-
Biochemia Medica Jun 2024Hairy cell leukemia (HCL) represents 2% of all leukemia cases, with men aged above 55 years being the most affected. The most common symptoms of this type of leukemia... (Review)
Review
Hairy cell leukemia (HCL) represents 2% of all leukemia cases, with men aged above 55 years being the most affected. The most common symptoms of this type of leukemia include splenomegaly, monocytopenia, and neutropenia. In the basic blood count examination, leukopenia with monocytopenia and granulocytopenia, as well as aplastic anemia and/or thrombocytopenia occur. The mutation of β-rapidly accelerated fibrosarcoma () proto-oncogene, which can be found in nearly 100% of patients, is an important feature of HCL. Immunophenotypic analysis of the HCL cells reveals high expression of B-lineage antigens, including CD19, CD20, and CD22. Additionally, CD11c, CD25, CD103, and CD123 belong to specific markers of HCL. Lactate dehydrogenase activity and β-2-microglobulin concentration are also important in the patient's assessment. The differential diagnosis between HCL, hairy cell leukemia variant (HCL-V) and splenic marginal zone lymphoma (SMZL) is of first importance. Currently, the main treatment for HCL involves the use of purine analogues, excluding pregnant women, individuals with severe infections, and those with relapsing HCL.
Topics: Humans; Male; Diagnosis, Differential; Leukemia, Hairy Cell; Mutation; Proto-Oncogene Mas; Proto-Oncogene Proteins B-raf; Sex Factors
PubMed: 38882583
DOI: 10.11613/BM.2024.020502 -
Frontiers in Immunology 2024Micronutrients, such as vitamins and trace minerals, are critical for supporting growth, performance, health and maintaining redox balance. Zinc (Zn), an essential... (Review)
Review
Micronutrients, such as vitamins and trace minerals, are critical for supporting growth, performance, health and maintaining redox balance. Zinc (Zn), an essential micronutrient, aids the functioning of innate and adaptive immune cells. This scoping review aims to assemble and evaluate the evidence available for the role of Zn within calf immunity. Relevant literature was identified within Web of Science, PubMed, and CABI using search terms specific to the major innate and adaptive immune cell populations. There was no evidence that Zn supplementation altered neutrophil, natural killer cell, or T-cell functions. However, there was limited evidence to support Zn supplementation with reduced monocyte numbers, but there was no evidence to associate the monocytopenia with improvements in monocyte function. There is moderate evidence to suggest that Zn supplementation was beneficial for maintaining epithelial barriers of integumental and mucosal surfaces. The evidence supports supplementation above the current industry recommendations for improving immunoglobulin (Ig) production, with the strongest results being observed for IgG and IgM. Moreover, Zn supplementation was associated with reduced proinflammatory cytokine production, which may reduce inflammation-associated hypophagia and warrants further investigation. Furthermore, Zn reduced the duration of clinical signs in animals facing respiratory disease and diarrhea. However, consensus is needed about the optimal dose, route, and Zn formulation most appropriate for supporting immunity. In conclusion, while the literature supports that Zn could enhance calf immunity, there is insufficient evidence to adequately determine the extent to which Zn impacts innate immune cell and T-cell functions. Determination of the immune cell functions susceptible to modification by Zn supplementation is an important knowledge gap for enhancing the understanding of Zn and calf immunity.
Topics: Zinc; Animals; Cattle; Dietary Supplements; Immunity, Innate; Adaptive Immunity
PubMed: 38799472
DOI: 10.3389/fimmu.2024.1387950 -
Journal of Zoo and Wildlife Medicine :... Mar 2024Multiple species of elephant endotheliotropic herpesvirus (EEHV) have caused fatal hemorrhagic disease in African () and Asian () elephants. To date, EEHV7 has been...
Multiple species of elephant endotheliotropic herpesvirus (EEHV) have caused fatal hemorrhagic disease in African () and Asian () elephants. To date, EEHV7 has been detected only in benign pulmonary and skin nodules and in saliva of African elephants and has not been associated with clinical illness. Low-level viremia due to EEHV7A was detected via qPCR in two subadult African elephants during routine surveillance. Hematologic changes were noted in both elephants, including leukopenia, lymphopenia, monocytopenia, and band heterophilia. Treatment was initiated with famciclovir, antimicrobials, and rectal fluids, and one elephant received plasma transfusions due to a progressive decrease in platelet count. Both elephants remained asymptomatic throughout the viremias, with rapid resolution of hematologic abnormalities. These cases add to the current understanding of the epidemiology of EEHV in African elephants; to the authors' knowledge, they represent the first documentation of clinical disease due to EEHV7 infection in any elephant.
Topics: Humans; Animals; Elephants; Herpesviridae Infections; Herpesviridae; Famciclovir; Antiviral Agents; Viremia
PubMed: 38453514
DOI: 10.1638/2023-0034 -
Journal of Zoo and Wildlife Medicine :... Mar 2024Detailed knowledge of biological variation can facilitate accurate interpretation of clinical pathology parameters. A recent biological variation study in Asian...
Detailed knowledge of biological variation can facilitate accurate interpretation of clinical pathology parameters. A recent biological variation study in Asian elephants () found that hematology parameters had high individuality, which suggests that population-derived reference intervals may be an insensitive diagnostic tool. In elephant medicine, sensitive hematology-related diagnostics are crucial for clinical decision-making, particularly in elephants at risk for elephant endotheliotropic herpesvirus hemorrhagic disease (EEHV-HD). The objective of this study was to assess biological variation of hematology parameters in African elephants to determine whether population-derived reference intervals are a sensitive diagnostic tool for interpreting results and to provide a useful alternative. Eight healthy African elephants had blood collected under behavioral training every other week for 8 wk. Complete blood cell count (CBC) analysis was performed in duplicate to assess analytical variation. Previous methods were used to determine between-individual variation, within-individual variation, index of individuality, and reference change values (RCV). This study found that most hematology parameters displayed intermediate-to-high individuality, which suggests that alternatives to population-derived reference intervals are necessary to detect pathologic changes. To test the results of our biological variation data, a case of EEHV-HD was retrospectively evaluated. Individual normal values and calculated RCV detected a clinically significant monocytopenia, leukopenia, and thrombocytopenia associated with EEHV2 viremia. However, none of these parameters fell outside a population-derived reference interval. This study highlights the utility of biological variation in clinical decision-making and demonstrates that individual normal values and RCV may be important diagnostic tools for CBC interpretation in African elephants.
Topics: Animals; Elephants; Hematology; Herpesviridae; Herpesviridae Infections; Retrospective Studies
PubMed: 38453500
DOI: 10.1638/2023-0055 -
American Journal of Clinical Pathology Jun 2024VEXAS syndrome is an adult-onset autoinflammatory disease caused by a somatic pathogenic mutation in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene....
Comprehensive morphologic characterization of bone marrow biopsy findings in a large cohort of patients with VEXAS syndrome: A single-institution longitudinal study of 111 bone marrow samples from 52 patients.
OBJECTIVES
VEXAS syndrome is an adult-onset autoinflammatory disease caused by a somatic pathogenic mutation in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. Patients present with rheumatologic manifestations and cytopenias and may have an increased predisposition to myelodysplastic syndrome (MDS) and plasma cell neoplasms. Prior studies have reported on the peripheral blood and bone marrow findings in patients with VEXAS syndrome. Due to the protean clinical presentation and lack of specificity of morphologic features (eg, vacuoles in early erythroid and granulocytic precursors), an optimal screening methodology to identify these patients in a timely fashion is desirable.
METHODS
To further evaluate and describe the salient diagnostic morphologic features in VEXAS syndrome, we carried out a comprehensive study of the largest single-institution cohort to date. Diagnostic and follow-up bone marrow biopsy specimens from 52 male patients with molecularly identified VEXAS syndrome underwent central review.
RESULTS
Cytopenias were common in all cases, primarily macrocytic anemia, monocytopenia, and thrombocytopenia. Bone marrow aspirate and biopsy were often hypercellular, with an increased myeloid/erythroid ratio, granulocytic hyperplasia with left shift, erythroid left shift, and megakaryocyte hyperplasia, which exhibited a range of striking morphologic findings. Distinctly vacuolated myeloid and erythroid precursors were seen in more than 95% of cases.
CONCLUSIONS
Our data reveal potential novel diagnostic features, such as a high incidence of monocytopenia and distinct patterns of atypical megakaryopoiesis, that appear different from dysmegakaryopoiesis typically associated with MDS. In our experience, those findings are suggestive of VEXAS, in the appropriate clinical context.
Topics: Humans; Male; Middle Aged; Bone Marrow; Adult; Aged; Longitudinal Studies; Biopsy; Ubiquitin-Activating Enzymes; Myelodysplastic Syndromes; Young Adult; Aged, 80 and over; Cohort Studies; Female; Mutation; Thrombocytopenia
PubMed: 38413044
DOI: 10.1093/ajcp/aqad186 -
Rheumatology (Oxford, England) Feb 2024VEXAS is a recently described acquired auto-inflammatory and hematologic syndrome caused by somatic mutations in UBA1. To date, VEXAS is not a recognized cause of...
OBJECTIVES
VEXAS is a recently described acquired auto-inflammatory and hematologic syndrome caused by somatic mutations in UBA1. To date, VEXAS is not a recognized cause of acquired immunodeficiency.
PATIENTS AND METHODS
Two of our 10 VEXAS patients developed a disseminated Mycobacterium avium infection. To shed light on this observation, we retrospectively studied all patients with disseminated non-tuberculous mycobacterial infections (NTMi) seen at our institution over 13 years. Inclusion criteria were a positive blood/bone marrow culture, or 2 positive cultures from distinct sites, or one positive culture with 2 involved sites.
RESULTS
patient 1 presented with fever, rash, orbital cellulitis and lung infiltrates. Patient 2 presented with fever and purpura. In both cases, Mycobacterium avium was identified on bone marrow culture. Twenty cases of disseminated NTMi were reviewed. Among 11 HIV-negative patients, three had chronic immune-mediated disease; three had untreated myeloid neoplasm; two had VEXAS; one had undergone kidney transplantation; one had GATA-2 deficiency; and one had no identified aetiology. None had lymphoid neoplasia or had undergone bone marrow transplantation. HIV-negative cases had higher CD4 counts than HIV-positive patients (median CD4: 515/mm3 vs 38/mm3, p< 0.001). Monocytopenia was present in seven cases. At 2 years, six patients had died, including both VEXAS patients.
DISCUSSION
VEXAS patients have an intrinsic susceptibility to disseminated NTMi, which may result from monocytic dysfunction. NTMi can mimic VEXAS flare. Clinicians should maintain a high suspicion for opportunistic infections before escalating immunosuppressive therapy. Further studies are needed to confirm and better decipher the herein reported observations.
PubMed: 38317027
DOI: 10.1093/rheumatology/keae087 -
Toxicology Reports Dec 2023The genus (Passifloraceae) comprises about 500 species. The stands out because of its economic and medicinal importance. It is widely planted in tropical and...
The genus (Passifloraceae) comprises about 500 species. The stands out because of its economic and medicinal importance. It is widely planted in tropical and subtropical regions worldwide, especially in South America, the Caribbean, South Africa, and Asia. The aqueous extract of Passiflora edulis Sims f. edulis (Gulupa) leaves is used in traditional medicine for its soothing and tranquilizing effects on the central nervous system. Therefore, evaluating its safety for human use is a fundamental requirement to continue the development of new therapies within the framework of regulatory, preclinical, and clinical guidelines. Here, the sub-acute toxicity study was conducted following the Organization for Economic Cooperation and Development (OECD) guideline 407 for 28 days in Wistar albino rats. The study showed that 1000 mg/kg/day of the aqueous extract in 10 adult Wistar rats (five males and five females) was well tolerated. The hematological results are at normal levels. However, monocytopenia and eosinopenia were observed with a significant difference (P < 0,05) for both male and female rats treated with the aqueous extract of . The results show that liver and kidney function profiles were conserved. However, an increase in ALT is observed with significant differences between male and female rats treated with the extract compared to the controls. Study findings were limited to non-adverse histopathological results of a slightly increased incidence of focal periportal lymphocytic infiltrate in the liver and focal corticomedullary nephrocalcinosis in the kidney compared to control. Therefore, the aqueous extract of has a good safety profile in oral administration, was well tolerated, and did not cause any lethality or adverse effects in the sub-acute toxicity study in male and female rats. The NOAEL (no observed adverse effect level) for the 28-day subacute toxicity study was considered to be 1000 mg/kg.
PubMed: 37955035
DOI: 10.1016/j.toxrep.2023.10.013 -
VEXAS syndrome: Clinical, hematologic features and a practical approach to diagnosis and management.American Journal of Hematology Feb 2024VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a newly identified disease caused by somatic alterations in UBA1 which produce a... (Review)
Review
VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a newly identified disease caused by somatic alterations in UBA1 which produce a recalcitrant inflammatory state along with hematologic disturbances. Patients with VEXAS can have a wide spectrum of clinical symptoms and providers should be familiar with the heterogeneity of associated clinical features. While hematologic parameters may be generally non-specific, peripheral blood features of macrocytosis, monocytopenia, and/or thrombocytopenia coupled with bone marrow vacuolization of erythroid or myeloid precursors should raise suspicion for this condition. Due to an increased mortality, prompt recognition and accurate diagnosis is paramount. Access to testing for confirmation of UBA1 variants is not yet universally available but clinicians should understand the current available options for genetic confirmation of this disease. Treatment options are limited due to lack of prospective clinical trials but cytokine directed therapies such as interleukin-6 inhibitors and JAK-STAT inhibitors as well as hypomethylating agents such as azacitidine have shown evidence of partial effect. Though cases are limited, allogeneic stem cell transplantation holds promise for durable response and potential cure. The intent of this review is to outline the pathophysiology of VEXAS syndrome and to provide a practical approach to diagnosis and treatment.
Topics: Humans; Thrombocytopenia; Azacitidine; Hematopoietic Stem Cell Transplantation; Immunotherapy; Mutation; Myelodysplastic Syndromes; Skin Diseases, Genetic
PubMed: 37950858
DOI: 10.1002/ajh.27156 -
Shock (Augusta, Ga.) Jan 2024Objective: This study aimed to test whether the prognostic value of tryptophanyl-tRNA synthetase 1 (WARS1) for 28-day mortality in patients with sepsis was affected by...
Objective: This study aimed to test whether the prognostic value of tryptophanyl-tRNA synthetase 1 (WARS1) for 28-day mortality in patients with sepsis was affected by monocytopenia. Methods: A prospective analysis of retrospectively collected samples from 74 sepsis patients was performed. WARS1, C-reactive protein (CRP), and procalcitonin were measured at admission and 24 and 72 h after admission. The prognostic value of WARS1, CRP, and procalcitonin for 28-day mortality was compared using repeated measures analysis of variance and the area under the receiver operating characteristic curve (AUROC). All analyses were performed in patients with or without monocytopenia, defined as an absolute monocyte count less than 0.1 × 10 9 cells/L. Results: WARS1 levels differed significantly between survivors and nonsurvivors when all patients and patients without monocytopenia were assessed ( P = 0.008, P < 0.001, respectively). In contrast, the WARS1 level did not differ between survivors and nonsurvivors with monocytopenia. C-reactive protein and procalcitonin levels were not different between survivors and nonsurvivors regardless of whether they had monocytopenia. The AUROCs of WARS1 at admission and 24 h for mortality were significantly higher in patients without monocytopenia (0.830, 0.818) than in patients with monocytopenia (0.232, 0.196; P < 0.001, both). When patients without monocytopenia were analyzed, the AUROCs of WARS1 for mortality were 0.830 and 0.818 at admission and 24 h, respectively, which were significantly higher than those of CRP (0.586, 0.653) and procalcitonin (0.456, 0.453) at the same time points ( P = 0.024 and 0.034, respectively). Conclusion: WARS1 is a useful biomarker for prognosis in sepsis patients without monocytopenia.
Topics: Humans; Prognosis; C-Reactive Protein; Procalcitonin; Tryptophan-tRNA Ligase; Retrospective Studies; Sepsis; Biomarkers; ROC Curve
PubMed: 37878497
DOI: 10.1097/SHK.0000000000002259 -
Frontiers in Immunology 2023Patients with septic shock caused by have mortality rates exceeding 50%, despite appropriate antibiotic therapy. Our objectives were to establish a rabbit model of...
Monoclonal antibodies neutralizing alpha-hemolysin, bicomponent leukocidins, and clumping factor A protected against -induced acute circulatory failure in a mechanically ventilated rabbit model of hyperdynamic septic shock.
BACKGROUND
Patients with septic shock caused by have mortality rates exceeding 50%, despite appropriate antibiotic therapy. Our objectives were to establish a rabbit model of septic shock and to determine whether a novel immunotherapy can prevent or halt its natural disease progression.
METHODS
Anesthetized rabbits were ventilated with lung-protective low-tidal volume, instrumented for advanced hemodynamic monitoring, and characterized for longitudinal changes in acute myocardial dysfunction by echocardiography and sepsis-associated biomarkers after intravenous challenge. To demonstrate the potential utility of this hyperdynamic septic shock model for preclinical drug development, rabbits were randomized for prophylaxis with anti-Hla/Luk/ClfA monoclonal antibody combination that neutralizes alpha-hemolysin (Hla), the bicomponent pore-forming leukocidins (Luk) including Panton-Valentine leukocidin, leukocidin ED, and gamma-hemolysin, and clumping factor A (ClfA), or an irrelevant isotype-matched control IgG (c-IgG), and then challenged with .
RESULTS
Rabbits challenged with , but not those with saline, developed a hyperdynamic state of septic shock characterized by elevated cardiac output (CO), increased stroke volume (SV) and reduced systemic vascular resistance (SVR), which was followed by a lethal hypodynamic state characterized by rapid decline in mean arterial pressure (MAP), increased central venous pressure, reduced CO, reduced SV, elevated SVR, and reduced left-ventricular ejection fraction, thereby reproducing the hallmark clinical features of human staphylococcal septic shock. In this model, rabbits pretreated with anti-Hla/Luk/ClfA mAb combination had 69% reduction in mortality when compared to those pretreated with c-IgG (<0.001). USA300-induced acute circulatory failure-defined as >70% decreased in MAP from pre-infection baseline-occurred in only 20% (2/10) of rabbits pretreated with anti-Hla/Luk/ClfA mAb combination compared to 100% (9/9) of those pretreated with c-IgG. Prophylaxis with anti-Hla/Luk/ClfA mAb combination halted progression to lethal hypodynamic shock, as evidenced by significant protection against the development of hyperlactatemia, hypocapnia, hyperkalemia, leukopenia, neutropenia, monocytopenia, lymphopenia, as well as biomarkers associated with acute myocardial injury.
CONCLUSION
These results demonstrate the potential utility of a mechanically ventilated rabbit model that reproduced hallmark clinical features of hyperdynamic septic shock and the translational potential of immunotherapy targeting virulence factors for the prevention of staphylococcal septic shock.
Topics: Humans; Animals; Rabbits; Staphylococcus aureus; Antibodies, Monoclonal; Hemolysin Proteins; Leukocidins; Shock, Septic; Respiration, Artificial; Stroke Volume; Ventricular Function, Left; Staphylococcal Infections; Shock; Immunoglobulin G
PubMed: 37781371
DOI: 10.3389/fimmu.2023.1260627