Feasibility of a randomized controlled trial to assess treatment of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Saudi Arabia: a survey of physicians

The Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging respiratory pathogen with a high mortality rate and no specific treatments available to date. The purpose of this study was to determine the feasibility of conducting a randomized controlled trial (RCT) of convalescent plasma therapy for MERS-CoV-infected patients by using MERS-CoV-specific convalescent plasma obtained from previously recovered patients.A survey was adapted from validated questionnaire originally aimed to measure network capacities and capabilities within the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC). The questionnaire was modified for this study to include 26 items that were divided into three main domains of interest: (1) the ability to care for critically ill MERS-CoV patients; (2) laboratory capacity to diagnose MERS-CoV and blood bank ability to prepare convalescent plasma; and (3), research capacity to conduct randomized controlled trials. The questionnaire was emailed to physicians.Of 582 physicians who were invited to the survey, 327 responded (56.2 %). The professional focus of the majority of respondents was critical care (106/249 (43 %)), pediatrics (59/249, (24 %)) or internal medicine (52/249 (21 %)) but none was blood banking. Nearly all respondents (251/263 (95 %)) reported to have access to ICU facilities within their institutions. Most respondents (219/270 (81 %)) reported that intensivists were the most physician group responsible for treatment decisions about critically ill SARI patients. While 125/165 respondents (76 %) reported that they conduct research in ICUs, and 80/161 (49.7 %) had been involved in the conduct of RCTs, including using a placebo comparison (60/161 (37 %)), only 49/226 (21 %) of respondents regularly participated in research networks.Our survey indicated that in the Kingdom of Saudi Arabia (KSA), ICUs are the most likely clinical locations for conducting a clinical trial of convalescent plasma therapy for MERS-CoV, and that most ICUs have experience with such research designs

Photoactive imaging and therapy for colorectal cancer using a CEA-Affimer conjugated Foslip nanoparticle

Theranostic nanoparticles hold a promising strategy for simultaneous imaging and therapy in colorectal cancer. Carcinoembryonic antigen can be used as a target for these nanoparticles because it is overexpressed in most colorectal cancers. Affimers reagents are synthetic proteins capable to binding specific targets, with additional advantages over antibodies for targeting. We fabricated silica nanoparticles using a water-in-oil microemulsion technique, loaded them with the photosensitiser Foslip, and functionalised the surface with anti-CEA Affimers to facilitate fluorescent imaging and photodynamic therapy of colorectal cancer. CEA-specific fluorescent imaging and phototoxicity was quantified in colorectal cancer cell lines and a LS174T murine xenograft colorectal cancer model. Anti-CEA targeted nanoparticles exhibited CEA specific fluorescence in LoVo, LS174T and HCT116 cell lines when compared to control particles (p<0.0001). No toxicity was observed in LS174T cancer mouse xenografts or other organs. Following photo-irradiation, anti-CEA targeted particles produced significant cell death in LoVo (60%), LS174T (90%) and HCT116 (70%) compared to controls (p<0.0001). Photodynamic therapy (PDT) at 24 h in vivo showed a 4-fold reduction in tumour volume compared to control mouse xenografts (p<0.0001). This study demonstrates the efficacy of targeted fluorescent imaging and PDT using Foslip nanoparticles conjugated to anti-CEA Affimer nanoparticles in in vitro and in vivo colorectal cancer models