Role of ANCA in necrotizing vasculitis and in chronic inflammatory intestinal disease

Background: Wegener's granulomatosis (WG), Microscopic Poliangitis and Churg-Strauss Syndrome, the necrotizing vasculitis, are a group of inflammatory diseases of the wall small-medium calibre blood vessels. This group of diseases are hystologically characterized by the presence of necrotic tissue with a consequent inflammatory infiltration and the formation of granulomas. GW is a disease which has periods of remission and recurrence treated by therapeutic cycles associated with several side-effects. It is caracterized by the presence in serum of anti-neutrophil cytoplasm antibodies (ANCA). ANCA are auto-antibodies against enzymatic antigens found in primary granules of neutrophyls and in peroxydase-positive lysosomes of monocytes.The two main antigens are serin proteinase-3 (PR3), a cytoplasmatic protein and leucocyte myeloperoxydase (MPO). Indirect immunofluorescence permits to differentiate two distinct patterns, cytoplasmic (c-ANCA) and perinuclear (p-ANCA), according to the involved antigen, accordingly PR3 and MPO. Both patterns of ANCA presentation, mainly p-ANCA, are found in chronic inflammatory intestinal disease (IBD), noticeably Crohn's disease (CD) and ulcerative colitis (UC). Study goal: To evaluate the prevalence of ANCA in a population of patients with WG and one with CIID. In these two groups we studied: presentation pattern, correlation among antibody titer, clinical phase and disease localization; the role of infective agents as factors initiating ANCA production. Finally we correlated ANCA titers with response to treatment and disease complications. Patients and methods: we studied 13 patients with WG, some of which we had treated for over 7 years. In all patients ANCA levels were titred at the moment of diagnosis and during recurrences. Cultures were performed during episdoes of infectious disease. 37 patients with IBD admitted to a general surgical department for colic resection or for treatment of anal abscesses or fistulas were also studied, of these 12 had UC and 15 CD. Patients were studied in 2 different stages: preoperatively and 3 months after surgery. We evalutated:ANCA dosage, erythrocyte sedimentation rate, CRP, fibrinogen levels, direct or anamnestic determination of infectious episodes. Serum ANCA levels were dosed according to indirect immunofluorescence and, if positive, their presence was confirmed by ELISA. Results: ANCA were useful, if not decisive, in 85% of patients with WG, with titers ranging from 1:160 to 1:280. c-ANCA were 100% specific in patients with WG. ANCAs reappeared during follow-up in only 3 patients . Infectious episodes seemed to have been the factor causing recurrence. The presence of Staphylococcus aureus seems to favor the reappearance of ANCA in patients with WG while bactertial and/or viral infections may be responsible for ANCA-negative. p-ANCA were detected in 83% of patients with CU and in only 20% of patients with MC before surgery. After surgical treatment, ANCA were detected in 75% of patients with CU, while remain 20% in MC patients, but with lower titer. Conclusions: also our study demonstrates to the usefulness of the search and dosage of the ANCA in the diagnosis and follow-up of the GW. P-ANCA had a clean prevalence in the UC but they aren't useful in other chronic diseases. Also not playing a determining role in the diagnosis and not predicting in the prognosis of the IBD, ANCA turns out from our study a useful additional test in the diagnostic one differentiates them between UC and MC

When heart team really counts: Radical excision of intracardiac leiomyomatosis

Intravenous leiomyomatosis (IVL) are rare and complex tumors, characterized by high rates of recurrences after surgical removal and the capability of multi-organ involvement including pulmonary embolization. Regarding the surgical treatment of Intracardiac Leiomiomatosis (ICL), only few articles have been published and no controlled data are available. A combined approach that involves a Team of Cardiologists, Heart Surgeons, Vascular surgeons and Radiologists seems to be successful in treating ICL

Cytokine network in chronic perianal Crohn's disease and indeterminate colitis after colectomy

Antitumor necrosis factor alpha (anti-TNF-alpha) therapy in perianal Crohn's disease (CD) is widely established but recent studies suggest that the underlying fistula tract and inflammation may persist. Treatment with a monoclonal antibody against interleukin (IL)-12 was reported to induce clinical responses and remissions in patients with active CD. The aim of our study was to analyze the cytokine network (TNF-alpha, IL-12, IL-1beta, and IL-6) in 12 patients with chronic perianal CD and a Crohn's disease activity index (CDAI) score <150 to exclude active intestinal disease, in 7 patients with indeterminate colitis (IC) after restorative proctocolectomy with perianal complications, in 7 patients with active intestinal CD without perianal manifestations, and in 19 healthy controls. Nonparametric Mann-Whitney U test and Spearman's rank correlation test were used. Serum TNF-alpha levels were significantly higher in patients with IC than perianal CD patients and healthy controls. Serum TNF-alpha levels significantly correlated with perianal CDAI score and with the presence of anal fistulas. Serum IL-12 levels correlated with the presence of anal strictures and were similar in all groups. Serum IL-6 levels were significantly higher in the presence of perianal fistulas and lower in the presence of anal strictures. Our study confirmed that TNF-alpha plays a major role in the perianal and intestinal CD. Furthermore, the significantly higher TNF-alpha serum levels in patients with IC suggest the use of anti-TNF-alpha in such patients. On the contrary, according to our results the efficacy of anti-IL-12 antibodies appears doubtful in chronic perianal CD or IC without anal strictures. The role of IL-6 as a systemic mediator for active chronic inflammation was confirmed and a possible role for its monoclonal antibody was suggested

Impact of residual pulmonary obstruction on the long-term outcome of patients with pulmonary embolism

The impact of residual pulmonary obstruction on the outcome of patients with pulmonary embolism is uncertain.We recruited 647 consecutive symptomatic patients with a first episode of pulmonary embolism, with or without concomitant deep venous thrombosis. They received conventional anticoagulation, were assessed for residual pulmonary obstruction through perfusion lung scanning after 6 months and then were followed up for up to 3 years. Recurrent venous thromboembolism and chronic thromboembolic pulmonary hypertension were assessed according to widely accepted criteria.Residual pulmonary obstruction was detected in 324 patients (50.1%, 95% CI 46.2-54.0%). Patients with residual pulmonary obstruction were more likely to be older and to have an unprovoked episode. After a 3-year follow-up, recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension developed in 34 out of the 324 patients (10.5%) with residual pulmonary obstruction and in 15 out of the 323 patients (4.6%) without residual pulmonary obstruction, leading to an adjusted hazard ratio of 2.26 (95% CI 1.23-4.16).Residual pulmonary obstruction, as detected with perfusion lung scanning at 6 months after a first episode of pulmonary embolism, is an independent predictor of recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension

Alirocumab and cardiovascular outcomes after acute coronary syndrome

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