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Acta Bio-medica : Atenei Parmensis Jul 2020Good knowledge of the various approaches of embolization of peripheral bleedings and different embolic materials available is of paramount importance for successful and... (Review)
Review
Good knowledge of the various approaches of embolization of peripheral bleedings and different embolic materials available is of paramount importance for successful and safe embolization. We review and illustrate the main endovascular and percutaneous techniques used for embolization, along with the characteristics of the different embolic materials, and the potential complications.
Topics: Embolism; Embolization, Therapeutic; Hemorrhage; Humans; Treatment Outcome
PubMed: 32945281
DOI: 10.23750/abm.v91i8-S.9974 -
Colombia Medica (Cali, Colombia) May 2021Damage control techniques applied to the management of thoracic injuries have evolved over the last 15 years. Despite the limited number of publications, information is... (Review)
Review
Damage control techniques applied to the management of thoracic injuries have evolved over the last 15 years. Despite the limited number of publications, information is sufficient to scatter some fears and establish management principles. The severity of the anatomical injury justifies the procedure of damage control in only few selected cases. In most cases, the magnitude of the physiological derangement and the presence of other sources of bleeding within the thoracic cavity or in other body compartments constitutes the indication for the abbreviated procedure. The classification of lung injuries as peripheral, transfixing, and central or multiple, provides a guideline for the transient bleeding control and for the definitive management of the injury: pneumorraphy, wedge resection, tractotomy or anatomical resection, respectively. Identification of specific patterns such as the need for resuscitative thoracotomy, or aortic occlusion, the existence of massive hemothorax, a central lung injury, a tracheobronchial injury, a major vascular injury, multiple bleeding sites as well as the recognition of hypothermia, acidosis or coagulopathy, constitute the indication for a damage control thoracotomy. In these cases, the surgeon executes an abbreviated procedure with packing of the bleeding surfaces, primary management with packing of some selected peripheral or transfixing lung injuries, and the postponement of lung resection, clamping of the pulmonary hilum in the most selective way possible. The abbreviation of the thoracotomy closure is achieved by suturing the skin over the wound packed, or by installing a vacuum system. The management of the patient in the intensive care unit will allow identification of those who require urgent reintervention and the correction of the physiological derangement in the remaining patients for their scheduled reintervention and definitive management.
Topics: Acidosis; Aorta; Blood Coagulation Disorders; Hemorrhage; Hemostatic Techniques; Humans; Hypothermia; Lung Injury; Medical Illustration; Photography; Therapeutic Occlusion; Thoracotomy; Wound Closure Techniques
PubMed: 34188322
DOI: 10.25100/cm.v52i2.4683 -
Clinical and Translational Medicine Feb 2024Intracranial aneurysms (IAs) represent a severe cerebrovascular disease that can potentially lead to subarachnoid haemorrhage. Previous studies have demonstrated the...
BACKGROUND
Intracranial aneurysms (IAs) represent a severe cerebrovascular disease that can potentially lead to subarachnoid haemorrhage. Previous studies have demonstrated the involvement of peripheral immune cells in the formation and progression of IAs. Nevertheless, the impact of metabolic alterations in peripheral immune cells and changes in neutrophil heterogeneity on the occurrence and progression of IAs remains uncertain.
METHODS
Single-cell Cytometry by Time-of-Flight (CyTOF) technology was employed to profile the single-cell atlas of peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) in 72 patients with IAs. In a matched cohort, metabolic shifts in PBMC subsets of IA patients were investigated by contrasting the expression levels of key metabolic enzymes with their respective counterparts in the healthy control group. Simultaneously, compositional differences in peripheral blood PMNs subsets between the two groups were analysed to explore the impact of altered heterogeneity in neutrophils on the initiation and progression of IAs. Furthermore, integrating immune features based on CyTOF analysis and clinical characteristics, we constructed an aneurysm occurrence model and an aneurysm growth model using the random forest method in conjunction with LASSO regression.
RESULTS
Different subsets exhibited distinct metabolic characteristics. Overall, PBMCs from patients elevated CD98 expression and increased proliferation. Conversely, CD36 was up-regulated in T cells, B cells and monocytes from the controls but down-regulated in NK and NKT cells. The comparison also revealed differences in the metabolism and function of specific subsets between the two groups. In terms of PMNs, the neutrophil landscape within patients group revealed a pronounced shift towards heightened complexity. Various neutrophil subsets from the IA group generally exhibited lower expression levels of anti-inflammatory functional molecules (IL-4 and IL-10). By integrating clinical and immune features, the constructed aneurysm occurrence model could precisely identify patients with IAs with high prediction accuracy (AUC = 0.987). Furthermore, the aneurysm growth model also exhibited superiority over ELAPSS scores in predicting aneurysm growth (lower prediction errors and out-of-bag errors).
CONCLUSION
These findings enhanced our understanding of peripheral immune cell participation in aneurysm formation and growth from the perspectives of immune metabolism and neutrophil heterogeneity. Moreover, the predictive model based on CyTOF features holds the potential to aid in diagnosing and monitoring the progression of human IAs.
Topics: Humans; Intracranial Aneurysm; Neutrophils; Leukocytes, Mononuclear; Aneurysm, Ruptured; B-Lymphocytes
PubMed: 38314932
DOI: 10.1002/ctm2.1572 -
Nature Communications Jul 2023Many hematological diseases are characterized by altered abundance and morphology of blood cells and their progenitors. Myelodysplastic syndromes (MDS), for example, are...
Many hematological diseases are characterized by altered abundance and morphology of blood cells and their progenitors. Myelodysplastic syndromes (MDS), for example, are a group of blood cancers characterised by cytopenias, dysplasia of hematopoietic cells and blast expansion. Examination of peripheral blood slides (PBS) in MDS often reveals changes such as abnormal granulocyte lobulation or granularity and altered red blood cell (RBC) morphology; however, some of these features are shared with conditions such as haematinic deficiency anemias. Definitive diagnosis of MDS requires expert cytomorphology analysis of bone marrow smears and complementary information such as blood counts, karyotype and molecular genetics testing. Here, we present Haemorasis, a computational method that detects and characterizes white blood cells (WBC) and RBC in PBS. Applied to over 300 individuals with different conditions (SF3B1-mutant and SF3B1-wildtype MDS, megaloblastic anemia, and iron deficiency anemia), Haemorasis detected over half a million WBC and millions of RBC and characterized their morphology. These large sets of cell morphologies can be used in diagnosis and disease subtyping, while identifying novel associations between computational morphotypes and disease. We find that hypolobulated neutrophils and large RBC are characteristic of SF3B1-mutant MDS. Additionally, while prevalent in both iron deficiency and megaloblastic anemia, hyperlobulated neutrophils are larger in the latter. By integrating cytomorphological features using machine learning, Haemorasis was able to distinguish SF3B1-mutant MDS from other MDS using cytomorphology and blood counts alone, with high predictive performance. We validate our findings externally, showing that they generalize to other centers and scanners. Collectively, our work reveals the potential for the large-scale incorporation of automated cytomorphology into routine diagnostic workflows.
Topics: Humans; Myelodysplastic Syndromes; Anemia; Anemia, Megaloblastic; Blood Cells; Neutrophils
PubMed: 37474506
DOI: 10.1038/s41467-023-39676-y -
Journal of Neuroinflammation Nov 2023Subarachnoid hemorrhage (SAH) is an uncommon type of potentially fatal stroke. The pathophysiological mechanisms of brain injury remain unclear, which hinders the...
BACKGROUND
Subarachnoid hemorrhage (SAH) is an uncommon type of potentially fatal stroke. The pathophysiological mechanisms of brain injury remain unclear, which hinders the development of drugs for SAH. We aimed to investigate the pathophysiological mechanisms of SAH and to elucidate the cellular and molecular biological response to SAH-induced injury.
METHODS
A cross-species (human and mouse) multiomics approach combining high-throughput data and bioinformatic analysis was used to explore the key pathophysiological processes and cells involved in SAH-induced brain injury. Patient data were collected from the hospital (n = 712). SAH was established in adult male mice via endovascular perforation, and flow cytometry, a bone marrow chimera model, qPCR, and microglial depletion experiments were conducted to explore the origin and chemotaxis mechanism of the immune cells. To investigate cell effects on SAH prognosis, murine neurological function was evaluated based on a modified Garcia score, pole test, and rotarod test.
RESULTS
The bioinformatics analysis confirmed that inflammatory and immune responses were the key pathophysiological processes after SAH. Significant increases in the monocyte levels were observed in both the mouse brains and the peripheral blood of patients after SAH. Ly6C-high monocytes originated in the bone marrow, and the skull bone marrow contribute a higher proportion of these monocytes than neutrophils. The mRNA level of Ccl2 was significantly upregulated after SAH and was greater in CD11b-positive than CD11b-negative cells. Microglial depletion, microglial inhibition, and CCL2 blockade reduced the numbers of Ly6C-high monocytes after SAH. With CCR2 antagonization, the neurological function of the mice exhibited a slow recovery. Three days post-SAH, the monocyte-derived dendritic cell (moDC) population had a higher proportion of TNF-α-positive cells and a lower proportion of IL-10-positive cells than the macrophage population. The ratio of moDCs to macrophages was higher on day 3 than on day 5 post-SAH.
CONCLUSIONS
Inflammatory and immune responses are significantly involved in SAH-induced brain injury. Ly6C-high monocytes derived from the bone marrow, including the skull bone marrow, infiltrated into mouse brains via CCL2 secreted from microglia. Moreover, Ly6C-high monocytes alleviated neurological dysfunction after SAH.
Topics: Humans; Mice; Male; Animals; Monocytes; Subarachnoid Hemorrhage; Brain Injuries; Macrophages; Stroke; Mice, Inbred C57BL
PubMed: 37978532
DOI: 10.1186/s12974-023-02939-y -
The Cochrane Database of Systematic... Mar 2023Traumatic hyphema is the entry of blood into the anterior chamber, the space between the cornea and iris, following significant injury to the eye. Hyphema may be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Traumatic hyphema is the entry of blood into the anterior chamber, the space between the cornea and iris, following significant injury to the eye. Hyphema may be associated with significant complications that uncommonly cause permanent vision loss. Complications include elevated intraocular pressure, corneal blood staining, anterior and posterior synechiae, and optic nerve atrophy. People with sickle cell trait or disease may be particularly susceptible to increases in intraocular pressure and optic atrophy. Rebleeding is associated with an increase in the rate and severity of complications.
OBJECTIVES
To assess the effectiveness of various medical interventions in the management of traumatic hyphema.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 3); MEDLINE Ovid; Embase.com; PubMed (1948 to March 2022); the ISRCTN registry; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The last date of the search was 22 March 2022.
SELECTION CRITERIA
Two review authors independently assessed the titles and abstracts of all reports identified by the electronic and manual searches. We included randomized and quasi-randomized trials that compared various medical (non-surgical) interventions versus other medical interventions or control groups for the treatment of traumatic hyphema following closed-globe trauma. We applied no restrictions on age, gender, severity of the closed-globe trauma, or level of visual acuity at time of enrollment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane and assessed the certainty of evidence using GRADE.
MAIN RESULTS
We included 23 randomized and seven quasi-randomized studies with a total of 2969 participants. Interventions included antifibrinolytic agents (systemic and topical aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid), corticosteroids (systemic and topical), cycloplegics, miotics, aspirin, conjugated estrogens, traditional Chinese medicine, monocular versus bilateral patching, elevation of the head, and bed rest. We found no evidence of an effect on visual acuity for any intervention, whether measured within two weeks (short term) or for longer periods. In a meta-analysis of two trials, we found no evidence of an effect of aminocaproic acid on long-term visual acuity (RR 1.03, 95% confidence interval (CI) 0.82 to 1.29) or final visual acuity measured up to three years after the hyphema (RR 1.05, 95% CI 0.93 to 1.18). Oral tranexamic acid appeared to provide little to no benefit on visual acuity in four trials (RR 1.12, 95% CI 1.00 to 1.25). The remaining trials evaluated the effects of various interventions on short-term visual acuity; none of these interventions was measured in more than one trial. No intervention showed a statistically significant effect (RRs ranged from 0.75 to 1.10). Similarly, visual acuity measured for longer periods in four trials evaluating different interventions was also not statistically significant (RRs ranged from 0.82 to 1.02). The evidence supporting these findings was of low or very low certainty. Systemic aminocaproic acid reduced the rate of recurrent hemorrhage (RR 0.28, 95% CI 0.13 to 0.60), as assessed in six trials with 330 participants. A sensitivity analysis omitting two studies not using an intention-to-treat analysis reduced the strength of the evidence (RR 0.43, 95% CI 0.17 to 1.08). We obtained similar results for topical aminocaproic acid (RR 0.48, 95% CI 0.20 to 1.10) in two trials with 131 participants. We assessed the certainty of the evidence as low. Systemic tranexamic acid had a significant effect in reducing the rate of secondary hemorrhage (RR 0.33, 95% CI 0.21 to 0.53) in seven trials with 754 participants, as did aminomethylbenzoic acid (RR 0.10, 95% CI 0.02 to 0.41), as reported in one study. Evidence to support an associated reduction in risk of complications from secondary hemorrhage (i.e. corneal blood staining, peripheral anterior synechiae, elevated intraocular pressure, and development of optic atrophy) by antifibrinolytics was limited by the small number of these events. Use of aminocaproic acid was associated with increased nausea, vomiting, and other adverse events compared with placebo. We found no evidence of an effect on the number of adverse events with the use of systemic versus topical aminocaproic acid or with standard versus lower drug dose. The number of days for the primary hyphema to resolve appeared to be longer with the use of systemic aminocaproic acid compared with no use, but this outcome was not altered by any other intervention. The available evidence on usage of systemic or topical corticosteroids, cycloplegics, or aspirin in traumatic hyphema was limited due to the small numbers of participants and events in the trials. We found no evidence of an effect between a single versus binocular patch on the risk of secondary hemorrhage or time to rebleed. We also found no evidence of an effect on the risk of secondary hemorrhage between ambulation and complete bed rest.
AUTHORS' CONCLUSIONS
We found no evidence of an effect on visual acuity of any of the interventions evaluated in this review. Although the evidence was limited, people with traumatic hyphema who receive aminocaproic acid or tranexamic acid are less likely to experience secondary hemorrhage. However, hyphema took longer to clear in people treated with systemic aminocaproic acid. There is no good evidence to support the use of antifibrinolytic agents in the management of traumatic hyphema, other than possibly to reduce the rate of secondary hemorrhage. The potentially long-term deleterious effects of secondary hemorrhage are unknown. Similarly, there is no evidence to support the use of corticosteroids, cycloplegics, or non-drug interventions (such as patching, bed rest, or head elevation) in the management of traumatic hyphema. As these multiple interventions are rarely used in isolation, further research to assess the additive effect of these interventions might be of value.
Topics: Humans; Adrenal Cortex Hormones; Aminocaproic Acid; Antifibrinolytic Agents; Aspirin; Glaucoma; Hyphema; Mydriatics; Tranexamic Acid
PubMed: 36912744
DOI: 10.1002/14651858.CD005431.pub5 -
Platelets Jan 2022The neonatal hemostatic system is different from that of adults. The differences in levels of procoagulant and anticoagulant factors and the evolving equilibrium in... (Review)
Review
The neonatal hemostatic system is different from that of adults. The differences in levels of procoagulant and anticoagulant factors and the evolving equilibrium in secondary hemostasis during the transition from fetal/neonatal life to infancy, childhood, and adult life are known as "developmental hemostasis." In regard to primary hemostasis, while the number (150,000-450,000/µl) and structure of platelets in healthy neonates closely resemble those of adults, there are significant functional differences between neonatal and adult platelets. Specifically, platelets derived from both cord blood and neonatal peripheral blood are less reactive than adult platelets to agonists, such as adenosine diphosphate (ADP), epinephrine, collagen, thrombin, and thromboxane (TXA) analogs. This platelet hyporeactivity is due to differences in expression levels of key surface receptors and/or in signaling pathways, and is more pronounced in preterm neonates. Despite these differences in platelet function, bleeding times and PFA-100 closure times (an test of whole-blood primary hemostasis) are shorter in healthy full-term infants than in adults, reflecting enhanced primary hemostasis. This paradoxical finding is explained by the presence of factors in neonatal blood that increase the platelet-vessel wall interaction, such as high von Willebrand factor (vWF) levels, predominance of ultralong vWF multimers, high hematocrit, and high red cell mean corpuscular volume. Thus, the hyporeactivity of neonatal platelets should not be viewed as a developmental deficiency, but rather as an integral part of a developmentally unique, but well balanced, primary hemostatic system. In clinical practice, due to the high incidence of bleeding (especially intraventricular hemorrhage, IVH) among preterm infants, neonatologists frequently transfuse platelets to non-bleeding neonates when platelet counts fall below an arbitrary limit, typically higher than that used in older children and adults. However, recent studies have shown that prophylactic platelet transfusions not only fail to decrease bleeding in preterm neonates, but are associated with increased neonatal morbidity and mortality. In this review, we will describe the developmental differences in platelet function and primary hemostasis between neonates and adults, and will analyze the implications of these differences to platelet transfusion decisions.
Topics: Blood Platelets; Humans; Platelet Transfusion
PubMed: 34392772
DOI: 10.1080/09537104.2021.1962837 -
PloS One 2022The objectives of this study were to evaluate the proper anticoagulants coated in blood-collecting tube for the peripheral blood mononuclear cells (PBMCs) isolation and...
The objectives of this study were to evaluate the proper anticoagulants coated in blood-collecting tube for the peripheral blood mononuclear cells (PBMCs) isolation and to evaluate the proper culture temperature for the Varanus salvator's PBMCs, in addition, the hematological characteristics also reported. The heparin treated blood (n = 10) and EDTA treated blood (n = 10) from Varanus salvator were obtained for PBMCs evaluation. The PBMCs obtained from the heparin treated blood was significantly higher than that of EDTA treated blood during the culture period (P < 0.05) indicated heparin would be more appropriated anticoagulant for blood collection. The PBMCs cultured under 37°C and 27°C were not significantly difference on first three days but 37°C showed significantly higher effect in the following days (P < 0.05) indicated both temperatures can be used which 37°C should be an optimal for PBMCs preparation. The peripheral blood cells of Varanus salvator (n = 49) were analyzed for hematological profiles and characteristics which the number of erythrocytes 1.19 ± 0.04 x 1012/L (1.17-1.35 x 1012/L) and WBC 2.41 ± 0.13 x 109/L (2.29-2.81 x 109/L) with absolute differential count of heterophils 0.92 ± 0.02 x 109/L (0.87-0.95 x 109/L), lymphocytes 1.17 ± 0.01 x 109/L (1.15-1.23 x 109/L), azurophils 0.40 ± 0.01 x 109/L (0.37-0.42 x 109/L), basophils 0.000 ± 0.001 x 109/L (0.004-0.011 x 109/L) and monocytes 0.027 ± 0.002 x 109/L (0.028-0.039 x 109/L). These results would play an important role on the cell immunological studies of the Varanus salvator in the future.
Topics: Animals; Anticoagulants; Edetic Acid; Hematology; Heparin; Leukocyte Count; Leukocytes, Mononuclear; Lizards
PubMed: 35867719
DOI: 10.1371/journal.pone.0269108 -
Blood Dec 2022Chronic graft-versus-host disease (cGVHD) is an autoimmune-like syndrome. CXCR5-PD-1hi peripheral T-helper (Tph) cells have an important pathogenic role in autoimmune...
Chronic graft-versus-host disease (cGVHD) is an autoimmune-like syndrome. CXCR5-PD-1hi peripheral T-helper (Tph) cells have an important pathogenic role in autoimmune diseases, but the role of Tph cells in cGVHD remains unknown. We show that in patients with cGVHD, expansion of Tph cells among blood CD4+ T cells was associated with cGVHD severity. These cells augmented memory B-cell differentiation and production of immunoglobulin G via interleukin 21 (IL-21). Tph cell expansion was also observed in a murine model of cGVHD. This Tph cell expansion in the blood is associated with the expansion of pathogenic tissue-resident T-helper (Trh) cells that form lymphoid aggregates surrounded by collagen in graft-versus-host disease (GVHD) target tissues. Adoptive transfer experiments showed that Trh cells from GVHD target tissues give rise to Tph cells in the blood, and conversely, Tph cells from the blood give rise to Trh cells in GVHD target tissues. Tph cells in the blood and Trh cells in GVHD target tissues had highly overlapping T-cell receptor α and β repertoires. Deficiency of IL-21R, B-cell lymphoma 6 (BCL6), or T-bet in donor T cells markedly reduced the proportions of Tph cells in the blood and Trh cells in GVHD target tissues and reduced T-B interaction in the lymphoid aggregates. These results indicate that clonally related pathogenic Tph cells and Trh cells traffic between the blood and cGVHD target tissues, and that IL-21R-BCL6 signaling and T-bet are required for the development and expansion of Tph and Trh cells in the pathogenesis of cGVHD.
Topics: Humans; Mice; Animals; T-Lymphocytes, Helper-Inducer; CD4-Positive T-Lymphocytes; B-Lymphocytes; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease; Chronic Disease
PubMed: 36084473
DOI: 10.1182/blood.2022016581 -
Leukemia Feb 2024T follicular helper (T) cell lymphomas (TFHLs) are characterized by T-like properties and accompanied by substantial immune-cell infiltration into tumor tissues....
T follicular helper (T) cell lymphomas (TFHLs) are characterized by T-like properties and accompanied by substantial immune-cell infiltration into tumor tissues. Nevertheless, the comprehensive understanding of tumor-cell heterogeneity and immune profiles of TFHL remains elusive. To address this, we conducted single-cell transcriptomic analysis on 9 lymph node (LN) and 16 peripheral blood (PB) samples from TFHL patients. Tumor cells were divided into 5 distinct subclusters, with significant heterogeneity observed in the expression levels of T markers. Copy number variation (CNV) and trajectory analyses indicated that the accumulation of CNVs, together with gene mutations, may drive the clonal evolution of tumor cells towards T-like and cell proliferation phenotypes. Additionally, we identified a novel tumor-cell-specific marker, PLS3. Notably, we found a significant increase in exhausted CD8 T cells with oligoclonal expansion in TFHL LNs and PB, along with distinctive immune evasion characteristics exhibited by infiltrating regulatory T, myeloid, B, and natural killer cells. Finally, in-silico and spatial cell-cell interaction analyses revealed complex networking between tumor and immune cells, driving the formation of an immunosuppressive microenvironment. These findings highlight the remarkable tumor-cell heterogeneity and immunoevasion in TFHL beyond previous expectations, suggesting potential roles in treatment resistance.
Topics: Humans; T-Lymphocytes, Helper-Inducer; CD8-Positive T-Lymphocytes; DNA Copy Number Variations; Lymphoma, Follicular; Biomarkers, Tumor; Phenotype; Killer Cells, Natural; Tumor Microenvironment
PubMed: 38012392
DOI: 10.1038/s41375-023-02093-7