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Prcis: In a diverse database (All of Us), we report significant dose-response associations between alcohol use frequency and glaucoma, with alcohol use of 4 or more drinks per week associated with significantly increased odds of glaucoma., Purpose: Current evidence on the association between alcohol use and primary open angle glaucoma (POAG) is mixed. We utilize the diverse All of Us Research Program to further examine this relationship., Methods: This is a retrospective cohort study using the diverse All of Us Research Program, a nationwide effort by the United States National Institutes of Health to recruit those historically under-represented in biomedical research. Electronic health records and survey data from the All of Us program was analyzed. A randomized 1:4 case/control ratio was utilized for POAG patients and randomly selected control patients. Chi-Square, bivariable, and multivariable regression were utilized to examine the associations between alcohol use and POAG., Results: Of the 3876 POAG patients, 2015 (52%) were female, 1943 (50%) were White, 1152 (30%) were Black, 117 (3%) were Asian, and 584 (15%) were Hispanic. Alcohol use of 4 or more drinks per week was significantly higher in the glaucoma cohort relative to controls (15% vs. 12%, P<0.001). On bivariate analysis, diagnosed alcohol misuse was associated with higher odds of POAG [Odds Ratio (OR): 1.20, 95% Confidence Interval (CI): 1.17-1.23, P<0.001]. In multivariable regression, more frequent alcohol use was associated with higher odds of glaucoma; alcohol use with a frequency of 4 or more drinks per week was significantly associated with increased odds of glaucoma (OR: 1.22, 95% CI: 1.03-1.44, P=0.023). This dose-response relationship was also observed and more pronounced for female participants, where alcohol use frequency of monthly or less was already associated with increase odds of glaucoma (OR: 1.21, 95% CI: 1.002-1.46, P=0.048)., Conclusion: In the diverse All of Us database, there was a dose-response relationship between alcohol consumption and POAG risk, which was more pronounced in female participants. Overall, higher frequency of alcohol consumption was associated with increased risk of POAG; 4 or more drinks per week significantly was associated with higher glaucoma risk., Competing Interests: Conflict of Interest: Sally Baxter reports equipment support from Topcon and Optomed, and consulting/speaking fees from Topcon, outside of the submitted work. Robert N. Weinreb reports grants from National Eye Institute, National Institute of Minority Health and Health Disparities, and Research to Prevent Blindness (New York, NY); Consultant for AbbVie, Alcon, Allergan, Amydis, Balance,Editas, Eyenovia, Iantrek, Implandata, iSTAR Medical, Nicox, Santen, and Topcon; Patents licensed to Toromedes from UCSD and licensed to Carl Zeiss Meditec from UCSD; non-financial support (research instruments) from Carl Zeiss Meditec, Centervue, Optovue, Topcon, co-Founder -Toromedes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Mitosis in eukaryotes involves reorganization of the nuclear envelope (NE) and microtubule-organizing centres (MTOCs). In Plasmodium , the causative agent of malaria, male gametogenesis mitosis is exceptionally rapid and divergent. Within 8 minutes, the haploid male gametocyte genome undergoes three replication cycles (1N to 8N), while maintaining an intact NE. Axonemes assemble in the cytoplasm and connect to a bipartite MTOC-containing nuclear pole and cytoplasmic basal body, producing eight flagellated gametes. The mechanisms coordinating NE remodelling, MTOC dynamics, and flagellum assembly remain poorly understood. Here, we identify the SUN1-ALLAN complex as a novel mediator of NE remodelling and bipartite MTOC coordination during Plasmodium male gametogenesis. SUN1, a conserved NE protein, localizes to dynamic loops and focal points near nuclear spindle poles. ALLAN, a divergent Allantoicase-like protein, has a location like that of SUN1 at nuclear MTOCs. SUN1 and ALLAN form a unique complex, detected by live-cell imaging, ultrastructural expansion microscopy, and interactomics. Deletion of either SUN1 or ALLAN gene disrupts nuclear MTOC organization, leading to basal body mis-segregation, defective spindle assembly, and impaired kinetochore attachment, but axoneme formation remains intact. Ultrastructural analysis revealed nuclear and cytoplasmic MTOC miscoordination, producing aberrant flagellated gametes lacking nuclear material. Sun1 deletion also alters parasite lipid composition, underscoring its role in NE homeostasis. These defects block parasite development in the mosquito and transmission, highlighting the essential functions of this complex. This study reveals a bipartite MTOC and a highly divergent mechanism of NE remodelling during Plasmodium male gametogenesis. The SUN1-ALLAN complex is an unusual adaptation of the LINC complex, in absence of canonical KASH-domain proteins in Plasmodium , providing new insights into the evolution of closed mitosis and highlighting potential targets for blocking malaria transmission.

The environmental challenges the human malaria parasite, Plasmodium falciparum , faces during its progression into its various lifecycle stages warrant the use of effective and highly regulated access to chromatin for transcriptional regulation. Microrchidia (MORC) proteins have been implicated in DNA compaction and gene silencing across plant and animal kingdoms. Accumulating evidence has shed light on the role MORC protein plays as a transcriptional switch in apicomplexan parasites. In this study, using the CRISPR/Cas9 genome editing tool along with complementary molecular and genomics approaches, we demonstrate that Pf MORC not only modulates chromatin structure and heterochromatin formation throughout the parasite erythrocytic cycle, but is also essential to the parasite survival. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) experiments suggests that Pf MORC binds to not only sub-telomeric regions and genes involved in antigenic variation but may also play a role in modulating stage transition. Protein knockdown experiments followed by chromatin conformation capture (Hi-C) studies indicate that downregulation of Pf MORC impairs key histone marks and induces the collapse of the parasite heterochromatin structure leading to its death. All together these findings confirm that Pf MORC plays a crucial role in chromatin structure and gene regulation, validating this factor as a strong candidate for novel antimalarial strategies., Competing Interests: ZC, MG, TL, TH, SA, CB, AS, JP, SB, LF, KL No competing interests declared, (© 2023, Chahine, Gupta, Lenz et al.)

Purpose: A midline extraperitoneal approach for retroperitoneal lymph node dissection (EP-RPLND) has been associated with decreased morbidity compared to the transperitoneal approach. We aimed to review our 11-year experience in patients with germ cell tumors (GCTs) who underwent EP-RPLND at a single institution., Materials and Methods: All patients with GCT who underwent EP-RPLND between 2010 and 2021 were reviewed. Surgical, perioperative, and oncologic outcomes were reported. A logistic regression model was developed to evaluate variables predictive of early discharge. Oncologic outcomes included 2-year recurrence-free survival (RFS) and recurrence patterns, which were analyzed according to pathology., Results: Overall, 237 patients underwent EP-RPLND, of which 72% were administered in the postchemotherapy (PC) setting. Median follow-up was 16.7 months (interquartile range [IQR] 3.9-39.6). Median size of retroperitoneal disease was 2.8 cm (IQR 1.8-5.4), of which 16 cases were ≥ 10 cm. There were no cases of postoperative ileus or readmission due to small-bowel obstruction. Median hospital stay was 2 days (IQR 1-3). From 2020 to 2021, 74% of patients were discharged on postoperative day 1 and 89% by postoperative day 2. Thirty-one complications occurred, including 4% grade III to IV complications. In the primary setting, 2-year RFS for seminoma and nonseminomatous GCT was 0.93 (95% CI 0.84-1.00) and 0.85 (95% CI 0.72-1.00), respectively. In the PC setting, 2-year RFS for seminoma and nonseminomatous GCT was 0.88 (95% CI 0.74-1.00) and 0.88 (95% CI 0.81-0.95), respectively. Overall, only 7 patients had in-field recurrence., Conclusions: Midline EP-RPLND is safe and associated with rapid gastrointestinal recovery, short hospital stay, and low complication rates. It also demonstrates acceptable oncologic outcomes in the primary and PC settings, with low rates of in-field relapse.

The environmental challenges the human malaria parasite, Plasmodium falciparum , faces during its progression into its various lifecycle stages warrant the use of effective and highly regulated access to chromatin for transcriptional regulation. Microrchidia (MORC) proteins have been implicated in DNA compaction and gene silencing across plant and animal kingdoms. Accumulating evidence has shed light into the role MORC protein plays as a transcriptional switch in apicomplexan parasites. In this study, using CRISPR/Cas9 genome editing tool along with complementary molecular and genomics approaches, we demonstrate that Pf MORC not only modulates chromatin structure and heterochromatin formation throughout the parasite erythrocytic cycle, but is also essential to the parasite survival. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) experiments suggest that Pf MORC binds to not only sub-telomeric regions and genes involved in antigenic variation but may also play a role in modulating stage transition. Protein knockdown experiments followed by chromatin conformation capture (Hi-C) studies indicate that downregulation of Pf MORC impairs key histone marks and induces the collapse of the parasite heterochromatin structure leading to its death. All together these findings confirm that Pf MORC plays a crucial role in chromatin structure and gene regulation, validating this factor as a strong candidate for novel antimalarial strategies., Competing Interests: Declarations of Interest The authors declare no competing interests.

Purpose: We assessed the effect of prophylactic biologic mesh on parastomal hernia (PSH) development in patients undergoing cystectomy and ileal conduit (IC)., Materials and Methods: This phase 3, randomized, controlled trial (NCT02439060) included 146 patients who underwent cystectomy and IC at the University of Southern California between 2015 and 2021. Follow-ups were physical exam and CT every 4 to 6 months up to 2 years. Patients were randomized 1:1 to receive FlexHD prophylactic biological mesh using sublay intraperitoneal technique vs standard IC. The primary end point was time to radiological PSH, and secondary outcomes included clinical PSH with/without surgical intervention and mesh-related complications., Results: The 2 arms were similar in terms of baseline clinical features. All surgeries and mesh placements were performed without any intraoperative complications. Median operative time was 31 minutes longer in patients who received mesh, yet with no statistically significant difference (363 vs 332 minutes, P = .16). With a median follow-up of 24 months, radiological and clinical PSHs were detected in 37 (18 mesh recipients vs 19 controls) and 16 (8 subjects in both arms) patients, with a median time to radiological and clinical PSH of 8.3 and 15.5 months, respectively. No definite mesh-related adverse events were reported. Five patients (3 in the mesh and 2 in the control arm) required surgical PSH repair. Radiological PSH-free survival rates in the mesh and control groups were 74% vs 75% at 1 year and 69% vs 62% at 2 years., Conclusions: Implementation of biologic mesh at the time of IC construction is safe without significant protective effects within 2 years following surgery.

Background: Women's sexual health after radical cystectomy is an important but poorly understood aspect of bladder cancer survivorship. Dedicated investigation is needed to elucidate patient perceptions on sexual function and dysfunction in this setting., Aims: In this study we sought to qualitatively examine women's perceptions and experiences of sexual health following radical cystectomy for bladder cancer., Methods: We conducted one-on-one qualitative telephone interviews with 40 women who underwent radical cystectomy in the past 6 months to 5 years and signed a research consent form to be contacted for future studies. We examined women's experiences of engaging in sexual activity after surgery and their attitudes toward sex and body image. We audio recorded, transcribed, and coded the interviews using ATLAS.ti software and applied grounded theory methods for analysis., Outcomes: For data that emerged during the qualitative interviews that was related to lack of knowledge about how physical and psychological sexual health would be affected after surgery, we reviewed and discussed transcripts that enabled coding of the data into emerging topic areas., Results: Our analysis yielded 4 main themes. (1) Women reported receiving little to no information from providers about female sexual dysfunction prior to or after radical cystectomy. Women wished they had been provided more information about female sexual dysfunction from their clinicians, including strategies for postoperative self-pleasure and nonintercourse methods of sexual pleasure with partners. (2) Women shared that they were not sexually active following surgery due to physical and mental barriers. (3) When women did try to engage in sex, they described feeling disappointed that it did not feel the same as prior to surgery. (4) Some women found that physical therapy helped them to physically and mentally recover their strength to engage in sexual activity again., Clinical Implications: Clinicians must directly address sexual health concerns with patients who undergo radical cystectomy., Strengths and Limitations: This study has several key strengths. Investigation into women's sexual function and dysfunction addresses a gap in understanding of this component of women's health-related quality of life after radical cystectomy, which represents an unmet need. The large number of interviews conducted as well as the in-depth information obtained through one-on-one interviews are additional strengths. This study also has limitations, including possible shortcomings of telephone interviews compared with in-person interviews. However, telephone interviews were beneficial because the interviews took place during the COVID-19 pandemic and spared patients from extra visits or from having to travel long distances to the respective medical centers. Other possible limitations were that patients may have been reluctant to share all of their experiences and that patients who underwent urostomies, also termed ileal conduits, were overrepresented in this study compared with women who underwent continent urine diversions, which allow greater control over urine output., Conclusion: Broadening the understanding of sexual health beyond sexual intercourse to encompass sexuality and self-pleasure can provide clinicians, patients, and their families with more effective preparation and strategies to care for an essential aspect of their wellbeing., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Little is known about how families make decisions regarding postoperative prescription opioid consumption. This qualitative study examines adolescent and parent perspectives on postoperative prescription opioid use., Methods: We recruited adolescents aged 13-20 years old who received a postoperative opioid prescription and their parents from a previous longitudinal cohort study. We employed purposive sampling for recruitment to reflect local community sociodemographics including race/ethnicity, health literacy, and Spanish-language preference then conducted thematic analysis of focus group feedback., Results: Participants met in four virtual focus groups: adolescents from English-speaking households(n = 2), adolescents from Spanish-speaking households(n = 5), English-speaking parents(n = 4), and Spanish-speaking parents (n = 4). Five themes emerged: Parents (1) feared opioid use would result in overdose or addiction and (2) desired information about alternative medical and behavioral strategies to minimize use. (3) Parents felt empowered to manage their adolescent's opioid use and trusted their adolescent to prompt them for opioids. Adolescents trusted their parents to manage their opioid use but maintained their autonomy to limit opioid consumption when experiencing undesirable side effects. (4) Some adolescents and parents endorsed a preference for "not taking medication" in their households. (5) Both parents and adolescents reported previous knowledge of opioids prior to surgery, with adolescents learning more nuanced information about opioid safety after their surgeries., Conclusions: Families feel empowered to manage their postoperative prescription opioid use but fear the negative effects of opioids and desire information on alternatives. Evidence-based, family-centric education from providers in a language preferred by the family could mitigate families' concerns and contribute to improved pain control and safety., Level of Evidence: IV., Competing Interests: Conflicts of interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

There is increasing interest in understanding potential bias in medical education. We used natural language processing (NLP) to evaluate potential bias in clinical clerkship evaluations. Data from medical evaluations and administrative databases for medical students enrolled in third-year clinical clerkship rotations across two academic years. We collected demographic information of students and faculty evaluators to determine gender/racial concordance (i.e., whether the student and faculty identified with the same demographic). We used a multinomial log-linear model for final clerkship grades, using predictors such as numerical evaluation scores, gender/racial concordance, and sentiment scores of narrative evaluations using the SentimentIntensityAnalyzer tool in Python. 2037 evaluations from 198 students were analyzed. Statistical significance was defined as P < 0.05. Sentiment scores for evaluations did not vary significantly by student gender, race, or ethnicity (P = 0.88, 0.64, and 0.06, respectively). Word choices were similar across faculty and student demographic groups. Modeling showed narrative evaluation sentiment scores were not predictive of an honors grade (odds ratio [OR] 1.23, P = 0.58). Numerical evaluation average (OR 1.45, P < 0.001) and gender concordance between faculty and student (OR 1.32, P = 0.049) were significant predictors of receiving honors. The lack of disparities in narrative text in our study contrasts with prior findings from other institutions. Ongoing efforts include comparative analyses with other institutions to understand what institutional factors may contribute to bias. NLP enables a systematic approach for investigating bias. The insights gained from the lack of association between word choices, sentiment scores, and final grades show potential opportunities to improve feedback processes for students., (© 2024. The Author(s).)

Background and Objective: Patients with intermediate-risk non-muscle-invasive bladder cancer (IR NMIBC) have a high risk of recurrence and need effective therapies to reduce the risk of disease recurrence or progression. This phase 1b study (NCT02720367) assessed the safety and tolerability of TAR-200, an intravesical drug delivery system, in participants with IR NMIBC., Methods: Participants with recurrent IR NMIBC were eligible. Participants received either two 7-d or two 21-d TAR-200 dosing cycles over a 4-6-wk period in a marker lesion/ablation design. TAR-200 was placed in the window between the cystoscopy showing recurrent papillary disease and the subsequent complete transurethral resection of the bladder tumour. The primary endpoint was TAR-200 safety. The secondary endpoints included TAR-200 tolerability, pharmacokinetics, and preliminary efficacy., Key Findings and Limitations: Twelve participants received TAR-200 treatment. No TAR-200-related serious or grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred. Nine participants had grade ≤ 2 TAR-200-related TEAEs, with urgency, dysuria, and haematuria being most common. Two participants refused a second dosing cycle due to urinary urgency and frequency. Insertion and removal of TAR-200 was successful in all cases. Plasma gemcitabine concentrations remained below the lower limit of detection. Five participants (42%) had complete response (CR): four had pathological CR and one had CR based on visual assessment., Conclusions and Clinical Implications: TAR-200 appears to be safe and well tolerated, with encouraging preliminary efficacy in participants with IR NMIBC. This study lays the groundwork for the multiple phase 2 and 3 global studies that are currently on-going for TAR-200., Patient Summary: In this study, researchers evaluated the safety of the novel drug delivery system TAR-200 in participants with intermediate-risk non-muscle-invasive bladder cancer. They concluded that TAR-200 was safe and well tolerated with promising antitumour activity., (© 2024 The Authors.)

Objective: To evaluate the incidence and predictors of early postoperative acute kidney injury (EP-AKI) during index hospitalization following radical cystectomy and its association with postoperative outcomes., Methods: All patients with bladder cancer who underwent radical cystectomy with intent-to-cure at our center between 2012 and 2020 were reviewed. EP-AKI during index hospitalization was evaluated using the Acute Kidney Injury Network criteria. The association between EP-AKI and demographics, clinicopathologic features, and perioperative outcomes, including length of hospital stay, complication rate, and readmission rate, were examined. A logistic regression analysis was performed to evaluate the predictors of EP-AKI., Results: Overall, 435 patients met eligibility, of whom 112 (26%) experienced EP-AKI during index hospitalization (90 [21%] stage 1, 17 [4%] stage 2, and 5 [1%] stage 3). EP-AKI was associated with a longer mean operative time (6.8 vs. 6.1 hours; P < 0.001), higher mean length of hospital stay (6.3 vs. 5.6; P = 0.02), 30-day complication rate (71% vs. 51%; P < 0.001), 90-day complication rate (81% vs. 69%; P = 0.01) and 90-day readmission rate (37% vs. 33%; P = 0.04). The rate of complications increased at higher stages of AKI. On multivariable analysis, perioperative blood transfusion (OR: 1.84, P = 0.02) and continent diversion (OR: 3.29, P < 0.001) were independent predictors of EP-AKI., Conclusion: A quarter of cystectomy patients experience acute kidney injury during index hospitalization, which is associated with higher length of stay, postoperative complication, and readmission rates. Perioperative blood transfusion and continent diversion are independent predictors of such injury., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Widespread electronic health record adoption has generated a large volume of data and emphasized the need for standardized terminology to describe clinical concepts. Here, we undertook a systematic concept coverage analysis to determine the representation of clinical concepts in ophthalmic infection and ophthalmic trauma among standardized medical terminologies, including the Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT), the International Classification of Diseases (ICD) version 10 with clinical modifications (ICD-10-CM), and ICD version 11 (ICD-11)., Design: Extraction of concepts related to ophthalmic infection and ophthalmic trauma and structured search in terminology browsers., Data Sources: The American Academy of Ophthalmology Basic and Clinical Science Course (BCSC), SNOMED-CT, and ICD-10-CM terminologies from the Observational Health Data Sciences and Informatics Athena browser, and the ICD-11 terminology browser., Methods: Concepts pertaining to ophthalmic infection and ophthalmic trauma were extracted from the 2022 BCSC free text and index terms. We searched terminology browsers to identify corresponding codes and classified the extent of semantic alignment as equal , wide , narrow , or unmatched in each terminology. The overlap of equal concepts in each terminology was represented in a Venn diagram., Main Outcome Measures: Proportions of clinical concepts with corresponding codes at various levels of semantic alignment., Results: A total of 443 concepts were identified: 304 concepts related to ophthalmic infection and 139 concepts related to ophthalmic trauma. The SNOMED-CT had the highest proportion of equal coverage, with 82.0% (249 of 304) among concepts related to ophthalmic infection and 82.0% (115 of 139) among concepts related to ophthalmic trauma. Across all concepts, 28% (124 of 443) were classified as equal in ICD-10-CM and 52.8% (234 of 443) were classified as equal in ICD-11., Conclusions: The SNOMED-CT had significantly better semantic alignment than ICD-10-CM and ICD-11 for ophthalmic infections and ophthalmic trauma. This demonstrates opportunity for continuing advancement of representation of ophthalmic concepts in standardized medical terminologies., (© 2023 by the American Academy of Ophthalmology.)

Purpose: We explored the accuracy of a urine-based epigenetic test for detecting upper tract urothelial carcinoma., Materials and Methods: Under an Institutional Review Board-approved protocol, urine samples were prospectively collected from primary upper tract urothelial carcinoma patients before radical nephroureterectomy, ureterectomy, or ureteroscopy between December 2019 and March 2022. Samples were analyzed with Bladder CARE, a urine-based test that measures the methylation levels of 3 cancer biomarkers (TRNA-Cys, SIM2, and NKX1-1) and 2 internal control loci using methylation-sensitive restriction enzymes coupled with quantitative polymerase chain reaction. Results were reported as the Bladder CARE Index score and quantitatively categorized as positive (>5), high risk (2.5-5), or negative (<2.5). The findings were compared with those of 1:1 sex/age-matched cancer-free healthy individuals., Results: Fifty patients (40 radical nephroureterectomy, 7 ureterectomy, and 3 ureteroscopy) with a median (IQR) age of 72 (64-79) years were included. Bladder CARE Index results were positive in 47, high risk in 1, and negative in 2 patients. A significant correlation was found between Bladder CARE Index values and tumor size. Urine cytology was available for 35 patients, of whom 22 (63%) results were false-negative. Upper tract urothelial carcinoma patients had significantly higher Bladder CARE Index values compared to the controls (mean 189.3 vs 1.6, P < .001). The sensitivity, specificity, positive predictive value, and negative predictive value of the Bladder CARE test for detecting upper tract urothelial carcinoma were 96%, 88%, 89%, and 96%, respectively . Conclusions:Bladder CARE is an accurate urine-based epigenetic test for the diagnosis of upper tract urothelial carcinoma, with much higher sensitivity than standard urine cytology.

Objective: To examine the oncological outcomes and recurrence patterns in patients with no residual disease at the time of radical cystectomy (RC)., Methods: A retrospective review of our IRB-approved bladder cancer database identified patients who underwent RC between 2000 and 2019 and were found to have no residual disease (pT0N0), either following neoadjuvant chemotherapy (NAC) or transurethral resection (TURBT) alone. The primary outcome was recurrence-free survival (RFS). Regression models assessed factors influencing recurrence, and a detailed description of recurrence patterns was compiled., Results: From a total of 2222 patients, 234 (10.5%) were included with a median age of 67 years. NAC was used in 89 (38%) patients and 145 (62%) cases were rendered pT0 following TURBT alone. At a median follow-up of 44 months, there were 16 (6.8%) recurrences, 10 (63%) of which occurred in the ypT0 group. None of the patients with clinical Ta/Tis disease had a recurrence after RC. The median time to recurrence was 9 months. Ninety-one percent (10/11) of recurrences in the ypT0 group were within 2 years of cystectomy, while half of the recurrences in the pT0 group occurred after 2 years. Patients with ypT0 had worse 2- and 5-year RFS compared to the pT0 group (85% and 84% vs. 99% and 95%, respectively; P = 0.003). Variant histology was noted in 49 (21%) patients; the recurrence rate was higher in this subgroup compared to those with pure urothelial carcinoma (12.2% vs. 5.4%, P = 0.02). Lung metastasis and involvement of distant organs, while rare, were noted at similar rates in both groups., Conclusion: Patients with pT0N0 pathology at the time of cystectomy should prudently undergo long-term surveillance as recurrence and metastasis can still develop up to 4 years after surgery. Patients achieving ypT0 after NAC exhibit worse prognosis and shorter times to recurrence, closer follow-up may be considered., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Studies have identified demographic, clinical, psychosocial, and perioperative variables associated with persistent pain after a variety of surgeries. This study aimed to perform a systematic review and meta-analysis of factors associated with persistent pain after total knee replacement (TKR) and total hip replacement (THR) surgeries. To meet the inclusion criteria, studies were required to assess variables before or at the time of surgery, include a persistent postsurgical pain (PPSP) outcome measure at least 2 months after a TKR or THR surgery, and include a statistical analysis of the effect of the risk factor(s) on the outcome measure. Outcomes from studies implementing univariate and multivariable statistical models were analyzed separately. Where possible, data from univariate analyses on the same factors were combined in a meta-analysis. Eighty-one studies involving 171,354 patients were included in the review. Because of the heterogeneity of assessment methods, only 44% of the studies allowed meaningful meta-analysis. In meta-analyses, state anxiety (but not trait anxiety) scores and higher depression scores on the Beck Depression Inventory were associated with an increased risk of PPSP after TKR. In the qualitative summary of multivariable analyses, higher preoperative pain scores were associated with PPSP after TKR or THR. This review systematically assessed factors associated with an increased risk of PPSP after TKR and THR and highlights current knowledge gaps that can be addressed by future research., Competing Interests: S. Haroutounian reports research grants from Disarm Therapeutics and personal fees from Rafa Laboratories and Vertex Pharmaceuticals, outside the scope of this paper. The remaining authors have no conflicts of interest to declare.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Species of the genus Phytophthora, the plant killer, cause disease and reduce yields in many crop plants. Although many Resistance to Phytophthora infestans (Rpi) genes effective against potato late blight have been cloned, few have been cloned against other Phytophthora species. Most Rpi genes encode nucleotide-binding domain, leucine-rich repeat-containing (NLR) immune receptor proteins that recognize RXLR (Arg-X-Leu-Arg) effectors. However, whether NLR proteins can recognize RXLR effectors from multiple Phytophthora species has rarely been investigated. Here, we identified a new RXLR-WY effector AVRamr3 from P. infestans that is recognized by Rpi-amr3 from a wild Solanaceae species Solanum americanum. Rpi-amr3 associates with AVRamr3 in planta. AVRamr3 is broadly conserved in many different Phytophthora species, and the recognition of AVRamr3 homologs by Rpi-amr3 activates resistance against multiple Phytophthora pathogens, including the tobacco black shank disease and cacao black pod disease pathogens P. parasitica and P. palmivora. Rpi-amr3 is thus the first characterized resistance gene that acts against P. parasitica or P. palmivora. These findings suggest a novel path to redeploy known R genes against different important plant pathogens., (Copyright © 2022 The Author. Published by Elsevier Inc. All rights reserved.)

Abstract: Persistent postsurgical pain (PPSP) is a common and often disabling postoperative morbidity, but many questions remain about factors associated with PPSP. This systematic review and meta-analysis aimed to identify preoperative, intraoperative, and postoperative factors associated with PPSP after gynecological surgeries, namely, hysterectomy and cesarean section, and urological surgeries, namely, prostatectomy and donor nephrectomy. Overall, 18 gynecological surgery studies, 4 prostatectomy studies, and 2 donor nephrectomy studies met the review criteria, providing data that could be meta-analyzed. The average (±SD) PPSP occurrence after gynecological surgery was 20 ± 11%; factors associated with increased risk of PPSP included smoking, preoperative abdominal or pelvic pain, preoperative pain elsewhere in the body, longer duration of surgery, more intense acute postoperative pain, and surgical wound infection. The use of neuraxial anesthesia was associated with decreased PPSP risk. The average PPSP occurrence was 20 ± 9% after prostatectomy and 15 ± 2% after donor nephrectomy. For urological procedures, the existing data did not allow for identification of significant factors associated with PPSP, except for laparoscopic and hand-assisted laparoscopic approaches that were associated with lower incidence of PPSP for donor nephrectomy, and the use of neuraxial anesthesia which was associated with lower incidence of PPSP after prostatectomy. Persistent postsurgical pain after gynecological and urological surgeries is common. This systematic review identified important factors associated with cesarean section and hysterectomy that can help identify women who are at high risk of PPSP. More high-quality studies with consistent methodology are needed to understand the factors associated with PPSP risk, particularly for surgeries such as prostatectomy and nephrectomy., (Copyright © 2021 International Association for the Study of Pain.)

Purpose: There are conflicting reports on outcome trends following radical cystectomy (RC) for bladder cancer., Materials and Methods: Evolution of modern bladder cancer management and its impact on outcomes was analyzed using a longitudinal cohort of 3,347 patients who underwent RC at an academic center between 1971 and 2018. Outcomes included recurrence-free survival (RFS) and overall survival (OS). Associations were assessed using univariable and multivariable models., Results: In all, 70.9% of cases underwent open RC in the last decade, although trend for robot-assisted RC rose since 2009. While lymphadenectomy template remained consistent, nodal submission changed to anatomical packets in 2002 with increase in yield (p <0.001). Neoadjuvant chemotherapy (NAC) use increased with time with concomitant decrease in adjuvant chemotherapy; this was notable in the last decade (p <0.001) and coincided with improved pT0N0M0 rate (p=0.013). Median 5-year RFS and OS probabilities were 65% and 55%, respectively. Advanced stage, NAC, delay to RC, lymphovascular invasion and positive margins were associated with worse RFS (all, multivariable p <0.001). RFS remained stable over time (p=0.73) but OS improved (5-year probability, 1990-1999 51%, 2010-2018 62%; p=0.019). Among patients with extravesical and/or node-positive disease, those who received NAC had worse outcomes than those who directly underwent RC (p ≤0.001)., Conclusions: Despite perioperative and surgical advances, and improved pT0N0M0 rates, there has been no overall change in RFS trend following RC, although OS rates have improved. While patients who are downstaged with NAC derive great benefit, our real-world experience highlights the importance of preemptively identifying NAC nonresponders who may have worse post-RC outcomes.

Objective: To examine the effect of diagnostic ureteroscopy (URS) and ureteral access sheath usage on bladder recurrence following radical nephroureterectomy (RNU)., Methods: We retrospectively reviewed the records of patients who underwent RNU between 2005 - 2019. Patients with a history of bladder cancer and those without a bladder cuff resection were excluded. Bladder recurrence was the primary outcome and cox regression modeling was used to assess the impact of URS adjusting for other factors., Results: Out of 271 RNU cases, 143 were included with a median age of 73 years (IQR 65 - 80). URS was performed in 104 cases (73%) and a ureteral access sheath was used in 26 (25%). With a median follow-up of 27 months, there were 36 (25%) bladder recurrences. The bladder recurrence rate (median time to recurrence) for patients who had URS vs no URS was 30.8% (9.0 months) and 7.7% (12.1 months), respectively (P = .02). A lower recurrence rate was noted in patients whom a ureteral access sheath was utilized (11.5%) vs those with no access sheath (39.7%, P = .01). Multivariable analysis revealed a significant increase in bladder recurrence if URS was performed prior to RNU (HR 5.6 [1.7 - 18.5], P <.004), however, this effect was mitigated if a ureteral access sheath was used (HR 1.3, [0.3 - 6.4], P = .76). Ureteral stent usage and performing a ureteroscopic biopsy had no significant effect on bladder recurrence., Conclusion: Diagnostic URS in patients undergoing RNU for UTUC significantly increases the risk of bladder recurrence. This effect may be mitigated by using a ureteral access sheath., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To investigate the prevalence of catheterisation and urinary retention in male patients with bladder cancer after radical cystectomy (RC) and orthotopic neobladder (ONB) and to identify potential predictors., Patients and Methods: Using an Institutional Review Board approved, prospectively maintained bladder cancer database, we collected information using a diversion-related questionnaire from 299 consecutive male patients with bladder cancer upon postoperative clinic visit. Urinary retention was defined as ≥3 catheterisations/day or a self-reported inability to void without a catheter. Uni- and multivariable Cox regression analysis was performed to identify predictors of catheterisation and urinary retention., Results: Self-catheterisation was reported in 51 patients (17%), of whom, 22 (7.4% of the total patients) were in retention. Freedom from any catheterisation at 3, 5, and 10 years after RC was 85%, 77%, and 62%, respectively. Freedom from retention at 3, 5, and 10 years after RC was 93%, 88%, and 79%, respectively. Multivariable Cox regression showed that higher body mass index (BMI; ≥27 kg/m 2 ) significantly increased the need for catheterisation (hazard ratio [HR] 2.34, 95% confidence interval [CI] 1.26-4.32) as well as retention (HR 5.20, 95% CI 1.74-15.51). Greater medical comorbidity (Charlson Comorbidity Index score ≥2) correlated with the need for any catheterisation (HR 1.84, 95% CI 1.02-3.3), but not retention. Pathological stage and type of diversion were not significant predictors of the need to catheterise or urinary retention., Conclusion: In males undergoing RC with ONB, retention requiring catheterisation to void is uncommon. Patients with a BMI of ≥27 kg/m 2 are at significantly increased risk of retention and need for self-catheterisation., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

Purpose: The aim of this study is to evaluate the intra/perioperative fluid management and early postoperative outcomes of patients who underwent radical cystectomy with Enhanced Recovery After Surgery protocol, using goal-directed fluid therapy compared to conventional fluid therapy., Methods: This cohort study included patients who underwent open RC for urothelial bladder carcinoma with intent to cure and Enhanced Recovery After Surgery protocol between May 2012 and August 2019. Patients who had palliative or salvage cystectomy and/or adjunct procedures, as well as those with missing detailed perioperative data were excluded. Data were compared between patients who received goal-directed fluid therapy using stroke volume variation by FloTrac™/Vigileo system (n = 119) and conventional fluid therapy based on the anesthesiologist discretion (n = 192). Primary outcome variable was 90-day complications and secondary outcome measures included in-hospital GFR trend, length of stay, and 90-day readmission., Results: The goal-directed fluid therapy group received less total and net intra/perioperative fluid, yet early postoperative glomerular filtration rate trends were similar between both groups (p = 0.7). Estimated blood loss, blood transfusion, index hospital stay, 90-day complication and readmission rates were also comparable between the two groups. Multivariable logistic regression showed no significant association between perioperative fluid management method and 90-day complication rate (OR 1.4, 95% CI 0.8-2.4, p = 0.2)., Conclusion: Stroke volume variation guided goal-directed fluid therapy is safe in radical cystectomy without compromising the renal function. It is associated with less intra- and perioperative fluid infusion; however, no association with hospital stay, 90-day complication or readmission rates were noted., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Muscle-invasive bladder cancer (MIBC) accounts for approximately 20% of all urothelial bladder carcinomas (UBC) at time of diagnosis, and up to 30% of patients with non-muscle invasive UBC will progress to MIBC over time. An increasing body of evidence has revealed a strong correlation between aberrant DNA methylation and tumorigenesis in MIBC., Results: Using The Cancer Genome Atlas (TCGA) molecular data for 413 patients, we described a DNA methylation-based signature as a prognostic factor for overall survival (OS) in MIBC patients. By using a least absolute shrinkage and selection operator (LASSO) model, differentially methylated regions were first identified using multiple criteria followed by survival and LASSO analyses to identify DNA methylation probes related to OS and build a classifier to stratify patients with MIBC. The prognostic value of the classifier, referred to as risk score (RS), was validated in a held-out testing set from the TCGA MIBC cohort. Finally, receiver operating characteristic (ROC) analysis was used to compare the prognostic accuracy of the models built with RS alone, RS plus clinicopathologic features, and clinicopathologic features alone. We found that our seven-probe classifier-based RS stratifies patients into high- and low-risk groups for overall survival (OS) in the testing set (n = 137) (AUC at 3 years, 0.65; AUC at 5 years, 0.65). In addition, RS significantly improved the prognostic model when it was combined with clinical information including age, smoking status, Tumor (T) stage, and Lymph node metastasis (N) stage., Conclusions: The DNA methylation-based RS can be a useful tool to predict the accuracy of preoperative and/or post-cystectomy models of OS in MIBC patients., Competing Interests: DW is a consultant for Zymo Research Corporation (Irvine, CA). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xu, Gujar, Fu, Ahmadi, Bhanvadia, Weisenberger, Jin, Gill, Gill, Daneshmand, Siegmund and Liang.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Late blight caused by Phytophthora infestans greatly constrains potato production. Many Resistance (R) genes were cloned from wild Solanum species and/or introduced into potato cultivars by breeding. However, individual R genes have been overcome by P. infestans evolution; durable resistance remains elusive. We positionally cloned a new R gene, Rpi-amr1, from Solanum americanum, that encodes an NRC helper-dependent CC-NLR protein. Rpi-amr1 confers resistance in potato to all 19 P. infestans isolates tested. Using association genomics and long-read RenSeq, we defined eight additional Rpi-amr1 alleles from different S. americanum and related species. Despite only ~90% identity between Rpi-amr1 proteins, all confer late blight resistance but differentially recognize Avramr1 orthologues and paralogues. We propose that Rpi-amr1 gene family diversity assists detection of diverse paralogues and alleles of the recognized effector, facilitating durable resistance against P. infestans.

Purpose: Adrenal incidentalomas are being discovered with increasing frequency, and their discovery poses a challenge to clinicians. Despite the 2002 National Institutes of Health consensus statement, there are still discrepancies in the most recent guidelines from organizations representing endocrinology, endocrine surgery, urology and radiology. We review recent guidelines across the specialties involved in diagnosing and treating adrenal incidentalomas, and discuss points of agreement as well as controversy among guidelines., Materials and Methods: PubMed®, Scopus®, Embase™ and Web of Science™ databases were searched systematically in November 2019 in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement to identify the most recently updated committee produced clinical guidelines in each of the 4 specialties. Five articles met the inclusion criteria., Results: There is little debate among the reviewed guidelines as to the initial evaluation of an adrenal incidentaloma. All patients with a newly discovered adrenal incidentaloma should receive an unenhanced computerized tomogram and hormone screen. The most significant points of divergence among the guidelines regard reimaging an initially benign appearing mass, repeat hormone testing and management of an adrenal incidentaloma that is not easily characterized as benign or malignant on computerized tomography. The guidelines range from actively recommending against any repeat imaging and hormone screening to recommending a repeat scan as early as in 3 to 6 months and annual hormonal screening for several years., Conclusions: After reviewing the guidelines and the evidence used to support them we posit that best practices lie at their convergence and have presented our management recommendations on how to navigate the guidelines when they are discrepant.

Purpose: To perform an internal audit 5 years after implementation of our enhanced recovery after surgery (ERAS) protocol for patients undergoing radical cystectomy and to investigate the importance of physician driven compliance on outcomes., Methods: Using a prospectively maintained database, 472 consecutive patients were identified who underwent radical cystectomy with ERAS from July 2013 to July 2017. Compliance was measured by a Composite Compliance Score (CCS) generated as a percentage of 16 interventions. Patients with higher than median compliance were compared to patients with lower compliance. The primary outcome was length of stay. Secondary outcomes included complication and readmission rates. Multivariable regressions were used to control for differences between groups., Results: In 2013, median CCS was 81% and subsequently ranged from 81 to 88%. Five-year median CCS was 88%. Patients with higher compliance (CCS ≥ 88%, n = 262), as compared to those with lower compliance (CCS < 88%, n = 210), were younger (median 70.3 vs 72.7 years, p = 0.047), healthier (ASA3-4 81% vs 89.9%, p = 0.007), received more orthotopic diversions (59.2% vs 37.6%, p < 0.0001), more often had open surgery (78.5% vs 51.9%, p < 0.0001) and had shorter median operative times (5.5 vs 6.3 h, p = 0.005). Median length of stay was 4 days. Higher compliance was associated with shorter hospital stays (β = - 0.85, 95% CI - 1.62 to - 0.07) and decreased 30-day readmissions (OR 0.58, 95% CI 0.35-0.96)., Conclusions: Greater ERAS compliance was achieved in younger and healthier patients. Patients with greater compliance had a decreased length of stay by almost 1 day and reduced odds of 30-day readmissions.

Oxidative stress is one of major causal factors in glaucomatous neurodegeneration. Ubiquinol promotes retinal ganglion cell (RGC) survival against glaucomatous insults such as oxidative stress. Here we investigated the effect of ubiquinol on RGC survival and/or visual function in mouse models of glaucoma and oxidative stress. DBA/2J and age-matched DBA/2J- Gpnmb + (D2- Gpnmb + ), which do not develop intraocular pressure elevation, or C57BL/6J mice were fed with ubiquinol (1%) or control diet daily for 5 or 2 months. We assessed RGC survival by Brn3a immunohistochemistry and measured expression levels of active and total BAX, peroxisome proliferator-activated receptor-gamma coactivator 1α, transcription factor A (TFAM) and oxidative phosphorylation (OXPHOS) complex protein. Following induction of oxidative stress by paraquat injection, we also assessed visual function. In glaucomatous retina, ubiquinol supplementation significantly promoted RGC survival, blocked BAX activation and increased TFAM and OXPHOS complex II protein expression. Also, ubiquinol supplementation ameliorated oxidative stress-induced visual dysfunction. These findings indicate that ubiquinol promotes RGC survival by increasing TFAM expression and OXPHOS complex II activity in glaucomatous neurodegeneration, and that ubiquinol enhances RGC survival and preserves visual function against oxidative stress. We propose that ubiquinol has a therapeutic potential for treating oxidative stress-associated glaucomatous neurodegeneration.

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Bladder cancer is the fourth most common cancer among males and poses a significant financial burden, yet there are no large-scale studies focused on the correlation between socioeconomic (SES) and insurance status and bladder cancer outcomes. The objective of this study was to determine the effect of SES and insurance type on outcomes in bladder cancer., Materials and Methods: A population-based search was performed using the National Cancer Institute's Surveillance, Epidemiology, and End Results 18 database. Patients aged 18 or older and diagnosed with bladder cancer between 2011 and 2015 were identified. Data on patient demographics, SES features, insurance status, tumor characteristics, and survival were collected. A county-level SES measure was created in a method consistent with prior literature. Primary outcomes were overall survival (OS) and disease-specific survival (DSS)., Results: A total of 91,308 patients were identified. Factors predictive of having muscle invasive disease included having Medicaid insurance, having no insurance, and being in the lowest SES quartile (all P < 0.001). Having Medicaid or no insurance was predictive of having node positive or metastatic disease (P < 0.001). Independent of T stage, patients in the lowest and second lowest SES quartiles had worse OS (P = 0.004 and P = 0.022, respectively) and DSS (P < 0.001 for both). Patients with Medicaid or no insurance had worse OS and DSS (P < 0.001 for all)., Conclusions: Lower SES status, Medicaid insurance, and having no insurance were all predictive of having higher tumor stage. Independent of tumor stage, being of lower SES, having Medicaid insurance, and having no insurance predicted worse OS and DSS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To validate the relationship between ABO blood type and risk of VTE post-RC in a large retrospective database., Methods: Patients with urothelial bladder cancer (UBC) who underwent RC (intent-to-cure) for whom ABO blood type was available between 2003 and 2015 were identified from our IRB-approved database. VTE was defined as deep vein thrombosis (DVT) or pulmonary embolism (PE) within 90 days of surgery. VTE prophylaxis consisted of immediate postoperative Coumadin (2003-2009), unfractionated heparin (UFH) during hospitalization (2009-2015), and UFH during hospitalization plus 4 weeks of enoxaparin after discharge (2013-2015). Univariable and multivariable analyses of the association of ABO blood type with postoperative, symptomatic VTE and oncologic outcomes were performed., Results: Of 1341 patients, 595 (44.4%) were ABO type O and 746 (55.6%) were non-O (A, B and AB). 90 patients were diagnosed with VTE within 90 days of surgery (6.7%) (43% DVT-only, 57% PE ± DVT). On multivariable analysis non-O blood type was associated with a nearly twofold increased risk of VTE (OR = 1.94, 95% CI 1.215-3.098, p = 0.004). No difference in recurrence-free survival or overall survival was seen between ABO groups., Conclusion: Non-O blood type is an independent, non-modifiable risk factor for postoperative VTE after RC. More comprehensive counseling and thromboprophylaxis should be considered in this high-risk group.

Objective: To improve confirmation of complete tumor thrombus removal in advanced malignancy, we report on our experience using intraoperative vena cavoscopy using a flexible cystoscope to confirm complete thrombus resection. Patients with renal cell carcinoma or testicular cancer associated with inferior vena caval tumor involvement benefit from surgical resection of the primary tumor and the tumor thrombus. Intraoperative assessment of the vena cava represents a technical challenge, particularly when the thrombus is friable and involves the hepatic veins, or there is caudal extension of thrombus toward the bifurcation., Material and Methods: From 2006 to 2014, 36 patients underwent tumor thrombectomy and vena cavoscopy. When residual caval thrombus was suspected, a flexible cystoscope was inserted into the vena cava for direct visual inspection of the caval lumen. Perioperative outcomes including residual tumor, changes in management, and postoperative complications were analyzed., Results: All patients underwent endoscopy of the caval lumen without complications. Eight of 36 (22%) patients were found to have residual tumor thrombus visualized during cavoscopy. Five of these patients had evidence of residual mass and caval invasion within the caval lumen that ultimately resulted in cavectomy. Two patients had residual tumor thrombus that was bluntly removed. One patient was found to have significant involvement of the hepatic veins., Conclusion: Vena cavoscopy using a flexible cystoscope is a practical technique that may be utilized intraoperatively to ensure clearance of residual thrombus burden within the inferior vena cava and to assess for caval invasion., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Retroperitoneal lymph node dissection (RPLND) is an important component of the management of testicular germ cell tumor (GCT) but carries significant surgical morbidity., Objective: To describe our experience with a midline extraperitoneal (EP) approach to RPLND for seminomatous and nonseminomatous GCT., Design, Setting, and Participants: From 2010 to 2015, 122 consecutive patients underwent RPLND from a prospective database. Patients requiring aortic resection or retrocrural dissection or with intraperitoneal disease were excluded. The remaining 69 patients underwent midline EP-RPLND., Surgical Procedure: Open midline EP-RPLND was performed using a standardized technique., Outcome Measurements and Statistical Analysis: Perioperative and long-term outcomes were analyzed. Complications were graded using the Clavien-Dindo classification. A descriptive analysis using SAS software was performed., Results and Limitations: A total of 68 patients underwent midline EP-RPLND successfully (98.6%). The median age was 28 yr (range 17-55). On preoperative imaging the size of the retroperitoneal mass or lymphadenopathy was <2cm in 29 patients, 2-4.9cm in 15 patients, and >5cm in 24 patients, of which 19 were >10cm. The median estimated blood loss was 325ml (interquartile range [IQR] 200-612.5). The median number of lymph nodes resected was 36 (IQR 24.5-49); the median number of positive nodes was one (IQR 0-4). The median time for return of bowel function was 2 d (IQR 1-2) and hospital stay 3 d (IQR 3-4). There were no cases of ileus. Eleven patients had 12 (17.6%) 90-d complications. Of these, six (55%) were Clavien grade 1, five (45%) were grade 2, and one was grade 3b (1.5%). Antegrade ejaculation rates were 91.6% in the primary group and 96.8% in the post-chemotherapy group., Conclusions: Midline EP-RPLND can be performed safely without compromising the completeness of the resection. This approach is associated with rapid return of bowel function, minimal rates of ileus, and short hospital stay., Patient Summary: A midline extraperitoneal approach for retroperitoneal lymph node dissection in testicular cancer is safe and effective and leads to faster return of bowel function and earlier discharge., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction and Objective: Perioperative blood transfusion (PBT) is commonplace in radical cystectomy (RC) and has been linked to poorer oncologic outcomes. Limiting PBT in this largely elderly and comorbid population has not been studied. Herein, we first investigate the safety of a restrictive transfusion protocol (RTP) in patients undergoing RC for urothelial carcinoma and then compare oncologic outcomes between patients who did and did not receive PBT., Methods: Outcomes for 173 consecutive patients meeting inclusion criteria undergoing RC for urothelial carcinoma from April 2010 to June 2014 by a single surgeon employing RTP were analyzed from an institutional review board-approved, prospectively collected database. Pairwise matching to a cohort undergoing RC during an earlier era of more liberal PBT was performed, and 90-day outcomes were compared., Results: Median follow-up for the RTP cohort was 3.1 years (range: 0-5.1y). Median age was 70 years (range: 38-93y). Forty-six patients (26.6%) received PBT. Eighty-seven matched pairs were generated from RTP cohort and liberal era where PBT rate was 94%. There were no differences in 90-day complication rates, mortality, or readmission rates (P>0.05). In the RTP cohort, patients who underwent PBT had higher estimated blood loss (500 vs. 350, P = 0.001), lower baseline hematocrit (28.9 vs. 33.3, P = 0.005), and similar operative time (5.8 vs. 5.3h, P = 0.01) and length of stay (5.5 vs. 5, P = 0.07). At discharge and 3-week follow-up, there was no difference in hematocrit (P>0.05). In the no-PBT group, 90-day (65.6% vs. 86.7%, P = 0.007) and high-grade (15.6% vs. 34.8%, P = 0.003) complication rates were lower. On multivariable analysis, predictors of PBT were age (odds ratio [OR] = 1.06, 95% CI [1.01-1.11]), Charlson comorbidity index≥2 (OR = 2.68, CI [1.09-7.04]), neoadjuvant chemotherapy (OR = 3.74, CI [1.46-10.19]),≥pT3 (OR = 5.5, CI [2.33-13.73]), baseline hematocrit (OR = 0.95, CI [0.87-1.00]), and estimated blood loss (OR = 1.001, CI [1-1.003]). PBT was associated with lower recurrence-free survival (hazard ratio = 2.16; CI [1.13-41.12]; P = 0.02) and overall survival (hazard ratio =2.25; CI [1.25-4.88]; P = 0.01)., Conclusions: The use of RTP in RC is safe. PBT was associated with poorer recurrence-free survival and overall survival independent of clinicopathologic characteristics., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Retroperitoneal lymph node dissection (RPLND) for the treatment of testicular germ cell tumor is technically difficult and associated with significant morbidity. We postulated that a novel midline extraperitoneal (EP) approach might minimize the morbidity., Technical Considerations: We describe a midline extraperitoneal approach in detail. The operative time, estimated blood loss, lymph node yield, return of bowel function, length of stay, and postoperative complications were retrospectively reviewed. From April 2010 to May 2011, 12 consecutive patients underwent EP-RPLND at 2 tertiary centers by a single surgeon, including 5 primary and 7 postchemotherapy RPLNDs. The clinical characteristics and outcomes were compared with those from a matched cohort of transperitoneal-RPLND patients., Results: The median follow-up was 173 and 201 days in the EP and transperitoneal groups, respectively. The EP group had a shorter mean operative time of 292 versus 337 minutes (P = .02) and lower estimated blood loss of 305 versus 575 mL (P = .05). More lymph nodes were retrieved in the EP group (44 vs 27 nodes, P = .0006). Finally, an earlier return of bowel function (1.7 vs 2.9 days, P = .0001) and a shorter median length of stay (3.3 vs 5.3 days, P = .0001) was seen in the EP group., Conclusion: EP-RPLND can be performed safely without prolonged operative times or compromised lymph node retrieval, even in the postchemotherapy setting, and is associated with a faster return of bowel function and shortened length of stay., (Copyright © 2012 Elsevier Inc. All rights reserved.)