Healthcare and economic burden of ANCA-associated vasculitis in Italy: an integrated analysis from clinical and administrative databases

ANCA-associated vasculitides (AAV) comprise a group of systemic vasculitides characterized by inflammation of small-sized blood vessels leading to multi-organ involvement. The worldwide annual incidence of AAV ranges from 1.2 to 3.3 cases per 100 000 individuals with a prevalence of 4.6\u201342.1 cases per 100 000 individuals. The prevalence of AAV is geographically heterogeneous; therefore, regional epidemiological studies can be more informative to improve health care systems. Even though clinicians are aware that the healthcare burden and the risk of hospitalization of AAV appear high, data on hospitalization and cost of illness due to AAV are still scarce or even lacking. This study aims to characterize the economic burden of AAV in Friuli Venezia Giulia (FVG), Italy. Thus, a retrospective study was conducted through the integration of many administrative health databases of the FVG as the source of information. From data integration, we estimated that more than two-thirds of AAV patients showed at least one hospitalization in their medical history, most frequently caused by the disease itself or superimposed infections. Around 10% of patients developed end-stage renal disease. In an 8-year follow-up, the overall healthcare cost was \u20ac 1,215,078, corresponding to \u20ac 6,168 patient-year. ANCA-positive patients showed much higher costs than ANCA-negative patients did. Overall, AAV are rare diseases, but imply very high healthcare costs. Early diagnosis and optimal treatment probably still remain unmet needs for AAV

AB0521 COST OF ILLNESS OF ANCA-ASSOCIATED VASCULITIS IN ITALY: DATA LINKAGE ANALYSIS OF MULTIPLE CLINICAL AND ADMINISTRATIVE DATABASES IN THE PROVINCE OF UDINE, ITALY

Background:ANCA-associated vasculitides (AAV) are a group of systemic vasculitis carrying a high risk of hospitalization because the multiorgan involvement, the acute nature of some clinical manifestations, the chronic but very disabling course of some other manifestations and finally the risk of severe infections due to chronic glucocorticoid and immunosuppressor administration. However, data on cost of illness due to AAV are lacking.Objectives:to estimate the cost of illness in patients suffering from AAV in the province of Udine (about 500,000 inhabitants), Friuli Venezia Giulia (FVG), Italy, from year 2010 to 2018.Methods:integration of the information coming from many administrative databases were used to this end. The Regional Health Information System of FVG was used as the source of information for this retrospective cohort study. The system covers the entire regional population and includes various electronic health administrative databases that can be linked with one another on an individual basis through a unique encrypted identifier. In particular, the following databases were matched: the database of the health care beneficiaries (including demographic information and the residential history of all of the subjects living in FVG), the hospital discharge database, the database of exemptions from medical charges, the database of the laboratories. The population under study was selected based on the following inclusion criteria: patients were residents in the province of Udine and they had to carry the exemption code for AAV, including GPA, or EGPA, or MPA. This population was observed from 2010 to 2018.Results:57 patients (201 patient-years) with AAV were identified. They were ANCA-positive in 44/57 (77%). GPA, EGPA and MPA was diagnosed in 18 (31,6%), 15 (26,3%), 11 (19,3%) patients, respectively. The mean age at diagnosis was 54,5 (17,5) years. The disease itself was the main cause of hospitalization in almost half of the hospital discharges (60/126, 47,6%). Four patients died during the observation period due to vasculitis itself (1), pneumonia (2), or haematological malignancy (1). Time to the first event (death or hospitalization) was significantly higher in ANCA-negative AAV patients than in ANCA-positive AAV patients (p=0,03, Log-Rank test), ANCA-positive AAV patients having a three-times higher risk (HR 3,38 95%CI 1,13-10,08, p=0,03). Total estimated cost was € 1,215,078, corresponding to € 6,168 patient-year. Costs for ANCA-positive AAV patients were much higher than those for ANCA-negative AAV patients (€ 1,115,253 vs € 99,825, and € 7058 per person-year vs € 2,559 per person-year, respectively). GPA and MPA showed the highest costs if compared to EGPA [GPA: € 239,168 (€ 5199 per person-year) vs MPA: € 281,502 (€ 4771 per person-year) vs EGPA: € 214,287 (2329 per person-year), respectively]. Costs for hospitalization were the highest [€ 734,957 (€ 3731 per person-year) vs other costs € 480,121 (€ 2437 per person-year)].Conclusion:costs for AAV are very high, confirming the high health care burden of this illness. Management of ANCA-positive patients rather than ANCA-negative patients was burdened by the highest costs. GPA and MPA showed the highest direct costs for hospitalization, which very frequently occurred due to the vasculitis itself.Disclosure of Interests:Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Elena Treppo: None declared, Salvatore De Vita Consultant of: Roche, GSK, Speakers bureau: Roche, GSK, Novartis, Francesca Valent: None declare

Post-covid-19 arthritis and sacroiliitis: Natural history with longitudinal magnetic resonance imaging study in two cases and review of the literature

Severe acute respiratory coronavirus-2 syndrome (SARS-CoV-2) is a well-known pandemic infectious disease caused by an RNA virus belonging to the coronaviridae family. The most important involvement during the acute phase of infection concerns the respiratory tract and may be fatal. However, COVID-19 may become a systemic disease with a wide spectrum of manifestations. Herein, we report the natural history of sacroiliac inflammatory involvement in two females who developed COVID-19 infection with mild flu-like symptoms. After the infection they reported inflammatory back pain, with magnetic resonance imaging (MRI) studies showing typical aspects of sacroiliitis. Symptoms improved with NSAIDs therapy over the following months while MRI remained positive. A literature review was performed on this emerging topic. To our knowledge, this is the first MRI longitudinal study of post-COVID-19 sacroiliitis with almost one year of follow-up. Predisposing factors for the development of articular involvement are unclear but a long-lasting persistence of the virus, demonstrated by nasopharyngeal swab, may enhance the probability of altering the immune system in a favourable background

Clinical, laboratory and immunohistochemical characterization of in situ pulmonary arterial thrombosis in fatal COVID-19

Background: COVID-19 patients carry an increased rate of thrombosis. It is controversial to which extent thrombi in the pulmonary arterial tree really contribute to disease severity with hypoxemia secondary to microvascular/lung parenchymal damage with viral alveolitis considered to play the main role in critical disease. Objectives: The primary objective was to compare post-mortem lung disease from fatal COVID-19 pneumonia in patients with macroscopically evident pulmonary arterial tree thrombosis and patients without, by characterizing the immunohistochemical nature of thrombi, and by comparing clinical and laboratory features of these patients with other COVID-19 patients who died but without evidence of pulmonary arterial thrombosis (controls). Patients and methods: 13 COVID-19 pneumonia cases (mean age ± standard deviation: 74 ± 6.5 years) with macroscopically visible pulmonary arterial thrombosis were compared to 14 controls. Hematoxylin and Eosin stained slides were reviewed choosing those with visible pulmonary thrombi which were further characterized by immunohistochemistry, in particular for the inflammatory infiltrates. Ante mortem serum markers relevant to pulmonary embolism were evaluated in both groups. Results: Twenty arterial thrombi (5 cases with multiple thrombi) were selected for study and were composed by white blood cells (WBC) [median, IQR range: 10 % (5–12.25)], mainly neutrophils [58 % (35.2–64.5)]. Cases with thrombosis showed significantly higher levels of platelet count [median, IQR range: 195000/mmc (157750–274,500) vs 143,500 (113000–175,250), p = 0.011], LDH [854 U/L (731–1315) vs 539 (391.5–660), p = 0.003] at admission, and D-dimer at ICU transfer [25,072 FEU (6951–50,531) vs 1024 (620–5501), p = 0.003]. Conclusions: Immunothrombotically driven arterial thrombi in COVID-19 patients are associated with D-Dimer and LDH elevations, thus linking inflammation, coagulopathy and organ damage in fatal COVID-19

Rituximab induction and maintenance in ANCA-associated vasculitis: State of the art and future perspectives

Antineutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV) is a group of rare autoimmune diseases characterized by inflammation of the vascular wall. The pathogenesis of AAV is strongly associated with B cell-derived ANCAs; thus, Rituximab (RTX) has become a promising drug in the induction and maintenance treatment of AAV. The purpose of this review is to describe the efficacy and safety of RTX in the induction of remission and maintenance therapy of AAV. Herein, we summarize the randomized controlled trials that have contributed to the refinement of the use of RTX in AAV in the past decades. RTX has been proven to be effective both in new-onset disease and in relapsing disease. Although the optimal duration of AAV maintenance therapy remains unknown, the ANCAs and the B-cell repopulation may offer support for the administration of further RTX cycles (or not). The safety of RTX is comparable with cyclophosphamide, with the advantage of a low risk of malignancy and no concern for fertility. In conclusion, RTX now plays an important role in the induction and maintenance therapy of AAV. Optimizing RTX-based treatment strategies in AAV is one of the main goals of the current research in AAV

Role of PET and SPECT in the study of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis has been defined as a "heterogeneous group of neurodegenerative syndromes characterized by progressive muscle paralysis caused by the degeneration of motor neurons allocated in primary motor cortex, brainstem, and spinal cord." A comprehensive diagnostic workup for ALS usually includes several electrodiagnostic, clinical laboratory and genetic tests. Neuroimaging exams, such as computed tomography, magnetic resonance imaging and spinal cord myelogram, may also be required. Nuclear medicine, with PET and SPECT, may also play a role in the evaluation of patients with ALS, and provide additional information to the clinicians.This paper aims to offer to the reader a comprehensive review of the different radiotracers for the assessment of the metabolism of glucose (FDG), the measurement of cerebral blood flow (CBF), or the evaluation of neurotransmitters, astrocytes, and microglia by means of newer and not yet clinically diffuse radiopharmaceuticals

Gitelman syndrome disclosed by calcium pyrophosphate deposition disease: Early diagnosis by ultrasonographic study

Gitelman's syndrome is a rare autosomal-recessive tubular disorder characterized by hypomagnesemia and hypocalciuria associated to hypokalemia. The clinical spectrum is wide and usually characterized by chronic fatigue, cramps, muscle weakness and paresthesiae. We describe a case of a 43 year-old male patient with early onset of knee arthritis and no other symptoms. Ultrasound revealed diffuse and confluent hyperechoic deposits in cartilage, fibrocartilage of the menisci and synovium and calcium pyrophosphate crystals were observed in the synovial fluid of the knee. The concomitant presence of hypomagnesemia, hypocalciuria and hypokalemia made clear the diagnosis of Gitelman's syndrome associated with chondrocalcinosis

18F-FDG PET-Derived Volume-Based Parameters to Predict Disease-Free Survival in Patients with Grade III Breast Cancer of Different Molecular Subtypes Candidates to Neoadjuvant Chemotherapy

We investigated whether baseline [F-18] Fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET)-derived semiquantitative parameters could predict disease-free survival (DFS) in patients with grade III breast cancer (BC) of different molecular subtypes candidate to neoadjuvant chemotherapy (NAC). For each F-18-FDG-PET/CT scan, the following parameters were calculated in the primary tumor (SUVmax, SUVmean, MTV, TLG) and whole-body (WB_SUVmax, WB_MTV, and WB_TLG). Receiver operating characteristic (ROC) analysis was used to determine the capability to predict DFS and find the optimal threshold for each parameter. Ninety-five grade III breast cancer patients with different molecular types were retrieved from the databases of the University Hospital of Padua and the University Hospital of Ferrara (luminal A: 5; luminal B: 34; luminal B-HER2: 22; HER2-enriched: 7; triple-negative: 27). In luminal B patients, WB_MTV (AUC: 0.75; best cut-off: WB_MTV > 195.33; SS: 55.56%, SP: 100%; p = 0.002) and WB_TLG (AUC: 0.73; best cut-off: WB_TLG > 1066.21; SS: 55.56%, SP: 100%; p = 0.05) were the best predictors of DFS. In luminal B-HER2 patients, WB_SUVmax was the only predictor of DFS (AUC: 0.857; best cut-off: WB_SUVmax > 13.12; SS: 100%; SP: 71.43%; p < 0.001). No parameter significantly affected the prediction of DFS in patients with grade III triple-negative BC. Volume-based parameters, extracted from baseline F-18-FDG PET, seem promising in predicting recurrence in patients with grade III luminal B and luminal B- HER2 breast cancer undergoing NAC

Unmet needs in ANCA-associated vasculitis: Physicians’ and patients’ perspectives

In recent years, clinical research has increased significantly and therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis have improved. However, there are still unanswered questions and unmet needs about AAV patients. The purpose of this review is to examine the frontiers of research related to emerging biomarkers eventually predicting relapse, and new therapeutic approaches, not to mention new quality of life assessment tools. Identifying predictors of relapse may help optimize therapeutic strategies, minimize disease recurrence, and reduce treatment-related side effects. In addition, it is important to recognize that patients may suffer long-term consequences of the disease and its treatment, which, although life-saving, is often associated with significant side effects. Our goal, therefore, is to highlight what has been achieved, the pitfalls, and what still needs to be done, comparing the views of physicians and patients