Isatuximab, carfilzomib and dexamethasone (Isa-Kd) for the management of relapsed multiple myeloma

The treatment of relapsed multiple myeloma remains challenging. Based on interim data from the randomized Phase III IKEMA study demonstrating a progression-free survival benefit with a combination of isatuximab (Isa, a CD38-targeted monoclonal antibody) and carfilzomib/dexamethasone (Kd) versus Kd alone, Isa-Kd recently received regulatory approval in the USA and Europe for patients with multiple myeloma who have received at least one prior line of therapy (in the USA, up to three prior lines). In this review we discuss the rationale and clinical trial experience to date with Isa-Kd. Although final IKEMA results are pending, Isa-Kd has emerged as an effective and tolerable therapy for patients with relapsed multiple myeloma. Given the growing number of antibody-containing triplet regimens in this setting, potential niches and limitations for Isa-Kd are also discussed.

Approaches to Establishing Tolerance in Immune Mediated Diseases

The development of rational approaches to restore immune tolerance requires an iterative approach that builds on past success and utilizes new mechanistic insights into immune-mediated pathologies. This article will review concepts that have evolved from the clinical trial experience of the Immune Tolerance Network, with an emphasis on lessons learned from the innovative mechanistic studies conducted for these trials and new strategies under development for induction of tolerance.

Virtual Screening and Molecular Docking: Discovering Novel c-KIT Inhibitors

: Gastrointestinal stromal tumors (GISTs) are unusual cancers which begin in specialized cells in the gastrointestinal tract wall. Various strategies involving single-agents, combinations, and rapid complementary inhibitor cycling are now being used to control such tumors. Based on promising early clinical trial experience, certain novel KIT, and PDGFRA tyrosine kinase inhibitors have begun advanced clinical development. Resistance to tyrosine kinase inhibitors has brought immense difficulties, with patients now requiring additional therapeutic options. This review describes and discusses the last five years (2016-2020) in developing novel c-KIT kinase inhibitors using virtual screening and docking approaches. Computational techniques can be used to complement experimental studies to identify new candidate molecules for therapeutic use. Molecular modeling strategies allow analysis of the required characteristics that compounds must have to effectively bind c-KIT. Through such analyses, it is possible to both discover and design novel inhibitors against cancer-related proteins that play a critical role in tumor development (including of mutant strains). Docking showed potential in the detection of the key residues responsible for ligand recognition and are very helpful to understand the interactions in the active site that can be used to develop new compounds/classes of anticancer drugs and help millions of cancer patients.

Wisconsin Assistive Technology Initiative framework for supporting assistive technology decision-making in Singapore schools: perspectives of in-service educators

PurposeThis study explored in-service educators' experience of using the Wisconsin Assistive Technology Initiative (WATI) for assistive technology (AT) decision-making within Singapore schools.Design/methodology/approachThe study adopted a qualitative design. Eight educators across both mainstream and special education schools were introduced to the WATI framework which they subsequently employed as a trial experience for a student under their care. Written feedback gathered from participants was analysed to identify common issues and themes regarding the use of the WATI framework for AT decision-making.FindingsThe comprehensive consideration of a broad scope of different factors, provision of a structured process for AT decision-making, as well as a common language for use by different stakeholders emerged as key benefits of implementing the WATI. Challenges encountered include administrative struggles in gathering different stakeholders together, time and resource constraints and difficulties in loaning AT devices for trial use.Practical implicationsBased on educators' feedback, recommendations to facilitate the adoption of the WATI for AT decision-making within Singapore schools are discussed and considered. This study also highlights the need for greater AT instruction within both preservice and in-service teacher preparation programmes in Singapore.Originality/valueSchools in Singapore currently rarely adopt any frameworks in place to guide educators through a systematic process of AT consideration. It is anticipated that this study will spearhead and drive the adoption of systematic frameworks such as the WATI for better AT decision-making within Singapore schools.Peer reviewThe peer review history for this article is available at: https://publons.com/publon 10.1108/JET-03-2021-0015

Food Allergy Management Has Been Negatively Impacted During the COVID-19 Pandemic

ABSTRACT Objective: The coronavirus disease 2019 (COVID-19) pandemic creates secondary problems for the health care system, and understanding specific issues can guide the management of the pandemic and its future consequences. We aimed to characterize the problems and related risk factors experienced with outpatient compliance and dietary compliance of children with food allergies during the COVID-19 pandemic. Materials and Methods: A cross-sectional survey was conducted on the mothers of children with ongoing food allergies, eight months after Turkey’s first confirmed case of COVID 19. Results: Of the 288 patients, 76.3% and 40.2% were non-adherent to their scheduled appointments and oral food challenge, respectively, during the pandemic. The group non-adherent to their scheduled visit was significantly older (p=0.005), had more frequent home food trials without the consent of their physicians (p<0.001), and had less usable epinephrine auto-injectors (EAI) available compared with the adherent group (p<0.001). Eighty-nine patients (30.9%) with home food trial experience had more essential food allergies (p<0.001) and experienced more allergic reactions (p=0.002), compared with patients who adhered to dietary elimination. Thirty parents (10.4%) eliminated some foods from their children’s diet because of the suspected reactions. Conclusion: The COVID-19 pandemic, significantly reduces adherence with scheduled appointments and OFC, and increases home food trials and food eliminations without physician approval. Keywords: The COVID-19 pandemic, food allergy, compliance, telemedicine, oral food challenge

Enhanced use of gaze cue in a face-following task after brief trial experience in individuals with autism spectrum disorder

Eye movements toward sequentially presented face images with or without gaze cues were recorded to investigate whether those with ASD, in comparison to their typically developing (TD) peers, could prospectively perform the task according to gaze cues. Line-drawn face images were sequentially presented for one second each on a laptop PC display, and the face images shifted from side-to-side and up-and-down. In the gaze cue condition, the gaze of the face image was directed to the position where the next face would be presented. Although the participants with ASD looked less at the eye area of the face image than their TD peers, they could perform comparable smooth gaze shift to the gaze cue of the face image in the gaze cue condition. This appropriate gaze shift in the ASD group was more evident in the second half of trials in than in the first half, as revealed by the mean proportion of fixation time in the eye area to valid gaze data in the early phase (during face image presentation) and the time to first fixation on the eye area. These results suggest that individuals with ASD may benefit from the short-period trial experiment by enhancing the usage of gaze cue.