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Journal of Lipid Research Mar 2024Finasteride is commonly prescribed to treat benign prostate hyperplasia and male-pattern baldness in cis men and, more recently, trans individuals. However, the effect...
Finasteride is commonly prescribed to treat benign prostate hyperplasia and male-pattern baldness in cis men and, more recently, trans individuals. However, the effect of finasteride on cardiovascular disease remains elusive. We evaluated the role of finasteride on atherosclerosis using low-density lipoprotein (LDL) receptor-deficient (Ldlr) mice. Next, we examined the relevance to humans by analyzing the data deposited between 2009 and 2016 in the National Health and Nutrition Examination Survey. We show that finasteride reduces total plasma cholesterol and delays the development of atherosclerosis in Ldlr mice. Finasteride reduced monocytosis, monocyte recruitment to the lesion, macrophage lesion content, and necrotic core area, the latter of which is an indicator of plaque vulnerability in humans. RNA sequencing analysis revealed a downregulation of inflammatory pathways and an upregulation of bile acid metabolism, oxidative phosphorylation, and cholesterol pathways in the liver of mice taking finasteride. Men reporting the use of finasteride showed lower plasma levels of cholesterol and LDL-cholesterol than those not taking the drug. Our data unveil finasteride as a potential treatment to delay cardiovascular disease in people by improving the plasma lipid profile.
Topics: Humans; Male; Animals; Mice; Finasteride; Cardiovascular Diseases; Nutrition Surveys; Atherosclerosis; Cholesterol; Receptors, LDL; Mice, Knockout
PubMed: 38272355
DOI: 10.1016/j.jlr.2024.100507 -
Journal of Vector Borne Diseases Jan 2024The correct association between Plasmodium falciparum parasite density and the cellular constituents of blood is not known in entirety in Nigerian children. Thus, we...
BACKGROUND OBJECTIVES
The correct association between Plasmodium falciparum parasite density and the cellular constituents of blood is not known in entirety in Nigerian children. Thus, we decided to study the association between cellular blood constituents and malaria parasite density in malaria infected children attending a Nigerian hospital.
METHODS
A study of all the children diagnosed with malaria fever at the Paediatric out-patient clinic, Cedar Crest Hospital, Abuja. Packed cell volume, white blood cells with differentials and platelet counts and malaria parasite densities obtained from blood samples were studied. Malaria parasites densities more than 2 pluses were classified as significant parasitemia and 1 plus non-significant. Information obtained were recorded and analysed with SPSS 22 software.
RESULTS
A total 143 children (74 boys and 69 girls) diagnosed with malaria with ages between 5 months to 17 years (mean 5.24 ±4.60) were studied. The majority 141 (98.6%) had non-significant P. falciparum parasitemia, while 2 (2.4%) had significant parasitemia. Of the 143 children with malaria 116 (81.1%) had a normal leucocyte count. All children with significant parasitemia had a normal leucocyte count. Of the 143 children 11 (7.7%) had anemia and 10 (7.0%) thrombocytopenia. Anemia, monocytosis and thrombocytopenia were significantly associated with significant malaria parasitemia (p<0.05). Mean platelet counts was significantly less amongst those with significant parasitemia (P <0.01).
INTERPRETATION CONCLUSION
All patients with significant malaria parasitemia had normal leucocyte counts. Significant malaria parasitemia is significantly associated with anemia, thrombocytopenia and monocytosis. Blood film appearances showing this changes are suggestive of significant malaria parasitemia.
PubMed: 38238851
DOI: 10.4103/0972-9062.393971 -
Animals : An Open Access Journal From... Jan 2024Stress leukogram includes eosinopenia as one of its main markers (neutrophilia, eosinopenia, lymphopenia, and mild monocytosis). Cortisol is the main stress biomarker,...
Stress leukogram includes eosinopenia as one of its main markers (neutrophilia, eosinopenia, lymphopenia, and mild monocytosis). Cortisol is the main stress biomarker, which is also strongly correlated with the severity of gastrointestinal diseases. This study aimed to determine the relationship between salivary cortisol and the eosinophil cell count (EC) in equids with abdominal pain. To do this, 39 horses with abdominal pain referred to an emergency service were included. All samples were taken on admission, and several parameters and clinical data were included. Equids were classified according to the outcome as survivors and non-survivors. Non-surviving equids presented higher salivary cortisol concentrations (Non-Survivors: 1.580 ± 0.816 µg/dL; Survivors 0.988 ± 0.653 µg/dL; < 0.05) and lower EC (Non-Survivors: 0.0000 × 10/µL (0.000/0.0075); Survivors: 0.0450 × 10/µL (0.010/0.1825); < 0.01). In addition, the relationship between salivary cortisol concentration, EC, and the WBC was determined. Only a strong correlation (negative) was observed between cortisol and EC (r = -0.523, < 0.01). Since cortisol is not an analyte that can be measured routinely in clinical settings such as emergencies, the EC could be a good alternative. While the results are promising, further studies are needed before EC can be used confidently in routine practice to predict survival in cases of abdominal pain.
PubMed: 38200895
DOI: 10.3390/ani14010164 -
African Journal of Laboratory Medicine 2023Automated haematology analysers such as the Sysmex XN-3000 (Sysmex Corporation, Kobe, Japan) utilise white blood cell (WBC) flags to identify quantitative and...
BACKGROUND
Automated haematology analysers such as the Sysmex XN-3000 (Sysmex Corporation, Kobe, Japan) utilise white blood cell (WBC) flags to identify quantitative and qualitative abnormalities. Owing to clinical and biological factors, the sensitivity and specificity of the flags vary when compared to microscopy, the gold-standard method for assessing peripheral blood smear (PBS) morphology.
OBJECTIVE
This study assessed the performance of the Sysmex XN-3000 haematology analyser in comparison to PBS microscopy for the detection of WBC abnormalities.
METHODS
We collected 250 random full blood count samples from the haematology laboratory at Inkosi Albert Luthuli Central Hospital, Durban, KwaZulu-Natal, South Africa, from March 2022 to April 2022. The performance of the automated WBC flags of the Sysmex XN-3000 was assessed in comparison to PBS microscopy, and the impact of established clinical variables on the performance of the flags was determined.
RESULTS
The sensitivity of the 'blast' flag was 96.3%, and the specificity was 84.9%. The efficiency of the flag was adversely impacted by low white cell counts (< 1.5 × 10/L; < 0.001), chemotherapy ( = 0.002), malignancy ( = 0.02), and infection ( = 0.02). The 'abnormal lymphocyte' flag demonstrated a sensitivity of 90% and a specificity of 96.2%, and its performance was adversely impacted by chemotherapy exposure ( = 0.03). Three cases (1.2%) erroneously flagged as 'monocytosis' demonstrated blasts on microscopy.
CONCLUSION
In our setting, PBS microscopy remains necessary to confirm blasts, abnormal lymphocytes, and monocytosis in patients with malignancy, current chemotherapy exposure, low white cell counts, and infection.
WHAT THIS STUDY ADDS
This study adds evidence that PBS morphology remains the gold standard for confirming WBC abnormalities in patients with a history of malignancy, chemotherapy, and leucopenia.
PubMed: 38094982
DOI: 10.4102/ajlm.v12i1.2140 -
Blood Mar 2024The World Health Organization (WHO) classification of hematolymphoid tumors and the International Consensus Classification (ICC) of 2022 introduced major changes to the...
The World Health Organization (WHO) classification of hematolymphoid tumors and the International Consensus Classification (ICC) of 2022 introduced major changes to the definition of chronic myelomonocytic leukemia (CMML). To assess its qualitative and quantitative implications for patient care, we started with 3311 established CMML cases (according to WHO 2017 criteria) and included 2130 oligomonocytosis cases fulfilling the new CMML diagnostic criteria. Applying both 2022 classification systems, 356 and 241 of oligomonocytosis cases were newly classified as myelodysplastic (MD)-CMML (WHO and ICC 2022, respectively), most of which were diagnosed as myelodysplastic syndrome (MDS) according to the WHO 2017 classification. Importantly, 1.5 times more oligomonocytosis cases were classified as CMML according to WHO 2022 than based on ICC, because of different diagnostic criteria. Genetic analyses of the newly classified CMML cases showed a distinct mutational profile with strong enrichment of MDS-typical alterations, resulting in a transcriptional subgroup separated from established MD and myeloproliferative CMML. Despite a different cytogenetic, molecular, immunophenotypic, and transcriptional landscape, no differences in overall survival were found between newly classified and established MD-CMML cases. To the best of our knowledge, this study represents the most comprehensive analysis of routine CMML cases to date, both in terms of clinical characterization and transcriptomic analysis, placing newly classified CMML cases on a disease continuum between MDS and previously established CMML.
Topics: Humans; Consensus; Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Leukocytosis; World Health Organization; Prognosis; Organic Chemicals
PubMed: 38064663
DOI: 10.1182/blood.2023021199 -
International Journal of Molecular... Nov 2023Chronic myelomonocytic leukemia (CMML) is a hematological neoplasm characterized by monocytosis, splenomegaly, thrombocytopenia, and anemia. Moreover, it is associated...
Chronic myelomonocytic leukemia (CMML) is a hematological neoplasm characterized by monocytosis, splenomegaly, thrombocytopenia, and anemia. Moreover, it is associated with mutations and, rarely, with variants. We present the case of an 84-year-old patient with persistent anemia and monocytosis. Due to the presence of dysmorphic granulocytes, monocyte atypia, and myeloid precursors in the peripheral blood cells, the patient was subjected to a bone marrow examination. The diagnosis was consistent with CMML type 2. The Hemocoagulative test showed an increase in fibrinolysis markers. Next-generation targeted sequencing showed and mutations, along with an unexpected germline missense variant, rarely encountered in CMML. The patient started Azacitidine treatment and achieved normal hemostatic process values. In conclusion, we identified a heterozygous germline mutation that, together with and variants, was responsible for the hemorrhagic manifestation.
Topics: Humans; Aged, 80 and over; Leukemia, Myelomonocytic, Chronic; Germ-Line Mutation; Genetic Predisposition to Disease; Mutation; Anemia; Germ Cells; Receptors, Colony-Stimulating Factor
PubMed: 38003211
DOI: 10.3390/ijms242216021 -
Haematologica Nov 2023Juvenile myelomonocytic leukemia (JMML) is a rare, generally aggressive myeloproliferative neoplasm affecting young children. It is characterized by granulomonocytic...
Juvenile myelomonocytic leukemia (JMML) is a rare, generally aggressive myeloproliferative neoplasm affecting young children. It is characterized by granulomonocytic expansion, with monocytosis infiltrating peripheral tissues. JMML is initiated by mutations upregulating RAS signaling. Approximately 10% of cases remain without an identified driver event. Exome sequencing of 2 unrelated cases of familial JMML of unknown genetics and analysis of the French JMML cohort identified 11 patients with variants in SH2B3, encoding LNK, a negative regulator of the JAK-STAT pathway. All variants were absent from healthy population databases, and mutation spectrum was consistent with a loss of function of the LNK protein. A stoploss variant was shown to affect both protein synthesis and stability. The other variants were either truncating or missense, the latter affecting the SH2 domain that interacts with activated JAK. Of the 11 patients, 8 from 5 families inherited pathogenic bi-allelic SH2B3 germline variants from their unaffected heterozygous parents. These children represent half of the cases with no identified causal mutation in the French cohort. They displayed typical clinical and hematological JMML features with neonatal onset and marked thrombocytopenia. They were characterized by absence of additional genetic alterations and a hypomethylated DNA profile with fetal characteristics. All patients showed partial or complete spontaneous clinical resolution. However, progression to thrombocythemia and immunity-related pathologies may be of concern later in life. Bi-allelic SH2B3 germline mutations thus define a new condition predisposing to a JMML-like disorder, suggesting that the JAK pathway deregulation is capable of initiating JMML, and opening new therapeutic options.
PubMed: 37981895
DOI: 10.3324/haematol.2023.283917 -
AME Case Reports 2023Chronic myelomonocytic leukemia (CMML) is a rare, malignant, clonal hematopoietic disorder with features of both myelodysplastic syndrome (MDS) and myeloproliferative...
BACKGROUND
Chronic myelomonocytic leukemia (CMML) is a rare, malignant, clonal hematopoietic disorder with features of both myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN). It is classified as MDS/MPN overlap syndrome by the World Health Organization (WHO), and the prognosis is generally poor. Solid tumors are rarely associated with or are secondary to CMML.
CASE DESCRIPTION
We here reported a case of a 75-year-old female patient with persistent peripheral blood monocytosis and bone marrow blasts ≤20%. A diagnosis of CMML was made. Unexpectedly, she presented with recurrent melena and red blood cell (RBC) transfusions were ineffective. Capsule endoscopy revealed gastric space-occupying lesions, and pathological biopsy confirmed gastric adenocarcinoma. Because of the patient's history of coronary heart disease and the fact that she underwent percutaneous coronary intervention with stenting less than half a year ago, the diagnosis and treatment of this patient required a multidisciplinary team of hematologists, oncologists, anesthesiologists and cardiologists.
CONCLUSIONS
Physicians should consider the possibility of other malignant solid tumors in patients with CMML. For patients at high risk for gastrointestinal endoscopy, capsule endoscopy may be a safer way to determine if a patient needs further endoscopic biopsy. There are currently no guidelines for the treatment of CMML with gastric cancer.
PubMed: 37942038
DOI: 10.21037/acr-23-12 -
Journal of Korean Neurosurgical Society Mar 2024Delayed cerebral ischemia (DCI) is a major cause of disability in patients who survive aneurysmal subarachnoid hemorrhage (aSAH). Systemic inflammatory markers, such as...
OBJECTIVE
Delayed cerebral ischemia (DCI) is a major cause of disability in patients who survive aneurysmal subarachnoid hemorrhage (aSAH). Systemic inflammatory markers, such as peripheral leukocyte count and systemic immune-inflammatory index (SII) score, have been considered predictors of DCI in previous studies. This study aims to investigate which systemic biomarkers are significant predictors of DCI.
METHODS
We conducted a retrospective, observational, single-center study of 170 patients with SAH admitted between May 2018 and March 2022. We analyzed the patients' clinical and laboratory parameters within 1 hour and 3-4 and 5-7 days after admission. The DCI and non-DCI groups were compared. Variables showing statistical significance in the univariate logistic analysis (p<0.05) were entered into a multivariate regression model.
RESULTS
Hunt-Hess grade "4-5" at admission, modified Fisher scale grade "3-4" at admission, hydrocephalus, intraventricular hemorrhage, and infection showed statistical significance (p<0.05) on a univariate logistic regression. Lymphocyte and monocyte count at admission, SII scores and C-reactive protein levels on days 3-4, and leukocyte and neutrophil counts on days 5-7 exhibited statistical significance on the univariate logistic regression. Multivariate logistic regression analysis revealed that monocyte count at admission (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.04-2.65; p=0.036) and SII score at days 3-4 (OR, 1.55; 95% CI, 1.02-2.47; p=0.049) were independent predictors of DCI.
CONCLUSION
Monocyte count at admission and SII score 3-4 days after rupture are independent predictors of clinical deterioration caused by DCI after aSAH. Peripheral monocytosis may be the primer for the innate immune reaction, and the SII score at days 3-4 can promptly represent the propagated systemic immune reaction toward DCI.
PubMed: 37734388
DOI: 10.3340/jkns.2023.0182 -
Frontiers in Immunology 2023The marine aquaculture industry has been witnessing a worldwide emergence of tenacibaculosis, a poorly understood bacterial disease caused by that affects commercially...
INTRODUCTION
The marine aquaculture industry has been witnessing a worldwide emergence of tenacibaculosis, a poorly understood bacterial disease caused by that affects commercially important fish. So far, knowledge on the virulence mechanisms is scarce and the pathogen-host interaction operating in tenacibaculosis remain to be disclosed. This study aimed at contributing to a better understanding of this disease, by evaluating the early innate immune response triggered in European sea bass () by a bath-challenge with .
METHODS
Groups of sea bass were bath-challenged with (challenged fish) or mock-challenged. Undisturbed fish were used as controls (time 0). Samples of blood, liver and mucosal organs (skin, gills and posterior-intestine) were collected at 0 h (control) and at 6, 24, 48 and 72 h post-challenge (n=12). Mucosal organs were used for analyzing the expression of immune-related genes by RT-qPCR, as well as blood samples for assessing haematological and innate humoral parameters and liver for oxidative stress assessment.
RESULTS
An increased expression of , , and was detected in all mucosal organs of infected fish when compared with control and mock-challenged fish, suggesting a pro-inflammatory response against transversal to all organs. The faster induction of these pro-inflammatory genes was observed in the gills. Regarding the systemic response, challenged fish presented neutrophilia, monocytosis, signs of anemia, and a decrease of bactericidal and lysozyme activities in plasma. Almost no variations were observed regarding hepatic oxidative stress.
DISCUSSION/CONCLUSIONS
The present study suggests that induces a local innate immune response upon bath infection not only in the skin of European sea bass, but also in the gills and posterior-intestine, likely triggered by the 's capacity to adhere, colonize and damage these organs that can function as entry ways to bacteria, leading ultimately to the seen host's systemic response.
Topics: Animals; Bass; Immunity, Innate; Tenacibaculum; Liver
PubMed: 37731496
DOI: 10.3389/fimmu.2023.1254677