RADX Promotes Genome Stability and Modulates Chemosensitivity by Regulating RAD51 at Replication Forks.

RAD51 promotes homology-directed repair (HDR), replication fork reversal, and stalled fork protection. Defects in these functions cause genomic instability and tumorigenesis but also generate hypersensitivity to cancer therapeutics. Here we describe the identification of RADX as an RPA-like, single-strand DNA binding protein. RADX is recruited to replication forks, where it prevents fork collapse by regulating RAD51. When RADX is inactivated, excessive RAD51 activity slows replication elongation and causes double-strand breaks. In cancer cells lacking BRCA2, RADX deletion restores fork protection without restoring HDR. Furthermore, RADX inactivation confers chemotherapy and PARP inhibitor resistance to cancer cells with reduced BRCA2/RAD51 pathway function. By antagonizing RAD51 at forks, RADX allows cells to maintain a high capacity for HDR while ensuring that replication functions of RAD51 are properly regulated. Thus, RADX is essential to achieve the proper balance of RAD51 activity to maintain genome stability.

Prevalence of Obstructive Sleep Apnea With Floppy Eyelid Syndrome: A Systematic Review and Meta-analysis.

PURPOSE: This study investigated the prevalence of obstructive sleep apnea (OSA) in floppy eyelid syndrome (FES) patients and evaluated the severity of OSA with FES prevalence. METHODS: Cochrane CENTRAL, Medline, Science Direct, Google Scholar, and PubMed databases were searched for studies on FES patients and its association with OSA syndrome, of any design, published from January 1, 1997, to January 1, 2022. A random-effects model that weighted the studies was used when there was heterogeneity between studies ( p < 0.10) and if I 2 values were more than 50%. All p values were 2-tailed and considered statistically significant if <0.05. RESULTS: A total of 12 studies comprising 511 patients were included in this meta-analysis. Of these, 368 were male (77.6%) and the average age was 55.10 years. The overall prevalence of OSA in FES patients was 57.1% (95% CI: 46.5-74.8%), M:F ratio was 48:1 (98% male), and 69.1% of patients received their OSA diagnosis at the time of the study. Of those with FES, tear film abnormalities were the most common ocular comorbidity (78.9%) followed by keratoconus (20.6%), glaucoma (9.8%), and lower eyelid ectropion (4.6%). Obesity was the most common systemic morbidity (43.7%) followed by hypertension (34.0%) and diabetes mellitus (17.9%). CONCLUSION: This meta-analysis demonstrates OSA is a common comorbidity in the FES population. Ophthalmologists are often the first to evaluate patients with FES, and considering this coincidence, routine screens for sleep apnea symptoms in at-risk FES patients should be undertaken. Large case-control studies are required to better elucidate the exact prevalence of OSA and other morbidities in patients with FES, and to better understand the etiology of FES.

Dermatological presentations to a regional Victorian hospital emergency department: A 1-year audit.

OBJECTIVES: The objective of this study is to describe the epidemiological features of each presentation with a primary dermatological diagnosis to a regional emergency department (ED). DESIGN: 1-year retrospective audit. SETTING: Regional Victorian hospital emergency department. PARTICIPANTS: Any presentation to this regional emergency department with a dermatological condition from 1 January 2020 to 31 December 2020. MAIN OUTCOME MEASURES: Dermatology presentations to the ED in 2020 and the prevalence of the associated primary diagnosis. RESULTS: In total, 4.7% (n = 1873) of ED presentations had a primary dermatological diagnosis. Of these, 1484 were ≥18 years of age and 389 were ≤17 years of age. Cellulitis (26.1%, n = 388) was the most common primary diagnosis among presentations ≥18 years. Non-specific rash was the most common diagnosis (23.6%, n = 92) in presentations ≤17 years. Indigenous Australians ≥18 years were more likely to be in a younger age group (p < 0.01), and dermatitis/eczema presentations ≥18 years (n = 10) were the largest diagnostic group referred to a dermatologist. A total of 134 (7.1%) patients ≥18 years travelled more than 50 km to the ED. There were no dermatological emergencies identified. CONCLUSIONS: A high proportion of presentations to this regional ED with a dermatological diagnosis could be well managed by a dermatologist or general practitioner (GP) as an outpatient. The findings of this study inform the need for future rural public dermatology services. Options include teledermatology, or a public weekly or fortnightly rapid review dermatology clinic with a visiting dermatologist, in the absence of a dermatologist onsite.

Is Time Spent on Prior Authorizations Associated With Approval?

Advanced practice providers increasingly assume responsibility for prior authorizations (PAs). We hypothesized that the time burden of PAs will be correlated with increased approval. We collected several variables (ie, type, method, time spent, use of peer to peer, and outcome) for all PAs completed by a departmental nurse practitioner in 1 region. Chi-square tests and 2 sample t tests were used to assess significance. There was no significant association between the method of request, the number of attempts, and the time spent to approved PA. Further research is needed to determine ways to decrease the time and opportunity cost associated with PAs.

Top-cited articles in andrology journals from 2013-2022: a bibliometric analysis.

Bibliometric analyses serve to identify influential articles that have shaped medical practice and fostered new research ideas. Over the past decade, research in andrology has witnessed exponential growth, with an increasing number of academic publications, collaborations, and research innovations. However, there is a lack of literature that has identified the top-cited andrology articles. We conducted a bibliometric analysis to identify the top 1000 citations in andrology journals, with a focus on the top funding agencies, authors, institutions, countries/regions, and journals. To perform this analysis, we identified the top-cited articles in andrology journals as indexed in the Web of Science Core Collection. From 2013 through 2022, we found a total of 9827 articles published in andrology journals. The top publishers included "Andrology," the "Asian Journal of Andrology," and "Andrologia." The top affiliations contributing to research include the Cleveland Clinic Foundation (269 publications), Egyptian Knowledge Bank (EKB) (265), and Shanghai Jiao Tong University (202). Funding was primarily provided by notable agencies such as the National Natural Science Foundation of China (905 grants), United States Department of Health Human Services (321), and National Institutes of Health (NIH USA) (317). The present bibliometric analysis highlights andrology research from 2013 through 2022, offering key insights into leading contributors, influential authors, prominent funding sources, and major trends in the field.

Restorative therapy clinical trials for erectile dysfunction: a scoping review of endpoint measures.

Given the lack of regulatory approval for restorative therapies for the treatment of erectile dysfunction, we hypothesized that clinical trials would vary in methodology and endpoint measurements. Our objective was to analyze methodological approaches and outcome measures of clinical trials evaluating restorative therapies for erectile dysfunction. Data was extracted from clinicaltrials.gov on trials which contained the keywords "erectile dysfunction". We evaluated trials initiated between 2004 and 2021 which listed a restorative therapy intervention. We identified 95 trials investigating energy-based/shockwave therapies (60/95), stem cell therapies (25/95), platelet-based therapies (6/95), and others (4/95). Only 41.1% of the trials evaluated safety. The most common efficacy endpoint was International Index of Erectile Function and Sexual Health Inventory for Men, and only 29.5% utilized penile Doppler. Thirty (31.6%) trials had been completed yet only 3 (3.2%) have published results. We found substantial heterogeneity in methodological approach in the trials. Subjective measures of erectile function were commonly reported, but definitions of inclusion criteria and objective outcome measures were inconsistent. These results provide a basis for the design of future clinical trials to improve the quality of trial data and aid in the development of standardized criteria for erectile dysfunction clinical trials.

Comparison of robotic-assisted laparoscopic radical prostatectomy: SP versus XI, a single surgeon experience.

Currently, there is a paucity of data regarding Single Port (SP) robotic-assisted laparoscopic prostatectomy (RALP). Our objective was to compare our single-institution single-surgeon SP RALP experience to our XI RALP experience with regard to patient selection, perioperative data, and outcomes. Patients who underwent prostatectomy at our institution between August 2019 and April 2021 were selected for analysis. All patients had biopsy confirmed prostate cancer. All surgeries were performed by one urologist at our institution to limit inter-surgeon variability. Demographic and clinical information were extracted from the medical record in standardized fashion. All documented classifications were graded using the Clavien-Dindo classification system. Patients with previous prostate cancer therapies were excluded. Categorical variables were compared using Chi-square or Fisher's exact test where appropriate. Continuous variables were compared using t tests or Wilcoxon rank sum tests where appropriate. Complete records were available for 208 patients. Of the total patient population 127 (61.1%) underwent SP prostatectomy compared to 81 (38.9%) underwent XI prostatectomy. There was no significant difference between the two cohorts in terms of mean age (65 vs. 66 years; p = 0.60), BMI (29.2 vs. 30.1; p = 0.22), preop ASA score ≥ 3 (68.5% vs. 64.2%; p = 0.52), or preop PSA (7.1 vs. 7.4, p = 0.94). There no difference in procedure time for SP prostatectomy (170 vs. 168 min, p = 0.035), estimated blood loss (100 vs. 100 mL; p = 0.14), or average length of stay (1 vs. 1 days; p = 0.22). There was a significant difference in Gleason grade group between the two cohorts with patients undergoing XI RALRP more likely to have higher stage disease (p = 0.025) and a trend towards higher D'Amico risk scores in the XI group (p = 0.053). There was no difference in rate of positive surgical margins (29.9% vs. 29.6%; p = 0.96). There was no difference in the distribution of complications between the two groups (p = 0.99) with 89% of patients having no complication. There was no difference in the number of lymph nodes removed by modality (p = 0.94). To date, this study represents one of the largest cohorts of patients who underwent SP RALP. Importantly, it is among the first studies comparing perioperative variables between the SP and XI platforms. As surgeons become more facile with the SP system there appear to minimal differences in patient factors, perioperative results, or outcomes between the platforms. These findings provide evidence that surgeons who are competent on the XI platform can confidently perform SP RALPs through a single incision without compromising outcomes.

The application of shear wave elastography with ultrasound for rotator cuff tears: a systematic review.

Background: Shear wave elastography (SWE) is an emerging ultrasound-based technology that provides a quantitative assessment of musculoskeletal tissue integrity. This systematic review investigates the use of SWE in the evaluation of rotator cuff tears. Methods: PubMed, Embase, Web of Science, Google Scholar, and the Cochrane Library databases were searched for relevant studies from 1901 up to June 2022. Articles utilizing SWE in rotator cuff tears were selected based on inclusion and exclusion criteria. The studies included involved the assessment of shear wave velocity, tendon thickness and stiffness after healing, and fatty infiltrates evaluation using SWE. The Newcastle-Ottawa Scale was used to evaluate the risk of bias in included observational studies. Double-sided P value < .05 was considered statistically significant. Results: Sixteen studies comprising 520 patients were included in the systematic review. SWE demonstrated that shear wave velocities in torn supraspinatus tendons were lower than in healthy supraspinatus tendons. A decrease in tendon SWE modulus elasticity was observed in tendinopathic tendons. Shear wave velocity decreased with increasing fat content and muscle atrophy. The velocity of SWE in muscle in re-tear groups was greater than in the healed group at 1 month after surgery (P < .05). Conclusion: SWE ultrasound of the supraspinatus tendon can be a useful diagnostic tool for orthopedic surgeons that provide quantitative information on tendinopathic stiffness, velocity, fatty infiltrate, and elasticity characteristics. Decreased tendon velocity of SWE may predict recurrent rotator cuff tears and be useful in postoperative evaluations for muscle healing to plan for future management.

Renal cell carcinoma with tumor thrombus: A review of relevant anatomy and surgical techniques for the general urologist.

Renal cell carcinoma (RCC) is estimated to account for 4.1% of all new cancer diagnoses and 2.4% of all cancer deaths in 2020 according to the National Cancer Institute SEER database. This will likely total 73,000 new cases and 15,000 deaths. RCC is one of the most lethal of the common cancers urologists will encounter with a 5-year relative survival of 75.2%. Renal cell carcinoma is one of a small subset of malignancies that are associated with tumor thrombus formation, which is tumor extension into a blood vessel. An estimated 4% to 10% of patients with RCC will have some degree of tumor thrombus extending into the renal vein or inferior vena cava at the time of diagnosis. Tumor thrombi change the staging of RCC and therefore are an important part of initial patient workup. It is known that such tumors are more aggressive with higher Fuhrman grades, N+ or M+ at time of surgery and have higher probability of recurrence with lower cancer-specific survival. Aggressive surgical intervention with radical nephrectomy and thrombectomy can be performed with survival benefits. Classifying the level of the tumor thrombus becomes vitally important in surgical planning as it will dictate the surgical approach. Level 0 thrombi may be amenable to simple renal vein ligation while level 4 can require thoracotomy and possible open-heart surgery with coordination of many surgical teams. Here we will review the anatomy associated with each level of tumor thrombus and attempt to construct an outline for surgical techniques that may be used. We aim to give a concise overview so that general urologists may use it to understand these potentially complicated cases.

Testosterone Therapy in Advanced Prostate Cancer.

Androgen deprivation therapy is a mainstay of advanced prostate cancer (PCa) but the resulting low testosterone levels leave men susceptible to a multitude of adverse effects. These can include vasomotor symptoms, reduced sexual desire and performance, and mood changes. Testosterone therapy (TTh) in advanced PCa has historically been contraindicated since Huggins and Hodges reported that testosterone activates PCa. Although TTh has been demonstrated to be safe in patients who have undergone treatment for localized PCa, there is extremely limited evidence on its safety in advanced PCa. Despite the lack of evidence, some men with advanced PCa still inquire about TTh, and recent publications have described its use. In this article, we review the potential implications of TTh in men with advanced PCa, defined here as biochemical recurrence after localized therapy or metastatic PCa that is either hormone sensitive or castration resistant.

Incidence of fertility preservation procedures in prepubertal individuals with cancer.

BACKGROUND: Fertility Preservation (FP) for children and adolescents with cancer is underutilized. In prepubertal individuals, ovarian and testicular tissue can be frozen; however, this is still considered largely experimental. Our objective was to identify trends of FP in prepubertal individuals. METHODS: We performed a retrospective study of prepubertal children with cancer identified through the Pediatric Health Information System from 2011 to 2020. Children who underwent a testicular or ovarian biopsy were included. Any patients with testicular or ovarian malignancy, or other diagnoses which may have required a gonadal biopsy were excluded. RESULTS: A total of 418 boys under 13 and 333 girls under 12 who underwent a gonadal biopsy were identified. There was a total of 66,929 new cancer diagnoses in girls and 86,001 new cancer diagnoses in boys during this time. The most common cancer diagnosis was hematologic in both boys (50.96%) and girls (36.64%). A concurrent procedure at time of gonadal biopsy was performed in 84% of boys and 62% of girls, with line insertion being the most common. The only predictive variable of receiving a gonadal biopsy was increasing year. Overall, only 0.04% of children had a gonadal biopsy for FP during this time period. CONCLUSIONS: Gonadal biopsy rates have increased in prepubertal children with cancer, presumably for FP. While recent international guidelines support FP in this group, our findings highlight the need to establish protocols and tracking for FP procedures in the US.

Do Women Have a Seat at the Table: Trends in Female Representation Among the Board of Directors in American Urological Association Subspecialty Societies.

Introduction Although women remain vastly underrepresented in urology, the proportion of female urology residents and practicing urologists has steadily increased over the last four decades. However, it remains critical to evaluate the representation of females in the pipeline when examining trainees and practicing urologists. As it pertains to leadership positions, the gender distribution among the board of directors (BOD) and committee chairs in the American Urological Association (AUA) subspecialties has not been studied to date. Therefore, we plan to analyze the proportion of females among the BOD and committee chairs in different subspecialty societies recognized by the AUA over time. Methods We conducted a cross-sectional observational study, quantitatively comparing the composition of gender in BOD and Committee Chair members belonging to different AUA-recognized subspecialty societies from 2014 to 2020. The websites for each subspecialty society were searched and contacted. Results We evaluated BODs from 10 AUA subspecialty societies and committee chair members from 6 AUA subspecialty societies. From 2014 to 2020, the total proportion of female BOD amongst all AUA sub-specialty societies did not change significantly, with a small increase from 10.6% (n = 29) to 13.5% (n = 36). However, female representation among committee chair members significantly increased from 9.8% (n = 20) to 19.2% (n = 44; p = 0.006), along with the total number of women in urology, from 897 (8.9%) to 1,375 (10.3%). Increases in female representation were seen in the Society for the Study of Male Reproduction (SSMR) from 0% to 9% and in the Indian American Urological Association (IAUA) from 4% to 13%. Of note, there were no elected female board members in the Society of Urologic Oncology (SUO) or the Urologic Society for Transplantation and Renal Surgery (USTRS) from 2014 to 2020. Conclusion Females remain a minority in leadership positions at AUA sub-specialty societies despite increased female representation in recent years. Future efforts should promote the advancement of women to positions of leadership to reflect the changing landscape of the urology workforce and surgical specialties.

Outcomes of organ-sparing surgery for adult testicular tumors: A systematic review of the literature.

OBJECTIVE: To perform a systematic review on the effects of testicular sparing surgery (TSS) on the oncological, functional, and hormonal outcomes of adults with testicular tumors. METHODS: A literature search was performed after PROSPERO registration (CRD42020200842) and reported in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methods. We conducted a systematic search of Medline (Ovid), Embase, Cochrane CENTRAL, CINAHL, Scopus, Web of Science, ClinicalTrials.gov, and the WHO/ICTRP from inception to November 20, 2020. Manuscripts and published abstracts were included if they involved testis-sparing surgery (TSS) and contained data on any outcomes related to fertility, hormonal parameters, or oncological control, or if they evaluated surgical technique. RESULTS: Our initial search yielded 3,370 manuscripts, with 269 of these screened for full-text eligibility. After our exclusion criteria were applied, 32 studies were included in the final analysis. Oncological outcomes were obtained from 12 studies (average follow-up 57.8 months), functional data from 26 studies (average follow-up 49.6 months), fertility information from 10 studies (average follow-up 55.8 months), and data on nonpalpable tumors from 11 studies (average follow-up 32.1 months). Oncological control appears to be excellent in studies that reported these outcomes. Presence of germ cell neoplasia in situ was controlled with adjuvant radiation in nearly all cases. Functional outcomes are also promising, as development of primary and compensated hypogonadism was rare. Semen parameters are poor preoperatively among men with benign and malignant testis tumors, with occasional decline after TSS. Frozen section analysis at the time of surgery appears to be very reliable, and the majority of nonpalpable tumors appear to be benign. CONCLUSIONS: TSS is a safe and efficacious technique with regards to oncological control and postoperative hormonal function based on retrospective, noncontrolled studies. TSS avoids unnecessary removal of benign testicular tissue, and should be given serious consideration in cases of nonpalpable, small tumors under 2 cm. In cases of malignancy, TSS can safely avoid anorchia in men with bilateral tumors and in men with solitary testicles. The use of the operating microscope, while theoretically promising, does not necessarily lead to better outcomes, however data are limited.

Undisplayed Bicarbonate ion Concentration in Arterial Blood Gas Analysis.

Blood bicarbonate ion concentration (BcHCO3 (-)) is a vital parameter in the management of acid base disorders. In an arterial blood gas (ABG) analyzer, the BcHCO3 (-) is calculated from the values of pH and pCO2. We received four samples in a span of one year, from December 2011 to November 2012 for arterial blood gas analysis, in which the BcHCO3 (-) was not displayed by the blood gas analyzer. Based on the information available in literature, the formula for calculating the BcHCO3 (-) from pH and pCO2 was obtained and BcHCO3 (-) was calculated in all four samples mentioned above. An attempt was made to establish a clinical correlation between laboratory and clinical data of these patients. All these values of BcHCO3 (-) were above the maximum display limit of our blood gas analyzer, which was 60 mmol/L and hence, they were not displayed. All four patients had chronic respiratory disease and they were taking furosemide and / or dexamethasone. High values of BcHCO3 (-) , sometimes falling beyond the display range of the ABG analyzer, could be observed in patients of chronic respiratory disease, treated with drugs like furosemide and dexamethasone, that result in bicarbonate retention.