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1.
Artigo em Inglês | MEDLINE | ID: mdl-33590843

RESUMO

OBJECTIVES: To determine whether disease remission or low disease activity state at the beginning of pregnancy in SLE patients is associated with better pregnancy outcome. METHODS: pregnancies in SLE patients prospectively monitored by pregnancy clinics at four rheumatology centres were enrolled. Patient demographics and clinical information were collected at baseline (pregnancy visit before 8 weeks of gestation) including whether patients were in remission according to DORIS criteria and and/or Lupus Low Disease Activity State (LLDAS). Univariate and multivariate analysis were performed to determine predictors of disease flare and adverse pregnancy outcomes (APOs) including preeclampsia, preterm delivery, small for gestational age infant, intrauterine growth restriction and intrauterine fetal death. RESULTS: 347 pregnancies were observed in 281 SLE patients. Excluding early pregnancy losses, 212 pregnancies (69.7%) occurred in patients who were in remission at baseline, 33 (10.9%) in patients in LLDAS, and the remainder in active patients. 73 flares (24%) were observed during pregnancy or puerperium, and 105 (34.5%) APOs occurred. Multivariate analysis revealed that patients in disease remission or taking hydroxychloroquine were less likely to have disease flare, while a history of lupus nephritis increased the risk. The risk of APOs was increased in patients with shorter disease duration, while being on hydroxychloroquine resulted a protective variable. An almost significant association between complete remission and a decreased risk of APOs was observed. CONCLUSIONS: Prenatal planning with a firm treat-to-target goal of disease remission is an important strategy to reduce the risk of disease flares and severe obstetrical complications in SLE pregnancies.

3.
Expert Opin Drug Saf ; : 1-14, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33599570

RESUMO

Introduction: Systemic lupus erythematosus (SLE) mainly affects young females during childbearing age; therefore, reproductive issues are of major interest.Areas covered: Pregnancy planning is crucial to adjust the treatment toward drugs that are safe throughout pregnancy and breastfeeding. The evidence about drug safety is limited to post-marketing surveillance, registries, case series, and case reports, as pregnant patients are excluded from randomized clinical trials. The aim of this review is to report the safety considerations when treating pregnant SLE patients. Regarding maternal side effects of drugs, we focused on metabolic, infectious, and hemorrhagic complications. Fetal safety was analyzed looking at drugs teratogenicity, their possible effects on immune system, and on the long-term neuropsychological development of children.Expert opinion: The management of pregnancy in SLE has changed when knowledge about the safety of drugs has become available. Keeping SLE disease activity under control before, during and after pregnancy is of fundamental importance to ensure the best possible outcomes for mother and child. All these issues must be discussed with the patient and her family during preconception counseling. International efforts in terms of pregnancy registries and reproductive health guidelines help physicians improve their communication with SLE patients.

4.
Nat Rev Rheumatol ; 17(3): 177-184, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33408338

RESUMO

During the COVID-19 pandemic, the need to provide high-level care for a large number of patients with COVID-19 has affected resourcing for, and limited the routine care of, all other conditions. The impact of this health emergency is particularly relevant in the rare connective tissue diseases (rCTDs) communities, as discussed in this Perspective article by the multi-stakeholder European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET). The clinical, organizational and health economic challenges faced by health-care providers, institutions, patients and their families during the SARS-CoV-2 outbreak have demonstrated the importance of ensuring continuity of care in the management of rCTDs, including adequate diagnostics and monitoring protocols, and highlighted the need for a structured emergency strategy. The vulnerability of patients with rCTDs needs to be taken into account when planning future health policies, in preparation for not only the post-COVID era, but also any possible new health emergencies.


Assuntos
/epidemiologia , Doenças do Tecido Conjuntivo/epidemiologia , Assistência à Saúde/organização & administração , Pandemias , Comorbidade , Doenças do Tecido Conjuntivo/terapia , Humanos
5.
Autoimmun Rev ; 20(3): 102757, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33476815

RESUMO

BACKGROUND: despite the absence of specific guidelines, the treatment with intravenous immunoglobulins (IvIg) is considered effective in patients with refractory idiopathic inflammatory myopathies (IIM). The aim of our study is to evaluate the effectiveness and the safety of IvIg and define the possible profile of IIM patients candidate to IvIg treatment. METHODS: we performed a retrospective study of IIM pts. treated with IvIg (2 g/kg/month). We collected demographic, epidemiological, laboratory and clinical data. Additionally, to evaluate the toxicity, the adverse events occurred during the treatment were collected. RESULTS: 123 patients with IIM were included in the study. The main indications for the prescription of IvIg were muscle (83.7% of patients) and esophageal involvement (45.5% of patients). IvIg were started mainly for refractory disease. At the end of treatment (mean duration 14 months), muscular necrosis enzymes decreased significantly and dysphagia VAS decreased significantly (p < 0.001), while MMT value increased (104.6 ± 24.2 vs. 127.0 ± 22.2 p < 0.001). Ninety-six pts. (78%) responded to IvIg. They had a shorter disease duration (p < 0.001), higher creatine kinase levels (p < 0.001), and higher prevalence of myalgias at the baseline (p = 0.023) compared to non-responders. The presence of Raynaud's phenomenon (p = 0.023-odds ratio 0.28 [0.11-0.72]) and skin involvement (p = 0.004, odds ratio 0.18 [0.06-0.55]), were associated to a worse response. Adverse events were mostly mild and transitory. CONCLUSIONS: Despite their high cost, IvIg confirmed their effectiveness in refractory IIM pts., particularly in muscular and esophageal manifestations. Specific clinical characteristics at the baseline may identify the patients with higher probability of response to the treatment.


Assuntos
Imunoglobulinas Intravenosas , Miosite , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Imunoglobulinas Intravenosas/uso terapêutico , Estudos Multicêntricos como Assunto , Miosite/tratamento farmacológico , Estudos Retrospectivos
6.
Clin Exp Rheumatol ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33337991

RESUMO

OBJECTIVES: Systemic sclerosis (SSc) is a heterogeneous systemic autoimmune disease with distinct subsets identified by specific autoantibodies. Some environmental agents might play a role in SSc pathogenesis, including silicone breast implants (SBI). This association has been controversial in previous literature and only few studies reported the auto-antibody status in these SSc women. The objective of this study was to evaluate the association of SBI with SSc in a large cohort of Italian patients, classified according to their SSc-related autoantibodies and to their history of breast cancer. METHODS: Three Italian referral centres retrospectively collected clinical and laboratory data of consecutive SSc women, that were included when fulfilling the 2013 ACR/EULAR criteria and when SSc specific auto-antibodies status was available (anti-centromere (ACA), anti-Topoisomerase I (anti-Topo I) and anti-RNA Polymerase III antibodies (anti-RNAP3)). Data regarding history of SBI, SBI rupture and breast cancer were recorded. RESULTS: Among 742 SSc women, a history of SBI was recorded in 12 patients (1.6%); in only 1 case the implantation occurred before SSc diagnosis. In SSc patients with anti- RNAP3+ a significantly higher frequency of SBI rupture and SBI rupture without breast cancer were observed, as compared to anti-RNAP3-negative patients. No association was noted for SBI without rupture. CONCLUSIONS: In this study we demonstrated a link between SBI rupture and induction of anti-RNAP3+ SSc; further studies are needed to better define the characteristics of this syndrome and the possible effects of SBI removal and immunosuppressive treatment.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33374003

RESUMO

OBJECTIVES: Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antigens in the analysis. METHODS: A total of 1052 SLE patients with (n = 479) and without (n = 573) LN, recruited at different times from the beginning of symptoms, were included in the study. Patients with primary APS (PAPS, n = 24), RA (RA, n = 24) and UCTD (UCTD, n = 96) were analysed for comparison. Anti-nucleosome (dsDNA, Histone2A, Histone3), anti-intracellular antigens (ENO1), anti-annexin A1 and anti-C1q IgG2 were determined by non-commercial techniques. RESULTS: The presence in the serum of the IgG2 panel was highly discriminatory for SLE/LN vs healthy subjects. Serum levels of anti-dsDNA and anti-C1q IgG2 were more sensitive than those of IgGs (Farr radioimmunoassay/commercial assays) in identifying SLE patients at low-medium increments. Of more importance, serum positivity for anti-ENO1 and anti-H2A IgG2 discriminated between LN and SLE (ROC T0-12 months), and high levels at T0-1 month were detected in 63% and 67%, respectively, of LN, vs 3% and 3%, respectively, of SLE patients; serum positivity for each of these was correlated with high SLEDAI values. Minor differences existed between LN/SLE and the other rheumatologic conditions. CONCLUSION: Nephritogenic IgG2 antibodies represent a specific signature of SLE/LN, with a few overlaps with other rheumatologic conditions. High levels of anti-ENO1 and anti-H2A IgG2 correlated with SLE activity indexes and were discriminatory between SLE patients limited to the renal complication and other SLE patients. TRIAL REGISTRATION: The Zeus study was registered at https://clinicaltrials.gov, NCT02403115.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33351137

RESUMO

OBJECTIVES: Circulating anti-ENO1 and anti-H2A IgG2 have been identified as specific signatures of LN in a cross-over approach. We sought to show whether the same antibodies identify selected population of patients with LN with potentially different clinical outcomes. METHODS: Here we report the prospective analysis over 36 months of circulating IgG2 levels in patients with newly diagnosed LN (n=91) and SLE (n=31) and in other patients with SLE recruited within 2 years from diagnosis (n=99). Anti-podocyte (ENO1), anti-nucleosome (DNA, histone 2 A, histone 3) and anti-circulating proteins (C1q, AnnexinA1-ANXA1) IgG2 antibodies were determined by home-made techniques. RESULTS: LN patients were the main focus of the study. Anti-ENO1, anti-H2A and anti-ANXA1 IgG2 decreased in parallel to proteinuria and normalized within 12 months in the majority of patients while anti-dsDNA IgG2 remained high over the 36 months. Anti-ENO1 and anti-H2A had the highest association with proteinuria (Heat Map) and identified the highest number of patients with high proteinuria (68% and 71% respectively) and/or with reduced estimated glomerula filtration rate (eGFR) (58% for both antibodies) compared with 23% and 17% of anti-dsDNA (agreement analysis). Anti-ENO1 positive LN patients had higher proteinuria than negative patients at T0 and presented the maximal decrement within 12 months. CONCLUSIONS: Anti-ENO1, anti-H2A and anti-ANXA1 antibodies were associated with high proteinuria in LN patients and Anti-ENO1 also presented the maximal reduction within 12 months that paralleled the decrease of proteinuria. Anti-dsDNA were not associated with renal outcome parameters. New IgG2 antibody signatures should be utilized as tracers of personalized therapies in LN. TRIAL REGISTRATION: The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).

9.
Front Immunol ; 11: 572876, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193356

RESUMO

Patients with systemic lupus erythematosus (SLE) have a significant increase in cardiovascular (CV) risk although they display a preserved number of circulating angiogenic CD3+CD31+CXCR4+ T cells (Tang), a subpopulation of T cells which promotes repair of damaged endothelium. This happens due to the concomitant expansion of a Tang subset with immunosenescent features, such as the loss of CD28. Therefore, the aim of this study was to elucidate the interplay between Tang subpopulations and endothelial cells in a group of young SLE patients without previous cardiovascular events. Twenty SLE female patients and 10 healthy controls (HCs) were recruited. Flow cytometric analysis of endothelial progenitor cells (EPCs) and Tang subsets were performed and serum levels of interleukin (IL)-6, -8, matrix metalloproteinase (MMP)-9 and interferon (IFN)-γ were measured. Human umbilical vein endothelial cells (HUVECs) proliferation and pro-inflammatory phenotype in response to subjects' serum stimulation were also evaluated. Results showed that the percentage of Tang and EPC subsets was reduced in SLE patients compared with HCs, with a marked increase of senescent CD28null cells among Tang subset. SLE disease activity index-2000 (SLEDAI-2K) was inversed related to Tang cells percentage. Furthermore, IL-8 serum levels were directly correlated with the percentage of Tang and inversely related to the CD28null Tang subsets. We indirectly evaluated the role of the Tang subset on the endothelium upon stimulation with serum from subjects with a low percentage of Tang CD3+ cells in HUVECs. HUVECs displayed pro-inflammatory phenotype with up-regulation of mRNA for IL-6, intercellular adhesion molecule (ICAM)-1 and endothelial leukocyte adhesion molecule (ELAM)-1. Cell proliferation rate was directly related to IL-8 serum levels and EPC percentage. In highly selected young SLE patients without previous CV events, we found that the deterioration of Tang compartment is an early event in disease course, preceding the development of an overt cardiovascular disease and potentially mediated by SLE-specific mechanisms. The overcome of the CD28null subset exerts detrimental role over the Tang phenotype, where Tang could exert an anti-inflammatory effect on endothelial cells and might orchestrate via IL-8 the function of EPCs, ultimately modulating endothelial proliferation rate.

10.
Front Immunol ; 11: 584241, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33178218

RESUMO

Background: Critically ill patients with coronavirus disease 2019 (COVID-19) have a profound hypercoagulable state and often develop coagulopathy which leads to organ failure and death. Because of a prolonged activated partial-thromboplastin time (aPTT), a relationship with anti-phospholipid antibodies (aPLs) has been proposed, but results are controversial. Functional assays for aPL (i.e., lupus anticoagulant) can be influenced by concomitant anticoagulation and/or high levels of C reactive protein. The presence of anti-cardiolipin (aCL), anti-beta2-glycoprotein I (anti-ß2GPI), and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies was not investigated systematically. Epitope specificity of anti-ß2GPI antibodies was not reported. Objective: To evaluate the prevalence and the clinical association of aPL in a large cohort of COVID-19 patients, and to characterize the epitope specificity of anti-ß2GPI antibodies. Methods: ELISA and chemiluminescence assays were used to test 122 sera of patients suffering from severe COVID-19. Of them, 16 displayed major thrombotic events. Results: Anti-ß2GPI IgG/IgA/IgM was the most frequent in 15.6/6.6/9.0% of patients, while aCL IgG/IgM was detected in 5.7/6.6% by ELISA. Comparable values were found by chemiluminescence. aPS/PT IgG/IgM were detectable in 2.5 and 9.8% by ELISA. No association between thrombosis and aPL was found. Reactivity against domain 1 and 4-5 of ß2GPI was limited to 3/58 (5.2%) tested sera for each domain and did not correlate with aCL/anti-ß2GPI nor with thrombosis. Conclusions: aPL show a low prevalence in COVID-19 patients and are not associated with major thrombotic events. aPL in COVID-19 patients are mainly directed against ß2GPI but display an epitope specificity different from antibodies in antiphospholipid syndrome.

12.
Autoimmun Rev ; 19(12): 102685, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33115633

RESUMO

Autoimmune rheumatic diseases (ARDs) are chronic conditions with a striking female predominance, frequently affecting women of childbearing age. Sex hormones and gender dimorphism of immune response are major determinants in the multifactorial pathogenesis of ARDs, with significant implications throughout reproductive life. Particularly, pregnancy represents a challenging condition in the context of autoimmunity, baring profound hormonal and immunologic changes, which are responsible for the bi-directional interaction between ARDs outcome and pregnancy course. In the latest years epigenetics has proven to be an important player in ARDs pathogenesis, finely modulating major immune functions and variably tuning the significant gender effects in autoimmunity. Additionally, epigenetics is a recognised influencer of the physiological dynamic modifications occurring during pregnancy. Still, there is currently little evidence on the pregnancy-related epigenetic modulation of immune response in ARDs patients. This review aims to overview the current knowledge of the role of epigenetics in the context of autoimmunity, as well as during physiologic and pathologic pregnancy, discussing under-regarded aspects in the interplay between ARDs and pregnancy pathology. The outline of a new ongoing European project will be presented.

13.
J Thromb Haemost ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33128325

RESUMO

BACKGROUND: Trial of Rivaroxaban in AntiPhospholipid Syndrome was a prospective randomized, open-label, noninferiority study conducted in 14 centers in Italy. Rivaroxaban was compared with warfarin for the prevention of thromboembolic events, major bleeding, and vascular death in high-risk, triple-positive patients with antiphospholipid syndrome. OBJECTIVE: The aim of this paper is to report the events during the 2-year follow-up after the study closure. METHODS: On January 28, 2018, the trial was prematurely stopped by adjudication and safety committee for an excess of events in the rivaroxaban group. Randomized patients were advised on trial results and those randomized to rivaroxaban were solicited to switch to warfarin. All 14 participating centers were asked and accepted to follow their patients for clinical events. This report describes the rate of events that occurred between January 28, 2018, and January 28, 2020. RESULTS: Of 120 randomized patients, 115 were available for follow-up. Outcome events were two in six (33.3%) patients who remained on direct oral anticoagulants (DOACs) and six in 109 (5.7%) patients on warfarin (hazard ratio [HR] 6.9; 95% confidence interval [CI] 1.4-34.5, P = .018). The two patients on DOACs (one taking dabigatran and one taking rivaroxaban) suffered from thromboembolic events, whereas of the six patients with composite outcomes on warfarin, three had thromboembolic events (HR for thrombosis 13.3; 95% CI 2.2-79.9, P = .005). CONCLUSION: These data further support the use of warfarin in high-risk patients with antiphospholipid syndrome.

14.
Biomolecules ; 10(10)2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33053910

RESUMO

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was first introduced in 2011 by Shoenfeld et al. and encompasses a cluster of related immune mediated diseases, which develop among genetically prone individuals as a result of adjuvant agent exposure. Since the recognition of ASIA syndrome, more than 4400 documented cases have been reported so far, illustrated by heterogeneous clinical manifestations and severity. In this review, five enigmatic conditions, including sarcoidosis, Sjögren's syndrome, undifferentiated connective tissue disease, silicone implant incompatibility syndrome (SIIS), and immune-related adverse events (irAEs), are defined as classical examples of ASIA. Certainly, these disorders have been described after an adjuvant stimulus (silicone implantation, drugs, infections, metals, vaccines, etc.) among genetically predisposed individuals (mainly the HLA-DRB1 and PTPN22 gene), which induce an hyperstimulation of the immune system resulting in the production of autoantibodies, eventually leading to the development of autoimmune diseases. Circulating autonomic autoantibodies in the sera of patients with silicone breast implants, as well as anatomopathological aspects of small fiber neuropathy in their skin biopsies have been recently described. To our knowledge, these novel insights serve as a common explanation to the non-specific clinical manifestations reported in patients with ASIA, leading to the redefinition of the ASIA syndrome diagnostic criteria.

15.
Clin Rheumatol ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32945981

RESUMO

To study disease activity during pregnancy and obstetric outcomes in patients with juvenile idiopathic arthritis (JIA) upon different subsets and with focus on medication use. Retrospective observational study of 22 pregnancies in 16 JIA patients (95.5% Caucasian) who were followed between 2010 and 2018. Disease activity, flares and medications were recorded before conception, during each trimester and postpartum period. Pregnancies occurred in 10 (45.5%) oligoarticular extended (OLA-E), 6 (27.3%) in polyarticular (PLA), 4 in (18.2%) systemic (SYS), 1 (4.5%) in oligoarticular persistent (OLA-P) and 1 (4.5%) in enthesitis-related arthritis (ERA) JIA patients. The median age at disease diagnosis and at conception was 5.5 and 28 years (respectively). The median disease duration was 20 years. Nineteen (95%) pregnancies started in a period of stable disease remission. Among the 22 pregnancies, 20 ended with a live birth (90.9%). No spontaneous miscarriages occurred; two voluntary interruption of pregnancy were performed. There were 7 flares in 6/20 pregnancies (35%) and 8 flares (8/22, 36.4%) occurred in postpartum period, all of them in OLA-E and PLA patients. Seven patients (35%) were taking biological disease-modifying anti-rheumatic drugs (bDMARDs) at conception, and 6 of them stopped this treatment at positive pregnancy test. Five patients resumed bDMARDs either during pregnancy (3 exposed during the third trimester) or puerperium due to a flare. Four preterm deliveries (20%) were recorded, all in patients who had a flare during pregnancy. The preconception counselling should include the evaluation of disease subset, as OLA-E and PLA may flare more than other subsets, especially if bDMARDs are discontinued at positive pregnancy test. Continuation of bDMARDs during pregnancy should be considered to minimize the risk of adverse pregnancy outcomes, particularly preterm delivery. Key Points • In our cohort, all the flares during pregnancy and 75% of postpartum flares were observed in patients who withdrew bDMARDs and cDMARDs at the beginning of pregnancy. • Flares were observed only in PLA and OLA-E patients. • Preterm delivery occurred in 20% of the pregnancies; all of these patients had a disease flare during pregnancy.

16.
Am J Reprod Immunol ; : e13331, 2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-32893404

RESUMO

PROBLEM: Antibody-mediated autoimmune diseases, such as autoimmune thyroid diseases (ATD), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS), often are associated with recurrent fetal loss. One of the ATD is Hashimoto's thyroiditis which recently showed association with complications of pregnancy with increased levels of circulating autoantibodies reactive with epitopes on thyroid tissue such as thyroid peroxidase (anti-TPO). In retrospective study of sera analyses in patients with Hashimoto's thyroiditis, all patients had mainly elevated circulating anti-TPO autoantibodies. AIM: We assessed the potential of human anti-TPO highly positive IgG, derived from patients with Hashimoto's thyroiditis sera associated with complications of pregnancy, to cause directly complications of pregnancy in murine model. METHOD OF STUDY: Naïve ICR female mice, infused intravenously with 100 µg of anti-TPO-positive IgG, showed increased fetal loss and embryo small for date (P < .001) in comparison with mice passively transferred with commercial IgG or PBS. Moreover, we observed embryos small for date in the mice passively transferred with anti-TPO-positive IgG, exemplified by reduced weight of embryos and placentae (P = .001). Histopathological examination revealed delay in fetal development in 50% cases of anti-TPO-positive IgG-treated mice. Importantly, pathological changes in the transition zone, state of glycogen cells, and significant structural changes in the labyrinth part of placenta were observed in all anti-TPO-positive IgG samples. CONCLUSION: The current study shows in the first time, a direct proof of concept, on the association of human TPO-positive IgG from Hashimoto's thyroiditis patients on fetal loss induction in murine model.

17.
Blood Rev ; : 100745, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32868115

RESUMO

COVID-19 is a new pandemic, caused by Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-Cov2) infection and characterized by a broad spectrum of clinical manifestations. Inflammation and the innate immune system have been recently recognized as pivotal players in the most severe forms, characterized by significantly elevated levels of pro-inflammatory cytokines. In this setting, several studies have also reported the presence of abnormalities in coagulation parameters and platelets count, possibly identifying a subgroup of patients with poor prognosis. Some reports of full-blown thromboembolic events are emerging. Among the possible mechanisms underlying coagulation dysfunction, the so-called "cytokine storm" seems to play a pivotal role. Other candidate factors include virus-specific mechanisms, related to the virus interaction with renin angiotensin system (RAS) and the fibrinolytic pathway, but also comorbidities affecting these patients. Coagulation dysfunction is therefore a candidate risk factor for adverse outcomes in COVID-19 and should be carefully addressed in clinical practice.

18.
Lupus ; 29(11): 1336-1345, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32752918

RESUMO

BACKGROUND: Antiphospholipid antibody syndrome (APS) is an autoimmune disease that affects women in childbearing age. In recent years, great improvements were achieved in the management of pregnancies in these women. Prematurity could be an issue in these pregnancies, mainly due to the direct pathogenic effect of antiphospholipid antibodies (aPL) on the placental surface. Maternal IgG aPL can cross the placenta and theoretically interact with the growing fetus; it could reach the fetal brain because of the incompleteness of the fetal blood-brain barrier: whether this can have an effect on brain development is still debated. Neonatal thrombosis episodes have been described in children positive for aPL, not always associated with maternal antibody positivity, suggesting the hypothesis of a possible aPL de novo synthesis in fetus and neonates. METHODS: A keyword-based literature search was conducted. We also described a case of neonatal catastrophic antiphospholipid syndrome (CAPS). RESULTS: Offspring of patients with APS are generally healthy but the occurrence of neonatal thrombosis or minor neurological disorders were reported. CONCLUSIONS: The limited number of the available data on this sensitive issue supports the need for further studies. Clinical follow-up of children of mothers with APS seems to be important to exclude, in the neonatal period, the occurrence of aPL associated pathological events such as thrombosis, and in the long-term, impairment in learning skills or behavioral problems.

19.
Ann Rheum Dis ; 79(10): 1286-1289, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32732245

RESUMO

OBJECTIVES: The outbreak of COVID-19 posed the issue of urgently identifying treatment strategies. Colchicine was considered for this purpose based on well-recognised anti-inflammatory effects and potential antiviral properties. In the present study, colchicine was proposed to patients with COVID-19, and its effects compared with 'standard-of-care' (SoC). METHODS: In the public hospital of Esine, northern Italy, 140 consecutive inpatients, with virologically and radiographically confirmed COVID-19 admitted in the period 5-19 March 2020, were treated with 'SoC' (hydroxychloroquine and/or intravenous dexamethasone; and/or lopinavir/ritonavir). They were compared with 122 consecutive inpatients, admitted between 19 March and 5 April 2020, treated with colchicine (1 mg/day) and SoC (antiviral drugs were stopped before colchicine, due to potential interaction). RESULTS: Patients treated with colchicine had a better survival rate as compared with SoC at 21 days of follow-up (84.2% (SE=3.3%) vs 63.6% (SE=4.1%), p=0.001). Cox proportional hazards regression survival analysis showed that a lower risk of death was independently associated with colchicine treatment (HR=0.151 (95% CI 0.062 to 0.368), p<0.0001), whereas older age, worse PaO2/FiO2, and higher serum levels of ferritin at entry were associated with a higher risk. CONCLUSION: This proof-of-concept study may support the rationale of use of colchicine for the treatment of COVID-19. Efficacy and safety must be determined in controlled clinical trials.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colchicina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , /tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Betacoronavirus , Estudos de Casos e Controles , Estudos de Coortes , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Dexametasona/uso terapêutico , Combinação de Medicamentos , Inibidores Enzimáticos/uso terapêutico , Feminino , Hospitalização , Humanos , Hidroxicloroquina/uso terapêutico , Itália , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Estudo de Prova de Conceito , Modelos de Riscos Proporcionais , /mortalidade , Ritonavir/uso terapêutico , Taxa de Sobrevida
20.
Rheumatol Adv Pract ; 4(2): rkaa017, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32685912

RESUMO

Objective: The efficacy of tocilizumab (TCZ) in GCA is supported by two randomized controlled studies, in which TCZ allowed remission to be achieved after 52 weeks of treatment. However, after discontinuation of treatment, half of the patients relapsed. The aim of this study was to analyse the efficacy and safety of long-term treatment with TCZ and the role of fluorodeoxyglucose (FDG)-PET/CT scanning in the follow-up of these patients. Methods: We collected the clinical data of a monocentric cohort of GCA patients retrospectively. Results: Thirty-two patients were treated with TCZ [25 males and 7 females; age = 74 (59-81) years]. Most of them achieved and maintained clinical remission (1 month: 69%; 3 months: 91%; 6 months: 96%; 12 months: 100%), with serological and FDG-PET/CT scan improvement and a reduction of concomitant glucocorticoid therapy. Nineteen patients were treated for >52 weeks, and in 13 of them a dose tapering was performed, whereas in 2 cases TCZ was suspended for disease remission. Only two patients relapsed: one during TCZ tapering and one after TCZ discontinuation. Ten cases of mild infections and a case of urinary sepsis were reported; in patients treated for >1 year there was no increase in the incidence of side effects compared with patients treated for <12 months. Conclusion: In our cohort of patients, we confirmed the efficacy of TCZ in the induction and maintenance of remission of GCA, demonstrating an important steroid-sparing effect and a good safety profile. Long-term treatment seems to prevent relapse of the disease, suggesting that TCZ treatment can be continued for >52 weeks with efficacy and safety.

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