Validation and clinical application of transactivation assays for RUNX1 variant classification

Familial platelet disorder with associated myeloid malignancies (RUNX1-FPD) is caused by heterozygous pathogenic germline variants of RUNX1. In the present study, we evaluate the applicability of transactivation assays to investigate RUNX1 variants in different regions of the protein. We studied 11 variants to independently validate transactivation assays supporting variant classification following the ClinGen Myeloid Malignancies variant curation expert panel guidelines. Variant classification is key for the translation of genetic findings. We showed that new assays need to be developed to assess C-terminal RUNX1 variants. Two variants of uncertain significance (VUS) were reclassified to likely pathogenic. Additionally, our analyses supported the (likely) pathogenic classification of two other variants. We demonstrated functionality of four VUS, but reclassification to (likely) benign was challenging and suggested the need to reevaluate current classification guidelines. Finally, clinical utility of our assays was illustrated in the context of seven families. Our data confirmed RUNX1-FPD suspicion in three families with RUNX1-FPD-specific family history. Whereas for three variants identified in non RUNX1-FPD-typical families, no functional defect was detected. Applying functional assays to support RUNX1 variant classification can be essential for adequate care of index patients and their relatives at risk. It facilitates translation of genetic data into personalized medicine.

Process Mapping Strategies to Prevent Subcutaneous Implantable Cardioverter-Defibrillator Infection

Background: Infection remains a major complication of cardiac implantable electronic devices (CIEDs) and can lead to significant morbidity and mortality. Extrathoracic devices that avoid epicardial or transvenous leads, such as the subcutaneous implantable cardioverter-defibrillator (S-ICD), can reduce the risk of serious infection-related complications, such as bloodstream infection and infective endocarditis. While the 2017 AHA/ACC/HRS guidelines include recommendations for S-ICD use for patients at high risk of infection, currently, there are no clinical trial data that address best practices for the prevention of S-ICD infections. Therefore, an expert panel was convened to develop consensus on these topics. Methods: An expert process mapping methodology was used to achieve consensus on the appropriate steps to minimize or prevent S-ICD infections. Two face-to-face meetings of high-volume S-ICD implanters and an infectious diseases specialist, with expertise on cardiovascular implantable electronic device infections, were conducted to develop consensus on useful strategies pre-, peri-, and post-implant to reduce S-ICD infection risk. Results: Expert panel consensus of recommended steps for patient preparation, S-ICD implantation, and post-operative management were developed to provide guidance in individual patient management. Conclusion: Achieving expert panel consensus by process mapping methodology for S-ICD infection prevention was attainable, and the results should be helpful to clinicians in adopting interventions to minimize risks of S-ICD infection.

Adaptation and Preliminary Validation of the Arabic Version of the Role Checklist Version 3 (RCv3)

Arab occupational therapists are in need either to develop their own outcome measures or to translate well-known outcome measures to their culture. The objective of this study was to translate, cross-culturally adapt, and validate preliminarily the Role Checklist Version 3 (RCv3) into Arabic language. The translation and cross-cultural adaptation process of the RCv3 into Arabic language was conducted in four main steps: (a) forward translation, (b) back translation, (c) expert panel review process, and (d) psychometric testing (Validity). The expert panel established the face validity and the content validity of the Arabic RCv3. Pilot testing was conducted, and the utility and content validity of the tool were confirmed. The final version of the Arabic RCv3 is now available for use in the Arab countries. However, further psychometric properties including reliability and responsiveness of this tool is warranted, thus supporting its wide use and proper application.

Management of Stage III Non–Small-Cell Lung Cancer: ASCO Guideline

PURPOSE To provide evidence-based recommendations to practicing clinicians on management of patients with stage III non–small-cell lung cancer (NSCLC). METHODS An Expert Panel of medical oncology, thoracic surgery, radiation oncology, pulmonary oncology, community oncology, research methodology, and advocacy experts was convened to conduct a literature search, which included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2021. Outcomes of interest included survival, disease-free or recurrence-free survival, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS The literature search identified 127 relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS Evidence-based recommendations were developed to address evaluation and staging workup of patients with suspected stage III NSCLC, surgical management, neoadjuvant and adjuvant approaches, and management of patients with unresectable stage III NSCLC. Additional information is available at www.asco.org/thoracic-cancer-guidelines .

Chaplain Leadership During COVID-19: An International Expert Panel

Chaplain leadership may have played a pivotal role in shaping chaplains’ roles in health care amidst the COVID-19 pandemic. We convened an international expert panel to identify expert perception on key chaplain leadership factors. Six leadership themes of professional confidence, engaging and trust-building with executives, decision-making, innovation and creativity, building integrative and trusting connections with colleagues, and promoting cultural competencies emerged as central to determining chaplains’ integration, perceived value, and contributions during the pandemic.

Promoting a Syndemic Approach for Cardiometabolic Disease Management During COVID-19: The CAPISCO International Expert Panel

Efforts in the fight against COVID-19 are achieving success in many parts of the world, although progress remains slow in other regions. We believe that a syndemic approach needs to be adopted to address this pandemic given the strong apparent interplay between COVID-19, its related complications, and the socio-structural environment. We have assembled an international, multidisciplinary group of researchers and clinical practitioners to promote a novel syndemic approach to COVID-19: the CArdiometabolic Panel of International experts on Syndemic COvid-19 (CAPISCO). This geographically diverse group aims to facilitate collaborative-networking and scientific exchanges between researchers and clinicians facing a multitude of challenges on different continents during the pandemic. In the present article we present our “manifesto”, with the intent to provide evidence-based guidance to the global medical and scientific community for better management of patients both during and after the current pandemic.