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.

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.

Candida arteritis occurring in a liver transplant recipient.

We report the first case, to our knowledge, of Candida arteritis in a liver transplant recipient. The patient presented with hemorrhagic shock requiring emergency arterial repair. As Candida albicans, Candida tropicalis, and Candida glabrata were growing in the arterial tissue, the patient received antifungal therapy for 5 months, but died because of chronic graft dysfunction. No evidence of fungal infection was found in the tissue on postmortem examination.

Measurement of arterial activity on routine FDG PET/CT images improves prediction of risk of future CV events.

OBJECTIVES: This study sought to determine whether arterial inflammation measured by (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) improves prediction of cardiovascular disease (CVD) beyond traditional risk factors. BACKGROUND: It is unknown whether arterial (18)F-FDG uptake measured with routine PET imaging provides incremental value for predicting CVD events beyond Framingham risk score (FRS). METHODS: We consecutively identified 513 individuals from 6,088 patients who underwent (18)F-FDG-PET and computed tomography (CT) imaging at Massachusetts General Hospital between 2005 and 2008 and who met additional inclusion criteria: ≥30 years of age, no prior CVD, and free of cancer. CVD events were independently adjudicated, while blinded to clinical data, using medical records to determine incident stroke, transient ischemic attack, acute coronary syndrome, revascularization, new-onset angina, peripheral arterial disease, heart failure, or CVD death. FDG uptake was measured in the ascending aorta (as target-to-background-ratio [TBR]), while blinded to clinical data. RESULTS: During follow-up (median 4.2 years), 44 participants developed CVD (2 per 100 person-years at risk). TBR strongly predicted subsequent CVD independent of traditional risk factors (hazard ratio: 4.71; 95% confidence interval [CI]: 1.98 to 11.2; p < 0.001) and (hazard ratio: 4.13; 95% CI: 1.59 to 10.76; p = 0.004) after further adjustment for coronary calcium score. Addition of arterial PET measurement to FRS scores improved the C-statistic (mean ± standard error 0.62 ± 0.03 vs. 0.66 ± 0.03). Further, incorporation of TBR into a model with FRS variables resulted in an integrated discrimination of 5% (95% CI: 0.36 to 9.87). Net reclassification improvements were 27.48% (95% CI: 16.27 to 39.92) and 22.3% (95% CI: 11.54 to 35.42) for the 10% and 6% intermediate-risk cut points, respectively. Moreover, TBR was inversely associated with the timing of CVD (beta -0.096; p < 0.0001). CONCLUSIONS: Arterial FDG uptake, measured from routinely obtained PET/CT images, substantially improved incident CVD prediction beyond FRS among individuals undergoing cancer surveillance and provided information on the potential timing of such events.

Long-term outcome of arterial lesions in Behçet disease: a series of 101 patients.

The vasculitis of Behçet disease (BD) is distinctive because of involvement of both arteries and veins of all sizes. The concept of vasculo-Behçet disease has been adopted for cases in which vascular manifestations are present and often dominate the clinical features. While venous manifestations are frequent and have been reported in many publications, data regarding arterial lesions in patients with BD are rare and often isolated. In this study, we report the main characteristics, treatment, and long-term outcome of 101 patients with arterial lesions among a cohort of 820 (12.3%) BD patients. Factors that affect prognosis were assessed by multivariate analysis. There were 93 (91.2%) male patients; the median (Q1-Q3) age at diagnosis of BD was 33 (27-41) years. Arterial lesions included aneurysms (47.3%), occlusions (36.5%), stenosis (13.5%), and aortitis (2.7%). Lesions mainly involved the aorta (n = 25) and femoral (n = 23) and pulmonary (n = 21) arteries. Patients with arterial lesions were more frequently male (91.2% vs. 62.4%, respectively; p = 0.017) and had higher rates of venous involvement (80.4% vs. 29.8%, respectively; p < 0.001) compared to patients without arterial manifestations. Thirty-nine (38.6%) patients achieved complete remission. In multivariate analysis, the presence of venous involvement (odds ratio [OR], 0.29; 95% confidence interval [CI], 0.08-1.11) and arterial occlusive lesions (OR, 0.13; 95% CI, 0.01-1.25) were negatively associated with complete remission. The use of immunosuppressants (OR, 3.38; 95% CI, 0.87-13.23) was associated with the occurrence of complete remission. The 20-year survival rate was significantly lower in BD patients with arterial involvement than in those without arterial lesions (73% vs. 89%, respectively; p < 0.0001). In conclusion, the long-term outcome of arterial lesions in BD is poor, especially in the case of occlusive lesions and associated venous involvement. The use of immunosuppressants improved the prognosis.

Pulmonary periarterial inflammation in fatal asthma.

BACKGROUND: To date, little information has been available about pulmonary artery pathology in asthma. The pulmonary artery supplies the distal parts of the lungs and likely represents a site of immunological reaction in allergic inflammation. The objective of this study was to describe the inflammatory cell phenotype of pulmonary artery adventitial inflammation in lung tissue from patients who died of asthma. METHODS: We quantified the different inflammatory cell types in the periarterial region of small pulmonary arteries in lung tissue from 22 patients who died of asthma [fatal asthma (FA)] and 10 control subjects. Using immunohistochemistry and image analysis, we quantified the cell density for T lymphocytes (CD3, CD4, CD8), B lymphocytes (CD20), eosinophils, mast cells (chymase and tryptase), and neutrophils in the adventitial layer of pulmonary arteries with a diameter smaller than 500 microm. RESULTS: Our data (median/interquartile range) demonstrated increased cell density of mast cells [FA=271.8 (148.7) cells/mm2; controls=177.0 (130.3) cells/mm2, P=0.026], eosinophils [FA=23.1 (58.6) cells/mm2; controls=0.0 (2.3) cells/mm2, P=0.012], and neutrophils [FA=50.4 (85.5) cells/mm2; controls=2.9 (30.5) cells/mm2, P=0.009] in the periarterial space in FA. No significant differences were found for B and T lymphocytes or CD4+ or CD8+ subsets. Chymase/tryptase positive (MCCT) mast cells predominated over tryptase (MCT) mast cells in the perivascular arterial space in both asthma patients and controls [MCCT/(MCCT+MCT)=0.91 (0-1) in FA and 0.75 (0-1) in controls, P=0.86]. CONCLUSIONS: Our results show that the adventitial layer of the pulmonary artery participates in the inflammatory process in FA, demonstrating increased infiltration of mast cells, eosinophils, and neutrophils, but not of T and B lymphocytes.

[Histopathological examination and analysis of mortality in DBA/2 mouse vasculitis induced with CAWS, a water-soluble extracellular polysaccharide fraction obtained from Candida albicans].

CAWS, a water-soluble extracellular polysaccharide fraction obtained from the culture supernatant of Candida albicans, is one of the fungal pathogen-associated molecular patterns (PAMPs). It has been reported to show potent activity inducing arteritis and coronaritis in mice. Especially, CAWS-induced arteritis has a 100% incidence and severe mortality in the DBA/2 mouse strain. This artificial vasculitis was reported to provide a good murine model of Kawasaki disease and other inflammatory vascular disease. However, severe mortality was observed only in DBA/2 mice, which is a CAWS-sensitive strain. In this study, to clarify the mechanisms of CAWS-induced arteritis and mortality, we investigated microscopic histopathological changes in cardiovascular tissues in DBA/2 mice. Severe inflammatory infiltration was observed from the external elastic lamina in the aorta and proximal coronary arteries within 1 week after CAWS administration. Severe stenosis of the aorta and coronary arteries was observed more than 3 weeks after CAWS administration. Fibrinoid necrosis was observed in these vessel walls. All CAWS-treated mice died between the fifth and twelfth week after administration. Severe inflammatory change with aortic valve transformation suggested that CAWS-treated mice died of valvular endocarditis or cardiac dysfunction. Based on the simple induction method and complete incidence, these data suggest that CAWS-induced arteritis is a good model of not only Kawasaki disease but also other cardiovascular diseases such as valvular endocarditis.

Lethal and severe coronary arteritis in DBA/2 mice induced by fungal pathogen, CAWS, Candida albicans water-soluble fraction.

CAWS is a microbial pathogen-associated molecular patterns (PAMPs) produced by Candida albicans. CAWS is a mannoprotein-beta-glucan complex and secreted into the culture supernatant. CAWS has various biological effects, causing acute shock and disrupting vascular permeability. Intraperitoneal administration of CAWS induces coronary arteritis in various strains of inbred mice. The CAWS-induced coronary arteritis is strain-dependent and most severe in DBA/2 mice with a significant number of these animals expiring with cardiomegaly during the observation period. In vivo and in vitro, splenocytes of DBA/2 mice produced various cytokines, such as IL-6, TNF-alpha, and IFN-gamma in response to CAWS. GM-CSF was also produced in response to CAWS. The production of cytokines was significantly enhanced in the presence of recombinant GM-CSF. In contrast, anti-GM-CSF significantly reduced the production of TNF-alpha and IFN-gamma. Augmented production of cytokines in response to CAWS would be a key to the severity of coronary arteritis.

[Primary bacterial infection of an artery]. / Die primär bakteriell infizierte Arterie.

INTRODUCTION: Primary bacterial infection of an artery is difficult to diagnose, especially at the beginning of the illness. Most of the patients come for emergency treatment in the phase of rupture. METHODS: The course of illness in four patients serves as background for discussion of the problems of diagnosis and therapy. RESULTS: Bacterial infection of arteries shows a high rate of complications and, for the aorta, high mortality. CONCLUSION: If fever of uncertain origin is combined with pain of the stomach or of the back, or with a painful reddish swelling on a limb, this rare disease should be considered in the differential diagnosis.

[Remote follow-up results of the surgery in patients with unspecified aortoarteritis]. / Otdalennye rezul'taty operatsii u bol'nykh s nespetsificheskim aortoarteriitom.

In 133 patients with nonspecific aortoarteritis 172 operations were conducted, 83.8% of them--reconstructive interventions. In 29 patients with isolated affection of truncus brachiocephalicus 32 operations were conducted. Good results of up to 13-year follow-up was 77%, mortality--13.8%. For the isolated affection of aortal arch in 26 patients 27 operations were conducted. Five-year survival have constituted 100%, of them in 79.9% good result was observed. For the isolated affection of aorto-femoral segment 38 patients were operated on. Up to 8-year follow-up was achieved in 32 of them, good result was noted in 73.1%. For the combined affection in 40 patients 51 operations were done. Seven-year follow-up was achieved in 36 patients, good result was noted in 74.2%.

The use of arterial allografts in aortic graft infections. A three year experience on eighteen patients.

BACKGROUND: We describe our experience in the treatment of aortic graft infections by replacing them with arterial homografts as suggested by the good results recently described. METHODS: Between March 1994 and March 1997 eighteen patients with infections of the aortofemoral bifurcation segments have been treated. All patients underwent a complete explantation of the infected graft and an in situ revascularization with arterial homograft harvested in multiorgan removal. Eight segments were freshly preserved, 10 were cryopreserved. Four patients were operated as emergencies, of which 3 for aorto-enteric fistulas. All others presented a serious septic state. RESULTS: Three patients died in the early postoperative period: one of acute infarction and two of homograft related causes. In the follow-up there was only one death from acute infarction, a branch occlusion and two allograft enteric fistulas successfully treated by surgery. All surviving patients are submitted to periodical haemodynamic and tomographic control with an average follow-up of 22 months (range 3 months to 3 years) and there has been no allograft degeneration so far. CONCLUSIONS: The use of homologue arterial allografts has shown good results in the treatment of serious aortic graft infections resulting in adequate peripheral vascularization. There have been no significant degenerations to date, either in fresh or cryopreserved allografts.

[Bilateral aorto-iliac prosthesis. Long-term results]. / Prothèses aorto-bi-fémorales. Résultats à long terme.

Over a 12-year period (1975-1987), 565 patients (male: 94.5 percent; female: 5.5 percent) underwent aorto-iliac bilateral reconstruction. The operations were performed by the same surgical team and all patients were followed up for 13 years. The patients' mean age was 59.4 years; 16.6 percent were over 70; 16 percent had a non-fissured aneurysm. The postoperative mortality rate was 2.8 percent, with relatively few deaths of cardiovascular origin (0.5 percent). The late mortality rate was significantly higher than that of an age-matched control population. Arteritis and its surgical treatment accounted for a low proportion of late deaths: 10.7 percent as opposed to other cardiovascular diseases (33 percent) and chiefly to cancer (39 percent)--a figure not found in other reports. Five percent of the patients had to be amputated soon after the operation or later; this is a low figure compared with the 33 percent of patients who had one limb threatened before reconstructive surgery. After the aorto-iliac reconstruction 81 percent of the patients remained considerably improved at 5 years and 67 percent at 10 years. Long-term arterial patency was satisfactory (95 percent at 5 years, 90 percent at 10 years). This type of surgery, therefore, benefits the patients' functions and their life: it avoids rupture of aneurysms and sedentarity due to a disabling intermittent claudication, and it considerably increases the duration of life.

Necrotizing vasculitis--relapse despite cytotoxic therapy.

The pattern of relapses is described in a consecutive series of 150 patients with vasculitis. Relapse occurred in 42 out of 124 patients who survived for more than 3 months.

[Study of static transcutaneous oximetry before amputation in patients with arteritis]. / Etude de l'oxymétrie transcutanée statique avant amputation chez l'artéritique.

Transcutaneous oximetry has been used to define the level of amputation in arteritic patients, with discrepant results. We have studied preoperative statix oximetry in 33 arteritic patients at the Leriche-Fontaine Stage IV, who underwent 36 amputations (thighs = 6, Legs+Symes = 14, transmetatarsal = 7, toes = 9). Oximetry included the measurement, at the level of amputation, of the transcutaneous partial oxygen pressure (tc pO2), of the tissue oxygenation ratio (TOR), preferably with a precordial electrode, of the tc pO2 gain after oxygen inhalation and of the gain ratio with the reference electrode. Two patients died postoperatively, the amputation stump did not heal in another 8 patients. The tc pO2 value was 36.6 +/- 16.2 mm Hg in the healed group and 21.1 +/- 19.9 mm Hg in the non healed group. The TOR respectively was 71.2 +/- 32.7% and 38.6 +/- 29.9% in these two groups. These differences were statistically significant. The difference between the two groups in the measurements made after the oxygenation test was not statistically significant. With a tc pO2 threshold at 26 mm Hg, the sensitivity was 73% and the specificity 75%, the positive predictive value 90%, the negative predictive value 46% and the value of the test 73.5%. The thresholds calculated to be 56% for TOR, 11 mm Hg for the gain and 32% for the gain ratio, did not improve the performances of oximetry. In our study, the tc pO2 was the parameter that best allowed predicting healing was obtained with smaller values than the threshold. Other elements such as the general condition and diabetes have played a role in the prognosis.

Management of infected aortoiliac aneurysms.

A 30-year retrospective review identified 13 patients treated for infected aneurysms of the abdominal aorta or iliac arteries, for an overall incidence of 0.65%. A constellation of clinical findings led to the correct preoperative diagnosis in 11 (85%) of 13 patients. Treatment methods included resection and in situ replacement grafting in seven patients, resection and extra-anatomic bypass in five patients, and resection-ligation in one patient. Four (31%) of 13 patients died within 30 days of operation, three of whom died of rupture. Overall, good results were achieved in five patients (38%), while poor results were noted in the remaining eight patients (62%). The determinants of outcome were aneurysm location or rupture, the presence of established infection, and the virulence of the infecting organism. In 10 (77%) of the 13 aneurysms, Salmonella species, Bacteroides fragilis, Staphylococcus aureus, and Pseudomonas aeruginosa accounted for all deaths, ruptures, and suprarenal aneurysm infections. These data suggest that patients with primary infections of the abdominal aorta or iliac arteries continue to present with advanced infections or aneurysm rupture that result in a high mortality.

[Fatal course of juvenile chronic arthritis]. / Fataler Verlauf einer juvenilen chronischen Arthritis.

Case report of a young man suffering from seropositive juvenile arthritis who succumbed to the consequences of cerebral vasculitis. Postmortem generalised arteritis was found affecting mainly brain and kidneys. There were no laboratory signs of an inflammatory process during the months before his death nor hypergammaglobinaemia or decrease of complement. The generalised arteritis manifested itself solely as mononeuritis multiplex with eosinophilia. Thus even with discrete signs such as these severe vasculitis ought to be considered for appropriate treatment to be instituted.

Microscopic polyarteritis: clinical features and treatment.

The clinical features, treatment and survival of 36 patients with microscopic polyarteritis diagnosed between 1957-1988 have been reviewed. All had a focal segmental necrotizing glomerulonephritis on renal biopsy with evidence of a small vessel vasculitis. Most had a prodromal illness of less than 1 month. Severity of renal disease varied from microscopic haematuria which has a good prognosis to acute oliguric renal failure which carries a high mortality. The prognosis of microscopic polyarteritis can be improved if the condition is recognized early and treated with steroids and cyclophosphamide.

Improved prognosis of renal microscopic polyarteritis in recent years.

To determine if the short- and long-term prognosis of renal micropolyarteritis (including Wegener's granulomatosis) had improved in our Unit in the last 5 years compared to our previous series from 1965 to 1980, we examined data from 26 recent patients, 1981-1986. Twenty were admitted during acute phase and six after a mean of 7.1 months of disease. The acute phase showed mild to severe impairment of renal function, and renal biopsies showed necrotising glomerulitis in all acute patients with extensive crescents in 67%. Acute patients (20) were treated with 'aggressive' immunosuppression including i.v. methylprednisolone (15), plasmapheresis (seven) and cyclophosphamide (ten). Chronic immunosuppressive treatment was continued in most patients. In the 20 acute-onset patients, life survival at 2 and 5 years was 77%; four of five deaths occurred during the acute phase in aged patients with severe renal failure. The notable improvement in life and kidney survival (only one patient underwent chronic dialysis) probably resulted from greater awareness of vasculitis in general practice with early referral of patients to specialised units, and to more aggressive treatment.