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  • 1
    In: JAMA, American Medical Association (AMA), Vol. 329, No. 14 ( 2023-04-11), p. 1183-
    Abstract: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02735707
    Type of Medium: Online Resource
    ISSN: 0098-7484
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    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 2
    In: JAMA, American Medical Association (AMA), Vol. 327, No. 13 ( 2022-04-05), p. 1247-
    Type of Medium: Online Resource
    ISSN: 0098-7484
    RVK:
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 3
    In: Arthritis & Rheumatology, Wiley, Vol. 72, No. 8 ( 2020-08), p. 1314-1324
    Abstract: To investigate predictors of response, remission, low disease activity, damage, and drug discontinuation in patients with systemic lupus erythematosus ( SLE ) who were treated with belimumab. Methods In this retrospective study of a multicenter cohort of SLE patients who received intravenous belimumab, the proportion of patients who achieved remission, low disease activity, and treatment response according to the SLE Responder Index 4 ( SRI ‐4) was determined, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index ( SDI ) was used to score disease damage yearly over the follow‐up. Predictors of outcomes were analyzed by multivariate logistic regression with the results expressed as odds ratios ( OR s) and 95% confidence intervals (95% CI s). Results The study included 466 patients with active SLE from 24 Italian centers, with a median follow‐up period of 18 months (range 1–60 months). An SRI ‐4 response was achieved by 49.2%, 61.3%, 69.7%, 69.6%, and 66.7% of patients at 6, 12, 24, 36, and 48 months, respectively. Baseline predictors of response at 6 months included a score of ≥10 on the SLE Disease Activity Index 2000 ( SLEDAI ‐2K) ( OR 3.14 [95% CI 2.033–4.860]) and a disease duration of ≤2 years ( OR 1.94 [95% CI 1.078‐3.473). Baseline predictors of response at 12 months included a score of ≥10 on the SLEDAI ‐2K ( OR 3.48 [95% CI 2.004–6.025]) and an SDI score of 0 ( OR 1.74 [95% CI 1.036–2.923]). Baseline predictors of response at 24 months included a score of ≥10 on the SLEDAI ‐2K ( OR 4.25 [95% CI 2.018–8.940]) and a disease duration of ≤2 years ( OR 3.79 [95% CI 1.039–13.52]). Baseline predictors of response at 36 months included a score of ≥10 on the SLEDAI ‐2K ( OR 14.59 [95% CI 3.54–59.79) and baseline status of current smoker ( OR 0.19 [95% CI 0.039–0.69]). Patients who were in remission for ≥25% of the follow‐up period (44.3%) or who had low disease activity for ≥50% of the follow‐up period (66.1%) accrued significantly less damage ( P = 0.046 and P = 0.007). A baseline SDI score of 0 was an independent predictor of achieving low disease activity in ≥50% of the follow‐up period and remission in ≥25% of the follow‐up period. Our findings suggest that the lower the baseline damage, the greater the probability of achieving remission over the course of ≥25% of the follow‐up. Further, there was a negative association between the number of flares reported prior to belimumab initiation and the frequency of belimumab discontinuation due to inefficacy ( P = 0.009). Conclusion In patients with active SLE and low damage at baseline, treatment with belimumab early in the disease may lead to favorable outcomes in a real‐life setting.
    Type of Medium: Online Resource
    ISSN: 2326-5191 , 2326-5205
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2754614-7
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  • 4
    In: Journal of Personalized Medicine, MDPI AG, Vol. 13, No. 4 ( 2023-04-20), p. 691-
    Abstract: Aim. To assess the efficacy of belimumab in joint and skin manifestations in a nationwide cohort of patients with SLE. Methods. All patients with skin and joint involvement enrolled in the BeRLiSS cohort were considered. Belimumab (intravenous, 10 mg/kg) effectiveness in joint and skin manifestations was assessed by DAS28 and CLASI, respectively. Attainment and predictors of DAS28 remission ( 〈 2.6) and LDA (≥2.6, ≤3.2), CLASI = 0, 1, and improvement in DAS28 and CLASI indices ≥20%, ≥50%, and ≥70% were evaluated at 6, 12, 24, and 36 months. Results. DAS28 〈 2.6 was achieved by 46%, 57%, and 71% of patients at 6, 12, and 24 months, respectively. CLASI = 0 was achieved by 36%, 48%, and 62% of patients at 6, 12, and 24 months, respectively. Belimumab showed a glucocorticoid-sparing effect, being glucocorticoid-free at 8.5%, 15.4%, 25.6%, and 31.6% of patients at 6, 12, 24, and 36 months, respectively. Patients achieving DAS-LDA and CLASI-50 at 6 months had a higher probability of remission at 12 months compared with those who did not (p = 0.034 and p = 0.028, respectively). Conclusions. Belimumab led to clinical improvement in a significant proportion of patients with joint or skin involvement in a real-life setting and was associated with a glucocorticoid-sparing effect. A significant proportion of patients with a partial response at 6 months achieved remission later on during follow-up.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662248-8
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  • 5
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2022
    In:  Clinical and Experimental Immunology Vol. 210, No. 3 ( 2022-12-31), p. 295-308
    In: Clinical and Experimental Immunology, Oxford University Press (OUP), Vol. 210, No. 3 ( 2022-12-31), p. 295-308
    Abstract: Autoinflammatory diseases represent a family of immune-mediated conditions characterized by the unchecked activation of innate immunity. These conditions share common clinical features such as recurrent fever, inflammatory arthritis, and elevation of acute phase reactants, in the absence of an identified infectious etiology, generally without detectable serum autoantibodies, with variable response to glucocorticoids and in some cases colchicine, which represented the mainstay of treatment until cytokine blockade therapies became available. The first autoinflammatory diseases to be described were monogenic disorders caused by missense mutations in inflammasome components and were recognized predominantly during childhood or early adulthood. However, the progress of genetic analyses and a more detailed immunological phenotyping capacity led to the discovery a wide spectrum of diseases, often becoming manifest or being diagnosed in the adult population. The beneficial role of targeting hyperinflammation via interleukin 1 in complex non-immune-mediated diseases is a field of growing clinical interest. We provide an overview of the autoinflammatory diseases of interest to physicians treating adult patients and to analyze the contribution of hyperinflammation in non-immune-mediated diseases; the result is intended to provide a roadmap to orient scientists and clinicians in this broad area.
    Type of Medium: Online Resource
    ISSN: 0009-9104 , 1365-2249
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2020024-9
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  • 6
    In: Autoimmunity Reviews, Elsevier BV, Vol. 20, No. 3 ( 2021-03), p. 102759-
    Type of Medium: Online Resource
    ISSN: 1568-9972
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2099325-0
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  • 7
    Online Resource
    Online Resource
    Informa UK Limited ; 2012
    In:  Expert Review of Gastroenterology & Hepatology Vol. 6, No. 6 ( 2012-12), p. 717-729
    In: Expert Review of Gastroenterology & Hepatology, Informa UK Limited, Vol. 6, No. 6 ( 2012-12), p. 717-729
    Type of Medium: Online Resource
    ISSN: 1747-4124 , 1747-4132
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2012
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-9-10)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-9-10)
    Abstract: Antineutrophil cytoplasmic antibodies (ANCA) are primarily involved in the pathogenesis of ANCA-associated vasculitides (AAV). However, ANCA may also be present in healthy subjects and in patients with autoimmune disorders different from AAV. We hypothesized that serum ANCA are associated with a worse prognosis in disorders other than AAV. Objective We investigated the association between the overall survival and the presence of serum ANCA in 1,024 Italian subjects with various testing indications in a 10-year interval. Methods In this retrospective cohort study, a population of 6,285 patients (many of whom were subsequently excluded due to our criteria) who tested for ANCA at a single center in 10 years was considered, and life status and comorbidities of subjects were collected. We compared the overall survival of ANCA-positive and ANCA-negative patients by means of Kaplan-Meier curves, while a multivariable adjusted Cox regression was used to evaluate the association between the ANCA status and the outcome (death) in terms of hazard ratios (HR) with 95% confidence intervals (CI). Results The positivity of perinuclear ANCA (pANCA) increased significantly mortality (HR, 1.60; 95% CI, 1.10–2.32), while cytoplasmic ANCA (cANCA) positivity failed to show a significant association (HR, 1.43; 95% CI, 0.77–2.68). The increased mortality rate was observed for both pANCA and cANCA in patients suffering from rheumatic disorders. No association was found between mortality and anti-MPO (HR, 0.63; 95% CI, 0.20–2.00) or anti-PR3 (HR, 0.98; 95% CI, 0.24–3.96) after adjusting for confounders. Conclusions Serum pANCA and cANCA are independent negative prognostic factors in patients with concurrent autoimmune diseases.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 9
    In: European Heart Journal Supplements, Oxford University Press (OUP), Vol. 24, No. Supplement_K ( 2022-12-15)
    Abstract: Post-operative atrial fibrillation (POAF) represents the most common arrhythmia in the post-operative setting, with a peak incidence from day 0 to 5 after surgery and it represents a main cause of morbidity, mortality, length of stay, thromboembolic events and stroke. Cardiothoracic surgery has the highest rates of POAF, while data about other surgeries are contrasting amongst various studies. Aim of this study was to detect POAF onset in the 28 days after surgery and to better assess its predictors, especially the role of inflammation. Methods This is a retrospective single center cohort study of 53.387 patients undergoing surgery from January 2016 to January 2020. Patients were classified in four groups according to types of surgery performed: (I) orthopedic surgery, (II) not thoracic nor abdominal surgery, (III) abdominal and esophageal surgery and (IV) lung and cardiovascular surgery. Kaplan–Meier estimates were used to draw the cumulative incidence curves by surgery groups; finally, they were compared with a log-rank test. Furthermore, multivariable Cox proportional hazards (PH) models of prognostic factors were used. Confounders were selected according to a review of the literature, statistical relevance, and consensus opinion by an expert group of physicians and methodologists. After fitting the model, the PH assumption was examined on the basis of Schoenfeld residual. Results The primary endpoint of AF onset occurred in 570 patients (1.1%) with a mean incidence after surgery of 3.4±2.6 days. 90 patients died (0.17%) after an average of 13.7±8.4 days. The Kaplan-Meier analysis showed the lowest 28-day event-free survival in group IV and the highest in group I (log-ranks test p=0.0001). In patients who developed AF, levels of C-Reactive Protein (CRP) were higher than the others (mean 0,70+0.03 log10 mg/dL versus mean 0,40+0.01 log10 mg/dl; p & lt;0.0001) with higher levels in group III and group IV. In the univariable Cox regression, CRP was a strong predictor of AF (HR per 1 unit increase in log-scale, 2.64; 95% C.I,1.74–4.0; p & lt;0.0001). This was confirmed at the multivariable analysis, adjusting for confounding factors like age, gender, length of stay in hospital and group of surgery (adjusted HR per 1 mg/dL increase in log-scale, 1.81; 95% CI,1.18–2.79; p = 0.007). Other strong predictors of POAF were age (HR per 1 year increase, 1.06; 95% CI, 1.04–1.08; p & lt; 0.0001) and surgery of group III and IV (HR, 23.62; 95% CI, 5.65–98.73; p & lt; 0.0001 and HR,6.26; 95% CI, 1.48–26.49; p 0.013, respectively).The PH assumption was not violated (p=0.12). Conclusions POAF represents a frequent complication of surgery and major burden for healthcare. Inflammation may represent a major driver in its pathophysiology, especially in non-cardiac surgery, in which manipulation of cardiac tissue is avoided. This may explain the poor response to antiarrhythmic drugs and its self-limiting nature, which expires when post-operative inflammation turns off.
    Type of Medium: Online Resource
    ISSN: 1520-765X , 1554-2815
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2141255-8
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  • 10
    Online Resource
    Online Resource
    Elsevier BV ; 2012
    In:  Autoimmunity Reviews Vol. 11, No. 6-7 ( 2012-5), p. A531-A537
    In: Autoimmunity Reviews, Elsevier BV, Vol. 11, No. 6-7 ( 2012-5), p. A531-A537
    Type of Medium: Online Resource
    ISSN: 1568-9972
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2012
    detail.hit.zdb_id: 2099325-0
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