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1.
J Neuroinflammation ; 21(1): 106, 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38658922

BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating neurological disease causing severe sensorimotor dysfunction and cognitive decline, yet there is no effective treatment strategy to alleviate outcomes of these patients. The Mas axis-mediated neuroprotection is involved in the pathology of various neurological diseases, however, the role of the Mas receptor in the setting of ICH remains to be elucidated. METHODS: C57BL/6 mice were used to establish the ICH model by injection of collagenase into mice striatum. The Mas receptor agonist AVE0991 was administered intranasally (0.9 mg/kg) after ICH. Using a combination of behavioral tests, Western blots, immunofluorescence staining, hematoma volume, brain edema, quantitative-PCR, TUNEL staining, Fluoro-Jade C staining, Nissl staining, and pharmacological methods, we examined the impact of intranasal application of AVE0991 on hematoma absorption and neurological outcomes following ICH and investigated the underlying mechanism. RESULTS: Mas receptor was found to be significantly expressed in activated microglia/macrophages, and the peak expression of Mas receptor in microglia/macrophages was observed at approximately 3-5 days, followed by a subsequent decline. Activation of Mas by AVE0991 post-treatment promoted hematoma absorption, reduced brain edema, and improved both short- and long-term neurological functions in ICH mice. Moreover, AVE0991 treatment effectively attenuated neuronal apoptosis, inhibited neutrophil infiltration, and reduced the release of inflammatory cytokines in perihematomal areas after ICH. Mechanistically, AVE0991 post-treatment significantly promoted the transformation of microglia/macrophages towards an anti-inflammatory, phagocytic, and reparative phenotype, and this functional phenotypic transition of microglia/macrophages by Mas activation was abolished by both Mas inhibitor A779 and Nrf2 inhibitor ML385. Furthermore, hematoma clearance and neuroprotective effects of AVE0991 treatment were reversed after microglia depletion in ICH. CONCLUSIONS: Mas activation can promote hematoma absorption, ameliorate neurological deficits, alleviate neuron apoptosis, reduced neuroinflammation, and regulate the function and phenotype of microglia/macrophages via Akt/Nrf2 signaling pathway after ICH. Thus, intranasal application of Mas agonist ACE0991 may provide promising strategy for clinical treatment of ICH patients.


Hematoma , Hemorrhagic Stroke , Mice, Inbred C57BL , Receptors, G-Protein-Coupled , Recovery of Function , Animals , Mice , Hematoma/drug therapy , Hematoma/pathology , Hematoma/metabolism , Male , Hemorrhagic Stroke/pathology , Hemorrhagic Stroke/drug therapy , Receptors, G-Protein-Coupled/agonists , Receptors, G-Protein-Coupled/metabolism , Recovery of Function/drug effects , Recovery of Function/physiology , Proto-Oncogene Proteins/metabolism , Brain Edema/etiology , Brain Edema/metabolism , Brain Edema/drug therapy , Microglia/drug effects , Microglia/metabolism
2.
Adv Sci (Weinh) ; 11(13): e2307050, 2024 Apr.
Article En | MEDLINE | ID: mdl-38273642

Bone fracture healing is regulated by mechanobiological cues. Both, extracellular matrix (ECM) deposition and microvascular assembly determine the dynamics of the regenerative processes. Mechanical instability as by inter-fragmentary shear or compression is known to influence early ECM formation and wound healing. However, it remains unclear how these external cues shape subsequent ECM and microvascular network assembly. As transcriptional coactivators, the mechanotransducers yes-associated protein 1 (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) translate physical cues into downstream signaling events, yet their role in sprouting angiogenesis into the hematoma after injury is unknown. Using bone healing as model system for scar-free regeneration, the role of endothelial YAP/TAZ in combination with tuning the extrinsic mechanical stability via fracture fixation is investigated. Extrinsically imposed shear across the gap delayed hematoma remodeling and shaped the morphology of early collagen fiber orientations and microvascular networks, suggesting that enhanced shear increased the nutrient exchange in the hematoma. In contrast, endothelial YAP/TAZ deletion has little impact on the overall vascularization of the fracture gap, yet slightly increases the collagen fiber deposition under semi-rigid fixation. Together, these data provide novel insights into the respective roles of endothelial YAP/TAZ and extrinsic mechanical cues in orchestrating the process of bone regeneration.


Hematoma , Mechanotransduction, Cellular , Collagen/metabolism , Mechanotransduction, Cellular/genetics , Transcription Factors/metabolism , YAP-Signaling Proteins/metabolism , Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism , Fracture Healing/physiology , Humans , Hematoma/metabolism , Hematoma/pathology , Bone and Bones/metabolism , Bone and Bones/pathology
3.
Eur Stroke J ; 9(2): 383-390, 2024 Jun.
Article En | MEDLINE | ID: mdl-38179883

INTRODUCTION: Perihematomal edema (PHE) represents secondary brain injury and a potential treatment target in intracerebral hemorrhage (ICH). However, studies differ on optimal PHE volume metrics as prognostic factor(s) after spontaneous, non-traumatic ICH. This study examines associations of baseline and 24-h PHE shape features with 3-month outcomes. PATIENTS AND METHODS: We included 796 patients from a multicentric trial dataset and manually segmented ICH and PHE on baseline and follow-up CTs, extracting 14 shape features. We explored the association of baseline, follow-up, difference (baseline/follow-up) and temporal rate (difference/time gap) of PHE shape changes with 3-month modified Rankin Score (mRS) - using Spearman correlation. Then, using multivariable analysis, we determined if PHE shape features independently predict outcome adjusting for patients' age, sex, NIH stroke scale (NIHSS), Glasgow Coma Scale (GCS), and hematoma volume. RESULTS: Baseline PHE maximum diameters across various planes, main axes, volume, surface, and sphericity correlated with 3-month mRS adjusting for multiple comparisons. The 24-h difference and temporal change rates of these features had significant association with outcome - but not the 24-h absolute values. In multivariable regression, baseline PHE shape sphericity (OR = 2.04, CI = 1.71-2.43) and volume (OR = 0.99, CI = 0. 98-1.0), alongside admission NIHSS (OR = 0.86, CI = 0.83-0.88), hematoma volume (OR = 0.99, CI = 0. 99-1.0), and age (OR = 0.96, CI = 0.95-0.97) were independent predictors of favorable outcomes. CONCLUSION: In acute ICH patients, PHE shape sphericity at baseline emerged as an independent prognostic factor, with a less spherical (more irregular) shape associated with worse outcome. The PHE shape features absolute values over the first 24 h provide no added prognostic value to baseline metrics.


Brain Edema , Cerebral Hemorrhage , Humans , Male , Female , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/therapy , Cerebral Hemorrhage/pathology , Aged , Middle Aged , Brain Edema/diagnostic imaging , Brain Edema/etiology , Hematoma/diagnostic imaging , Hematoma/pathology , Prognosis , Glasgow Coma Scale , Tomography, X-Ray Computed
4.
Asian J Surg ; 47(1): 389-393, 2024 Jan.
Article En | MEDLINE | ID: mdl-37775380

OBJECTIVE: To investigate the application of high-resolution magnetic resonance vessel wall image (HRMR-VWI) in treating middle cerebral artery (MCA) M1 segment stenosis. METHODS: We retrospectively analyzed preoperative clinical data, imaging data, preoperative evaluation, stent procedure, and postoperative complications in 35 patients with atherosclerotic stenosis of the MCA M1 segment. And the 30-day postoperative mortality and disability and the 12-month restenosis were followed up. RESULTS: There were 21 males and 14 females, with a median age of 55 and a median duration of 1 month from onset to stenting. DSA confirmed that the stenosis locates in the M1 segment, with a stenosis degree of (75.00 ± 17.15) %, a stenosis length of (4.34 ± 1.51) mm, and a blood vessel diameter of (2.25 ± 0.42) mm. After the operation, there was 1 case of death after a craniotomy to remove hematoma + decompression due to reperfusion hemorrhage. There were two technical complications during the procedure (1 case of asymptomatic occlusion of the A1 segment due to the covering of stent at the initial part of A1, 1 case of intraparenchymal hematoma in the temporal lobe due to penetrating distal small blood vessel with guide wire). CONCLUSION: HRMR-VWI is of great value in observing plaques' location, morphology, and stability. It can improve the safety and effectiveness of stenting treatment of MCA M1 segment stenosis.


Magnetic Resonance Imaging , Middle Cerebral Artery , Male , Female , Humans , Constriction, Pathologic/surgery , Middle Cerebral Artery/diagnostic imaging , Middle Cerebral Artery/surgery , Middle Cerebral Artery/pathology , Retrospective Studies , Magnetic Resonance Imaging/methods , Hematoma/pathology , Magnetic Resonance Spectroscopy
5.
J Pediatr Hematol Oncol ; 46(2): 104-105, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-37867238

Three-year-old boy who presented with colicky abdominal pain, diarrhoea and vomiting was investigated with computed tomography which revealed a mass in the peripancreatic region. An imaging possibility of duodenal intramural hematoma was considered after reassessment with ultrasound which was subsequently confirmed by magnetic resonance imaging. The development of a spontaneous duodenal hematoma lead to further evaluation of the patient and revealed X linked hyper IgM syndrome.


Duodenal Diseases , Hyper-IgM Immunodeficiency Syndrome, Type 1 , Hyper-IgM Immunodeficiency Syndrome , Male , Humans , Duodenal Diseases/etiology , Duodenal Diseases/pathology , Duodenum/diagnostic imaging , Duodenum/pathology , Gastrointestinal Hemorrhage , Hematoma/diagnostic imaging , Hematoma/etiology , Hematoma/pathology
6.
Neuroscience ; 537: 93-104, 2024 Jan 26.
Article En | MEDLINE | ID: mdl-38056621

The inflammatory mechanism of intracerebral hemorrhage (ICH) has been widely studied, and it is believed that the regulation of this mechanism is of great significance to the prognosis. In the early stage of the acute phase of ICH, the release of a large number of inflammatory factors around the hematoma can recruit more inflammatory cells to infiltrate the area, further release inflammatory factors, cause an inflammatory cascade reaction, aggravate the volume of cerebral hematoma and edema and further destroy the blood-brain barrier (BBB), according to this, the crosstalk between cells may be of great significance in secondary brain injury (SBI). Because most of the cells recruited are inflammatory immune cells, this paper mainly discusses the cells based on the inflammatory mechanism to discuss their functions after ICH, we found that among the main cells inherent in the brain, glial cells account for the majority, of which microglia are the most widely studied and it can interact with a variety of cells, which is reflected in the literature researches on its pathogenesis and treatment. We believe that exploring multi-mechanism and multi-cell regulated drugs may be the future development trend, and the existing research, the comparison and unification of modeling methods, and the observation of long-term efficacy may be the first problem that researchers need to solve.


Brain , Cerebral Hemorrhage , Humans , Brain/pathology , Cerebral Hemorrhage/drug therapy , Blood-Brain Barrier/pathology , Inflammation/drug therapy , Hematoma/complications , Hematoma/drug therapy , Hematoma/pathology
7.
J Neuroimaging ; 34(1): 26-43, 2024.
Article En | MEDLINE | ID: mdl-37933199

Skull lesions in pediatric population are common findings on imaging and sometimes with heterogeneous manifestations, constituting a diagnostic challenge. Some lesions can be misinterpreted for their aggressiveness, as with larger lesions eroding cortical bone, containing soft tissue components, leading to excessive and, in some cases, invasive inappropriate etiological investigation. In this review, we present multiple several conditions that may present as skull lesions or pseudolesions, organized by groups (anatomic variants, congenital and development disorders, traumatic injuries, vascular issues, infectious conditions, and tumoral processes). Anatomic variants are common imaging findings that must be recognized by the neuroradiologist. Congenital malformations are rare conditions, such as aplasia cutis congenita and sinus pericranii, usually seen at earlier ages, the majority of which are benign findings. In case of trauma, cephalohematoma, growing skull fractures, and posttraumatic lytic lesions should be considered. Osteomyelitis tends to be locally aggressive and may mimic malignancy, in which cases, the clinical history can be the key to diagnosis. Vascular (sickle cell disease) and tumoral (aneurismal bone cyst, eosinophilic granuloma, metastases) lesions are relatively rare lesions but should be considered in the differential diagnosis, in the presence of certain imaging findings. The main difficulty is the differentiation between the benign and malignant nature; therefore, the main objective of this pictorial essay is to review the main skull lytic lesions found in pediatric age, describing the main findings in different imaging modalities (CT and MRI), allowing the neuroradiologist greater confidence in establishing the differential diagnosis, through a systematic and simple characterization of the lesions.


Magnetic Resonance Imaging , Skull , Humans , Child , Skull/diagnostic imaging , Skull/pathology , Magnetic Resonance Imaging/methods , Head , Diagnosis, Differential , Hematoma/pathology
8.
J Pharmacol Sci ; 153(4): 208-214, 2023 Dec.
Article En | MEDLINE | ID: mdl-37973218

Natural compounds with sulfur moiety produce various biological actions that may be beneficial for the therapies of several devastative disorders of the central nervous system. Here we investigated potential therapeutic effect of allicin, an organosulfur compound derived from garlic, in a mouse model of intracerebral hemorrhage (ICH) based on intrastriatal collagenase injection. Daily intraperitoneal administration of allicin (50 mg/kg) from 3 h after induction of ICH afforded neuroprotective effects, as evidenced by the increase of surviving neurons in the hematoma, reduction of axonal transport impairment, and prevention of axon tract injury. In addition, allicin inhibited accumulation of activated microglia/macrophages around the hematoma and infiltration of neutrophils within the hematoma. Allicin also suppressed ICH-induced mRNA upregulation of pro-inflammatory factors such as interleukin 6 and C-X-C motif ligand 2 in the brain, suggesting its anti-inflammatory effect. Moreover, ICH-induced increase of malondialdehyde as well as decrease of total glutathione in the brain was attenuated by allicin. Finally, allicin-treated mice showed better recovery of sensorimotor functions after ICH than vehicle-treated mice. These results indicate that allicin produces a therapeutic effect on ICH pathology via alleviation of neuronal damage, inflammatory responses and oxidative stress in the brain.


Brain , Cerebral Hemorrhage , Mice , Animals , Cerebral Hemorrhage/drug therapy , Brain/pathology , Microglia/pathology , Hematoma/pathology
9.
Oral Oncol ; 147: 106619, 2023 Dec.
Article En | MEDLINE | ID: mdl-37925895

Sinonasal organizing hematomas (SOH) are rare, benign lesions that can be mistaken for malignancies due to their unfamiliarity among clinicians and aggressive appearance on imaging, which can lead to aggressive and unnecessary therapeutic interventions. Herein, we report an unusual case of SOH in an 87-year-old female patient who sought care at a maxillofacial surgery service due to persistent right nasal obstruction and imaging findings that suggested the possibility of sinonasal malignancy. We highlight the importance of recognizing these lesions to ensure adequate treatment through a conservative approach.


Paranasal Sinus Neoplasms , Female , Humans , Aged, 80 and over , Paranasal Sinus Neoplasms/surgery , Tomography, X-Ray Computed/methods , Hematoma/diagnostic imaging , Hematoma/pathology , Magnetic Resonance Imaging/methods
10.
Life Sci ; 334: 122204, 2023 Dec 01.
Article En | MEDLINE | ID: mdl-37871676

AIMS: Muscle-bone interactions during fracture healing are rarely known. Here we investigated the presence and significance of myosin heavy chain 2 (MYH2), a component of myosin derived from muscles, in fracture healing. MAIN METHODS: We collected five hematoma and seven soft callus tissues from patients with distal radius fractures patients, randomly selected three of them, and performed a liquid chromatography-mass spectrometry (LC-MS) proteomics analysis. Proteomic results were validated by histological observation, immunohistochemistry, and immunofluorescence for MYH2 expression. These findings were further confirmed in a murine femoral fracture model in vivo and investigated using various methods in vitro. KEY FINDINGS: The LC-MS proteomics analysis showed that MYH proteins were enriched in human soft calluses compared to hematoma. Notably, MYH2 protein is upregulated as high rank in each soft callus. The histological examination showed that MYH2 expression was elevated in hypertrophic chondrocytes within the human soft callus. Consistent with human data, Myh2 were significantly co-localized with Sox9 in hypertrophic chondrocytes of murine femoral fracture, in comparison to pre-hypertrophic and proliferating chondrocytes. Soluble MYH2 protein treatment increased MMP13 and RUNX2 expression in chondrocytes. In soluble MYH2 treatment, proliferation of chondrocytes was not altered, but the osteogenic and chondrogenic features of chondrocytes increased and decreased during differentiation, respectively. SIGNIFICANCE: These findings indicate the potential of soluble MYH2 protein as a promising therapeutic strategy for promoting endochondral bone formation in chondrocytes following fracture.


Femoral Fractures , Osteogenesis , Animals , Humans , Mice , Bony Callus/pathology , Chondrocytes/metabolism , Cytoskeletal Proteins/metabolism , Femoral Fractures/metabolism , Fracture Healing/physiology , Hematoma/metabolism , Hematoma/pathology , Hypertrophy/metabolism , Myosin Heavy Chains/metabolism , Proteomics
11.
Pharmacol Res ; 196: 106912, 2023 Oct.
Article En | MEDLINE | ID: mdl-37696483

Microglia are first responders to acute brain insults and initiate neuroinflammation to drive secondary tissue injury. Yet the key molecular switches in control of the inflammatory activity of microglia remain poorly understood. Intracerebral hemorrhage (ICH) is a devastating stroke subtype whereby a hematoma is formed within the brain parenchyma and associated with high mortality. Using a mouse model of ICH, we found upregulation of CD22 that predominantly occurred in microglia. Antibody blockade of CD22 led to a reduction in neurological deficits, brain lesion and hematoma volume. This was accompanied by reduced inflammatory activity, increased expression of alternative activation markers (CD206 and IL-10) and enhanced phagocytosis activity in microglia after ICH. CD22 blockade also led to an increase of phosphorylated SYK and AKT after ICH. Notably, the benefits of CD22 blockade were ablated in ICH mice subjected to microglial depletion with a colony-stimulating factor 1 receptor inhibitor PLX5622. Additionally, the protective effects of CD22 blockade was diminished in ICH mice receiving a SYK inhibitor R406. Together, our findings highlight CD22 as a key molecular switch to control the detrimental effects of microglia after acute brain injury, and provide a novel strategy to improve the outcome of ICH injury.


Brain Injuries , Microglia , Sialic Acid Binding Ig-like Lectin 2 , Brain/metabolism , Cerebral Hemorrhage/drug therapy , Cerebral Hemorrhage/metabolism , Hematoma/complications , Hematoma/metabolism , Hematoma/pathology , Neuroinflammatory Diseases , Sialic Acid Binding Ig-like Lectin 2/antagonists & inhibitors , Sialic Acid Binding Ig-like Lectin 2/metabolism , Animals , Mice
12.
Medicine (Baltimore) ; 102(27): e34197, 2023 Jul 07.
Article En | MEDLINE | ID: mdl-37417636

RATIONALE: Coronavirus disease 2019 (COVID-19) can damage the central nervous system. Although there have been reports of cerebral hemorrhage and infarction caused by COVID-19, hematomyelia due to COVID-19 has never been reported. PATIENT CONCERNS: A 40-year-old male was admitted to the hospital with positive nucleic acid detection for COVID-19 after experiencing fever for 2 weeks, urinary retention, fecal retention, and pain in both lower extremities for a week. DIAGNOSES: The patient diagnosis was established using thoracic and lumbar magnetic resonance imaging (MRI). Contrast-enhanced thoracic and lumbar MRI revealed subdural (dorsal predominant) short T1 and slightly long T2 bands in the T12-S2 infundibular canal in the scan field, and the subdural hematoma was yet to be distinguished from other diseases. Spinal cord edema was observed in the left vertebral plate and facet joint of the T11 vertebral body, indicative of inflammation. The cerebrospinal fluid (CSF) was positive for COVID-19 nucleic acid. INTERVENTIONS: Antiinfection, immunomodulation, correction of acid-base balance and electrolyte disorders, improvement of circulation, nerve nutrition, and other symptomatic supportive treatments were administered to the patient. OUTCOMES: The patient symptoms significantly improved after 4 weeks of anti-infection and immunomodulatory therapy. Repeat thoracolumbar MRI revealed absorption of the spinal cord hematoma, and the patient was discharged from the hospital. To date, COVID-19-related hematomyelia has not been reported and anti-infective and immunomodulatory therapies may be effective. LESSONS: COVID-19 not only easily leads to brain injury but can also cause spinal cord injury and even spinal cord hemorrhage. When patients with COVID-19 experience symptoms and signs of spinal cord injury, spinal cord injury and bleeding caused by COVID-19 should be considered, and MRI and lumbar puncture should be performed as soon as possible to make a clear diagnosis.


COVID-19 , Spinal Cord Diseases , Spinal Cord Injuries , Spinal Cord Vascular Diseases , Male , Humans , Adult , COVID-19/complications , Spine/pathology , Hematoma/pathology , Magnetic Resonance Imaging
13.
Cells ; 12(8)2023 04 13.
Article En | MEDLINE | ID: mdl-37190062

Intracerebral hemorrhage (ICH) is a significant health concern associated with high mortality. Cofilin plays a crucial role in stress conditions, but its signaling following ICH in a longitudinal study is yet to be ascertained. In the present study, we examined the cofilin expression in human ICH autopsy brains. Then, the spatiotemporal cofilin signaling, microglia activation, and neurobehavioral outcomes were investigated in a mouse model of ICH. Human autopsy brain sections from ICH patients showed increased intracellular cofilin localization within microglia in the perihematomal area, possibly associated with microglial activation and morphological changes. Various cohorts of mice were subjected to intrastriatal collagenase injection and sacrificed at time points of 1, 3, 7, 14, 21, and 28 days. Mice suffered from severe neurobehavioral deficits after ICH, lasting for 7 days, followed by a gradual improvement. Mice suffered post-stroke cognitive impairment (PSCI) both acutely and in the chronic phase. Hematoma volume increased from day 1 to 3, whereas ventricle size increased from day 21 to 28. Cofilin protein expression increased in the ipsilateral striatum on days 1 and 3 and then decreased from days 7 to 28. An increase in activated microglia was observed around the hematoma on days 1 to 7, followed by a gradual reduction up to day 28. Around the hematoma, activated microglia showed morphological changes from ramified to amoeboid. mRNA levels of inflammatory [tumor necrosis factor-α (TNF-α), interleukin 1ß (IL-1ß), and interleukin-6 (IL-6) and anti-inflammatory markers [interleukin-10 (IL-10), transforming growth factor-ß TGF-ß, and arginase I (Arg1)] increased during the acute phase and decreased in the chronic phase. Blood cofilin levels increased on day 3 and matched the increase in chemokine levels. slingshot protein phosphatase 1 (SSH1) protein, which activates cofilin, was increased from day 1 to 7. These results suggest that microglial activation might be the sequel of cofilin overactivation following ICH, leading to widespread neuroinflammation and consequent PSCI.


Brain Injuries , Stroke , Humans , Mice , Animals , Microglia/metabolism , Neuroinflammatory Diseases , Actin Depolymerizing Factors/metabolism , Longitudinal Studies , Cerebral Hemorrhage/pathology , Hematoma/pathology , Brain Injuries/pathology , Stroke/metabolism
14.
Eur J Neurol ; 30(6): 1686-1695, 2023 06.
Article En | MEDLINE | ID: mdl-36847734

BACKGROUND AND PURPOSE: Neoplastic intracerebral hemorrhage (ICH) may be incorrectly identified as non-neoplastic ICH on imaging. Relative perihematomal edema (relPHE) on computed tomography (CT) has been proposed as a marker to discriminate neoplastic from non-neoplastic ICH but has not been externally validated. The purpose of this study was to evaluate the discriminatory power of relPHE in an independent cohort. METHODS: A total of 291 patients with acute ICH on CT and follow-up magnetic resonance imaging (MRI) were included in this single-center retrospective study. ICH subjects were dichotomized into non-neoplastic or neoplastic ICH based on the diagnosis on the follow-up MRI. ICH and PHE volumes and density values were derived from semi-manually segmented CT scans. Calculated PHE characteristics for discriminating neoplastic ICH were evaluated using receiver-operating characteristic (ROC) curves. ROC curve-associated cut-offs were calculated and compared between the initial and the validation cohort. RESULTS: A total of 116 patients (39.86%) with neoplastic ICH and 175 (60.14%) with non-neoplastic ICH were included. Median PHE volumes, relPHE, and relPHE adjusted for hematoma density were significantly higher in subjects with neoplastic ICH (all p values <0.001). ROC curves for relPHE had an area under the curve (AUC) of 0.72 (95% confidence interval [CI] 0.66-0.78) and an AUC of 0.81 (95% CI 0.76-0.87) for adjusted relPHE. The cut-offs were identical in the two cohorts, with >0.70 for relPHE and >0.01 for adjusted relPHE. CONCLUSIONS: Relative perihematomal edema and adjusted relPHE accurately discriminated neoplastic from non-neoplastic ICH on CT imaging in an external patient cohort. These results confirmed the findings of the initial study and may improve clinical decision making.


Brain Edema , Humans , Retrospective Studies , Brain Edema/diagnostic imaging , Brain Edema/etiology , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/pathology , Edema/diagnostic imaging , Edema/etiology , Magnetic Resonance Imaging , Hematoma/diagnostic imaging , Hematoma/pathology
15.
Vet Pathol ; 60(2): 235-244, 2023 03.
Article En | MEDLINE | ID: mdl-36601786

Hemorrhagic bowel syndrome (HBS) is a sporadic and fatal disease of predominantly lactating dairy cattle, characterized by segmental hemorrhage and luminal clot formation in the small intestine. Although, Clostridium perfringens and Aspergillus fumigatus have been associated with HBS, the pathogenesis and cause are currently unknown. In this study, 18 naturally occurring cases of HBS (7 necropsied immediately following euthanasia, 11 with 12-48 hour postmortem intervals) were investigated to characterize the pathology and the intestinal microbiome. Hemorrhagic bowel syndrome was characterized by a single small-intestinal, intramucosal hematoma with dissection of the lamina muscularis mucosae. In most cases necropsied immediately after euthanasia (4/7), the intestinal mucosa proximal to the hematoma contained 9 to 14, dispersed, solitary or clustered, erosions or lacerations measuring 4 to 45 mm. In 77% (37/48) of these mucosal lesions, microscopic splitting of the lamina muscularis mucosae comparable to the hematoma was present. These findings suggest the intramucosal hematoma to originate from small mucosal erosions through dissecting hemorrhage within the lamina muscularis mucosae. No invasive fungal growth was observed in any tissue. Bacteriological cultivation and nanopore sequencing showed a polymicrobial population at the hematoma and unaffected intestine, with mostly mild presence of C perfringens at selective culture. Gross and microscopic lesions, as well as the culture and sequencing results, were not in support of involvement of C perfringens or A fumigatus in the pathogenesis of HBS.


Intestines , Lactation , Female , Cattle , Animals , Intestines/pathology , Clostridium perfringens , Gastrointestinal Hemorrhage/microbiology , Gastrointestinal Hemorrhage/pathology , Gastrointestinal Hemorrhage/veterinary , Hematoma/pathology , Hematoma/veterinary , Syndrome
16.
Phytomedicine ; 108: 154530, 2023 Jan.
Article En | MEDLINE | ID: mdl-36356328

BACKGROUND: Intracerebral hemorrhage (ICH) is a life-threatening stroke subtype with high rates of disability and mortality. Naoxueshu oral liquid is a proprietary Chinese medicine that absorbs hematoma and exhibits neuroprotective effects in patients with ICH. However, the underlying mechanisms remain obscure. PURPOSE: Exploring and elucidating the pharmacological mechanism of Naoxueshu oral liquid in the treatment of ICH. STUDY DESIGN AND METHODS: The Gene Expression Omnibus (GEO) database was used to download the gene expression data on ICH. ICH-related hub modules were obtained by weighted gene co-expression network analysis (WGCNA) of differentially co-expressed genes (DEGs). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the obtained key modules to identify the ICH-related signaling pathways. Network pharmacology technology was applied to forecast the targets of Naoxueshu oral liquid and to establish a protein-protein interaction (PPI) network of overlapping targets between Naoxueshu oral liquid and ICH. Functional annotation and enrichment pathway analyses of the intersectional targets were performed using the omicsbean database. Finally, we verified the therapeutic role and mechanism of Naoxueshu oral liquid in ICH through molecular docking and experiments. RESULTS: Through the WGCNA analysis, combined with network pharmacology, it was found that immune inflammation was closely related to the early pathological mechanism of ICH. Naoxueshu oral liquid suppressed the inflammatory response; hence, it could be a potential drug for ICH treatment. Molecular docking further confirmed that the effective components of Naoxueshu oral liquid docked well with CD163. Finally, the experimental results showed that Naoxueshu oral liquid treatment in the ICH rat model attenuated neurological deficits and neuronal injury, decreased hematoma volume, and promoted hematoma absorption. In addition, Naoxueshu oral liquid treatment also significantly increased the levels of Arg-1, CD163, Nrf2, and HO-1 around hematoma after ICH. CONCLUSION: This study demonstrated that Naoxueshu oral liquid attenuated neurological deficits and accelerated hematoma absorption, possibly by suppressing inflammatory responses, which might be related to the regulation of Nrf2/CD163/HO-1 that interfered with the activation of M2 microglia, thus accelerating the clearance and decomposition of hemoglobin in the hematoma.


Cerebral Hemorrhage , NF-E2-Related Factor 2 , Animals , Rats , NF-E2-Related Factor 2/metabolism , Molecular Docking Simulation , Cerebral Hemorrhage/drug therapy , Cerebral Hemorrhage/genetics , Hematoma/metabolism , Hematoma/pathology , Gene Ontology
17.
Eur Radiol ; 33(1): 417-428, 2023 Jan.
Article En | MEDLINE | ID: mdl-35895121

OBJECTIVES: To evaluate the feasibility of contrast-enhanced mammography (CEM)-guided biopsy at Hospital del Mar, a Spanish university hospital. METHODS: We retrospectively reviewed all consecutive women with a suspicious enhancing finding eligible for CEM-guided biopsy, who were prospectively enrolled in a pre-marketing clinical validation and feasibility study (October 2019 to September 2021). CEM-guided biopsy is a stereotactic-based procedure that, by using intravenous iodinated contrast media administration and dual-energy acquisition, provides localisation of enhancing lesions. All the biopsies were performed using a vacuum-assisted device. We collected procedural characteristics (patient position and type of approach), and histopathological results. Feasibility endpoints included success (visualisation of the enhancing lesion, post-procedural biopsy changes and clip placement), procedural time, number of scout acquisitions and complications. RESULTS: A total of 66 suspicious enhancing lesions (18.0% foci, 44.0% mass, 38.0% non-mass enhancement; median size 8.5 mm) in 64 patients (median age 59 years, mostly minimal [48.4%] or mild [32.8%] background parenchymal enhancement) were referred for CEM-guided biopsy in the study period. The success rate was 63/66 (95.4%). Amongst successful procedures, patients were most frequently seated (52/63, 82.5%) and the preferred approach was horizontal (48/63, 76.2%). Median total time per procedure was 15 min. Median number of acquisitions needed before targeting was 2 (range 1-4). Complications consisted of hematoma (17/63, 27%) and vasovagal reaction (2/63, 3.2%). At histology, the malignancy rate was 25/63 (39.7%). CONCLUSION: In this first patient series, CEM-guided breast biopsy was feasible, with success and complication rates similar to those previously reported for magnetic resonance guidance. KEY POINTS: • CEM may be used to guide biopsy of enhancing lesions through a stereotactic-based procedure combined with intravenous iodinated contrast media administration and dual-energy acquisition. • In this first patient series (n = 64), the success rate of CEM-guided biopsy was above 95%, the only complications were hematoma (22.2%) and vasovagal reaction (3.2%), and median total time per procedure was 15 min. • CEM-guided biopsy is feasible and could potentially be a widely available biopsy technique for enhancing-only lesions.


Breast Neoplasms , Iodine Compounds , Humans , Female , Middle Aged , Contrast Media/pharmacology , Retrospective Studies , Feasibility Studies , Mammography , Biopsy , Breast/diagnostic imaging , Breast/pathology , Hematoma/pathology , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Image-Guided Biopsy/methods
18.
Am J Sports Med ; 51(1): 58-65, 2023 01.
Article En | MEDLINE | ID: mdl-36440714

BACKGROUND: Bone bruises observed on magnetic resonance imaging (MRI) can provide insight into the mechanisms of noncontact anterior cruciate ligament (ACL) injury. However, it remains unclear whether the position of the knee near the time of injury differs between patients evaluated with different patterns of bone bruising, particularly with regard to valgus angles. HYPOTHESIS: The position of the knee near the time of injury is similar between patients evaluated with 2 commonly occurring patterns of bone bruising. STUDY DESIGN: Descriptive laboratory study. METHODS: Clinical T2- and T1-weighted MRI scans obtained within 6 weeks of noncontact ACL rupture were reviewed. Patients had either 3 (n = 20) or 4 (n = 30) bone bruises. Patients in the 4-bone bruise group had bruising of the medial and lateral compartments of the femur and tibia, whereas patients in the 3-bone bruise group did not have a bruise on the medial femoral condyle. The outer contours of the bones and associated bruises were segmented from the MRI scans and used to create 3-dimensional surface models. For each patient, the position of the knee near the time of injury was predicted by moving the tibial model relative to the femoral model to maximize the overlap of the tibiofemoral bone bruises. Logistic regressions (adjusted for sex, age, and presence of medial collateral ligament injury) were used to assess relationships between predicted injury position (quantified in terms of knee flexion angle, valgus angle, internal rotation angle, and anterior tibial translation) and bone bruise group. RESULTS: The predicted injury position for patients in both groups involved a flexion angle <20°, anterior translation >20 mm, valgus angle <10°, and internal rotation angle <10°. The injury position for the 3-bone bruise group involved less flexion (odds ratio [OR], 0.914; 95% CI, 0.846-0.987; P = .02) and internal rotation (OR, 0.832; 95% CI, 0.739-0.937; P = .002) as compared with patients with 4 bone bruises. CONCLUSION: The predicted position of injury for patients displaying both 3 and 4 bone bruises involved substantial anterior tibial translation (>20 mm), with the knee in a straight position in both the sagittal (<20°) and the coronal (<10°) planes. CLINICAL RELEVANCE: Landing on a straight knee with subsequent anterior tibial translation is a potential mechanism of noncontact ACL injury.


Anterior Cruciate Ligament Injuries , Contusions , Knee Injuries , Humans , Anterior Cruciate Ligament Injuries/diagnostic imaging , Anterior Cruciate Ligament Injuries/pathology , Knee Injuries/diagnostic imaging , Knee Injuries/pathology , Knee Joint/diagnostic imaging , Knee Joint/pathology , Tibia/pathology , Femur/pathology , Contusions/diagnostic imaging , Contusions/pathology , Epiphyses/pathology , Magnetic Resonance Imaging/methods , Hematoma/pathology , Biomechanical Phenomena
20.
Acta Dermatovenerol Croat ; 31(4): 192-197, 2023 Dec.
Article En | MEDLINE | ID: mdl-38651845

BACKGROUND: The diagnosis of subcorneal hematoma (SH) can be challenging because the clinical presentation of SH can resemble melanocytic lesions. Few studies have examined the characteristic dermoscopic features of SH, but a more detailed large-scale study is needed to overcome the diagnostic challenge of differentiating it from acral melanoma. OBJECTIVES: To describe the dermoscopic features of SH. METHODS: We evaluated the clinical and dermoscopic features of 50 SH lesions from 43 patients at the Pusan National University Hospitals (Busan and Yangsan). RESULTS: In the color analysis, 86% of cases showed the bruise color sign; 7 cases had a single color (red to purple: 2; black: 1; brown: 4). Typical dermoscopic features of SH, acral nevi, and acral melanoma-associated patterns were observed in 60%, 0%, and 72% of lesions, respectively. Hematoma-associated patterns were homogenously red-to-black with or without satellite globules (32%) and pebbles on the ridges (28%). Acral melanoma-associated patterns showed a parallel ridge pattern (PRP) (52%), irregular dots and globules (50%), polychromia (34%), asymmetry (24%), irregular blotches (10%), and ulcers (10%). No case showed blue-white veils, regression structures, atypical vascular patterns, or irregular fibrillar patterns. The bruise color sign was positive in most cases, with acral melanoma-associated patterns (88.9%).


Dermoscopy , Hematoma , Melanoma , Skin Neoplasms , Humans , Melanoma/pathology , Melanoma/complications , Male , Female , Middle Aged , Skin Neoplasms/pathology , Skin Neoplasms/complications , Aged , Hematoma/pathology , Adult , Diagnosis, Differential , Aged, 80 and over , Retrospective Studies , Hand/pathology
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