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Kidney International Jul 2024Parietal epithelial cells (PECs) are kidney progenitor cells with similarities to a bone marrow stem cell niche. In focal segmental glomerulosclerosis (FSGS) PECs become...
Parietal epithelial cells (PECs) are kidney progenitor cells with similarities to a bone marrow stem cell niche. In focal segmental glomerulosclerosis (FSGS) PECs become activated and contribute to extracellular matrix deposition. Colony stimulating factor-1 (CSF-1), a hematopoietic growth factor, acts via its specific receptor, CSF-1R, and has been implicated in several glomerular diseases, although its role on PEC activation is unknown. Here, we found that CSF-1R was upregulated in PECs and podocytes in biopsies from patients with FSGS. Through in vitro studies, PECs were found to constitutively express CSF-1R. Incubation with CSF-1 induced CSF-1R upregulation and significant transcriptional regulation of genes involved in pathways associated with PEC activation. Specifically, CSF-1/CSF-1R activated the ERK1/2 signaling pathway and upregulated CD44 in PECs, while both ERK and CSF-1R inhibitors reduced CD44 expression. Functional studies showed that CSF-1 induced PEC proliferation and migration, while reducing the differentiation of PECs into podocytes. These results were validated in the Adriamycin-induced FSGS experimental mouse model. Importantly, treatment with either the CSF-1R-specific inhibitor GW2580 or Ki20227 provided a robust therapeutic effect. Thus, we provide evidence of the role of the CSF-1/CSF-1R pathway in PEC activation in FSGS, paving the way for future clinical studies investigating the therapeutic effect of CSF-1R inhibitors on patients with FSGS.
Topics: Glomerulosclerosis, Focal Segmental; Animals; Humans; Podocytes; Macrophage Colony-Stimulating Factor; Hyaluronan Receptors; Mice; Cell Proliferation; Epithelial Cells; Receptor, Macrophage Colony-Stimulating Factor; Kidney Glomerulus; Male; Disease Models, Animal; Cells, Cultured; Female; Up-Regulation; Cell Movement; MAP Kinase Signaling System; Signal Transduction; Mice, Inbred C57BL; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
PubMed: 38428734
DOI: 10.1016/j.kint.2024.02.010 -
NMC Case Report Journal 2024Meningiomas originating within the bones of the skull are rare and have been reported as primary intraosseous meningiomas (PIOM). Moreover, PIOMs with a skull base...
Meningiomas originating within the bones of the skull are rare and have been reported as primary intraosseous meningiomas (PIOM). Moreover, PIOMs with a skull base location or malignant pathology are predisposed to recurrence; however, recurrence is quite rare among PIOMs characterized by a convexity location and benign pathology. Here, we present a case of extensive recurrence of a convex intraosseous meningioma with benign pathology. A 72-year-old woman presented with a headache to our hospital. Gd contrast-enhanced magnetic resonance imaging revealed an enhanced tumor in the left frontal to the parietal region extending through the calvarial bone and invading the subdural space and subcutaneous tissue. Skull radiograph and computed tomography identified a remarkable osteolytic change in the lesion. Macroscopic complete resection (MCR) of the tumor and the surrounding tissues was performed. The tumor was histopathologically diagnosed as a transitional meningioma (World Health Organization grade 1). Seven years after the surgery, the patient presented with dysarthria, and the recurrence of the tumor was identified as massive lesions extending through the calvarial bone to the orbital bone, partially protruding into the brain and scalp. MCR was performed again, with the reconstruction of the skull for an extensive calvarial area using a titanium plate. This case is unique due to the extensiveness of the recurrent tumor and its rarity. Here, we report the details of the clinical course and discuss the characteristics of this case.
PubMed: 38410174
DOI: 10.2176/jns-nmc.2023-0171 -
Diagnostics (Basel, Switzerland) Feb 2024Parietal thinning was detected in a 72-year-old with recurrent headaches. Quantification of bone loss was performed applying two- and three-dimensional methods using...
Parietal thinning was detected in a 72-year-old with recurrent headaches. Quantification of bone loss was performed applying two- and three-dimensional methods using computerized tomographies. Two-dimensional methods provided accurate measurements using single-line analyses of bone thicknesses (2.13 to 1.65 and 1.86 mm on the left and 4.44 to 3.08 and 4.20 mm on the right side), single-point analyses of bone intensities (693 to 375 and 403 on the left and 513 to 393 and 411 Houndsfield Units on the right side) and particle-size analyses of low density areas (16 to 22 and 12 on the left and 18 to 23 and 14 on the right side). Deteriorations between days 0 and 220 followed by bone stability on day 275 were paralleled using the changed volumes of bone defects to 1200 and finally 1133 mm on the left side and to 331 and finally 331 mm on the right side. Interfolding as measurement of the bones' shape provided changes to -1.23 and -1.72 mm on the left and to -1.42 and -1.30 mm on the right side. These techniques suggest a stabilizing effect of corticosteroids between days 220 and 275. Reconstruction of computerized tomographies appears justified to allow for quantification of bone loss during long-term follow-up.
PubMed: 38396485
DOI: 10.3390/diagnostics14040446 -
International Journal of Legal Medicine Jul 2024Post-mortem computed tomography (PMCT) enables the creation of subject-specific 3D head models suitable for quantitative analysis such as finite element analysis (FEA)....
Post-mortem computed tomography (PMCT) enables the creation of subject-specific 3D head models suitable for quantitative analysis such as finite element analysis (FEA). FEA of proposed traumatic events is an objective and repeatable numerical method for assessing whether an event could cause a skull fracture such as seen at autopsy. FEA of blunt force skull fracture in adults with subject-specific 3D models in forensic pathology remains uninvestigated. This study aimed to assess the feasibility of FEA for skull fracture analysis in routine forensic pathology. Five cases with blunt force skull fracture and sufficient information on the kinematics of the traumatic event to enable numerical reconstruction were chosen. Subject-specific finite element (FE) head models were constructed by mesh morphing based on PMCT 3D models and A Detailed and Personalizable Head Model with Axons for Injury Prediction (ADAPT) FE model. Morphing was successful in maintaining subject-specific 3D geometry and quality of the FE mesh in all cases. In three cases, the simulated fracture patterns were comparable in location and pattern to the fractures seen at autopsy/PMCT. In one case, the simulated fracture was in the parietal bone whereas the fracture seen at autopsy/PMCT was in the occipital bone. In another case, the simulated fracture was a spider-web fracture in the frontal bone, whereas a much smaller fracture was seen at autopsy/PMCT; however, the fracture in the early time steps of the simulation was comparable to autopsy/PMCT. FEA might be feasible in forensic pathology in cases with a single blunt force impact and well-described event circumstances.
Topics: Humans; Finite Element Analysis; Skull Fractures; Male; Imaging, Three-Dimensional; Tomography, X-Ray Computed; Forensic Pathology; Adult; Female; Middle Aged; Autopsy; Aged
PubMed: 38386034
DOI: 10.1007/s00414-024-03186-3 -
Oral and Maxillofacial Surgery Jun 2024We report a case of fibrous dysplasia (FD) with aneurysmal bone cyst (ABC)-like change in a child with orbital involvement, review the related cases, and discuss... (Review)
Review
PURPOSE
We report a case of fibrous dysplasia (FD) with aneurysmal bone cyst (ABC)-like change in a child with orbital involvement, review the related cases, and discuss clinical features, therapy, and prognosis of this disease.
CASE PRESENTATION
A 10-year-old girl had right proptosis (degree of exophthalmos: OD 16 mm, OS 13 mm) and limited vision (visual acuity: OD 1.0, OS 0.8) without trauma. Preoperative CT showed a 5.0*4.3 cm right-sided crania-orbital communicating tumor. MRI indicated a well-defined multicystic mass with scattered fluid levels and soap bubble-like alterations. The child underwent total tumor resection and orbital parietal titanium mesh reconstruction. At 20 months of follow-up, the child has recovered from ocular problems, and the tumor has not recurred.
CONCLUSION
FD combined with ABC rarely occurs in orbit and generally begins with ocular symptoms. The etiology is uncertain. Early diagnosis and surgery are essential. Complete resection is suggested whenever possible because residual lesions may recur.
Topics: Humans; Female; Child; Bone Cysts, Aneurysmal; Exophthalmos; Tomography, X-Ray Computed; Orbital Diseases; Magnetic Resonance Imaging; Fibrous Dysplasia of Bone; Surgical Mesh; Plastic Surgery Procedures
PubMed: 38378934
DOI: 10.1007/s10006-024-01217-2 -
Medicine Feb 2024As the second leading cause of death and disability worldwide, stroke is mainly caused by atherosclerosis and cardiac embolism, particularly in older individuals.... (Review)
Review
INTRODUCTION
As the second leading cause of death and disability worldwide, stroke is mainly caused by atherosclerosis and cardiac embolism, particularly in older individuals. Nevertheless, in young and otherwise healthy individuals, the causes of stroke can be more diverse and may include conditions such as patent foramen ovale, vasculitis, coagulopathies, genetic factors, or other undetermined causes. Although these other causes of stroke account for a relatively small proportion compared to ischemic stroke, they are becoming increasingly common in clinical practice and deserve attention. Here, we present a rare female patient with polycythemia vera (PV) who was admitted to the hospital as a stroke patient without any previous medical history.
PATIENT CONCERNS
A 40-year-old young woman felt sudden dizziness and slow response. After 4 days of being admitted, she developed blurry vision on the right.
DIAGNOSES
Cranial magnetic resonance imaging revealed aberrant signals in the left temporal and parietal lobe, as well as multiple small focal signal abnormalities were observed in the left frontal lobe. Magnetic resonance angiography revealed partial stenosis of the left internal carotid artery. The patient's blood routine examination revealed a significant elevation in complete blood counts, particularly the increase in red blood cells, as well as prolonged clotting time. An abdominal ultrasound and abdomen computed tomography showed splenomegaly. The outcome of the genetic testing was positive for the Janus kinase JAK2 exon V617F mutation (JAK2/V617F). The patient was diagnosed with PV-related stroke.
INTERVENTIONS
The patient was treated with phlebotomy, cytoreductive therapy, and low-dose aspirin antiplatelet therapy and was regularly followed up in hematology and neurology clinics after discharge.
OUTCOMES
The patient's red blood cell, leukocyte, and thrombocyte counts had fully normalized, with her hemoglobin level measuring at 146 g/L and hematocrit value at 43%. Furthermore, there had been a significant improvement in neurological symptoms.
LESSONS
PV, a rare hematological disorder, can present with ischemic stroke as the initial performance, and the diagnosis mainly relies on routine blood tests, bone marrow biopsies, and genetic test. Therefore, clinicians should pay attention to PV, a low-prevalence disease, when encountering stroke in youth.
Topics: Female; Humans; Young Adult; Aged; Adolescent; Adult; Male; Polycythemia Vera; Ischemic Stroke; Janus Kinase 2; Bone Marrow; Mutation
PubMed: 38363912
DOI: 10.1097/MD.0000000000036953 -
Effect of direct oral anticoagulant dabigatran on early bone healing: An experimental study in rats.Journal of Advanced Periodontology &... 2023Dabigatran belongs to the new generation of direct oral anticoagulants (DOACs). Its advantages are oral administration and no need for international normalized ratio...
BACKGROUND
Dabigatran belongs to the new generation of direct oral anticoagulants (DOACs). Its advantages are oral administration and no need for international normalized ratio (INR) monitoring. Although its use has increased, its potential side effects on bone healing and remodeling have not been fully investigated. The present study aimed to evaluate the possible effects of dabigatran on early bone healing.
METHODS
Sixteen male Wistar rats were divided into two groups; in group A, 20-mg/kg dabigatran dose was administered orally daily for 15 days, while group B served as a control. Two circular bone defects (d=6 mm) were created on either side of the parietal bones. Two weeks after surgery and euthanasia of the animals, tissue samples (parietal bones that contained the defects) were harvested for histological and histomorphometric analysis. Statistical analysis was performed with a significance level of α=0.5.
RESULTS
No statistically significant differences were found between the two groups regarding the regenerated bone (21.9% vs. 16.3%, =0.172) or the percentage of bone bridging (63.3% vs. 53.5%, =0.401).
CONCLUSION
Dabigatran did not affect bone regeneration, suggesting that it might be a safer drug compared to older anticoagulants known to lead to bone healing delay.
PubMed: 38357331
DOI: 10.34172/japid.2023.020 -
Pediatric extra-axial glioblastoma with bone invasion leading to a subcutaneous mass: A case report.Surgical Neurology International 2024Pediatric glioblastoma multiforme (p-GBM) is an exceptionally rare and aggressive brain tumor, with even fewer reported cases with radiographic and intraoperative...
BACKGROUND
Pediatric glioblastoma multiforme (p-GBM) is an exceptionally rare and aggressive brain tumor, with even fewer reported cases with radiographic and intraoperative characteristics that mimic those of extra-axial lesions, often posing a diagnostic challenge. Despite advancements in imaging technologies, the diagnosis of GBM can still be intricate, relying primarily on histopathological confirmation.
CASE DESCRIPTION
We present a unique case of a 15-year-old female who presented to our hospital with a new-onset focal-to-bilateral tonic-clonic seizure described as clonic movements of her left hemicorps; on clinical examination, a subcutaneous mass was evident in the right parietal region. Magnetic resonance imaging of the brain revealed a sizable extra-axial enhancing mass measuring 9 cm, located in the right parieto-occipital region with notable bone invasion. Moreover, the intraoperative findings revealed an extra-axial mass attached to the dura. Total resection was achieved. The histopathological analysis confirmed the diagnosis of glioblastoma multiforme. Subsequently, the patient underwent adjuvant radiotherapy in conjunction with temozolomide chemotherapy. Postoperatively, she exhibited clinical improvement and remained stable throughout the 6-month follow-up period.
CONCLUSION
We present the first case of extra-axial p-GBM in a young patient, which remarkably led to the destruction of the bone and finally resulted in a sizable parietal subcutaneous lesion in the absence of prior surgery or radiation.
PubMed: 38344102
DOI: 10.25259/SNI_809_2023 -
Surgical Neurology International 2024Solitary plasmacytoma of the calvarium (SPC), without evidence of multiple myeloma (MM), is extremely rare. We report a case of a long-standing large SPC that was...
BACKGROUND
Solitary plasmacytoma of the calvarium (SPC), without evidence of multiple myeloma (MM), is extremely rare. We report a case of a long-standing large SPC that was treated successfully by surgical excision and adjuvant radiotherapy with a long follow-up period.
CASE DESCRIPTION
A 58-year-old male patient presented with a 5-year history of painless skull swelling. On the physical examination, the mass was 6 × 6 cm in size, oval, not tender, and firm in consistency with normal skin color. A brain computed tomography scan showed a destructive skull lesion. A brain magnetic reasoning imaging (MRI) showed a large expansile lytic mass lesion arising from the skull vault in the frontal-parietal region with multiple internal septa. The patient underwent a craniectomy and excision of the lesion, followed by cranioplasty using methyl methacrylate. The final diagnosis was consistent with plasmacytoma based on the histopathological features. One month follow-up brain MRI showed no evidence of residual tumor. The skeletal survey and bone marrow biopsy did not reveal any evidence of MM. The patient was referred to medical oncology for further treatment and received radiation therapy. During nine years of clinical and radiological follow-up, there was no evidence of any metastasis or recurrence.
CONCLUSION
SPC is a rare disease with high rates of misdiagnosis. Careful evaluations are crucial to exclude systemic involvement. Surgical resection followed by radiotherapy may be adequate for the disease control. Close follow-up with regular lifelong examinations is important to avoid a generalized incurable disease.
PubMed: 38344097
DOI: 10.25259/SNI_817_2023 -
Surgical Neurology International 2024FD is relatively rare in the craniofacial region, accounting for only 20% of all cases. Currently, two general subtypes of FD are recognized: monostotic and polyostotic....
BACKGROUND
FD is relatively rare in the craniofacial region, accounting for only 20% of all cases. Currently, two general subtypes of FD are recognized: monostotic and polyostotic. The monostotic form is more frequent, accounting for 75% to 80% of fibrous dysplasia cases.
CASE DESCRIPTION
An 18-year-old male presented with the complaint of bony-hard swelling over the forehead for 8 years. Radiology showed an expansile osseous lesion involving frontal bones. The patient underwent bi-frontal craniectomy with gross total resection of tumour mass with titanium mesh cranioplasty. His postoperative period was uneventful and was discharged on the seventh postoperative day.
CONCLUSION
The cases of monostotic skull fibrous dysplasia should be treated by resection of the affected bone and cranioplasty. However, a more conservative re-contouring may be carried out in cases with multifocal involvement or when the excision is considered risky due to proximity to the major venous sinuses.
PubMed: 38344095
DOI: 10.25259/SNI_201_2023