Acute Promyelocytic Leukemia: an Experience on 95 Greek Patients Treated in the All-Trans-Retinoic Acid Era

Acute promyelocytic leukemia (APL) is highly curable with the combination of all-transretinoic acid (ATRA) and anthracycline based chemotherapy, but the percentage of early deaths remains high. In the present study, we report the clinical, immunophenotypic, cytogenetic and molecular characteristics and outcome of APL patients diagnosed and treated in various Hospitals of Greece and Cyprus

Acute fibrinous and organising pneumonia: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Organising pneumonia is a distinct histopathological entity characterized by intra-alveolar buds of granulation tissue, called Masson bodies, which mainly comprise of activated fibroblasts and loose connective tissue. This histopathologic pattern has been described in idiopathic cases, characterizing cryptogenic organising pneumonia as well as in the context of pulmonary infection, drug-induced pneumonitis and following lung transplantation. Although distinct as a clinical and pathological entity, community organising pneumonia may present with atypical clinical and pathological features, such as intra-alveolar fillings of fibrin balls and organising tissue that resembles acute respiratory distress syndrome or diffuse alveolar damage. The latter characteristics constitute a recently described anatomoclinical entity called acute fibrinous and organising pneumonia.</p> <p>Case presentation</p> <p>Here, we describe a rare case of acute fibrinous and organising pneumonia, in an otherwise healthy 65-year-old Greek woman who complained of dry cough, fever, weight loss and progressive dyspnoea. She had never been a smoker. Her clinical symptoms showed a rapid deterioration in the two weeks before admission, despite a course of oral antibiotics. After excluding infection and malignancy with routine laboratory tests and flexible bronchoscopy, high resolution computed tomography and video assisted thoracoscopic lung biopsy were performed. Diagnosis was based on radiological features typical of community organising pneumonia coupled with pathologic features characteristic of acute fibrinous and organising pneumonia. The patient was treated with corticosteroids and showed excellent clinical and radiological response three months after treatment initiation.</p> <p>Conclusion</p> <p>Acute fibrinous and organising pneumonia is an extremely rare pathologic entity, often misdiagnosed as typical community organising pneumonia. To our knowledge, this is the seventh case of acute fibrinous and organising pneumonia in the literature, with no identifiable cause or association in a female patient, with no underlying lung disease or known exposures and with an unremarkable previous medical history. We highlight the need for careful review of lung biopsies from patients with clinical and radiologic characteristics typical of community organising pneumonia. Although it remains uncertain whether fibrin alters the favourable prognosis and treatment response of community organising pneumonia, it becomes obvious that a thorough pathologic review, apart from establishing the diagnosis of acute fibrinous and organising pneumonia, may predict a more unfavorable outcome therefore alerting the clinician to administer more aggressive and prolonged therapeutic regimens.</p

JAK2 V617F hematopoietic clones are present several years prior to MPN diagnosis and follow different expansion kinetics.

TO THE EDITOR: The JAK2 V617F mutation is the most common somatic mutation in the classical myeloproliferative neoplasms (MPNs), present in >95% of cases of polycythemia vera (PV) and ∼50% of essential thrombocythemia (ET) and myelofibrosis (MF).1⇓⇓-4 It is usually the sole identifiable driver mutation in MPNs5 and was recently also identified as a driver of age-related clonal hemopoiesis in healthy individuals.6⇓⇓-9 In order to investigate the preclinical clonal evolution of MPNs, we identified 12 individuals with a JAK2 V617F mutant MPN, who 4.6 to 15.2 years previously (median 10.2 years) had also donated blood to register with the Cyprus Bone Marrow Donor Registry at the Karaiskakio FoundationThis work was supported by the Wellcome Trust Sanger Institute (WT098051). T. McKerrell is funded by a Wellcome Trust Clinician Scientist Fellowship (100678/Z/12/Z). G.S.V. is funded by a Wellcome Trust Senior Fellowship in Clinical Science (WT095663MA), and work in his laboratory is also funded by Cancer Research UK, Bloodwise, the Kay Kendall Leukaemia Fund, and Celgene. I.V. is supported by the Spanish Ministerio de Economía y Competitividad, Programa Ramón y Cajal

Assessing the dynamics and complexity of disease pathogenicity using 4-dimensional immunological data

Investigating disease pathogenesis and personalized prognostics are major biomedical needs. Because patients sharing the same diagnosis can experience different outcomes, such as survival or death, physicians need new personalized tools, including those that rapidly differentiate several inflammatory phases. To address these topics, a pattern recognition-based method (PRM) that follows an inverse problem approach was designed to assess, in <10min, eight concepts: synergy, pleiotropy, complexity, dynamics, ambiguity, circularity, personalized outcomes, and explanatory prognostics (pathogenesis). By creating thousands of secondary combinations derived from blood leukocyte data, the PRM measures synergic, pleiotropic, complex and dynamic data interactions, which provide personalized prognostics while some undesirable features—such as false results and the ambiguity associated with data circularity-are prevented. Here, this method is compared to Principal Component Analysis (PCA) and evaluated with data collected from hantavirus-infected humans and birds that appeared to be healthy. When human data were examined, the PRM predicted 96.9 % of all surviving patients while PCA did not distinguish outcomes. Demonstrating applications in personalized prognosis, eight PRM data structures sufficed to identify all but one of the survivors. Dynamic data patterns also distinguished survivors from non-survivors, as well as one subset of non-survivors, which exhibited chronic inflammation. When the PRM explored avian data, it differentiated immune profiles consistent with no, early, or late inflammation. Yet, PCA did not recognize patterns in avian data. Findings support the notion that immune responses, while variable, are rather deterministic: a low number of complex and dynamic data combinations may be enough to, rapidly, unmask conditions that are neither directly observable nor reliably forecasted.Conacyt of Mexico (Consejo Nacional de Ciencia y Tecnologíahttp://www.frontiersin.org/Immunologyam2020Veterinary Tropical Disease

Adipose tissue-derived WNT5A regulates vascular redox signaling in obesity via USP17//RAC1-mediated activation of NADPH oxidases

Obesity is associated with changes in the secretome of adipose tissue (AT), which affects the vasculature through endocrine and paracrine mechanisms. Wingless-related integration site 5A (WNT5A) and secreted frizzled-related protein 5 (SFRP5), adipokines that regulate noncanonical Wnt signaling, are dysregulated in obesity. We hypothesized that WNT5A released from AT exerts endocrine and paracrine effects on the arterial wall through noncanonical RAC1-mediated Wnt signaling. In a cohort of 1004 humans with atherosclerosis, obesity was associated with increased WNT5A bioavailability in the circulation and the AT, higher expression of WNT5A receptors Frizzled 2 and Frizzled 5 in the human arterial wall, and increased vascular oxidative stress due to activation of NADPH oxidases. Plasma concentration of WNT5A was elevated in patients with coronary artery disease compared to matched controls and was independently associated with calcified coronary plaque progression. We further demonstrated that WNT5A induces arterial oxidative stress and redox-sensitive migration of vascular smooth muscle cells via Frizzled 2–mediated activation of a previously uncharacterized pathway involving the deubiquitinating enzyme ubiquitin-specific protease 17 (USP17) and the GTPase RAC1. Our study identifies WNT5A and its downstream vascular signaling as a link between obesity and vascular disease pathogenesis, with translational implications in humans

High throughput sequencing technologies as a new toolbox for deep analysis, characterization and potentially authentication of protection designation of origin cheeses?

Protected Designation of Origin (PDO) labeling of cheeses has been established by the European Union (EU) as a quality policy that assures the authenticity of a cheese produced in a specific region by applying traditional production methods. However, currently used scientific methods for differentiating and establishing PDO are limited in terms of time, cost, accuracy and their ability to identify through quantifiable methods PDO fraud. Cheese microbiome is a dynamic community that progressively changes throughout ripening, contributing via its metabolism to unique qualitative and sensorial characteristics that differentiate each cheese. High Throughput Sequencing (HTS) methodologies have enabled the more precise identification of the microbial communities developed in fermented cheeses, characterization of their population dynamics during the cheese ripening process, as well as their contribution to the development of specific organoleptic and physio-chemical characteristics. Therefore, their application may provide an additional tool to identify the key microbial species that contribute to PDO cheeses unique sensorial characteristics and to assist to define their typicityin order to distinguish them from various fraudulent products. Additionally, they may assist the cheese-makers to better evaluate the quality, as well as the safety of their products. In this structured literature review indications are provided on the potential for defining PDO enabling differentiating factors based on distinguishable microbial communities shaped throughout the ripening procedures associated to cheese sensorial characteristics, as revealed through metagenomic and metatranscriptomic studies. Conclusively, HTS applications, even though still underexploited, have the potential to demonstrate how the cheese microbiome can affect the ripening process and sensorial characteristics formation via the catabolism of the available nutrients and interplay with other compounds of the matrix and/or production of microbial origin metabolites and thus their further quality enhancement