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International Journal of Molecular... Feb 2023Lower-than-normal platelet counts are a hallmark of the acquired autoimmune illness known as immune thrombocytopenia, which can affect both adults and children. Immune... (Review)
Review
Lower-than-normal platelet counts are a hallmark of the acquired autoimmune illness known as immune thrombocytopenia, which can affect both adults and children. Immune thrombocytopenia patients' care has evolved significantly in recent years, but the disease's diagnosis has not, and it is still only clinically achievable with the elimination of other causes of thrombocytopenia. The lack of a valid biomarker or gold-standard diagnostic test, despite ongoing efforts to find one, adds to the high rate of disease misdiagnosis. However, in recent years, several studies have helped to elucidate a number of features of the disease's etiology, highlighting how the platelet loss is not only caused by an increase in peripheral platelet destruction but also involves a number of humoral and cellular immune system effectors. This made it possible to identify the role of immune-activating substances such cytokines and chemokines, complement, non-coding genetic material, the microbiome, and gene mutations. Furthermore, platelet and megakaryocyte immaturity indices have been emphasized as new disease markers, and prognostic signs and responses to particular types of therapy have been suggested. Our review's goal was to compile information from the literature on novel immune thrombocytopenia biomarkers, markers that will help us improve the management of these patients.
Topics: Child; Adult; Humans; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Blood Platelets; Megakaryocytes; Biomarkers
PubMed: 36901864
DOI: 10.3390/ijms24054438 -
Blood Advances Jul 2023Graduate medical education training in hematology in North America is accredited by the Accreditation Council for Graduate Medical Education (ACGME). Trainees routinely...
Graduate medical education training in hematology in North America is accredited by the Accreditation Council for Graduate Medical Education (ACGME). Trainees routinely review peripheral blood smears (PBS) in providing clinical care. Competency in PBS review at graduation is required by the ACGME. However, there are no consensus guidelines on best practices surrounding PBS review, education, or competency. We describe the generation of proposed theory and the consensus recommendations developed through a multi-institutional focus group, developed using constructivist grounded theory and a modified nominal group technique. Eight academic hematologists, spanning classical and malignant hematology, enrolled and participated in 2 one-hour focus groups. All routinely worked with fellows and half had formally instructed trainees on PBS interpretation. Focus group data were analyzed using mixed-methods techniques. Tenets of emerging theory were identified through inductive coding. Consensus recommendations (CR) were generated. Participants reviewed CR in an iterative fashion until consensus was reached. Strong consensus was reached on multiple aspects of PBS education. All agreed that trainees should learn PBS review through a systematic approach. Group discussion focused on disorders of red and white blood cells. The diagnoses of acute leukemia and thrombotic microangiopathies were most commonly discussed, with specific emphasis on disorders in which prompt recognition was required to avert significant patient morbidity. These CR offer external validity to future research and curricular development for both PBS review and other visuospatial tasks in medical education.
Topics: Humans; Clinical Competence; Education, Medical, Graduate; Accreditation; Hematology; North America
PubMed: 36930800
DOI: 10.1182/bloodadvances.2023009843 -
Current Medicinal Chemistry 2022Clinical situations arise in which blood for transfusion becomes scarce or unavailable. Considerable demand for a transfusion alternative persists because of various... (Review)
Review
Clinical situations arise in which blood for transfusion becomes scarce or unavailable. Considerable demand for a transfusion alternative persists because of various difficulties posed by blood donation and transfusion systems. Hemoglobin-vesicles (Hb- V) are artificial oxygen carriers being developed for use as a transfusion alternative. Just as biomembranes of red blood cells (RBCs) do, phospholipid vesicles (liposomes) for Hb encapsulation can protect the human body from the toxic effects of molecular Hb. The main HbV component, Hb, is obtained from discarded human donated blood. Therefore, HbV can be categorized as a biologic agent targeting oxygen for peripheral tissues. The purification procedure strictly eliminates the possibility of viral contamination. It also removes all concomitant unstable enzymes present in RBC for utmost safety from infection. The deoxygenated HbVs, which are storable for over the years at ambient temperature, can function as an alternative to blood transfusion for resuscitation from hemorrhagic shock and O2 therapeutics. Moreover, a recent study clarified beneficial effects for anti- oxidation and anti-inflammation by carbon monoxide (CO)-bound HbVs. Autoxidation of HbV (HbO2 → metHb + O2 -.) is unavoidable after intravenous administration. Co-injection of methylene blue can extract the intraerythrocytic glycolytic electron energy effectively and reduce metHb. Other phenothiazine dyes can also function as electron mediators to improve the functional life span of HbV. This review paper summarizes recent progress of the research and development of HbV, aimed at clinical applications.
Topics: Blood Transfusion; Erythrocytes; Hemoglobins; Humans; Oxygen; Shock, Hemorrhagic; Translational Research, Biomedical
PubMed: 33845721
DOI: 10.2174/0929867328666210412130035 -
The Journal of Hand Surgery Apr 2017To review the causes, clinical course, and management of patients with catheter-associated radial artery pseudoaneurysm (PSA).
PURPOSE
To review the causes, clinical course, and management of patients with catheter-associated radial artery pseudoaneurysm (PSA).
METHODS
We reviewed all patients diagnosed with radial artery PSA resulting from arterial line placement or radial artery access for cardiac procedures from 2010 to 2015.
RESULTS
We identified 11 cases: 5 caused by arterial lines and 6 by cardiac procedures. The diagnosis was confirmed by duplex ultrasound in all cases; PSA size ranged from less than 1 cm to 5 cm in diameter. Spontaneous thrombosis (over a mean of 27 days) occurred in 4 patients; each PSA was smaller than 3 cm. Surgery was performed in 7 patients with excision of the stalk and repair of the artery as the most common procedure. Only one case was performed emergently for acute carpal tunnel syndrome. Complications occurring owing to either the PSA or the treatment were recorded in 5 patients.
CONCLUSIONS
Spontaneous thrombosis may occur in smaller lesions over a few weeks. When required, surgery to evacuate the hematoma and repair the artery was effective in all cases.
TYPE OF STUDY/LEVEL OF EVIDENCE
Therapeutic IV.
Topics: Aged; Aged, 80 and over; Aneurysm, False; Catheterization, Peripheral; Computed Tomography Angiography; Female; Hematoma; Humans; Male; Middle Aged; Radial Artery; Retrospective Studies; Thrombosis; Ultrasonography
PubMed: 28258867
DOI: 10.1016/j.jhsa.2017.01.024 -
Contrast Media & Molecular Imaging 2022The purpose of this study was to investigate the absolute value of peripheral blood lymphocytes in patients with primary immune thrombocytopenia and the diagnostic...
The purpose of this study was to investigate the absolute value of peripheral blood lymphocytes in patients with primary immune thrombocytopenia and the diagnostic effect on patients with primary immune thrombocytopenia. From January 2020 to June 2021, 76 patients with primary immune thrombocytopenia and 80 healthy check-ups admitted to our hospital were selected as study subjects and divided into a control group (80 patients, healthy check-ups) and an observation group (76 patients, primary immune thrombocytopenia), according to the health status of the organism. Early morning fasting venous blood was collected from both groups, and the absolute value of peripheral blood lymphocytes was measured and compared using a fully automated hematology analyzer to investigate the diagnostic value of absolute peripheral blood lymphocytes in primary immune thrombocytopenia. The CD3+, CD3+CD4+, CD4+/CD8+, and CD16+CD56+ assay values in the observation group were lower than those in the control group, and the CD3+CD8+, CD19+, and ALC assay values were higher than those in the control group ( < 0.05). The CD3+CD8+ detection values of newly diagnosed patients were similar to those of relapsed refractory patients ( > 0.05); CD3+, CD3+CD4+, CD4+/CD8+, and CD16+CD56+ detection values of newly diagnosed patients were lower than those of relapsed refractory patients, and CD19+ and ALC detection values were higher than those of relapsed refractory patients; CD3+, CD3+CD4+, CD4+, CD4+/CD8+, and CD16+CD56+ detection values of mild patients were lower than those of relapsed refractory patients; CD3+, CD3+CD4+, CD4+/CD8+, and CD16+CD56+ detection values were higher in mild patients than in severe patients, and CD3+CD8+, CD19+, and ALC detection values were lower than in severe patients ( < 0.05). The absolute lymphocyte values were of high diagnostic value in primary immune thrombocytopenia, with a sensitivity and specificity of 93.42% and 90.00%. The application of absolute peripheral blood lymphocyte value in the clinical diagnosis of primary immune thrombocytopenia can achieve a better detection and diagnosis effect, which has a positive impact on the early diagnosis rate and can help patients to obtain more timely, effective and targeted treatment, and is worthy of promotion.
Topics: Humans; Lymphocytes; Purpura, Thrombocytopenic, Idiopathic
PubMed: 36072617
DOI: 10.1155/2022/9833941 -
Biosensors Dec 2022Hemorrhage is the leading cause of preventable death from trauma. Accurate monitoring of hemorrhage and resuscitation can significantly reduce mortality and morbidity...
Hemorrhage is the leading cause of preventable death from trauma. Accurate monitoring of hemorrhage and resuscitation can significantly reduce mortality and morbidity but remains a challenge due to the low sensitivity of traditional vital signs in detecting blood loss and possible hemorrhagic shock. Vital signs are not reliable early indicators because of physiological mechanisms that compensate for blood loss and thus do not provide an accurate assessment of volume status. As an alternative, machine learning (ML) algorithms that operate on an arterial blood pressure (ABP) waveform have been shown to provide an effective early indicator. However, these ML approaches lack physiological interpretability. In this paper, we evaluate and compare the performance of ML models trained on nine ABP-derived features that provide physiological insight, using a database of 13 human subjects from a lower-body negative pressure (LBNP) model of progressive central hypovolemia and subsequent progressive restoration to normovolemia (i.e., simulated hemorrhage and whole blood resuscitation). Data were acquired at multiple repressurization rates for each subject to simulate varying resuscitation rates, resulting in 52 total LBNP collections. This work is the first to use a single ABP-based algorithm to monitor both simulated hemorrhage resuscitation. A gradient-boosted regression tree model trained on only the half-rise to dicrotic notch (HRDN) feature achieved a root-mean-square error (RMSE) of 13%, an R of 0.82, and area under the receiver operating characteristic curve of 0.97 for detecting decompensation. This single-feature model's performance compares favorably to previously reported results from more-complex black box machine learning models. This model further provides physiological insight because HRDN represents an approximate measure of the delay between the ABP ejected and reflected wave and therefore is an indication of cardiac and peripheral vascular mechanisms that contribute to the compensatory response to blood loss and replacement.
Topics: Humans; Blood Pressure; Blood Volume; Hemorrhage; Hypovolemia; Vital Signs
PubMed: 36551134
DOI: 10.3390/bios12121168 -
Journal of Stroke and Cerebrovascular... Jul 2022There is limited evidence on the effect and relevance of cardiovascular parameters on the cerebrovascular system when an intracerebral hemorrhage (ICH) occurs. While...
BACKGROUND
There is limited evidence on the effect and relevance of cardiovascular parameters on the cerebrovascular system when an intracerebral hemorrhage (ICH) occurs. While recent studies evaluating this relationship are conflicting, one evaluating the effect of systolic cardiac function on clinical outcomes in ICH patients, found low cardiac ejection fractions to be associated with poor clinical outcomes. Our primary objective was to study such correlations and identify various cardiovascular disease states that may be associated with hematoma expansion.
METHODS
This is an IRB-approved single-center retrospective study utilizing our institutional "Get with the Guidelines"-Stroke registry between 2013 and 2017. Patients included were older than 18 years of age, admitted with an acute ICH, and had an echocardiogram during their hospitalization. Univariate and multivariate logistical regression analyses were used to identify cardiovascular predictors of hematoma expansion.
RESULTS
Two-hundred forty-nine patients were identified from our GWTG-S registry that met initial inclusion criteria. Of these patients, a history of peripheral arterial disease (PAD) (p = 0.015), presence of aortic stenosis (AS) on the echocardiogram (p = 0.025), and a positive spot sign on the CT-angiogram (CTA) of the head (p < 0.001) were found to be independently associated with ICH expansion. Both a history of hypertension and elevated blood pressure on presentation were not significant predictors. Additionally, patients with a history of congestive heart failure had decreased odds of hematoma expansion (p = 0.027).
CONCLUSION
This exploratory study highlights potential novel cardiac predictors of hematoma expansion, including PAD and AS, which warrant further study. Larger prospective studies are needed to further investigate such associations to ultimately optimize cardio-cerebral health.
Topics: Cerebral Angiography; Cerebral Hemorrhage; Hematoma; Humans; Predictive Value of Tests; Retrospective Studies
PubMed: 35523053
DOI: 10.1016/j.jstrokecerebrovasdis.2022.106527 -
Clinical and Translational Medicine Sep 2023Peripheral immune cells play important roles in the maintenance of systemic and microenvironmental hemostasis. Measurements of circulating blood cells by single-cell RNA...
Peripheral immune cells play important roles in the maintenance of systemic and microenvironmental hemostasis. Measurements of circulating blood cells by single-cell RNA sequencing (scRNA-seq) were proposed as one of the routine measures in clinical biochemistry of hematology. Out of translational challenges, defining precise identities of cell subsets and states is more difficult, due to the complexity of immune cell development, location, regulation, function, and metabolism. It is also a challenge to precisely interpret clinical significance and impact of each cell identity marker gene panel (ciMGPs). ciMGPs have potential to advance the understanding of systemic responses of the disease, identify disease-specific biomarkers, and to define cell heterogeneity. Recently, a large number of peripheral cell subsets and expending/activating states have been identified and validated for use in the fast developments in clinical single cell biomedicine. Defining specificity, measurability, and repeatability of cell subsets/states is important for translation of peripheral scRNA-seq in clinical hematology and biochemistry. The development of standard operating procedure and performance of clinical trials in large populations at various ages, diseases, and therapies will promote the clinical translation of ciMGPs to measures. Thus, defining cell subset/state identities will provide the multi-dimensional and comprehensive readouts of systemic immune cells, the precision monitoring of immune dynamics, and deeper-understanding of the disease and response to therapy.
Topics: Cell Differentiation; Clinical Relevance; Hematology
PubMed: 37700496
DOI: 10.1002/ctm2.1401 -
Experimental Neurology Sep 2023Intracerebral hemorrhage (ICH) is a severe neurological condition with high mortality and morbidity. Microglia activation and peripheral inflammatory cells infiltration...
Recruitment of regulatory T cells with rCCL17 promotes M2 microglia/macrophage polarization through TGFβ/TGFβR/Smad2/3 pathway in a mouse model of intracerebral hemorrhage.
AIMS
Intracerebral hemorrhage (ICH) is a severe neurological condition with high mortality and morbidity. Microglia activation and peripheral inflammatory cells infiltration play an important role in ICH prognosis. Previous studies demonstrated that regulatory T cells (Tregs) ameliorated neuroinflammation following experimental ICH. However, the molecular mechanism underlying such effects of Tregs remains unclear. The objective was to examine how Tregs recruitment induced by recombinant CC chemokine ligand 17 (rCCL17) influences microglia/macrophage polarization in an intrastriatal autologous blood injection ICH animal model, and to determine if TGFβ/TGFβ-R/Smad2/3 pathway was involved.
METHODS
380 adult CD1 mice (male, eight weeks old) were subjected to sham surgery or autologous blood injection induced ICH. A CD25-specific mouse antibody or isotype control mAb was injected intraventricular (i.c.v) 48 h prior to ICH induction to deplete Tregs. rCCL17, a CC chemokine receptor 4 (CCR4) ligand, was delivered intranasally at 1 h post-ICH. SB431542, a specific inhibitor of TGF-β was administered intraperitoneally 1 h before ICH induction. Following the ICH, neurobehavioral testing, brain edema, hematoma volume, hemoglobin content, western blotting, double immunofluorescence labeling, and immunohistochemistry were performed.
RESULTS
Endogenous expressions of CCL17, Tregs marker Foxp3, and the number of Tregs in perihematomal region increased following ICH. Tregs depletion with a CD25 antibody aggravated neurological deficits and brain edema, increased inflammatory cytokines, neutrophil infiltration, oxidative stress, and reduced the rate of hematoma resolution in ICH mice. rCCL17 treatment increased the number of Tregs in the brain, ameliorated neurological deficits and brain edema after ICH, and promoted microglia/macrophage polarization toward M2 phenotype which was reversed with CD25 antibody. Moreover, rCCL17 increased the expressions of brain TGF-β/phosphorylated-Smad2/3 which was abrogated with the selective TGFβ inhibitor SB431542.
CONCLUSIONS
rCCL17-mediated Tregs recruitment may be a potential therapeutic strategy to promote M2 microglia/macrophages polarization and alleviate early brain injury following ICH.
Topics: Mice; Male; Animals; Microglia; Brain Edema; Chemokines, CC; T-Lymphocytes, Regulatory; Ligands; Macrophages; Cerebral Hemorrhage; Immunologic Factors; Disease Models, Animal; Transforming Growth Factor beta; Hematoma
PubMed: 37257716
DOI: 10.1016/j.expneurol.2023.114451 -
Cellular and Molecular Neurobiology Oct 2018Cerebral hemorrhage is a series of devastating cerebrovascular diseases with high mortality, morbidity and recurrence rate. Localized and systemic immuno-reactions are... (Review)
Review
Cerebral hemorrhage is a series of devastating cerebrovascular diseases with high mortality, morbidity and recurrence rate. Localized and systemic immuno-reactions are involved. Aggregation of immunocytes, which were both recruited from the peripheral circulation and resident in the central nervous system, is induced and activated by hematoma-related blood components. Subsequently, various cytokines, chemokines, free radicals and toxic chemicals are secreted to participant host defense responses. Among these, neuro-inflammation plays critical roles in both the pathologic processes of secondary injuries and recovery of neural damages. Numerous treatment strategies have been proposed, aiming at controlling the balance between anti- and proinflammation. Here, we summarized our current understanding and potential clinical applications for cytokines of the interleukin family in the pathogenesis of hemorrhagic stroke. In addition, we conducted protein-protein network, gene ontology and KEGG analysis on the interleukins using online bioinformatic tools to further elaborate the comprehensive mechanisms of interleukins in cerebral hemorrhage.
Topics: Animals; Cerebral Hemorrhage; Cytokines; Humans; Inflammation; Inflammation Mediators; Interleukins; Signal Transduction
PubMed: 30027390
DOI: 10.1007/s10571-018-0601-x