Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Descriptive study of enteric zoonoses in Ontario, Canada, from 2010 – 2012

Abstract Background Contact with animals and their environment has long been recognized as an important source of enteric zoonoses. However, there are limited data available on the burden of illness associated with specific types of animals in Canada. This study describes the overall burden of enteric zoonoses in Ontario, Canada from 2010 to 2012. Methods Confirmed cases of seven enteric zoonotic diseases (campylobacteriosis, cryptosporidiosis, giardiasis, listeriosis, salmonellosis, verotoxin-producing E. coli (VTEC) infection, and yersiniosis) with episode dates from 2010 to 2012 were extracted from the integrated Public Health Information System (iPHIS). Reported exposures were categorized as animal contact, foodborne, waterborne and ‘other’, with animal contact grouped into nine sub-categories based on the type of animal or transmission setting. Overall incidence rates and proportions by animal exposure categories, age and sex-specific incidence rates and hospitalization and death proportions were calculated and sex proportions compared. Results Our study found that approximately 26% of the enteric pathogens assessed during the 2010 to 2012 period reported contact with animals and their environments as the mode of transmission. Of enteric disease cases reporting animal contact, farm exposures were reported for 51.3%, dog or cat exposures for 26.3%, and reptile or amphibian exposures for 8.9%. Conclusions Contact with animals was reported more frequently during the period 2010 to 2012 in comparison to the period 1997 to 2003 when 6% or less of enteric cases were associated with animal contact. Public health professionals, stakeholders associated with animals and their related industries (e.g., pet treats, mobile zoos, abattoirs), and the public should recognize that animal contact is an important source of enteric illnesses in order to take measures to reduce the burden of illness from animal sources

Consensus Statement for the Management and Treatment of Sturge-Weber Syndrome: Neurology, Neuroimaging, and Ophthalmology Recommendations.

BackgroundSturge-Weber syndrome (SWS) is a sporadic, neurocutaneous syndrome involving the skin, brain, and eyes. Because of the variability of the clinical manifestations and the lack of prospective studies, consensus recommendations for management and treatment of SWS have not been published.ObjectiveThis article consolidates the current literature with expert opinion to make recommendations to guide the neuroimaging evaluation and the management of the neurological and ophthalmologic features of SWS.MethodsThirteen national peer-recognized experts in neurology, radiology, and ophthalmology with experience treating patients with SWS were assembled. Key topics and questions were formulated for each group and included (1) risk stratification, (2) indications for referral, and (3) optimum treatment strategies. An extensive PubMed search was performed of English language articles published in 2008 to 2018, as well as recent studies identified by the expert panel. The panel made clinical practice recommendations.ConclusionsChildren with a high-risk facial port-wine birthmark (PWB) should be referred to a pediatric neurologist and a pediatric ophthalmologist for baseline evaluation and periodic follow-up. In newborns and infants with a high-risk PWB and no history of seizures or neurological symptoms, routine screening for brain involvement is not recommended, but brain imaging can be performed in select cases. Routine follow-up neuroimaging is not recommended in children with SWS and stable neurocognitive symptoms. The treatment of ophthalmologic complications, such as glaucoma, differs based on the age and clinical presentation of the patient. These recommendations will help facilitate coordinated care for patients with SWS and may improve patient outcomes

Marital status, living arrangement, and survival among individuals with advanced prostate cancer in the International Registry for Men with Advanced Prostate Cancer

BACKGROUND: Studies have shown improved survival among individuals with cancer with higher levels of social support. Few studies have investigated social support and overall survival (OS) in individuals with advanced prostate cancer in an international cohort. We investigated the associations of marital status and living arrangements with OS among individuals with advanced prostate cancer in the International Registry for Men with Advanced Prostate Cancer (IRONMAN).METHODS: IRONMAN is enrolling participants diagnosed with advanced prostate cancer (metastatic hormone-sensitive prostate cancer, mHSPC; castration resistant prostate cancer, CRPC) from 16 countries. Participants in this analysis were recruited between July 2017 and January 2023. Adjusting for demographics and tumor characteristics, the associations were estimated using Cox regression and stratified by disease state (mHSPC, CRPC), age (&lt;70, 70+ years), and continent of enrollment (North America, Europe, Other).RESULTS: We included 2,119 participants with advanced prostate cancer, of whom 427 died during up to 5 years of follow-up (median 6 months). Two-thirds had mHSPC. Most were married/in a civil partnership (79%) and 6% were widowed. Very few married participants were living alone (1%), while most unmarried participants were living alone (70%). Married participants had better OS than unmarried participants (adjusted HR: 1.44; 95% CI: 1.02, 2.02). Widowed participants had the worst survival compared to married individuals (adjusted HR: 1.89; 95% CI: 1.22, 2.94).CONCLUSIONS: Among those with advanced prostate cancer, unmarried and widowed participants had worse OS compared to married participants.IMPACT: This research highlighted the importance of social support in OS within this vulnerable population.</p

Supplementary Table 1. from Marital Status, Living Arrangement, and Survival among Individuals with Advanced Prostate Cancer in the International Registry for Men with Advanced Prostate Cancer

A table showing baseline characteristics at enrollment of individuals with advanced prostate cancer in IRONMAN, by outcome status (N=2,119).</p

Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET

Tumor-derived exosomes are emerging mediators of tumorigenesis with tissue-specific addresses and messages. We explored the function of melanoma-derived exosomes in the formation of primary tumor and metastases in mouse and human subjects. Exosomes from highly metastatic melanoma increased the metastatic behavior of primary tumors by permanently “educating” bone marrow (BM) progenitors via the MET receptor. Melanoma-derived exosomes also induced vascular leakiness at pre-metastatic sites, and reprogrammed BM progenitors towards a c-Kit(+)Tie2(+)Met(+) pro-vasculogenic phenotype. Reducing Met expression in exosomes diminished the pro-metastatic behavior of BM cells. Importantly, MET expression was elevated in circulating CD45(−)C-KIT(low/+)TIE2(+) BM progenitors from metastatic melanoma subjects. RAB1a, RAB5b, RAB7, and RAB27a were highly expressed in melanoma cells and Rab27a RNA interference decreased exosome production, preventing BM education, tumor growth and metastasis. Finally, we identified an exosome-specific “melanoma signature” with prognostic and therapeutic potential, comprised of TYRP2, VLA-4, HSP70, an HSP90 isoform and the MET oncoprotein

COS Ambassadors

A collection of materials and resources for COS ambassadors