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SWItch/sucrose non-fermentable (SWI/SNF) is a large protein complex with a central role in chromatin remodeling and genome transcription. The catalytic subunits of the SWI/SNF related BAF chromatin remodeling complex subunit ATPase 2 (SWI/SNF SMARCA2; also called BRM) and SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4 (SMARCA4; also called BRG1) are encoded by the SMARCA2 and SMARCA4 genes, respectively, and are mutually exclusive. Loss of either SMARCA2 and/or SMARCA4 has been previously reported in several types of malignant solid tumors of the gastrointestinal and genitourinary tract. So far, their absence in non-small cell lung cancer (SCLC) has been observed in a series of studies involving primary tumors and cell lines, where it is associated with loss of differentiation and heightened tumorigenic potential leading to an unfavorable prognosis. SMARCA2 and SMARCA4 deficiency is frequent in solid predominant adenocarcinomas and tumors with low levels of bronchial epithelial markers, including thyroid transcription factor 1. A rare case of SMARCA4 deficiency in SCLC is described. A 57-year-old male patient, with no medical history of past illness, was admitted to our center for the investigation and management of a space-occupying lesion in the right upper lung lobe with tracheal and mediastinal infiltration. Biopsy of a lymph node in the right supraclavicular region was diagnostic for SCLC with regional loss of SMARCA4. The patient demonstrated progressive respiratory failure and clinical deterioration and eventually deceased despite intubation and transfer to the intensive care unit. This case indicates that SMARCA4-deficient SCLC may present with an aggressively deteriorating phenotype with poor outcomes for the patients.

Background and Aim: There is limited data on the prevalence of SARS-COV-2 in sarcoidosis patients and the underlying parameters linked to severity. We aimed to conduct a national multicenter study to explore the prevalence of SARS-COV-2 in sarcoidosis patients and investigate its impact on hospitalization and infection rates, describe the characteristics of the infected population and assess the role of these characteristics in determining the likelihood of infection or hospitalization., Methods: We recruited all the adult sarcoidosis patients with who were examined across eight Greek Health Interstitial Lung Disease Referral Centers from the beginning of the pandemic until August 1, 2022. All the data was collected using structured questionnaires., Results: 530 sarcoidosis patients with a mean age of 54±12 years, 60% of whom were females, were recruited. 43% of them were under corticosteroid treatment, and 39% were under additional immunosuppression. 18% of Greek sarcoidosis patients were infected by the virus, which is a lower rate than the general population. The infection was mainly mild. Only one-fifth of the infected sarcoidosis patients required hospitalization, and no deaths or ICU admissions were recorded. Vaccination was found to be associated with a reduced likelihood of infection. Younger age, a longer period since diagnosis, abnormal PET-CT findings, and immunosuppression were associated with an increased probability of infection., Conclusions: The COVID-19 infection rate among Greek sarcoidosis patients was lower than the general population. Fewer than 20% needed hospitalization. There were no deaths or ICU admissions. Vaccination reduces the likelihood of infection. Younger age, longer diagnosis, abnormal PET-CT findings, and immunosuppression increased the chance of infection.

Competing Interests: The authors declare no conflict of interest.

Early career members of Assembly 3 (Basic and Translational Sciences) of the European Respiratory Society (ERS) summarise the key messages discussed during six selected sessions that took place at the ERS International Congress 2023 in Milan, Italy. Aligned with the theme of the congress, the first session covered is "Micro- and macro-environments and respiratory health", which is followed by a summary of the "Scientific year in review" session. Next, recent advances in experimental methodologies and new technologies are discussed from the "Tissue modelling and remodelling" session and a summary provided of the translational science session, "What did you always want to know about omics analyses for clinical practice?", which was organised as part of the ERS Translational Science initiative's aims. The "Lost in translation: new insights into cell-to-cell crosstalk in lung disease" session highlighted how next-generation sequencing can be integrated with laboratory methods, and a final summary of studies is presented from the "From the transcriptome landscape to innovative preclinical models in lung diseases" session, which links the transcriptome landscape with innovative preclinical models. The wide range of topics covered in the selected sessions and the high quality of the research discussed demonstrate the strength of the basic and translational science being presented at the international respiratory conference organised by the ERS., Competing Interests: Conflict of interest: A. Schweikert report grants or contracts from Health Research Board (HRB) and support for attending meetings and/or travel from Irish Lung Fibrosis Association, outside the submitted work. Conflict of interest: C.X. Lim reports support for the present manuscript from the Ludwig Boltzmann Institute for Lung Health; and a grant from Austrian Society for Pneumology (ÖGP) Science and support for attending meetings and/or travel from Medical University of Vienna, Austrian Science Fund (FWF P34266-B), outside the submitted work. Conflict of interest: K.M. Lodge reports support for the present manuscript from National Institute for Health and Care Research (NIHR) Imperial Biomedical Research Centre; and consulting fees from NetScientific PLC and ProAxis Ltd, outside the submitted work. Conflict of interest: N. Ubags is Secretary of ERS Group 3.03. Conflict of interest: A.M. van der Does is Secretary of ERS Group 3.02. Conflict of interest: S.M. Cloonan reports grants or contracts from PETA Science Consortium Award for 3-D Human Tissue Models and Irish Research Council; consulting fees from AstraZeneca GRLF Innovation Forum; support for attending meetings and/or travel from ERS Annual Conference, ATS Annual Conference and AstraZeneca GRLF Innovation Forum; and leadership or fiduciary roles in other boards, societies, committees or advocacy groups for ERS Group 3.02 (Chair), ATS AAI Program Committee and ERS Fellowship and Awards Committee, outside the submitted work. Conflict of interest: N.L. Reynaert reports being supported by ERS to attend this meeting and is Secretary of ERS Assembly 3. Conflict of interest: I.H. Heijink reports grants or contracts from Dutch Longfonds, ZonMW and Health Holland, outside the submitted work; and is Head of ERS Assembly 3. Conflict of interest: S. Cuevas-Ocaña reports receiving support from the ERS to attend the ERS Congress, outside the submitted work; and is Early Career Member Committee Chair and Early Career representative of ERS Assembly 3. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

The umbilical cord blood (UCB) donated in public UCB banks is a source of hematopoietic stem cells (HSC) alternative to bone marrow for allogeneic HSC transplantation (HSCT). However, the high rejection rate of the donated units due to the strict acceptance criteria and the wide application of the haploidentical HSCT have resulted in significant limitation of the use of UCB and difficulties in the economic sustainability of the public UCB banks. There is an ongoing effort within the UCB community to optimize the use of UCB in the field of HSCT and a parallel interest in exploring the use of UCB for applications beyond HSCT i.e., in the fields of cell therapy, regenerative medicine and specialized transfusion medicine. In this report, we describe the mode of operation of the three public UCB banks in Greece as an example of an orchestrated effort to develop a viable UCB banking system by (a) prioritizing the enrichment of the national inventory by high-quality UCB units from populations with rare human leukocyte antigens (HLA), and (b) deploying novel sustainable applications of UCB beyond HSCT, through national and international collaborations. The Greek paradigm of the public UCB network may become an example for countries, particularly with high HLA heterogeneity, with public UCB banks facing sustainability difficulties and adds value to the international efforts aiming to sustainably expand the public UCB banking system.

Coronavirus disease 2019 (COVID-19) pneumonia is associated with extensive pulmonary microangiopathy and the enlargement of the pulmonary artery (PA), while its progression after the remission of the disease has not been investigated yet. The aim was to assess the diametral increase in the PA in COVID-19 pneumonia, as revealed on chest computed tomography (CT), and further investigate its progression. This was a retrospective cohort study of patients with COVID-19 pneumonia, without prior history of pulmonary hypertension, who underwent CT pulmonary angiography before, during, and after the infection. Pulmonary embolism was excluded in all cases. The main PA diameter (MPAD) was assessed in consecutive chest imaging. Statistical analysis was performed with the non-parametric Wilcoxon and Kruskal-Wallis tests, while correlations were performed with the non-parametric Spearman test. A mean ± SD MPAD of 3.1 ± 0.3 cm in COVID-19 pneumonia was significantly decreased to 2.8 ± 0.3 cm in the post-infectious state after 2-18 months in 31 patients ( p -value: <0.0001). In a subgroup of six patients with more than one post-COVID-19 CT, a significant further decline in the diameter was observed ( p -value: 0.0313). On the other hand, in accordance with the literature, a significant increase in the MPAD during COVID-19 pneumonia was noted in a group of 10 patients with a pre-COVID-19 CT ( p -value: 0.0371). The enlargement of the PA is a common finding in COVID-19 pneumonia that regresses after the remission of the disease, indicating that this reversible cardiovascular event is a potential marker of disease activity, while its course in long COVID is yet to be determined.

Myeloid-derived suppressor cells (MDSCs) are notable innate immune cells, which are further divided into two subpopulations, i.e., monocytic and granulocytic. These cells are traditionally considered to mainly suppress the T-cell responses. However, more updated data indicate that their properties are rather immunomodulatory than solely immunosuppressive. Indeed, MDSCs display extensive crosstalk with other either innate or adaptive immune cells, and, according to the situation under which they are triggered, they may enhance or attenuate the immune response. However, their positive role in host's defense mechanisms under specific conditions is rarely discussed in the literature. In this mini-review, the authors briefly summarise the mechanisms of action of MDSCs under distinct conditions, such as infections and malignancies, with a particular emphasis on their role as components of the innate immunity system., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Myeloid-derived suppressor cells (MDSCs) are immature cells of myeloid origin that have gained researchers' attention, as they constitute promising biomarkers and targets for novel therapeutic strategies (i.e., blockage of development, differentiation, depletion, and deactivation) in several conditions, including neoplastic, autoimmune, infective, and inflammatory diseases, as well as pregnancy, obesity, and graft rejection. They are characterised in humans by the typical immunophenotype of CD11b + CD33 + HLA-DR -/low and immune-modulating properties leading to decreased T-cell proliferation, induction of T-regulatory cells (T-regs), hindering of natural killer (NK) cell functionality, and macrophage M2-polarisation. The research in the field is challenging, as there are still difficulties in defining cell-surface markers and gating strategies that uniquely identify the different populations of MDSCs, and the currently available functional assays are highly demanding. There is evidence that MDSCs display altered frequency and/or functionality and could be targeted in immune-mediated and malignant haematologic diseases, although there is a large variability of techniques and results between different laboratories. This review presents the current literature concerning MDSCs in a clinical point of view in an attempt to trigger future investigation by serving as a guide to the clinical haematologist in order to apply them in the context of precision medicine as well as the researcher in the field of experimental haematology.

Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of myeloid cells that suppress immune responses in cancer, infection, and trauma. They mainly act by inhibiting T-cells, natural-killer cells, and dendritic cells, and also by inducing T-regulatory cells, and modulating macrophages. Although they are mostly associated with adverse prognosis of the underlying disease entity, they may display positive effects in specific situations, such as in allogeneic hematopoietic stem cell transplantation (HSCT), where they suppress graft-versus-host disease (GVHD). They also contribute to the feto-maternal tolerance, and in the fetus growth process, whereas several pregnancy complications have been associated with their defects. Human umbilical cord blood (UCB) is a source rich in MDSCs and their myeloid progenitor cells. Recently, a number of studies have investigated the generation, isolation, and expansion of UCB-MDSCs for potential clinical application associated with their immunosuppressive properties, such as GVHD, and autoimmune and inflammatory diseases. Given that a significant proportion of UCB units in cord blood banks are not suitable for clinical use in HSCT, they might be used as a significant source of MDSCs for research and clinical purposes. The current review summarizes the roles of MDSCs in the UCB, as well as their promising applications.

Acute fibrinous and organizing pneumonia (AFOP) is an entity that can be secondary to various conditions leading to lung injury, such as infections, malignancies, and various autoimmune conditions or idiopathic interstitial lung disease, when no obvious underlying cause is identified. Myelodysplastic syndromes (MDS), on the other hand, are a spectrum of clonal myeloid disorders, with a higher risk of acute leukemia, characterized by ineffective bone marrow (BM) hematopoiesis and, thus, peripheral blood (PB) cytopenias. Immune deregulation is thought to take part in the pathophysiology of the disease, including abnormal T and/or B cell responses, innate immunity, and cytokine expression. In the literature, there are a few case reports of patients with MDS that have presented pulmonary infiltrates and were diagnosed as having AFOP or organizing pneumonia (OP). It is rare, though, to have isolated pulmonary infiltrates without Sweet's syndrome or even the pulmonary infiltrates to precede the diagnosis and treatment of MDS, which was our case. We present a 72-year-old female developing new lung infiltrates refractory to antibiotic treatment that responded well to corticosteroids and was histologically described as having OP. The treatment was gradually successfully switched to mycophenolate mofetil (MMF). The patient was later diagnosed with MDS. This interesting case report suggests firstly that a diagnosis of AFOP or OP should alert the clinician to search for an underlying cause including MDS and vice versa , the use of systemic steroids should not be postponed, and, finally, that MMF can successfully be used in these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bizymi, Pitsidianakis, Ierodiakonou, Stathakis, Vasarmidi, Hiraki, Bolaki, Karagiannis, Fanaridis, Liopyrakis, Marinos, Xilouri, Antoniou and Tzanakis.)

Immune deregulation has a critical role in the pathogenesis of lower risk myelodysplastic syndromes (MDS). The cells of the macrophage/monocyte lineage have been reported to contribute to the inflammatory process in MDS through impaired phagocytosis of the apoptotic hemopoietic cells and abnormal production of cytokines. In the present study we assessed the number of peripheral blood (PB) monocyte subsets, namely the classical CD14 bright /CD16 - , intermediate CD14 bright /CD16 + and non-classical CD14 dim /CD16 + cells, in patients with lower risk (low/intermediate-I) MDS (n = 32). We also assessed the production of tumor necrosis factor (TNF)α by patient PB monocytes in response to immune stimulus as well as their transcriptome profile. Compared to age- and sex-matched healthy individuals (n = 19), MDS patients had significantly lower number of classical and increased number of intermediate monocytes. Patient intermediate monocytes displayed increased production of TNFα following stimulation with lipopolysaccharide, compared to healthy individuals. Transcriptional profiling comparison of CD16 + monocytes from patients and controls revealed 43 differentially expressed genes mostly associated with biological pathways/processes relevant to hemopoiesis, immune signaling and cell adhesion. These data provide evidence for the first-time that distinct monocyte subsets display abnormal quantitative and functional characteristics in lower risk MDS substantiating their role in the immune deregulation associated with the disease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immature myeloid cells that exist at very low numbers in healthy subjects but can expand significantly in malignant, infectious, and chronic inflammatory diseases. These cells are characterized as early-MDSCs, monocytic-MDSCs, and polymorphonuclear-MDSCs and can be studied on the basis of their immunophenotypic characteristics and their functional properties to suppress T-cell activation and proliferation. MDSCs have emerged as important contributors to tumor expansion and chronic inflammation progression by inducing immunosuppressive mechanisms, angiogenesis and drug resistance. Most experimental and clinical studies concerning MDSCs have been mainly focused on solid tumors. In recent years, however, the implication of MDSCs in the immune dysregulation associated with hematologic malignancies, immune-mediated cytopenias and allogeneic hemopoietic stem cell transplantation has been documented and the potential role of these cells as biomarkers and therapeutic targets has started to attract a particular interest in hematology. The elucidation of the molecular and signaling pathways associated with the generation, expansion and function of MDSCs in malignant and immune-mediated hematologic diseases and the clarification of mechanisms related to the circulation and the crosstalk of MDSCs with malignant cells and other components of the immune system are anticipated to lead to novel therapeutic strategies. This review summarizes all available evidence on the implication of MDSCs in hematologic diseases highlighting the challenges and perspectives arising from this novel field of research., (Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Chronic Obstructive Pulmonary Disease (COPD) is very a common, with great morbidity and mortality, disease. Since the beginning of the disease cannot be detected with precision and by using only FEV1 to monitor the evolution of the disease, the Natural History of COPD is rather obscure and sometimes controversial. Therefore, the terms EARLY COPD and MILD COPD have been used indistinguishably in the medical literature. In this review we discuss the two terms trying to clarify some of the definition issues, starting with a synopsis of the Naturel History of the disease. We recommend to use the term EARLY COPD for the pre-clinical stage of the disease (stage 0) and the term MILD COPD when the diagnosis is confirmed by spirometry and FEV1 is above 80% predicted. However, COPD is a complex disease and spirometric evaluation alone (MILD COPD, stage I), cannot fully describe the clinical status of the patient. We conclude that biomarkers to detect the starting point and been able to follow the natural history of the disease more accurately, beyond FEV, are urgently needed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)