Special considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global public health crisis. Multiple observations indicate poorer post-infection outcomes for patients with cancer than for the general population. Herein, we highlight the challenges in caring for patients with acute leukaemias and myeloid neoplasms amid the COVID-19 pandemic. We summarise key changes related to service allocation, clinical and supportive care, clinical trial participation, and ethical considerations regarding the use of lifesaving measures for these patients. We recognise that these recommendations might be more applicable to high-income countries and might not be generalisable because of regional differences in health-care infrastructure, individual circumstances, and a complex and highly fluid health-care environment. Despite these limitations, we aim to provide a general framework for the care of patients with acute leukaemias and myeloid neoplasms during the COVID-19 pandemic on the basis of recommendations from international experts

In the quest for degenerative lumbar spinal stenosis etiology: the Schmorl’s nodes model

Abstract Background Degenerative lumbar spinal stenosis (DLSS) is a common health problem in the elderly and usually associated with three-joint complex degeneration. Schmorl’s nodes (SNs) are described as vertical herniation of the disc into the vertebral body through a weakened part of the end plate that can lead to disc degeneration. Since SNs can harm the spine unit stability, the association between DLSS and SNs is expected. The aim of this study is to shed light on the relationship between degenerative lumbar spinal stenosis and SNs. Methods Two groups of individuals were studied: the first included 165 individuals with DLSS (age range: 40–88, sex ratio: 80 M/85 F) and the second 180 individuals without spinal stenosis related symptoms (age range: 40–99, sex ratio: 90 M/90 F). The presence or absence of SNs on the cranial and caudal end plate surfaces at the lumbosacral region (from L1 to S1 vertebra) was recorded, using CT images (Brilliance 64 Philips Medical System, Cleveland Ohio, thickness of the sections was 1–3 mm and MAS, 80–250). Chi-Square test was taken to compare the prevalence of SNs between the study groups (control and stenosis) by lumbar disc level, for each gender separately. Multivariable logistic regression analysis was also used to determine the association between DLSS and SNs. Results The prevalence rate of SNs was significantly greater in the stenosis males (L1-2 to L5-S1) and females (L4-5 and L4-S1) compared to their counterparts in the control (P < 0.001). In addition, the presence of SNs in both males and females was found to increase the likelihood for DLSS. Conclusions Our results indicate that SNs prevalence is significantly greater in the DLSS group compared to the control. Furthermore, SNs are strongly associated with DLSS

Eradication of CD48-positive tumors by selectively enhanced YTS cells harnessing the lncRNA NeST

Summary: Natural killer (NK) cells are currently used in clinical trials to treat tumors. However, such therapies still suffer from problems such as donor variability, reproducibility, and more, which prevent a wider use of NK cells therapeutics. Here we show a potential immunotherapy combining NK cell-mediated tumor eradiation and long non-coding (lnc) RNAs. We overexpressed the interferon (IFN) γ secretion-enhancing lncRNA nettoie Salmonella pas Theiler’s (NeST) in the NK cell-like cell line YTS. YTS cells express the co-stimulatory receptor 2B4 whose main ligand is CD48. On YTS cells, 2B4 functions by direct activation. We showed that NeST overexpression in YTS cells resulted in increased IFNγ release upon interaction with CD48 (selectively enhanced (se)YTS cells). Following irradiation, the seYTS cells lost proliferation capacity but were still able to maintain their killing and IFNγ secretion capacities. Finally, we demonstrated that irradiated seYTS inhibit tumor growth in vivo. Thus, we propose seYTS cells as off-the-shelve therapy for CD48-expressing tumors

Invasive meningococcal disease epidemiology and characterization of Neisseria meningitidis serogroups, sequence types, and clones; implication for use of meningococcal vaccines

Background and aims: Neisseria meningitidis (N. meningitidis) is a Gram-negative bacterium that can cause life-threatening invasive infections referred to as invasive meningococcal disease (IMD). In the last decade the incidence of IMD in Israel is about 1/100,000 population annually. We aimed to describe the epidemiology of IMD in Israel combining epidemiological data and characterization of N. meningitidis isolates. Methods: Invasive infection caused by N. meningitidis is a notifiable disease in Israel. Data were collected by epidemiological investigations and control measures were employed. Laboratory work-up included serogrouping, N. meningitides molecular characterization and whole-genome sequencing. Results: During 1998–2017, 1349 cases of IMD were notified in Israel (mean annual incidence rate 0.94/100,000). The peak incidence rates were observed in infants under 1 year of age (10.9/100,000). Case fatality rate was 9.7%. The majority of the N. meningitidis isolates were of serogroup B (67.9%). During 2007–2017, three clonal complexes (CC) 32, 41/44 and 23 (hyper-invasive clonal complexes) were the leading CC (61%). CC32 was the leading CC causing meningococcemia and mortality. In 2017, 35 isolates were tested for 4CMenB antigens variants; of the serogroup B isolates tested 46.7% showed a match to one or more antigens (fHbp or PorA:VR1), most were ST32 (CC32). Conclusions: Preliminary analysis based on limited number of samples suggests that the 4CMenB coverage would be about half the strains; further research is necessary. Integration of clinical, epidemiological and laboratory data is essential to support decision-making on the introduction of the novel MENB vaccines in Israel

Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity

Background The use of checkpoint inhibitors has revolutionized cancer therapy. Unfortunately, these therapies often cause immune-related adverse effects, largely due to a lack of tumor specificity. Methods We stained human natural killer cells using fusion proteins composed of the extracellular portion of various tumor markers fused to the Fc portion of human IgG1, and identified Nectin4 as a novel TIGIT ligand. Next, we generated a novel Nectin4 blocking antibody and demonstrated its efficacy as a checkpoint inhibitor in killing assays and in vivo. Results We identify Nectin4 to be a novel ligand of TIGIT. We showed that, as opposed to all other known TIGIT ligands, which bind also additional receptors, Nectin4 interacts only with TIGIT. We show that the TIGIT-Nectin4 interaction inhibits natural killer cell activity, a critical part of the innate immune response. Finally, we developed blocking Nectin4 antibodies and demonstrated that they enhance tumor killing in vitro and in vivo. Conclusion We discovered that Nectin4 is a novel ligand for TIGIT and demonstrated that specific antibodies against it enhance tumor cell killing in vitro and in vivo. Since Nectin4 is expressed almost exclusively on tumor cells, our Nectin4-blocking antibodies represent a combination of cancer specificity and immune checkpoint activity, which may prove more effective and safe for cancer immunotherapy

IFNG-AS1 Enhances Interferon Gamma Production in Human Natural Killer Cells

Summary: Long, non-coding RNAs (lncRNAs) are involved in the regulation of many cellular processes. The lncRNA IFNG-AS1 was found to strongly influence the responses to several pathogens in mice by increasing interferon gamma (IFNγ) secretion. Studies have looked at IFNG-AS1 in T cells, yet IFNG-AS1 function in natural killer cells (NKs), an important source of IFNγ, remains unknown. Here, we show a previously undescribed sequence of IFNG-AS1 and report that it may be more abundant in cells than previously thought. Using primary human NKs and an NK line with IFNG-AS1 overexpression, we show that IFNG-AS1 is quickly induced upon NK cell activation, and that IFNG-AS1 overexpression leads to increased IFNγ secretion. Taken together, our work expands IFNG-AS1's activity to the innate arm of the type I immune response, helping to explain its notable effect in animal models of disease. : Molecular Biology; Molecular Mechanism of Gene Regulation; Immunology; Immune Response Subject Areas: Molecular Biology, Molecular Mechanism of Gene Regulation, Immunology, Immune Respons