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Annales de Pathologie Mar 2024A 78-year-old woman with hypertrophic cardiomyopathy underwent a septal myomectomy and valve replacement. In the immediate postoperative period she developed shock of...
A 78-year-old woman with hypertrophic cardiomyopathy underwent a septal myomectomy and valve replacement. In the immediate postoperative period she developed shock of mixed etiology and died. At autopsy, hepatomegaly and splenomegaly were identified, with PAS and Giemsa positive intracellular ceroid granular deposits. Sea-blue histiocytosis is an extremely rare, chronic and benign deposit disease. It is characterized by hepatosplenomegaly, thrombocytopenia and lymphadenopathy. The presence of ceroid substance in granules in PAS and Giemsa stains should establish the diagnosis of suspicion.
Topics: Female; Humans; Aged; Sea-Blue Histiocyte Syndrome; Ceroid; Splenomegaly; Hepatomegaly
PubMed: 37865572
DOI: 10.1016/j.annpat.2023.10.001 -
The Lancet. Haematology Jan 2024New options for medical therapy and risk scoring systems containing molecular data are leading to increased complexity in the management of patients with myelofibrosis.... (Review)
Review
New options for medical therapy and risk scoring systems containing molecular data are leading to increased complexity in the management of patients with myelofibrosis. To inform patients' optimal care, we updated the 2015 guidelines on indications for and management of allogeneic haematopoietic stem-cell transplantation (HSCT) with the support of the European Society for Blood and Marrow Transplantation (EBMT) and European LeukemiaNet (ELN). New recommendations were produced using a consensus-building methodology after a comprehensive review of articles released from January, 2015 to December, 2022. Seven domains and 18 key questions were selected through a series of questionnaires using a Delphi process. Key recommendations in this update include: patients with primary myelofibrosis and an intermediate-2 or high-risk Dynamic International Prognostic Scoring System score, or a high-risk Mutation-Enhanced International Prognostic Score Systems (MIPSS70 or MIPSS70-plus) score, or a low-risk or intermediate-risk Myelofibrosis Transplant Scoring System score should be considered candidates for allogeneic HSCT. All patients who are candidates for allogeneic HSCT with splenomegaly greater than 5 cm below the left costal margin or splenomegaly-related symptoms should receive a spleen-directed treatment, ideally with a JAK-inhibitor; HLA-matched sibling donors remain the preferred donor source to date. Reduced intensity conditioning and myeloablative conditioning are both valid options for patients with myelofibrosis. Regular post-transplantation driver mutation monitoring is recommended to detect and treat early relapse with donor lymphocyte infusion. In a disease where evidence-based guidance is scarce, these recommendations might help clinicians and patients in shared decision making.
Topics: Humans; Primary Myelofibrosis; Splenomegaly; Transplantation, Homologous; Hematopoietic Stem Cell Transplantation; Spleen; Transplantation Conditioning
PubMed: 38061384
DOI: 10.1016/S2352-3026(23)00305-8 -
Emerging Microbes & Infections Dec 2023The zoonotic bacteria, , is becoming the leading cause of canine brucellosis in Europe. In dogs, it causes reproductive problems as well as non-specific lameness or... (Review)
Review
The zoonotic bacteria, , is becoming the leading cause of canine brucellosis in Europe. In dogs, it causes reproductive problems as well as non-specific lameness or discospondilitis. In humans, can be origin of chronic debilitating conditions characteristic to its genus such as undulant fever, splenomegaly, and lymphadenopathy. Although shows some pathogenic characteristics similar to and , it lacks surface O-polysaccharide, like nonzoonotic . This review shows that host- interactions are still poorly understood, with many knowledge and capability gaps, causing relatively poor sensitivity and specificity of existing diagnostic tools. Currently, there is no vaccine for this rough species. Besides, antimicrobial therapy does not guarantee bacterial elimination, and infection relapses are frequently reported, increasing the risks of antibiotic resistance development. has been detected in dogs in almost all European countries which increased human exposure, but currently there is no systematic surveillance. Moreover, caused brucellosis is not included in Animal Health Law, and therefore there is no legal framework to tackle this emerging infectious disease. To map out the diagnostic strategies, identify risks for human infections and propose management scheme for infected pet and kennel dogs, we present current understanding of canine caused brucellosis, outline major knowledge gaps and propose future steps. To address and highlight challenges veterinary and public health services encounter in Europe, we developed two infection scenarios: of a single household pet and of a kennel dog in larger group.
Topics: Animals; Dogs; Humans; Sheep; Brucella canis; Public Health; Dog Diseases; Brucellosis; Europe
PubMed: 37649455
DOI: 10.1080/22221751.2023.2249126 -
Hematology. American Society of... Dec 2023Myelofibrosis is a devastating myeloid malignancy characterized by dysregulation of the JAK-STAT pathway, resulting in splenomegaly, constitutional symptoms, anemia,... (Review)
Review
Myelofibrosis is a devastating myeloid malignancy characterized by dysregulation of the JAK-STAT pathway, resulting in splenomegaly, constitutional symptoms, anemia, thrombocytopenia, leukocytosis, and an increased likelihood of progression to acute leukemia. The only curative option is allogeneic stem cell transplantation. The numbers of transplants have been increasing every year, and although there have been improvements in survival, there remain many unanswered questions. In this review, we will evaluate patient selection and appropriate timing for transplantation. We will cover the current prognostic scoring systems, which can aid in the decision of when to move forward with transplant. We will also review the different donor options, as well as the conditioning regimens. The peritransplant management of splenomegaly will be reviewed. We will discuss management of posttransplant complications such as loss of donor chimerism or disease relapse. Finally, we will review what is known about the outlook of patients who have undergone allogeneic stem cell transplant with regards to quality of life and long-term survival.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Janus Kinases; Primary Myelofibrosis; Quality of Life; Signal Transduction; Splenomegaly; STAT Transcription Factors; Transplantation Conditioning; Treatment Outcome
PubMed: 38066916
DOI: 10.1182/hematology.2023000453 -
European Journal of Internal Medicine Aug 2023
Topics: Humans; Splenomegaly; Splenectomy; Retrospective Studies
PubMed: 37137780
DOI: 10.1016/j.ejim.2023.04.031 -
La Revue de Medecine Interne Dec 2023
Topics: Humans; Splenomegaly; Lymphohistiocytosis, Hemophagocytic; Fever
PubMed: 37550135
DOI: 10.1016/j.revmed.2023.07.004 -
Current Hematologic Malignancy Reports Oct 2023Chronic myeloproliferative neoplasms (MPN) represent a group of diseases characterised by constitutive activation of the JAK/STAT pathway in a clonal myeloid precursor.... (Review)
Review
PURPOSE OF REVIEW
Chronic myeloproliferative neoplasms (MPN) represent a group of diseases characterised by constitutive activation of the JAK/STAT pathway in a clonal myeloid precursor. The therapeutic approach aims to treat the symptom burden (headache, itching, debilitation), splenomegaly, slow down the fibrotic proliferation in the bone marrow and reduce the risk of thrombosis/bleeding whilst avoiding leukaemic transformation.
RECENT FINDINGS
In recent years, the advent of JAK inhibitors (JAKi) has significantly broadened treatment options for these patients. In myelofibrosis, symptom control and splenomegaly reduction can improve quality of life with improved overall survival, not impacting progression into acute leukaemia. Several JAKi are available and used worldwide, and combination approaches are now being explored. In this chapter, we review the approved JAKi, highlighting its strengths, exploring potential guidelines in choosing which one to use and reasoning towards future perspectives, where the combinations of therapies seem to promise the best results.
Topics: Humans; Janus Kinase Inhibitors; Polycythemia Vera; Janus Kinases; Splenomegaly; Quality of Life; Thrombocythemia, Essential; Signal Transduction; STAT Transcription Factors; Myeloproliferative Disorders
PubMed: 37395943
DOI: 10.1007/s11899-023-00702-x -
Frontiers in Immunology 2023We describe a novel, severe autoinflammatory syndrome characterized by neuroinflammation, systemic autoinflammation, splenomegaly, and anemia (NASA) caused by bi-allelic...
We describe a novel, severe autoinflammatory syndrome characterized by neuroinflammation, systemic autoinflammation, splenomegaly, and anemia (NASA) caused by bi-allelic mutations in . IRAK-4 is a serine/threonine kinase with a pivotal role in innate immune signaling from toll-like receptors and production of pro-inflammatory cytokines. In humans, bi-allelic mutations in result in IRAK-4 deficiency and increased susceptibility to pyogenic bacterial infections, but autoinflammation has never been described. We describe 5 affected patients from 2 unrelated families with compound heterozygous mutations in (c.C877T (p.Q293*)/c.G958T (p.D320Y); and c.A86C (p.Q29P)/c.161 + 1G>A) resulting in severe systemic autoinflammation, massive splenomegaly and severe transfusion dependent anemia and, in 3/5 cases, severe neuroinflammation and seizures. IRAK-4 protein expression was reduced in peripheral blood mononuclear cells (PBMC) in affected patients. Immunological analysis demonstrated elevated serum tumor necrosis factor (TNF), interleukin (IL) 1 beta (IL-1β), IL-6, IL-8, interferon α2a (IFN-α2a), and interferon β (IFN-β); and elevated cerebrospinal fluid (CSF) IL-6 without elevation of CSF IFN-α despite perturbed interferon gene signature. Mutations were located within the death domain (DD; p.Q29P and splice site mutation c.161 + 1G>A) and kinase domain (p.Q293*/p.D320Y) of IRAK-4. Structure-based modeling of the DD mutation p.Q29P showed alteration in the alignment of a loop within the DD with loss of contact distance and hydrogen bond interactions with IRAK-1/2 within the myddosome complex. The kinase domain mutation p.D320Y was predicted to stabilize interactions within the kinase active site. While precise mechanisms of autoinflammation in NASA remain uncertain, we speculate that loss of negative regulation of IRAK-4 and IRAK-1; dysregulation of myddosome assembly and disassembly; or kinase active site instability may drive dysregulated IL-6 and TNF production. Blockade of IL-6 resulted in immediate and complete amelioration of systemic autoinflammation and anemia in all 5 patients treated; however, neuroinflammation has, so far proven recalcitrant to IL-6 blockade and the janus kinase (JAK) inhibitor baricitinib, likely due to lack of central nervous system penetration of both drugs. We therefore highlight that bi-allelic mutation in may be associated with a severe and complex autoinflammatory and neuroinflammatory phenotype that we have called NASA (neuroinflammation, autoinflammation, splenomegaly and anemia), in addition to immunodeficiency in humans.
Topics: Humans; Leukocytes, Mononuclear; Interleukin-1 Receptor-Associated Kinases; Splenomegaly; Interleukin-6; Neuroinflammatory Diseases; Anemia; Mutation
PubMed: 37744344
DOI: 10.3389/fimmu.2023.1231749