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Background Despite promising early results, mid-term failures of the Nellix endovascular aneurysm sealing (EVAS) system (Endologix Inc, Irvine, Calif) have been reported at higher than expected rates. The management of proximal endoleaks and migration differs from those after conventional endovascular aortic aneurysm repair (EVAR) owing to the peculiar design of the Nellix device. In the present study, we report a monocentric experience in the management of EVAS complications using various techniques. We also performed a comprehensive review of the relevant literature on both open surgical and endovascular management of proximal failure of EVAS from the MEDLINE database. Methods We retrospectively analyzed the reinterventions for type Ia endoleak and migration after elective infrarenal EVAS at our institution. We collected preoperative, intraoperative, and follow-up data. Open and endovascular techniques are described. Overall survival, aortic-related mortality, and the technical success rate (rate of exclusion of endoleaks) with endovascular techniques were the primary outcomes. Results We performed 101 infrarenal elective EVAS procedures from 2013 to 2018. Of the 101 patients, 20 (19.8%) had required reintervention for proximal sealing failure. The indications were type Ia (Is2, Is3) endoleak, migration >5 mm, sac expansion >5 mm, and secondary rupture. Of the 20 patients, 6 (30%) were treated with endovascular techniques—2 with a chimney Nellix-in-Nellix application and 4 with proximal relining with a covered stent. The remaining 14 patients (70%) were treated with late open conversion (OC). The average time from EVAS to reintervention was 36.1 months (range, 3-65 months). Six patients (30%) had undergone OC in an emergent setting because of secondary rupture. The technical success rate for the patients treated with endovascular reinterventions was 100%. The 30-day mortality was 20% (4 of 20), all emergent cases (four of six emergent repairs; 67%). The overall survival for the 20 patients was 75% (n = 15) at a mean follow-up of 15.1 months (range, 2-47 months). One patient had died after 7 months of non–aortic-related causes. Conclusions The high reintervention rate of the Nellix graft mandates careful evaluation for its further use with the revised instructions for use, and it should not be used off-label. OC remains the strategy of choice when managing Nellix proximal sealing failures in fit patients. Chimney Nellix-in-Nellix application and transcatheter embolization are feasible alternative techniques. Proximal relining also appears to be an effective alternative to more complex interventions, although it requires further studies for validation.

Objective Sjogren's syndrome (SS) is a chronic autoimmune disease with a highly variable presentation. This study aims to describe childhood SS (cSS) features to help guide clinicians in their consideration of and workup for cSS. Methods We retrospectively reviewed medical records of patients with cSS referred to three Italian pediatric rheumatology centers from 2015 to 2019 and we conducted a literature review of cSS. Statistical analysis was performed to detect associations between clinical/laboratory features. Results We reviewed 12 cases (9 female) followed in 3 Italian centers and 240 cases (191 female) in the published literature reporting individual information. The median age at disease onset was 10 years for both cohorts. The most frequently reported clinical SS-specific feature was parotitis in both cohorts (67% each). Extraglandular manifestations were very common and joint involvement was the most frequent. In the cluster analysis, we identified a significant association between parotitis and younger patients ( Conclusion We described cSS features with relative frequencies and we found that parotid involvement was related to cSS in younger patients. The majority of patients showed various combinations of exocrine gland inflammation, exocrine gland dysfunction, and presence of autoantibodies giving a theoretical basis for future research to pave the way for the development of cSS specific diagnostic criteria.

Objectives To investigate survival of IL-1 inhibitors in monogenic autoinflammatory disorders (mAID) through drug retention rate (DRR) and identify potential predictive factors of drug survival from a real-life perspective. Patients and methods Multicentre retrospective study analysing patients affected by the most common mAID treated with anakinra or canakinumab. Survival curves were analysed with the Kaplan-Meier method. Statistical analysis included a Cox-proportional hazard model to detect factors responsible for drug discontinuation. Results Seventy-eight patients for a total of 102 treatment regimens were enrolled. The mean treatment duration was 29.59 months. The estimated DRR of IL-1 inhibitors at 12, 24 and 48 months of follow-up was 75.8%, 69.7% and 51.1%, respectively. Patients experiencing an adverse event had a significantly lower DRR (P=0.019). In contrast, no significant differences were observed between biologic-naïve patients and those previously treated with biologic drugs (P=0.985). Patients carrying high-penetrance mutations exhibited a significantly higher DRR compared with those with low-penetrance variants (P=0.015). Adverse events were the only variable associated with a higher hazard of treatment withdrawal [hazard ratio (HR) 2.573 (CI: 1.223, 5.411), P=0.013] on regression analysis. A significant glucorticoid-sparing effect was observed (P Conclusions IL-1 inhibitors display an excellent long-term effectiveness in terms of DRR, and their survival is not influenced by the biologic line of treatment. They display a favourable safety profile, which deserves, however, a close monitoring given its impact on treatment continuation. Special attention should be paid to molecular diagnosis and mutation penetrance, as patients carrying low-penetrance variants are more likely to interrupt treatment.

Familial Mediterranean fever (FMF) is characterized by self limited episodes of fever and polyserositis.1 MEFV gene en codes for a protein named Pyrin, which plays a pivotal role in the activation and secretion of IL-1.2 Daily colchicine is highly effective in preventing attacks in this disorder in a dose-related fashion.3 Many definitions of colchicine resistance are available in the literature. The European League Against Rheumatism (EULAR) guidelines defined resistance as one or more attacks per month in compliant patients who had been receiving the maxi mally tolerated dose for at least 6 months.4 A similar definition was confirmed by a recent consensus among experts.5 In the present national multicentric longitudinal study, we analyze the impact of colchicine treatment on disease activity and quality of life in real life in pediatric and adult patients with FMF.

Noninfectious uveitis represents one of the leading causes of blindness in developed Countries, compromising patients' quality of life and social functioning. The main treatment goals are the control of ocular inflammation, to avert and treat sight-threatening complications, thus preserving and/or restoring visual function.This manuscript deals with systemic therapy with biologic drugs for noninfectious uveitis. An extensive literature search in the MEDLINE database (via PubMed) has been performed up to June 2020. The major classes of biologic molecules employed in ocular inflammatory diseases have been reviewed, focusing on TNF inhibitors, IL-1, IL-6, IL-17, IL-23 inhibitors, interferons, rituximab, and abatacept efficacy and safety. An overview of most recent developments in the field has been provided as well, with reference to the experience with JAK inhibitors and with biosimilar drugs.The development of the concept of targeted therapy and the subsequent introduction of biologic molecules in clinical practice have revolutionized the prognosis of uveitis. The target of a rapid and sustained steroid-free remission of ocular inflammation should be pursued for all patients early in the disease course, in order to have a better chance to improve the final visual outcome.

Summary Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding UK Medical Research Council and Health Technology Assessment Programme.

Objective: To describe the role of biotechnological therapies in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) and to identify any predictor of complete response.Methods: Clinical, laboratory, and therapeutic data from 44 Caucasian TRAPS patients treated with biologic agents were retrospectively collected in 16 Italian tertiary Centers.Results: A total of 55 biological courses with anakinra (n = 26), canakinumab (n = 16), anti-TNF-α agents (n = 10), and tocilizumab (n = 3) were analyzed. A complete response was observed in 41 (74.5%) cases, a partial response in 9 (16.4%) cases and a treatment failure in 5 (9.1%) cases. The frequency of TRAPS exacerbations was 458.2 flare/100 patients-year during the 12 months prior to the start of biologic treatment and 65.7 flare/100 patients-years during the first 12 months of therapy (p < 0.0001). The median duration of attacks was 5.00 (IQR = 10.50) days at the start of biologics and 1.00 (IQR = 0.00) days at the 12-month assessment (p < 0.0001). Likewise, a significant reduction was observed in the Autoinflammatory Disease Activity Index during the study period (p < 0.0001). A significant corticosteroid sparing effect was observed as early as the first 12 months of treatment both in the number of patients requiring corticosteroids (p = 0.025) and in the dosages employed (p < 0.0001). A significant reduction was identified in the erythrocyte sedimentation rate (p < 0.0001), C reactive protein (p < 0.0001), serum amyloid A (p < 0.0001), and in the 24-h proteinuria dosage during follow-up (p = 0.001). A relapsing-remitting disease course (OR = 0.027, C.I. 0.001–0.841, p = 0.040) and the frequency of relapses at the start of biologics (OR = 0.363, C.I. 0.301–0.953, p = 0.034) were significantly associated with a complete response. No serious adverse events were observed.Conclusions: Treatment with biologic agents is highly effective in controlling clinical and laboratory TRAPS manifestations. Patients with a relapsing-remitting course and a lower frequency of flares at the start of treatment show more likely a complete response to biologic agents.

This study explores demographic, clinical, and therapeutic features of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a cohort of 80 patients recruited from 19 Italian referral Centers. Patients’ data were collected retrospectively and then analyzed according to age groups (disease onset before or after 16 years) and genotype (high penetrance (HP) and low penetrance (LP) TNFRSF1A gene variants). Pediatric- and adult-onset were reported, respectively, in 44 and 36 patients; HP and LP variants were found, respectively, in 32 and 44 cases. A positive family history for recurrent fever was reported more frequently in the pediatric group than in the adult group (p<0.05). With reference to clinical features during attacks, pericarditis and myalgia were reported more frequently in the context of adult-onset disease than in the pediatric age (with p<0.01 and p<0.05, respectively), while abdominal pain was present in 84% of children and in 25% of adults (p<0.01). Abdominal pain was significantly associated also to the presence of HP mutations (p<0.01), while oral aphthosis was more frequently found in the LP variant group (p<0.05). Systemic amyloidosis occurred in 25% of subjects carrying HP variants. As concerns laboratory features, HP mutations were significantly associated to higher ESR values (p<0.01) and to the persistence of steadily elevated inflammatory markers during asymptomatic periods (p<0.05). The presence of mutations involving a cysteine residue, abdominal pain, and lymphadenopathy during flares significantly correlated with the risk of developing amyloidosis and renal impairment. Conversely, the administration of colchicine negatively correlated to the development of pathologic proteinuria (p<0.05). Both NSAIDs and colchicine were used as monotherapy more frequently in the LP group compared to the HP group (p<0.01). Biologic agents were prescribed to 49 (61%) patients; R92Q subjects were more frequently on NSAIDs monotherapy than other patients (p<0.01); nevertheless, they required biologic therapy in 53.1% of cases. At disease onset, the latest classification criteria for TRAPS were fulfilled by 64/80 (80%) patients (clinical plus genetic items) and 46/80 (57.5%) patients (clinical items only). No statistically significant differences were found in the sensitivity of the classification criteria according to age at onset and according to genotype (p<0.05). This study describes one of the widest cohorts of TRAPS patients in the literature, suggesting that the clinical expression of this syndrome is more influenced by the penetrance of the mutation rather than by the age at onset itself. Given the high phenotypic heterogeneity of the disease, a definite diagnosis should rely on both accurate working clinical assessment and complementary genotype.

Chronic anterior uveitis is the most frequent among extra-articular manifestations of juvenile idiopathic arthritis (JIA) and a relevant cause of ocular morbidity in children. Asymmetric arthritis, early onset disease, female sex, and anti-nuclear antibody (ANA) positivity are counted among risk factors for developing this complication. It usually has insidious onset and asymptomatic chronic-relapsing course, but the persistence of low-grade chronic inflammation can lead to irreversible structural ocular damage and to vision-threatening complications. For such reasons, achieving a complete absence of inflammation through early targeted and aggressive treatments is a primary therapeutic goal in these patients. This review is aimed at summarizing scientific evidence about biologic rescue therapy of JIA-related uveitis in patients who fail to achieve clinical remission, in spite of being treated with conventional disease-modifying anti-rheumatic drugs (cDMARDs) and at least one biologic tumor necrosis factor (TNF)-α inhibitor. Interleukin (IL)-6 inhibition appears a promising and safe option for refractory JIA-related uveitis. Abatacept and rituximab proved to be beneficial as well, but their efficacy together with some safety concerns needs to be more extensively evaluated.

Background While the experience with PCSK9i in patients with coronary artery disease has been wide, and coronary plaque regression has been documented, little is known regarding the role of these drugs on carotid plaque regression. The CARotid plaqUe StabilizatiOn and regression with evolocumab (CARUSO) study is a randomized, single-center, investigator-initiated trial aiming at evaluating carotid plaque morphological stabilization and regression following, respectively, 6 and 12 months of therapy with evolocumab. Methods Asymptomatic patients with uni- or bilateral de novo carotid artery stenosis ≥50% and LDL-C values ≥100 mg/dl despite maximum tolerated lipid lowering therapy (LLT) will be randomized to evolocumab 140 mg s.c. every 2 weeks on top of ongoing LLT, or no additional treatment. 100 patients (50 in each arm) will be enrolled. Serial carotid duplex ultra-sonography will be performed to monitor the carotid plaque morphology and stenosis over time. Results The primary end point of the study is, (a) carotid plaque morphological stabilization at 6 months, defined as defined as the disappearance of ulcerations and fluffy components and the achievement of a regular plaque morphology with prevalence of fibrous atheroma and/or (b) carotid plaque regression at 12 months, defined as reduction of the entity of the stenosis and/or peak systolic velocity by at least 5%, as compared with baseline. Conclusion The CARUSO trial will test the superiority of evolocumab on top of ongoing LLT versus ongoing LLT alone regarding carotid plaque morphological stabilization and regression. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

PURPOSE Several concerns have arisen with biosimilars in terms of immunogenicity, safety issues, loss of efficacy, and extrapolation to other indications. The study aim was to evaluate the efficacy of SB5, an adalimumab biosimilar, in noninfectious uveitis (NIU). DESIGN Retrospective nonrandomized study. METHODS Data from patients with refractory NIU treated with SB5 (Imraldi, Biogen) were analyzed at baseline, 3 months after SB5 initiation and at the last follow-up in terms of uveitis relapses, occurrence of retinal vasculitis, resolution of uveitic macular edema (UME), best-corrected visual acuity, glucocorticoids (GCs)-sparing effect and drug survival. RESULTS Uveitis relapses decreased from 121 relapses/100 patients/year in the 12 months before SB5 initiation to 4 relapses/100 patients/year during the first 12 months of treatment (P = 0.0004). Uveitis was inactive in 46/47 eyes at the end of the study period. The number of eyes with active retinal vasculitis decreased during the study period (P

Background and Objective: Only a few studies have reported long-term efficacy of interleukin (IL)-1 inhibition in systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still disease (AOSD). Herein we report on the effectiveness of anakinra (ANA), expressed in terms of drug retention rate (DRR), and evaluate the predictive factors of drug survival in a cohort of patients with sJIA and AOSD. Patients and Methods: This is a multicenter study reviewing retrospectively the medical records from 61 patients with sJIA and 76 with AOSD, all treated with ANA in 25 Italian tertiary referral centers. Results: The cumulative retention rate of ANA at 12-, 24-, 48-, and 60-month of follow-up was 74.3%, 62.9%, 49.4%, and 49.4%, respectively, without any significant differences between sJIA and AOSD patients (p = 0.164), and between patients treated in monotherapy compared with the subgroup coadministered with conventional diseasemodifying antirheumatic drugs (cDMARDs) (p = 0.473). On the other hand, a significant difference in DRR was found between biologic-naïve patients and those previously treated with biotechnologic drugs (p = 0.009), which persisted even after adjustment for pathology (p = 0.013). In the regression analysis, patients experiencing adverse events (AEs) {hazards ratio (HR) = 3.029 [confidence interval (CI) 1.750–5.242], p < 0.0001} and those previously treated with other biologic agents [HR = 1.818 (CI 1.007–3.282), p = 0.047] were associated with a higher HR of ANA discontinuation. The median treatment delay was significantly higher among patients discontinuing ANA (p < 0.0001). Significant corticosteroid-sparing (p = 0.033) and cDMARD-sparing effects (p < 0.0001) were also recorded. Less than one-third of our cohort developed AEs, and 85% were deemed mild in nature, with 70% of them involving the skin. Conclusions: Our findings display an overall excellent DRR of ANA on the long run for both sJIA and AOSD, that may be further optimized by closely monitoring patient’s safety issues and employing this IL-1 inhibitor as a first-line biologic as early as possible. Moreover, ANA allowed a significant drug-sparing effect and showed an overall good safety profile.

Introduction: The advent of biologic agents has revolutionized therapeutic approaches in systemic juvenile idiopatic arthritis (sJIA) as their introduction has been shown to modify disease course and improve overall outcomes, particularly when initiated early. Few studies have reported the drug retention rate (DRR) of biologic drugs in JIA, and none of them has specifically investigated the DRR of interleukin (IL)-1 inhibitors on sJIA. Objectives: The primary aim of the study was to examine the overall DRR of IL-1 blockers in sJIA patients. Secondary aims of our study were to: (i) explore the influence of biologic line of treatment, adverse events (AEs), type of anti-IL-1 agent and the concomitant use of conventional disease modifying anti-rheumatic drugs (cDMARDs) on DRR; (ii) find eventual predictive factors associated with events leading to drug discontinuation. The corticosteroid sparing effect and the impact of disease duration and treatment delay on survival constituted ancillary aims. Methods: sJIA patients – diagnosed according to the revised International League of Association for Rheumatology (ILAR) criteria – treated with anakinra (ANA) and canakinumab (CAN) were enrolled in 15 Italian tertiary referral centers. Demographic, clinical and therapeutic data collected from medical records were retrospectively collected and statistically analyzed. Results: Seventy seven patients were enrolled for a total of 86 treatment courses. The cumulative retention rate of the IL-1 inhibitors at 12-, 24-, 48-, and 60-months of follow-up was 79.9, 59.5, 53.5, and 53.5%, respectively, without any statistically significant differences between ANA and CAN (p = 0.056), and between patients treated in monotherapy compared to the subgroup co-administered with conventional immunosuppressors (p = 0.058). On the contrary, significant differences were found between biologic-naive patients and those previously treated with biologic drugs (p = 0.038) and when distinguishing according to AEs occurrence (p = 0.04). In regression analysis, patients pre-treated with other biologics (HR = 3.357 [CI: 1.341–8.406], p = 0.01) and those experiencing AEs (HR = 2.970 [CI: 1.186–7.435], p = 0.020) were associated with a higher hazard ratio of IL-1 inhibitors withdrawal. The mean treatment delay was significantly higher among patients discontinuing IL-1 inhibitors (p = 0.0002). Conclusion: Our findings suggest an excellent overall DRR for both ANA and CAN that might be further augmented by paying attention to AEs and employing these agents as first-line biologics in an early disease phase.

Background: Aim of this study was to search for any difference in the outcome of patients with adult onset Still's disease (AOSD) treated with anakinra (ANK) in relation with the interval between disease onset and the start of anti-interleukin(IL)-1 treatment and according with the different lines of ANK treatment. Patients and Methods: One hundred and forty-one AOSD patients treated with ANK have been retrospectively assessed. Statistically significant differences (p < 0.05) were analyzed in the frequency of ANK effectiveness, primary or secondary inefficacy to ANK and rate of resolution of clinical and laboratory AOSD manifestations after 3, 6, and 12 months since ANK treatment according with different lines of treatment and different times between AOSD onset and start of ANK. Results: No significant differences were identified in the ANK effectiveness and frequency of primary or secondary inefficacy for patients starting ANK within 6 months (p = 0.19, p = 0.14, and p = 0.81, respectively) or 12 months (p = 0.37, p = 0.23, and p = 0.81, respectively) since AOSD onset compared with patients starting ANK thereafter; no significant differences were identified in ANK effectiveness and primary or secondary inefficacy according with different lines of ANK treatment (p = 0.06, p = 0.19, and p = 0.13, respectively). Patients starting ANK within 6 and 12 months since AOSD onset showed a significantly quicker decrease of erythrocyte sedimentation rate and C-reactive protein than observed among patients undergoing ANK treatment after 6 and 12 months. The number of swollen joints at the 3 month follow-up visit was significantly lower among patients undergoing ANK within 6 months since AOSD onset (p = 0.01), while no significance was identified at the 6 and 12 month assessments (p = 0.23 and p = 0.45, respectively). At the 3 and 6 month visits, the number of swollen joints was significantly higher among patients previously treated with conventional and biological disease modifying anti-rheumatic drugs (DMARDs) compared with those formerly treated only with conventional DMARDs (p < 0.017). Conclusions: Clinical and therapeutic outcomes are substantially independent of how early ANK treatment is started in AOSD patients. However, a faster ANK effectiveness in controlling systemic inflammation and resolving articular manifestations may be observed in patients benefiting from IL-1 inhibition as soon as after disease onset.

Background Endovascular aneurysm repair (EVAR) is currently accepted as an alternative to open repair for the treatment of abdominal aortic aneurysm (AAA). Approximately 40–60% of AAA patients are not considered eligible for EVAR due to unfavorable anatomy. There is currently no consensus on the definition of “hostile” aortic neck for EVAR procedure. Methods An Expert Panel (EP), made up of 9 Italian vascular surgeons from high-volume centers (>50 EVAR procedures/year), was assembled to share their opinion about the definition of hostile aortic neck anatomy for EVAR procedure. The process included a review of the current literature by the EP, a face-to-face meeting, and an on-line survey completed by the EP prior to and following the face-to-face meeting, using the Delphi method. Results Of the 66 reviewed studies, only 38 (58%) reported at least 1 aortic neck hostility criterion. Five anatomic parameters were identified, namely, aortic neck length, aortic neck angulation, aortic neck diameter, conical neck, and presence of circumferential calcification. Based on the results of the first survey round, these criteria and related definitions were discussed in depth during the face-to-face meeting. For 3 parameters (aortic neck diameter, aortic neck angulation, conical neck), the agreement among the EP members was already high during the first survey round while for the remaining 2 (aortic neck length, circumferential calcification) it remarkably increased from the first to the second survey round. For each of these criteria, as well as combinations of at least 2 of these criteria, specific threshold values were identified above or below which a standard EVAR approach was not considered ideal by the EP due to high/moderate risk of complications. Conclusions EP agreed on the definition of 5 aortic neck hostility criteria, according to which they gave their opinion on the feasibility and risks of a standard EVAR approach. Further agreement will be needed and examined on the best nonstandard EVAR technique which may be offered in the presence of different combinations of hostility criteria.

Behçet’s syndrome (BS) represents an understudied topic in pediatrics: the main aims of our study were to characterize demographic and clinical features of a cohort of BS patients with juvenile-onset managed in three tertiary referral centers in Italy, evaluate their evolution in the long-term, and detect any potential differences with BS patients having an adult-onset. Medical records of 64 juvenile-onset and 332 adult-onset BS followed-up over a 2-year period were retrospectively analyzed and compared. Mean age ± SD of first symptom-appearance was 10.92 ± 4.34 years with a female-to-male ratio of 1.06:1. Mucocutaneous signs were the most frequent initial manifestations, followed by uveitis. Throughout the disease course, genital aphthae (76.56%) and pseudofolliculitis (40.63%) prevailed among the mucocutaneous signs, while major organ involvement was represented by gastrointestinal and ocular involvement (43.75 and 34.38%, respectively). No significant differences emerged for both mucocutaneous signs and specific major organ involvement between juvenile-onset and adult BS patients. After excluding nonspecific abdominal pain, juvenile-onset BS patients were less frequently characterized by the development of major organ involvement (p = 0.027). Logistic regression detected the juvenile-onset as a variable associated with reduced risk of long-term major organ involvement (OR 0.495 [0.263–0.932],p = 0.029). In our cohort, juvenile-onset BS resembled the clinical spectrum of adult-onset patients. Pediatric patients with a full-blown disease at onset showed a more frequent mucocutaneous involvement. In addition, patients with juvenile-onset seemed to develop less frequently major organ involvement and had an overall less severe disease course.

Background:Schnitzler’s syndrome is an autoinflammatory disease characterized by monoclonal gammopathy and recurrent episodes of urticaria accompanied by clinical and laboratory signs of acute inflammation. Interleukin (IL)-1 inhibitors proved to be useful in the treatment, but data on long-term safety and efficacy of these agents are sparse.Objectives:To evaluate the retention rate of IL-1 inhibitors in patients with Schnitzler’s Syndrome.Methods:Retrospective analysis of an Italian multicenter cohort (9 Centers). All patients fulfilled Strasbourg diagnostic criteria. Data are expressed as median [IQR].Results:We identified 15 patients (8 females, 7 males) who received a total of 24 treatment courses with IL-1 inhibitor treatment (16 anakinra and 8 canakinumab) between January 2001 and December 2019, with a median treatment duration of 19 months [8.5-51.3]. Median age at diagnosis was 64.0 years [56.0-72.5] and median follow up was 5.0 years [2.0-8.0]. Before the biological treatment, all patients were treated with corticosteroids and 11 with at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD): methotrexate (5), colchicine (5), cyclosporine (3), azathioprine (1), mycophenolate mofetil (1), cyclophosphamide (1).Fifteen patients received 16 courses of Anakinra, which was the 1st line biological treatment in 14 patients. Seven patients continued it with benefit, while 7 patients discontinued it: 3 for secondary inefficacy; 3 for adverse events (2 injection site reactions, 1 severe allergic reaction); 1 for secondary inefficacy and leukopenia. Anakinra was used as 2nd line treatment in 1 case (after tocilizumab failure); in 1 patient anakinra was resumed after temporary discontinuation and an attempt with infliximab. One patient died for multiple myeloma progression while on treatment with anakinra. The median duration of the courses with anakinra was 20.0 months [6.0-58.3].Seven patients received 8 courses of canakinumab (150 mg/8weeks in 5 cases and 150 mg/4weeks in 3). In 5 cases the drug was administered as 2nd line biological treatment (after anakinra failure) and in 2 cases as 3rd line treatment (1 after tocilizumab and anakinra failures and 1 after anakinra and adalimumab failure). In 1 patient, it was resumed after temporary discontinuation and an attempt with etanercept. One patient died while on treatment with canakinumab due to a presumably unrelated adverse event. The median duration of canakinumab treatment courses was 19.0 months [13.5-31.0].At last follow-up visit, all patients were on treatment with an IL-1 inhibitor: 8 with anakinra (7 at the dosage of 100 mg/day, 1 at the dosage of 200 mg/day) and 7 with canakinumab (2 at the dosage of 150 mg/8 weeks, 4 at the dosage of 150 mg/4 weeks and 1 at the dosage of 300 mg/4 weeks). Notably, in 3 patients the dosage of canakinumab was increased since the start of the treatment.Among 9 patients who were on treatment with prednisone at the start of the last IL-1 inhibitor, the prednisone median dose was 12.5 mg/day [10.0-18.8] while at the last follow-up visit it was 5.0 mg/day [0-7.5] (p= 0.02).The retention rate of IL-1 inhibitors was 73.4% [SE 9.4] at 1 year and 63.6% [SE 10.4] at 2 years (Figure 1a). There was no significant difference between the retention rate of anakinra (at 1 year: 67.0% [12.2]; at 2 years: 59.6% [12.9]) and canakinumab (at 1 year: 85.7% [13.2]; at 2 years 71.4% [17.1]) (log-rank test: p=0.41) (Figure 1b).Figure 1.a) Retention rate of IL-1 inhibitors (24 courses); b) Retention rate of canakinumab (8 courses) and anakinra (16 courses).Conclusion:In this multicentric cohort of patients affected by Schnitzler’s syndrome, the treatment with IL-1 inhibitors as 1st, 2nd or 3rd line biological treatment permitted a good disease control and corticosteroid reduction in patients who did not respond to csDMARDs and/or to prior other biological DMARDs. The optimal dosage of these drugs needs to be tailored for every patient.Acknowledgements:AIDA NetworkDisclosure of Interests:Francesca Crisafulli: None declared, Antonio Vitale: None declared, Carla Gaggiano: None declared, Lorenzo Dagna: None declared, Giulio Cavalli Speakers bureau: SOBI, Novartis, Paid instructor for: SOBI, Novartis, Consultant of: SOBI, Novartis, Rolando Cimaz: None declared, Ombretta Viapiana: None declared, Florenzo Iannone: None declared, Giuseppe Lopalco: None declared, Roberto Bortolotti: None declared, Masen Abdel Jaber: None declared, Carlomaurizio Montecucco: None declared, Sara Monti: None declared, Silvia Balduzzi: None declared, Giacomo Emmi: None declared, Paolo Airò: None declared, Franco Franceschini: None declared, Luca Cantarini Speakers bureau: SOBI, Novartis, Paid instructor for: SOBI, Grant/research support from: SOBI, Novartis, Micol Frassi: None declared

Background: Anakinra (ANA) is an effective treatment choice in patients with adult onset Still’s disease (AOSD). Variables affecting treatment survival include loss of efficacy or adverse events, but also the decision to discontinue treatment after long-term clinical remission. Objectives: Aims of this study were: (i) to assess the drug retention rate (DRR) of ANA during a long-term follow-up looking for any difference related to the line of biologic treatment, the concomitant use of conventional disease modifying anti-rheumatic drugs (cDMARDs) and the different type of AOSD (systemic versus chronic articular); (ii) to identify predictive factors of lack of efficacy, loss of efficacy, and ANA withdrawal owing to long-term remission. Methods: AOSD patients classified according with Yamaguchi criteria and treated with ANA were retrospectively enrolled in 18 Italian tertiary Centers. Demographic, laboratory, clinical and therapeutic data related to the start of ANA (baseline), the 3-month assessment and the last follow-up visit while on ANA treatment were retrospectively collected and statistically analyzed. Results: One hundred and forty-one AOSD patients (48 males, 93 females) treated with ANA for a mean period of 35.96 ± 36.05 months were enrolled. The overall DRR of ANA was 44.6 and 30.5% at the 60- and 120-month assessments, respectively, with no significant differences between: (i) biologic naïve patients and those previously treated with other biologics (log-rank p = 0.97); (ii) monotherapy and concomitant use of cDMARDs (log-rank p = 0.45); (iii) systemic and chronic articular types of AOSD (log-rank p = 0.67). No variables collected at baseline could predict primary inefficacy, while the number of swollen joints at baseline was significantly associated with secondary inefficacy (p = 0.01, OR = 1.194, C.I. 1.043–1.367). The typical AOSD skin rash was negatively related with ANA withdrawal owing to long-term remission (p = 0.03, OR = 0.224, C.I. 0.058–0.863). Conclusion: Long-term DRR of ANA has been found excellent and is not affected by different lines of biologic treatment, concomitant use of cDMARDs, or type of AOSD. The risk of losing ANA efficacy increases along with the number of swollen joints at the start of therapy, while the typical skin rash is a negative predictor of ANA withdrawal related to sustained remission.

Aims The aim of the present study was to evaluate periprocedural and 30-day outcomes in a prospective series of patients treated with the CGuard Embolic Prevention System (EPS). Methods and results From April 2015 to June 2016, a physician-initiated prospective multicentre study was performed in 200 consecutive patients admitted for protected carotid artery stenting (CAS) and treated using the CGuard EPS in twelve vascular centres. Outcome measures were: technical success, periprocedural (0-24 hours) and post-procedural (24 hours-30 days) major and minor strokes, death, acute myocardial infarction (AMI), transient ischaemic attack (TIA), and external carotid occlusion. In three centres, consecutive diffusion-weighted magnetic resonance cerebral imaging (DW-MRI) was performed ≤72 hours prior to and within 72 hours after the intervention. A distal embolic protection device was employed in 182 patients (91%). Technical success was 100%. No death, AMI or major stroke occurred periprocedurally. There were two TIAs and five periprocedural minor strokes (2.5%), including one thrombosis solved by surgery. In the remaining patients (199/200; 99.5%) one-month follow-up duplex ultrasound revealed optimal technical results. Post-procedural clinical follow-up was uneventful. No external carotid artery occlusion occurred. New post-procedural DW-MRI lesions were detected in 12 patients out of 61 (19.6%), including bilateral in five (8.2%) and isolated ipsilateral in six (9.8%), whereas one patient (1.6%) had contralateral only lesions. Conclusions Multicentre multi-specialty use of the CGuard EPS in routine clinical practice was associated with no major periprocedural neurologic complications and a total elimination of post-procedural neurologic complications by 30 days.

Intoxications, both accidental and intentional, are common in children and adolescents and often require hospitalisation and intensive treatment. Antiepileptic drugs are a possible cause of poisoning and intoxications because this category of medications has shown a rising trend in recent years. They might be responsible for multi-organ dysfunctions of variable severity, ranging from subtle symptoms to life-threatening complications. No guidelines on the management of these intoxications in the paediatric population are currently available, and treatment is mainly supportive. Activated charcoal administration and extracorporeal circulation techniques for drug removal have been proposed. Facing the complexity of this clinical scenario, it is of utmost importance to maintain a high index of suspicion to guarantee a prompt intervention and ensure the best possible management for the patient.

Interest in understanding the aging process has recently risen in the scientific community. Aging, commonly defined as the functional decline in the function of organs and tissues, is indeed the major risk factor for the development of many chronic diseases, such as cardiovascular diseases, pathologies of nervous system, or cancer. To date, the influence of aging in the pathophysiology of liver and biliary diseases is not fully understood. Although liver cells have a high regenerative capacity, hepatocytes and cholangiocytes undergo extensive molecular changes in response to aging. Following time-dependent damage induced by aging, liver cells initially activate compensatory mechanisms that, if hyperstimulated, may lead to the decline of regenerative capacity and the development of pathologies. A deeper understanding of molecular aging has undoubtedly the potential to improve the clinical management of patients, possibly unveiling new pathways for selective drug treatment.

Monogenic autoinflammatory diseases (mAIDs) are inherited errors of innate immunity characterized by systemic inflammation recurring with variable frequency and involving the skin, serosal membranes, synovial membranes, joints, the gastrointestinal tube, and/or the central nervous system, with reactive amyloidosis as a potential severe long-term consequence. Although individually uncommon, all mAIDs set up an emerging chapter of internal medicine: recent findings have modified our knowledge regarding mAID pathophysiology and clarified that protean inflammatory symptoms can be variably associated with periodic fevers, depicting multiple specific conditions which usually start in childhood, such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, cryopyrin-associated periodic syndrome, and mevalonate kinase deficiency. There are no evidence-based studies to establish which potential genotype analysis is the most appropriate in adult patients with clinical phenotypes suggestive of mAIDs. This review discusses genetic and clinical hints for an ideal diagnostic approach to mAIDs in adult patients, as their early identification is essential to prompt effective treatment and improve quality of life, and also highlights the most recent developments in the diagnostic work-up for the most frequent hereditary periodic febrile syndromes worldwide.

Background Endovascular aneurysm sealing (EVAS) is an innovative alternative to conventional endovascular aneurysm repair (EVAR). EVAS relies on sac anchoring without proximal fixation to achieve sealing and should have allowed for the treatment of a broader range of anatomic features compared with standard EVAR. Despite the encouraging early reports, the mid- and long-term follow-up data have shown increased rates of failure. To address the issue, the manufacturer introduced revised instructions for use (IFU) in 2016. The present study reports the outcomes of this system after a median follow-up of 45 months. Methods Data for all patients electively treated with EVAS at our institution were retrospectively collected. The patients were retrospectively reclassified according to the 2016 revised IFU of the device. All patients in the present series had undergone EVAS for the treatment of infrarenal abdominal aortic aneurysms (AAAs). The primary end point was therapeutic failure: graft migration >5 mm, sac expansion >5 mm, type IA endoleak (Is2 and Is3 using the Van den Ham classification), type Ib endoleak, and secondary rupture. The overall mortality, aortic-related mortality, and reintervention rates were also analyzed. Results A total of 101 patients had undergone elective treatment by EVAS from 2013 to 2018 for infrarenal AAAs. The median follow-up was 3.75 years. Therapeutic failure was observed in 31 of the 101 patients (30.7%), with no significant difference between the in-IFU and off-IFU 2016 subgroups. Failure occurred at a median interval of 34 months from the index procedure. Of the 101 patients, 6.9% had presented with secondary rupture. Freedom from aneurysm-related mortality was 96.9% at 1 and 2 years and 89.9% at 5 years. Freedom from reintervention decreased over time: 94.7% at 1 year, 77% at 4 years, and 52.1% at 6 years. Of the 101 patients, 14 (13.9%) had undergone emergent or elective graft explantation. Conclusions EVAS performed worse than conventional endografts for several critical end points, regardless of any preoperative anatomic parameter s . The incidence of therapeutic failures tended to increase over time, especially 4 years after the index procedure.

Background:The EULAR recommendations for the management of systemic lupus erythematosus (SLE) suggest a hydroxychloroquine (HCQ) dose of ≤5.0 mg/kg/day instead of 6.5 mg/kg/day to reduce the risk of HCQ-induced retinopathy (1). This change in HCQ dose may potentially lead to undertreatment with blood levels below the presumed therapeutic range.Objectives:The aim of this study was to compare flare rates and HCQ blood levels between the two different oral dosages in patients with SLE in remission.Methods:Eligible patients were SLE patients in clinical remission according to the preliminary Definitions of Remission in SLE (DORIS) criteria for at least one year and treatment with stable dose of HCQ for at least six months and stable dose of glucocorticoids and/or immunosuppressants (2). Flares were defined by SELENA-SLEDAI Flare Index (3). A venous blood sample was collected on two different occasions from all patients, reflecting actual therapeutic adherence. The biosamples were analyzed in a UPLC-MS/MS system composed of a Nexera chromatograph (Shimadzu) coupled with a Q-trap 6500 spectrometer (AB Sciex). A mean [HCQ] value ([HCQm]) for each patient was then calculated. Predictors of flares were analyzed by Cox regression.Results:We selected 66 patients who were stratified according to HCQ oral dose in two groups (Table 1). We observed 23 (35%) flares that developed in mean 26,0 (±15,1) months: 8/32 (25%) patients taking HCQ 5 mg/kg/day; 15/34 (44%) in the other group. No statistically significant difference was observed between the two group in number of flares (p=0,106), mean time of occurrence (p=0,904) and median [HCQm] (p=0,983). At regression analysis, older age at baseline was protective against flare occurrence (HR 0,93), while concomitant immunosuppressive therapy showed significant positive association (HR 3,66).Conclusion:Our study suggests that low dosage of HCQ (5 mg/kg/day) may safely be prescribed in SLE patients in remission, without significant differences in terms of blood concentration and impact on the clinical course of SLE.References:[1]Fanouriakis A, et al. Ann Rheum Dis 2019;78:736-745.[2]van Vollenhoven R, et al. Ann Rheum Dis 2017;76:554-561.[3]Petri M, et al. Arthritis Rheum. 2012;64(8):2677-2686.Table 1.Demographic, clinical and therapeutic features of the cohort and follow up data.All patients (n= 66)HCQ≤5mg/Kg/die(n=32)HCQ6,5mg/Kg/die (n=34)PSex, female65 (99)31 (97)34 (100)0,3026Age, y, mean (SD)42,00±11,2741,80±10,2542,10±12,300,9140Disease duration, y, mean (SD)15,70 (9,02)17,80 (8,01)13,67 (9,50)0,0624SLEDAI, median (range)2 (0-4)1 (0-4)2 (0-4)0,6480SLICC, median (range)0 (0-2)0 (0-2)0 (0-1)0,8556[HCQm] ng/mL, median (range)512,60(104,41-3105,66)457,16(104,41-3105,66)538,49(149,24-1239,15)0,5989[DCQ] ng/mL,median (range)73,41(4,16-649,84)66,84(4,16-649,84)66,31(10,75-258,41)0,9380Time remission, y, median (range)2,00 (1-11)2,96 (1-10)2,00 (1-11)0,6588Previous renal involvement31 (47)15 (47)16 (47)0,9882Time HCQ, y, median (range)5 (0-32)8 (0-26)5 (1-32)0,2391Glucocorticoids33 (50)18 (56)15 (44)0,4700Mycophenolate mofetil6 (9)2 (6)4 (12)0,4396Azathioprine7 (11)4 (14)3 (9)0,6305Methotrexate1 (2)01 (3)0,3320Cyclosporine2 (3)1 (3)1 (3)0,9655Belimumab1 (2)01 (3)0,3320Follow up time, m, median (range)49 (4-67)52 (7-67)43 (4-67)0,1115Number of flares23 (35)8 (25)15 (44)0,1060Time to flare, m, mean (SD)26,0 (±15,1)26,6 (±16,4)25,8 (±14,9)0,9042Ocular alterations6 (9)4 (12)2 (6)0,0947Figure 1.Predictors of flares analyzed by Cox regression. *Serena Fasano and Valentina Messiniti contributed equally to this abstractDisclosure of Interests:None declared

Background:The new coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) is a source of concern for the management of patients suffering from rheumatic and musculoskeletal diseases (RMDs) treated with immunomodulatory therapies (1).Objectives:We aimed to analyze the prevalence of SARS-CoV-2 infection in patients with RMDs living in Italy.Methods:During the first wave (March-May 2020) and during the second wave (October-December 2020) of COVID-19, we conducted a survey to investigate the incidence of SARS-CoV-2 infection in patients with RMDs followed at the Rheumatology Unit of the University of Campania, Italy. The demographic data, medication use, the frequency of respiratory symptoms and the incidence of COVID-19 confirmed by nasopharyngeal swab were collected with questionnaires administered by phone. The prevalence of COVID-19 of our cohort was compared to that of the general population (2).Results:During the first wave, we collected data from 900 patients with RMDs (Table 1): 320 patients with rheumatoid arthritis (RA), 295 patients with spondyloarthropathies (SpA), 283 patients with systemic lupus erythematosus (SLE), 2 patients with vasculitis. 546 (60%) were treated with bDMARD/tsDMARDs. Overall, a total of 11/900 (1%) cases were tested for COVID-19 due to compatible symptoms. 2 (0.2%) adult patients treated with bDMARDs were registered as swab test positive by PCR for COVID-19. 2 patients without confirmed COVID-19 developed pneumonia that required admission to hospital. No deaths occurred among the patients with confirmed COVID-19.During the second wave, data were collected from 470 patients who accepted to take part of the study (Table 1). 49 presented with symptoms that were compatible with COVID-19. 139 patients were tested whereas 30 patients (6%) had a swab confirmation of SARS-CoV-2 infection. Among them, 16 (53%) were treated with bDMARDs and a patient was treated with tofacitinib. we found no increase in COVID-19 prevalence in patients treated with bDMARD/tsDMARDs (p>0.05). A patient with SLE developed pneumonia that required admission to hospital and died.Lacking distinct prevalence data between first and second waves, we found no differences in total COVID-19 prevalence between general population living in Campania (215.752/5.802.000; 3.7%) and patients with RMDs (32/900; 3.5%). However, we had a significant increase in COVID-19 prevalence in our cohort during the second wave compared to the first. Nevertheless, no increase in mortality or hospitalization was recorded, confirming the safety of immunomodulatory therapies in patients with RMDs.Conclusion:In this cohort of patients with RMDs in a geographical region with a high prevalence of COVID-19, the risk of SARS-CoV-2 infection does not appear different from that observed in the general population.References:[1]Wang L., Wang Y., Ye D. Int J Antimicrob Agents. 2020:105948.[2]http://www.protezionecivile.gov.it/ (accessed 28.01.21)Table 1.Demographics and clinical characteristics of 900 patients with rheumatic diseases during the COVID-19 Pandemic.First waveSecond waveWomen, n 660 (73 %) 366(77%)Age, years, median (range)56 (54-57)53 (51-55)Rheumatoid Arthritis320 (35.5%)143 (30%)Spondyloarthritis295 (32%)110 (23%)Systemic Lupus Erythematosus283 (31%)217 (46 %)Vasculitis2 (0.2%)1 (0.2%)Prior ILD56 (6%)22 (4.6%)Smokers220 (24%)118 (25%)Hydroxychloroquine215 (23%)155 (32%)Steroids337 (37%)194 (41%)Prednisone equivalent dose, median (range)5 (0-75)5 (0-50)bDMARD/tsDMARDs546 (60%)247 (52%)csDMARDS387 (43%)185 (39%)Angiotensin-converting enzyme (ACE) inhibitors178 (19.8%)101 (21%)Angiotensin II receptor blockers(ARBs)153 (17%)61 (13%)Fever64 (7%)30 (6.3%)Cough83 (9%)36 (7%)Shortness of breath34 (3%)15 (3%)Sore throat32 (3%)11 (2.3%)Rhinorrhoea36 (3%)11 (2.3%)Headache5 (0.5%)2 (0.4%)Anosmia10 (1%)24 (5%)Myalgia2 (0.2%)1 (0.2%)Gastrointestinal symptoms24 (2.6%)3 (0.6%)Pneumonia2 (0.2%)2 (0.4%)Admission to hospital2 (0.2%)9 (1.9%)Swab confirmation of SARS-CoV-2 infection230Disclosure of Interests:None declared.

The safe long-term disposal of radioactive waste arising primarily from power generation is a complex proposition. Safety assessment modelling typically incorporates up to one million years, which is an engineering requirement without precedent. In order to perform this modelling, it is imperative that the behaviour of the materials comprising the repository are well understood over the timescales in question. This article describes a method developed for studying the behaviour of metals under anoxic conditions via the corrosion reaction end product, hydrogen. At its simplest, test cells are left for periods of time, up to several months, to accumulate hydrogen. This gas is then expelled from the cell and analysed using a hydrogen sensor. As such, the method is limited to characterising gas generation and consequently only uniform corrosion, but does permit direct monitoring of corrosion rates as low as 0.01 nm/year, which is necessary in order to accurately monitor the very low long-term corrosion rates expected in a deep geological repository.

Background Acute lower limb ischemia (ALLI) poses a major threat to limb survival. For many years, surgical thromboembolectomy was the mainstay of treatment. Recent years have brought an endovascular revolution to the management of ALLI. It seems that the newly designed endovascular thrombectomy devices may shift treatment recommendations toward endovascular options. This protocol study aims to collect evidence supporting the latest hypothesis. Objective The devices under investigation are the Penumbra/Indigo Systems (Penumbra Inc). The objective of this clinical investigation is to evaluate, in a controlled setting, the early safety and effectiveness of the devices and to define the optimal technique for the use of these systems in patients with confirmed peripheral acute occlusions. Methods This study will be an interventional prospective trial of patients with a diagnosis of ALLI treated with Penumbra/Indigo devices. This project is intended to be a national platform where every physician invited to participate could register his or her own data procedure. The primary outcome is the technical success of thromboaspiration with the Indigo System. Assessment of vessel patency will be recorded using the Thrombolysis in Myocardial Infarction (TIMI) score classifications before and after use of the device. Clinical success at follow-up is defined as an improvement of Rutherford classification at 1-month follow-up of one class or more as compared to the preprocedure Rutherford classification. Secondary endpoints include the following: (1) safety rate at discharge, defined as the absence of any serious adverse events; (2) primary patency at 1 month, defined as a target lesion without a hemodynamically significant stenosis or reocclusion on duplex ultrasound (>50%) and without target lesion reintervention within 1 month; and (3) limb salvage at 1 month. Results The study is currently in the recruitment phase and the final patient is expected to be treated by the end of March 2019. A total of 150 patients will be recruited. Analyses will focus on primary and secondary endpoints. Conclusions These new endovascular thrombectomy devices that are specifically designed for peripheral intervention in this difficult set of patients, as those under investigation in the proposed registry, may offer improved clinical outcomes with lower rates of major systemic and local complications. Following completion of this study, it is expected that the value of the Indigo Thrombectomy System in the treatment of ALLI will be better defined. As a result, a shift of treatment recommendations toward endovascular options may be observed in the near future. International Registered Report Identifier (IRRID) DERR1-10.2196/9972

Background/aim The identification of novel prognostic biomarkers for melanoma metastasis is essential to improve patient outcomes. To this aim, we characterized miRNA expression profiles in relation to metastasis in melanoma and correlated miRNAs expression with clinical-pathological factors. Materials and methods MiR-145-5p, miR-150-5p, miR-182-5p, miR-203-3p, miR-205-5p and miR-211-5p expression levels were analyzed in primary cutaneous melanomas, including thin and thick melanomas, and in melanoma metastases by quantitative Real-Time PCR. Results A significantly lower miR-205-5p expression was found in metastases compared to primary melanomas. Furthermore, a progressive down-regulation of miR-205-5p expression was observed from loco-regional to distant metastasis. Significantly lower miR-145-5p and miR-203-3p expression levels were found in cases with Breslow thickness >1 mm, high Clark level, ulceration and mitotic rate ≥1/mm2 Conclusion: Our findings point to miR-205-5p as potential biomarker of distant metastases and to miR-145-5p and miR-203-3p as markers of aggressiveness in melanoma.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most frequent non-hereditary autoinflammatory disorder in childhood: Its onset is usually observed before 5 years, though reports regarding adulthood are increasing. The pathogenesis of the syndrome is not completely understood, but a multifactorial origin, probably based on a polygenic pattern of susceptibility, is the most probable rational pathogenetic hypothesis. Treatment of PFAPA syndrome relies on the administration of low-dose corticosteroids, which promptly abort flares but cannot prevent subsequent disease episodes over time. Tonsillectomy with or without adenoidectomy has proved to be successful in some pediatric patients, as proven by different studies. On the other hand, colchicine, cimetidine, nonsteroidal anti-inflammatory drugs, and interleukin-1 inhibitors have shown efficacy, which require further definite confirmations. This review is aimed at summarizing all the recent evidence about treatment options available for PFAPA syndrome both in pediatric and adult patients.

Atherosclerotic superficial femoral artery (SFA) true aneurysm is rare and often associated with other aortic or peripheral aneurysms, usually discovered when it reaches a considerable diameter or becomes symptomatic. We present the case of a 92-year-old woman admitted in the emergency department with a huge ruptured SFA aneurysm. The patient underwent successful aneurysmectomy, followed by bypass grafting. Degenerative SFA aneurysms differ from other peripheral aneurysms, being usually larger and symptomatic at presentation, occurring in old people, and representing life-threatening situations. The commonest symptom is rupture.

Objectives Several plaque and lesion characteristics have been associated with an increased risk for procedural stroke during or shortly after carotid artery stenting (CAS). While technical advancements in stent design and cerebral protection devices (CPD) may help reduce the procedural stroke risk, and anatomy remains important, tailoring stenting procedures according to plaque and lesion characteristics might be a useful strategy in reducing stroke associated with CAS. In this descriptive report of the ongoing Asymptomatic Carotid Surgery Trial-2 (ACST-2), it was assessed whether choice for stent and use or type of CPD was influenced by plaque and lesion characteristics. Materials and methods Trial patients who underwent CAS between 2008 and 2015 were included in this study. Chi-square statistics were used to study the effects of plaque echolucency, ipsilateral preocclusive disease (90–99%), and contralateral high-grade stenosis (>50%) or occlusion of the carotid artery on interventionalists' choice for stent and CPD. Differences in treatment preference between specialties were also analysed. Results In this study, 831 patients from 88 ACST-2 centres were included. Almost all procedures were performed by either interventional radiologists (50%) or vascular surgeons (45%). Plaque echolucency, ipsilateral preocclusive disease (90–99%), and significant contralateral stenosis (>50%) or occlusion did not affect the choice of stent or either the use of cerebral protection and type of CPD employed (i.e., filter/flow reversal). Vascular surgeons used a CPD significantly more often than interventional radiologists (98.6% vs. 76.3%; p < .001), but this choice did not appear to be dependent on patient characteristics. Conclusions In ACST-2, plaque characteristics and severity of stenosis did not primarily determine interventionalists' choice of stent or use or type of CPD, suggesting that other factors, such as vascular anatomy or personal and centre preference, may be more important. Stent and CPD use was highly heterogeneous among participating European centres.

External carotid artery pseudoaneurysm (ECAP) is very rare. The usual mechanism is trauma or iatrogenic. We report a case of a patient with an asymptomatic, chronic ECAP secondary to partial parathyroidectomy. Percutaneous injection of the 2-component Fibrin Sealant (Tisseel; Baxter int, Deerfield, IL) with the 2 active ingredients (Sealer Protein Solution and Thrombin Solution) was carried out with successful occlusion of the pseudoaneurysmal sac. The 6-month follow-up computed tomographic scan confirmed the ECAP thrombosis. The ECAP endovascular approach is less invasive and reduces the complications of the open surgical intervention, especially in high-risk patients or presenting with hostile neck.

Introduction Cette etude retrospective unicentrique sequentielle comparait les resultats de l’endarteriectomie carotidienne (EAC) sous anesthesie generale a l’EAC sous anesthesie generale. Methodes De Novembre 2002 a Octobre 2004, 428 EACs etaient realisees dans notre unite vasculaire. Deux groupes etaient formes : groupe AG (anesthesie generale) : 219 patients operes sous anesthesie generale ; groupe AL (anesthesie locale) : 209 patients operes sous anesthesie locale. Resultats Il n’y avait aucun deces dans les deux groupes. Apres chirurgie, trois accidents vasculaires constitues etaient notes dans le groupe AG et trois dans le groupe AL (AG 1,36% vs. AL 1,43%, p = 0,9540) ; Apres EAC, il y avait trois AITs dans le groupe AG et aucun dans le groupe AL (AG 0,42% vs. AL 0%, p = 0,2634). Conclusion La morbi-mortalite n’etait pas influencee par le type d’anesthesie utilisee en chirurgie carotidienne. Aucune difference statistique n’etait detectee en termes de taux de complications neurologiques et cardio-pulmonaires entre l’AG et l’AL.

The early risk of stroke after transient ischemic attack (TIA)/stroke is of the order of 5-10% at 1 week and 10-20% at 3 months. Even if carotid endarterectomy (CEA) is the treatment of choice in symptomatic internal carotid artery stenosis, the timing of carotid intervention after acute stroke is not yet codified. The authors want to determinate whether early CEA is safely carried out in the first few hours (48 hours) successive to the nondebilitating neurological event and whether the outcome (TIA/stroke/death) in these cases is comparable with the results of those treated by delayed/deferred surgery (range, 48 hours-24 weeks).In 4 years, the authors performed 1,184 CEA (285 symptomatic). Five groups were formed from 285 symptomatic patients, according to interval between TIA/stroke onset and performance of CEA: G1, less than 48 hours; G2, 48 hours-2 weeks; G3, 2-4 weeks; G4, 4-8 weeks; G5, 8-24 weeks. Surgery was never performed on patients with disabling neurological deficit (modified Rankin Scale, 5) at the time of admittance, cerebral lesions greater than 3 cm at magnetic resonance/computed tomography scan, presence or suspect of parenchymal hemorrhage associated with ischemic damage, condition considered unfit for surgery (American Society of Anesthesiology classification grade V), and occlusion of the cerebral middle artery. Neurological and diagnostic examinations (duplex-scanning and computed tomography/magnetic resonance scan) were used in determining the selection for early CEA.Cumulative TIA/stroke/death rate after CEA was 3.8% (11/285) and at 30 days was 2.8% (8/285). The cumulative TIA rate after CEA and at 30 days was 0% (0/285). The cumulative stroke rate after CEA was 3.5% (10/285) and at 30 days was 2.4% (7/285). The cumulative death rate after CEA and at 30 days was 0.3% (1/285). Stroke rate after CEA in each group was: G1 4.2% (3/70); G2 3.2% (2/61); G3 0% (0/22); G4 3.4% (1/29); G5 3.8% (4/103). Any statistically significant difference between G1 and the other four groups was not detected with regard to postoperative stroke: G1 (4.2%) versus G2 (3.2%), p = 0.7641; G1 (4.2%) versus G3 (0%), p = 0.7648; G1 (4.2%) versus G4 (3.4%), p = 0.8473; G1 (4.2%) versus G5 (3.8%), p = 0.8952. No hemorrhagic stroke was detected after early CEA. The type of anesthesia and the use of a shunt didn't show any significant difference between the five groups.The analysis of these records suggests that early CEA in the acute post stroke phase, for patients clinically selected, does not result in greater complications than when performed delayed or deferred . Furthermore, the advantage of early CEA is the reduction of recurrent strokes, as untreated patients present a higher incidence of neurological events.

Objectif Le risque precoce de survenue d’un accident vasculaire cerebral apres un accident ischemique transitoire (AIT)/accident vasculaire cerebral (AVC) varie entre 5 et 10% a une semaine et 10 et 20% a trois mois. Bien que l’endarteriectomie carotidienne (EAC) soit le traitement de choix des stenoses symptomatiques de l’artere carotide interne, le delai de realisation des interventions carotidiennes apres un accident vasculaire aigu n’est toujours pas codifie. Les auteurs ont voulu determiner si une EAC precoce pouvait etre realisee de maniere sure au cours des premieres heures ( Methodes En quatre ans, les auteurs ont effectue 1184 EAC (285 symptomatiques). Cinq groupes ont ete formes a partir des 285 patients symptomatiques, selon l’intervalle separant la survenue de l’AIT (accident cerebral) et la realisation de l’EAC : G1, moins de 48 heures ; G2, 48 heures-2 semaines ; G3, 2-4 semaines ; G4, 4-8 semaines ; G5, 8-24 semaines. La chirurgie n’a jamais ete effectuee lorsque les patients presentaient des deficits neurologiques invalidants (echelle de Rankin modifiee, 5) a l’admission, des lesions cerebrales superieures a 3 cm sur l’IRM ou le scanner, presence ou suspicion d’hemorragie parenchymateuse associee aux lesions ischemiques, patients consideres comme mauvais candidats a la chirurgie (classification de l’American Society of Anesthesiology grade V) et en cas d’occlusion de l’artere cerebrale moyenne. Des examens neurologiques et diagnostiques (echographie Doppler et scanner/IRM) ont ete utilises pour selectionner les candidats a l’EAC precoce. Resultats Le taux cumulatif AIT/AVC/deces apres EAC a ete de 3,8% (11/285) et de 2,8% (8/285) a 30 jours. Le taux cumulatif d’AIT apres EAC et a 30 jours a ete de 0% (0/285). Le taux cumulatif d’AVC apres EAC a ete de 3,5% (10/285) et a 30 jours de 2,4% (7/285). Le taux cumulatif de deces apres EAC et a 3 jours a ete de 0,3% (1/285). Le taux d’AVC apres EAC dans chaque groupe a ete : G1 4,2% (3/70) ; G2 3,2% (2/61) ; G3 0% (0/22) ; G4 3,4% (1/29) ; G5 3,8% (4/103). Il n’a pas ete montre de difference statistiquement significative entre les groupes G1 et les quatre autres groupes concernant la survenue d’un AVC post-operatoire : G1 (4,2%) versus G2 (3,2%), p = 0,7641 ; G1 (4,2%) versus G3 (0%), p = 0,7648 ; G1 (4,2%) versus G4 (3,4%), p = 0,8473 ; G1 (4,2%) versus G5 (3,8%), p = 0,8952. Il n’y a eu aucun accident hemorragique compliquant une EAC precoce. Le type d’anesthesie et l’utilisation d’un shunt n’etaient pas significativement differents entre les 5 groupes. Conclusions L’analyse de ces donnees suggere qu’une EAC precoce dans la phase suivant un evenement neurologique aigu, chez les patients cliniquement selectionnes, ne semble pas augmenter le risque de complications comparee a la chirurgie retardee ou differee. De plus, l’avantage de l’EAC precoce est de reduire les taux de recidive d’evenement neurologique, les patients non traites en presentant une plus forte incidence.

We compared the intra-operative diagnostic value of CDS vs IA-DSA in identifying major and minor technical defects after CEA. Between August 1997 and December 1998, 138 consecutive patients undergoing 141 carotid endarterectomies were intra-operatively investigated with colour duplex scan and intra-arterial digital subtraction angiography. Thirty-six (25.5%) technical defects were identified. Four (11.1%) major defects were detected by both methods and they were immediately corrected. Fifteen (41.6%) minor defects were detected by both methods, thirteen (36.1%) minor defects were detected by colour duplex but ignored by angiography. Angiography detected four (11.1%) kinkings missed with the colour duplex. The overall sensitivity of both methods for major defect was 100%. The sensitivity of colour duplex for minor defects was 87% vs 59% for angiography. On the basis of our study, colour duplex could be considered the choice method for quality control after carotid endarterectomy.

Background Coral reef aorta (CRA) is a rare, potential lethal disease of the visceral aorta as it can cause visceral and renal infarction. Various surgical approaches have been proposed for the CRA treatment. The purpose of this article is to report different extensive extra-anatomic CRA treatment modalities tailored on the patients' clinical and anatomic presentation. Methods From April 2006 to October 2012, 4 symptomatic patients with extensive CRA were treated at our department. Extra-anatomic aortic revascularization with selective visceral vessels clamping was performed in all cases. Results Technical success was 100%. No perioperative death was registered. All patients remained asymptomatic during the follow-up period (62, 49, 25, and 94 months, respectively), with bypasses and target vessels patency. Conclusions The extra-anatomic bypass with selective visceral vessels clamping reduces the aortic occlusion time and the risk of organ ischemia. All approaches available should be considered on a case-by-case basis and in high-volume centers.

The most frequent complication during carotid artery stenting (CAS) is intraoperative distal embolization. Three categories of embolic protection devices (EPDs) are routinely used through a transfemoral or transcervical approach: distal occlusion devices, distal EPDs with flow preservation using filters, and the proximal occlusive protective systems. We report the case of the internal carotid artery (ICA) plaque rupture during CAS using a proximal EPD (the Mo.Ma system; INVATEC), treated with immediate surgery. The proximal occlusive protective system permitted the common carotid artery and ICA endoclamping for the time necessary to prepare the patient for the carotid endarterectomy. The EPDs should always be chosen considering the patient's and lesion's characteristics. This knowledge allows their use even as "bridge" endovascular devices.

Aim. The purpose of this report is to describe our early experience with a minimal extracorporeal circulation system (MECC), a compact closed heparin coated system consisting of a centrifugal pump and a membrane oxygenator, during thoracoabdominal aortic aneurysm (TAAA) repair. Methods. Between January and December 2002 the MECC system was employed in seven consecutive patients (four TAAA type II, two TAAA type I and one TAAA type III according to the Crawford classification). In all patients distal aortic, selective renal and visceral perfusion was performed with this compact closed heparin coated system consisting of a centrifugal pump and a membrane oxygenator. Results. The MECC system was used in all cases with no technical malfunctions. Six out seven patients were discharged from the unit. One patient developed paraplegia after TAAA repair and died on the third post-operative day from multi-organ failure. In this case the total spinal ischaemic time was 120 min and the distal aortic perfusion pressure was

Cancer affects millions of people worldwide. Tumor mortality is substantially due to diagnosis at stages that are too late for therapies to be effective. Advances in screening methods have improved the early diagnosis, prognosis, and survival for some cancers. Several validated biomarkers are currently used to diagnose and monitor the progression of cancer, but none of them shows adequate specificity, sensitivity, and predictive value for population screening. So, there is an urgent need to isolate novel sensitive, specific biomarkers to detect the disease early and improve prognosis, especially in high-mortality tumors. Proteomic techniques are powerful tools to help in diagnosis and monitoring of treatment and progression of the disease. During the last decade, mass spectrometry has assumed a key role in most of the proteomic analyses that are focused on identifying cancer biomarkers in human serum, making it possible to identify and characterize at the molecular level many proteins or peptides differentially expressed. In this paper we summarize the results of mass spectrometry serum profiling and biomarker identification in high mortality tumors, such as ovarian, liver, lung, and pancreatic cancer.

True aneurysms of tibial artery are rare occurrences and their rupture is really rare. We report the case of a 59-year-old man who, after an episode of bacterial endocarditis, presented a posterior tibial aneurysm formation evolved in rupture. To our knowledge, this is the first case of a true giant aneurysm rupture of the posterior tibial artery (diameter, 6 cm). The treatment consisted of aneurysmectomy and surgical arterial ligation. A follow-up of 24 months was performed with good results.

We report the case of a 54-year-old man with acute stroke caused by left internal carotid artery (ICA) occlusion secondary to pleural mesothelioma, discovered later. The cranial computed tomography scan revealed a left hemisphere ischemic lesion. At neurological examination, the modified National Institutes of Health Stroke Scale (mNIHSS) score was 9. The carotid duplex scan (DS) showed a complete thrombotic occlusion of the left ICA. The patient underwent emergency carotid thrombectomy. The screening tests revealed thrombocytosis, hyperfibrinogenemia, increased C-reactive protein values, and multiple left pleural mesothelioma nodularity confirmed at the immunohistochemical investigation. After surgery, the patient's neurological symptoms improved, with an mNIHSS score of 3. At 30 and 120 days, the DS follow-up showed regular patency of the ICA.

Background This sequential retrospective monocentric study compares the results between general and local anesthesia for carotid endarterectomy (CEA). Methods Between November 2002 and October 2004, 428 CEAs were performed in our vascular unit. Two groups were formed: group GA (general anesthesia): 219 patients operated under general anesthesia; group LA (local anesthesia): 209 patients operated under local anesthesia. Results No mortality was found in both groups. After surgery, three strokes were detected in group GA and three in group LA (GA 1.36% vs. LA 1.43%, p = .9540); After CEA, there were three TIAs in GA group and none in LA group (GA 0.42% vs. LA 0%, p = .2634). Conclusion The morbi-mortality was not influenced by the type of anesthesia used for carotid surgery. No statistical difference was detected in the perioperative neurological and cardiopulmonary complication rates between GA and LA.

We report the cases of two patients with mobile floating carotid plaques (MFCP). Two men were referred to us for carotid investigation after trauma. The duplex ultrasonography scan (DUS) showed the presence of a mobile floating plaque into the internal carotid artery associated with a stenosis of 40% and 65%, respectively (ECST criteria). Both patients were asymptomatic. Early CEA was performed (

BACKGROUND: The effect of carotid endarterectomy in lowering the risk of stroke ipsilateral to severe atherosclerotic carotid-artery stenosis is offset by complications during or soon after surgery. We compared surgery under general anaesthesia with that under local anaesthesia because prediction and avoidance of perioperative strokes might be easier under local anaesthesia than under general anaesthesia. METHODS: We undertook a parallel group, multicentre, randomised controlled trial of 3526 patients with symptomatic or asymptomatic carotid stenosis from 95 centres in 24 countries. Participants were randomly assigned to surgery under general (n=1753) or local (n=1773) anaesthesia between June, 1999 and October, 2007. The primary outcome was the proportion of patients with stroke (including retinal infarction), myocardial infarction, or death between randomisation and 30 days after surgery. Analysis was by intention to treat. The trial is registered with Current Control Trials number ISRCTN00525237. FINDINGS: A primary outcome occurred in 84 (4.8%) patients assigned to surgery under general anaesthesia and 80 (4.5%) of those assigned to surgery under local anaesthesia; three events per 1000 treated were prevented with local anaesthesia (95% CI -11 to 17; risk ratio [RR] 0.94 [95% CI 0.70 to 1.27]). The two groups did not significantly differ for quality of life, length of hospital stay, or the primary outcome in the prespecified subgroups of age, contralateral carotid occlusion, and baseline surgical risk. INTERPRETATION: We have not shown a definite difference in outcomes between general and local anaesthesia for carotid surgery. The anaesthetist and surgeon, in consultation with the patient, should decide which anaesthetic technique to use on an individual basis. FUNDING: The Health Foundation (UK) and European Society of Vascular Surgery.

Long-term success of endovascular treatment of infrarenal abdominal aortic aneurysms (AAA) depends on secure "attachment" of the stent to the proximal and distal necks of the aneurysm. The purpose of this retrospective study was to detect changes in the proximal neck early after endovascular treatment of infrarenal AAA. Between November 1997 and December 1998, we performed endovascular treatment of infrarenal AAA in 43 patients. A bifurcated modular stent (AneuRx by Medtronic) was used in all patients. An oversized stent with a diameter 10% greater than the preoperative diameter of the proximal neck of the AAA was used in all cases. Follow-up examinations were carried out at 1, 6, and 12 months using plain roentgenography, color Doppler ultrasound, and CT scan with contrast injection. Statistical analysis was performed using the Student's t-test. Deterioration of the aortic neck is the result of a variety of mechanisms. The natural history of the infrarenal neck of AAA following endovascular repair (as well as conventional open repair) is progressive enlargement. Stenting could be an added risk factor for expansion. Strict follow-up is essential for early detection of this complication.