The transcription factor musculin promotes the unidirectional development of peripheral Treg cells by suppressing the TH2 transcriptional program.

Although master transcription factors (TFs) are key to the development of specific T cell subsets, whether additional transcriptional regulators are induced by the same stimuli that dominantly repress the development of other, non-specific T cell lineages has not been fully elucidated. Through the use of regulatory T cells (Treg cells) induced by transforming growth factor-ß (TGF-ß), we identified the TF musculin (MSC) as being critical for the development of induced Treg cells (iTreg cells) by repression of the T helper type 2 (TH2) transcriptional program. Loss of MSC reduced expression of the Treg cell master TF Foxp3 and induced TH2 differentiation even under iTreg-cell-differentiation conditions. MSC interrupted binding of the TF GATA-3 to the locus encoding TH2-cell-related cytokines and diminished intrachromosomal interactions within that locus. MSC-deficient (Msc-/-) iTreg cells were unable to suppress TH2 responses, and Msc-/- mice spontaneously developed gut and lung inflammation with age. MSC therefore enforced Foxp3 expression and promoted the unidirectional induction of iTreg cells by repressing the TH2 developmental program.

THE COMBINATION OF ORAL VALACYCLOVIR WITH TOPICAL CLOBETASOL THERAPY WAS THE MOST EFFECTIVE IN REDUCING THE TIME TO HEAL FROM HERPES LABIALIS.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Koe KH, Veettil SK, Maharajan MK, Syeed MS, Nair AB, Gopinath D. comparative efficacy of antiviral agents for prevention and management of herpes labialis: A systematic review and network meta-analysis. J Evid Based Dent Pract. 2023 Mar; 23(1):101778. doi: 10.1016/j.jebdp.2022.101778. Epub 2022 Sep 14. PMID: 36914303. SOURCE OF FUNDING: None. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis.

Peyronie's disease: what do we know and how do we treat it?

INTRODUCTION: Peyronie's disease is a common, benign condition characterized by an acquired penile abnormality due to fibrosis of the tunica albuginea. This may lead to penile curvature, deformity, discomfort, pain, and erectile dysfunction, resulting in emotional and psychosocial effects on patients. Therefore, it is important for urologists to thoroughly evaluate the extent of the patient's bother and discuss treatment goals, therapeutic options, and expectations. MATERIALS AND METHODS: We provide a review of the current landscape for the diagnosis, management, and treatment of Peyronie's disease, including oral, topical, intralesional, external energy, and surgical therapies. RESULTS: The hallmark of managing Peyronie's disease is attentive patient counseling. Patients may be hesitant to discuss their symptoms unless inquired directly and may not be aware that treatments exist. It is not uncommon for Peyronie's disease to be diagnosed incidentally during a routine or unrelated healthcare visit, with reported rates of incidental diagnosis as high as 16%. Treatment options are stratified by disease phase which is defined by whether symptoms (e.g. penile deformity and discomfort) are actively changing or have stabilized. Conservative therapy is the most common recommendation during the active phase with more invasive treatments reserved for the passive phase. Conservative therapy may include oral or topical medication, intralesional injection, and external energy therapy. These treatments may also have a role in improving symptoms during the passive phase prior to undergoing more definitive surgical treatment. Surgical interventions include tunical plication, plaque incision or excision with or without grafting, and penile prosthesis implantation. Despite the variety of treatment options available to patients, each has a distinct efficacy and adverse effect profile, warranting thorough discussion to meet patients' goals and manage expectations. CONCLUSION: Peyronie's disease is a common condition that is underdiagnosed and undertreated. Patients with Peyronie's disease will benefit from a comprehensive evaluation and in-depth counseling so that they may become familiar with the natural disease course and have appropriate expectations of each treatment option.

Benign prostatic hyperplasia: an update on minimally invasive therapy including Aquablation.

INTRODUCTION: Lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) is a common condition affecting older men. New interventional treatments have emerged and evolved over the years, each with their own distinct efficacy and safety profiles. While some have fallen out of favor, new options continue to be explored. MATERIALS AND METHODS: We provide a review and update on minimally invasive treatment modalities for BPH, including prostatic artery embolization (PAE), Aquablation, convective water vapor thermal therapy (Rezum), and prostatic urethral lift (Urolift). RESULTS: While current urologic guidelines recommend against PAE outside of the context of clinical trials, Aquablation, Rezum, and Urolift have demonstrated excellent efficacy and durability in relieving LUTS in the BPH patient. When compared to the gold standard, transurethral resection of the prostate (TURP), these novel therapies yield equivalent or superior objective outcomes, with the additional benefit of significantly reduced sexual side effects. Additionally, Rezum and Urolift may be performed as outpatient procedures under local anesthesia, allowing for decreased hospitalizations, operative times, catheterization duration, and financial burden on the health care system. CONCLUSIONS: Aquablation, Rezum and Urolift are minimally invasive surgical treatment options capable of providing rapid, significant, and durable relief of LUTS secondary to BPH. Each technique demonstrates comparable efficacy to TURP with the added advantages of preserving sexual function, decreasing patient morbidity, and limiting healthcare costs.

Holmium laser enucleation of the prostate (HoLEP): size-independent gold standard for surgical management of benign prostatic hyperplasia.

INTRODUCTION: Holmium laser enucleation of the prostate (HoLEP) has become an increasingly common surgical management option for treatment of symptomatic benign prostatic hyperplasia (BPH). Transurethral resection of the prostate (TURP) has long been considered the gold standard, contemporary literature and newer guidelines indicate that HoLEP has become the new size-independent endoscopic gold standard for surgical BPH treatment. MATERIALS AND METHODS: We provide a review and update on current HoLEP surgical techniques, outcomes, safety, and durability according to the growing body of literature. RESULTS: The current body of literature and guidelines indicate HoLEP as a safe and effective surgical treatment for symptomatic BPH regardless of prostate size. Durable long term subjective and objective outcomes have been demonstrated in previous studies, extending beyond 10 years. CONCLUSIONS: HoLEP continues to demonstrate durable long term efficacy for treating patients suffering from lower urinary tract symptoms (LUTS) due to BPH. The American Urological Association (AUA) guidelines recommend its use as a size-independent endoscopic treatment option. HoLEP has proven itself to be the new gold standard in surgical treatment for LUTS secondary to BPH with the ability to endoscopically treat prostates independent of size, with durable long term outcomes.

Simple frameshifts in minimally invasive surgery postoperative pain management significantly reduce opiate prescriptions.

INTRODUCTION: To evaluate the impact of an 'opt-in' non-narcotic postoperative pain regimen on narcotic utilization and patient-reported pain scores. MATERIALS AND METHODS: A prospective, non-blinded pre- and post-interventional trial was conducted, including a lead-in period for baseline evaluation. The intervention group received a new pain protocol prioritizing non-narcotic medications, an 'opt-in' requirement for opiates, and standardized patient education. Study outcomes included opiate prescription and utilization (measured in Morphine Equivalent Doses) and reported pain scores on postoperative day (POD) 1, discharge and follow up. RESULTS: At discharge, 70% fewer patients were prescribed any opioids (ARR: -0.7; p < 0.001); the amount prescribed was reduced by 95% (pre-intervention 69.3 mg versus post-intervention 3.5 mg, p < 0.001). Mean opioids used following discharge decreased by 76% (14.7 mg versus 3.5 mg, p = 0.011). In a subgroup analysis of robotic prostatectomies, there was a 95% reduction in mean opioids prescribed at discharge (64.6 mg versus 3.2 mg, p < 0.001) and 82% reduction in utilization over entire postoperative course (87.6 mg versus 15.7 mg, p = 0.001). There was no significant difference in pain scores between intervention groups at POD 1, discharge and follow up for patients (entire cohort and post-prostatectomy). CONCLUSION: A standardized pain protocol with 'opt-in' requirements for opiate prescription, emphasis on non-narcotic medications, and patient education, resulted in significant reductions in opioid use. Simple frameshifts in pain management can yield significant gains in the opioid epidemic.

Predictors of Disease Recurrence after Venoplasty and Stent Placement for May-Thurner Syndrome.

PURPOSE: To identify factors independently associated with disease recurrence after venoplasty and stent placement for May-Thurner syndrome (MTS). MATERIALS AND METHODS: Fifty-nine consecutive patients (age, 47 y ± 15; 93% female) were identified who had undergone endovascular stent placement for MTS. Patient charts were reviewed for demographic data, risk factors for venous thrombosis, comorbidities, and venous inflow or outflow at first follow-up (3 wk to 6 mo after treatment). Logistic regression was used to identify independent predictors of symptom recurrence or repeat intervention, and multivariate analysis of variance and receiver operator characteristic curve analysis were used to assess relationships between degrees of in-stent stenosis and other variables in the 73% of patients with available cross-sectional imaging. Median follow up was 20.7 months (interquartile range, 4.7-49.5 mo). RESULTS: All procedures were technically successful. Disease recurrence, defined as symptom recurrence following initial postprocedural resolution, was observed in 38% of patients. No preprocedural variable was found to be independently predictive of disease recurrence; however, poor venous inflow or outflow were both strongly associated with recurrent disease, with adjusted odds ratios and 95% confidence intervals of 38.02 (3.76-384.20; P = .002) and 7.00 (1.15-42.71; P = .04), respectively. Higher degrees of in-stent stenosis were also associated with symptom recurrence, with an area under the curve of 0.93 (P = .000002) and 39%-41% stenosis being 78%-83% sensitive and 88%-92% specific for symptom recurrence. CONCLUSIONS: These results suggest that cross-sectional imaging can help differentiate patients in whom closer follow-up may be warranted after venoplasty and stent placement for MTS and also guide counseling regarding prognosis.

MRI at diagnostic versus confirmatory biopsy during MRI-based active surveillance of prostate cancer.

OBJECTIVES: Active surveillance (AS) is a management strategy for patients with favorable risk prostate cancer. Multi-parametric magnetic resonance imaging (mpMRI) may impact upgrading rates, but there is mixed evidence on the appropriate timing to introduce mpMRI. We evaluated timing of initial mpMRI use for patients on AS and compared upgrading and intervention rates for AS candidates who received initial mpMRI before diagnostic biopsy vs. confirmatory biopsy. SUBJECTS AND METHODS: Patients enrolled in AS captured by the Prospective Loyola Urology mpMRI (PLUM) Prostate Biopsy Cohort which captures men undergoing MRI-fusion prostate biopsy. We included patients enrolled in AS between January 2014 and October 2022. We conducted a retrospective analysis of patients who underwent MRI-fusion prostate biopsy while on AS at our institution. The cohort was stratified by men who underwent first mpMRI prior to diagnostic biopsy (MRI-DBx), confirmatory biopsy (MRI-CBx), or a subsequent surveillance biopsy. Oncologic outcomes including pathologic reclassification, intervention-free survival, progression-free survival, and overall survival were evaluated. RESULTS: Of 346 patients identified on AS, 94 (27.2%) received mpMRI at the time of diagnostic biopsy, 182 (52.6%) at confirmatory biopsy, and 70 (20.2%) at a later biopsy. At confirmatory biopsy (median 14 months), there was no difference in upgrading (HR 0.95, P = 0.78) or intervention rates (HR 0.97, P = 0.88) between MRI-DBx and MRI-CBx. PI-RADS score on initial mpMRI was associated with upgrading during AS follow-up relative to men with negative mpMRI (HR 4.20 (P = 0.04), 3.24 (P < 0.001), and 1.99 (P < 0.001) for PI-RADS 5, 4, and 3, respectively), and PSA density was associated with intervention (HR 1.52, P = 0.03). CONCLUSION: mpMRI can serve as a prognostic tool to select and monitor AS patients, but there was no difference in upgrading or intervention rates based on initial timing of MRI.

Conversion of Holmium Laser Enucleation of Prostate to Open Prostatectomy.

OBJECTIVE: To determine the incidence and predictive factors for conversion to an open procedure during Holmium Laser Enucleation of Prostate (HoLEP). METHODS: A retrospective review was performed on files of all patients that underwent HoLEP at our institution between 2013 and 2020. Data collected included demographics, pre-operative estimated prostate size, intraoperative data, pathologic data, and functional baseline. A univariate and multivariate comparison between the pre-operative data of converted and un-converted cases was conducted. RESULTS: Among a total of 807 HoLEP procedure performed during the above period, 20 cases were converted to open procedures (2.4%). Median pre-operative estimated prostate size in cases of conversion was 228ml compared to 95ml for unconverted cases (P <.001). The reasons for conversion were anatomical in 8 cases (40%), bleeding that was difficult to control endoscopically in 4 cases (20%), expected procedure to be too long due to large prostate size in 6 cases (30%), one case of morcellation technical malfunction, and one case with very large bladder stones not suitable for endoscopic treatment. Prostate size was the only factor that was found to be associated with conversion in univariate and multivariate analysis. CONCLUSION: The risk of conversion of HoLEP to open procedures is size-dependent. The risk for conversion to open prostatectomy/cystotomy must be communicated to patients who choose HoLEP to improve the informed consent process and provide the highest quality of patient care and transparency. Open prostatectomy/cystotomy should be a part of the armamentarium of every HoLEP surgeon operating on large prostates.

Holmium Laser Enucleation of the Prostate Following Previous Prostatic Urethral Lift.

Purpose: To determine the feasibility and operative challenges of holmium laser enucleation of the prostate (HoLEP) in patients with previous prostatic urethral lift (PUL) procedure. Materials and Methods: A retrospective review was performed on files of all patients that underwent HoLEP at our institution between 2013 and 2021. Seven hundred ninety-three consecutive HoLEP cases were identified. Data collected included demographics, the time elapsed since previous PUL, number of PUL implants, preoperative prostate size, intraoperative complications/challenges, and postoperative follow-up. Results: Twenty-two men with a mean preoperative prostate size of 90 g (range 32-180 g) underwent HoLEP at a median of 14.4 months (range 2.8-48) after PUL. 63.6% (14/22) of cases involved prostates with preoperative sizes ≥80 g. Three cases involved PUL implant jamming of morcellator blades, which required replacing the blades. Fifteen cases (68.2%) required using a grasper or a basket device to remove free PUL implants or adenoma parts with PUL implants embedded in them. One patient needed a second procedure to remove a relatively large piece of calcified adenoma. Nonpost-PUL HoLEP was more time efficient than post-PUL HoLEP (0.77 vs 0.55 mL/minute respectively). There was no difference in functional outcome between post-PUL and nonpost-PUL HoLEP cases. Conclusions: While HoLEP can be performed safely and effectively in the PUL failure population, unique challenges arise. PUL implants may distort prostate anatomy, jam morcellator blades, and may be encountered in aberrant locations. Patients with borderline indications for PUL should be aware of the possibility of performing HoLEP in case of PUL failure.

Setting the Standards: Examining Research Productivity Among Academic Urologists in the USA and Canada in 2019.

BACKGROUND: Research productivity among academic urologists is strongly encouraged, but little data are available on productivity metrics within the field. OBJECTIVE: To provide the first comprehensive survey of research productivity among academic urologists in the USA and Canada. DESIGN, SETTING, AND PARTICIPANTS: Using the Accreditation Council for Graduate Medical Education, the Canadian Resident Matching Service, and individual program websites, all active accredited urology faculties were identified. For each individual, we collected data on American Urological Association section, title, gender, fellowship training, Scopus H-index, and citations. Comprehensive searches were completed during March-May 2019. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive statistics for demographic comparisons were performed using analysis of variance for continuous variables and chi-square test for categorical variables. Multivariable logistic regressions were used to identify the predictors of H-index greater than the median. RESULTS AND LIMITATIONS: A total of 2214 academic urology faculties (2015 in USA and 199 in Canada) were identified. The median and mean H-indices for the entire cohort of physicians were 11 and 16.1, respectively. On multivariable analysis, physicians in the North Central and Western Sections (vs mid-Atlantic), who were fellowship trained (vs no fellowship training), and of higher academic rank (professor and associate professor vs clinical instructor) were more likely to have H-index values greater than the median. Additionally, female physicians (vs male) were more likely to have H-index values less than the median. CONCLUSIONS: This study represents the first comprehensive assessment of research productivity metrics among academic urologists. These represent key benchmarks for trainees considering careers in academics and for practicing physicians gauging their own productivity in relation to their peers. PATIENT SUMMARY: In this study, we provide the first comprehensive assessment of research productivity among academic urologists in the USA and Canada. Our results help provide key benchmarks for trainees considering careers in academics and for practicing physicians gauging their own productivity in relation to peers.

Preventing Prostate Biopsy Complications: to Augment or to Swab?

OBJECTIVE: To use data from a large, prospectively- acquired regional collaborative database to compare the risk of infectious complications associated with three American Urologic Association- recommended antibiotic prophylaxis pathways, including culture-directed or augmented antibiotics, following prostate biopsy. METHODS: Data on prostate biopsies and outcomes were collected from the Pennsylvania Urologic Regional Collaborative, a regional quality collaborative working to improve the diagnosis and treatment of prostate cancer. Patients were categorized as receiving one of three prophylaxis pathways: culture-directed, augmented, or provider-discretion. Infectious complications included fever, urinary tract infections or sepsis within one month of biopsy. Odds ratios of infectious complication by pathway were determined, and univariate and multivariate analyses of patient and biopsy characteristics were performed. RESULTS: 11,940 biopsies were included, 120 of which resulted in infectious outcomes. Of the total biopsies, 3246 used "culture-directed", 1446 used "augmented" and 7207 used "provider-discretion" prophylaxis. Compared to provider-discretion, the culture-directed pathway had 84% less chance of any infectious outcome (OR= 0.159, 95% CI = [0.074, 0.344], P < 0.001). There was no difference in infectious complications between augmented and provider-discretion pathways. CONCLUSIONS: The culture-directed pathway for transrectal prostate biopsy resulted in significantly fewer infectious complications compared to other prophylaxis strategies. Tailoring antibiotics addresses antibiotic-resistant bacteria and reduces future risk of resistance. These findings make a strong case for incorporating culture-directed antibiotic prophylaxis into clinical practice guidelines to reduce infection following prostate biopsies.

Efficacy of endovascular Z-configuration stenting for malignant versus nonmalignant caval obstruction.

OBJECTIVE: The objective of this study was to assess factors associated with symptom resolution after endovascular stenting for superior or inferior vena cava syndrome. METHODS: Eighty-six consecutive vena cava Z-configuration stent placements in 82 patients (53 ± 14 years old) at a single institution were reviewed for patient demographics, comorbidities, and durability of stent patency (also evaluated were persistent or recurrent symptoms, stent occlusion, and need for repeated stenting). Logistic regression was used to identify independent factors associated with stent patency, and Φ coefficients and analysis of variance were used to compare cases subdivided by lesion location (superior vena cava, inferior vena cava) and the presence or absence of malignant disease. RESULTS: Clinical follow-up was available in 77 of 86 (90%) cases. Technical success with clinical failure (persistent symptoms) occurred in 40% of these cases with a median follow-up of 67 (interquartile range, 14-570) days and mortality rate of 63% during this period. Malignant obstructions had a significantly higher clinical failure rate of 54% compared with 15% for nonmalignant obstructions (Φ = 0.34; P = .002). However, only metastatic disease was independently associated with clinical failure when controlling for demographics, other comorbidities, and differential follow-up (adjusted odds ratio, 8.27; 95% confidence interval, 2.79-24.50). CONCLUSIONS: Vena cava Z-stenting effectively resolves symptoms in 85% of nonmalignant obstructions compared with only 46% of malignant obstructions. Patients should be counseled accordingly, and those with malignant obstructions may require closer follow-up to evaluate the need for reintervention and goals of care.

SGK1 Governs the Reciprocal Development of Th17 and Regulatory T Cells.

A balance between Th17 and regulatory T (Treg) cells is critical for immune homeostasis and tolerance. Our previous work has shown Serum- and glucocorticoid-induced kinase 1 (SGK1) is critical for the development and function of Th17 cells. Here, we show that SGK1 restrains the function of Treg cells and reciprocally regulates development of Th17/Treg balance. SGK1 deficiency leads to protection against autoimmunity and enhances self-tolerance by promoting Treg cell development and disarming Th17 cells. Treg cell-specific deletion of SGK1 results in enhanced Treg cell-suppressive function through preventing Foxo1 out of the nucleus, thereby promoting Foxp3 expression by binding to Foxp3 CNS1 region. Furthermore, our data suggest that SGK1 also plays a critical role in IL-23R-mediated inhibition of Treg and development of Th17 cells. Therefore, we demonstrate that SGK1 functions as a pivotal node in regulating the reciprocal development of pro-inflammatory Th17 and Foxp3+ Treg cells during autoimmune tissue inflammation.