Wall Inflammation Research Articles

Exploring the comorbidity mechanisms between atherosclerosis and hashimoto’s thyroiditis based on microarray and single-cell sequencing analysis

Abstract Atherosclerosis (AS) is a chronic vascular disease characterized by inflammation of the arterial wall and the formation of cholesterol plaques. Hashimoto’s thyroiditis (HT) is an autoimmune disorder marked by chronic inflammation and destruction of thyroid tissue. Although previous studies have identified common risk factors between AS and HT, the specific etiology and pathogenic mechanisms underlying these associations remain unclear. We obtained relevant datasets for AS and HT from the Gene Expression Omnibus (GEO). By employing the Limma package, we pinpointed common differentially expressed genes (DEGs) and discerned co-expression modules linked to AS and HT via Weighted Gene Co-expression Network Analysis (WGCNA). We elucidated gene functions and regulatory networks across various biological scenarios through enrichment and pathway analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Core genes were identified using Cytoscape software and further validated with external datasets. We also conducted immune infiltration analysis on these core genes utilizing the CIBERSORT method. Lastly, Single-cell analysis was instrumental in uncovering common diagnostic markers. Based on differential analysis and WGCNA, we identified 119 candidate genes within the cohorts for AS and HT. KEGG and GO enrichment analyses indicate that these genes are significantly involved in antigen processing and presentation, along with various immune-inflammatory pathways. Two pivotal genes, PTPRC and TYROBP, were identified using five algorithms from the cytoHubba plugin. Validation through external datasets confirmed their substantial diagnostic value for AS and HT. Moreover, the results of Gene Set Enrichment Analysis (GSEA) indicated that these core genes are significantly enriched in various receptor interactions and signaling pathways. Immune infiltration analysis revealed a strong association of lymphocytes and macrophages with the pathogenesis of AS and HT. Single-cell analysis demonstrated predominant expression of the core genes in macrophages, monocytes, T cells and Common Myeloid Progenitor (CMP). This study proposes that an aberrant immune response might represent a shared pathogenic mechanism in AS and HT. The genes PTPRC and TYROBP are identified as critical potential biomarkers and therapeutic targets for these comorbid conditions. Furthermore, the core genes and their interactions with immune cells could serve as promising targets for future diagnostic and therapeutic strategies.

Inflammation of adenohypophysis is commonly associated with headache in surgically managed Rathke's cleft cysts.

Rathke's cleft cysts (RCC) are present in up to 20% of autopsy studies but only a minority necessitate surgical treatment. Inflammation of RCC is thought to be significant in three processes: the development of classical symptoms, a predisposition to rupture or apoplexy, and increasing the rate of RCC recurrence. We aim to characterize clinical presentation, histological and radiological findings in patients with surgically managed RCC. We conducted a retrospective case series of 31 RCC, which had undergone surgical management between April 2016 and April 2024. Histopathology and radiology were independently reviewed by neuropathologist and neuroradiologist, and case notes were reviewed for clinical and biochemical data. Median age was 43 years (IQR 32-63); 77% were female. 23/31 demonstrated inflammation of RCC cyst epithelium (n = 13), cyst wall (n = 20) or anterior pituitary (adenohypophysitis) (n = 12). 8 cases were not inflamed. Preoperative features included pituitary dysfunction (70%), headache (65%), visual disturbance (26%) and polyuria/polydipsia (7%). Six patients presented with features of apoplexy. Headache was more prevalent (92%) in patients with adenohypophysitis vs. those without (47%), p = 0.020, and present in all 11 cases where inflammation in the adenohypophysis was chronic. Pituitary dysfunction was not associated with inflammation overall (76% vs. 70% p = ns), nor specifically within the adenohypophysis (75 vs. 63% p = 0.69). Histological inflammation was associated with radiological loss of posterior bright spot (70% vs. 14% p = 0.024). Headache but not pituitary dysfunction was associated with adenohypophyseal inflammation. A trend of increasing headache prevalence was seen with increasing degree of inflammatory infiltrate within RCC.

Current state of epigenetics in giant cell arteritis: Focus on microRNA dysregulation.

Giant cell arteritis (GCA) is a primary systemic vasculitis affecting the elderly, characterized by a granulomatous vessel wall inflammation of large- and medium-sized arteries. The immunopathology of GCA is complex, involving both the innate and adaptive arms of the immune system, where a maladaptive inflammatory-driven vascular repair process ultimately results in vessel wall thickening, intramural vascular smooth muscle cell proliferation, neovascularization and vessel lumen occlusion, which can lead to serious ischemic complications such as visual loss and ischemic stroke. Over the past decade, microRNA (miRNA) dysregulation has been highlighted as an important contributing factor underlying the pathogenesis of GCA. Since current understanding of miRNA involvement in GCA remains largely based on extrapolation of previously determined miRNA functions in vitro or in loss- or gain-of-function studies, an overall insight into the role of miRNA alteration in GCA pathophysiology remains limited. In this narrative review, we summarize the current knowledge on aberrantly expressed miRNAs in GCA and thoroughly discuss the impact of their altered regulatory role in the context of GCA setting. Furthermore, we address challenges and future perspectives in utilization of miRNA-based diagnostic and prognostic biomarkers of GCA in clinical settings.

Vasculitic Myopathy: Clinical Characteristics and Long-Term Outcomes.

Peripheral neuropathy is a common manifestation of systemic and nonsystemic vasculitides; however, there is limited literature on vasculitic myopathy. We aim to describe the clinical, laboratory, and pathologic characteristics and treatment outcomes of vasculitic myopathy. A retrospective chart review of patients with a diagnosis of vasculitis and myopathy (1980-2022) was performed. Patients were included with either biopsy-proven vasculitic myopathy or biopsy-proven vasculitis (of nonmuscle tissue) and concomitant active myopathy after excluding alternative causes. All muscle biopsy slides were reviewed, and additional immunohistochemistry studies were performed. Twenty-five patients with vasculitic myopathy were identified, 60% were female, and the median age at diagnosis was 63 (interquartile range 38-81) years. Ten patients (40%) had a primary systemic vasculitis, 12 secondary systemic vasculitis (48%), and 3 had nonsystemic vasculitic myopathy (12%). Myopathy was the initial manifestation of vasculitis in 20 of 25 patients (80%). Weakness was proximal and symmetric in most cases. Nineteen patients (76%) had pain at presentation: 2 with only neuropathic pain, 10 with only myalgia, and 7 had a combination of neuropathic pain distally and myalgia proximally. Creatine kinase (CK) was elevated in 3 of 23 patients (13%) and aldolase elevated in 10 of 16 patients (63%). Electromyography revealed short duration motor unit potentials in proximal and axial muscles in 23 of 24 patients (96%) and superimposed peripheral neuropathy in 15 of 24 (63%). Muscle biopsy showed perivascular inflammation in all biopsies, vessel wall inflammation and destruction in 18 of 21 (86%), and fibrinoid necrosis in 13 of 21 biopsies (62%). Masson trichrome stain facilitated the detection of fibrinoid necrosis. All muscle specimens had increased major histocompatibility complex class I sarcolemmal reactivity in nonnecrotic fibers. In most patients, the inflammatory infiltrates were predominantly CD4+ T cells, with complement deposition on blood vessels in some. Twenty-four patients improved with immunotherapy, and only 3 patients relapsed. Seven patients died during the study period, 1 from vasculitis complications. Probability of survival at 1 and 5 years was 96% and 84%, respectively. Myopathy can be the initial manifestation of a primary or secondary systemic vasculitis or may occur as a nonsystemic form. Most patients present with proximal predominant weakness with normal CK and elevated aldolase levels. Patients usually respond well to immunotherapy.

Comparison of the Effects of Perineural and Intraperitoneal Ozone Therapy on Nerve Healing in an Experimental Sciatic Nerve Injury Model.

Background and Objectives: The aim was to evaluate nerve healing using immunohistochemical, histological, and functional techniques and to compare the effects of two different therapeutic ozone application methods by perineural and intraperitoneal ozone treatment in rats with a crush injury model of sciatic nerve. Materials and Methods: Forty male Sprague Dawley rats were divided into four subgroups of ten rats each: (1) Control group: The left sciatic nerve incised and closed without crush injury, no treatment; (2) Paralyzed group: Crush injury to the left sciatic nerve, no treatment; (3) Perineural ozone group: Crush injury to the left sciatic nerve, treated with perineural ozone therapy; (4) Intraperitoneal ozone group: Crush injury to the left sciatic nerve, treated with intraperitoneal ozone therapy. The treatments were administered for a 14-day period. Hematoxylin and eosin (H&E) and toluidine blue staining were used for histological examination; TUNEL staining was used for immunohistochemical examination. Pinch test and rotarod performance assessment were utilized for functional evaluation. Results: The pinch test scores showed significant improvement in perineural and intraperitoneal ozone treatment groups after treatment (p < 0.001 and p = 0.003, respectively). The scores of myelin degeneration, vascular congestion, vascular wall thickness, inflammation, and toluidine blue and TUNEL staining were significantly lower in both ozone treatment groups compared to the paralyzed group (p < 0.001). Vascular wall thickness scores were significantly higher in the perineural ozone group compared to the control and intraperitoneal ozone groups (p = 0.004 and p = 0.013, respectively). The Schwann cell proliferation scores were significantly higher in the perineural ozone group compared to the control group and intraperitoneal ozone groups (p < 0.001). Conclusions: Both applications of ozone therapy accelerated the healing of nerve regeneration, reduced inflammation and apoptosis based on histopathological results, and enhanced nerve function in rats with sciatic nerve injury. Perineural ozone therapy has been demonstrated to be an efficacious alternative to systemic ozone treatments in the management of sciatic nerve injury. Further studies are needed to determine optimal ozone dosage and administration protocols for the treatment of nerve injury.

Effect of statins on arterial wall inflammation as assessed by 18F-FDG PET CT: an updated systematic review and meta-analysis

BackgroundPathogenesis of atherosclerosis is largely mediated by inflammatory process. Statins are lipid-lowering drugs which also have anti-inflammatory effects. 18 fluorine radiolabeled fluorodeoxyglucose (18 F-FDG) positron emission tomography-computed tomography (PET-CT) is considered to be a good indicator of arterial wall inflammation. Therefore, in this meta-analysis the role of statins on inflammatory process in the artery wall was evaluated using this method since its actual validity for this purpose is not yet well established.MethodsPubMed, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases were searched using MESH terms and keywords. Funnel plot, Begg’s rank correlation, and Egger’s weighted regression tests evaluated publication bias in the meta-analysis. In cases where funnel plot asymmetry was observed, the “trim and fill” method was used to check the input of potentially missing studies.ResultsFindings of 10 clinical trials involving 373 subjects showed a remarkable reduction of arterial wall 18 F-FDG uptake according to target-to-background ratio (TBR) index after treatment with statins. Subgroup analysis showed a significant decrease in TBR with high-intensity and non-significant reduction of TBR with low-to-moderate-intensity statin therapy.ConclusionTreatment with statins suppressed arterial wall inflammation as shown by using 18 F-FDG PET-CT.

ВЛИЯНИЕ ПРЕПАРАТА ОМНИК НА ИНТЕНСИВНОСТЬ КЛЕТОЧНЫХ РЕАКЦИЙ В ОЧАГЕ ЭКСПЕРИМЕНТАЛЬНОГО ВОСПАЛЕНИЯ

Relevance. The effect of the drug Omnic (Tamsulosin) reduces the tone of the smooth muscles of the prostate gland, bladder neck, prostatic part of the urethra, improves urine flow, reduces the symptoms of obstruction and irritation of the urinary tract in benign prostatic hypertrophy. However, there are no data on its anti-inflammatory effect. Objective. To determine the mechanisms of the anti-inflammatory effect of the drug Omnic on the model of purulent inflammation in rats. Material and methods. The study was conducted on 50 outbred white male rats divided into 2 series: Series 1 - control (they were implanted with diffusion chambers filled with an aqueous suspension of a one-day culture of staphylococcus aureus under the skin of the thigh; Series 2 - experimental (the animals of this series were modeled with purulent inflammation similar to the control, but from the 1st day of inflammation, the rats were injected intramuscularly with 0.02 ml of the Omnic preparation for 10 days). The materials were collected 2, 3, 5, 7, 10, 15, 20, 30, 60 days after implantation. The material was fixed in a 10 % solution of neutral formalin. In the peripheral zone of the inflammation focus, the state of the microvessels was qualitatively assessed, the concentration of mast cells, eosinophils, neutrophils, mononuclear cells and poorly differentiated fibroblasts was counted. Results. After 48 Hours after the onset of inflammation, a cellular wall with a thickness of 313.18 ± 30.19 μm is observed around the chamber wall. Three days after the introduction of the chambers, the thickness of the leukocyte wall remains the same and is 334.38 ± 25.69 μm. Five days after the onset of inflammation, the thickness of the leukocyte wall decreases sharply compared to the previous period and is 157.86 ± 46.08 μm. Seven days after the introduction of the chambers, the thickness of the cellular wall increases to 220 ± 29.67 μm. On the 10th day from the onset of inflammation, the thickness of the wall decreases to 129.52 ± 21.01 μm. On the 15th day of inflammation, the thickness and condition of the leukocyte wall do not change. On days 20-30-60 from the moment of implantation of the chambers, the remains of the leukocyte shaft with a thickness of 117.86 ± 29.6 μm were observed around them. Conclusion. The effect of Omnic on the dynamics of cellular reactions in the inflammation focus enhances the migration capacity of leukocytes, concentrates fibroblasts around the leukocyte shaft. At the same time, the synthesis of collagen by fibroblasts does not correspond to the thickness of the connective tissue capsule, which disrupts the maturation process of the capsule. Presumably, the action of Omnic is associated with the effect of the drug on the tone of capillaries and venules

CXCR4-targeted sensitive magnetic particle imaging for abdominal aortic aneurysm early detection and prognosis evaluation by recognizing total inflammatory cells.

The maximum aortic diameter remains the diagnostic criteria and the indicator for prognosis prediction of abdominal aortic aneurysms (AAA). An additional imaging modality is currently needed to help evaluate the prognosis of AAA as well as early detection of AAA formation. This study evaluated the most effective inflammatory markers for AAA using single-cell sequencing and, from these, developed probes to facilitate in vivo multimodal imaging of AAA inflammation. Single-cell RNA sequencing (scRNAseq) of the human aortic aneurysms, GSE155468 and GSE166676 datasets, identified CXCR4 as the most representative marker. Anti-CXCR4-PE antibody was conjugated to superparamagnetic iron oxide nanoparticles to synthesise Fe3O4-anti-CXCR4-PE probes. The biocompatibility and specificity of the probes were validated in vivo and in vitro. Magnetic particle imaging (MPI) and fluorescence imaging (FLI) were performed to assess inflammation in early and advanced AAA mouse models. CXCR4-specific receptor inhibitor, AMD3100, was used for confirming CXCR4 as an excellent target for AAA imaging and therapy.scRNAseq indicated that chemokine-related pathways were upregulated in aortic aneurysms, and CXCR4 was the chemokine receptor that markers all AAA-related immune cells and inflammatory vascular cells. Fe3O4-anti-CXCR4-PE effectively recognised immune cells and inflammatory vascular cells, as strong MPI and FLI signals corresponded to increased CXCR4, CD45, and CD68 levels which represented AAA severity and rupture risk. Importantly, Fe3O4-anti-CXCR4-PE can help identify early AAA formation when ultrasound is undiagnosable. Finally, AMD3100 treatment in AAA mouse model inhibited AAA expansion and rupture and reduced aortic wall inflammation by inhibiting accumulation of immune cells and hematopoietic stem cells. CXCR4 markers immune cells and inflammatory vascular cells in AAA and is associated with AAA prognosis in a mouse model of AAA. CXCR4-targeting multimodal MPI/FLI provides a novel approach for AAA prognosis prediction and early detection.

PSMA - Targeted Clinical Molecular Imaging of Atherosclerosis: Correlation with Cardiovascular Risk Factors.

The early diagnosis of atherosclerotic changes to prevent ischemic events represents a clinical challenge.Prostate-specific membrane antigen (PSMA) as an established diagnostic in the field of prostate cancer also appears to detect neovascularization and inflammation in other diseases. We hypothesized that it might be also suited for detection of inflammation in atherosclerosis. We analyzed data of 78 prostate cancer patients who received a PSMA ligand PET/CT for re-staging. The cardiovascular risk factors (CVRF) of each patient were documented. Target-to-background-ratios (TBR) were calculated from the individual uptake values for three different sections of thoracic aorta [ascending (AA) and descending aorta (AD), aortic arch (AoAC)]. Statistical analyses included a linear regression analysis with the PSMA ligand uptake values of the different arterial segments versus different CVRF as independent variables. The meanTBRmax was measured highest in the AoAC (1.66 ± 0.33) compared to both other vessel sections (AA: 1.46 ± 0.21, p=0.001; AD: 1.59 ± 0.41, p=0.371). There was a correlation between the PSMA ligand uptake in all measured segments of the aorta and BMI, but only a significant correlation in the ascending aorta (r=0.347, p=0.001). This was confirmed in a subgroup analysis, which showed significantly higher uptake values in preadiposity (BMI >25) and obesity (BMI >30) patients in the ascending aorta (p=0.048). PSMA ligand uptake in the ascending aorta was linked to BMI. PET detection of vascular PSMA ligand uptake may be indicative of vessel wall inflammation to some extent. However, PSMA ligands appear to be less suitable than other tracers for this purpose, given their absent correlation with most established CVRFs.

The use of glucocorticoids in Behçet’s disease

Behçet’s disease (BD) is a chronic, multifactorial inflammatory disorder characterized by episodic involvement of multiple systems, including mucocutaneous, ocular, vascular, gastrointestinal, joint, and neurological domains. Glucocorticoids (GC) play a pivotal role in managing BD, especially during acute flares and severe organ involvement. This review highlights the tailored use of GC across various manifestations of BD. For mucocutaneous lesions, topical GC are effective, where as short-term low-dose systemic GC are reserved for colchicine-resistantcases. In ocular BD, systemic GC are in dispensable for sight-threatening conditions, often combined with disease-modifying anti-rheumatic drugs (DMARDs) or biologics to minimize GC dependency. In vascular involvement, particularly pulmonary artery aneurysms, high-dose or pulse GC are essential to control vessel wall inflammation, often alongside immunosuppressive agents like cyclophosphamide. Neurological BD necessitate surgent high-dose GC therapy, complemented by DMARDs for sustained control. Joint involvement can be managed with intraarticular GC, reducing systemic exposure. In gastrointestinal BD, GC use is limited due to potential mucosal irritation, with biologics and DMARDs serving as adjunctive options. Across all manifestations, GC tapering is prioritized to mitigate adverse effects, while combination therapy with DMARDs or biologics ensures comprehensive disease control. This comprehensive review underscores the critical role of GC in BD management, advocating for individualized treatment strategies to balance efficacy and safety.

Retinal vasculitis – Current approach to diagnosis, investigations, and management

Retinal vasculitis is defined as the inflammation of the retinal vessel wall, which may involve the veins (periphlebitis), arteries (periarteritis), capillaries (capillaritis), or a combination of these. It is an uncommon sight-threatening retinal vascular inflammatory disorder resulting in a plethora of clinical features. It may be associated with systemic inflammatory conditions, infections, neoplastic diseases, or may be idiopathic. Reaching a diagnostic etiology for retinal vasculitis is often a diagnostic challenge. Meticulous examination, essential laboratory investigations, fundus photography, autofluorescence, fundus fluorescein angiography, indocyanine green angiography, optical coherence tomography (OCT), OCT angiography, B scan ultrasonography, and widefield fundus imaging enable us to arrive at a diagnosis. Antivascular endothelial growth factor and laser photocoagulation help to arrest neovascularization. Newer agents, such as immunomodulators and biologics, are effective against these sight-threatening conditions. Early management often helps to salvage vision and minimize comorbidities in these conditions. This review highlights on diagnosis and management of retinal vasculitis.

A Rare Case of Eosinophilic Myocarditis Described With 18F-FDG PET/CT.

Late-stage eosinophilic myocarditis (or Löffler endocarditis) is known to occur in patients with hypereosinophilic syndrome and can cause restrictive cardiomyopathy. Eosinophilic myocarditis is an acute life-threatening inflammatory disease of the heart that can be associated with cancer. We report a case of a 70-year-old White woman, previously treated for diffuse large B-cell lymphoma in remission, admitted for acute dyspnea with a 1-year history of hypereosinophilia. 18F-FDG PET/CT revealed endocardial uptake consistent with MRI gadolinium enhancement, suggesting left ventricular wall inflammation.

Pathogenesis of Pyometra: Treatment and Diagnosis

Pyometra refers to an acute or persistent suppurative inflammation of the uterine wall. A six-year-old Persian cat was admitted to Pet Hospital, with history of anorexia and chronic emaciation. During abdominal examination, the uterus felt larger and firmer than usual. Then ultrasonography examination was done and it revealed anechoic multiple pus pockets. Blood analysis showed that the level of AST, ALT, urea, creatinine increased, and PCV and Hb% decreased. All the findings confirmed that cat had suffering from pyometra. After confirmation, it was decided to do ovariohysterectomy under general anaesthesia. The suture was removed after fourteen days. The cat had a complete recovery without any complication.

Assessing Changes in Vascular Inflammation and Urate Deposition in the Vasculature of Gout Patients After Administration of Pegloticase Using Positron Emission Tomography and Dual-Energy Computed Tomography—A Pilot Study

We assessed changes in vascular inflammation and monosodium urate (MSU)-coded deposits after administration of Pegloticase in the vasculature of tophaceous gout patients using 18F-fluorodeoxyglucose (18F-FDG) Positron emission tomography/computed tomography (PET/CT) and dual-energy CT (DECT). Ten patients with tophaceous gout, intolerant or refractory to urate-lowering therapy (ULT), were treated with Pegloticase every two weeks for six months. 18F-FDG PET/CT and DECT were performed at baseline and after Pegloticase therapy to detect vessel wall inflammation (Standard uptake value, SUVmean, and SUVmax) and vascular MSU-coded deposition (MSU volume). Data were summarized using means and standard deviations. Baseline and follow-up values were compared for each variable using mixed-effect models. Significant decreases in SUVmean (p = 0.0003) and SUVmax (p = 0.009) were found with a trend towards a decrease in vessel wall MSU volume after treatment. There was a significant decrease in serum urate, correlating with reduction in SUVmean (R2 = 0.65), with a trend towards a decrease in CRP and blood pressure in all patients. Despite the small sample size, we were able to demonstrate a decrease in vessel wall inflammation and a trend towards a decrease in MSU volume by intensively lowering serum urate. These findings suggest that MSU-coded deposits and hyperuricemia may play a role in vascular wall inflammation. It remains to be seen whether this correlates with a decrease in adverse cardiovascular outcomes.

High-Resolution Vessel Wall Imaging in Primary CNS Vasculitis: A Case Series

High-resolution vessel wall imaging (HRVWI) is a relatively new technique in which vessel walls can be imaged suppressing the cerebrospinal fluid and blood signals. If there is inflammation of the vessel wall (vasculitis) it will show contrast enhancement. This is the only modality which is available to study vessel walls. All angiography techniques including Magnetic Resonance Angiography(MRA), Contrast computerized tomography angiography (CT -Angiography), and digital subtraction angiography (DSA) shows only the state of the lumen of the blood vessel. Involvement of blood vessels in Central Nervous system (CNS) can occur in systemic vasculitis (like microscopic polyangiitis, Polyarteritis nodosa, etc) where there is evidence of other organ involvement or primary CNS vasculitis (PCNSV) in which only involvement of the brain and spinal cord occurs. PCNSV is a rare disease and till now only the brain biopsy is the gold standard for definitive diagnosis. Brain biopsy is an invasive procedure, not always available, and many patients don’t give consent for the procedure. HRWVI can complement the angiography in the diagnosis of CNS vasculitis, especially PCNSV. Here we describe a case series of 4 cases of CNS vasculitis (3 cases of possible PCNSV and one vasculitic moya- moya syndrome) who had presented with stroke, All had abnormal Cerebrospinal fluid (CSF) and HRVWI showed contrast enhancement of the vessel wall indicating the possibility of vasculitis. In two cases, there was involvement of medium-sized arteries (middle cerebral artery), one patient had unilateral internal carotid artery (ICA) involvement and one had bilateral supra- clinoid stenosis of ICA associated with hyperthyroidism (vasculitic Moyamoya syndrome).

The Correlation of Vessel Wall Macrophage Infiltration With Hemosiderin in Arteriovenous Malformations

Endothelial dysfunction, induced by high shear stress from increased nidal blood flow, may promote a cycle of inflammation, possibly leading to instability and cerebral arteriovenous malformations (AVMs) rupture. Macrophages, identified with CD68, are key inflammatory components in AVM pathology. We aim to evaluate the relationship of inflammation with AVM flow and hemosiderin. This is a retrospective study of archived tissue. Adult patients (2002-2022) with baseline quantitative magnetic resonance angiography (QMRA) imaging, no embolization, and history of microsurgical resection (n=17), with both ruptured (n=9) and unruptured cases (n=8). Brain AVM sections were stained with CD68 to quantify vessel wall macrophage infiltration and hematoxylin and eosin stain as a control and to quantify hemosiderin. QMRA with noninvasive optimal vessel analysis (NOVA) was reviewed, and AVM flow was calculated. Statistical analyses were performed. There were no significant differences between macrophage infiltration and patient demographics, Spetzler-Martin grade, eloquence, venous stenosis, nidus compactness, volume, and AVM flow. Vessel wall macrophage infiltration positively correlated with patients who presented with confirmed AVM rupture (163.8 +/- 46.7 vs. 101.3 +/- 49.4, p=0.017). Increases in vessel wall macrophage infiltration were found to positively correlate with higher grades of hemosiderin (p=0.023), except for grade 4 hemosiderin. Venous anomaly showed a negative association with macrophage infiltration (p=0.035). These findings suggest a relationship between AVM vessel wall inflammation, hemosiderin, and hemorrhage presentation. Further investigations with larger sample sizes are warranted to understand the role of altered hemodynamics, hemosiderin deposition and inflammation in AVM vessel walls.

Percutaneous Sclerotherapy of Cystic Lesions at Kenyatta National Hospital: Indications, Outcomes, Efficacy, and Complications

Background: Percutaneous sclerotherapy is a minimally invasive treatment for cystic lesions and has emerged as a preferred alternative to traditional surgical methods due to its faster recovery times and lower complication rates. A sclerosing agent is instilled into the lesion causing cyst wall inflammation and lesion shrinkage. It has a significant role in managing cystic lesions, with better health outcomes. Objectives: To evaluate the indications, outcomes, efficacy, and complications of percutaneous sclerotherapy in the management of cystic lesions. Methodology: The study was a prospective cross-sectional study involving patients with cystic lesions referred for percutaneous sclerotherapy. Data was collected, analyzed, and presented in percentages, graphs, tables. Technical and clinical success rates were calculated. Efficacy was analyzed using chi-square test. Results: 27 patients with cystic lesions were treated. Most were females (77.8%), and males (22.2%), with a male-to-female ratio of 1:3.5. The commonest indication was pain (26.1%), followed by pressure symptoms (22.7%) and abnormal swelling (20.5%). Most lesions were located in the liver (25.9%), followed by the kidney (18.5%). Majority had significant improvement in clinical symptoms and size reduction with p-values &lt; 0.05. The technical success rate was 100% and the clinical success rate was 96.3%. Minor complications were encountered including mild pain (7.4%), catheter blockage, cyst abscess formation, catheter insertion site infection, and inflammatory cyst septations (each 3.7%). Conclusion: Percutaneous sclerotherapy is a safe, efficacious treatment of cystic lesions with a high technical and clinical success rate. It should be considered as a first line of treatment for cystic lesions.

Evaluation of aortic inflammation in marfan syndrome patients with 18-fluorodeoxyglucose positron emission and computed tomography

Abstract Background The role of inflammation in Marfan Syndrome (MS) has been well studied in current research. These studies have investigated the role of serum Interleukin 6 (IL-6), Transforming Growth Factor-b (TGF-b) and Macrophage Colony Stimulating Factor (MCSF) as biomarkers of disease severity and progression. Surgical repair is the recommended treatment of aortic aneurysms when aortic diameter reaches the indication threshold. It has been observed however that dissection may occur even before this threshold is reached. 18-fluorodeoxyglucose (18 F-FDG) positron emission tomography / computed tomography (PET/CT) is the gold standard imaging modality to noninvasively assess vascular inflammation. Purpose Our aim was to investigate whether MS patients have increased aortic wall inflammation as assessed by 18F-FDG PET/CT, and the relationship between aortic wall inflammation with serum levels of IL-6, TGF-b and MCSF. Methods The study population consisted of fifteen MS patients and seventeen sex and age matched controls. In all subjects, serum levels of circulating IL-6, TGF-b and MCSF were measured. In PET/CT, the arterial target-to-background ratio (TBR) was calculated for aortic root (AR), ascending aorta(As), aortic arch (AA) and descending aorta (DA). Also, all patients were assessed with transthoracic echocardiography where the diameters of AR, As, AA, and DA were estimated at baseline and were reexamined at the end of the follow up period. Results TBR for MS vs. controls was 2.17±0.75 vs 2.01±0.36, p=0.75 at AR; 2.15±0.67 vs 1.84±0.35, p=0.040 at As; 2.16±0.64 vs 1.70±0.25, p=0.03 at AA and 1.97±0.52 vs 1.83±0.42, p=0.23 at DA respectively. Additionally, Marfan patients had increased levels of serum biomarkers. However, this difference was statistically significant (SS) only for IL-6 serum levels; 2.17±0.46 vs 1.08±0.12 p=0.011 and IL-6 was SS associated with AR TBR (rho=0.572, p=0.033), As TBR (rho=0.604, p=0.022) and DA TBR (rho=0.714, p=0.004). Two of our patients were operated due to severe dilatation of the aortic root and the surgical specimens showed aortic wall inflammation of moderate severity along with fibrosis. Conclusion MS patients have increased of aortic wall inflammation as assessed by 18F-FDG PET/CT, a finding that highlights the role of inflammation in the pathway of disturbed TGF signaling. Further research is needed to determine its prognostic role and value in identifying patients with an indication for early intervention.

Synthetic Flavonoid 3,7-Dihydroxy-Isoflav-3-Ene (DHIF) Reduces In-Stent Restenosis in an Atherosclerotic Watanabe Heritable Hyperlipidemic Rabbit Stent Model.

Inflammation is a major component of the pathogenesis of atherosclerosis and the formation of in-stent restenosis (ISR). A novel flavonoid, DHIF, attenuates reactive oxygen species and nf-κB signaling and has potential to limit ISR via antioxidant action. While current drug eluting stents (DESs) perform well in clinical practice, new therapies to prevent ISR without dependance on cytotoxic drugs are warranted. Our objective was to test whether DHIF reduces ISR in a hyperlipidemic rabbit aorta model of ISR via attenuated inflammatory responses. WHHL rabbit aortas (n = 24) were denuded. Six weeks after injury, stents were implanted into the denuded aortas. DHIF was dissolved in carboxymethyl cellulose (CMC) and administered orally with two doses. CMC served as a control. The animals were sacrificed six weeks after stenting. ISR was evaluated from stent histomorphometry and immunohistology was used to assess the inflammatory and antiproliferative effects of the treatment. ISR was reduced from 20.9 ± 3.0% in controls to 15.2 ± 2.4% (p = 0.0009) and 16.4 ± 2.1% (p = 0.004) in the low- and high-dose groups, respectively. The neointimal area covered by macrophages was 32 ± 9.3% in the controls, 17.2 ± 5.9% (p = 0.005) in the low-dose group and 19.4 ± 7.9% (p = 0.008) in the high-dose group. DHIF significantly reduces ISR and local inflammation in stented arterial regions and could be used to reduce ISR when bare metal stents are used. Targeting local inflammation in the arterial wall may provide a way to reduce ISR in a clinical setting and further studies are warranted.

NIK Is a Mediator of Inflammation and Intimal Hyperplasia in Endothelial Denudation-Induced Vascular Injury.

Neointimal hyperplasia is the main cause of vascular graft failure in the medium term. NFκB is a key mediator of inflammation that is activated during neointimal hyperplasia following endothelial injury. However, the molecular mechanisms involved in NFκB activation are poorly understood. NFκB may be activated through canonical (transient) and non-canonical (persistent) pathways. NFκB-inducing kinase (NIK, MAP3K14) is the upstream kinase of the non-canonical pathway. We have now explored the impact of NIK deficiency on neointimal hyperplasia following guidewire-induced endothelial cell injury and on local inflammation by comparing NIK activity-deficient alymphoplasia mice (NIKaly/aly) with control wild-type (NIK+/+) mice. Guidewire-induced endothelial cell injury caused neointimal hyperplasia and luminal stenosis and upregulated the local expression of NIK and the NFκB target chemokines monocyte chemoattractant protein-1 (MCP-1/CCL2) and chemokine ligand 5 (RANTES/CCL5). Immunohistochemistry disclosed the infiltration of the media and intima by F4/80 positive macrophages. The intima/media ratio and percentage of stenosis were milder in the NIKaly/aly than in the NIK+/+ mice. Additionally, the gene expression for MCP-1 and RANTES was lower and F4/80+ cell infiltration was milder in the NIKaly/aly than in the NIK+/+ mice. Finally, circulating MCP-1 levels were lower in the NIKaly/aly than in the NIK+/+ mice, reflecting milder systemic inflammation. In conclusion, NIK is a driver of vascular wall inflammation and stenosis following guidewire-induced endothelial cell injury. NIK targeting may be a novel therapeutic approach to limit arterial stenosis following endothelial cell injury.