Biological Monitoring of Hexavalent Chromium and Serum Levels of the Senescence Biomarker Apolipoprotein J/Clusterin in Welders

Welding fumes contain metals and other toxic substances known or strongly suspected to be related with oxidative stress and premature cellular senescence. Apolipoprotein J/Clusterin (ApoJ/CLU) is a glycoprotein that is differentially regulated in various physiological and disease states including ageing and age-related diseases. In vitro data showed that exposure of human diploid fibroblasts to hexavalent chromium (Cr(VI)) resulted in premature senescence and significant upregulation of the ApoJ/CLU protein. In this study we analyzed blood and urine samples from shipyard industry welders being exposed to different levels of Cr(VI) over a period of five months in order to assay in vivo the relation of ApoJ/CLU serum levels with Cr(VI). Our findings confirmed the previously reported in vitro data since reduction of Cr levels, after a worksite intervention, associated with lower levels of ApoJ/CLU serum levels. We concluded that the human ApoJ/CLU gene is responsive to the acute in vivo oxidative stress induced by heavy metals such as hexavalent chromium

Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): a multicentre, double-blind, randomised, phase 3 trial

Background No phase 3 trial has yet shown improved survival for patients with pleural or peritoneal malignant mesothelioma who have progressed following platinum-based chemotherapy. The aim of this study was to assess the efficacy and safety of nivolumab, an anti-PD-1 antibody, in these patients. Methods This was a multicentre, placebo-controlled, double-blind, parallel group, randomised, phase 3 trial done in 24 hospitals in the UK. Adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1, with histologically confirmed pleural or peritoneal mesothelioma, who had received previous first-line platinum-based chemotherapy and had radiological evidence of disease progression, were randomly assigned (2:1) to receive nivolumab at a flat dose of 240 mg every 2 weeks over 30 min intravenously or placebo until disease progression or a maximum of 12 months. The randomisation sequence was generated within an interactive web response system (Alea); patients were stratified according to epithelioid versus non-epithelioid histology and were assigned in random block sizes of 3 and 6. Participants and treating clinicians were masked to group allocation. The co-primary endpoints were investigator-assessed progression-free survival and overall survival, analysed according to the treatment policy estimand (an equivalent of the intention-to-treat principle). All patients who were randomly assigned were included in the safety population, reported according to group allocation. This trial is registered with Clinicaltrials.gov, NCT03063450. Findings Between May 10, 2017, and March 30, 2020, 332 patients were recruited, of whom 221 (67%) were randomly assigned to the nivolumab group and 111 (33%) were assigned to the placebo group). Median follow-up was 11·6 months (IQR 7·2–16·8). Median progression-free survival was 3·0 months (95% CI 2·8–4·1) in the nivolumab group versus 1·8 months (1·4–2·6) in the placebo group (adjusted hazard ratio [HR] 0·67 [95% CI 0·53–0·85; p=0·0012). Median overall survival was 10·2 months (95% CI 8·5–12·1) in the nivolumab group versus 6·9 months (5·0–8·0) in the placebo group (adjusted HR 0·69 [95% CI 0·52–0·91]; p=0·0090). The most frequently reported grade 3 or worse treatment-related adverse events were diarrhoea (six [3%] of 221 in the nivolumab group vs two [2%] of 111 in the placebo group) and infusion-related reaction (six [3%] vs none). Serious adverse events occurred in 90 (41%) patients in the nivolumab group and 49 (44%) patients in the placebo group. There were no treatment-related deaths in either group. Interpretation Nivolumab represents a treatment that might be beneficial to patients with malignant mesothelioma who have progressed on first-line therapy. Funding Stand up to Cancer–Cancer Research UK and Bristol Myers Squibb

You've got to use street talk - Australian medical practice and international medical graduates

http://www.anzame.unsw.edu.au/conf_past.ht

Displaced granulosa cells in peritoneal washings : a rare diagnostic pitfall

Developing follicles and follicular cysts in the ovary\ud are lined by granulosa cells. Approximately the size of\ud histiocytes, non-neoplastic granulosa cells have scant\ud granular to foamy cytoplasm and mildly atypical\ud hyperchromatic nuclei, which may be mitotically\ud active.\ud 1\ud Displaced granulosa cells, derived from normal\ud follicles and introduced into ovarian vascular\ud channels, ovarian stroma and the fallopian tube, have\ud been reported to cause diagnostic difficulty in histol-\ud ogy, as they may mimic small cell carcinoma or other\ud metastatic carcinomas.\ud 2–4\ud The cells are thought to be\ud displaced artefactually due to surgical trauma or\ud during sectioning in the laboratory or during ovulation..

What Are Patients Asking and Reading Online? An Analysis of Online Patient Searches for Rotator Cuff Repair

BACKGROUND: Patients undergoing rotator cuff surgery often search the internet for information regarding the procedure. One popular source, Google, compiles frequently asked questions and links to websites that may provide answers. This study provides an analysis of the most frequently searched questions associated with rotator cuff surgery. We hypothesize that there are distinct search patterns associated with online queries about rotator cuff surgery that could provide unique insights into patient concerns. METHODS: A set of search terms were entered into Google Web Search using a clean-install Google Chrome browser. Frequently associated questions and their webpages were extracted to a database via a data mining extension. Questions were categorized by topics relevant for rotator cuff arthroscopy. Websites were categorized by source and scored for quality utilizing JAMA Benchmark criteria. Pearson\u27s chi-squared tests were used to analyze nominal data. Student t-tests were performed to compare JAMA Benchmark Scores. RESULTS: Of the 595 questions generated from the initial search, 372 unique questions associated with 293 websites were extracted and categorized. The most popular question topics were Activities/Restrictions (20.7%), Pain (18.8%), and Indications/Management (13.2%). The two most common websites searched were Academic (35.2%) and Medical Practice (27.4%). Commercial websites were significantly more likely to be associated with questions about cost (57.1% of all Cost questions, P = 0.01), Anatomy/Function (62.5%, P = 0.001), and Evaluation of Surgery (47.6%, P \u3c 0.001). Academic websites were more likely to be associated with questions about Technical Details of Surgery (58.1%, P \u3c 0.001). Medical Practice and Social Media websites were more likely associated with activities/restrictions (48.1%, P \u3c 0.001, and 15.6%, P \u3c 0.001, respectively). Government websites were more likely associated with timeline of recovery (12.8%, P = 0.01). On a scale of 0-4, Commercial and Academic websites had the highest JAMA scores (3.06 and 2.39, respectively). CONCLUSION: Patients seeking information regarding rotator cuff repair primarily utilize the Google search engine to ask questions regarding postoperative activity and restrictions, followed by pain, indications, and management. Academic websites, which were associated with technical details of surgery, and medical practice websites, which were associated with activities/restrictions, were the two most commonly searched resources. These results emphasize the need for orthopedic surgeons to provide detailed and informative instructions to patients undergoing rotator cuff repair, especially in the postoperative setting