Sex differences in M2 polarization, chemokine and IL-4 receptors in monocytes and macrophages from asthmatics.

Allergic asthma affects more women than men. It is mediated partially by IL-4/IL-13-driven polarization of monocyte-derived macrophages in the lung. We tested whether sex differences in asthma are due to differential IL-4 responsiveness and/or chemokine receptor expression in monocytes and monocyte-derived macrophages from healthy and allergic asthmatic men and women. We found female cells expressed M2 genes more robustly following IL-4 stimulation than male cells, as did cells from asthmatics than those from healthy controls. This likely resulted from increased expression ofγC, part of the type I IL-4 receptor, and reduced IL-4-induced SOCS1, a negative regulator of IL-4 signaling, in asthmatic compared to healthy macrophages. Monocytes from asthmatic women expressed more CX3CR1, which enhances macrophage survival. Our findings highlight how sex differences in IL-4 responsiveness and chemokine receptor expression may affect monocyte recruitment and macrophage polarization in asthma, potentially leading to new sex-specific therapies to manage the disease.

Benign Cardiac Neoplasms in the United States: A Thirteen-Year Review.

Cardiac neoplasms are uncommon tumors. For epidemiological purposes, they can be divided into benign and malignant subtypes, with the former occurring at a significantly higher rate than the latter. Due to their uncommon nature, there are few data-driven studies examining the characteristics and trends of benign cardiac neoplasms. Our retrospective HCUP-NIS data review purports to illuminate some of the trends surrounding benign cardiac neoplasms and their associated co-occurrences. The data consisted of 482,872,274 weighted discharges. There were 45,568 weighted discharges that included a benign cardiac neoplasm. Benign cardiac neoplasms were more often observed in women (64.33%), and the average age was 63.8 years. The most common cardiovascular co-occurrences in patients with benign cardiac neoplasm were atrial tachyarrhythmias (28.93%), heart failure (19.61%), and embolic events such as stroke, myocardial infarct, or pulmonary embolism (19.82%). Other co-occurrences included pulmonary hypertension (7.55%), ventricular arrhythmias (3.23%), and other EKG abnormalities (3.70%). Procedures were numerous in patients with benign cardiac neoplasms. 43% of patients with this diagnosis had some form of cardiac surgery during their hospitalization. Overall, this study found low incidence of benign cardiac neoplasms in the USA during this 13-year study period. However, in the presence of benign cardiac neoplasms, our study showed that cardiovascular co-occurrences are not uncommon and may help to illuminate this otherwise rare diagnosis.

Androgen and Androgen Receptor as Enhancers of M2 Macrophage Polarization in Allergic Lung Inflammation.

Allergic asthma is a disease initiated by a breach of the lung mucosal barrier and an inappropriate Th2 inflammatory immune response that results in M2 polarization of alveolar macrophages (AM). The number of M2 macrophages in the airway correlates with asthma severity in humans. Sex differences in asthma suggest that sex hormones modify lung inflammation and macrophage polarization. Asthmatic women have more M2 macrophages than asthmatic men and androgens have been used as an experimental asthma treatment. In this study, we demonstrate that although androgen (dihydrotestosterone) reconstitution of castrated mice reduced lung inflammation in a mouse model of allergic lung inflammation, it enhanced M2 polarization of AM. This indicates a cell-specific role for androgens. Dihydrotestosterone also enhanced IL-4-stimulated M2 macrophage polarization in vitro. Using mice lacking androgen receptor (AR) in monocytes/macrophages (ARfloxLysMCre), we found that male but not female mice exhibited less eosinophil recruitment and lung inflammation due to impaired M2 polarization. There was a reduction in eosinophil-recruiting chemokines and IL-5 in AR-deficient AM. These data reveal an unexpected and novel role for androgen/AR in promoting M2 macrophage polarization. Our findings are also important for understanding pathology in diseases promoted by M2 macrophages and androgens, such as asthma, eosinophilic esophagitis, and prostate cancer, and for designing new approaches to treatment.

Functional Recovery, Oncologic Outcomes and Postoperative Complications after Robot-Assisted Radical Prostatectomy: An Evidence-Based Analysis Comparing the Retzius Sparing and Standard Approaches.

PURPOSE: We report a 1-year update of functional urinary and sexual recovery, oncologic outcomes and postoperative complications in patients who completed a randomized controlled trial comparing posterior (Retzius sparing) with anterior robot-assisted radical prostatectomy. MATERIALS AND METHODS: A total of 120 patients with clinically low-intermediate risk prostate cancer were randomized to undergo robot-assisted radical prostatectomy via the posterior and anterior approach in 60 each. Surgery was performed by a single surgical team at an academic institution. An independent third party ascertained urinary and sexual function outcomes preoperatively, and 3, 6 and 12 months after surgery. Oncologic outcomes consisted of positive surgical margins and biochemical recurrence-free survival. Biochemical recurrence was defined as 2 postoperative prostate specific antigen values of 0.2 ng/ml or greater. RESULTS: Median age of the cohort was 61 years and median followup was 12 months. At 12 months in the anterior vs posterior prostatectomy groups there were no statistically significant differences in the urinary continence rate (0 to 1 security pad per day in 93.3% vs 98.3%, p = 0.09), 24-hour pad weight (median 12 vs 7.5 gm, p = 0.3), erection sufficient for intercourse (69.2% vs 86.5%) or postoperative Sexual Health Inventory for Men score 17 or greater (44.6% vs 44.1%). In the posterior vs anterior prostatectomy groups a nonfocal positive surgical margin was found in 11.7% vs 8.3%, biochemical recurrence-free survival probability was 0.84 vs 0.93 and postoperative complications developed in 18.3% vs 11.7%. CONCLUSIONS: Among patients with clinically low-intermediate risk prostate cancer randomized to anterior (Menon) or posterior (Bocciardi) approach robot-assisted radical prostatectomy the differences in urinary continence seen at 3 months were muted at the 12-month followup. Sexual function recovery, postoperative complication and biochemical recurrence rates were comparable 1 year postoperatively.

Predicting lymph node invasion in patients treated with robot-assisted radical prostatectomy.

INTRODUCTION: To develop a nomogram to predict lymph node invasion (LNI) in the contemporary North American patient treated with robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: We included 2,007 patients treated with RARP and pelvic lymph node dissection (PLND) at a single institution between 2008 and 2012. D'Amico low risk patients underwent an obturator and hypogastric PLND, while extended PLND was reserved for intermediate/high risk patients. Logistic regression analysis tested the relationship between LNI and all available predictors. Independent predictors of LNI were used to develop a novel nomogram. Discrimination, calibration and decision-curve analysis were used to analyze the performance of our novel nomogram, and compare it to open radical prostatectomy (ORP)-based models, namely the Godoy nomogram. RESULTS: Overall, 5.3% of our patients harbored LNI. Median number of lymph nodes removed was 6.0 (interquartile range: 4-11). The most parsimonious multivariable model to predict LNI consisted of the following independent predictors: PSA value, clinical stage, and primary and secondary Gleason scores (all p ≤ 0.02). The discrimination of our novel model was 86.2%, and its calibration was virtually optimal. Using a 2% nomogram cut off, 58% of patients would be spared PLND, while missing only 9.4% of individuals with LNI. The novel nomogram compared favorably to the Godoy nomogram, when discrimination, calibration and net-benefit were used as benchmarks. CONCLUSIONS: Approximately 5% of contemporary North American patients harbor LNI at RARP. Our novel nomogram can accurately identify these patients, and this may help to improve patient selection, and avoid unnecessary PLND in the majority of patients.

Predicting pathological outcomes in patients undergoing robot-assisted radical prostatectomy for high-risk prostate cancer: a preoperative nomogram.

OBJECTIVE: To identify which high-risk patients with prostate cancer may harbour favourable pathological outcomes at radical prostatectomy (RP). PATIENTS AND METHODS: We evaluated 810 patients with high-risk prostate cancer, defined as having one or more of the following: PSA level of >20 ng/mL, Gleason score ≥8, clinical stage ≥T2c. Patients underwent robot-assisted RP (RARP) with pelvic lymph node dissection, between 2003 and 2012, in one centre. Only 1.6% (13/810) of patients received any adjuvant treatment. Favourable pathological outcome was defined as specimen-confined disease (SCD; pT2-T3a, node negative, and negative surgical margins) at RARP-specimen. Logistic regression models were used to test the relationship among all available predicators and harbouring SCD. A logistic regression coefficient-based nomogram was constructed and internally validated using 200 bootstrap resamples. Kaplan-Meier method estimated biochemical recurrence (BCR)-free and cancer-specific mortality (CSM)-free survival rates, after stratification according to pathological disease status. RESULTS: Overall, 55.2% patients harboured SCD at RARP. At multivariable analysis, PSA level, clinical stage, primary/secondary Gleason scores, and maximum percentage tumour quartiles were all independent predictors of SCD (all P < 0.04). A nomogram based on these variables showed 76% discrimination accuracy in predicting SCD, and very favourable calibration characteristics. Patients with SCD had significantly higher 8-year BCR- (72.7% vs 31.7%, P < 0.001) and CSM-free survival rates (100% vs 86.9%, P < 0.001) than patients with non-SCD. CONCLUSIONS: We developed a novel nomogram predicting SCD at RARP. Patients with SCD achieved favourable long-term BCR- and CSM-free survival rates after RARP. The nomogram may be used to support clinical decision-making, and aid in selection of patients with high-risk prostate cancer most likely to benefit from RARP.

Most infants with dilating vesicoureteral reflux can be treated nonoperatively.

PURPOSE: Dilating vesicoureteral reflux provokes concern for physicians and parents that often leads to corrective surgery in young children. Since there are limited data describing the natural history of dilating vesicoureteral reflux in infants, we identified factors predictive of resolution/improvement in infants initially treated nonoperatively. MATERIALS AND METHODS: We reviewed the medical records of 90 infants 6 months old or younger from 2004 to 2010 who were referred for prenatal hydronephrosis or initial febrile urinary tract infection and found to have dilating vesicoureteral reflux (grade 3 or greater). Variables of interest included presentation, dimercapto-succinic acid results, sex, breakthrough febrile urinary tract infections, reflux grade and bilateral reflux. Cox regression analysis was performed to determine predictors of spontaneous resolution and/or improvement to reflux grade less than 3 as well as predictors of surgical intervention. RESULTS: Included in final analysis were 80 infants (113 renal units). Of the patients 51 (64%) experienced spontaneous resolution/improvement with a mean followup of 29 months before resolution, discharge home and/or end of followup. Only 20 patients (25%) underwent surgery. Cox regression analysis revealed that a normal initial dimercapto-succinic acid scan, initial reflux grade less than 5 and absent breakthrough febrile urinary tract infections were predictive of reflux resolution/improvement (p <0.05). Dimercapto-succinic acid scan abnormalities, prenatal hydronephrosis and breakthrough febrile urinary tract infections were significant predictors of surgery (p <0.05). CONCLUSIONS: Dilating vesicoureteral reflux in infancy often resolves/improves spontaneously. Therefore, surgery should be directed toward patients unlikely to experience resolution, ie those with an abnormal initial dimercapto-succinic acid scan, grade 5 vesicoureteral reflux and breakthrough febrile urinary tract infections.

Evaluation and treatment of cryptorchidism: AUA guideline.

PURPOSE: Cryptorchidism is one of the most common pediatric disorders of the male endocrine glands and the most common genital disorder identified at birth. This guideline is intended to provide physicians and non-physician providers (primary care and specialists) with a consensus of principles and treatment plans for the management of cryptorchidism (typically isolated non-syndromic). MATERIALS AND METHODS: A systematic review and meta-analysis of the published literature was conducted using controlled vocabulary supplemented with key words relating to the relevant concepts of cryptorchidism. The search strategy was developed and executed by reference librarians and methodologists to create an evidence report limited to English-language, published peer-reviewed literature. This review yielded 704 articles published from 1980 through 2013 that were used to form a majority of the guideline statements. Clinical Principles and Expert Opinions were used for guideline statements lacking sufficient evidence-based data. RESULTS: Guideline statements were created to inform clinicians on the proper methods of history-taking, physical exam, and evaluation of the boy with cryptorchidism, as well as the various hormonal and surgical treatment options. CONCLUSIONS: Imaging for cryptorchidism is not recommended prior to referral, which should occur by 6 months of age. Orchidopexy (orchiopexy is the preferred term) is the most successful therapy to relocate the testis into the scrotum, while hormonal therapy is not recommended. Successful scrotal repositioning of the testis may reduce but does not prevent the potential long-term issues of infertility and testis cancer. Appropriate counseling and follow-up of the patient is essential.

[Comparison of serum uric acid and liver enzyme levels in adolescents with obesity and with metabolic syndrome]. / Comparación de los niveles séricos de ácido úrico y enzimas hepáticas entre adolescentes con obesidad y con síndrome metabólico.

INTRODUCTION: a relationship has been observed between elevated levels of liver enzymes and uric acid with the presence of metabolic syndrome (MS) in the pediatric population. OBJECTIVE: to compare serum liver enzyme and uric acid levels between adolescents with and without MS. METHODS: a cross-sectional study was carried out in adolescents with obesity between 10 and 18 years old. Somatometric data, serum insulin, lipid profile, uric acid levels and liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT] and gamma-glutamyl transferase [GGT]) were analyzed. STATISTICAL ANALYSIS: Student's t test or the Chi-square test was used to evaluate differences between groups. RESULTS: a total of 1095 adolescents with obesity were included (444 with MS and 651 without MS). The group with MS had a higher BMI (with MS 2.28 vs without MS 2.11 p < 0.001), with no difference in body fat (42.9 % vs 42.9 %, p = 0.978). The MS group had significantly higher levels of AST (34.4 vs. 29.5, p = 0.013), ALT (42.2 vs. 34.6, p = 0.003), and uric acid (6.17 vs. 5.74, p = 0.002). comparison to the group without MS. The proportion of ALT (40.5 % vs 29.5 %, p = 0.029) and altered uric acid (58.1 % vs. 45.6 %, p = 0.019) was higher in the MS group. CONCLUSIONS: serum levels of ALT, AST and uric acid in adolescents with obesity and MS were higher compared to those without MS. Altered ALT was a risk factor for SM.

Follow-up for Clinically Localized Renal Neoplasms: AUA Guideline.

PURPOSE: The purpose of this guideline is to provide a clinical framework for follow-up of clinically localized renal neoplasms undergoing active surveillance, or following definitive therapy. MATERIALS AND METHODS: A systematic literature review identified published articles in the English literature between January 1999 and 2011 relevant to key questions specified by the Panel related to kidney neoplasms and their follow-up (imaging, renal function, markers, biopsy, prognosis). Study designs consisting of clinical trials (randomized or not), observational studies (cohort, case-control, case series) and systematic reviews were included. RESULTS: Guideline statements provided guidance for ongoing evaluation of renal function, usefulness of renal biopsy, timing/type of radiographic imaging and formulation of future research initiatives. A lack of studies precluded risk stratification beyond tumor staging; therefore, for the purposes of postoperative surveillance guidelines, patients with localized renal cancers were grouped into strata of low- and moderate- to high-risk for disease recurrence based on pathological tumor stage. CONCLUSIONS: Evaluation for patients on active surveillance and following definitive therapy for renal neoplasms should include physical examination, renal function, serum studies and imaging and should be tailored according to recurrence risk, comorbidities and monitoring for treatment sequelae. Expert opinion determined a judicious course of monitoring/surveillance that may change in intensity as surgical/ablative therapies evolve, renal biopsy accuracy improves and more long-term follow-up data are collected. The beneficial impact of careful follow-up will also need critical evaluation as further study is completed.

Making Outbreak Investigations Real to Learners.

Frequent outbreaks and the COVID-19 pandemic underscore the need for delivering hands-on outbreak investigation content to learners. This work aimed at assessing the effectiveness of using a combined experiential, competency, and team-based learning activity for teaching outbreak investigations to first-year medical students (M1). Two prospective cohorts of 84 M1 students each in 2019 and 2020 underwent an interactive endeavor. This project evaluated the competencies gained as portrayed in a team presentation, students' perception of those competencies, and activity's utility. Students gained most competencies, particularly those linked to their role as clinicians. There is still room for improvement in detecting an outbreak, labeling the epidemic curve type, and designing a study suitable for answering the hypothesis. Based on 55 and 43 (65% and 51%) responders, most of the groups agreed that the learning activity was useful in providing the necessary skills to conduct an outbreak investigation. Facilitating experiential learning opportunities in which students can practice their recently acquired medical skills (i.e., recognize symptoms, elaborate differential diagnosis) engaged them in the non-clinical components. Such opportunities can also gauge in lieu of a formal evaluation the level of mastery achieved and deficiencies not only in specific but also in related competencies. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01756-5.

Hospital admissions for mitral stenosis in pregnancy in the United States: a thirteen-year analysis.

BACKGROUND: Cardiac conditions are a significant cause of maternal morbidity and mortality, significantly exacerbated during the hemodynamic demands of pregnancy. Mitral stenosis in pregnancy (MSp) is rare in the USA however, it has a high risk for maternal complications. METHODS: We aim to outline the burden of MSp hospitalizations nationally. A retrospective review of HCUP/NIS data from 2002-2014 was conducted. RESULTS: There were 2014 weighted discharges for both pregnancy and mitral stenosis (MS). Patients diagnosed with MS had a more considerable mean cost per discharge than the comparison group. Pulmonary Hypertension (PH), Atrial Arrhythmias (AA), Stroke, and Heart Failure (HF) were respectively reported in 25.71%, 7.14%, 0.95%, and 19.28% of the discharges. Our study identified a low incidence of MS in the US over the 12-year period; no deaths were identified. CONCLUSION: Our results substantiate MSp as a risk factor for PH, AA, HF, and stroke in pregnancy. Even though the mortality is low, it is essential that clinicians be aware of this diagnosis due to higher associated morbidity and costs.

[Correlation of uric acid with carotid intima media thickness in obese adolescents]. / Correlación del ácido úrico con el grosor de la íntima media de la carótida en adolescentes con obesidad.

Introduction: Introduction: obesity in the pediatric population is a public health problem. The correlation of uric acid and carotid intima media thickness in adults has been demonstrated. Objective: to identify the correlation of uric acid and carotid intima media thickness in adolescents with obesity. Material and methods: an observational, cross-sectional study was carried out. Patients aged ten to 16 years with a diagnosis of obesity were included. Uric acid, lipid profile and carotid intima media thickness were determined. In relation to the statistical analysis, carotid intima media thickness was correlated with uric acid levels through Spearman's correlation coefficient. Results: one hundred and sixty-nine adolescents were included with a median age of 13 years, without predominance of sex. A positive correlation of uric acid with carotid intima media thickness was identified (r = 0.242, p = 0.001). When stratified according to sex, there was no correlation in women (r = -0.187, p = 0.074), while in men it increased (r = 0.36, p = 0.001) and by pubertal stage, pubertal male adolescents had a positive correlation (p = 0.384, p = 0.002). Conclusion: a weak positive correlation was identified between carotid intimal thickness and uric acid in obese adolescents.

Introducción: Introducción: la obesidad en la población pediátrica es un problema de salud pública. Se ha demostrado la correlación del ácido úrico y el grosor de la íntima media de la carótida en adultos. Objetivo: identificar la correlación del ácido úrico y el grosor de la íntima media de la carótida en adolescentes con obesidad. Material y métodos: se realizó un estudio observacional, transversal. Se incluyeron pacientes de diez a 16 años con diagnóstico de obesidad. Se determinó ácido úrico, perfil de lípidos y grosor de la íntima media carotidea. En el análisis estadístico, se correlacionó el grosor de la íntima media carotídea con los niveles de ácido úrico a través del coeficiente de correlación de Spearman. Resultados: se incluyeron 169 adolescentes con una mediana para la edad de 13 años, sin predominio de sexo. Se identificó una correlación positiva del ácido úrico con el grosor de la íntima media carotídea (r = 0,242, p = 0,001). Al estratificarse de acuerdo con el sexo, no hubo correlación en las mujeres (r = -0,187, p = 0,074), mientras que en los hombres aumentó (r = 0,36, p = 0,001) y por estadio puberal, los adolescentes varones púberes tuvieron una correlación positiva (p = 0,384, p = 0,002). Conclusión: se identificó una correlación positiva débil entre el grosor de la íntima de la carótida y el ácido úrico en adolescentes con obesidad.

Long-term follow-up of patients undergoing percutaneous suprapubic tube drainage after robot-assisted radical prostatectomy (RARP).

UNLABELLED: Study Type - Therapy (case series). Level of Evidence 4 What's known on the subject? and What does the study add? • Initial reports of percutaneous suprapubic tube (PST) drainage following RARP demonstrated feasibility and short-term safety, while decreasing patient discomfort and utilization of anti-cholinergic medication. • This study demonstrates the long-term safety and efficacy of bladder drainage by PST; splinting the urethrovesical anastomosis is simply not essential if mucosal apposition is ensured. OBJECTIVES: • To evaluate the long-term safety and functional outcomes of patients undergoing percutaneous suprapubic tube (PST) drainage after robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: • Between January 2008 and October 2009, 339 patients undergoing RARP by one surgeon experienced in RA surgery (M.M.) had postoperative bladder drainage with PST and a minimum of 1-year follow-up for urinary function. • Functional outcomes were obtained via patient-administered questionnaire. • Complications were captured by exhaustive review of multiple datasets, including our prospective prostate cancer database, claims data, as well as electronic medical and institutional morbidity and mortality records. RESULTS: • Urinary function assessed by patient-administered questionnaire was analysed at a mean (sd) follow-up of 11.5 (1.7) months; after RARP with PST placement, 293 patients (86.4%) had total urinary control and only nine (2.7%) required >1 pad/day. • In all, 86 patients (25.4%) never wore a pad; the median time to 0-1 pad/day was 2 weeks (interquartile range [IQR] 0,6); median time to total control was 6 weeks (IQR 1,22). • The mean (sd) follow-up for complications was 23.7 (6.1) months. In all, 15 patients (4.4%) had a procedure-specific complication, of which 13 were minor (Clavien Class I/II 3.8%); one patient had a bladder neck contracture. • In all, 16 patients (4.7%) required Foley placement after RARP for gross haematuria (two patients), urinary retention (three), tube malfunction (four) or need for prolonged Foley catheterization (seven). CONCLUSIONS: • PST placement after RARP is safe and efficacious on long-term follow-up. • Splinting of the urethrovesical anastomosis is not a critical step of RP if a watertight anastomosis and excellent mucosal apposition are achieved.

A modified Altis® mid-urethral sling that allows immediate post-operative adjustment: experience in 197 patients.

OBJECTIVES: The transobturator mid-urethral Altis® "mini-sling" uses a static and a dynamic anchor on either end of a pulley suture for intraoperative tension adjustment. Given the potential for incorrect tensioning with sling placement, we adopted a modification for post-operative adjustment should stress urinary incontinence (SUI) persist. The objective is to describe technique, rate of postoperative adjustment driven by patient symptoms, and impact of preoperative/intraoperative variables. METHODS: In this single-surgeon experience, retrospective chart review, demographic and clinical data were collected on patients who received the Altis® sling for SUI between 2014 and 2019. We used descriptive statistics and three-group comparison tests to assess difference in variables among tightening, loosening, or no adjustment. RESULTS: Altis® sling placement was performed on 197 female patients with an average age of 58.7 years. Eighty-four percent (165/197) did not receive post-operative adjustment. Of the 32 patients with post-operative adjustment, 8 (4.1%) had loosening and 24 (12.2%) had tightening at an average of 10.5 days post-operatively. All tightening procedures were done in the clinic. Of the 8 patients with post-operative loosening, 6 were performed in clinic and 2 in the operating room. Preoperative and intraoperative variables were not significantly different among tightening, loosening, and no adjustment cohorts. CONCLUSIONS: This modification of the Altis® sling provides surgeons with the ability to tighten and loosen the sling for persistent SUI. All tightening and most loosening procedures were able to be performed in the clinic. The ability to easily tighten a sling in the early post-operative period may be a critical advantage.

Robotic partial nephrectomy in the setting of prior abdominal surgery.

OBJECTIVE: • To evaluate our experience with robotic partial nephrectomy in patients with previous abdominal surgery and evaluate the effect of previous abdominal surgery on perioperative outcomes. We also describe a technique for intraperitoneal access for patients with prior abdominal surgery utilizing the 8 mm robotic camera for direct-vision trocar placement. PATIENTS AND METHODS: • From a prospective cohort of 197 consecutive patients who underwent robotic renal surgery at a single academic institution, a total of 95 patients underwent transperitoneal robotic partial nephrectomy (RPN). • Patients with and without previous abdominal surgery were compared. Patients with prior abdominal surgery were subcategorized into two groups: upper midline or ipsilateral upper quadrant scar or lower abdominal, contralateral, or minimally-invasive scar. • Demographic and perioperative variables were compared between the surgery and no surgery groups. Access was obtained using a Veress needle or Hassan technique. • We utilized a technique of direct vision placement of the initial trocar on our 10 most recent cases, using an 8 mm robotic camera placed through the obturator of 12 mm clear-tipped trocar. • Lysis of adhesions was performed as needed to allow for placement of additional robotic ports. RESULTS: • A total of 95 patients underwent transperitoneal RPN, of which 41 (43%) had a history of prior abdominal surgery and six had upper midline or ipsilateral upper quadrant scars. • There were no statistically significant differences between patients with previous abdominal surgery and patients with no previous abdominal surgery in BMI (30.4 vs 29.4 kg/m(2) ), median tumor size (2.5 cm vs 2.3), median total operative time (246 vs 250 min), median warm ischemia time (21 vs 16 min), median EBL (150 vs100 ml), clinical stage, transfusion rate, or complications. • A total of six patients underwent 7 previous upper midline or ipsilateral upper quadrant surgeries, including open cholecystectomy-2 patients (33%), open partial gastrectomy-2 patients (33%) and exploratory laparotomy-1 patient (17%). • Complications in this group were an enterotomy during lysis of adhesions that was repaired robotically without sequelae and a mesenteric hematoma during Veress needle placement. A total of 35 patients underwent 16 other prior abdominal surgeries, including abdominal hysterectomy-10 patients (29%), umbilical/inguinal hernia repair-9 patients (26%) and appendectomy-7 patients (20%). There were no access related injuries in the 10 cases in which the robotic 8 mm camera was used for initial trocar placement. CONCLUSIONS: • Transperitoneal robotic partial nephrectomy is feasible in the setting of prior abdominal surgery. The majority of these patients can have their procedure performed safely without an increase in complications. • Direct-vision intraperitoneal placement of initial trocar may be achieved by using an 8 mm robotic camera, without the need to switch between conventional and robotic cameras.

Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 2.

Evidence-based health care decision making requires comparison of all relevant competing interventions. In the absence of randomized controlled trials involving a direct comparison of all treatments of interest, indirect treatment comparisons and network meta-analysis provide useful evidence for judiciously selecting the best treatment(s). Mixed treatment comparisons, a special case of network meta-analysis, combine direct evidence and indirect evidence for particular pairwise comparisons, thereby synthesizing a greater share of the available evidence than traditional meta-analysis. This report from the International Society for Pharmacoeconomics and Outcomes Research Indirect Treatment Comparisons Good Research Practices Task Force provides guidance on technical aspects of conducting network meta-analyses (our use of this term includes most methods that involve meta-analysis in the context of a network of evidence). We start with a discussion of strategies for developing networks of evidence. Next we briefly review assumptions of network meta-analysis. Then we focus on the statistical analysis of the data: objectives, models (fixed-effects and random-effects), frequentist versus Bayesian approaches, and model validation. A checklist highlights key components of network meta-analysis, and substantial examples illustrate indirect treatment comparisons (both frequentist and Bayesian approaches) and network meta-analysis. A further section discusses eight key areas for future research.

Prognostic significance of histomorphologic features of lymph node metastases in prostate cancer patients treated with radical prostatectomy: A single center study.

OBJECTIVE: We assessed the prognostic value of histomorphologic features of lymph node (LN) metastases in patients with prostate cancer treated with radical prostatectomy MATERIALS AND METHODS: We evaluated the effect of the features of LN metastasis on the risk of biochemical recurrence (BCR) in 280 LN-positive patients who underwent radical prostatectomy between 2006 to 2018. LN specific parameters recorded included number of metastatic LNs, size of the largest metastatic focus, Gleason Grade (GG) of the metastatic focus, and extranodal extension (ENE). RESULTS: A solitary positive LN was found in 166/280 (59%), 95/280 (34%) patients had 2-4 positive LNs, and 19/280 (7%) had 5 or more positive LNs. The size of the largest metastatic focus > 2 mm (macrometastasis) in 154/261 (59%). GG of the metastatic focus was as follows: GG 1-2: 29/224 (13%); GG 3: 27/224 (12%); and GG 4-5: 168/224 (75%). ENE was identified in 99/244 (41%). We found the number of LNs positive (2-4 vs. 1 Hazard ratio (HR) = 1.60; 95% CI: 1.02 to 2.5; P = 0.04) and GG of the metastatic focus (GG 4&5 vs. 1-3 HR = 1.90; 95% CI: 1.14-3.2; P= 0.014) to be independent predictors of the risk of BCR after surgery on multivariate analysis. CONCLUSIONS: Our study showed the number of LNs positive and GG of the LN metastatic focus to be significant independent predictors of BCR after radical prostatectomy. We recommend reporting histomorphologic parameters of LN metastasis as they may help in defining BCR risk categorization.

STAT1-Dependent Recruitment of Ly6ChiCCR2+ Inflammatory Monocytes and M2 Macrophages in a Helminth Infection.

Signal Transducer and Activator of Transcription (STAT) 1 signaling is critical for IFN-γ-mediated immune responses and resistance to protozoan and viral infections. However, its role in immunoregulation during helminth parasitic infections is not fully understood. Here, we used STAT1-/- mice to investigate the role of this transcription factor during a helminth infection caused by the cestode Taenia crassiceps and show that STAT1 is a central molecule favoring susceptibility to this infection. STAT1-/- mice displayed lower parasite burdens at 8 weeks post-infection compared to STAT1+/+ mice. STAT1 mediated the recruitment of inflammatory monocytes and the development of alternatively activated macrophages (M2) at the site of infection. The absence of STAT1 prevented the recruitment of CD11b+Ly6ChiLy6G- monocytic cells and therefore their suppressive activity. This failure was associated with the defective expression of CCR2 on CD11b+Ly6ChiLy6G- cells. Importantly, CD11b+Ly6ChiLy6G- cells highly expressed PDL-1 and suppressed T-cell proliferation elicited by anti-CD3 stimulation. PDL-1+ cells were mostly absent in STAT1-/- mice. Furthermore, only STAT1+/+ mice developed M2 macrophages at 8 weeks post-infection, although macrophages from both T. crassiceps-infected STAT1+/+ and STAT1-/- mice responded to IL-4 in vitro, and both groups of mice were able to produce the Th2 cytokine IL-13. This suggests that CD11b+CCR2+Ly6ChiLy6G- cells give rise to M2 macrophages in this infection. In summary, a lack of STAT1 resulted in impaired recruitment of CD11b+CCR2+Ly6ChiLy6G- cells, failure to develop M2 macrophages, and increased resistance against T. crassiceps infection.

Pediatric Vesicoureteral Reflux Guidelines Panel Summary Report: Clinical Practice Guidelines for Screening Siblings of Children With Vesicoureteral Reflux and Neonates/Infants With Prenatal Hydronephrosis.

PURPOSE: The American Urological Association established the Vesicoureteral Reflux Guideline Update Committee in July 2005 to update the management of primary vesicoureteral reflux in children guideline. The Panel defined the task into 5 topics pertaining to specific vesicoureteral reflux management issues, which correspond to the management of 3 distinct index patients and the screening of 2 distinct index patients. This report summarizes the existing evidence pertaining to screening of siblings and offspring of index patients with vesicoureteral reflux and infants with prenatal hydronephrosis. From this evidence clinical practice guidelines are developed to manage the clinical scenarios insofar as the data permit. MATERIALS AND METHODS: The Panel searched the MEDLINE(R) database from 1994 to 2008 for all relevant articles dealing with the 5 chosen guideline topics. The database was reviewed and each abstract segregated into a specific topic area. Exclusions were case reports, basic science, secondary reflux, review articles and not relevant. The extracted article to be accepted should have assessed a cohort of children, clearly stating the number of children undergoing screening for vesicoureteral reflux. Vesicoureteral reflux should have been diagnosed with a cystogram and renal outcomes assessed by nuclear scintigraphy. The screening articles were extracted into data tables developed to evaluate epidemiological factors, patient and renal outcomes, and results of treatment. The reporting of meta-analysis of observational studies elaborated by the MOOSE group was followed. The extracted data were analyzed and formulated into evidence-based recommendations regarding the screening of siblings and offspring in index cases with vesicoureteral reflux and infants with prenatal hydronephrosis. RESULTS: In screened populations the prevalence of vesicoureteral reflux is 27.4% in siblings and 35.7% in offspring. Prevalence decreases at a rate of 1 screened person every 3 months of age. The prevalence is the same in males and females. Bilateral reflux prevalence is similar to unilateral reflux. Grade I-II reflux is estimated to be present in 16.7% and grade III-V reflux in 9.8% of screened patients. The estimate for renal cortical abnormalities overall is 19.3%, with 27.8% having renal damage in cohorts of symptomatic and asymptomatic children combined. In asymptomatic siblings only the rate of renal damage is 14.4%. There are presently no randomized, controlled trials of treated vs untreated screened siblings with vesicoureteral reflux to evaluate health outcomes as spontaneous resolution, decreased rates of urinary infection, pyelonephritis or renal scarring. In screened populations with prenatal hydronephrosis the prevalence of vesicoureteral reflux is 16.2%. Reflux in the contralateral nondilated kidney accounted for a mean of 25.2% of detected cases for a mean prevalence of 4.1%. In patients with a normal postnatal renal ultrasound the prevalence of reflux is 17%. The prenatal anteroposterior renal pelvic diameter was not predictive of reflux prevalence. A diameter of 4 mm is associated with a 10% to 20% prevalence of vesicoureteral reflux. The prevalence of reflux is statistically significantly greater in females (23%) than males (16%) (p=0.022). Reflux grade distribution is approximately a third each for grades I-II, III and IV-V. The estimate of renal damage in screened infants without infection is 21.8%. When stratified by reflux grade renal damage was estimated to be present in 6.2% grade I-III and 47.9% grade IV-V (p <0.0001). The risk of urinary tract infection in patients with and without prenatal hydronephrosis and vesicoureteral reflux could not be determined. The incidence of reported urinary tract infection in patients with reflux was 4.2%. CONCLUSIONS: The meta-analysis provided meaningful information regarding screening for vesicoureteral reflux. However, the lack of randomized clinical trials for screened patients to assess clinical health outcomes has made evidence-based guideline recommendations difficult. Consequently, screening guidelines are based on present practice, risk assessment, meta-analysis results and Panel consensus.