[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.

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

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. (AU)

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. (AU)

[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.

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.

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.

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.

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.

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.

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.

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.

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

Cardiac disease is still the leading cause of non-pregnancy related maternal morbidity and mortality. Valvular disease is one of the most concerning cardiac conditions in pregnancy. Aortic stenosis (AS) is rare in young populations but deadly complications have been reported in pregnant women. This study is a retrospective review of data from the HCUP-NIS Database from 2002-2014. There were 1108 weighted discharges for both pregnancy and AS. The data contained ten or fewer unweighted discharges with AS in pregnancy that underwent a cardiac intervention: open heart surgery or percutaneous cardiac intervention. Patients who had at least one diagnosis for AS had a greater mean cost per discharge than the comparison groups. No deaths were identified in this group. We found a statistically significant increase in the billing codes for pulmonary hypertension and heart failure. Conditions commonly associated with AS such as atrial arrhythmias, ventricular arrhythmias, diastolic dysfunction, ischemic heart disease and stroke were poorly reported. Our study identified a low incidence of AS and its complications in pregnancy in the USA over our 13-year study period. Even though, the morbidity and mortality are low, it is important that clinicians be aware of this diagnosis due higher costs and risk of complications.

Androgen and Androgen Receptors as Regulators of Monocyte and Macrophage Biology in the Healthy and Diseased Lung.

Androgens, the predominant male sex hormones, drive the development and maintenance of male characteristics by binding to androgen receptor (AR). As androgens are systemically distributed throughout the whole organism, they affect many tissues and cell types in addition to those in male sexual organs. It is now clear that the immune system is a target of androgen action. In the lungs, many immune cells express ARs and are responsive to androgens. In this review, we describe the effects of androgens and ARs on lung myeloid immune cells-monocytes and macrophages-as they relate to health and disease. In particular, we highlight the effect of androgens on lung diseases, such as asthma, chronic obstructive pulmonary disease and lung fibrosis. We also discuss the therapeutic use of androgens and how circulating androgens correlate with lung disease. In addition to human studies, we also discuss how mouse models have helped to uncover the effect of androgens on monocytes and macrophages in lung disease. Although the role of estrogen and other female hormones has been broadly analyzed in the literature, we focus on the new perspectives of androgens as modulators of the immune system that target myeloid cells during lung inflammation.

Outcomes of Intradetrusor Onabotulinum Toxin A Therapy in Overactive Bladder Refractory to Sacral Neuromodulation.

PURPOSE: Intradetrusor onabotulinum toxin A (BTXA) and sacral neuromodulation (SNM) are effective third-line therapies for overactive bladder (OAB). We aimed to measure the outcomes of BTXA for treatment of OAB refractory to initial SNM and identify patient characteristics associated with these outcomes. METHODS: This retrospective cohort study included patients who failed to respond to initial SNM treatment for OAB and subsequently received BTXA at a single provider's clinic between January 2013 and December 2016. Treatment successes were defined as patients willing to continue BTXA or who found symptom relief whereas treatment failures discontinued BTXA due to adverse effects or lack of symptom relief. Symptoms and patient-reported outcomes on validated questionnaires were compared before the initial BTXA trial to 2 months after the last BTXA treatment. The SNM failure BTXA groups were also compared to BTXA SNM naïve groups. RESULTS: Of 18 patients who received BTXA after failed SNM treatment, 7 (39%) achieved treatment success. Successfully treated patients demonstrated decreased urinary frequency from a median 11 voids/day pre-BTXA to 8 voids/day with BTXA (P=0.042). Patients whose treatment failed reported increased complaints of a weak urinary stream (P=0.03) and higher frequency of straining to urinate (P=0.016) than the successful treatment group pre-BTXA. Compared to BTXA patients without prior SNM, the odds of failing BTXA after initial SNM were 3.6 times higher (P=0.016). CONCLUSION: BTXA appears effective for OAB refractory to SNM, although the success rate is lower compared to BTXA patients without SNM exposure.

Contemporary Trends in the Incidence of Metastatic Prostate Cancer Among US Men: Results from Nationwide Analyses.

Studies have noted contrasting findings with regard to the contemporary incidence of metastatic prostate cancer (PCa) in the USA, especially in light of the United States Preventive Services Task Force (USPSTF) recommendations against prostate-specific antigen (PSA) screening in recent years. We used data from the 18 population- based tumor registries of the Surveillance, Epidemiology and End Results (SEER) 2004-2013 database to study trends in the incidence of metastatic PCa among men stratified by age and race. Joinpoint regression analyses were performed to identify time points associated with any statistically significant change in incidence. Overall, there was a significant increase in incidence between 2009 and 2013 (annual percentage change [APC] 3.10%; p<0.05). In age-stratified analyses, there was a continuous increase in the incidence of metastatic PCa from 2004 to 2013 among men aged 45-54 yr and 55-64 yr (APC 1.77% and 1.43% respectively; both p<0.05). For men aged ≥75 yr there was a significant decline in the incidence of metastatic PCa from 2004 to 2011 (APC -2.07%; p<0.05) and a nonsignificant increase from 2011 onwards (APC 6.09%). Distinct incidence trends were noted for white and black men. While it is too early to presume that the recent decline in PSA screening secondary to the USPSTF statement is causally associated with our findings, our results highlight a concerning trend of increasing metastatic disease. Our results thus warrant validation in future longer-term studies on the contemporary incidence and mortality of metastatic PCa. PATIENT SUMMARY: We noted increasing incidence of metastatic prostate cancer from 2009 onwards among US men (especially those aged 45-74 yr) in a population-based tumor registry. Pending validation in longer-term studies, our results suggest the need for close surveillance of trends for metastatic prostate cancer incidence and mortality.

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.

New perspectives on the regulation of type II inflammation in asthma.

Asthma is a chronic inflammatory disease of the lungs which has been thought to arise as a result of inappropriately directed T helper type-2 (Th2) immune responses of the lungs to otherwise innocuous inhaled antigens. Current asthma therapeutics are directed towards the amelioration of downstream consequences of type-2 immune responses (i.e. ß-agonists) or broad-spectrum immunosuppression (i.e. corticosteroids). However, few approaches to date have been focused on the primary prevention of immune deviation. Advances in molecular phenotyping reveal heterogeneity within the asthmatic population with multiple endotypes whose varying expression depends on the interplay between numerous environmental factors and the inheritance of a broad range of susceptibility genes. The most common endotype is one described as "type-2-high" (i.e. high levels of interleukin [IL]-13, eosinophilia, and periostin). The identification of multiple endotypes has provided a potential explanation for the observations that therapies directed at typical Th2 cytokines (IL-4, IL-5, and IL-13) and their receptors have often fallen short when they were tested in a diverse group of asthmatic patients without first stratifying based on disease endotype or severity. However, despite the incorporation of endotype-dependent stratification schemes into clinical trial designs, variation in drug responses are still apparent, suggesting that additional genetic/environmental factors may be contributing to the diversity in drug efficacy. Herein, we will review recent advances in our understanding of the complex pathways involved in the initiation and regulation of type-2-mediated immune responses and their modulation by host factors (genetics, metabolic status, and the microbiome). Particular consideration will be given to how this knowledge could pave the way for further refinement of disease endotypes and/or the development of novel therapeutic strategies for the treatment of asthma .

A Pragmatic Randomized Controlled Trial Examining the Impact of the Retzius-sparing Approach on Early Urinary Continence Recovery After Robot-assisted Radical Prostatectomy.

BACKGROUND: Retzius-sparing (posterior) robot-assisted radical prostatectomy (RARP) may expedite postoperative urinary continence recovery. OBJECTIVE: To compare the short-term (≤3 mo) urinary continence (UC), urinary function (UF), and UF-related bother outcomes of posterior RARP compared with standard anterior approach RARP. DESIGN, SETTING, AND PARTICIPANTS: A total of 120 patients aged 40-75 yr with low-intermediate-risk prostate cancer (per the National Comprehensive Cancer Network guidelines) underwent primary RARP at a tertiary care institution. INTERVENTION: Eligible men were randomized to receive either posterior (n=60) or anterior (n=60) RARP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Primary outcome was UC (defined as 0 pads/one security liner per day) 1 week after catheter removal. Secondary outcomes were short-term (≤3 mo) UC recovery, and UF and UF-related bother scores (measured by the International Prostate Symptom Score [IPSS] and IPSS quality-of-life scores, respectively) assessed at 1 and 2 wk, and 1 and 3 mo following catheter removal. Continence outcomes were objectively verified using 24-hr pad weights. UC recovery was analyzed using Kaplan-Meier method and Cox proportional hazards regression; UF and UF-related bother outcomes were compared using linear generalized estimating equations (GEEs). Perioperative complications, positive surgical margin, and biochemical recurrence-free survival (BCRFS) represent secondary outcomes reported in the study. RESULTS AND LIMITATIONS: Compared with 48% in the anterior arm, 71% men undergoing posterior RARP were continent 1 wk after catheter removal (p=0.01); corresponding median 24-h pad weights were 25 and 5g (p=0.001). Median time to continence in posterior versus anterior RARP was 2 and 8 d postcatheter removal, respectively (log-rank p=0.02); results were confirmed on multivariable regression analyses. GEE analyses showed that UF-related bother (but not UF) scores were significantly lower in the posterior versus anterior RARP group at 1 wk, 2 wk, and 1 mo on GEE analyses. Incidence of postoperative complications (12% anterior vs 18% posterior) and probability of BCRFS (0.91 vs 0.91) were comparable in the two arms. CONCLUSIONS: In this single-center randomized study, the Retzius-sparing approach of RARP resulted in earlier recovery of UC and lower UF-related bother compared with standard RARP. These results require long-term validation and reproduction by other centers, as well as studies on men with high-risk localized disease. PATIENT SUMMARY: In our hands, men with low-intermediate-risk prostate cancer undergoing Retzius-sparing robot-assisted radical prostatectomy (RARP) had earlier recovery of urinary continence and lower urinary function-related bother than those undergoing standard RARP.

Adding a newly trained surgeon into a high-volume robotic prostatectomy group: are outcomes compromised?

This study evaluates whether a new staff surgeon early in the learning curve can be integrated into a high-volume robotic practice with an established robotic team and mentorship without compromising robot-assisted radical prostatectomy (RARP) outcomes of the practice. We analyzed outcomes of 3064 patients who underwent RARP from 2007 to 2012 at a high-volume tertiary center by a robotic practice comprising three experienced robotic surgeons (2846 patients) and a newly hired surgeon (218 patients) immediately out of training (residency and oncology fellowship with 2 years of RARP exposure). The new surgeon performed RARP with intraoperative mentorship by the senior surgeons during the first year. Complications, biochemical recurrence (BCR), positive surgical margins rate (PSM), operating time (OR time), estimated blood loss (EBL) for the new and senior surgeons were compared. Multivariable linear, logistic and exact logistic regression adjusting for disease and patient characteristics were performed. On regression analyses, case number was the most significant predictor of decrease in probability of major complications (p = 0.025) and BCR (p = 0.004) for the new surgeon. Increasing case number was not associated with decrease in minor complications, PSM, OR time, or EBL (p > 0.05). Inclusion of the new surgeon's outcomes did not adversely impact outcomes of the practice. In conclusion, a new surgeon joining a high-volume robotic prostatectomy program with an established robotic team and mentorship can progress through the learning curve without compromising overall outcomes of the practice. Our results may be relevant for programs hiring newly trained staff to join an established robotic practice.