N-glycosylation of the SARS-CoV-2 spike protein at Asn331 and Asn343 is involved in spike-ACE2 binding, virus entry, and regulation of IL-6.

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global public health crisis. The causative agent, the SARS-CoV-2 virus, enters host cells via molecular interactions between the viral spike protein and the host cell ACE2 surface protein. The SARS-CoV-2 spike protein is extensively decorated with up to 66 N-linked glycans. Glycosylation of viral proteins is known to function in immune evasion strategies but may also function in the molecular events of viral entry into host cells. Here, we show that N-glycosylation at Asn331 and Asn343 of SARS-CoV-2 spike protein is required for it to bind to ACE2 and for the entry of pseudovirus harboring the SARS-CoV-2 spike protein into cells. Interestingly, high-content glycan binding screening data have shown that N-glycosylation of Asn331 and Asn343 of the RBD is important for binding to the specific glycan molecule G4GN (Galß-1,4 GlcNAc), which is critical for spike-RBD-ACE2 binding. Furthermore, IL-6 was identified through antibody array analysis of conditioned media of the corresponding pseudovirus assay. Mutation of N-glycosylation of Asn331 and Asn343 sites of the spike receptor-binding domain (RBD) significantly reduced the transcriptional upregulation of pro-inflammatory signaling molecule IL-6. In addition, IL-6 levels correlated with spike protein levels in COVID-19 patients' serum. These findings establish the importance of RBD glycosylation in SARS-CoV-2 pathogenesis, which can be exploited for the development of novel therapeutics for COVID-19.

Interleukin-11 (IL11) inhibits myogenic differentiation of C2C12 cells through activation of extracellular signal-regulated kinase (ERK).

Cancer-associated cachexia (CAC) is a multifactorial wasting syndrome characterized by loss of skeletal muscle. Interleukin-11 (IL11), one of the IL6 family cytokines, is highly expressed in various types of cancer including cancers frequently associated with cachexia. However, the impact of IL11 on muscle metabolism remains to be determined. Since one of the mechanisms of muscle wasting in cachexia is defective muscle regeneration due to impaired myogenic differentiation, we examined the effect of IL11 on the differentiation of C2C12 mouse myoblasts. Treatment of C2C12 cells with recombinant mouse IL11 resulted in decreased myotube formation. In addition, IL11 treatment reduced the protein and mRNA levels of myosin heavy chain (MHC), a marker of myogenic differentiation. Moreover, the levels of myogenic regulatory factors including myogenin and Mrf4 were significantly reduced by IL11 treatment. IL11 treatment increased the number of BrdU-positive cells and the level of phosphorylated retinoblastoma (Rb) protein, while the levels of p21Waf1 and p27Kip1 were reduced by IL11 treatment in differentiating C2C12 cells, suggesting that IL11 interferes with cell cycle exit during the early stages of myogenic differentiation. Consistent with this, IL11 treatment at the late stage of differentiation did not affect myotube formation and MHC expression. IL11 treatment resulted in an activation of ERK, STAT3, and AKT in differentiating C2C12 cells. However, only ERK inhibitors including PD98059 and U0126 were able to ameliorate the suppressive effect of IL11 on the expression of MHC and myogenin. Additionally, pretreatment with PD98059 and U0126 resulted in improved myotube formation and reduced BrdU staining in IL11-treated cells. Together, our results suggest that IL11 inhibits myogenic differentiation through delayed cell cycle exit in an ERK-dependent manner. To our knowledge, this study is the first to demonstrate an inhibitory role of IL11 in myogenic differentiation and identifies the previously unrecognized role of IL11 as a possible mediator of CAC.

Creating a Natural Vascular Scaffold by Photochemical Treatment of the Extracellular Matrix for Vascular Applications.

The development of bioscaffolds for cardiovascular medical applications, such as peripheral artery disease (PAD), remains to be a challenge for tissue engineering. PAD is an increasingly common and serious cardiovascular illness characterized by progressive atherosclerotic stenosis, resulting in decreased blood perfusion to the lower extremities. Percutaneous transluminal angioplasty and stent placement are routinely performed on these patients with suboptimal outcomes. Natural Vascular Scaffolding (NVS) is a novel treatment in the development for PAD, which offers an alternative to stenting by building on the natural structural constituents in the extracellular matrix (ECM) of the blood vessel wall. During NVS treatment, blood vessels are exposed to a photoactivatable small molecule (10-8-10 Dimer) delivered locally to the vessel wall via an angioplasty balloon. When activated with 450 nm wavelength light, this therapy induces the formation of covalent protein-protein crosslinks of the ECM proteins by a photochemical mechanism, creating a natural scaffold. This therapy has the potential to reduce the need for stent placement by maintaining a larger diameter post-angioplasty and minimizing elastic recoil. Experiments were conducted to elucidate the mechanism of action of NVS, including the molecular mechanism of light activation and the impact of NVS on the ECM.

Retained Functionality of Atherosclerotic Human Arteries Following Photoactivated Linking of the Extracellular Matrix by Natural Vascular Scaffolding Treatment.

In this study, we investigated natural vascular scaffolding (NVS) treatment on vascular functionality using freshly isolated human popliteal arteries in vitro. Arteries were exposed to intraluminal NVS treatment consisting of a compound (4 amino-1,8-naphthalimide) photoactivated by a 450-nm light-emitting light fiber placed inside the artery. This procedure results in covalent linking between the extracellular matrix proteins to achieve a larger vessel diameter post-angioplasty and minimizing elastic recoil. Immediately following NVS treatment, rings were cut from the treated arteries and mounted in organ baths for contractility testing in response to U46619 and sodium nitroprusside. We also investigated the effect of NVS treatment on IL-6 cytokine release from vascular rings following a 4-h organoculture post-NVS treatment. Based on our results, we conclude that exposure of the vessels to NVS treatment does not adversely affect the contractile responsiveness of the vascular smooth muscle and exerts no pro-inflammatory effect. Graphical abstract.

Adverse Outcomes Associated With Inpatient Administration of Beers List Medications Following Total Knee Replacement.

PURPOSE: Beers List drugs are potentially harmful in older adults and are grouped by level of risk. Over 9000 total knee arthroplasties (TKAs) are performed each year Veterans Affairs (VA) hospitals, primarily on older adults. Minimal data on the administration of Beers List drugs following arthroplasty currently exists in the literature. Our goal was to quantify the risks of these drugs following TKA. We hypothesized that increasing doses of Beers List drugs would be associated with increased risks for readmission, reoperation, emergency department (ED) visits, and mortality. METHODS: In this retrospective cohort study, data from TKAs performed in VA hospitals from 2010 to 2014 were examined, with complicated or bilateral procedures excluded. The data were obtained from the VA Corporate Data Warehouse. The outcomes examined were readmission, postoperative ED visits, reoperation on ipsilateral knee, and mortality. Beers List drugs were divided into 3 categories: medications to use with caution (Beers 0); medications to avoid in older adults (Beers 1); and medications to avoid in certain disease states (Beers 2). Beers 2 was not included in the final analysis due to an inability to verify appropriate diagnostic criteria without manual chart review. Logistic regression was performed looking at the total number of doses in the first 48 h after surgery compared to the above-mentioned outcomes. FINDINGS: Data from 12,639 TKAs were analyzed; the mean age of the patients was 65.06 years, and 77.8% of patients received Beers List drugs while admitted. The most frequently administered Beers List drugs were proton pump inhibitors, NSAIDs, insulin, α-blockers, benzodiazepines, antihistamines, muscle relaxants, and antipsychotics. There was a dose-dependent increase in readmission and ED visits in the Beers 1 group. The odds ratios were 1.03 for 30-day readmission and 1.02 at 90 days. The odds ratios for ED visits were 1.05 for 72-h ED visits and 1.04 for ED visits within 7 and 30 days. The odds ratios were set at 1-unit dose intervals. All results were found after control for VA facility, sex, age, American Society of Anesthesiologists class, Charlson score, case length, and body mass index. IMPLICATIONS: The group of medications to avoid (Beers 1) from the 2015 Beers List showed associations with increased frequency of readmission and postoperative ED visits. Reinforcement of the need to avoid those drugs during surgical care will hopefully reduce such complications. Limitations included not controlling for overall discharge drug count and reliance on the outpatient problem list for outpatient diagnoses. Additional subgroup analysis will be performed to see whether specific drugs pose a higher than risk others.

Trends and Perioperative Outcomes Across Major Benign Prostatic Hyperplasia Procedures from the ACS-NSQIP 2011-2015.

BACKGROUND AND PURPOSE: There are currently several different surgical options for patients with benign prostatic hyperplasia (BPH). The literature has demonstrated equivalent or superior results for holmium laser enucleation of prostate (HoLEP) but with exceptional long-term durability compared to other minimally invasive options. Despite this, HoLEP is not widely practiced. Herein, we investigate trends and outcomes from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) to support a need for further adoption of HoLEP. METHODS: Using ACS-NSQIP data from 2011 to 2015, trends, baseline characteristics, and perioperative outcomes were collected for major BPH procedures: transurethral resection of prostate (TURP), TURP for regrowth, photovaporization of prostate (PVP), HoLEP, and simple prostatectomy. RESULTS: The most common procedure performed every year was TURP with PVP performed about half as often, while HoLEP (4%-5%) was performed about as infrequently as simple prostatectomy (3%). More African American men underwent simple prostatectomy except in 2011. International normalized ratio (INR) was highest every year for PVP. Hospital stay and transfusion rates were lowest with PVP and HoLEP. Transfusion rates for simple prostatectomy were high (16.0%-25.4%). Lower rates of readmission, reoperation, and urinary tract infection were seen in some years with HoLEP. CONCLUSIONS: Given the previously reported favorable outcomes and long-term durability of HoLEP, these ACS-NSQIP data further support that HoLEP should be more often practiced for patients undergoing surgery for BPH.

Initial Experience with Narcotic-Free Ureteroscopy: A Feasibility Analysis.

BACKGROUND AND PURPOSE: In the United States, there is an opioid abuse epidemic fueled by prescription medications. Concerns that uncontrolled pain after surgical procedures will result in poor patient satisfaction and increased workload for ancillary staff are potential factors that influence provider prescription habits. Currently, there is a paucity of literature on analgesic requirements after ureteroscopy (URS) for nephrolithiasis. Our study objective was to evaluate the safety of narcotic-free ureteroscopy (nf-URS) and assess its impact on provider workload. METHODS: We performed a retrospective chart review of 104 patients, between October 2017 and May 2018, who underwent URS and who required a stent postprocedure. Starting February 2018, patients without absolute contraindication or allergies to nonsteroidal anti-inflammatory drugs received a prescription for diclofenac instead of hydrocodone or oxycodone. Postoperative phone calls to nurses and residents, emergency room visits, and prescription monitoring reports were evaluated for all patients, and compared between the nf-URS and the standard ureteroscopy (s-URS). RESULTS: There were 52 nf-URS and 52 s-URS procedures. In the postoperative period, 9 (17%) nf-URS and 10 (19%) s-URS patients called with postoperative pain issues. Five (10%) nf-URS vs 9 (17%) s-URS patients obtained narcotics after seeking additional medical care after URS because of inadequate pain control. There were no postoperative complications in our cohort. Compared with s-URS, 6871.5 mg less of morphine equivalent dosage (1375 hydrocodone tablets) was administered to nf-URS patients immediately after surgery. CONCLUSIONS: Attempts to reduce the number of narcotic prescriptions are paramount in the fight against narcotic addiction in the United States. Although our initial cohort is small, this feasibility study provides compelling evidence that nf-URS is a safe and effective practice. Furthermore, nf-URS resulted in a dramatic decrease in the number of narcotics circulating in the community.

Extended Duration Enoxaparin Decreases the Rate of Venous Thromboembolic Events after Radical Cystectomy Compared to Inpatient Only Subcutaneous Heparin.

PURPOSE: Venous thromboembolic events are a significant source of morbidity after radical cystectomy. At our institution subcutaneous heparin was historically given to patients undergoing radical cystectomy immediately before incision and throughout the inpatient stay. In an effort to decrease the overall rate of venous thromboembolism and post-discharge venous thromboembolism, a regimen including extended duration enoxaparin was initiated for patients undergoing radical cystectomy. MATERIALS AND METHODS: In January 2013 thromboprophylaxis was modified for patients undergoing radical cystectomy by replacing a regimen of subcutaneous heparin before induction and then every 8 hours until discharge home with enoxaparin daily for postoperative prophylaxis continued until 28 days after discharge. Data from our institutional radical cystectomy database for patients undergoing surgery from January 2011 to May 2014 were reviewed. The primary outcome was clinically symptomatic postoperative venous thromboembolism. Secondary outcomes included timing of venous thromboembolism and blood transfusions. Multivariate logistic regression was used to control for differences between cohorts. RESULTS: Of the 402 patients 234 underwent radical cystectomy before the change and 168 after. The enoxaparin regimen decreased the rate of venous thromboembolism (12% vs 5%, p=0.024) with the main benefit on post-discharge venous thromboembolism (6% vs 2%, p=0.039). Overall 17 of 37 (46%) venous thromboembolisms occurred after discharge home. Multivariate analysis confirmed that the enoxaparin regimen was independently associated with reduced odds of venous thromboembolism (OR 0.33, 95% CI 0.14-0.76, p=0.009). Intraoperative and postoperative transfusion rates were similar between cohorts. CONCLUSIONS: Thromboprophylaxis with extended duration enoxaparin decreased the rate of venous thromboembolism after radical cystectomy compared to inpatient only subcutaneous heparin with no increased risk of bleeding.

Extraprostatic Extension Is Extremely Rare for Contemporary Gleason Score 6 Prostate Cancer.

BACKGROUND: A significant proportion of men with Gleason score 6 (GS6) prostate cancer undergo treatment with radiation or surgery. OBJECTIVE: To assess pathologic stage of pure GS6 at radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: In the period 2003-2014, 7817 patients underwent RP at two institutions. Of 2502 patients with GS6 at surgery, 60 were identified as stage pT3a-b on initial pathologic review, 55 with pT3a (extraprostatic extension, EPE), and five with pT3b (seminal vesicle invasion; SVI). All cases of GS6 with pT3 disease underwent contemporary pathologic evaluation for Gleason grade, stage, and extent of EPE. At one institution, all GS≥7 pT3b cases were re-reviewed for downgrading. The 2014 International Society of Urological Pathology (ISUP) Gleason grading criteria and 2009 ISUP recommendations on pT3 staging were applied. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Calculated incidence (%) of pT3a, pT3b, pT4, and lymph node-positive disease. RESULTS AND LIMITATIONS: Of the 60 GS6 pT3a-b cases identified in the period 2003-2014, seven (0.28% of entire GS6 cohort) with GS6 and pT3a were identified after re-review, all focal EPE. Among the re-examined cohort, no cases of GS6 with pT3b were observed. None of the 132 GS≥7 pT3b cases were downgraded to GS6. Limitations include partial embedding of specimens and separate pathologic review at each institution. CONCLUSIONS: In a large prostatectomy cohort, GS6 never had seminal vesicle invasion (0%) and was very rarely (0.28%) associated with extraprostatic extension. PATIENT SUMMARY: GS6 prostate cancer rarely spreads outside the prostate. A new finding in this study was that GS6 prostate cancer never spread to the seminal vesicles.

Megacystis microcolon intestinal hypoperistalsis syndrome: Case series and updated review of the literature with an emphasis on urologic management.

INTRODUCTION: Megacystis microcolon intestinal hypoperistalsis (MMIHS) is a rare disorder characterized by distended nonobstructed bladder, microcolon, and decreased intestinal peristalsis. MMIHS has a particularly poor prognosis; however, when appropriately managed, survival can be prolonged. STUDY DESIGN: A systematic review (1996-2016) was performed with the key words "megacystis microcolon intestinal hypoperistalsis syndrome." In addition, a case series of four patients is presented as well as algorithms for the diagnosis and treatment of MMIHS. RESULTS: 135 patients with MMIHS were identified in the literature. 73% (88/121) of the patients were female, 65% underwent diagnostic biopsy (64/99), and 63% (66/106) were identified with prenatal imaging. The majority of patients were treated with TPN as well as gastrostomy or ileostomy and CIC, however 15% (18/116) received multivisceral or intestinal transplant, and 30% (22/73) had a vesicostomy. The survival rate was 57% (68/121). CONCLUSION: Appropriate management of MMIHS patients is crucial. An enlarged, acontractile bladder in a child with bowel motility problems should be considered diagnostic. Bladder distension can be managed with CIC or vesicostomy in addition to prophylactic antibiotics if frequent urinary tract infections are present. These patients often require gastrostomy or ileostomy as well as total parenteral nutrition. This management has led to significant improvement in survival rates.

Prognostic Significance of Percentage and Architectural Types of Contemporary Gleason Pattern 4 Prostate Cancer in Radical Prostatectomy.

The International Society of Urological Pathology (ISUP) 2014 consensus meeting recommended a novel grade grouping for prostate cancer that included dividing Gleason score (GS) 7 into grade groups 2 (GS 3+4) and 3 (GS 4+3). This division of GS 7, essentially determined by the percent of Gleason pattern (GP) 4 (< or >50%), raises the question of whether a more exact quantification of the percent GP 4 within GS 7 will yield additional prognostic information. Modifications were also made by ISUP regarding the definition of GP 4, now including 4 main architectural types: cribriform, glomeruloid, poorly formed, and fused glands. This study was conducted to analyze the prognostic significance of the percent GP 4 and main architectural types of GP 4 according to the 2014 ISUP grading criteria in radical prostatectomies (RPs). The cohort included 585 RP cases of GS 6 (40.2%), 3+4 (49.0%), and 4+3 (10.8%) prostate cancers. Significantly different 5-year biochemical recurrence (BCR)-free survival rates were observed among GS 6 (99%, 95% confidence interval [CI]: 97%-100%), 3+4 (81%, 95% CI: 76%-86%), and 4+3 (60%, 95% CI: 45%-71%) cancers (P<0.01). Dividing the GP 4 percent into quartiles showed a 5-year BCR-free survival of 84% (95% CI: 78%-89%) for 1% to 20%, 74% (95% CI: 62%-83%) for 21% to 50%, 66% (95% CI: 50%-78%) for 51% to 70%, and 32% (95% CI: 9%-59%) for >70% (P<0.001). Among the GP 4 architectures, cribriform was the most prevalent (43.7%), and combination of architectures with cribriform present was more frequently observed in GS 4+3 (60.3%). Glomeruloid was mostly (67.1%) seen combined with other GP 4 architectures. Unlike the other GP 4 architectures, glomeruloid as the sole GP 4 was observed only as a secondary pattern (ie, 3+4). Among patients with GS 7 cancer, the presence of cribriform architecture was associated with decreased 5-year BCR-free survival when compared with GS 7 cancers without this architecture (68% vs. 85%, P<0.01), whereas the presence of glomeruloid architecture was associated with improved 5-year BCR-free survival when compared with GS 7 cancers without this architecture (87% vs. 75%, P=0.01). However, GS 7 disease having only the glomeruloid architecture had significantly lower 5-year BCR-free survival than GS 6 cancers (86% vs. 99%, P<0.01). Multivariable Cox proportional hazards regression model for factors associated with BCR among GS 7 cancers identified age (hazard ratio [HR] 0.95, P<0.01), preoperative prostate-specific antigen (HR 1.07, P<0.01), positive surgical margin (HR 2.70, P<0.01), percent of GP 4 (21% to 50% [HR 2.21], 51% to 70% [HR 2.59], >70% [HR 6.57], all P<0.01), presence of cribriform glands (HR 1.78, P=0.02), and presence of glomeruloid glands (HR 0.43, P=0.03) as independent predictors. In conclusion, our study shows that increments in percent of GP 4 correlate with increased risk for BCR supporting the ISUP recommendation of recording the percent of GP 4 in GS 7 prostate cancers at RP. However, additional larger studies are needed to establish the optimal interval for reporting percent GP 4 in GS 7 cancers. Among the GP 4 architectures, cribriform independently predicts BCR, whereas glomeruloid reduces the risk of BCR. Distinction should be made between cribriform and glomeruloid architectures, despite glomeruloid being considered as an early stage of cribriform, as cribriform confers a higher risk for poorer outcome.

A multi-institutional study of perioperative and functional outcomes for pediatric robotic-assisted laparoscopic Mitrofanoff appendicovesicostomy.

BACKGROUND: Robotic techniques are increasingly being used for reconstructive procedures in the pediatric population. OBJECTIVE: The present study reported the functional and perioperative outcomes of a multi-institutional cohort of pediatric patients who underwent robotic-assisted laparoscopic Mitrofanoff appendicovesicostomy (RALMA). STUDY DESIGN: Pediatric patients who underwent RALMA at five different centers were included. Positioning is shown (Summary Figure). Demographics were gathered, and intraoperative parameters included concomitant procedures, detrusor tunnel length, estimated blood loss (EBL) and operative time. Perioperative outcomes included length of hospital stay (LOS), morphine use and 30-day complications. Outcomes were reported in terms of stomal continence and surgical revisions. RESULTS: Eighty-eight patients with a mean age of 10.4 ± 4.0 years were included in the analysis. Median follow-up was 29.5 months (IQR 11.8-45.0). Bladder augmentation was performed concomitantly in 15 (17%) patients, and bladder neck procedures in 34 (39%). Mean detrusor tunnel length was 3.9 ± 1.0 cm, EBL was 54 ± 70 ml, and operative time was 424 ± 120 min. Postoperatively, mean LOS was 5.2 ± 2.8 days. Patients who underwent concomitant augmentation had higher EBL and operative times (both P < 0.05). At 90 days, complications occurred in 26 patients (29.5%) with six Clavien grade ≥3 (6.8%). During follow-up, 11 (12.5%) patients required appendicovesicostomy revision. Regarding functional outcomes, 75 (85.2%) patients were initially continent. After additional procedures, 81 (92.0%) patients were continent at last follow-up. DISCUSSION: Compared to previous open series, initial stomal continence rates with RALMA were acceptable, with a minority of patients requiring subsequent procedures to manage complications and achieve continence. CONCLUSION: RALMA is safe and effective in a pediatric population with regard to perioperative complications and stomal continence.

The effect of broader, directed antimicrobial prophylaxis including fungal coverage on perioperative infectious complications after radical cystectomy.

OBJECTIVES: Radical cystectomy (RC) with urinary diversion has a significant risk of infection. In an effort to decrease the rate of infectious complications, we instituted a broader, culture-based preoperative antimicrobial regimen, including fungal coverage, and studied its effect on infectious complications after RC. MATERIALS AND METHODS: In May 2013, antimicrobial prophylaxis for RC was changed at our institution after review of previous positive cultures. Ampicillin-sulbactam 3g, gentamicin 4mg/kg, and fluconazole 400mg replaced cefoxitin. Patients undergoing RC from May 2011 to May 2014 were included. Before and after implementation of the new regimen, 30-day infectious complications (positive blood culture, urinary tract infection, wound infection, abscess, and pneumonia) and adverse events (Clostridium difficile, readmission, and mortality) were compared. Multivariate logistic regression was used to identify independent risk factors for infection while controlling for covariates. RESULTS: In total, 386 patients were studied (258 before the change and 128 after). The overall infection rate decreased with the new regimen (41% vs. 30%, P = 0.043) with improvements in wound (14% vs. 6%, P = 0.025) and fungal (10% vs. 3%, P = 0.021) infections. Median length of stay decreased from 8 (interquartile range [IQR]: 7-12) to 7 (IQR: 7-10) days (P = 0.008). On multivariate analysis, the new regimen decreased the risk of infections (odds ratio [OR] = 0.58, 95% CI [0.35-0.99], P = 0.044) whereas body mass index, operating room time, smoking, and total parenteral nutrition increased the risk (all P< 0.05). CONCLUSIONS: Risk factors for infection after RC include body mass index, operating room time, smoking, and total parenteral nutrition use. Changing from cefoxitin to broader, culture-directed antimicrobial prophylaxis, based on institutional data to include antifungal coverage, decreased postoperative infections.

The impact of days off between cases on perioperative outcomes for robotic-assisted laparoscopic prostatectomy.

PURPOSE: To examine the effect of days off between cases on perioperative outcomes for robotic-assisted laparoscopic prostatectomy (RALP). METHODS: We analyzed a single-surgeon series of 2036 RALP cases between 2003 and 2014. Days between cases (DBC) was calculated as the number of days elapsed since the surgeon's previous RALP with the second start cases assigned 0 DBC. Surgeon experience was assessed by dividing sequential case experience into cases 0-99, cases 100-249, cases 250-999, and cases 1000+ based on previously reported learning curve data for RALP. Outcomes included estimated blood loss (EBL), operative time (OT), and positive surgical margins (PSMs). Multiple linear regression was used to assess the impact of the DBC and surgeon experience on EBL, OT, and PSM, while controlling for patient characteristics, surgical technique, and pathologic variables. RESULTS: Overall median DBC was 1 day (0-3) and declined with increasing surgeon case experience. Multiple linear regression demonstrated that each additional DBC was independently associated with increased EBL [ß = 3.7, 95% CI (1.3-6.2), p < 0.01] and OT [ß = 2.3 (1.4-3.2), p < 0.01], but was not associated with rate of PSM [ß = 0.004 (-0.003-0.010), p = 0.2]. Increased experience was also associated with reductions in EBL and OT (p < 0.01). Surgeon experience of 1000+ cases was associated with a 10% reduction in PSM rate (p = 0.03) compared to cases 0-99. CONCLUSIONS: In a large single-surgeon RALP series, DBC was associated with increased blood loss and operative time, but not associated with positive surgical margins, when controlling for surgeon experience.

Prospective Lymphedema Surveillance in a Clinic Setting.

The potential impact of breast cancer-related lymphedema (LE) is quite extensive, yet it often remains under-diagnosed until the later stages. This project examines the effectiveness of prospective surveillance in post-surgical breast cancer patients. A retrospective analysis of 49 out of 100 patients enrolled in a longitudinal prospective study at a Midwestern breast center evaluates: (1) time required for completion of bilateral limb measurements and Lymphedema Breast Cancer Questionnaire (LBCQ); (2) referral to LE management with limb volume increase (LVI) and/or LBCQ symptoms; and (3) cost of LE management at lower LVI (≥5%-≤10%) versus traditional (≥10%). Findings revealed a visit timeframe mean of 40.3 min (range = 25-60); 43.6% of visits were ≤30-min timeframe. Visit and measurement times decreased as clinic staff gained measurement experience; measurement time mean was 17.9 min (range = 16.9-18.9). LBCQ symptoms and LVI were significantly (p < 0.001) correlated to LE referral; six of the nine patients referred (67%) displayed both LBCQ symptoms/LVI. Visits with no symptoms reported did not result in referral, demonstrating the importance of using both indicators when assessing early LE. Lower threshold referral provides compelling evidence of potential cost savings over traditional threshold referral with reported costs of: $3755.00 and $6353.00, respectively (40.9% savings).

Rhabdomyolysis After Major Urologic Surgery: Epidemiology, Risk Factors, and Outcomes.

OBJECTIVE: To study the epidemiology, risk factors, and outcomes of rhabdomyolysis (RM) after major urologic surgery. MATERIALS AND METHODS: The National Inpatient Sample (2003-2011) was used to identify patients who underwent radical prostatectomy, radical or partial nephrectomy, or radical cystectomy. Demographics included age, sex, race, and comorbidities. Factors examined included bleeding, hospital teaching status, minimally invasive technique, and development of RM. Multivariate logistic regression was used to identify independent risk factors of RM. Outcomes of mortality, acute kidney injury (AKI), length of stay, and charges in patients with RM were compared with those of controls. RESULTS: A weighted population of 1,016,074 patients was identified with 870 (0.1%) developing RM, which was significantly more likely for radical or partial nephrectomy and radical cystectomy patients compared with radical prostatectomy patients. On multivariate analysis, independent risk factors for RM included younger age, male sex, diabetes, chronic kidney disease, obesity, and bleeding. Race, minimally invasive technique, and teaching status were not associated with RM when controlling for other factors. Patients with RM experienced increases in mortality, AKI, length of stay, and hospital charges. CONCLUSION: Rhabdomyolysis is a rare complication after urologic surgery. Risk factors include male sex, younger age, diabetes, chronic kidney disease, obesity, and perioperative bleeding. Patients who develop RM have a higher risk of AKI, mortality, prolonged hospital stay, and increased charges.

Comparison of Patients Undergoing PVP Versus TURP for LUTS/BPH.

Transurethral resection of the prostate (TURP) and photoselective vaporization of the prostate (PVP) are currently the two most commonly performed procedures for the treatment of benign prostatic hyperplasia (BPH). While each procedure has been shown to be efficacious, TURP or PVP may be preferred in certain clinical scenarios. A number of factors may influence the choice of which patients undergo PVP or TURP. This decision may take into account patient characteristics, such as age, co-morbidities, predominance of irritative symptoms, and/or ongoing anticoagulation. Additionally, balancing desired outcomes with possible risks is critical. Considerations should include possible effects on sexual function, rates of reoperation, cost, and need for tissue specimen in those at risk for prostate cancer. The primary objective of this article is to summarize the comparative research of PVP and TURP and the implications on differences between patients who undergo either procedure.

The robotic appendicovesicostomy and bladder augmentation: the next frontier in robotics, are we there?

There is growing interest in applying robotic-assisted laparoscopic techniques to complex reconstructive pelvic surgery owing to inherent benefits of precision, tissue handling, and articulating instruments for suturing. This review examines preliminary experiences with robotic-assisted laparoscopic augmentation ileocystoplasty and Mitrofanoff appendicovesicostomy (RALIMA) as either an isolated or combined procedure. These series suggest RALIMA is feasible, with the benefit of early recovery and improved cosmetic results in selected patients. The robotic approach incurs functional outcomes and complication rates similar to those of open techniques. Given the steep learning curve, only surgeons with extensive robotic experience are currently adopting this technique.

Outcomes of infants undergoing robot-assisted laparoscopic pyeloplasty compared to open repair.

PURPOSE: Robotic surgery has evolved from simple extirpative surgery to complex reconstructions even in infants. Data are lacking comparing surgical and direct costs to open approaches. We describe the feasibility, salient tips and outcomes of robot-assisted laparoscopic pyeloplasty compared to an open approach. MATERIALS AND METHODS: We evaluated patients undergoing open pyeloplasty or robot-assisted laparoscopic pyeloplasty. Ten patients in each group met inclusion criteria. RESULTS: Mean patient age was 3.31 months in the open group and 7.3 months in the robotic group (p=0.02). Postoperative outcomes including length of stay (2.2 vs 2.1 days), estimated blood loss (6.5 vs 7.6 ml), days to regular diet (1 vs 1.1) and days to Foley catheter removal (1.3 vs 1.3) were similar between the open and robotic groups. Total operating time (199 vs 242 minutes) was significantly longer in the robotic group. Postoperative improvement in hydronephrosis was identical in both groups. Direct costs, excluding amortization, robotic cost, maintenance and depreciation, were $4,410 in the open group and $4,979 in the robotic group (p=0.10). CONCLUSIONS: In our preliminary experience robotic pyeloplasty in infants is feasible and safe. The immediate outcomes are similar to those of an open approach. The robotic technique in infants currently has the benefits of improved esthetic appearance, improved pain control and similar direct costs compared to the traditional open approach.

Long term prostate-specific antigen trends following subcapsular prostatectomy.

INTRODUCTION: The purpose of this study was to evaluate the utility of prostate-specific antigen (PSA) screening for prostate cancer after subcapsular prostatectomy. MATERIALS AND METHODS: Data from 41 consecutive patients who underwent subcapsular prostatectomy at a single institution over a 15 year period were collected retrospectively. Patients were categorized into benign and malignant groups based on a diagnosis of prostate cancer identified in the surgical specimen or during subsequent follow up. Collected data included patient age, preoperative and postoperative PSA values, prostate volume determined by surgical specimen weight, and pathologic diagnosis. Preoperative and postoperative PSA velocities were calculated for patients with adequate data and average values were compared to determine factors that were predictive of a confirmed prostate cancer diagnosis. RESULTS: Thirty-one patients had adequate PSA values and follow up and were included in the analysis. Six (19%) were ultimately diagnosed with prostate cancer and 25 (81%) were never diagnosed with prostate cancer. Postoperative PSA velocity was found to be significantly higher for patients in the malignant group (1.22 ± 1.32 ng/mL/yr) as compared to patients in the benign group (0.06 ± 0.15 ng/mL/yr) (p = 0.003). CONCLUSIONS: After subcapsular prostatectomy, patients with prostate cancer in the surgical specimen or who developed prostate cancer during long term follow up had elevated PSA velocity compared to patients who had no evidence of cancer in the surgical specimen or in follow up.