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Despite aging and the enormous cellular output required of the marrow every day of the lifespan, most aged patients do not suffer significant marrow failure or cytopenias, an attestation to the proliferative capacity of this system. However, as marrow and its hematopoietic stem cells age, a reduction in ability to maintain homeostasis after stress or with exposure to prolonged chronic inflammation, so-called "inflammaging," may contribute to cytopenias, inadequate immune responses, and dysplasia/leukemia. In some instances, these changes may be intrinsic to the stem cell but in others, there may be extrinsic environmental influences. In this review, the role of aging as it relates to stem cell changes, immune function, and anemia are reviewed.Hypoplastic MDS is a subset of MDS characterized by marrow hypocellularity diagnosed in 10-15% of MDS patients. The pathogenesis of this disease shares features of aplastic anemia with activation of the effector T cells against hematopoietic stem and progenitor cells and high-risk MDS with acquisition of somatic mutations that provide survival and growth advantage of these cells in the inflammatory bone marrow microenvironment. Clonal evolution in hypoplastic MDS may be associated with accumulation of DNA damage and progression to AML while clonal hematopoiesis in aplastic anemia is strongly related to immune escape of the hematopoietic cells. Distinction of hypoplastic MDS from other acquired and inherited bone marrow failure syndromes is frequently challenging but it is critical for the appropriate clinical management of the patients. Treatment with immunosuppression is an important component of the clinical approach to patients with hypoplastic MDS while hypomethylating agents and early allogeneic bone marrow transplantation are also considerations in some patients. In this review, we summarize the current literature on the biology of hypoplastic MDS, the differences between this disease and other bone marrow failure syndromes, and the treatment algorithm for patients with this subtype of MDS.Inherited bone marrow failure syndromes (IBMFS) are a heterogenous group of diseases caused by pathogenic germline variants in key pathways associated with haematopoiesis and genomic stability. Germline variants in IBMFS-related genes are known to reduce the fitness of hematopoietic stem and progenitor cells (HSPC), which has been hypothesized to drive clonal selection in these diseases. In many IBMFS, somatic mosaicism predominantly impacts cells by two distinct mechanisms, with contrasting effects. An acquired variation can improve cell fitness towards baseline levels, providing rescue of a deleterious phenotype. Alternatively, somatic mosaicism may result in a fitness advantage that results in malignant transformation. This review will describe these phenomena in IBMFS and delineate their relevance for diagnosis and clinical management. In addition, we will discuss which samples and methods can be used for detection of mosaicism according to clinical phenotype, type of mosaicism, and sample availability.Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare inherited bone marrow failure syndrome (IBMFS) that is characterized by severe thrombocytopenia at birth due to ineffective megakaryopoiesis and development towards aplastic anemia during the first years of life. CAMT is not a single monogenetic disorder; rather, many descriptions of CAMT include different entities with different etiologies. CAMT in a narrow sense, which is primarily restricted to the hematopoietic system, is caused mainly by mutations in the gene for the thrombopoietin receptor (MPL), sometimes in the gene for its ligand (THPO). CAMT in association with radio-ulnar synostosis, which is not always clinically apparent, is mostly caused by mutations in MECOM, rarely in HOXA11. Patients affected by other IBMFS - especially Fanconi anemia or dyskeratosis congenita - may be misdiagnosed as having CAMT when they lack typical disease features of these syndromes or have only mild symptoms. This article reviews scientific and clinical aspects of the various disorders associated with the term "CAMT" with a main focus on the disease caused by mutations in the MPL gene.Bone marrow transplantation is a major therapeutic option for patients with acquired severe aplastic anaemia improved survival has been achieved in younger patients, thanks to better donor selection, conditioning regimens and graft versus host disease prophylaxis, together with improved supportive care, including diagnosis and treatment of opportunistic infections. This has not been the case for older patients over the age of 40 years. We will discuss transplantation platforms as used for different donor types and we will analyse major breakthroughs of the last years the combination of Fludarabine and cyclophosphamide as a conditioning regimen, the use of alternative donors including HLA haploidentical related donors and new strategies to prevent acute and chronic graft versus host disease, including post transplantation Cyclophosphamide. These changes extend the option of a bone marrow transplantation for patients who lack an HLA matched donor and appear to improve engraftment and reduce graft versus host disease whether this will be true for all age groups is currently being investigated.GATA2 gene encodes a zinc finger transcription factor crucial for normal hematopoiesis. Its haploinsufficiency, caused by a great variety of heterozygous loss-of-function mutations, underlies one of the most common causes of inherited bone marrow failure, recognized as GATA2 deficiency. Its phenotype is characterized by a broad spectrum of clinical presentations, including haematological malignancies; immunodeficiency leading to invasive viral, mycobacterial and fungal infections; recurrent warts; lymphedema; pulmonary alveolar proteinosis; deafness; and miscarriage. The onset of symptoms ranges from early childhood to late adulthood, more frequently between adolescence and early adulthood. The only curative treatment is allogenic hematopoietic stem cell transplantation (HSCT), that can restore the function of both hematopoietic and immune system and prevent lung deterioration. Currently, there are no consensus guidelines about the management of patients affected by GATA2 deficiency, especially with regard to the optimal time to proceed to HSCT.Acquired bone marrow failure (BMF) syndromes comprise a diverse group of diseases with variable clinical manifestations but overlapping features of immune activation, resulting in haematopoietic stem and progenitor cells (HSPC) damage and destruction. This review focuses on clinical presentation, pathophysiology, and treatment of four BMF acquired aplastic anaemia, large granular lymphocytic leukaemia, paroxysmal nocturnal haemoglobinuria, and hypoplastic myelodysplastic syndrome. Autoantigens are speculated to be the inciting event that result in immune activation in all of these diseases, but specific pathogenic antigens have not been identified. Oligoclonal cytotoxic T cell expansion and an active role of proinflammatory cytokines, primarily interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α), are two main contributors to HSPC growth inhibition and apoptosis in BMF. Emerging evidence also suggests involvement of the innate immune system.Distinguishing constitutional from immune bone marrow failure (BMF) has important clinical implications. However, the diagnosis is not always straightforward, and immune aplastic anemia, the commonest BMF, is a diagnosis of exclusion. In this review, we discuss a general approach to the evaluation of BMF, focusing on clinical presentations particular to immune and various constitutional disorders as well as the interpretation of bone marrow histology, flow cytometry, and karyotyping. Additionally, we examine the role of specialized testing in both immune and inherited BMF, and discuss genetic testing, both its role in patient evaluation and interpretation of results.Bone marrow failure is characterized by a disruption of hematopoietic stem cell (HSC) homeostasis and function, which causes decreased blood counts. Germline and somatic mutations within HSCs and immune dysregulation contribute to the pathogenesis of marrow failure. Allogeneic HSC transplant is a potentially curative therapy for marrow failure, although not all patients are candidates for this procedure. Immune suppressive therapy (IST) is an effective treatment for patients with aplastic anemia (AA) and select patients with myelodysplastic syndromes, but some patients fail to respond or relapse after IST. Over the past decade, the oral thrombopoietin receptor agonist eltrombopag has become a therapeutic option for AA in combination with frontline IST, and as a single agent for relapsed and refractory patients after IST. In this review, we highlight current knowledge of thrombopoietin receptor agonist mechanisms of action, and clinical indications and toxicities in patients with marrow failure, including the risk of clonal evolution.Bone marrow failure syndromes (BMF) are a group of conditions characterized by inefficient hematopoiesis frequently associated with extra-hematopoietic phenotypes and variable risk of progression to myeloid malignancies. They can be acquired or inherited and mediated by either cell extrinsic factors or cell intrinsic impairment of hematopoietic stem cell (HSC) function. The pathophysiology includes immune-mediated attack (e.g., acquired BMFs) or germline defects in DNA damage repair machinery, telomeres maintenance or ribosomes biogenesis. (e.g., inherited BMF). Clonal hematopoiesis (CH) that frequently accompanies BMF may provide a mechanism of improved HSC fitness through the evasion of extracellular pressure or somatic reversion of germline defects. The mechanism for the CH selective advantage differs depending on the condition in which it occurs. However, this adaptation mechanism, particularly when involving putative oncogenes or tumor suppressors, may lead to increased risk of myeloid malignancies. Surveillance and early detection of leukemogenic clones may lead to timely implementation of curative therapies and improved survival.
Minimally invasive surgery of benign middle ear tumours is possible by using the endoscope. The optimal lighting and the broadest vision it offers, allow a transcanal approach to these rare tumours. find more The objective of this work is to summarize its key points through a case series.

Retrospective study of benign middle ear tumours that underwent exclusive endoscopic surgery in a third-level adult university hospital between June 2018 and June 2020. Postoperative follow-up was performed by otoendoscopy and audiometry.

Six patients underwent surgery during the study period. Five patients were female and one male, with an average age of 57.8 years (± 21.9). Four tumours were in the left ear and 2 in the right ear. These included 4tympanic paragangliomas (3 type I and one type II), a chorda tympani neuroma, and a congenital cholesteatoma. There were no serious postoperative complications. At present, no tumour recurrence has been found in either case, with a minimum follow-up of 7 months.

The present study adds evidence on the safety and efficacy of endoscopic transcanal ear surgery, as a minimally invasive technique, for the treatment of benign middle ear tumours confined to the tympanic cavity.
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