, eNOS activation, and nitric oxide production in 85 subjects with type 2 diabetes mellitus (n=42) and age- and sex-matched nondiabetic controls (n=43) and in human aortic endothelial cells treated with Wnt5a. Endothelial cells from patients with diabetes mellitus displayed 1.3-fold higher Wnt5a levels (P=0.01) along with 1.4-fold higher JNK activation (P<0.01) without a difference in total JNK levels. Higher JNK activation was associated with lower flow-mediated dilation, consistent with endothelial dysfunction (r=0.53, P=0.02). Inhibition of Wnt5a and JNK signaling restored insulin and A23187-mediated eNOS activation and improved nitric oxide production in endothelial cells from patients with diabetes mellitus. In endothelial cells from nondiabetic controls, rWnt5a treatment inhibited eNOS activation replicating the diabetic endothelial phenotype. In human aortic endothelial cells, Wnt5a-induced impairment of eNOS activation and nitric oxide production was reversed by Wnt5a and JNK inhibition. CONCLUSIONS: Our findings demonstrate that noncanonical Wnt5a signaling and JNK activity contribute to vascular insulin resistance and endothelial dysfunction and may represent a novel therapeutic opportunity to protect the vasculature in patients with diabetes mellitus.