Nonarteritic anterior ischemic optic neuropathy and incidence of Parkinson's disease based on a nationwide population based study.

This study aimed to investigate the association between nonarteritic anterior ischemic optic neuropathy (NAION) and Parkinson's disease (PD) using a retrospective, nationwide, population-based cohort in South Korea. This study utilized data from the Korean National Health Insurance database, including 43,960 NAION patients and 219,800 age- and sex-matched controls. Cox proportional hazards regression models were used to assess the risk of developing PD in the NAION group compared to the control group after adjusting for various confounding factors. Subgroup analyses were conducted based on sex, age, and comorbidities. The incidence rate of PD was higher in the NAION group (1.326 per 1000 person-years) than in the control group (0.859 per 1000 person-years). After adjusting for confounding factors, the risk of developing PD was significantly higher in the NAION group (adjusted hazard ratio [aHR] 1.516, 95% confidence interval [CI] 1.300-1.769). Subgroup analyses did not reveal a significant difference in the risk of PD development based on sex, age, or comorbidities. This retrospective, nationwide, population-based cohort study revealed a significant association between NAION and an increased risk of developing PD in a South Korean population. The incidence rate of PD was observed to be higher in individuals diagnosed with NAION than in age- and sex-matched controls even after adjusting for potential confounding variables, with the risk being approximately 51.6% higher in the NAION group. Further research is necessary to elucidate the underlying pathophysiological mechanisms linking NAION to PD and to determine whether similar associations exist in other ethnic and geographical populations.

C-reactive protein concentration has limited value in the diagnosis of meningoencephalitis of unknown origin in dogs.

OBJECTIVES: To evaluate blood and cerebrospinal fluid (CSF) concentrations of C-reactive protein (CRP) in dogs with meningoencephalitis of unknown origin (MUO); to evaluate whether blood CRP concentration is associated with epidemiological, clinicopathologic, and MRI findings; and to investigate blood CRP predictive power in survival. ANIMALS: 30 client-owned dogs with MUO, 15 client-owned dogs with steroid-responsive meningitis arteritis (SRMA; positive control group), and 15 healthy dogs (negative control group). METHODS: Blood CRP concentration was measured in each group, while it was performed in CSF only in the MUO and SRMA groups. The analysis of epidemiological data included breed, age, sex, duration of clinical signs, and history of seizures. Blinded analysis of MRI was performed based on a classification grid, and traditional CSF analysis parameters were assessed. The predictive power of blood CRP concentration regarding survival at 6 months was investigated. RESULTS: Of the 30 dogs with MUO, 9 (30%) had an increased CRP concentration in blood, and 3 (10%) showed a measurable CRP in CSF. Median blood CRP concentration in dogs with MUO was 0.1 mg/L (range, 0.1 to 102 mg/L), which was not statistically different from the healthy dog group but significantly lower than the SRMA control group. Only the duration of clinical signs was positively associated with an increased blood CRP level. Blood CRP concentration was not associated with survival at 6 months. CLINICAL RELEVANCE: Blood CRP concentration is of limited value for the diagnosis and prognosis of dogs with MUO. Chronicity of the disease may be associated with an increased concentration of blood CRP.

Clinical and histopathological features of rostrolateral nasal alar arteriopathy of German shepherd dogs.

BACKGROUND: Dermal arteritis of the nasal philtrum (DANP) has been described in large-breed dogs. OBJECTIVES: To characterise clinically distinct, discrete fissures of the dorsolateral nasal alae associated with severe bleeding in German shepherd dogs (GSDs). ANIMALS: Fourteen privately owned GSDs with linear rostrolateral nasal alar fissures and a histopathological diagnosis of nasal vasculopathy. MATERIALS AND METHODS: Retrospective analysis of medical records and histological slides. RESULTS: Mean age of onset was 6 years. Before biopsy, episodic arteriolar bleeding was noted in 11 of the 14 (79%) dogs. Slide analysis revealed enlarged nasal arterioles with expanded vascular tunics and luminal stenosis beneath ulcers. Histopathological lesions consistent with mucocutaneous pyoderma and/or facial discoid lupus erythematosus were present in 5 of the 14 (36%) dogs. Enlarged arterioles stained blue with Alcian blue and Masson's trichrome stains, consistent with deposition of mucin and collagen, respectively. Immunohistochemical stains (neutrophil myeloperoxidase, IBA1, CD3) were performed. CD3 was negative for all dogs, whilst neutrophil myeloperoxidase and IBA1 occasionally demonstrated intramural neutrophils (3 of the 14 dogs, 21%) or histiocytes (1 of the 14 dogs, 7%) in altered vessels, respectively. All dogs underwent medical management and/or surgical excision. Treatments included tacrolimus, prednisone, ciclosporin-modified, pentoxifylline, antimicrobials and doxycycline/niacinamide. No dogs were treated with antimicrobials alone. For seven dogs with long-term follow-up, treatment response was complete in five (71%) and partial in two (29%), with six of the seven (86%) receiving immunomodulatory treatments to maintain remission. CONCLUSION AND CLINICAL RELEVANCE: Nasal alar arteriopathy of GSDs shares histopathological changes with DANP. It has characteristic clinical and histopathological features and appears amenable to immunomodulation.

Cannabis arteritis presenting with Raynaud's and digital ulcerations: a case-based review of a controversial thromboangiitis obliterans-like condition.

Thromboangiitis obliterans (TAO), or Buerger's disease, is a non-atherosclerotic inflammatory disease of the small and medium-sized arteries, veins, and nerves of the legs and arms, strongly associated with the use of tobacco products in young adults. Cannabis arteritis (CA), an entity with similar clinical and pathological features, has been described in marijuana users as a subtype of TAO. Distinction between TAO and CA is challenging, given that most patients use tobacco and marijuana products concomitantly. Herein, we report the case of a male in his late forties who was referred to rheumatology with a 2-month history of hand swelling and bilateral painful digital ulcers with blue discoloration on his fingers and toes. The patient reported daily use of marijuana in blunt wraps and denied tobacco use. His laboratory work-up was negative for scleroderma and other connective tissue diseases. His angiogram confirmed the diagnosis of thromboangiitis obliterans, which was attributed to cannabis arteritis. The patient was started on aspirin and nifedipine daily and discontinued marijuana use. His symptoms resolved within 6 months and have not recurred for more than a year with continued avoidance of marijuana. Our case is one of the few that features primarily marijuana-driven CA and highlights the importance of not only considering marijuana use but also blunt wrap use in patients presenting with Raynaud's phenomenon and ulcerations as cannabis use rises globally.

Cutaneous arteritis with intimal fibrin ring and immature myeloid cell infiltrate: lymphocytic thrombophilic arteritis or histiocytoid polyarteritis nodosa?

The ongoing debate on whether lymphocytic thrombophilic arteritis (LTA) is a separate disease or a type of polyarteritis nodosa (PAN) has yet to be settled. In this study, we analyzed the nature of infiltrating cells in LTA to resolve this controversy. Skin biopsies from five female patients (mean age 29.4 years, age range 16-45 years) diagnosed with LTA were immunostained for CD3, CD20, CD68, lysozyme, myeloid cell nuclear differentiation antigen, myeloperoxidase, and PU.1. Immunohistochemistry revealed that the majority of mononuclear cells in all five cases were not lymphocytes but myelomonocytic cells. Given that the infiltrating cells are of the myelomonocyte lineage including immature myeloid cells, PAN was deemed the more appropriate diagnosis for the five cases rather than LTA. Whether PAN with immature myeloid cells (histiocytoid PAN) is the same disease as conventional PAN with mature neutrophils requires further investigation.

IgG4-related disease as a variable-vessel vasculitis: A case series of 13 patients with medium-sized coronary artery involvement.

INTRODUCTION: IgG4-related disease (IgG4-RD) is a systemic autoimmune fibroinflammatory disease that can affect multiple organ systems. Although large-vessel vasculitis is a well-recognized manifestation of IgG4-RD, this condition is generally not regarded as a vasculitis. We aimed to describe coronary artery involvement (CAI), a vascular distribution about which little is known in IgG4-RD. MATERIAL AND METHODS: Patients with IgG4-related CAI were identified from a large, prospective IgG4-RD cohort. CAI was confirmed by imaging evidence of arterial or periarterial inflammation in any coronary artery. We extracted details regarding demographics, features of IgG4-RD, and manifestations of CAI. RESULTS: Of 361 cases in the cohort, 13 (4%) patients had IgG4-related CAI. All were male and all had highly-elevated serum IgG4 concentrations, with a median value of 955 mg/dL (interquartile range [IQR]: 510-1568 mg/dL; reference: 4-86 mg/dL). Median disease duration at the time of CAI diagnosis was 11 years (IQR: 8.23-15.5 years). Extensive disease in the coronary arteries was the rule: all three major coronary arteries were involved in 11 patients (85%). The coronary artery manifestations included wall thickening or periarterial soft tissue encasement (85%), stenosis (69%), calcification (69%), and aneurysms or ectasia (62%). Five patients (38%) had myocardial infarctions, 2 (15%) required coronary artery bypass grafting, and 2 (15%) developed ischemic cardiomyopathy. DISCUSSION: Coronary arteritis and periarteritis are important manifestations of IgG4-RD, which should be regarded as a variable-vessel vasculitis that is among the most diverse forms of vasculitis known. Potential complications of CAI include coronary artery aneurysms, myocardial infarction, and ischemic cardiomyopathy.

Hormone Replacement Therapy and the Incidence of Nonarteritic Anterior Ischemic Optic Neuropathy: a Nationwide Population-Based Study (2009-2018).

PURPOSE: This study aimed to assess the association between hormone replacement therapy (HRT) and the prevalence of nonarteritic anterior ischemic optic neuropathy (NAION) in menopausal women using national data from the entire Korean population. METHODS: The health screening data of 1,381,605 women between 40 and 90 years of age collected by the National Health Insurance Service (NHIS) of Korea between January 1, 2009, and December 31, 2018, were retrospectively reviewed. Before data analysis, the potential cofounders were adjusted for among all participants. Based on HRT use and its duration (classified into four groups), the hazard ratio (HR) and 95% confidence interval (CI) of NAION development were calculated via a Cox proportional hazards regression analysis using the nonuser group as a reference. RESULTS: Overall, 7824 NAION diagnoses were made during the mean follow-up of 8.22 years (standard deviation: 1.09 years) in 1,381,605 post-menopausal women. NAION was more common in the HRT group than in the non-HRT group (HR [95% CI]: 1.268 [1.197-1.344]). Furthermore, the risk of NAION increased along with increased HRT duration (p < 0.0001). In the multivariate analysis, the adjusted HRs of the < 2-year HRT group, the 2-5-year HRT group, and the ≥ 5-year HRT group were 1.19 (95% CI: 1.10-1.28), 1.3 (95% CI: 1.17-1.45), and 1.473 (95% CI: 1.31-1.65), respectively. Compared to women younger than 65 years, the HR of HRT for NAION was significantly higher than that of women older than 65 years (p < 0.0001). CONCLUSION: Our population-based cohort study found that HRT was significantly associated with increased incidence of NAION. The incidence of NAION also increased with the duration of HRT.

Paracentral Acute Middle Maculopathy as a Specific Sign of Arteritic Anterior Ischemic Optic Neuropathy.

PURPOSE: The purpose of this study is to assess the diagnostic accuracy of paracentral acute middle maculopathy (PAMM) in the setting of anterior ischemic optic neuropathy (AION) to distinguish arteritic (A-AION) from nonarteritic (NA-AION) type. DESIGN: Retrospective cross-sectional diagnostic evaluation. METHODS: PAMM was evaluated by 3 physicians blinded to diagnosis using macular spectral-domain optical coherence tomography. We studied 45 patients with AION. Of those, 28 had NA-AION and 17 had A-AION. The study was conducted in the Department of Ophthalmology at the Hospital of Marseille-Assistance Publique, France, from January 1, 2018, to March 31, 2022. RESULTS: PAMM were only found in the A-AION group (N = 4) (P = .0143). As a distinctive sign of A-AION, we found a specificity of 100% (95% IC, 88.06%-100%) and a positive predictive value of 100%. In contrast, sensitivity and negative predictive value were lower, 19.1% (95% IC, 5.5-42.0) and 63.0% (95% CI, 58.1-67.7), respectively. CONCLUSIONS: The PAMM finding is highly specific for A-AION in the setting of AION. According to our results, macular spectral-domain optical coherence tomography looking for PAMM should be performed with any patient presenting with AION.

Left Ventricular Dysfunction Caused by IgG4-related Small Intramural Coronary Periarteritis.

IgG4-related disease (IgG4-RD) is a systemic autoimmune disorder known to affect multiple organs. However, IgG4-RD rarely affects the myocardium. We herein report a case of left ventricular dysfunction due to cardiac involvement of IgG4-RD.

Endovascular treatment of upper extremity ischemia due to radiation-induced arteritis.

Symptomatic occlusion of the peripheral arteries due to radiation-induced arteritis (RIA) is an extremely rare condition. Patients generally present with the symptoms of ischemic claudication months or years after radiotherapy. Treatment options for symptomatic patients include surgical or endovascular interventions. Although success rate of percutaneous angioplasty in RIA is lower than in atherosclerotic disease, there are several case reports in the literature to demonstrate successful percutaneous angioplasty for RIA. In this report, we presented a case with right upper extremity occlusion due to RIA treated by percutaneous angioplasty successfully.

Relationship between cerebral venous sinus thrombosis and intracranial arteritis during pregnancy and post partum.

Our study was conducted to explore the relationship between cerebral venous sinus thrombosis (CVST) and intracranial arteritis during the time of pregnancy as well as puerperium. The current retrospective case study involved a total of 153 patients with pregnancy-related CVST. CVST was diagnosed mainly based on clinical manifestations and imaging results. Detailed information on demographics, risk factors (excluding intracranial arteritis), and pregnancy outcomes was systematically recorded. The average age of patients diagnosed with CVST was 28.67±3.54 years old. Among these patients, there were 62 cases of puerperal CVST and 91 cases of pregnancy-related CVST. The clinical manifestations of patients with CVST included headache in 55 cases (35.95%), symptomatic seizures in 26 cases (16.99%), symptomatic limb weakness in 22 cases (14.38%), symptomatic nausea/vomiting in 18 cases (11.76%), symptomatic disturbance of consciousness in 15 cases (9.80%), symptomatic blurred vision in 10 cases (6.54%), and symptomatic fever in 7 cases (4.58%). A proportion of patients reported higher abnormal cerebrospinal fluid pressure (98.28%), white cell count (79.31%), total cholesterol (71.55%) and low-density lipoprotein (62.93%) (p<0.01). The proportion of intracranial arteritis lesions and CVST lesions was high, including 51 cases (43.97%) on the left side and 31 cases (26.72%) on the right side. Bilateral CVST lesions occurred in 13 cases (11.20%) of unilateral intracranial arteritis lesions, and bilateral intracranial arteritis lesions occurred in 16 cases (13.79%) of unilateral CVST lesions. In summary, CVST indicates a potential positive link to intracranial arteritis at the time of pregnancy and puerperium.

Coronary (peri)-arteritis in patients with IgG4-related disease: A case series from the Central Anatolia Region of Turkey.

OBJECTIVE: Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory disease which affects many systems, as well as the cardiovascular system. Identifying the coronary involvement like periaortitis, coronary periarteritis and pericarditis is important, as they often cause unfavorable outcomes. METHODS: Eighty-one patients with IgG4-RD were retrospectively evaluated for symptomatic coronary artery involvement from Hacettepe University Vasculitis Research Center (HUVAC) database. The demographic, laboratory, radiologic and clinical characteristics of the patients were assessed. RESULTS: Among 81 patients with IgG4-RD, 6 patients (M/F:5/1) had coronary artery involvement. The patients' median age was 57 and serum IgG4 levels were above normal except for one case. All patients with coronary arteritis revealed an increased coronary vessel wall thickening and stenotic lesions. The coronary aneurysm and pericarditis were observed in half of the patients. Immunosuppressive treatments were given to all the patients and most of them followed in stable condition. CONCLUSION: Coronary arteritis is a rare but notable manifestation of IgG4-RD. Although coronary periarteritis can cause significant morbidity and mortality, it seems better results can be achieved with early diagnosis and treatment.

Biomarkers of non-infectious inflammatory CNS diseases in dogs: Where are we now? Part 2 - Steroid responsive meningitis-arteritis.

Steroid responsive meningitis-arteritis (SRMA) in dogs causes severe inflammation of meningeal arteries leading to generalized meningitis with possible neurological signs, as well as a systemic inflammatory response. The etiology and exact pathogenesis are unknown, but an immune-mediated origin has been suggested and is supported by a positive response to immunosuppressive treatment with corticosteroids. A collection of clinical and paraclinical characteristics may be highly indicative of SRMA, but a single and conclusive diagnostic test or biomarker is currently not available. The aim of this review is to provide an overview of the current understanding and knowledge on SRMA, with special emphasis on potential biomarkers and their applicability in the diagnostic work-up. Though no specific markers for SRMA currently exist, clinically useful markers include IgA and several acute phase proteins e.g. C-reactive protein. A frequent problem of both acknowledged and proposed biomarkers, is, however, their inability to effectively differentiate SRMA from other systemic inflammatory conditions. Other proposed diagnostic markers include genetic markers, acute phase proteins such as serum amyloid A, cytokines such as interleukin-17 and CC-motif ligand 19, endocannabinoid receptors and heat shock protein 70; these suggestions however either lack specificity or need further investigation.

Reappraisal of Renal Arteritis in ANCA-associated Vasculitis: Clinical Characteristics, Pathology, and Outcome.

BACKGROUND: Renal involvement in ANCA-associated vasculitis (AAV) is associated with poor outcomes. The clinical significance of arteritis of the small kidney arteries has not been evaluated in detail. METHODS: In a multicenter cohort of patients with AAV and renal involvement, we sought to describe the clinicopathologic characteristics of patients with AAV who had renal arteritis at diagnosis, and to retrospectively analyze their prognostic value. RESULTS: We included 251 patients diagnosed with AAV and renal involvement between 2000 and 2019, including 34 patients (13.5%) with arteritis. Patients with AAV-associated arteritis were older, and had a more pronounced inflammatory syndrome compared with patients without arteritis; they also had significantly lower renal survival (P=0.01). In multivariable analysis, the ANCA renal risk score, age at diagnosis, history of diabetes mellitus, and arteritis on index kidney biopsy were independently associated with ESKD. The addition of the arteritis status significantly improved the discrimination of the ANCA renal risk score, with a concordance index (C-index) of 0.77 for the ANCA renal risk score alone, versus a C-index of 0.80 for the ANCA renal risk score plus arteritis status (P=0.008); ESKD-free survival was significantly worse for patients with an arteritis involving small arteries who were classified as having low or moderate risk, according to the ANCA renal risk score. In two external validation cohorts, we confirmed the incidence and phenotype of this AAV subtype. CONCLUSIONS: Our findings suggest AAV with renal arteritis represents a different subtype of AAV with specific clinical and histologic characteristics. The prognostic contribution of the arteritis status remains to be prospectively confirmed.

Lipidomics links oxidized phosphatidylcholines and coronary arteritis in Kawasaki disease.

AIMS: Coronary arteritis is a life-threatening complication that may arise in the acute stage of Kawasaki disease (KD), the leading cause of systemic vasculitis in childhood. Various microorganisms and molecular pathogens have been reported to cause KD. However, little is known about the key molecules that contribute to the development of coronary arteritis in KD. METHODS AND RESULTS: To identify causative molecules for coronary arteritis in KD, we prospectively recruited 105 patients with KD and 65 disease controls in four different parts of Japan from 2015 to 2018. During this period, we conducted lipidomics analyses of their sera using liquid chromatography-mass spectrometry (LC-MS). The comprehensive LC-MS system detected a total of 27 776 molecules harbouring the unique retention time and m/z values. In the first cohort of 57 KD patients, we found that a fraction of these molecules showed enrichment patterns that varied with the sampling region and season. Among them, 28 molecules were recurrently identified in KD patients but not in controls. The second and third cohorts of 48 more patients with KD revealed that these molecules were correlated with inflammatory markers (leucocyte counts and C-reactive proteins) in the acute stage. Notably, two of these molecules (m/z values: 822.55 and 834.59) were significantly associated with the development of coronary arteritis in the acute stage of KD. Their fragmentation patterns in the tandem MS/MS analysis were consistent with those of oxidized phosphatidylcholines (PCs). Further LC-MS/MS analysis supported the concept that reactive oxygen species caused the non-selective oxidization of PCs in KD patients. In addition, the concentrations of LOX-1 ligand containing apolipoprotein B in the plasma of KD patients were significantly higher than in controls. CONCLUSION: These data suggest that inflammatory signals activated by oxidized phospholipids are involved in the pathogenesis of coronary arteritis in KD. Because the present study recruited only Japanese patients, further examinations are required to determine whether oxidized PCs might be useful biomarkers for the development of coronary arteritis in broad populations of KD.

Temporal Arteritis Revealing Antineutrophil Cytoplasmic Antibody-Associated Vasculitides: A Case-Control Study.

OBJECTIVE: Temporal arteritis (TA) is a typical manifestation of giant cell arteritis (GCA). Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are rarely revealed by TA manifestations, leading to a risk of misdiagnosis of GCA and inappropriate treatments. This study was undertaken to describe the clinical, biologic, and histologic presentations and outcomes in cases of TA revealing AAV (TA-AAV) compared to controls with classic GCA. METHODS: In this retrospective case-control study, the characteristics of patients with TA-AAV were compared to those of control subjects with classic GCA. Log-rank test, with hazard ratios (HRs) and 95% confidence intervals (95% CIs), was used to assess the risk of treatment failure. RESULTS: Fifty patients with TA-AAV (median age 70 years) were included. Thirty-three patients (66%) presented with atypical symptoms of GCA (ear, nose, and throat involvement in 32% of patients, and renal, pulmonary, and neurologic involvement in 26%, 20%, and 16% of patients, respectively). Blood samples were screened for ANCAs at the time of disease onset in 33 patients, and results were positive in 88%, leading to a diagnosis of early TA-AAV in 20 patients. The diagnosis of AAV was delayed a median interval of 15 months in 30 patients. Compared to controls with GCA, patients with TA-AAV were younger (median age 70 years versus 74 years), were more frequently men (48% versus 30%), and had high frequencies of atypical manifestations and higher C-reactive protein levels (median 10.8 mg/dl versus 7.0 mg/dl). In patients with TA-AAV, temporal artery biopsy (TAB) showed fibrinoid necrosis and small branch vasculitis in 23% of patients each, whereas neither of these characteristics was evident in controls with GCA. Treatment failure-free survival was comparable between early TA-AAV cases and GCA controls, whereas those with delayed TA-AAV had a significantly higher risk of treatment failure compared to controls (HR 3.85, 95% CI 1.97-7.51; P < 0.0001). CONCLUSION: TA-AAV should be considered diagnostically in cases of atypical manifestations of GCA, refractoriness to glucocorticoid treatment, or early relapse. Analysis of TAB specimens for the detection of small branch vasculitis and/or fibrinoid necrosis could be useful. Detection of ANCAs should be performed in cases of suspected GCA with atypical clinical features and/or evidence of temporal artery abnormalities on TAB.

A Case of IgG4-Related Ophthalmic Disease With Coronary Arteritis.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition characterized by lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells, often with elevated serum IgG4. Multiple organs may be affected. Coronary arteritis may be one form of fatal involvement in IgG4-RD. IgG4-RD can manifest as periocular lesions, called IgG4-related ophthalmic disease (IgG4-ROD). Here, the authors describe a patient with asymptomatic coronary arteritis detected after the diagnosis of IgG4-ROD. A 58-year-old male complained of eyelid swelling and diplopia without systemic symptoms. Swelling of bilateral lacrimal glands and infraorbital nerves, high serum IgG4 levels, and histopathology of lacrimal gland tissue fulfilled diagnostic criteria for IgG4-ROD. After diagnosis, systemic and coronary CT showed coronary lesions and coronary artery stenosis. After prednisolone at 40 mg/day was administered, swelling of the lacrimal glands, diplopia, and coronary lesions improved. This case emphasizes the importance of systemic screening, even if initial symptoms are solely associated with periocular regions.

Amylin, Aß42, and Amyloid in Varicella Zoster Virus Vasculopathy Cerebrospinal Fluid and Infected Vascular Cells.

BACKGROUND: Varicella zoster virus (VZV) vasculopathy is characterized by persistent arterial inflammation leading to stroke. Studies show that VZV induces amyloid formation that may aggravate vasculitis. Thus, we determined if VZV central nervous system infection produces amyloid. METHODS: Aß peptides, amylin, and amyloid were measured in cerebrospinal fluid (CSF) from 16 VZV vasculopathy subjects and 36 stroke controls. To determine if infection induced amyloid deposition, mock- and VZV-infected quiescent primary human perineurial cells (qHPNCs), present in vasculature, were analyzed for intracellular amyloidogenic transcripts/proteins and amyloid. Supernatants were assayed for amyloidogenic peptides and ability to induce amyloid formation. To determine amylin's function during infection, amylin was knocked down with small interfering RNA and viral complementary DNA (cDNA) was quantitated. RESULTS: Compared to controls, VZV vasculopathy CSF had increased amyloid that positively correlated with amylin and anti-VZV antibody levels; Aß40 was reduced and Aß42 unchanged. Intracellular amylin, Aß42, and amyloid were seen only in VZV-infected qHPNCs. VZV-infected supernatant formed amyloid fibrils following addition of amyloidogenic peptides. Amylin knockdown decreased viral cDNA. CONCLUSIONS: VZV infection increased levels of amyloidogenic peptides and amyloid in CSF and qHPNCs, indicating that VZV-induced amyloid deposition may contribute to persistent arterial inflammation in VZV vasculopathy. In addition, we identified a novel proviral function of amylin.

Contemporary management and outcomes of complex vascular surgical groin wound infections.

OBJECTIVE: Vascular surgical groin wound infection (VS-GWI) has multiple causes and frequently is manifested as a limb- or life-threatening problem, resulting in significant morbidity and mortality. For patients undergoing operative extirpation, in situ repair, extra-anatomic bypass, or ligation can be used; however, limited data exist describing comparative results of the different operative choices or conduit subtypes. Therefore, we sought to describe our experience with management of VS-GWI and to detail outcomes of the different strategies. METHODS: Patients (2003-2017) undergoing surgical treatment of VS-GWI (Szilagyi grade III) secondary to primary infectious arteritis or infected pseudoaneurysm after percutaneous intervention as well as previous prosthetic graft placement were reviewed. The primary end point was major adverse limb events (MALEs; major amputation, graft occlusion, or unplanned reintervention). Secondary end points included 30-day mortality, wound healing, amputation-free survival (AFS), and all-cause mortality. Cox proportional hazards modeling was used to determine relative risk of end points; Kaplan-Meier methodology was employed to estimate freedom from outcomes. RESULTS: There were 149 patients (age, 65 ± 11 years; body mass index, 27 ± 6 kg/m2; 70% male; 32% diabetes) identified, of whom 120 (81%) had unilateral and 29 (19%) had bilateral VS-GWI. Indications included infected prosthetic bypass (88% [n = 131]; infrainguinal, 107; suprainguinal, 24) and primary infectious femoral artery complications (12% [n = 18]). A majority underwent single-stage operations (87% [n = 129]). In situ reconstruction occurred in 87% (n = 129); 9% (n = 13) underwent ligation, and 6% (n = 7) received extra-anatomic revascularization. Autogenous conduit was used most commonly (68% [n = 101/149]; 88% single stage), of which 81% (n = 80) were femoral vein. The remaining patients received cadaveric (15% [n = 23]; 87% single stage) or prosthetic (8% [n=12]; 67% single stage) grafts. Adjunctive myocutaneous flap was used in 37% (n = 54). Length of stay was 19 ± 15 days and 30-day mortality was 7% (n = 10), with no difference between conduit repair types. All femoral wounds healed (mean follow-up, 17 ± 11 months); however, 33% (n = 49) underwent reoperation (unplanned graft reintervention, 33%; graft occlusion, 16%; wound débridement, 15%; major amputation, 11%). Reinfection occurred in 17% (n = 27), with no difference between groups. MALE rate was 22% (n = 33; most were arterial reinterventions, 19%), with no difference in single-stage vs multistage, in situ vs extra-anatomic, or autogenous vs nonautogenous conduit strategies Predictors of MALE included younger age (hazard ratio [HR], 1.6 per decade; 95% confidence interval [CI], 1.1-2.5; P = .02) and lower body mass index (<25 kg/m2; HR, 1.6 per BMI category; 95% CI, 1.1-2.5; P = .02). Overall, 1- and 3-year freedom from MALE, AFS, and survival were as follows: MALE, 74% ± 5% and 63% ± 6%; AFS, 68% ± 4% and 58% ± 5%; survival, 78% ± 3% and 70% ± 4%. Autogenous conduit use was associated with better survival (HR, 0.5; 95% CI, 0.3-0.8; 1-year: 83% ± 4% vs nonautogenous, 78% ± 4%; 3-year: 68% ± 8% vs 53% ± 9%; log-rank, P = .006). CONCLUSIONS: An individualized approach to operative strategy and conduit choice leads to comparable outcomes in this challenging group of patients. VS-GWI can be safely managed with in situ, autogenous reconstruction in a majority of patients with acceptable mortality, excellent wound healing rates, and improved overall survival. However, a significant proportion of patients experience reinfection and MALEs, the preponderance of which are arterial reintervention, mandating need for close follow-up and graft surveillance.

Atypical pediatric presentation of lymphocytic thrombophilic arteritis: Diagnostic difficulties and recent nosological clarification.

A 4-year-old girl presented with a 2-month history of round, hypopigmented, slightly scaly patches measuring 1-6 cm and encircled by an erythematous halo, first appearing on the lower limbs then spreading to the whole body. Three biopsies were taken as the condition progressed, each showing a lymphocytic infiltrate affecting a medium-sized artery at the dermal-subcutaneous junction, with a concentric fibrin ring. These findings are characteristic of lymphocytic thrombophilic arteritis (LTA). The young age of our patient and the type of skin lesions she developed make this an atypical presentation of LTA, which usually manifests as hyperpigmented macules on the lower extremities, predominantly in dark-skinned women.