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Journal of Comparative Pathology Apr 2023A 12-year-old male neutered Australian Shepherd Dog was presented to Charlotte Animal Referral & Emergency with a history of a thoracic mass. On physical examination,...
A 12-year-old male neutered Australian Shepherd Dog was presented to Charlotte Animal Referral & Emergency with a history of a thoracic mass. On physical examination, physiological parameters were within the normal ranges, and a complete haemogram and serum biochemistry profile were unremarkable except for mild thrombocytopenia. A computed tomography scan revealed a 21 × 15 × 12.7 cm thoracic mass encompassing the cranial mediastinum and extending to the right caudal thorax. The mass was surgically removed and histopathological evaluation revealed that it comprised remnants of the thymus and a neoplasm composed of large blood-filled vascular spaces lined by a single layer of endothelial cells with mild anisocytosis and anisokaryosis. The neoplastic cells had diffuse strong immunolabeling for endothelial cell marker CD31. Multifocally, there were large cystic degenerated areas of thymic tissue lined by plump cytokeratin AE1/AE3-positive epithelial cells. Based on these findings, a diagnosis of thymic cavernous haemangioma (CH) was made. Thymic CH is rare in animals, with the only reported case in a cross bred cow. To our knowledge, this is the first case of a thymic CH in a dog.
Topics: Male; Female; Cattle; Dogs; Animals; Endothelial Cells; Australia; Hemangioma, Cavernous; Dog Diseases; Tomography, X-Ray Computed; Cattle Diseases
PubMed: 36931010
DOI: 10.1016/j.jcpa.2023.02.001 -
Cureus Mar 2023Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML) characterized by abnormal megakaryoblasts expressing platelet-specific surface...
Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML) characterized by abnormal megakaryoblasts expressing platelet-specific surface antigens. 4%-16% of childhood AMLs are AMKL. Childhood AMKL is usually associated with Down syndrome (DS). It is 500 times more common in patients with DS when compared to the general population. In contrast, non-DS-AMKL is much rarer. We describe a case of de novo non-DS-AMKL in a teenage girl child who presented with a history of excessive tiredness, fever, abdominal pain for three months, and vomiting for four days. She had lost appetite, and weight. On examination she was pale; there was no clubbing, hepatosplenomegaly or lymphadenopathy. There were no dysmorphic features or neurocutaneous markers. Laboratory tests showed bicytopenia (Hb: 6.5g/dL, total WBC count: 700/µL, platelet count: 216,000/ µL, Reticulocyte %: 0.42) and 14% blasts on the peripheral blood smear. Platelet clumps and anisocytosis were also noted. Bone marrow aspirate showed a few hypocellular particles with dilute cell trails but showed 42% blasts. Mature megakaryocytes showed marked dyspoiesis. Flow cytometry on bone marrow aspirate showed myeloblasts and megakaryoblasts. Karyotyping showed 46 XX. Hence, a final diagnosis of non-DS-AMKL was established. She was treated symptomatically. However, she was discharged on request. Interestingly, the expression of erythroid markers such as CD36 and lymphoid markers like CD7 is usually seen in DS-AMKL and not in non-DS-AMKL. AMKL is treated with AML-directed chemotherapies. Although complete remission rates are similar to other AML subtypes, overall survival is only about 18-40 weeks.
PubMed: 36911590
DOI: 10.7759/cureus.35965 -
Cureus Feb 2023During therapeutic intervention for adult T-cell leukemia-lymphoma (ATLL), transient red blood cell (RBC) deformations and rapid anemia progression are often observed....
OBJECTIVES
During therapeutic intervention for adult T-cell leukemia-lymphoma (ATLL), transient red blood cell (RBC) deformations and rapid anemia progression are often observed. These RBC responses are characteristically observed during the treatment of ATLL, and we examined the details and significance of these RBC responses.
METHODS
Seventeen patients with ATLL were enrolled. Peripheral blood smears and laboratory findings were collected during the first two weeks after treatment intervention. We examined the transition of erythrocyte morphology and the factors associated with the induction of anemia.
RESULTS
RBC abnormalities (i.e., elliptocytes, anisocytosis, and schistocytes) rapidly progressed following therapeutic intervention in five of the six cases for whom evaluable consecutive blood smears were available, with significant improvement evident after two weeks. Changes in RBC morphology were significantly associated with the red cell distribution width (RDW). Laboratory findings from all 17 patients showed various levels of anemia progression. A transient increase in RDW values was observed in 11 cases after therapeutic intervention. The degree of progressive anemia during the two-week period was significantly correlated with increased lactate dehydrogenase and soluble interleukin-2 receptor levels and an increase in RDW (P <0.01).
CONCLUSIONS
In cases of ATLL, transient progression of RBC morphological abnormalities and RDW value were observed early after therapeutic intervention. These RBC responses may be associated with tumor and tissue destruction. RBC morphology or RDW values may provide important information about the tumor dynamics and general condition of the patients.
PubMed: 36895533
DOI: 10.7759/cureus.34641 -
Clinical Chemistry and Laboratory... Jul 2023Extracellular histone levels are associated with the severity of many human pathologies, including sepsis and COVID-19. This study aimed to investigate the role of...
OBJECTIVES
Extracellular histone levels are associated with the severity of many human pathologies, including sepsis and COVID-19. This study aimed to investigate the role of extracellular histones on monocyte distribution width (MDW), and their effect on the release of cytokines by blood cells.
METHODS
Peripheral venous blood was collected from healthy subjects and treated with different doses of a histone mixture (range 0-200 μg/mL) to analyze MDW modifications up-to 3 h and digital microscopy of blood smears. Plasma obtained after 3 h of histone treatment were assayed to evaluate a panel of 24 inflammatory cytokines.
RESULTS
MDW values significantly increased in a time- and dose-dependent manner. These findings are associated with the histone-induced modifications of cell volume, cytoplasmic granularity, vacuolization, and nuclear structure of monocytes, promoting their heterogeneity without affecting their count. After 3 h of treatment almost all cytokines significantly increased in a dose-dependent manner. The most relevant response was shown by the significantly increased G-CSF levels, and by the increase of IL-1β, IL-6, MIP-1β, and IL-8 at the histone doses of 50, 100, and 200 µg/mL. VEGF, IP-10, GM-CSF, TNF-α, Eotaxin, and IL-2 were also up-regulated, and a lower but significant increase was observed for IL-15, IL-5, IL-17, bFGF, IL-10, IFN-γ, MCP-1, and IL-9.
CONCLUSIONS
Circulating histones critically induce functional alterations of monocytes mirrored by MDW, monocyte anisocytosis, and hyperinflammation/cytokine storm in sepsis and COVID-19. MDW and circulating histones may be useful tools to predict higher risks of worst outcomes.
Topics: Humans; Histones; Monocytes; Cytokine Release Syndrome; COVID-19; Cytokines; Sepsis
PubMed: 36847604
DOI: 10.1515/cclm-2023-0093 -
International Journal of Molecular... Feb 2023Liver disease is one of the leading public health problems faced by healthcare practitioners regularly. As such, there has been a search for an inexpensive, readily... (Review)
Review
Liver disease is one of the leading public health problems faced by healthcare practitioners regularly. As such, there has been a search for an inexpensive, readily available, non-invasive marker to aid in monitoring and prognosticating hepatic disorders. Recently, red blood cell distribution width (RDW) has been found to be associated with various inflammatory conditions with implications for its use as a potential marker for assessing disease progression and prognosis in multiple conditions. Multiple factors effect red blood cell production whereby a dysfunction in any process can lead to anisocytosis. Furthermore, a chronic inflammatory state leads to increased oxidative stress and produces inflammatory cytokines causing dysregulation and increased intracellular uptake and use of both iron and vitamin B12, which leads to a reduction in erythropoiesis causing an increase in RDW. This literature review reviews in-depth pathophysiology that may lead to an increase in RDW and its potential correlation with chronic liver diseases, including hepatitis B, hepatitis C, hepatitis E, non-alcoholic fatty liver disease, autoimmune hepatitis, primary biliary cirrhosis, and hepatocellular carcinoma. In our review, we examine the use of RDW as a prognostic and predictive marker for hepatic injury and chronic liver disease.
Topics: Humans; Erythrocyte Indices; Prognosis; Carcinoma, Hepatocellular; Hepatitis B; Liver Neoplasms
PubMed: 36834895
DOI: 10.3390/ijms24043487 -
Antioxidants (Basel, Switzerland) Jan 2023Viral infections activate the innate immune response and the secretion of inflammatory cytokines. They also alter oxidative stress markers, which potentially can have an...
Viral infections activate the innate immune response and the secretion of inflammatory cytokines. They also alter oxidative stress markers, which potentially can have an involvement in the pathogenesis of the disease. The aim of this research was to study the role of the oxidative stress process assessed through lactate dehydrogenase (LDH) on the severity of COVID-19 measured by oxygen saturation (SaO) and the putative interaction with inflammation. The investigation enrolled 1808 patients (mean age of 68 and 60% male) with COVID-19 from the HM Hospitals database. To explore interactions, a regression model and mediation analyses were performed. The patients with lower SaO presented lymphopenia and higher values of neutrophils-to-lymphocytes ratio and on the anisocytosis coefficient. The regression model showed an interaction between LDH and anisocytosis, suggesting that high levels of LDH (>544 U/L) and an anisocytosis coefficient higher than 10% can impact SaO in COVID-19 patients. Moreover, analysis revealed that LDH mediated 41% ( value = 0.001) of the effect of anisocytosis on SaO in this cohort. This investigation revealed that the oxidative stress marker LDH and the interaction with anisocytosis have an important role in the severity of COVID-19 infection and should be considered for the management and treatment of the oxidative phenomena concerning this within a precision medicine strategy.
PubMed: 36829793
DOI: 10.3390/antiox12020234 -
Journal of Internal Medicine May 2023Anisocytosis reflects unequal-sized red blood cells and is quantified using red blood cell distribution width (RDW). RDW increases with age and has been consistently...
BACKGROUND
Anisocytosis reflects unequal-sized red blood cells and is quantified using red blood cell distribution width (RDW). RDW increases with age and has been consistently associated with adverse health outcomes, such as cardiovascular disease and mortality. Why RDW increases with age is not understood. We aimed to identify plasma metabolomic markers mediating anisocytosis with aging.
METHODS
We performed mediation analyses of plasma metabolomics on the association between age and RDW using resampling techniques after covariate adjustment. We analyzed data from adults aged 70 or older from the main discovery cohort of the Baltimore Longitudinal Study of Aging (BLSA, n = 477, 46% women) and validation cohorts of the Health, Aging and Body Composition Study (Health ABC, n = 620, 52% women) and Invecchiare in Chianti, Aging in the Chianti Area (InCHIANTI) study (n = 735, 57% women). Plasma metabolomics was assayed using the Biocrates MxP Quant 500 kit in BLSA and Health ABC and liquid chromatography with tandem mass spectrometry in InCHIANTI.
RESULTS
In all three cohorts, symmetric dimethylarginine (SDMA) significantly mediated the association between age and RDW. Asymmetric dimethylarginine (ADMA) and 1-methylhistidine were also significant mediators in the discovery cohort and one validation cohort. In the discovery cohort, we also found choline, homoarginine, and several long-chain triglycerides significantly mediated the association between age and RDW.
CONCLUSIONS AND RELEVANCE
This metabolomics study of three independent aging cohorts identified a specific set of metabolites mediating anisocytosis with aging. Whether SDMA, ADMA, and 1-methylhistidine are released by the damaged erythrocytes with high RDW or they affect the physiology of erythrocytes causing high RDW should be further investigated.
Topics: Humans; Female; Aged; Male; Longitudinal Studies; Erythrocytes; Aging; Cardiovascular Diseases; Triglycerides; Erythrocyte Indices
PubMed: 36739565
DOI: 10.1111/joim.13612 -
Cureus Dec 2022Background The red cell distribution width (RDW), an index of variation of erythrocyte volume (anisocytosis), has traditionally been used in the differential diagnosis...
Background The red cell distribution width (RDW), an index of variation of erythrocyte volume (anisocytosis), has traditionally been used in the differential diagnosis of anemia. However, recent studies reported that increased RDW may be associated with adverse aging-related health outcomes. Methods The present cross-sectional study analyzed data from the National Health and Nutrition Examination Survey to examine the association between RDW categories (≤ 13.0%, 13.1 - 14.0%, 14.1 - 15.0%, ≥ 15.1%) and maximum grip strength (GS) (kg) in a nationally representative sample of adults aged 60 years and older. Anemia was defined according to the WHO criteria as a hemoglobin concentration of < 13 g/dl in men and < 12 g/dl in women. Results A total of 2,955 participants with a mean age of 69.3 years represented the study sample. General linear models demonstrated that men and women with RDW ≥ 15.1% were 3.2 kg and 1.4 kg weaker than their counterparts with RDW ≤ 13.0%, respectively. Notably, non-anemic older men in the highest RDW category had a mean GS 3.9 kg lower than those in the lowest RDW category. In contrast, this association was attenuated in women without anemia. Conclusion RDW was inversely associated with GS, particularly in older men. Moreover, this association remained unchanged even among men without anemia.
PubMed: 36721603
DOI: 10.7759/cureus.33049 -
La Revue de Medecine Interne Feb 2023Alpha thalassemia-myelodysplastic syndrome (ATMDS) is one of the possible complications related to the genetic instability typical of clonal hemopoietic disorders such...
BACKGROUND
Alpha thalassemia-myelodysplastic syndrome (ATMDS) is one of the possible complications related to the genetic instability typical of clonal hemopoietic disorders such as myelodysplastic syndromes (MDS). Hemoglobin H acquisition, which is hemoglobin without alpha chains and with 4 beta chains is the hallmark of this disease.
OBSERVATION
An 86-year-old male with chronic, microcytic anemia was referred due to a fall in his hemoglobin level. The blood smear was remarkable for intense anisocytoses and poikilocytosis. Bone marrow analysis was followed by a diagnosis of MDS with a good prognostic score. Peripheral blood coloration with brilliant cresyl blue showed "golf ball-like" erythrocytes. Hemoglobin electrophoresis is notable for the presence of H hemoglobin. The new generation sequencing confirmed the diagnosis of ATMDS showing a non-sense mutation in the gene ATRX.
CONCLUSION
The diagnosis of ATMDS should be considered in the presence of the association of MDS, microcytic anemia and marked blood smear abnormalities such as anisocytosis and poikilocytosis. A little less than 10% of all MDS are complicated by ATMDS.
Topics: Male; Humans; Aged, 80 and over; alpha-Thalassemia; X-linked Nuclear Protein; Myelodysplastic Syndromes; Mutation
PubMed: 36646614
DOI: 10.1016/j.revmed.2022.12.005 -
Clinical Chemistry and Laboratory... May 2023The SARS-CoV-2 infection is characterized by both systemic and organ hyper-thromboinflammation, with a clinical course ranging from mild up-to critical systemic... (Meta-Analysis)
Meta-Analysis Review
The SARS-CoV-2 infection is characterized by both systemic and organ hyper-thromboinflammation, with a clinical course ranging from mild up-to critical systemic dysfunction and death. In patients with coronavirus disease 2019 (COVID-19) the monocyte/macrophage population is deeply involved as both trigger and target, assuming the value of useful diagnostic/prognostic marker of innate cellular immunity. Several studies correlated morphological and immunophenotypic alterations of circulating monocytes with clinical outcomes in COVID-19 patients, concluding that monocyte distribution width (MDW) may retain clinical value in stratifying the risk of disease worsening. Through an electronic search in Medline and Scopus we performed an updated literature review and meta-analysis aimed to explore the association between increased MDW levels and illness severity in COVID-19 patients, deciphering role(s) and function(s) of monocytes in the harmful network underlining SARS-CoV-2 infection. We found that significantly elevated MDW values were frequently present in COVID-19 patients who developed unfavorable clinical outcomes, compounded by a significant association between monocyte anisocytosis and SARS-CoV-2 outcomes. These findings suggest that blood MDW index and its scatter plot could represent useful routine laboratory tools for early identification of patients at higher risk of unfavorable COVID-19 and for monitoring the progression of viral infection, clinical outcomes, and therapeutic efficacy throughout hospitalization. According to this evidence, therapeutic decisions in patients with SARS-CoV-2 infection could benefit from monitoring MDW value, with administration of drugs limiting thrombo-inflammation due to monocyte hyper-activation in patients with severe/critical COVID-19 disease.
Topics: Humans; COVID-19; Monocytes; SARS-CoV-2; Inflammation; Thrombosis
PubMed: 36626568
DOI: 10.1515/cclm-2022-0936