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Clinical Laboratory Oct 2021Monocytes play a central role in Covid-19 infection. Monocytopenia is especially observed in patients with severe infection. In our study, we aimed to investigate the...
BACKGROUND
Monocytes play a central role in Covid-19 infection. Monocytopenia is especially observed in patients with severe infection. In our study, we aimed to investigate the effects of monocytopenia on survival in patients presenting with the suspicion of Covid-19.
METHODS
Patients diagnosed with Covid-19 who received inpatient or outpatient treatment in the pandemic clinic of Umraniye Training and Research Hospital between April 2020 and July 2020 were included in our retrospective cohort study. Patients were divided into two groups, severe and non-severe. Demographic data, laboratory parameters, those who were monocytopenic at presentation, those who developed monocytopenia during follow-up, and those with persistent monocytopenia were noted.
RESULTS
The study included 471 patients with a mean age of 50.4 ± 18.2 years. Sixty-seven (14.2%) patients had severe and 404 (85.8%) had non-severe disease. The minimum value of monocytes detected during the follow-up in severe patients was significantly lower (p < 0.001). As patients were grouped into those with monocytopenia at the time of admission, those with monocytopenia developing during their follow-up, and those whose monocytopenia at admission persisted, they were compared with regards to the presence or absence of severe disease. Newly developing monocytopenia and persistent monocytopenia were significant in patients with severe disease (p < 0.001, p = 0,001 respectively). Also, among non-surviving patients, there was a significant difference in survival times in the monocytopenia group (p = 0.029).
CONCLUSIONS
In our study, we found more developing and persistent monocytopenia in the severe group, and the survival time was low, especially in those with newly developing monocytopenia. The development of monocytopenia in the daily hemogram follow-up of the patients may increase the possibility of mortality, which suggests that monocytopenia may be a new marker in determining survival.
Topics: Adult; Aged; COVID-19; Hospitalization; Humans; Middle Aged; Pandemics; Retrospective Studies; SARS-CoV-2
PubMed: 34655211
DOI: 10.7754/Clin.Lab.2021.210215 -
The Lancet. Infectious Diseases May 2017Listeriosis is a severe foodborne infection and a notifiable disease in France. We did a nationwide prospective study to characterise its clinical features and... (Observational Study)
Observational Study
BACKGROUND
Listeriosis is a severe foodborne infection and a notifiable disease in France. We did a nationwide prospective study to characterise its clinical features and prognostic factors.
METHODS
MONALISA was a national prospective observational cohort study. We enrolled eligible cases declared to the National Reference Center for Listeria (all microbiologically proven) between Nov 3, 2009, and July 31, 2013, in the context of mandatory reporting. The outcomes were analysis of clinical features, characterisation of Listeria isolates, and determination of predictors of 3-month mortality or persisting impairment using logistic regression. A hierarchical clustering on principal components was also done for neurological and bacteraemic cases. The study is registered at ClinicalTrials.gov, number NCT01520597.
FINDINGS
We enrolled 818 cases from 372 centres, including 107 maternal-neonatal infections, 427 cases of bacteraemia, and 252 cases of neurolisteriosis. Only five (5%) of 107 pregnant women had an uneventful outcome. 26 (24%) of 107 mothers experienced fetal loss, but never after 29 weeks of gestation or beyond 2 days of admission to hospital. Neurolisteriosis presented as meningoencephalitis in 212 (84%) of 252 patients; brainstem involvement was only reported in 42 (17%) of 252 patients. 3-month mortality was higher for bacteraemia than neurolisteriosis (hazard ratio [HR] 0·54 [95% CI 0·41-0·69], p<0·0001). For both bacteraemia and neurolisteriosis, the strongest mortality predictors were ongoing cancer (odds ratio [OR] 5·19 [95% CI 3·01-8·95], p<0·0001), multi-organ failure (OR 7·98 [4·32-14·72], p<0·0001), aggravation of any pre-existing organ dysfunction (OR 4·35 [2·79-6·81], p<0·0001), and monocytopenia (OR 3·70 [1·82-7·49], p=0·0003). Neurolisteriosis mortality was higher in blood-culture positive patients (OR 3·67 [1·60-8·40], p=0·002) or those receiving adjunctive dexamethasone (OR 4·58 [1·50-13·98], p=0·008).
INTERPRETATION
The severity of listeriosis is higher than reported elsewhere. We found evidence of a significantly reduced survival in patients with neurolisteriosis treated with adjunctive dexamethasone, and also determined the time window for fetal losses. MONALISA provides important new data to improve management and predict outcome in listeriosis.
FUNDING
Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.
Topics: Adult; Aged; Bacteremia; Female; Foodborne Diseases; France; Hospitalization; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infectious Disease Transmission, Vertical; Listeria monocytogenes; Listeriosis; Male; Mandatory Reporting; Meningoencephalitis; Population Surveillance; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Prospective Studies; Risk Factors
PubMed: 28139432
DOI: 10.1016/S1473-3099(16)30521-7 -
Clinical Chemistry and Laboratory... Feb 2021
Topics: Humans; Leukemia, Hairy Cell; Leukopenia
PubMed: 32383689
DOI: 10.1515/cclm-2020-0253 -
Immunology Letters Oct 2014Recurrent or prolonged severe infections associated to panleukopenia strongly suggest primary immune disorders. In recent years, new immunodeficiency syndromes turned... (Review)
Review
Recurrent or prolonged severe infections associated to panleukopenia strongly suggest primary immune disorders. In recent years, new immunodeficiency syndromes turned up: besides the importance of continuous clinical characterization throughout added reports, the phenotype can easily lead to diagnosis of known rare entities. Our purpose is to review main emerging genetic syndromes featuring lymphopenia combined to neutropenia and/or monocytopenia in order to facilitate diagnosis of rare primary immune deficiencies.
Topics: Diagnosis, Differential; GATA2 Transcription Factor; Glucosephosphate Dehydrogenase Deficiency; Humans; Immunologic Deficiency Syndromes; Intracellular Signaling Peptides and Proteins; Leukopenia; Lymphopenia; Monocytes; Neutropenia; Primary Immunodeficiency Diseases; Protein Serine-Threonine Kinases; Warts
PubMed: 24316408
DOI: 10.1016/j.imlet.2013.11.018 -
International Journal of Molecular... Jun 2019The PI3K/Akt pathway plays a crucial role in the survival, proliferation, and migration of macrophages, which may impact the development of atherosclerosis. Changes in... (Review)
Review
The PI3K/Akt pathway plays a crucial role in the survival, proliferation, and migration of macrophages, which may impact the development of atherosclerosis. Changes in Akt isoforms or modulation of the Akt activity levels in macrophages significantly affect their polarization phenotype and consequently atherosclerosis in mice. Moreover, the activity levels of Akt signaling determine the viability of monocytes/macrophages and their resistance to pro-apoptotic stimuli in atherosclerotic lesions. Therefore, elimination of pro-apoptotic factors as well as factors that antagonize or suppress Akt signaling in macrophages increases cell viability, protecting them from apoptosis, and this markedly accelerates atherosclerosis in mice. In contrast, inhibition of Akt signaling by the ablation of Rictor in myeloid cells, which disrupts mTORC2 assembly, significantly decreases the viability and proliferation of blood monocytes and macrophages with the suppression of atherosclerosis. In addition, monocytes and macrophages exhibit a threshold effect for Akt protein levels in their ability to survive. Ablation of two Akt isoforms, preserving only a single Akt isoform in myeloid cells, markedly compromises monocyte and macrophage viability, inducing monocytopenia and diminishing early atherosclerosis. These recent advances in our understanding of Akt signaling in macrophages in atherosclerosis may have significant relevance in the burgeoning field of cardio-oncology, where PI3K/Akt inhibitors being tested in cancer patients can have significant cardiovascular and metabolic ramifications.
Topics: Animals; Apoptosis; Atherosclerosis; Blood Cells; Cell Survival; Humans; Macrophage Activation; Macrophages; Phosphatidylinositol 3-Kinases; Protein Isoforms; Proto-Oncogene Proteins c-akt; Signal Transduction
PubMed: 31159424
DOI: 10.3390/ijms20112703 -
EMBO Molecular Medicine Oct 2020Early in the COVID-19 pandemic, type 2 diabetes (T2D) was marked as a risk factor for severe disease and mortality. Inflammation is central to the aetiology of both... (Observational Study)
Observational Study
Early in the COVID-19 pandemic, type 2 diabetes (T2D) was marked as a risk factor for severe disease and mortality. Inflammation is central to the aetiology of both conditions where variations in immune responses can mitigate or aggravate disease course. Identifying at-risk groups based on immunoinflammatory signatures is valuable in directing personalised care and developing potential targets for precision therapy. This observational study characterised immunophenotypic variation associated with COVID-19 severity in T2D. Broad-spectrum immunophenotyping quantified 15 leucocyte populations in peripheral circulation from a cohort of 45 hospitalised COVID-19 patients with and without T2D. Lymphocytopenia and specific loss of cytotoxic CD8 lymphocytes were associated with severe COVID-19 and requirement for intensive care in both non-diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia restricted to classical CD14 CD16 monocytes was specifically associated with severe COVID-19 in patients with T2D requiring intensive care. Increased expression of inflammatory markers reminiscent of the type 1 interferon pathway (IL6, IL8, CCL2, INFB1) underlaid the immunophenotype associated with T2D. These immunophenotypic and hyperinflammatory changes may contribute to increased voracity of COVID-19 in T2D. These findings allow precise identification of T2D patients with severe COVID-19 as well as provide evidence that the type 1 interferon pathway may be an actionable therapeutic target for future studies.
Topics: Aged; COVID-19; Chemokine CCL2; Diabetes Mellitus, Type 2; Female; Humans; Immunophenotyping; Inflammation; Interleukin-6; Leukocytes, Mononuclear; Lipopolysaccharide Receptors; Lymphopenia; Male; Middle Aged; Monocytes; Risk Factors; SARS-CoV-2; Severity of Illness Index
PubMed: 32816392
DOI: 10.15252/emmm.202013038 -
BMJ Case Reports Jan 2019A 26-year-old man with history of schizophrenia was admitted for neutropaenia. He was started on clozapine 3 months prior to admission. As a result he had weekly...
A 26-year-old man with history of schizophrenia was admitted for neutropaenia. He was started on clozapine 3 months prior to admission. As a result he had weekly monitoring of his blood counts and on day of admission was noted to have an absolute neutrophil count (ANC) of 450 cells/μL. He was admitted for clozapine-induced agranulocytosis. Clozapine was held and the patient was started on granulocyte colony-stimulating factor (G-CSF) filgrastim and received two doses without any signs of ANC recovery. On further review, it was noted that the absolute monocyte count (AMC) was also low and tracked with the trend of ANC. We then theorised that the impact of clozapine was on a haematopoietic precursor (colony-forming unit granulocyte-macrophage, CFU-GM) which gives rise to both monocytic and myeloid lineages. Therefore, sargramostim GM-CSF was started. After two doses, the ANC and AMC started trending up and by the third dose, both counts had fully recovered. He was discharged from the hospital and there are no plans to rechallenge with clozapine. Thus, we demonstrate a case of monocytopenia accompanying clozapine-induced agranulocytosis with successful use of GM-CSF. At least in this case, the target of the clozapine injury appears to be the CFU-GM, explaining the rapid and full response to GM-CSF after lack of response to G-CSF.
Topics: Adult; Agranulocytosis; Clozapine; Filgrastim; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Monocytes; Neutropenia; Recombinant Proteins; Schizophrenia; Treatment Outcome
PubMed: 30661042
DOI: 10.1136/bcr-2018-226016 -
Shock (Augusta, Ga.) Aug 2020
Topics: Case-Control Studies; Hospital Mortality; Humans; Monocytes; Sepsis; Shock, Septic
PubMed: 31851122
DOI: 10.1097/SHK.0000000000001493 -
Bulletin of Mathematical Biology Jul 2020In spite of the recent focus on the development of novel targeted drugs to treat cancer, cytotoxic chemotherapy remains the standard treatment for the vast majority of...
In spite of the recent focus on the development of novel targeted drugs to treat cancer, cytotoxic chemotherapy remains the standard treatment for the vast majority of patients. Unfortunately, chemotherapy is associated with high hematopoietic toxicity that may limit its efficacy. We have previously established potential strategies to mitigate chemotherapy-induced neutropenia (a lack of circulating neutrophils) using a mechanistic model of granulopoiesis to predict the interactions defining the neutrophil response to chemotherapy and to define optimal strategies for concurrent chemotherapy/prophylactic granulocyte colony-stimulating factor (G-CSF). Here, we extend our analyses to include monocyte production by constructing and parameterizing a model of monocytopoiesis. Using data for neutrophil and monocyte concentrations during chemotherapy in a large cohort of childhood acute lymphoblastic leukemia patients, we leveraged our model to determine the relationship between the monocyte and neutrophil nadirs during cyclic chemotherapy. We show that monocytopenia precedes neutropenia by 3 days, and rationalize the use of G-CSF during chemotherapy by establishing that the onset of monocytopenia can be used as a clinical marker for G-CSF dosing post-chemotherapy. This work therefore has important clinical applications as a comprehensive approach to understanding the relationship between monocyte and neutrophils after cyclic chemotherapy with or without G-CSF support.
Topics: Antineoplastic Agents; Granulocyte Colony-Stimulating Factor; Humans; Models, Biological; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 32737602
DOI: 10.1007/s11538-020-00777-0 -
Nature Immunology Jun 2022Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting...
Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.
Topics: Animals; Humans; Hypoxia; Inflammation; Lung; Lung Injury; Mice; Respiratory Distress Syndrome
PubMed: 35624205
DOI: 10.1038/s41590-022-01216-z