Do poor environmental conditions drive trachoma transmission in Burundi? A mathematical modelling study

Trachoma is an infectious disease and it is the leading cause of preventable blindness worldwide. To achieve its elimination, the World Health Organization set a goal of reducing the prevalence in endemic areas to less than 55% by 2020, utilizing the SAFE (surgery, antibiotics, facial cleanliness, environmental improvement) strategy. However, in Burundi, trachoma prevalences of greater than 55% are still reported in 11 districts and it is hypothesized that this is due to the poor implementation of the environmental improvement factor of the SAFE strategy. In this paper, a model based on an ordinary differential equation, which includes an environmental transmission component, is developed and analysed. The model is calibrated to recent field data and is used to estimate the reductions in trachoma that would have occurred if adequate environmental improvements were implemented in Burundi. Given the assumptions in the model, it is clear that environmental improvement should be considered as a key component of the SAFE strategy and, hence, it is crucial for eliminating trachoma in Burundi. doi:10.1017/S1446181121000389

Talbina as a functional food and a source of health-beneficial ingredients: a narrative review

During the past two decades, several researchers have claimed that traditional foods are healthier products and better sources of micronutrients. Talbina is a well-known traditional food in North Africa, Middle East and South East Asia. Talbina is made by adding 1-2 tablespoons of barley (100% wholegrain barley) to cup of water. Cook on low heat for15 minutes in a water bath. After that a cup of Laban (fermented milk) or milk is added. It can be sweetened with honey. This broth can be used as a stock for soups or stews or as a thickener. Talbina is a healthy food helps in depression and stress relief. It has high antioxidant activity as well as anti-inflammatory. Its consumption regularly proves to be an effective and safe strategy for treating different chronic diseases. It is a rich source of different essential nutrients and antimicrobials, both of which have been linked to a reduction in chronic disease. However, Talbina has not been well studied or defined by the scientific community. This review defines Talbina and discusses the various bioactive compounds in this food and their health benefits. Keywords: Barley wholegrain; fermented milk; natural honey; functional food; nutraceutical ingredients.

Small Extracellular Vesicles Derived from Human Chorionic MSCs as Modern Perspective towards Cell-Free Therapy

Mesenchymal stem cells (MSCs) are of great interest to scientists due to their application in cell therapy of many diseases, as well as regenerative medicine and tissue engineering. Recently, there has been growing evidence surrounding the research based on extracellular vesicles (EVs), especially small EVs (sEVs)/exosomes derived from MSCs. EVs/exosomes can be secreted by almost all cell types and various types of EVs show multiple functions. In addition, MSCs-derived exosomes have similar characteristics and biological activities to MSCs and their therapeutic applications are considered as a safe strategy in cell-free therapy. The aim of this study was the characterization of MSCs isolated from the chorion (CHo-MSCs) of human full-term placenta, as well as the isolation and analysis of small EVs obtained from these cells. Accordingly, in this study, the ability of small EVs’ uptake is indicated by synovial fibroblasts, osteoblasts and periosteum-derived MSCs. Improvement in the understanding of the structure, characteristics, mechanism of action and potential application of MSCs-derived small EVs can provide new insight into improved therapeutic strategies.

Venous thromboembolism chemical prophylaxis after endoscopic trans-sphenoidal pituitary surgery

Purpose There is no compelling outcome data or clear guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using low molecular weight heparin (chemoprophylaxis) in patients undergoing pituitary surgery. Here we describe our experience of early chemoprophylaxis (post-operative day 1) following trans-sphenoidal pituitary surgery. Methods Single-centre review of a prospective surgical database and VTE records. Adults undergoing first time trans-sphenoidal pituitary surgery were included (2009–2018). VTE was defined as either deep vein thrombosis and/or pulmonary embolism within 3 months of surgery. Postoperative haematomas were those associated with a clinical deterioration together with radiological evidence. Results 651 Patients included with a median age of 55 years (range 16–86 years). Most (99%) patients underwent trans-sphenoidal surgery using a standard endoscopic single nostril or bi-nostril trans-sphenoidal technique. More than three quarters had pituitary adenomas (n = 520, 80%). Postoperative chemoprophylaxis to prevent VTE was administered in 478 patients (73%). Chemoprophylaxis was initiated at a median of 1 day post-procedure (range 1–5 days postoperatively; 92% on postoperative day 1). Tinzaparin was used in 465/478 patients (97%) and enoxaparin was used in 14/478 (3%). There were no cases of VTE, even in 78 ACTH-dependent Cushing’s disease patients. Six patients (1%) developed postoperative haematomas. Chemoprophylaxis was not associated with a significantly higher rate of postoperative haematoma formation (Fisher’s Exact, p = 0.99) or epistaxis (Fisher’s Exact, p > 0.99). Conclusions Chemoprophylaxis after trans-sphenoidal pituitary surgery on post-operative day 1 is a safe strategy to reduce the risk of VTE without significantly increasing the risk of postoperative bleeding events.

DO POOR ENVIRONMENTAL CONDITIONS DRIVE TRACHOMA TRANSMISSION IN BURUNDI? A MATHEMATICAL MODELLING STUDY

Trachoma is an infectious disease and it is the leading cause of preventable blindness worldwide. To achieve its elimination, the World Health Organization set a goal of reducing the prevalence in endemic areas to less than $5$ % by 2020, utilizing the SAFE (surgery, antibiotics, facial cleanliness, environmental improvement) strategy. However, in Burundi, trachoma prevalences of greater than $5$ % are still reported in 11 districts and it is hypothesized that this is due to the poor implementation of the environmental improvement factor of the SAFE strategy. In this paper, a model based on an ordinary differential equation, which includes an environmental transmission component, is developed and analysed. The model is calibrated to recent field data and is used to estimate the reductions in trachoma that would have occurred if adequate environmental improvements were implemented in Burundi. Given the assumptions in the model, it is clear that environmental improvement should be considered as a key component of the SAFE strategy and, hence, it is crucial for eliminating trachoma in Burundi.

O18 LONG-TERM CROSSOVER RATE FROM WATCHFUL WAITING TO SURGERY OF INITIALLY MIDLY SYMPTOMATIC OR ASYMPTOMATIC INGUINAL HERNIAS IN MEN AGES 50 YEARS AND OLDER

Aim Inguinal hernia (IH) belongs to the most common surgical pathology worldwide. Approximately, one third of patients are asymptomatic. Watchful waiting (WW) has been regarded as a justifiable treatment option, but doubts still exist since high crossover (CO) rates to surgery may occur. The aim of this study is to assess the CO rates after 13-year follow-up of our randomized controlled trial (RCT). Material and Methods In our original study, 496 men with an asymptomatic or mildly symptomatic IH were randomly assigned to elective repair or WW. A retrospective review was conducted of patients initially assigned to WW. Primary outcome was CO rate to surgery. Secondary outcomes included reason for crossing over and time between initial randomisation and the CO to surgery. Results In the original RCT, 95 of 262 WW patients electively crossed over to surgery (35.4%) after 32.9 months. Currently, 212 of the 262 (81.0%) WW patients were reviewed, and 133/212 (62.7%) crossed over to surgery. Median follow-up was 13 years (range, 8-15 years). Mean time to CO was 35.2 months SD (40.8). Motivations for crossing over to surgery were predominantly due to progression of symptoms (83.5%), and in 8 (3.8%) cases due to an emergency event. Conclusions In the presented population, WW on the long-term remains a safe strategy, saving one third of patients an operation, although CO to surgery will likely occur. Insights into the natural course of untreated inguinal hernia that are valuable during patient counseling can be offered in the form of long-term CO rate due to progression of symptoms.

746 Vectorized Treg-depleting anti-CTLA-4 elicits antigen cross-presentation and CD8+ T cell immunity to reject “cold” tumors

BackgroundImmune checkpoint blockade (ICB) is a clinically proven concept to treat cancer. Still, a majority of cancer patients including those with poorly immune infiltrated “cold” tumors are resistant to currently available ICB therapies. CTLA-4 is one of few clinically validated targets for ICB, but toxicities linked to efficacy in approved anti-CTLA-4 regimens have restricted their use and precluded full therapeutic dosing. At a mechanistic level, accumulating preclinical and clinical data indicate dual mechanisms for anti-CTLA-4; immune checkpoint blockade and Treg depletion are both thought to contribute efficacy and toxicity in available, systemic, anti-CTLA-4 regimens. Accordingly, strategies to deliver highly effective, yet safe, anti-CTLA-4 therapies have been lacking. Here, BioInvent and Transgene present and preclinically characterize a highly efficacious and potentially safe strategy to target CTLA-4 in the context of oncolytic virotherapy.MethodsA novel human IgG1 CTLA-4 antibody (4-E03) was identified using function-first screening for mAbs and targets associated with superior Treg depleting activity. A tumor-selective oncolytic Vaccinia vector was then engineered to encode this novel, strongly Treg-depleting, checkpoint-blocking, anti-CTLA-4 antibody and GM-CSF (VVGM-ahCTLA4, BT-001). Viruses encoding a matching Treg-depleting mouse surrogate antibody were additionally generated, enabling proof-of-concept studies in syngeneic immune competent mouse tumor models.ResultsOur studies demonstrate that intratumoral (i.t.) administration of VVGM-aCTLA4 achieved tumor-restricted CTLA-4 receptor saturation and Treg-depletion, which elicited antigen cross-presentation and stronger systemic expansion of tumor-specific CD8+ T cells and antitumor immunity compared with systemic anti-CTLA-4 antibody therapy. Efficacy correlated with FcgR-mediated intratumoral Treg-depletion and the reduction of exhausted CD8+ T cells. Remarkably, in a clinically relevant mouse model resistant to systemic immune checkpoint blockade, i.t. VVGM-aCTLA4 synergized with anti-PD-1 to reject “cold” tumors.ConclusionsOur findings demonstrate in vivo proof-of-concept for spatial restriction of strongly Treg-depleting, immune checkpoint blocking, vectorized anti-CTLA-4 as a highly effective and safe strategy to target CTLA-4 which is able to overcome current limitations of approved anti-CTLA-4 regimens. A clinical trial evaluating i.t. VVGM-ahCTLA4 (BT-001) alone and in combination with anti-PD-1 in metastatic or advanced solid tumors has commenced.Ethics ApprovalAll mouse experiments were approved by the local ethical committee for experimental animals (Malmö/Lunds djurförsöksetiska nämnd); at BioInvent under permit numbers 17196/2018 or 2934/2020; or at Transgene APAFIS Nr21622 project 2019072414343465 and performed in accordance with local ethical guidelines.

The results of a 24-month controlled, prospective study of relapsing multiple sclerosis patients at risk for progressive multifocal encephalopathy, who switched from prolonged use of natalizumab to teriflunomide

Background Natalizumab (NTZ) is a highly effective disease modifying treatment for relapsing multiple sclerosis (RMS), but it increases risk of progressive multifocal leukoencephalopathy (PML) in patients with serum anti- John Cunningham virus (JCV) antibodies. Objective To assess the safety and efficacy of rapid transition, from NTZ to teriflunomide (TFM) in RMS patients. Methods Clinically stable NTZ-treated, anti-JCV antibody positive RMS patients were switched to TFM 28 ± 7 days after their last dose of NTZ. The primary endpoint was proportion of relapse free patients at 24 months. Results Median [IQR] age of the 55 enrolled patients was 47 [40.7, 56.3] years, 76% were female. The median [IQR] number of prior NTZ treatments was 34 [18, 64]. annualized relapse rate (ARR) was 0.07 and 77% of the patients were relapse free at 24 months. Mean time to first GAD + lesion was 19.6 months, and to new/enlarging T2 lesion was 19.2 months. Mean time to 3 month sustained disability worsening (SDW) was 22 months and proportion free of 3-month SDW was 0.87. There were no cases of PML. Conclusions The washout-free transition of NTZ to TFM was an efficacious and safe strategy for patients at risk of developing PML. ClinicalTrials.gov Identifier: NCT01970410