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The corona virus outbreak in Wuhan, China, at the end of 2019 has rapidly evolved into a pandemic which is still virulent in many countries. An infection with SARS-CoV-2 can lead to corona virus disease (Covid-19). This paper presents an overview of the knowledge gained so far with regard to histopathological lung lesions in fatal courses of Covid-19. The main findings were diffuse alveolar damage and micro-angiopathies. These included the development of hyaline membranes, thrombi, endothelial inflammation, haemorrhages and angiogenesis. Overall, the vessel lesions seemed to be more lethal than the diffuse alveolar damage. There was obvious hyperreactivity and hyperinflammation of the cellular immune system. An expanded T-cell memory may explain the increased risk of a severe course in the elderly.

Aims To investigate the association between pericoronary adipose tissue (PCAT) computed tomography (CT) attenuation derived from coronary computed tomography angiography (CTA) and coronary flow reserve (CFR) by positron emission tomography (PET) in patients with suspected coronary artery disease (CAD). Methods and results PCAT CT attenuation was measured in proximal segments of all major epicardial coronary vessels of 105 patients with suspected CAD. We evaluated the relationship between PCAT CT attenuation and other quantitative/qualitative CT-derived anatomic parameters with CFR by PET. Overall, the mean age was 60 ± 12 years and 93% had intermediate pre-test probability of obstructive CAD. Obstructive CAD (≥50% stenosis) was detected in 37 (35.2%) patients and impaired CFR ( Conclusion Coronary perivascular inflammation by CTA was independently associated with downstream myocardial perfusion by PET. In patients with low CCS or without obstructive CAD, CFR was lower in the presence of higher perivascular inflammation. PCAT CT attenuation might help identifying myocardial ischaemia particularly among patients who are traditionally considered non-high risk for future cardiovascular events.

Background Coronary atherosclerosis is a frequent complication of type 2 diabetes mellitus (DM2). Considering the contiguity with the vascular wall, perivascular adipose tissue (PVAT) could play a crucial role in the pathogenic microenvironment of atherosclerosis. The PVAT attenuation index (p-FAI) is a non-invasive marker that reveals the change in peri-coronary adipose tissue (PCAT). High values of p-FAI are associated with increased cardiovascular mortality and poor prognosis. Emerging as an indication, contributor to, and therapeutic target for atherosclerosis, PCAT warrants further investigation in DM2. Purpose We aimed to characterize the association of PCAT by p-FAI and DM2, and to compare coronary inflammation in DM2 versus non DM2 patients with coronary artery disease (CAD), and versus healthy controls. Methods 15 consecutive DM2 patients (9 male, age 63±10 years) without symptoms/signs of cardiovascular disease were included in the study and compared to 8 non DM2 patients with CAD and 13 healthy volunteers without cardiovascular diseases, matched for age and sex. All patients and controls underwent coronary computed tomography angiography (CCTA) for the evaluation of coronary arteries and p-FAI. All scans were performed using a 320-slice multidetector computed tomography (Toshiba Aquilion) and a prospective ECG-triggered sequential acquisition. p-FAI analysis was performed using a dedicated workstation (Aquarius iNtuition Edition version 4.4.13. P3; TeraRecon Inc., Foster City, CA, USA). The proximal 40-mm segment of the right coronary artery (RCA) was identified and the inner and the outer wall were automatically traced, excluding the 10 mm from the ostium. The adipose tissue localized within a radial distance from the outer wall equal to a medium diameter of the RCA was evaluated. Voxel histograms of CT attenuation were traced and included between −190 to −30 HU within the PCAT volume. p-FAI was calculated as the median CT attenuation value of PCAT of the proximal 40-mm segment of the RCA (Figure 1). Results CAD was present in 10 DM2 patients (5 males, aged 63.1±10.5 years); in 5 DM2 patients (4 males, aged 63±11 years) epicardial coronary arteries were normal. p-FAI was higher in DM2 patients than in healthy controls (p=0.004). The presence of CAD did not impact on p-FAI in DM2 patients, presenting a comparable value (p=0.37). p-FAI was higher in DM2 patients with CAD than in non DM2 patients with CAD (p=0.04). Moreover, p-FAI was higher in DM2 patients without CAD than in non DM2 patients with CAD (p=0.002, Figure 2). Finally, p-FAI was not different in non DM2 patients with CAD compared to healthy controls (p=0.65), suggesting the limited role of CAD in the progression of peri-coronary inflammation when compared to DM2. Conclusions Coronary inflammation evaluated by p-FAI measurement was higher in DM2 patients, also without CAD. Therefore, our results suggest that DM2 is a determinant of coronary inflammation stronger than CAD. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Carotidynia remains mired in controversy. Whether to identify this self-limiting unilateral neck pain as a distinct clinical entity or a diagnostic sign associated with a variety of conditions remains a topic of ongoing debate. Adding to the discussion is the occasional finding on imaging studies of a transient inflammatory process surrounding the carotid artery in a number of individuals who present with unilateral neck pain. Although some use carotidynia as the designation of choice by which to identify this inflammatory process, the acronym TIPIC (transient perivascular inflammation of the carotid artery) syndrome is being touted as a far more descriptive and less contentious alternative. Having TIPIC syndrome replace carotidynia, however, need not necessarily signal the latter’s outright elimination as some have advocated. When used as a diagnostic sign, carotidynia provides an appreciation of the many conditions that may be associated with idiopathic unilateral neck pain.

Pulmonary arterial hypertension (PAH) is a chronic, incurable condition characterized by pulmonary vascular remodeling, perivascular inflammation, and right heart failure. Regulatory T cells (Tregs) stave off autoimmunity, and there is increasing evidence for their compromised activity in the inflammatory milieu of PAH. Abnormal Treg function is strongly correlated with a predisposition to PAH in animals and patients. Athymic Treg-depleted rats treated with SU5416, an agent causing pulmonary vascular injury, develop PAH, which is prevented by infusing missing CD4+CD25highFOXP3+ Tregs. Abnormal Treg activity may also explain why PAH disproportionately affects women more than men. This mini review focuses on the role of Tregs in PAH with a special view to sexual dimorphism and the future promise of Treg therapy.

A 44-year-old man presented to the emergency department with a painful, palpable mass in the area of the right carotid triangle lasting for 1 week. He was otherwise healthy without any trauma or further otorhinolaryngological symptoms. Other than a pain at the right carotid triangle on pressure

Rheumatoid vasculitis is a rare etiology for pulmonary hypertension (PH) in patients with connective tissue disease. We encountered a case of acute PH crisis in a case with rheumatoid vasculitis eight months after undergoing adalimumab reduction. Since no repetition of arthralgia occurred after the adalimumab reduction, we decided to not increase the dose of adalimumab. However, hemodynamic collapse thereafter developed and even though steroid pulse therapy was administered, the patient nevertheless died. The autopsy showed clusters of acute and chronic inflammation around the remodeled pulmonary arteries along with micro-thrombi in the vessel lumen. We should consider the possibility of critical worsening of PH as a phenotype of vasculitis related to immunosuppressive therapy reduction.

Idiopathic carotidynia (IC) is a rare, possibly under-diagnosed clinico-radiologic entity that consists of acute unilateral neck pain and tenderness over the carotid bifurcation. Lecler et al. have recently described this condition associated with characteristic imaging features of transient perivascular soft tissue inflammation at the level of the affected carotid bifurcation, by a new term TIPIC (transient perivascular inflammation of the carotid artery) syndrome. We report the case of an Indian man, with recurrent right-sided TIPIC syndrome and past history of transient left-sided symptoms. On initial presentation, the clinical history, ultrasound (US) features, magnetic resonance imaging (MRI) findings, and laboratory investigations of the patient were correlated to establish the diagnosis of TIPIC syndrome. Doppler US was performed for imaging follow-up of this patient, when he presented again with recurrence of similar symptoms of right neck pain. In this 45-year-old patient, US demonstrated a characteristic perivascular echogenic soft tissue around the symptomatic carotid artery. MRI confirmed these imaging findings and ruled out carotid dissection. Patient responded to anti-inflammatory medications. Recurrence and resolution of the soft tissue thickening surrounding the affected carotid arteries were documented on serial follow-up US examinations. This case report illustrates that US can be effectively used in the diagnosis as well as follow-up of TIPIC syndrome.

Introduction The term “carotidynia” has been used to describe a symptom or a nosologic entity characterized by pain in the lateral neck region and over the carotid bifurcation. Recent advances in diagnostic imaging and the introduction of diagnostic criteria have led to the adoption of term “Transient perivascular inflammation of the carotid artery” (TIPIC) syndrome. Method A retrospective analysis of the Radiology Department’s database was performed to identify cases with the diagnosis of TIPIC syndrome. The purpose was to identify ultrasound images including B-mode technique, colour, power Doppler technique and contrast-enhanced ultrasound (CEUS). Findings In total, five patients with the diagnosis of TIPIC syndrome are presented in this review. TIPIC syndrome is a clinic-radiologic entity characterized by pain over the carotid area, a symptom referring to a wide differential diagnosis where imaging plays a crucial role for proper diagnosis and treatment. Characteristic imaging findings on conventional ultrasound and CEUS are presented in this review. Discussion TIPIC syndrome can be investigated with virtually any imaging modality. Ultrasound typically reveals perivascular infiltration and a hypoechoic intimal plaque, while no significant luminal narrowing is appreciated. Computed tomography angiography and magnetic resonance angiography also demonstrate these vascular wall changes primarily affecting the distal common carotid artery, the carotid bulb and possibly the internal carotid artery proximal part. Contrast enhancement is a very characteristic and constant finding of TIPIC lesions, suggestive of the inflammatory nature of the disease and can be appreciated on computed tomography angiography and magnetic resonance angiography. CEUS has been recently used and successfully observed contrast enhancement of the lesions, similar to computed tomography angiography and magnetic resonance angiography. Conclusion Ultrasound remains the first-line modality for the evaluation of TIPIC syndrome, capable of providing all the information needed, especially if supplemented with the administration of microbubbles so that the enhancement of lesions can be evaluated.

Background Recent accumulating evidence suggests that toll‐like receptor 9 (TLR9) is involved in the pathogenesis of cardiovascular diseases. However, its role in pulmonary hypertension remains uncertain. We hypothesized that TLR9 is involved in the development of pulmonary hypertension. Methods and Results A rat model of monocrotaline‐induced pulmonary hypertension was used to investigate the effects of TLR9 on hemodynamic parameters, vascular remodeling, and survival. Monocrotaline‐exposed rats significantly showed increases in plasma levels of mitochondrial DNA markers, which are recognized by TLR9, TLR9 activation in the lung, and interleukin‐6 mRNA level in the lung on day 14 after monocrotaline injection. Meanwhile, monocrotaline‐exposed rats showed elevated right ventricular systolic pressure, total pulmonary vascular resistance index and vascular remodeling, together with macrophage accumulation on day 21. In the preventive protocol, administration (days −3 to 21 after monocrotaline injection) of selective (E6446) or nonselective TLR9 inhibitor (chloroquine) significantly ameliorated the elevations of right ventricular systolic pressure and total pulmonary vascular resistance index as well as vascular remodeling and macrophage accumulation on day 21. These inhibitors also significantly reduced NF‐κB activation and interleukin‐6 mRNA levels to a similar extent. In the short‐term reversal protocol, E646 treatment (days 14–17 after monocrotaline injection) almost normalized NF‐κB activation and interleukin‐6 mRNA level, and reduced macrophage accumulation. In the prolonged reversal protocol, E6446 treatment (days 14–24 after monocrotaline injection) reversed total pulmonary vascular resistance index and vascular remodeling, and improved survival in monocrotaline‐exposed rats. Conclusions TLR9 is involved in the development of pulmonary hypertension concomitant via activation of the NF‐κB‒IL‐6 pathway. Inhibition of TLR9 may be a novel therapeutic strategy for pulmonary hypertension.

The blood-brain barrier (BBB) is important to maintain brain homeostasis, which is crucial for the functionality of neuronal networks. BBB dysfunction is observed in several neurological diseases, including epilepsy. Prolonged BBB dysfunction and subsequent perivascular inflammation as well as alterations in the extracellular matrix (ECM) play an important role in epileptogenesis. In this chapter we aim to give an overview of the processes involved in BBB dysfunction and epileptogenesis and provide evidence from animal as well as from human studies. We will focus on modulators of BBB function including specific cell types, inflammatory mediators as well as ECM molecules. Furthermore, we will discuss new therapeutic targets and the results of intervention studies that are important for the development of novel therapeutic approaches in epilepsy.

Perivascular inflammation is a prominent pathologic feature in most animal models of pulmonary hypertension (PH) as well as in pulmonary arterial hypertension (PAH) patients. Accumulating evidence suggests a functional role of perivascular inflammation in the initiation and/or progression of PAH and pulmonary vascular remodeling. High levels of cytokines, chemokines, and inflammatory mediators can be detected in PAH patients and correlate with clinical outcome. Similarly, multiple immune cells, including neutrophils, macrophages, dendritic cells, mast cells, T lymphocytes, and B lymphocytes characteristically accumulate around pulmonary vessels in PAH. Concomitantly, vascular and parenchymal cells including endothelial cells, smooth muscle cells, and fibroblasts change their phenotype, resulting in altered sensitivity to inflammatory triggers and their enhanced capacity to stage inflammatory responses themselves, as well as the active secretion of cytokines and chemokines. The growing recognition of the interaction between inflammatory cells, vascular cells, and inflammatory mediators may provide important clues for the development of novel, safe, and effective immunotargeted therapies in PAH.

Rationale: Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular remodeling, accompanied by varying degrees of perivascular inflammation. Niacin, a commonly used lipid-lowering drug, possesses vasodilating and proresolution effects by promoting the release of prostaglandin D 2 (PGD 2 ). However, whether or not niacin confers protection against PAH pathogenesis is still unknown. Objective: This study aimed to determine whether or not niacin attenuates the development of PAH and, if so, to elucidate the molecular mechanisms underlying its effects. Methods and Results: Vascular endothelial growth factor receptor inhibitor SU5416 and hypoxic exposure were used to induce pulmonary hypertension (PH) in rodents. We found that niacin attenuated the development of this hypoxia/SU5416–induced PH in mice and suppressed progression of monocrotaline-induced and hypoxia/SU5416–induced PH in rats through the reduction of pulmonary artery remodeling. Niacin boosted PGD 2 generation in lung tissue, mainly through H-PGDS (hematopoietic PGD 2 synthases). Deletion of H-PGDS, but not lipocalin-type PGDS, exacerbated the hypoxia/SU5416–induced PH in mice and abolished the protective effects of niacin against PAH. Moreover, H-PGDS was expressed dominantly in infiltrated macrophages in lungs of PH mice and patients with idiopathic PAH. Macrophage-specific deletion of H-PGDS markedly decreased PGD 2 generation in lungs, aggravated hypoxia/SU5416–induced PH in mice, and attenuated the therapeutic effect of niacin on PAH. Conclusions: Niacin treatment ameliorates the progression of PAH through the suppression of vascular remodeling by stimulating H-PGDS–derived PGD 2 release from macrophages.

Transient perivascular inflammation of the carotid artery (TIPIC) syndrome, previously referred to as 'carotidynia', is an unclassified clinicoradiological entity associating atypical acute neck pain, eccentric perivascular infiltration on imaging and improvement of symptoms either spontaneously or with anti-inflammatory treatment. This case report presents a patient with TIPIC syndrome who underwent five different types of imaging modality, including contrast-enhanced ultrasonography (CEUS) of the carotids, and describes the CEUS appearances of TIPIC syndrome.

Introduction Hypertension is associated with enhanced NADPH oxidase activation and increased accumulation of immune cells leading to perivascular inflammation. However, while aging and oxidative stress are a major factor for the development of hypertension, their effect on perivascular inflammation remains unclear. Purpose We aimed to establish the interaction between aging, oxidative stress and perivascular inflammation. We hypothesize that the modulation of oxidative stress, by NADPH oxidase inhibition, could affect perivascular inflammation during the aging. Methods Using flow cytometry, we studied leukocyte infiltration in the perivascular adipose tissue (PVAT) in 1-, 3-, 6- and 12-month-old SHR (Spontaneously Hypertensive Rats) and normotensive WKY (Wistar-Kyoto) rats (n=5–12). Additionally, 1-month-old rats were treated with GKT137831 or ML171 (60mg/kg; NOX1/4 and NOX1 inhibitor, respectively) for 4 weeks. Blood pressure (PB) was measured by tail cuff. Statistical analysis was performed using two-way ANOVA or t-test. Data are presented as means±SEM. Results Aging in SHRs was associated with an increase of BP (139±4 vs. 180±4 vs. 203±3 vs. 209±3, mmHg) and an elevation of PVAT leukocytes (2090±164 vs. 2255±359 vs. 2502±496 vs. 3255±408, cell/mg) in 1-, 3-, 6- and 12-month-old rats, respectively. These effects were not seen in WKY. These were associate with similar changes of NK cells (p int While an age-related increase of Nox4 mRNA in the vessels was observed in both groups, this increase was more dynamic in SHRs, (p int Interestingly, GKT137831 increased BP in both WKY and SHR rats (p Conclusion Aging and spontaneous hypertension is associated with a trajectory of BP elevation and perivascular inflammation. This state is hastened after NOX1/4 inhibition, while ML171 treatment protects against perivascular inflammation. Acknowledgement/Funding National Science Centre 2013/11/N/NZ4/00310

Background/Introduction Perivascular inflammation plays an important role in the pathogenesis of pulmonary arterial hypertension (PAH). Recent studies have demonstrated that damaged mitochondrial DNA induces sterile inflammation by activating toll-like receptor (TLR)9 in spontaneous hypertensive rats. However, it remains unclear whether TLR9 is involved in perivascular inflammation and subsequent development of PAH. Purpose The purpose of the present study is to investigate whether chronic inhibition of TLR9 can ameliorate monocrotaline (MCT)-induced PAH in rats. Methods Male Sprague-Dawley rats were injected with MCT (60 mg/kg). First, we conducted immunohistochemistory to examine which cell types express TLR9 in lungs of normal rats and MCT-exposed rats. Second, we extracted cell-free DNA from plasma of rats and amplified genes of COX2 by real-time PCR to detect circulating cell-free mitochondrial DNA, a ligand of TLR9. Third, the administration of a selective TLR9 inhibitor (E6446, 10mg/kg/day, drinking water) or non-selective TLR9 inhibitor (chloroquine: 50mg/kg/day, ip) started three days before MCT injection and sacrificed on day 21. We assessed hemodynamic data and histopathological analysis (EVG stain for medial wall thickness (MWT) in pulmonary arteries (outer diameter: 50 ∼ 100 μm) and CD68 for macrophage accumulation around pulmonary arteries (outer diameter: Results TLR9 was expressed dominantly in pulmonary endothelial cells and macrophages in the lungs of both normal rats and MCT-exposed rats. Compared with normal rats, MCT-exposed rats showed increased gene expression of COX2 (0.048±0.001 vs. 0.052±0.001 expressed by 1/Ct) in plasma on day 14. MCT-exposed rats also had increased right ventricular systolic pressure (RVSP: 21±1 vs. 60±2 mmHg), total pulmonary vascular resistance index (TPRI: 0.07±0.01 vs. 0.43±0.02 mmHg/min/mL/kg), MWT (0.07±0.01 vs. 0.26±0,02) and accumulation of macrophages (1.6±0.3 vs. 20.0±1.7 cells/HPF) on day 21. In the prevention protocol, either E6446 or chloroquine significantly prevented the elevations of RVSP (49±4 or 48±3 mmHg) and TPRI (0.29±0.04 or 0.27±0.03 mmHg/min/mL/kg) with reducing MWT (0.18±0.01 or 0.18±0.01) and macrophage accumulation (9.7±1.3 or 9.8±2.5 cell/HPF) on day 21. In addition, these drugs significantly reduced the levels of IL-6 mRNA compared with MCT group (4.4±1.0 or 4.8±1.4 vs. 11.9±1.0). In the reversal protocol, the treatment of E6446 had significantly increased the survival rate (50 vs. 10%). Conclusions TLR9 largely contributes to the development of PAH by reducing perivascular inflammation. Inhibition of TLR9 could be a novel therapeutic target for PAH.

Erythema papulatum centrifugum (EPC), also known as erythema papulosa semicircularis recidivans (EPSR), is distinct from eczema and other well-described figurate erythemas characterised by annular erythematous lesions. We report 7 cases of EPC and propose new diagnostic criteria including the following: (i) EPC is characterised by single or multiple recurrent expanding annular or semi annular erythema with central regression, surrounded by tiny red papules; (ii) the lesions regularly relapse and resolve; (iii) the histopathologic feature shows superficial perivascular inflammation with or without mild inflammation around sweat glands in the mid dermis and (iv) patients lack other associated cutaneous or internal abnormalities.

Background and purpose Hypertension is a multifactorial disease, manifested by vascular dysfunction, increased superoxide production, and perivascular inflammation. In this study, we have hypothesized that 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG) would inhibit vascular inflammation and protect from vascular dysfunction in an experimental model of hypertension. Experimental approach PGG was administered to mice every 2 days at a dose of 10 mg·kg-1 i.p during 14 days of Ang II infusion. It was used at a final concentration of 20 μM for in vitro studies in cultured cells. Key results Ang II administration increased leukocyte and T-cell content in perivascular adipose tissue (pVAT), and administration of PGG significantly decreased total leukocyte and T-cell infiltration in pVAT. This effect was observed in relation to all T-cell subsets. PGG also decreased the content of T-cells bearing CD25, CCR5, and CD44 receptors and the expression of both monocyte chemoattractant protein 1 (CCL2) in aorta and RANTES (CCL5) in pVAT. PGG administration decreased the content of TNF+ and IFN-γ+ CD8 T-cells and IL-17A+ CD4+ and CD3+ CD4- CD8- cells. Importantly, these effects of PGG were associated with improved vascular function and decreased ROS production in the aortas of Ang II-infused animals independently of the BP increase. Mechanistically, PGG (20 μM) directly inhibited CD25 and CCR5 expression in cultured T-cells. It also decreased the content of IFN-γ+ CD8+ and CD3+ CD4- CD8- cells and IL-17A+ CD3+ CD4- CD8- cells. Conclusion and implication PGG may constitute an interesting immunomodulating strategy in the regulation of vascular dysfunction and hypertension. Linked articles This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc.

Transient Perivascular Inflammation of the Carotid Artery (TIPIC) syndrome; is a rare, under-diagnosed clinico-radiologic entity comprising of acute unilateral neck pain and tenderness over the affected carotid bifurcation. In patients with TIPIC syndrome or idiopathic carotidynia, diagnostic imaging demonstrates a characteristic transient perivascular soft tissue thickening at the level of the affected carotid bifurcation. This article presents a short review of literature and highlights the role of Ultrasound in the diagnosis and follow-up of patients with a presumptive diagnosis of TIPIC syndrome.

Introduction: Hypertension is associated with enhanced oxidative stress and perivascular inflammation. Although, that aging and oxidative stress are major factors in the development of hypertension their effect on perivascular inflammation remains unclear. Methods: Using flow cytometry we studied leukocytes infiltrating perivascular adipose tissue (PVAT) in 1-, 3-, 6- and 12-month-old SHR (Spontaneously Hypertensive Rats) and normotensive WKY (Wistar-Kyoto) rats. Additionally, 1-month-old rats were treated with GKT137831 (60mg/kg) or ML171 (NOX1/4 and NOX1 inhibitor, respectively) for 4 weeks. Blood pressure (PB) was measured by the tail cuff. Results: Aging in SHRs was associated with elevation of BP (139±4 vs 180±4 vs 202±2 vs 208±2 mmHg; 1 vs 3 vs 6 vs 12-month-old, respectively) when this effect was not seen in WKY rats. While the total number of leukocytes infiltrating PVAT were comparable between 1-month-old WKY and SHR (p=0.8) aging escalated their numbers only in SHRs (2096±164 vs 1994±296 vs 2311±470 vs 3255±408 cell/mg; p int int int int Conclusions: Aging in spontaneous hypertension is associated with elevation of BP and aggravation of perivascular inflammation which are hastened after NOX1/4 inhibitor treatment.

Juvenile dermatomyositis is a complex illness characterized by vascular/perivascular inflammation, primarily in the skin and muscles. In this review, we discuss how proteomic and genomic technologies have expanded our understanding of the immune pathogenesis of this disease. We will also discuss further directions that the field may take to use existing and developing technologies to further our understanding of this often-perplexing disease.

Perimesencephalic subarachnoid hemorrhage (PM-SAH) refers to intracranial hemorrhage located in the perimesencephalic cistern. The etiology remains mainly unclear, although venous leakage or rupture has been postulated. We report an interesting case of a 57-year-old healthy man who presented initially with PM-SAH with worsening of subcortical lesions on follow-up neuroimaging. Histopathological examination demonstrated cerebral amyloid angiopathy with perivascular inflammation.

Objective: Hypertension (HT) is associated with perivascular inflammation and increased vascular fibrosis. MicroRNAs (miR) are a novel gene expression regulation mechanism and play a pivotal role in a range of pathological processes. The role and mechanism of miR214 in vascular fibrosis is unknown. Methods: 3-month-old C57BL/6, miR214KO and wild-type littermates were treated with angiotensin II (AngII, 490ng/kg/min; n=6-10) or control buffer for 14 days. PVATs from C57BL/6 animals were analysed using TaqMan_Rodent_microRNA_Arrays. Histological studies, wire myography, lucigenin-enhanced luminometry and cytometrical analysis was conducted, followed by statistical analysis with ANOVA or t-test. Data are expressed as a mean±SEM. Results: Out of 381 miRs, 16 were significantly overexpressed in C57BL/6 AngII animals, with only miR214 showing 8-fold induction (p Conclusions: MiR-214 plays a major role in modulation of aortic fibrosis, vascular function, oxidative stress and perivascular inflammation.

ObjectiveTo investigate the spatiotemporal evolution of venous narrowing in newly developing MS lesions in a longitudinal MRI study including susceptibility-weighted images (SWIs).MethodsWe retrospectively investigated serial MR examinations of 18 patients with MS acquired on a 3T MRI system including SWI for acute contrast-enhancing lesions with at least 1 MRI examination before contrast enhancement. The mean diameter of veins at the time point of contrast enhancement was compared with the mean diameter of veins before and after contrast enhancement.ResultsA total of 40 acute contrast-enhancing lesions with a corresponding intralesional central vein were included in the study. The mean diameter of intralesional veins at the time of contrast enhancement (0.80 ± 0.12 mm) was smaller than that at before (1.16 ± 0.19 mm) and after contrast enhancement (1.07 ± 0.15 mm; p < 0.001 for all comparisons).ConclusionsOur findings contribute to the increasing database of plaque development and evolution. The smaller diameter of intralesional veins on SWI at the time of blood-brain barrier breakdown may reflect morphologic changes because of perivascular inflammation and/or decreased levels of deoxygenated hemoglobin.

Cerebral amyloid angiopathy–related inflammation (CAA-I) was first described in 2004 with 7 cases of perivascular inflammation in patients with CAA.1 So far

Epicardial adipose tissue (EAT), deposited around subepicardial coronary vessels, may contribute directly to perivascular inflammation and smooth muscle cell proliferation. This study assessed the relationship between EAT and in-stent restenosis.Four hundred and seven patients had received successful coronary intervention. EAT thickness was measured by echocardiography. Angiographic follow-up was obtained between 6 months and 2 years. Restenosis was defined as target lesion revascularization (TLR). EAT thickness of patients was compared by TLR controlling for additional well-known predictors of restenosis. The TLR-free survival analysis according to EAT thickness was estimated using the Kaplan-Meier method and the differences between groups were assessed by the log-rank test.Median EAT thickness was significantly increased in patients undergoing TLR compared with those without restenosis (3.7 vs. 3.0 mm, p = 0.001). EAT thickness was one of the independent factors associated with restenosis (Odds ratio = 1.19, 95% confidence interval = 1.01-1.33, p = 0.007). The TLR-free survival of patients with thick EAT was significantly worse than patients with thin EAT (log-rank p = 0.001).EAT thickness is related with restenosis and may provide additional information for future restenosis.

Pulmonary arterial hypertension (PAH) is a devastating progressive disease associated with a high mortality despite current vasodilator therapies. Perivascular inflammation and high levels of neutrophil elastase are thought to play a pivotal role in the adverse vascular remodeling of small pulmonary arteries that causes PAH. Despite this, the function of neutrophils and in particular, their interaction with the pulmonary arterial endothelium has not been studied in PAH. We hypothesized that neutrophil functions such as adhesion to a substratum or to endothelial cells and transmigration across a substratum or trans-endothelial migration (TEM) are abnormal in PAH on the basis of dysfunction of both cell types. Using a neutrophil like cell line dHL-60 and isolated human neutrophils from donors and PAH patients, we demonstrated no significant difference in adhesion to PAH vs. control PAECs when stimulated with TNF-α (100μg/mL). However, TEM of both IL-8 (100ng/ml) and fMLP (100nM) stimulated dHL-60 cells and donor neutrophils was enhanced in PAH vs. control PAECs (p

Background Lobular keloid appears to be a consequence of hypertrophic inflammation secondary to ear piercings performed under unsterile conditions. We wish to understand the pathogenesis of lobular keloids and report operative outcomes with a literature review. Methods A retrospective review identified 40 cases of lobular keloids between January, 2005 and December, 2010. Patient records were reviewed for preclinical factors such as presence of inflammation after ear piercing prior to keloid development, surgical management, and histopathologic correlation to recurrence. Results The operation had been performed by surgical core extirpation or simple excision, postoperative lobular compression, and scar ointments. Perivascular infiltration was noted in intra- and extra-keloid tissue in 70% of patients. The postoperative recurrence rate was 10%, and most of the patients satisfied with treatment outcomes. Conclusion Histological perivascular inflammation is a prominent feature of lobular keloids. Proper surgical treatment, adjuvant treatments, and persistent follow-up observation were sufficient in maintaining a relatively low rates of recurrence.

Aims: To study the histological features on muscle biopsy and correlate them with clinical features, other laboratory data in adult patients to make a diagnosis of dermatomyositis (DM), applying the European Neuromuscular center (ENMC) criteria. Materials and Methods: Adult patients who fulfilled clinical, laboratory, and muscle biopsy findings according to ENMC criteria for DM during the period 2010-2013 were included in the study. Cryostat sections of muscle biopsy were reviewed with emphasis on Perifascicular atrophy (PFA), perivascular/endomysial inflammation. Muscular dystrophies and metabolic myopathies were excluded by appropriate immunohistochemistry and special stains. Results: The diagnosis of adult DM was made in 45 patients out of 170 clinically suspected idiopathic inflammatory myopathies. These included 33 definite, 4 probable, 7 possible sine dermatitis, and 1 amyopathic DM. All patients with definite DM had typical rash and proximal muscle weakness and muscle biopsy showed PFA with or without inflammation. Thirteen patients had quadriparesis, neck muscle weakness, dysphagia/dysphonia at presentation. Patients with probable DM had rash and showed perivascular/endomysial inflammation with no PFA. Possible DM sine dermatitis showed PFA with perivascular/endomysial infiltrates. One patient of amyopathic DM had typical heliotrope rash and characteristic skin biopsy. Conclusions: Histological features are important for the diagnosis of DM. Relying on PFA for diagnosis of definite DM underestimates the true frequency of DM.

The current understanding of the pathology that underlies pulmonary vascular and right ventricular remodeling in pulmonary hypertension is discussed. Although recent studies underscored the importance of intima and media remodeling and, for the first time, the relevance of perivascular inflammation, much is needed to move the field forward. Reassessment of distribution and extension of the different vascular lesions requires state-of-the-art stereological tools, allied to three-dimensional casting and integration with data concerning cellular and molecular pathobiological processes. This integrated approach is ever more pressing in the right ventricle, because our understanding of key structural alterations of the failing right ventricle in pulmonary hypertension is lacking. This enterprise will enable better translation of pathogenetic processes to the human disease and provide key data to guide diagnostic and prognostic imaging approaches.

Hypertension in obesity occurs as a result of abnormal increases in sympathetic nerve density over arteries controlling blood pressure; the causative factors underlying these changes are unknown. H...

Experimental autoimmune encephalomyelitis (EAE) induction in TNF gene-targeted mice has resulted in conflicting reports in part due to the strong association of TNF with the MHC locus. To define the participation of TNF in EAE development, we back-crossed TNF-deficient mice (H-2b) into the SJL/J strain and directly compared them to H-2b congenic SJL or inbred SJL/J mice. Induction of EAE with myelin basic protein (MBP) revealed that H-2b congenic SJL mice are fully susceptible, indicating that the H-2b haplotype does not affect disease susceptibility. Using H-2b congenic SJL mice we show here that TNF deficiency modifies the normal course of EAE by considerably delaying the onset for approximately 5 days, suggesting that TNF is required for the normal initiation of MBP-induced EAE. However, TNF-deficient mice eventually developed severe EAE with perivascular inflammation and primary demyelination similar to wild-type controls, indicating that TNF is not essential during these processes. Taken together, these results indicate that although TNF is not required for the progression of MBP-induced EAE, it contributes positively by advancing the onset of disease.

Four infants developed progressive muscle weakness after a normal initial postnatal development. All patients had a moderate elevation of serum creatine kinase (CK) activity. Muscle biopsies revealed, in addition to myopathic features, endomysial and perivascular inflammation. Electron microscopy disclosed prominent myonuclear abnormalities. Corticosteroids in 3 patients were moderately beneficial. This appears to be a clinicopathologically distinct form of inflammatory myopathy of infants.

Migraine is more common than previously reported. Three large epidemiological studies showed that the prevalence of migraine in the general population is 12-14% for women and 5-7% for men. Animal experiments suggest that the headache in migraine might be due to alterations of a trigemino-vascular reflex resulting in vasodilatation, plasma extravasation and perivascular inflammation of dural arteries. In addition to sumatriptan a number of other 5-HT-1D receptor agonists are under investigation and will be available for the treatment of acute migraine attacks in the near future. For the prevention of migraine, valproic acid has been shown to be effective in cases that are refractory to traditional migraine prophylaxis. Neurophysiological data indicate that the central pain threshold may be altered in chronic tension-type headache. Die Migrane ist haufiger als bisher angenommen. Drei grose epidemiologische Studien zeigen, dass die Pravalenz der Migrane bei Frauen zwischen 12-14% und bei Mannern zwischen 5-7% betragt. Fur die Entstehung der Kopfschmerzen bei der Migrane wird ein pathologischer trigemino-vaskularer Reflex verantwortlich gemacht, der zur Vasodilatation, Plasmaextravasation und perivaskularer Entzundung im Bereich von Duraarterien fuhrt. Eine Vielzahl neuer Serotonin (5HT-lD)-Rezeptor-Agonisten werden neben Sumatriptan in den nachsten Jahren Eingang in die Therapie der akuten Migraneattacke finden. Als neues Medikament fur die Migraneprophylaxe hat sich im letzten Jahr die Valproinsaure etabliert. Neue neurophysiologische Untersuchungen zeigen, dass beim chronischen Spannungskopfschmerz eine veranderte zentrale Schmerzschwelle besteht.

Fifty-eight cases of septal granulomatous panniculitis were reviewed; 14 cases were diagnosed as erythema nodosum migrans (migratory panniculitis) and 36 as chronic erythema nodosum on the basis of clinical and histopathologic features. Erythema nodosum migrans was characterized by markedly thickened and fibrotic septae, marked capillary proliferation (like granulation tissue), and massive granulomatous reaction (with giant cells) along the borders of the widened septa. Hemorrhage was rare, and phlebitis was not seen. Chronic erythema nodosum showed mild septal change, little fibrosis, and lymphohistiocytic perivascular inflammation with only focal granulomatous formation. Phlebitis and hemorrhage were common. The condition termed erythema nodosum migrans has many of the same clinical features as chronic erythema nodosum, and we think this term is preferable to migratory panniculitis. We believe that there are sufficient clinical and histopathologic features to justify considering erythema nodosum migrans as a unique clinicopathologic entity.

Carotidynia is a rare diagnosis for unilateral neck pain without a clear physical substrate. As such, it may be encountered in surgery practice when analysing carotid artery status in symptomatic patients. Here, a case is presented which outlines the diagnostic process and subsequent treatment of carotidynia. As opposed to vascular causes of unilateral neck pain, carotidynia can be easily treated conservatively. Relief of complaints as well as regression of perivascular inflammation on magnetic resonance imaging can be effectively achieved with the use of non-steroidal anti-inflammatory drugs.

We have recently developed a non-adhesive liquid embolic agent, hydroxyethylmethacrylate methylmethacrylate copolymer (HEMA-MMA), and used it for arteriovenous malformations (AVMs) in the central nervous system. To evaluate the toxicity and usefulness of this agent, we made a clinicopathological study of AVMs that were embolized with it and then excised surgically. This study includes ten cases: nine with pial AVM and one with scalp AVM. In a pathological study, special attention was paid to vascular and perivascular inflammation, angionecrosis, recanalization of the embolized vessels, and foreign body reactions. Inflammation was absent or very mild regardless of the interval between embolization and excision. There was no angionecrosis. Recanalization could be expected to occur in the partially occluded vessel. Foreign body reactions such as infiltration of monocytes or giant cells, and proliferation of fibroblasts or capillaries were also not seen in any case. It was concluded that HEMA-MMA is an excellent embolic material that is easy to handle, less vasotoxic than other agents, and highly his-tocompatible.

Sustained improvement with prolonged topical tretinoin for photodamaged skin has been well documented for up to 22 months of continuous treatment. We now report long-term (4 years) histologic effects of topical tretinoin in photodamaged skin of 27 patients, the longest study to date. The observed decreases in dermal elastin content and perivascular inflammation and increase in epidermal mucin in facial biopsies obtained after up to 4 years of treatment may be partly responsible for the continued clinical improvement. Furthermore, the study shows that there are no untoward effects on keratinocytes or melanocytes during long-term use of topical tretinoin.