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EClinicalMedicine Sep 2020The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 overlaps with the flu season.
BACKGROUND
The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 overlaps with the flu season.
METHODS
We compared clinical and laboratory results from 719 influenza and 973 COVID-19 patients from January to April 2020. We compiled laboratory results from the first 14 days of the hospitalized patients using parameters that are most significantly different between COVID-19 and influenza and hierarchically clustered COVID-19 patients.
FINDINGS
Compared to influenza, patients with COVID-19 exhibited a continued increase in white blood cell count, rapid decline of hemoglobin, more rapid increase in blood urea nitrogen (BUN) and D-dimer, and higher level of alanine transaminase, C-reactive protein, ferritin, and fibrinogen. COVID-19 patients were sub-classified into 5 clusters through a hierarchical clustering analysis. Medical records were reviewed and patients were risk stratified based on the clinical outcomes. The cluster with the highest risk showed 27·8% fatality, 94% ICU admission, 94% intubation, and 28% discharge rates compared to 0%, 38%, 22%, and 88% in the lowest risk cluster, respectively. Patients in the highest risk cluster had leukocytosis including neutrophilia and monocytosis, severe anemia, increased red blood cell distribution width, higher BUN, creatinine, D-dimer, alkaline phosphatase, bilirubin, and troponin.
INTERPRETATION
There are significant differences in the clinical and laboratory courses between COVID-19 and influenza. Risk stratification in hospitalized COVID-19 patients using laboratory data could be useful to predict clinical outcomes and pathophysiology of these patients.
FUNDING
National Institute of Diabetes and Digestive and Kidney Disease, Department of Defense, and National Heart, Lung, and Blood Institute.
PubMed: 33089115
DOI: 10.1016/j.eclinm.2020.100475 -
Blood Advances Oct 2020Oligomonocytic chronic myelomonocytic leukemia (OM-CMML) is defined as those myelodysplastic syndromes (MDSs) or myelodysplastic/myeloproliferative neoplasms,...
Oligomonocytic chronic myelomonocytic leukemia (OM-CMML) is defined as those myelodysplastic syndromes (MDSs) or myelodysplastic/myeloproliferative neoplasms, unclassifiable with relative monocytosis (≥10% monocytes) and a monocyte count of 0.5 to <1 × 109/L. These patients show clinical and genomic features similar to those of overt chronic myelomonocytic leukemia (CMML), although most of them are currently categorized as MDS, according to the World Health Organization 2017 classification. We analyzed the clinicopathologic features of 40 patients with OM-CMML with well-annotated immunophenotypic and molecular data and compared them to those of 56 patients with overt CMML. We found similar clinical, morphological, and cytogenetic features. In addition, OM-CMML mirrored the well-known complex molecular profile of CMML, except for the presence of a lower percentage of RAS pathway mutations. In this regard, of the different genes assessed, only CBL was found to be mutated at a significantly lower frequency. Likewise, the OM-CMML immunophenotypic profile, assessed by the presence of >94% classical monocytes (MO1s) and CD56 and/or CD2 positivity in peripheral blood monocytes, was similar to overt CMML. The MO1 percentage >94% method showed high accuracy for predicting CMML diagnosis (sensitivity, 90.7%; specificity, 92.2%), even when considering OM-CMML as a subtype of CMML (sensitivity, 84.9%; specificity, 92.1%) in our series of 233 patients (39 OM-CMML, 54 CMML, 23 MDS, and 15 myeloproliferative neoplasms with monocytosis and 102 reactive monocytosis). These results support the consideration of OM-CMML as a distinctive subtype of CMML.
Topics: Genomics; Humans; Immunophenotyping; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Myeloproliferative Disorders
PubMed: 33108455
DOI: 10.1182/bloodadvances.2020002206 -
Journal of Tropical Medicine 2023Nepal faced a major dengue outbreak in 2022. The majority of hospitals and laboratories had limited resources for dengue confirmation and had to rely on rapid dengue...
BACKGROUND
Nepal faced a major dengue outbreak in 2022. The majority of hospitals and laboratories had limited resources for dengue confirmation and had to rely on rapid dengue diagnostic tests. The purpose of the study is to find the predictive hematological and biochemical parameters in each serological phase of dengue infection (NS1 and IgM) that may assist in dengue diagnosis, severity assessment, and patient management via the use of rapid serological tests.
METHOD
A laboratory-based cross-sectional study was conducted among dengue patients. Rapid antigen (NS1) and serological test (IgM/IgG) was performed to diagnose positive dengue cases. Furthermore, hematological and biochemical investigations were carried out and compared between NS1 and/or IgM-positive participants. A logistic regression analysis was used to identify the validity of the hematological and biochemical characteristics for dengue diagnosis as well as patient management. Receiver-operating characteristic (ROC) curve analysis was used to define the best cut-off, sensitivity, and specificity.
RESULT
Multiple logistic regression showed thrombocytopenia (OR = 1.000; = 0.006), leukopenia (OR = 0.999; < 0.001), glucose level (OR = 1.028; = 0.029), aspartate aminotransferase (OR = 1.131; = 0.001), and monocytosis (OR = 2.332; = 0.020) as significant parameters in the NS1-only positive group. Similarly, thrombocytopenia (OR = 1.000; = 0.001), glucose level (OR = 1.037; = 0.004), and aspartate aminotransferase (OR = 1.141; < 0.001) were significant in IgM-only positive patients. Moreover, thrombocytopenia (OR = 1.000; < 0.001), leukopenia (OR = 0.999; < 0.001), glucose (OR = 1.031; = 0.017), aspartate aminotransferase (OR = 1.136; < 0.001), and lymphopenia (OR = 0.520; = 0.067) were independent predictors in both NS1 + IgM positive groups. Platelets consistently demonstrated a higher area under the curve with increased sensitivity and specificity throughout all models, while aspartate aminotransferase (AUC = 0.811) and glucose (AUC = 0.712) demonstrated better results when single IgM positivity was observed. The total leukocyte count performed better when both NS1 + IgM were positive (AUC = 0.814).
CONCLUSION
Hence, thrombocytopenia, elevated AST, high glucose level, leukopenia with monocytosis, and leukopenia with lymphopenia may predict dengue diagnosis and its severity during an active infection. Therefore, these laboratory parameters can be used to complement less sensitive rapid tests, improve dengue diagnosis, and help with proper patient management.
PubMed: 36873099
DOI: 10.1155/2023/2904422 -
American Journal of Hematology Jun 2023Clonal hematopoiesis (CH) refers to age-associated expansion of somatic variants in hematopoietic stem and progenitor cells (HSPC).
CONDITION OVERVIEW
Clonal hematopoiesis (CH) refers to age-associated expansion of somatic variants in hematopoietic stem and progenitor cells (HSPC).
DIAGNOSIS
CH of indeterminate potential (CHIP) is operationally defined as pathogenic variants in HSPCs at a variant allele frequency ≥2%.
CLINICAL ASSOCIATIONS
CH is associated with increased occurrence of several hematological conditions such as cytopenias (also called clonal cytopenia of undetermined significance), hematological (predominantly myeloid but also lymphoid) neoplasms, cytosis (including monocytosis), and non-hematological conditions such as atherosclerotic cardiovascular and cerebrovascular disease, ischemic congestive heart failure, venous thromboembolism, type 2 diabetes mellitus, chronic obstructive pulmonary disease, osteoporosis, gout, with a potential protective effect in Alzheimer's disease (AD).
MANAGEMENT RECOMMENDATIONS
As of now, there is limited prospective data for CH testing; however, CH detection is becoming increasingly prevalent due to ubiquitous use of somatic and germline NGS testing. This in addition to data suggesting that therapy related myeloid neoplasm (tMN) in many cases is preceded by the detection of CH clones, has led to the establishment of CH clinics at several institutions. At our institution, on a research basis, we currently recommend testing for CH for individuals with persistent (≥4 months) unexplained cytopenias, in patients with malignancies prior to adjuvant cytotoxic chemotherapy and/or radiation or radionuclide therapy, screening prior to autologous hematopoietic stem cell transplantation and chimeric antigen receptor T cell (CAR-T) therapy and to assess as to whether or not, potential germline mosaic variants actually represent CH.
Topics: Humans; Clonal Hematopoiesis; Diabetes Mellitus, Type 2; Prospective Studies; Hematopoiesis; Clone Cells; Mutation
PubMed: 36938794
DOI: 10.1002/ajh.26915 -
The Journal of Clinical Investigation Oct 2011Leukocytosis is associated with increased cardiovascular disease risk in humans and develops in hypercholesterolemic atherosclerotic animal models. Leukocytosis is...
Leukocytosis is associated with increased cardiovascular disease risk in humans and develops in hypercholesterolemic atherosclerotic animal models. Leukocytosis is associated with the proliferation of hematopoietic stem and multipotential progenitor cells (HSPCs) in mice with deficiencies of the cholesterol efflux-promoting ABC transporters ABCA1 and ABCG1 in BM cells. Here, we have determined the role of endogenous apolipoprotein-mediated cholesterol efflux pathways in these processes. In Apoe⁻/⁻ mice fed a chow or Western- type diet, monocytosis and neutrophilia developed in association with the proliferation and expansion of HSPCs in the BM. In contrast, Apoa1⁻/⁻ mice showed no monocytosis compared with controls. ApoE was found on the surface of HSPCs, in a proteoglycan-bound pool, where it acted in an ABCA1- and ABCG1-dependent fashion to decrease cell proliferation. Accordingly, competitive BM transplantation experiments showed that ApoE acted cell autonomously to control HSPC proliferation, monocytosis, neutrophilia, and monocyte accumulation in atherosclerotic lesions. Infusion of reconstituted HDL and LXR activator treatment each reduced HSPC proliferation and monocytosis in Apoe⁻/⁻ mice. These studies suggest a specific role for proteoglycanbound ApoE at the surface of HSPCs to promote cholesterol efflux via ABCA1/ABCG1 and decrease cell proliferation, monocytosis, and atherosclerosis. Although endogenous apoA-I was ineffective, pharmacologic approaches to increasing cholesterol efflux suppressed stem cell proliferative responses.
Topics: ATP Binding Cassette Transporter 1; ATP Binding Cassette Transporter, Subfamily G, Member 1; ATP-Binding Cassette Transporters; Animals; Apolipoprotein A-I; Apolipoproteins E; Atherosclerosis; Cell Proliferation; Cholesterol; Disease Models, Animal; Hematopoietic Stem Cells; Humans; Leukocytosis; Lipoproteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Cardiovascular; Monocytes; Proteoglycans; Receptors, LDL
PubMed: 21968112
DOI: 10.1172/JCI57559 -
Journal of Clinical Immunology Oct 2023
Topics: Humans; Child; Lung Diseases, Interstitial; Leukocyte Disorders; Antigens, Neoplasm
PubMed: 37291413
DOI: 10.1007/s10875-023-01529-0 -
American Journal of Hematology Jun 2012Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder that is classified as a myelodysplastic/myeloproliferative neoplasm by the 2008 World... (Review)
Review
DISEASE OVERVIEW
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder that is classified as a myelodysplastic/myeloproliferative neoplasm by the 2008 World Health Organization classification of hematopoietic tumors. It is characterized by absolute monocytosis (>1 × 10(9) L(-1) ) in the peripheral blood that persists for at least 3 months. Patients may present with symptoms related to cytopenias and/or an underlying hypercatabolic state with drenching night sweats, splenomegaly, and weight loss.
DIAGNOSIS
The diagnosis of CMML rests on a combination of morphologic, histopathologic, and chromosomal abnormalities in the bone marrow, after careful exclusion of other conditions (both malignant and nonmalignant) that can cause monocytosis. Numerous molecular abnormalities have been recently recognized in patients with CMML-unfortunately, no single pathognomonic finding specific to CMML has been identified thus far.
RISK STRATIFICATION
The International Prognostic Scoring System for myelodysplastic syndrome (MDS) cannot be used to risk stratify patients with CMML because this model excluded patients with a leukocyte count >12 × 10(9) L(-1) . Other risk stratification models such as the MD Anderson prognostic score and Dusseldorf score have been published. In the only model that took karyotype into account, bone marrow blasts ≥ 10%, leukocyte count ≥ 13 × 10(9) L(-1) , hemoglobin < 10 g/dL, platelet count < 100 × 10(9) L(-1) , and presence of trisomy 8, abnormalities of chromosome 7, or complex karyotype were found to be independent predictors of adverse survival.
RISK-ADAPTED THERAPY
The Food and Drug Administration has approved azacitidine and decitabine for the treatment of patients with CMML based on two pivotal trials in MDS. Novel classes of agents including immunomodulatory drugs, nucleoside analogs, and small-molecule tyrosine kinase inhibitors are being investigated in the treatment of CMML. With the advent of reduced intensity conditioning, an allogeneic stem cell transplant has also become a viable option for a subset of patients.
Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Bone Marrow Examination; Chromosome Aberrations; Clinical Trials as Topic; Combined Modality Therapy; Decitabine; Diagnosis, Differential; Disease Management; Female; Genes, Neoplasm; Humans; Leukemia, Myelomonocytic, Chronic; Leukocyte Count; Male; Risk Assessment; Stem Cell Transplantation; Transplantation, Homologous
PubMed: 22615103
DOI: 10.1002/ajh.23203 -
Blood Mar 2019
Topics: Flow Cytometry; Humans; Leukocyte Disorders; Monocytes
PubMed: 30898774
DOI: 10.1182/blood-2019-01-896084 -
American Journal of Blood Research 2021COVID-19 is a systemic viral infection with a significant impact on the hematopoietic system, hemostasis as well as immune system. It would be of utmost importance to...
BACKGROUND
COVID-19 is a systemic viral infection with a significant impact on the hematopoietic system, hemostasis as well as immune system. It would be of utmost importance to explore if the most routinely used tests could serve as an aid in determining patient's clinical status or predicting severity of the disease.
METHODS
A prospective cross-sectional study was conducted on 506 Covid-19 positive patients and 200 controls over a period of two months (June and July 2020). The cases were sub-classified based on disease severity into mild to moderate (n=337), severe (n=118) and very severe (n=51) and based on survivor status into survivors (n=473) and non-survivors (n=33).
RESULTS
There were statistically significant differences in WBC count, Absolute neutrophil count (ANC), Absolute lymphocyte count (ALC), absolute monocyte count (AMC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) Red blood cell distribution width (RDW-SD) and RDW CV between covid cases vs controls; among the clinical subgroups and among the survivors and non-survivors. There was a significant strong positive correlation between various parameters, that is, NLR and MLR (r: 0.852, P=0), MPV and PDW (r: 0.912, P=0), MPV and PLCR (r: 0.956, P=0), PDW and PLCR (r: 0.893, P=0). NLR (AUC: 0.676, P=0) was the best single parameter and NLR+RDW-CV was best combination parameter as per area under curve (0.871) of ROC to distinguish severe from mild to moderate disease.
CONCLUSIONS
Leucocytosis, neutrophilia, lymphopenia and monocytosis were characteristic findings in covid cases while NLR and NLR+RDW-CV emerged as the most effective single and combination CBC parameters in distinguishing mild to moderate and severe cases respectively.
PubMed: 34079633
DOI: No ID Found -
Parasites & Vectors May 2023In Europe, feline leishmaniosis is commonly caused by Leishmania infantum. There is little knowledge regarding pathogenesis, ocular manifestations and long-term...
BACKGROUND
In Europe, feline leishmaniosis is commonly caused by Leishmania infantum. There is little knowledge regarding pathogenesis, ocular manifestations and long-term follow-ups in cats with leishmaniosis.
FINDINGS
A 6-year-old female, spayed European Shorthair cat was imported from Spain to Germany 2 years prior to its first clinical presentation. The cat showed lethargy, weight loss, ulcerative lesions on the front limbs and high-grade chronic uveitis. The diagnosis of L. infantum infection was based on the cytological finding of amastigotes in skin lesions, positive qPCR of EDTA-blood and positive PCR of a cyto-brush sample from the conjunctiva. Supportive findings included positive serology by IFAT, serum protein capillary electrophoresis with peaks in alpha2- and gamma-globulin sections and marked elevation of SAA. Enucleation had to be performed on day 288 on both eyes because of blindness, glaucoma and high-grade uveitis. Histologically, high numbers of Leishmania spp. amastigotes were found in histiocytes. IFAT and PCR were positive in the aqueous humor in both eyes, respectively. Feline leukemia virus antigen and feline immunodeficiency virus antibody testings were positive. Hematological and biochemical results revealed mild leukocytosis with lymphocytosis, monocytosis and eosinopenia as well as marked elevation of SAA and hyperglobulinemia. The cat was treated with allopurinol, responded well and was still alive at follow-up on day 288 after first presentation. However, enucleation was necessary because of refractory glaucoma and uveitis. CONCLUSION: For the first time, ocular evidence of Leishmania IgG antibodies was demonstrated in the aqueous humor of both eyes in cats. There is limited knowledge about the pathogenesis, treatment options and outcomes in cats infected with L. infantum. This case report supports the hypothesis that immunosuppression increases the risk of clinical signs of leishmaniasis in cats. Alpha2- and gamma-globulin peaks in serum protein capillary electrophoresis are supportive criteria for the diagnosis of L. infantum infection. SAA is valuable for monitoring. Regarding ophthalmology, uveitis and glaucoma may have a poor prognosis.
Topics: Female; Cats; Animals; Leishmaniasis; Europe; Leishmania infantum; Glaucoma; gamma-Globulins; Blood Proteins; Cat Diseases; Leishmaniasis, Visceral
PubMed: 37173777
DOI: 10.1186/s13071-023-05741-0