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Medical Mycology Dec 2023Fusarium species represent an opportunistic fungal pathogen. The data in Mexico about Fusarium infections in humans are scarce. Here, we present a retrospective series...
Fusarium species represent an opportunistic fungal pathogen. The data in Mexico about Fusarium infections in humans are scarce. Here, we present a retrospective series of patients with a confirmed diagnosis of fusariosis in eight different hospitals in Mexico from January 2010 to December 2019. The diagnosis of proven fusariosis was made according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORT/MSG) criteria. A total of 49 cases were identified in our series. Most patients had burn injuries (49%), and 37% had hematological malignancies. Most patients had fire injuries (40%), followed by electric injuries (8%), febrile neutropenia (10%), and pancytopenia (6%). Patients had skin and soft tissue involvement in 49%, followed by blood culture isolation and biopsies from different sites of the body (lung, sinuses, bone tissue, and eyes). Febrile neutropenia (10%) and fungemia (8%) were the most common clinical syndromes in immunosuppressed patients. Most patients received monotherapy (67%), where voriconazole was used in 30% of the cases, followed by conventional amphotericin B (16%), and lipidic formulations of amphotericin B in 10% (either liposomal amphotericin B or amphotericin B lipid complex). Combination therapy was used in 20% of the cases, and the most common combination therapy was triazole plus any lipidic formulation of amphotericin B (10%). Mortality related to Fusarium infection occurred in 22% of patients. Fusariosis is a serious threat. Burn injuries and hematologic malignancies represent the most common causes of infection in this small series from Mexico.
Topics: Humans; Fusariosis; Amphotericin B; Antifungal Agents; Retrospective Studies; Mexico; Fusarium; Voriconazole; Hematologic Neoplasms; Burns; Febrile Neutropenia
PubMed: 37944000
DOI: 10.1093/mmy/myad112 -
Public Health Action Dec 2023Deaths related to multidrug-resistant TB among patients who had received a second-line anti-TB drugs in Ethiopia were analysed. Respectively 38/704 (5.4%) and 44/995...
Deaths related to multidrug-resistant TB among patients who had received a second-line anti-TB drugs in Ethiopia were analysed. Respectively 38/704 (5.4%) and 44/995 (4.4%) deaths were identified in two cohorts (2015 and 2022). In the 2015 cohort, severe malnutrition was less prevalent, previous treatment rates were three times higher, hypokalaemia was more frequent, and the use of the Xpert® MTB/RIF assay, respiratory failure and severe anaemia/pancytopenia were less common than in the 2022 cohort. We observed that there were variations in adverse events when different treatment regimens were used over different time periods. To ensure proper patient care, correct guidance must be consistently implemented.
PubMed: 38077723
DOI: 10.5588/pha.23.0030 -
Innere Medizin (Heidelberg, Germany) Nov 2023Hemophagocytic lymphohistiocytosis (HLH) is a hyperferritinemic hyperinflammatory syndrome. A primary hereditary form can be distinguished from a secondary acquired...
Hemophagocytic lymphohistiocytosis (HLH) is a hyperferritinemic hyperinflammatory syndrome. A primary hereditary form can be distinguished from a secondary acquired form. In adults the secondary form accounts for the vast majority of cases. Infections, malignancies and autoimmune disorders are common triggering factors of secondary HLH. Persistent fever, bicytopenia or pancytopenia and splenomegaly represent major symptoms in HLH and occur in virtually all patients. The diagnosis of HLH is made on the basis of the HLH-2004 criteria. The probability of the presence of HLH can be estimated using the HScore. Patients with HLH require immunosuppressive treatment. Hence, high doses of corticosteroids represent the cornerstone of treatment. Furthermore, immunoglobulins, anakinra, ruxolitinib or etoposide are given depending on the triggering factor. The course and prognosis of HLH are dependent on the early initiation of treatment, the triggering factor and the response to treatment.
Topics: Adult; Humans; Lymphohistiocytosis, Hemophagocytic; Immunosuppressive Agents; Adrenal Cortex Hormones; Prognosis; Interleukin 1 Receptor Antagonist Protein
PubMed: 37855882
DOI: 10.1007/s00108-023-01596-w -
Journal of the Association of Genetic... 2024The Fanconi anemia (FA) genes are a family of at least 23 known genes that are spread across many chromosomes and participate in interstrand crosslink (ICLs) DNA repair....
The Fanconi anemia (FA) genes are a family of at least 23 known genes that are spread across many chromosomes and participate in interstrand crosslink (ICLs) DNA repair. In this pathway, FA proteins are involved in sensing sites of ICLs, translocating repair enzymes from the cytoplasm to the nucleus, excising the area of damage, and facilitating repair of the fractured DNA. Mutations in these genes lead to Fanconi anemia, a syndrome characterized primarily by pancytopenia but with associated symptoms involving nearly every organ system; the majority of patients present with dermatological symptoms and growth deficits. Additionally, individuals with Fanconi anemia are known to be predisposed individuals to an increased risk of malignancies, particularly acute myeloid dystrophy and myelodysplastic syndrome, but also in the head, neck, esophagus, reproductive organs, brain, skin, liver, and kidneys. In fact, the cytogenetic aberrations seen in those with FA-associated AML differ from those in typical AML. In contrast, the cytogenetic changes seen in FA-associated MDS are similar to those in typical MDS.
PubMed: 38824651
DOI: No ID Found -
British Journal of Haematology Dec 2023Individuals with telomere biology disorders (TBDs) have very short telomeres, high risk of bone marrow failure (BMF), and reduced survival. Using data from TBD patients,...
Individuals with telomere biology disorders (TBDs) have very short telomeres, high risk of bone marrow failure (BMF), and reduced survival. Using data from TBD patients, a mean leukocyte Southern blot telomere length (TL) of 5 kilobases (kb) was estimated as the 'telomere brink' at which human survival is markedly reduced. However, the shortest telomere, not the mean TL, signals replicative senescence. We used the Telomere Shortest Length Assay (TeSLA) to tally TL of all 46 chromosomes in blood-derived DNA and examined its relationship with TBDs. Patients (n = 18) had much shorter mean TL (TeSmTL) (2.54 ± 0.41 kb vs. 4.48 ± 0.52 kb, p < 0.0001) and more telomeres <3 kb than controls (n = 22) (70.43 ± 8.76% vs. 33.05 ± 6.93%, p < 0.0001). The proportion of ultrashort telomeres (<1.6 kb) was also higher in patients than controls (39.29 ± 10.69% vs. 10.40 ± 4.09%, p < 0.0001). TeS <1.6 kb was associated with severe (n = 11) compared with non-severe (n = 7) BMF (p = 0.027). Patients with multi-organ manifestations (n = 10) had more telomeres <1.6 kb than those with one affected organ system (n = 8) (p = 0.029). Findings suggest that TBD clinical manifestations are associated with a disproportionately higher number of haematopoietic cell telomeres reaching a telomere brink, whose length at the single telomere level is yet to be determined.
Topics: Humans; Biology; Bone Marrow Failure Disorders; Dyskeratosis Congenita; Pancytopenia; Telomere; Telomere Shortening
PubMed: 37354000
DOI: 10.1111/bjh.18945 -
Molecular Therapy : the Journal of the... Sep 2023Lymphodepleting pre-conditioning is a nearly universal component of T cell adoptive transfer protocols. The side effects of pre-conditioning regimens used in adoptive...
Lymphodepleting pre-conditioning is a nearly universal component of T cell adoptive transfer protocols. The side effects of pre-conditioning regimens used in adoptive cell therapy are clinically significant and include pan-cytopenia, immune suppression, and reactive myelopoiesis. We conducted studies to test the hypothesis that the mechanisms underlying effective engraftment are cell autonomous and not dependent on a lymphodepleted host immune status. These studies leveraged mouse models to examine the role of Stat5 signaling during T cell adoptive transfer. We observed that, by transiently expressing a constitutively active mutamer of Stat5b during the process of adoptive transfer, we could completely obviate the need for lymphodepletion prior to adoptive transfer. Using several functional assays, we benchmark the function of the engrafted T cells against T cells transferred after conventional lymphodepletion. These studies identify a cell-autonomous mechanism driven by transient Stat5b signaling with lasting effects on T cell phenotype and function. Furthermore, the results presented suggest that adoptive T cell therapy could be improved by removing lymphodepletion protocols entirely and replacing them with RNA transfection of T cells with transcripts encoding active Stat5.
Topics: Mice; Animals; T-Lymphocytes; Adoptive Transfer; Signal Transduction; Immunotherapy, Adoptive
PubMed: 37481703
DOI: 10.1016/j.ymthe.2023.07.015 -
Platelets Dec 2023gene encodes the uridine diphosphate [UDP]-galactose-4-epimerase, which catalyzes the bidirectional interconversion of UDP-glucose to UDP-galactose, and...
gene encodes the uridine diphosphate [UDP]-galactose-4-epimerase, which catalyzes the bidirectional interconversion of UDP-glucose to UDP-galactose, and UDP-N-acetyl-glucosamine to UDP-N-acetyl-galactosamine. In that way, GALE balances, through reversible epimerization, the pool of four sugars that are essential during the biosynthesis of glycoproteins and glycolipids. -related disorder presents an autosomal recessive inheritance pattern, and it is commonly associated with galactosemia. Peripheral galactosemia generally associates with non-generalized forms or even asymptomatic presentations, while classical galactosemia may be related to complications such as learning difficulties, developmental delay, cardiac failure, or dysmorphic features. Recently, variants have been related to severe thrombocytopenia, pancytopenia, and in one patient, to myelodysplastic syndrome.
Topics: Humans; Galactose; Galactosemias; Hemorrhage; Thrombocytopenia; UDPglucose 4-Epimerase
PubMed: 36846897
DOI: 10.1080/09537104.2023.2176699 -
Journal of Community Hospital Internal... 2023Methotrexate is a commonly prescribed immunosuppressant and chemotherapy agent, which is closely monitored by healthcare providers for its adverse effects. As a result,...
Methotrexate is a commonly prescribed immunosuppressant and chemotherapy agent, which is closely monitored by healthcare providers for its adverse effects. As a result, methotrexate toxicity occurs infrequently. We present a case of a 51-year-old woman with a past medical history of rheumatoid arthritis on methotrexate and prednisone. She presented to the emergency room with altered mental status, jaundice, and mucosal ulceration. She was subsequently admitted to the intensive care unit for septic shock in the setting of severe pancytopenia, acute renal failure and acute liver failure. This case demonstrates the importance of recognizing the signs and symptoms of methotrexate toxicity due to its infrequent presentation.
PubMed: 38596556
DOI: 10.55729/2000-9666.1255 -
Biomedicine & Pharmacotherapy =... Dec 2023Acquired aplastic anemia (AA) is a bone marrow failure (BMF) disease, characterized by fatty bone marrow (BM) and BM hypocellularity resulted from auto-immune...
Acquired aplastic anemia (AA) is a bone marrow failure (BMF) disease, characterized by fatty bone marrow (BM) and BM hypocellularity resulted from auto-immune dysregulated T cells-mediated destruction of BM haemopoietic stem cells (HPSC). The objective of this study was to investigate potential therapeutic effect of irisin, a molecule involved in adipose tissue transition, on AA mouse model. Our results showed that the concentration of irisin in serum was lower in AA patients than in healthy controls, suggesting a role of irisin in the pathogenesis of AA. In the AA mice, irisin administration prolonged the survival rate, prevented or attenuated peripheral pancytopenia, and preserved HPSC in the BM. Moreover, irisin also markedly reduced BM adipogenesis. In vitro results showed that irisin increased both cell proliferation and colony numbers of HPSC. Furthermore, our results demonstrated that irisin upregulated the expression of mitochondrial ATPase Inhibitory Factor 1 (IF1) in HPSC, inhibited the activation of mitochondrial fission protein (DRP1) and enhanced aerobic glycolysis. Taken together, our findings indicate novel roles of irisin in the pathogenesis of AA, and in the protection of HPSC through stimulation of proliferation and regulation of mitochondria function, which provides a proof-of-concept for the application of irisin in AA therapy.
Topics: Animals; Humans; Mice; Anemia, Aplastic; Bone Marrow; Bone Marrow Cells; Fibronectins; Pancytopenia; Hematopoietic Stem Cells
PubMed: 37952356
DOI: 10.1016/j.biopha.2023.115863 -
Blood Reviews Nov 2023Despite recent advancements, treatment of cytopenia due to bone marrow failures (BMF) and myeloid neoplasms remains challenging. Androgens promote renewal and maturation... (Review)
Review
Despite recent advancements, treatment of cytopenia due to bone marrow failures (BMF) and myeloid neoplasms remains challenging. Androgens promote renewal and maturation of blood cells and may be beneficial in these forms. Here we report a systematic review of androgens use as single agent in hematologic conditions. Forty-six studies, mainly retrospective with various androgen types and doses, were included: 12 on acquired aplastic anemia (AA), 11 on inherited BMF, 17 on myelodysplastic syndromes (MDS), and 7 on myelofibrosis. Responses ranged from 50 to 70% in inherited BMF, 40-50% in acquired AA and MDS, while very limited evidence emerged for myelofibrosis. In acquired AA, response was associated with presence of non-severe disease; in MDS androgens were more effective on thrombocytopenia or mild to moderate anemia, whilst limited benefit was observed for transfusion dependent anemia. Toxicity profile mainly consisted of virilization and liver enzyme elevation, whilst the risk of leukemic evolution remains controversial.
Topics: Humans; Androgens; Primary Myelofibrosis; Retrospective Studies; Neoplasms; Anemia, Aplastic; Myelodysplastic Syndromes; Bone Marrow Failure Disorders; Pancytopenia; Myeloproliferative Disorders; Thrombocytopenia
PubMed: 37709654
DOI: 10.1016/j.blre.2023.101132