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Context: The European Association of Urology (EAU) guidelines panel on upper urinary tract urothelial carcinoma (UTUC) has updated the guidelines to aid clinicians in evidence-based management of UTUC., Objective: To provide an overview of the EAU guidelines on UTUC as an aid to clinicians., Evidence Acquisition: The recommendations provided in these guidelines are based on a review of the literature via a systematic search of the PubMed, Ovid, EMBASE, and Cochrane databases. Data were searched using the following keywords: urinary tract cancer, urothelial carcinomas, renal pelvis, ureter, bladder cancer, chemotherapy, ureteroscopy, nephroureterectomy, neoplasm, (neo)adjuvant treatment, instillation, recurrence, risk factors, metastatic, immunotherapy, and survival. The results were assessed by a panel of experts., Evidence Synthesis: Even though data are accruing, for many areas there is still insufficient high-level evidence to provide strong recommendations. Patient stratification on the basis of histology and clinical examination (including imaging) and assessment of patients at risk of Lynch syndrome will aid management. Kidney-sparing management should be offered as a primary treatment option to patients with low-risk UTUC and two functional kidneys. In particular, for patients with high-risk or metastatic UTUC, new treatment options have become available. In high-risk UTUC, platinum-based chemotherapy after radical nephroureterectomy, and adjuvant nivolumab for unfit or patients who decline chemotherapy, are options. For metastatic disease, gemcitabine/carboplatin chemotherapy is recommended as first-line treatment for cisplatin-ineligible patients. Patients with PD-1/PD-L1-positive tumours should be offered a checkpoint inhibitor (pembrolizumab or atezolizumab)., Conclusions: These guidelines contain information on the management of individual patients according to the current best evidence. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen according to the risk stratification of these tumours., Patient Summary: Cancer of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis, timely and appropriate diagnosis is most important. A number of known risk factors exist., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: A small but growing body of evidence suggests individualized support services and improved access to contraception can promote healthy birth spacing among adolescent mothers. This study examines the effectiveness of Steps to Success, a 2-year home visiting program in San Angelo, Texas, enhanced with content designed to reduce rapid repeat pregnancy among young mothers, increase fathers' involvement, and support mothers' education and career aspirations., Methods: The study used a randomized controlled trial, with 594 young mothers ages 14-20 randomly assigned to either a program group that received Steps to Success or a control group that received an existing home visiting program focused only on parenting and child development. Women in both research groups completed a baseline survey upon enrolling in the study and 1- and 2-year follow-up surveys., Results: After 2 years, participants in the Steps to Success and existing home visiting groups had similar rates of repeat pregnancy. However, women in the Steps to Success group were more likely to use long-acting reversible contraceptives (effect size = 0.18, p = 0.066), particularly younger adolescent mothers ages 14-18 (effect size = 0.34, p = 0.010). Steps to Success also decreased the incidence of unprotected sex for younger adolescent mothers (effect size = -0.25, p = 0.035). Steps to Success did not improve outcomes in other domains., Discussion: Steps to Success improved some outcomes related to healthy birth spacing among younger adolescent mothers. Communities interested in similar programming may want to consider focusing their services on this age group., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To test the hypothesis that mesothelial cells play a role in regulating inflammatory responses within the pleural space, we examined neutrophil chemotactic activity released by cytokine-stimulated mesothelial cells. Human mesothelial cells were isolated from patients with transudative pleural effusions and cultured. The purity of the cell population was assessed by morphologic, immunocytochemical, and biochemical characteristics. Confluent fourth passage mesothelial cell plates were exposed to varying concentrations of the recombinant human cytokines IL-1 alpha, TNF-alpha, or IFN-gamma, or Escherichia coli endotoxin (LPS). Polymorphonuclear neutrophil (PMN) chemotactic activity in the conditioned media was measured in microchemotaxis chambers. Although none of the cytokines demonstrated inherent chemotactic activity, each stimulated mesothelial cells to produce PMN chemotactic activity in a dose-dependent manner. TNF-alpha stimulated the release of the greatest quantity, whereas stimulation with IFN-gamma and IL-1 alpha resulted in the release of lesser but still significant quantities of PMN chemotactic activity. By contrast, LPS did not increase the basal level of chemotactic activity produced by the cells. The cytokine-induced chemotactic activity was proteinaceous, required de novo synthesis, and had a predominant m.w. of 10,000. Significant quantities of immunoreactive neutrophil-activating peptide-1 (NAP-1)/IL-8 were detected in mesothelial cell supernatants after stimulation with each of the cytokines. The neutrophil chemotactic activity of supernatants from mesothelial cells stimulated with either IL-1 alpha or IFN-gamma was completely neutralized with rabbit anti-human NAP-1/IL-8 polyclonal antiserum. The same antiserum neutralized the majority, but not all, of the neutrophil chemotactic activity in supernatants from TNF-stimulated mesothelial cells. Stimulated mesothelial cells also expressed an inducible mRNA transcript that hybridized with a specific oligonucleotide probe for human NAP-1/IL-8. These observations provide a mechanism whereby mesothelial cells could respond to inflammatory stimuli in the underlying lung and regulate inflammatory responses within the pleural space.

In this randomised, double-blind study carried out in 28 centres, azithromycin (500 mg single dose on day 1, followed by 250 mg once-daily on days 2-5) was compared with cefaclor (500 mg t.i.d. for 10 days) in the treatment of acute bacterial pneumonia. A total of 119 patients entered the study, and of these 71 were evaluable and included in the efficacy analysis. The overall satisfactory clinical response was 97.3% for azithromycin patients and 100% for cefaclor patients. The clinical cure rates of azithromycin and cefaclor were 46.9% and 41.0%, respectively; improvement was seen in an additional 46.9% of azithromycin-treated patients and in 59.0% of the cefaclor group. The bacteriological eradication rates were 80.4% and 92.6%, respectively. These rates of clinical and bacteriological efficacy, were not statistically different. Both antibiotics were well tolerated during the study; only two patients (one on each study drug) discontinued medication due to adverse events. The overall incidence of side effects was 18.9% (10 of 53 patients) for azithromycin- and 12.1% (eight of 66 patients) for cefaclor-treated patients. Gastrointestinal disturbances were the most commonly reported side effects (nine of 10 azithromycin-treated patients and six of eight cefaclor-treated patients). In addition, two cefaclor patients reported headache. All azithromycin side effects were mild or moderate in severity, but there were two severe occurrences in the cefaclor group (1 nausea, 1 vomiting) the later leading to discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS)