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Frontiers in Immunology 2021Preclinical and clinical research has demonstrated that inflammation is a critical factor regulating intracerebral hemorrhage (ICH)-induced brain injury. Growing...
Preclinical and clinical research has demonstrated that inflammation is a critical factor regulating intracerebral hemorrhage (ICH)-induced brain injury. Growing evidence suggests that myeloid cells and lymphocytes have an effect on the pathophysiological processes associated with ICH, such as inflammation, immune responses, perihematomal edema formation, blood-brain barrier (BBB) integrity, and cell death. However, the underlying mechanisms remain largely unknown. We aimed to explore the role immune cells played at different stages of the ICH. To achieve this, novel bioinformatics algorithms were employed to analyze the gene expression profiles and three different analytical tools were utilized to predict the abundances of cell types. In this study, we found that natural killer (NK) cells infiltrated into the brain parenchyma after ICH. Infiltrating NK cells may mediate brain injury through degranulation and recruitment of other cells. Besides, in the acute phase of ICH, monocytes in peripheral blood carried out phagocytosis and secretion of cytokines. On the other hand, in the subacute stage, non-classical monocytes were activated and showed a stronger ability to carry out heme metabolism, wound healing, and antigen processing and presentation. In conclusion, our findings emphasize the significance of intracerebral infiltrating immunocytes in ICH and demonstrate that ICH is a systemic disease affected by peripheral blood. The hub genes identified might be promising therapeutic targets. We also provide a reference on how to use bioinformatics approaches to explore non-neoplastic immune-related diseases.
Topics: Animals; Brain; Cerebral Hemorrhage; Disease Models, Animal; Disease Susceptibility; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Immunohistochemistry; Killer Cells, Natural; Leukocytes; Male; Mice; Monocytes
PubMed: 33659003
DOI: 10.3389/fimmu.2021.617163 -
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 -
Blood Reviews Jan 2024Immune thrombocytopenia (ITP) is a rare autoimmune condition, due to peripheral platelet destruction through antibody-dependent cellular phagocytosis,... (Review)
Review
Immune thrombocytopenia (ITP) is a rare autoimmune condition, due to peripheral platelet destruction through antibody-dependent cellular phagocytosis, complement-dependent cytotoxicity, cytotoxic T lymphocyte-mediated cytotoxicity, and megakaryopoiesis alteration. This condition may be idiopathic or triggered by drugs, vaccines, infections, cancers, autoimmune disorders and systemic diseases. Recent advances in our understanding of ITP immunobiology support the idea that other forms of thrombocytopenia, for instance, occurring after immunotherapy or cellular therapies, may share a common pathophysiology with possible therapeutic implications. If a decent pipeline of old and new agents is currently deployed for classical ITP, in other more complex immune-mediated thrombocytopenic disorders, clinical management is less harmonized and would deserve further prospective investigations. Here, we seek to provide a fresh overview of pathophysiology and current therapeutical algorithms for adult patients affected by this disorder with specific insights into poorly codified scenarios, including refractory ITP and post-immunotherapy/cellular therapy immune-mediated thrombocytopenia.
Topics: Adult; Humans; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Immunotherapy; Blood Platelets
PubMed: 37980261
DOI: 10.1016/j.blre.2023.101141 -
Experimental Biology and Medicine... Apr 2017The ability to quickly diagnose hemorrhagic shock is critical for favorable patient outcomes. Therefore, it is important to understand the time course and involvement of... (Review)
Review
The ability to quickly diagnose hemorrhagic shock is critical for favorable patient outcomes. Therefore, it is important to understand the time course and involvement of the various physiological mechanisms that are active during volume loss and that have the ability to stave off hemodynamic collapse. This review provides new insights about the physiology that underlies blood loss and shock in humans through the development of a simulated model of hemorrhage using lower body negative pressure. In this review, we present controlled experimental results through utilization of the lower body negative pressure human hemorrhage model that provide novel insights on the integration of physiological mechanisms critical to the compensation for volume loss. We provide data obtained from more than 250 human experiments to classify human subjects into two distinct groups: those who have a high tolerance and can compensate well for reduced central blood volume (e.g. hemorrhage) and those with low tolerance with poor capacity to compensate.We include the conceptual introduction of arterial pressure and cerebral blood flow oscillations, reflex-mediated autonomic and neuroendocrine responses, and respiration that function to protect adequate tissue oxygenation through adjustments in cardiac output and peripheral vascular resistance. Finally, unique time course data are presented that describe mechanistic events associated with the rapid onset of hemodynamic failure (i.e. decompensatory shock). Impact Statement Hemorrhage is the leading cause of death in both civilian and military trauma. The work submitted in this review is important because it advances the understanding of mechanisms that contribute to the total integrated physiological compensations for inadequate tissue oxygenation (i.e. shock) that arise from hemorrhage. Unlike an animal model, we introduce the utilization of lower body negative pressure as a noninvasive model that allows for the study of progressive reductions in central blood volume similar to those reported during actual hemorrhage in conscious humans to the onset of hemodynamic decompensation (i.e. early phase of decompensatory shock), and is repeatable in the same subject. Understanding the fundamental underlying physiology of human hemorrhage helps to test paradigms of critical care medicine, and identify and develop novel clinical practices and technologies for advanced diagnostics and therapeutics in patients with life-threatening blood loss.
Topics: Arterial Pressure; Blood Volume; Hemodynamics; Humans; Models, Cardiovascular; Oxygen; Shock, Hemorrhagic
PubMed: 28346013
DOI: 10.1177/1535370217694099 -
Journal of Clinical Laboratory Analysis Oct 2022Chronic subdural hematoma (CSDH) is a common neurosurgical disease with an increasing incidence. The absorption route of CSDH is not clear. Whether inflammatory factors...
BACKGROUND
Chronic subdural hematoma (CSDH) is a common neurosurgical disease with an increasing incidence. The absorption route of CSDH is not clear. Whether inflammatory factors enter the peripheral blood and cause systemic reactions is unknown.
METHODS
We screened 105 CSDH patients and 105 control individuals. Their clinical characteristics and blood routine results were collected and compared. The blood routine changes of CSDH patients before and after treatment were compared. Age-stratified analysis was performed due to age may affect the inflammatory markers.
RESULTS
The white blood cell count, absolute neutrophil count, neutrophil percentage, neutrophil-lymphocyte count ratio (NLR), and platelet to lymphocyte count ratio (PLR) of CSDH patients before treatment were within the normal range, while were significantly higher than the control individuals (p < 0.001). The absolute lymphocyte count and lymphocyte percentage of control individuals were higher than those of patients (p < 0.001). The inflammatory cells in patients of different age groups were similar. After the patient was cured, the white blood cell count, the absolute value and percentage of neutrophils decreased (p < 0.05), while the number of monocytes increased.
CONCLUSIONS
CSDH caused slight systemic inflammatory responses in the peripheral blood, implying that there is a non-hematologic route for the absorption of hematoma.
Topics: Hematoma, Subdural, Chronic; Humans; Leukocyte Count; Lymphocyte Count; Lymphocytes; Neutrophils; Retrospective Studies
PubMed: 36114782
DOI: 10.1002/jcla.24706 -
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 -
The Cochrane Database of Systematic... Nov 2016Drains are often used in leg wounds after vascular surgery procedures despite uncertainty regarding their benefits. Drains are placed with the aim of reducing the... (Review)
Review
BACKGROUND
Drains are often used in leg wounds after vascular surgery procedures despite uncertainty regarding their benefits. Drains are placed with the aim of reducing the incidence and size of blood or fluid collections. Conversely, drains may predispose patients to infection and may prolong hospitalisation. Surgeons need robust data regarding the effects of drains on complications following lower limb arterial surgery.
OBJECTIVES
To determine whether routine placement of wound drains results in fewer complications following lower limb arterial surgery than no drains.
SEARCH METHODS
In June 2016 we searched: the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. We also searched clinical trial registries for ongoing studies.There were no restrictions with respect to language, date of publication or study setting.
SELECTION CRITERIA
We considered randomized controlled trials (RCTs) that evaluated the use of any type of drain in lower limb arterial surgery.
DATA COLLECTION AND ANALYSIS
Two authors independently determined study eligibility, extracted data and performed an assessment of bias. An effort was made to contact authors for missing data. The methods and results of each eligible study were summarised and we planned to pool data in meta-analyses when it was considered appropriate, based upon clinical and statistical homogeneity.
MAIN RESULTS
We identified three eligible trials involving a total of 222 participants with 333 groin wounds. Suction drainage was compared with no drainage in all studies. Two studies were parallel-group, randomized controlled trials, and one was a split-body, randomized controlled trial. Trial settings were not clearly described. Patients undergoing bypass and endarterectomy procedures were included, but none of the studies provided details on the severity of the underlying arterial disease.We deemed all of the studies to be at a high risk of bias in three or more domains of the 'Risk of bias' assessment and overall the evidence was of very low quality. Two out of three studies had unit of analysis errors (with multiple wounds within patients analysed as independent) and it was not possible to judge the appropriateness of the analysis of the third. Meta-analysis was not appropriate, firstly because of clinical heterogeneity, and secondly because we were not able to adjust for the analysis errors in the individual trials. One trial yielded data on surgical site infections (SSI; the primary outcome of the review): there was no clear difference between drained and non-drained wounds for SSI (risk ratio 1.33; 95% confidence interval 0.30 to 5.94; 50 participants with bilateral groin wounds; very low quality evidence). It was not possible to evaluate any other outcomes from this trial. The results from the other two studies are unreliable because of analysis errors and reporting omissions.
AUTHORS' CONCLUSIONS
The data upon which to base practice in this area are limited and prone to biases. Complete uncertainty remains regarding the potential benefits and harms associated with the use of wound drains in lower limb arterial surgery due to the small number of completed studies and weaknesses in their design and conduct. Higher quality evidence is needed to inform clinical decision making. To our knowledge, no trials on this topic are currently active.
Topics: Aged; Drainage; Female; Groin; Hematoma; Humans; Lower Extremity; Male; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Reoperation; Suction; Surgical Wound Infection; Vascular Surgical Procedures
PubMed: 27841438
DOI: 10.1002/14651858.CD011111.pub2 -
Journal of Thrombosis and Haemostasis :... Jan 2017The recent discovery that von Willebrand factor (VWF) regulates blood vessel formation has opened a novel perspective on the function of this complex protein. VWF was... (Review)
Review
The recent discovery that von Willebrand factor (VWF) regulates blood vessel formation has opened a novel perspective on the function of this complex protein. VWF was discovered as a key component of hemostasis, capturing platelets at sites of endothelial damage and synthesized in megakaryocytes and endothelial cells (EC). In recent years, novel functions and binding partners have been identified for VWF. The finding that loss of VWF in EC results in enhanced, possibly dysfunctional, angiogenesis is consistent with the clinical observations that in some patients with von Willebrand disease (VWD), vascular malformations can cause severe gastrointestinal (GI) bleeding. In vitro and in vivo studies indicate that VWF can regulate angiogenesis through multiple pathways, both intracellular and extracellular, although their relative importance is still unclear. Investigation of these pathways has been greatly facilitated by the ability to isolate EC from progenitors circulating in the peripheral blood of normal controls and patients with VWD. In the next few years, these will yield further evidence on the molecular pathways controlled by VWF and shed light on this novel and fascinating area of vascular biology. In this article, we will review the evidence supporting a role for VWF in blood vessel formation, the link between VWF dysfunction and vascular malformations causing GI bleeding and how they may be causally related. Finally, we will discuss how these findings point to novel therapeutic approaches to bleeding refractory to VWF replacement therapy in VWD.
Topics: Angiodysplasia; Animals; Blood Coagulation; Blood Platelets; Endothelial Cells; Gastrointestinal Hemorrhage; Glycoproteins; Hemorrhage; Hemostasis; Humans; Megakaryocytes; Mice; Neovascularization, Pathologic; Neovascularization, Physiologic; Signal Transduction; Stem Cells; Vascular Endothelial Growth Factor Receptor-2; von Willebrand Diseases; von Willebrand Factor
PubMed: 27778439
DOI: 10.1111/jth.13551 -
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 -
Bioengineered May 2022Immune thrombocytopenia (ITP), characterized by decreased platelet counts, is a complex immune-mediated disorder with unelucidated pathogenesis. Accumulating evidence...
Identification and verification of differentially expressed key genes in peripheral blood-derived T cells between chronic immune thrombocytopenia patients and healthy controls.
Immune thrombocytopenia (ITP), characterized by decreased platelet counts, is a complex immune-mediated disorder with unelucidated pathogenesis. Accumulating evidence shows that T cell-mediated platelet destruction is one crucial process during the progression of ITP. Here, we attempted to identify core genes in peripheral blood-derived T-cells of chronic ITP through the analysis of microarray data (GSE43179) and clinical verification, with the aim to further understand the pathogenesis and progression of ITP. Compared with healthy controls, 97 differentially expressed genes (DEGs), including 63 up-regulated and 34 down-regulated were identified in ITP patients. Functional enrichment analysis showed that the DEGs were mainly enriched in innate immune response, inflammatory response, and IL-17 signaling pathway. Among the DEGs, top 15 hub genes ranked by degree score were identified via protein-protein interaction (PPI) network and were further confirmed by quantitative reverse transcription PCR (qRT-PCR). Among top 15 hub genes, the expression levels of 14 DEGs like , and were significantly up-regulated, while one DEG was down-regulated in ITP patients. Noticeably, exhibited the highest degree score, and had the largest fold change in qRT-PCR analysis. Altogether, our results suggested that the pathogenesis and progression of ITP are related with multiple immune-related pathways, and that and are likely to play crucial roles.
Topics: Computational Biology; Gene Expression Profiling; Humans; Protein Interaction Maps; Purpura, Thrombocytopenic, Idiopathic; T-Lymphocytes; Toll-Like Receptor 4
PubMed: 35796625
DOI: 10.1080/21655979.2022.2080422