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7 months vs. 6.3 months , P less then 0.001; hazard ratio 0.14, 95% CI 0.08-0.25) and significantly shorter median overall survival (8.2 months vs. 22.6 months , P less then 0.001; hazard ratio 0.27, 95% CI 0.15-0.49). Multivariate analysis revealed that RP was independently predicted by the presence of ≥3 metastatic sites (P = 0.039) and a neutrophil-to-lymphocyte ratio of ≥3 (P = 0.044). CONCLUSIONS Among NSCLC patients, RP was a common response to ICI monotherapy and was associated with dramatically reduced progression-free and overall survival. Care is needed when selecting ICI monotherapy for these patients, especially if they have ≥3 metastatic sites or a neutrophil-to-lymphocyte ratio of ≥3. © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.Systemic sclerosis (SSc) is an autoimmune rheumatic disease with heterogeneous clinical manifestations and variable disease course in which the severity of pathology dictates the disease prognosis and course. Among autoimmune rheumatic diseases, SSc carries the highest mortality, but there are exciting new therapeutic targets that appear to halt the progression of SSc manifestations such as skin or lung fibrosis. In selected patients, high-intensity regimens with autologous stem cell transplantation can favorably modify the disease course. From what was once thought to be an untreatable disease, targeted therapies have now changed the outlook of SSc to a treatable disease. Our review discusses the targeted therapies that are modifying the outlook of selected organ involvement and creating opportunities for the future. We also define a framework for low disease activity in SSc. This article is protected by copyright. All rights reserved.Hypocellular bone marrow failure (BMF) has myriad differential diagnoses, most simply considered as acquired and inherited disorders, which are frequently indistinguishable upon morphologic examination of the blood and bone marrow. Accurate diagnosis is critical to optimization of management and begins with a detailed history (including family history) and physical examination. Next-generation sequencing technologies complement traditional testing techniques (such as chromosomal fragility and telomere length assessment) and have a broad application in the diagnosis and prognostication of BMF, with the importance of detection of both germline changes and also somatic variants increasingly well understood and appreciated. There is increasing awareness of germline predisposition to haematological malignancy, which incorporates but is not limited to the traditional inherited BMF syndromes and which raises challenges for counselling, monitoring and treatment of people who harbour a germline lesion. There are many benefits to both patients and their kindred of accurate determination of the precise germline change underlying heritable bone marrow diseases, along with its associated mode of inheritance. While individually, these diseases are rare, collectively they are not so and there are many collaborative efforts underway to document the natural history of these disorders, the associated phenotypes and the ever-increasing list of variants which have sufficient evidence to warrant the ascription of a pathogenic classification. We describe the many diagnostic considerations when evaluating newly presenting patients with hypocellular BMF, with a focus on genomic assessment, which is relevant in both germline and acquired diseases. © 2020 John Wiley & Sons Ltd.Internal tandem duplication of Fms-like tyrosine kinase 3 (FLT3/ITD) occurs in about 30% of acute myeloid leukemia (AML) and is associated with poor response to conventional treatment and adverse outcome. Here, we reported that human FLT3/ITD expression led to axis duplication and dorsalization in about 50% of zebrafish embryos. The morphologic phenotype was accompanied by ectopic expression of a morphogen follistatin (fst) during early embryonic development. Increase in fst expression also occurred in adult FLT3/ITD-transgenic zebrafish, Flt3/ITD knock-in mice, and human FLT3/ITD AML cells. Overexpression of human FST317 and FST344 isoforms enhanced clonogenicity and leukemia engraftment in xenotransplantation model via RET, IL2RA, and CCL5 upregulation. Specific targeting of FST by shRNA, CRISPR/Cas9, or antisense oligo inhibited leukemic growth in vitro and in vivo. MDL-28170 Importantly, serum FST positively correlated with leukemia engraftment in FLT3/ITD AML patient-derived xenograft mice and leukemia blast percentage in primary AML patients. In FLT3/ITD AML patients treated with FLT3 inhibitor quizartinib, serum FST levels correlated with clinical response. These observations supported FST as a novel therapeutic target and biomarker in FLT3/ITD AML. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.AIM Studies have demonstrated that a majority of the decline in health status and functioning emerges during the first few years following the onset of psychosis. This knowledge led to the development of specialized early intervention services (EIS) targeting patients experiencing their first episode of psychosis (FEP). The central component of EIS is often assertive case management delivered by a multidisciplinary team, where an appointed key worker is responsible for coordinating treatment and delivering various psychosocial interventions to service users. The aim of this scoping review was to examine how key workers can enhance the physical health outcomes in people with FEP by addressing the factors associated with increased mortality in this population. METHODS The scoping review framework comprised a five-stage process developed by Arksey and O’Malley. The search process was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS A total of 27 studies conducted across 10 countries were analysed. These studies discussed the various ways in which key workers can mediate enhancements in the various factors contributing to the increased mortality rates in FEP patients. CONCLUSIONS A broad range of key worker-mediated outcomes was identified, which were broadly classified into three themes influences on lifestyle, influences on effects of psychosis and influences on organizational barriers. Our findings suggest that key workers primarily mediated the amelioration of psychosis-induced effects and the reduction of organizational barriers. Further trials of key worker interventions to enhance physical health outcomes in this cohort are warranted. © 2020 John Wiley & Sons Australia, Ltd.