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2.
Reumatismo ; 74(1)2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35506318

RESUMO

The current coronavirus disease 2019 (COVID-19) pandemic is a global challenge with strong medical and socioeconomic implications. Hopes have been placed in the development of various vaccines. As the vaccination campaign is in progress, adverse effects need to be monitored closely. Possible side effects range from minor events to more serious manifestations. In this article, we describe two cases of erythema nodosum (EN) after COVID-19 vaccination in two previously healthy female patients of 59 and 51 years, respectively. Most of the usual etiologies of EN were excluded by laboratory testing. EN was successfully treated with corticosteroids. Remarkably, in the first case, a relapse occurred 48 hours after the second dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. In this case series, we describe two unusual occurrences of EN after vaccination with an mRNA COVID-19 vaccine and a viral vector vaccine, respectively, and we discuss the available related literature.


Assuntos
COVID-19 , Eritema Nodoso , Vacinas Virais , Vacinas contra COVID-19/efeitos adversos , Eritema Nodoso/induzido quimicamente , Feminino , Humanos , SARS-CoV-2 , Vacinas Virais/efeitos adversos
3.
J R Soc Interface ; 19(187): 20210642, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35104431

RESUMO

Bone has a sophisticated architecture characterized by a hierarchical organization, starting at the sub-micrometre level. Thus, the analysis of the mechanical and structural properties of bone at this scale is essential to understand the relationship between its physiology, physical properties and chemical composition. Here, we unveil the potential of Brillouin-Raman microspectroscopy (BRaMS), an emerging correlative optical approach that can simultaneously assess bone mechanics and chemistry with micrometric resolution. Correlative hyperspectral imaging, performed on a human diaphyseal ring, reveals a complex microarchitecture that is reflected in extremely rich and informative spectra. An innovative method for mechanical properties analysis is proposed, mapping the intermixing of soft and hard tissue areas and revealing the coexistence of regions involved in remodelling processes, nutrient transportation and structural support. The mineralized regions appear elastically inhomogeneous, resembling the pattern of the osteons' lamellae, while Raman and energy-dispersive X-ray images through scanning electron microscopy show an overall uniform distribution of the mineral content, suggesting that other structural factors are responsible for lamellar micromechanical heterogeneity. These results, besides giving an important insight into cortical bone tissue properties, highlight the potential of BRaMS to access the origin of anisotropic mechanical properties, which are almost ubiquitous in other biological tissues.


Assuntos
Osso e Ossos , Ósteon , Anisotropia , Osso e Ossos/diagnóstico por imagem , Osso Cortical , Ósteon/fisiologia , Humanos , Microscopia Eletrônica de Varredura , Análise Espectral Raman/métodos
4.
Autoimmun Rev ; 21(4): 103038, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34995765

RESUMO

BACKGROUND: Fertility is thought to be not affected in women with systemic lupus erythematosus (SLE), however disease-related factors, psychosocial effects of chronic disease, as well as medications exposure might impair gonadal function. OBJECTIVE: This systematic literature review (SLR) aimed to explore clinical, hormonal, serological and treatment factors associated with fertility outcomes in women of childbearing age with SLE. METHODS: This SLR was conducted following the Preferred Reporting Items for systematic reviews and Meta-analysis (PRISMA) statement. All articles available in English (1972 - 30th April 2021) in Pubmed, EMBASE, Scopus and Cochrane Library were screened. Studies selection and data collection were performed by two independent reviewers. All data were extracted using a standardized template. The risk of bias of the included studies was assessed using the NIH risk-of-bias tool. RESULTS: Of 789 abstracts evaluated, we included in this review 46 studies, of which 1 SLR, 16 cross-sectional studies, 18 cohort studies, 10 observational studies and 1 case-series, with data pertaining to 4704 patients (mean age 31.5 ± 3.7 years, disease duration 83.27 ± 38.3 months). Definitions of premature ovarian failure (POF) adopted in the studies varied in terms of the number of months of amenorrhea considered and the age of onset of amenorrhea. Clinical factors associated with the development of POF were older age at the time of initiation of therapy, and older age at the onset of SLE disease. Cyclophosphamide exposure (CYC) and its cumulative dose influenced gonadal function in SLE women, leading to amenorrhoea and POF, as reported in 19 studies. Mycophenolate, azathioprine, calcineurin inhibitors and steroids associated with a lower risk of POF compared to CYC. POF was less frequent in patients co-treated with CYC and gonadotropin-releasing hormone analogues (GnRH-a) compared with patients not receiving GnRH-a (risk ratio 0.28, 95%-CI [0.14; 0.55]). 11 studies evaluated the impact of damage accrual and disease activity on ovarian reserve with conflicting evidence. Finally, 18 studies investigated exposure to hormonal and serological factors and, among others, neither anti-Müllerian Hormone nor anti-corpus luteum antibodies were associated with POF. CONCLUSION: The strongest evidence regarding management factors associated with fertility in SLE women of childbearing age remains the treatment with CYC, as well as its cumulative dosage. Hormonal and serological factors appeared not to impact fertility outcomes, but they might be used as a surrogate of fertility, especially during the treatment with disease-specific drugs.


Assuntos
Lúpus Eritematoso Sistêmico , Insuficiência Ovariana Primária , Adulto , Estudos Transversais , Ciclofosfamida/uso terapêutico , Feminino , Fertilidade , Humanos , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/complicações , Insuficiência Ovariana Primária/tratamento farmacológico
5.
Reumatismo ; 73(3)2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34814659

RESUMO

Since the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) pandemic outbreak, vaccines gained a growing role. Possible vaccine-related side effects range from minor local events to more prominent systemic manifestations up to anaphylactic reactions. A heterogeneous spectrum of cutaneous reactions has been reported, ranging from local injection site reactions to urticarial and morbilliform eruptions, pernio/chilblains and zoster flares. Here, we describe a case of varicella zoster virus reactivation following mRNA coronavirus 2019 vaccine and discuss the available literature upon the topic published so far.


Assuntos
COVID-19 , Herpes Zoster , Espondilite Anquilosante , Vacinas contra COVID-19 , Humanos , RNA Mensageiro , SARS-CoV-2
6.
Scand J Rheumatol ; 50(5): 333-342, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33660559

RESUMO

Objectives: This study aimed to evaluate the impact of different comorbidities on thereflecting its safety profile persistence of biological disease-modifying anti-rheumatic drugs (bDMARDs) in rheumatoid arthritis (RA), taking advantage of a retrospective analysis of administrative healthcare databases (AHDs).Method: A retrospective observational study was conducted on AHDs of the Lombardy region, Italy (2004-2013). Among RA patients treated with bDMARDs, drug survival was estimated using Cox proportional hazard models [hazard ratio (HR), 95% confidence interval (CI)], crude and adjusted for prespecified confounders (gender, age, disease duration, concomitant use of non-steroidal anti-inflammatory drugs, glucocorticoids, conventional DMARDs, specific bDMARDs), in first-line and subsequent lines of treatment. The role of comorbidities in administration of specific bDMARDs was analysed through multinomial logistic models.Results: The study included 4657 RA patients. In the first-line treatment strategy, the Charlson Comorbidity Index (CCI) (RA excluded) was significantly associated with an increased rate of bDMARD failure (CCI = 1: HR 1.28, 95% CI 1.13-1.46; CCI ≥ 2: HR 1.26, 95% CI 1.03-1.53). Among selected comorbidities, chronic obstructive pulmonary disease (HR 1.38, 95% CI 1.01-1.91), diabetes (HR 1.18, 95% CI 1.01-1.37), and previous-year bacterial infections (HR 1.18, 95% CI 1.07-1.30) were slightly associated with risk of bDMARD failure, while acute myocardial infarction (HR 1.30, 95% CI 0.97-1.75), mild liver disease (HR 1.21, 95% CI 0.91-1.60), and solid tumours (HR 1.19, 95% CI 0.93-1.53) were not. In the following treatment lines, neoplasms were associated with reduced risk of failure (HR 0.64, 95% CI 0.41-0.99). Multiple comorbidities were associated with first-line abatacept and rituximab administration.Conclusions: Comorbidities affect treatment decisions in RA and influence bDMARD failure, and should be considered when analysing the persistence of biological therapy.


Assuntos
Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Fatores Biológicos , Produtos Biológicos/uso terapêutico , Comorbidade , Atenção à Saúde , Humanos , Estudos Retrospectivos
7.
Eur Rev Med Pharmacol Sci ; 25(3): 1548-1556, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33629324

RESUMO

OBJECTIVE: The study was aimed to investigate the role of radiotherapy (RT) as a risk factor for reactivation or worsening of symptoms in patients affected by rheumatoid arthritis (RA) PATIENTS AND METHODS: This is a single-center retrospective observational study on RA patients who developed cancer requiring RT during the course of the disease. The control group consisted of RA patients with cancer who did not undergo RT. In both groups, the disease activity was evaluated at baseline and at 6 and 12 months through the DAS28 index. A relapse was defined as an increase of >20% in DAS28. A radiotherapist evaluated total and daily doses and timing of radiation. Acute and late toxicity was defined as events occurring within 90 days from the start and more than 90 days after the completion of RT, respectively. RESULTS: Seventy-two RA patients (38F/34M; mean age: 70±9 years; mean disease duration: 13±9 years), 29 (40.2%) of whom received radiotherapy (mean age 72.9±9 years), were enrolled. The most frequent malignancies were breast (27.2%), thyroid (9.8%), and skin (7%). Between radio-treated and non-radio-treated patients, no significant differences in RA reactivation (6/29 vs. 17/43; p=0.12) or mean exacerbation time (6.7 ± 4.9 months compared to 6.4 ± 4.1 months; p=0.78) were found. Overall, RT was well tolerated with low rates of both acute and late toxicity. CONCLUSIONS: In RA patients, RT was well tolerated and not associated with an increased risk of articular flares. Properly designed prospective clinical studies with a larger number of patients should be performed to confirm these data.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Neoplasias/radioterapia , Idoso , Feminino , Humanos , Masculino , Estudos Retrospectivos
8.
Sci Rep ; 10(1): 17341, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060731

RESUMO

Brillouin-Raman microspectroscopy is presented as an innovative label-free all-optical investigation approachable to characterize the chemical composition and the mechanical properties of human tissues at micrometric resolution. Brillouin maps unveil mechanical heterogeneities in a human femoral diaphysis, showing a ubiquitous co-existence of hard and soft components, even in the most compact sections. The novel correlative analysis of Brillouin and Raman maps shows that the relative intensity of Brillouin peaks is a good proxy for the fraction of mineralized fibers and that the stiffness (longitudinal elastic modulus) of the hard component is linearly dependent on the hydroxyapatite concentration. For the soft component, a gradient of composition is found, ranging from an abundance of proteins in the more compact, external, bone to abundance of lipids, carotenoids, and heme groups approaching the trabecular, inner, part of the diaphysis. This work unveils the strong potential of correlative mechano-chemical characterization of human tissues at a micrometric resolution for both fundamental and translational research.


Assuntos
Diáfises/química , Fêmur/química , Análise Espectral Raman/métodos , Fenômenos Biomecânicos , Módulo de Elasticidade , Humanos , Pesquisa Translacional Biomédica
9.
Lupus ; 29(5): 499-504, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32138582

RESUMO

INTRODUCTION: Neuropsychiatric (NP) manifestations occur mostly in the early phases of the systemic lupus erythematosus (SLE) course. Nonspecific alterations are evident in conventional brain magnetic resonance imaging (MRI), regardless of clinically overt NP symptoms. The main aims of this study were to assess the prevalence of MRI abnormalities in newly diagnosed SLE, and to evaluate the impact of MRI changes during follow-up (FU) and the clinical course of NP symptoms. MATERIALS AND METHODS: Newly diagnosed SLE patients with a baseline brain MRI and with available repeated MRI during FU were retrospectively evaluated. White-matter lesions and atrophy were recorded, comparing NPSLE and non-NPSLE patients. Cox proportional hazard models were used to compare NP events during FU with MRI data. RESULTS: Forty-four patients were included, 22 with NP events attributed to SLE. The baseline MRI scan was abnormal in 21 patients (47.73%). New NP events occurred in 17 patients, and worsening was found in repeated MRIs in 12 (27.27%). A worsening of MRI was associated with higher occurrence of new NP events during FU (adjusted hazard ratio 3.946 (1.175-13.253)). CONCLUSION: Baseline MRI is useful in patients with an early diagnosis of SLE, allowing comparison with subsequent scans. In our study, radiological worsening of repeated brain MRI was associated with new NP events.


Assuntos
Encéfalo/patologia , Lúpus Eritematoso Sistêmico/patologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Substância Branca/patologia , Adulto , Atrofia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Adulto Jovem
10.
Lupus ; 28(9): 1091-1100, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31291846

RESUMO

BACKGROUND: The study aimed to investigate whether HLA-G antigen is expressed in the kidneys of patients affected by lupus nephritis (LN) and whether its detection in renal biopsies could be adopted as a marker of treatment response and prognosis. METHODS: Thirty renal biopsies from patients with LN were selected and analyzed through immunohistochemistry. Laboratory and clinical data were retrospectively collected at baseline, 6 and 12 months and at the latest clinical appointment. A number of patients (63.3%) were treated with rituximab (RTX) +/- methylprednisolone in the induction phase. The expression of HLA-G in glomeruli, tubules and infiltrating cells was examined and compared between lupus patients who achieved either complete or partial renal response and those who did not respond to treatment. RESULTS: HLA-G staining was observed in the glomeruli of 20 of 30 samples from patients with LN. The expression of the antigen was detected in podocytes, along glomerular capillary walls, on parietal glomerular epithelial cells and within the juxtaglomerular apparatus. Seventy per cent of patients whose glomeruli expressed HLA-G achieved partial or complete response at 6 months and 75% at the latest available follow up compared with 30% and 40%, respectively, of those who did not show any expression. The pattern of staining in tubules and infiltrating cells was highly variable precluding any clinical correlation. CONCLUSION: This study demonstrates that HLA-G is expressed in renal tissue in LN. Our retrospective data suggest that its expression could correlate with response to treatment.


Assuntos
Antígenos HLA-G/imunologia , Nefrite Lúpica/tratamento farmacológico , Metilprednisolona/administração & dosagem , Rituximab/administração & dosagem , Adulto , Anti-Inflamatórios/administração & dosagem , Biópsia , Feminino , Seguimentos , Humanos , Fatores Imunológicos/administração & dosagem , Nefrite Lúpica/imunologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
11.
Biomed Opt Express ; 10(5): 2606-2611, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31143505

RESUMO

Brillouin micro-spectroscopy is applied for investigating the mechanical properties of bone and cartilage tissues of a human femoral head. Distinctive mechanical properties of the cartilage surface, subchondral and trabecular bone are reported, with marked heterogeneities at both micrometric and millimetric length scales. A ubiquitous soft component is reported for the first time, characterized by a longitudinal modulus of about 4.3 GPa, possibly related to the amorphous phase of the bone. This phase is mixed, at micrometric scales, with a harder component, ascribed to mineralized collagen fibrils, characterized by a longitudinal modulus ranging between 16 and 25 GPa.

12.
Lupus ; 28(4): 465-474, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30739544

RESUMO

BACKGROUND: Despite its potentially significant impact on disease outcome, peripheral nervous system involvement in systemic lupus erythematosus has received little attention. OBJECTIVE: The objective of this study was to assess the prevalence and clinical features of peripheral nervous system involvement in a large cohort of systemic lupus erythematosus patients. METHODS: The records of systemic lupus erythematosus patients examined at two tertiary referral centres over a period of 14 years (from 2000 to 2014) were analyzed. Peripheral nervous system events were ascertained according to the 1999 American College of Rheumatology case definitions and by using an attribution algorithm for neuropsychiatric events. Prevalence of peripheral nervous system in systemic lupus erythematosus and demographic, clinical and laboratory features were assessed. Patients with peripheral nervous system events were compared with a control group of systemic lupus erythematosus patients without peripheral nervous system involvement. RESULTS: In a retrospective cohort of 1224 patients, the overall prevalence of peripheral nervous system involvement was 6.9% (85 patients, 95% confidence interval 0.06-0.08), with 68% of peripheral nervous system events attributable to systemic lupus erythematosus. Polyneuropathy was the most common manifestation observed (38 events, 39.2%), followed by cranial neuropathy in 30 cases (30.9%) and 12 cases of single (12.4%) or multiple (eight events, 8.2%) mononeuritis. The average age of systemic lupus erythematosus onset was significantly higher in patients with peripheral nervous system events than in controls (mean ± standard deviation: 45.9 ± 14.8 vs. 37.1 ± 14.0) and they were more likely to have higher SLEDAI-2K and SLICC/ACR Damage Index scores, as well as hypertension and livedo reticularis. A subgroup analysis of events deemed to be systemic lupus erythematosus-related provided similar results. CONCLUSION: Peripheral nervous system manifestations are a potential complication of systemic lupus erythematosus. Careful neurological assessment should therefore be included in the diagnostic workup of patients with systemic lupus erythematosus, especially in those with later onset and greater damage and disease activity.


Assuntos
Doenças dos Nervos Cranianos/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Mononeuropatias/epidemiologia , Miastenia Gravis/epidemiologia , Polineuropatias/epidemiologia , Adulto , Antipsicóticos/uso terapêutico , Doenças dos Nervos Cranianos/tratamento farmacológico , Doenças dos Nervos Cranianos/etiologia , Feminino , Hospitais Universitários , Humanos , Itália/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade , Mononeuropatias/tratamento farmacológico , Mononeuropatias/etiologia , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/etiologia , Miastenia Gravis/fisiopatologia , Sistema Nervoso Periférico/fisiopatologia , Polineuropatias/tratamento farmacológico , Polineuropatias/etiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Centros de Atenção Terciária , Resultado do Tratamento , Adulto Jovem
13.
Lupus ; 27(9): 1479-1488, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29779436

RESUMO

Objective To describe the clinical and serological features of a prospectively followed cohort of early diagnosed systemic lupus erythematosus (SLE) patients during a one-year follow-up period. Methods SLE patients with disease duration less than 12 months were consecutively enrolled in a multicentre, prospective study. At study entry and then every 6 months, a large panel of data was recorded. Results Of 260 patients enrolled, 185 had at least 12 months of follow-up; of these, 84.3% were female, 92.4% were Caucasians. Mean diagnostic delay was about 20 months; higher values of European Consensus Lupus Activity Measurement (ECLAM) and of organs/systems involved were both associated with shorter diagnostic delay. Clinical and serological parameters improved after study entry. However, patients' quality of life deteriorated and cardiovascular risk factors significantly increased. About one-third of patients with active disease at study entry went into remission (ECLAM = 0). Negative predictors for remission were: oral ulcers, arthritis, low C4, anti-SSB (Ro) antibodies and therapy with mycophenolate. There was a widespread use of glucocorticoids both at baseline and during follow-up. Conclusion Clinical symptoms and serological parameters improve during the first period after diagnosis. However, patients' quality of life deteriorates. The widespread use of glucocorticoids is probably the reason for the early significant increase of some cardiovascular risk factors.


Assuntos
Lúpus Eritematoso Sistêmico/epidemiologia , Adulto , Anticorpos Antinucleares/sangue , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Humanos , Itália/epidemiologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
14.
Clin Rheumatol ; 37(2): 315-321, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28980085

RESUMO

To assess the long-term effectiveness and safety of tocilizumab, abatacept, and tumor necrosis factor-α inhibitors (TNFi), in the Italian real-world setting of rheumatoid arthritis (RA). The records of adult RA patients from the Italian biologics' registry Gruppo Italiano Studio Early Arthritis (GISEA) were analyzed. Demographic and clinical data were obtained at entry. The disease remission rate (28-joint disease activity score calculated using the erythrocyte sedimentation rate [DAS28-ESR] ≤ 2.6) and frequency of adverse events (AEs) were evaluated at 2 years. From 1999 to 2014, 7539 patients were treated with biologics (61.3% in first- and 22.6% in second-line), 68% of cases received TNFi, 9.1% tocilizumab, and 8.6% abatacept. Treatment groups showed a similar DAS28 at entry. As first-line, tocilizumab induced a significantly higher remission rate than abatacept or TNFi at 6 (51 vs 23.3 and 26.2%, respectively; p < 0.0001) and 24 months (52.3 vs 33.3 and 34.4%, respectively; p < 0.01). A similar pattern was observed in later lines. The most common AEs reported were infections, reactions to biologics (more frequent among TNFi-treated patients), increased transaminase (more frequent among TCZ-treated patients), and cardiovascular events. In clinical practice, TCZ induced a rapid and long-lasting remission and in a higher percentage of patients compared to abatacept and TNFi, with a good safety profile.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Abatacepte/efeitos adversos , Abatacepte/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Produtos Biológicos/efeitos adversos , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Indução de Remissão/métodos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
15.
Lupus ; 26(6): 616-622, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27703051

RESUMO

Objectives The objectives of this study were to analyse the performance of the Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria for systemic lupus erythematosus (SLE) in a large cohort of undifferentiated connective tissue disease (UCTD) population at onset of the disease and during a long-term follow-up of 15 years (1999-2013) and to evaluate the transition from UCTD to SLE, according to American College of Rheumatology (ACR) 1997 and SLICC 2012 classification criteria. Methods A cohort of patients who met the classification criteria proposed by Mosca et al. for UCTD, were analysed. The SLICC 2012 classification criteria for SLE were retrospectively applied to each patient at the time of the diagnosis (T0) and also periodically re-applied and compared to ACR 1997 criteria at three different time points in the follow-up. Results 329 patients were enrolled. According to inclusion criteria at T0 no patient met the SLE/ACR criteria, whilst, retrospectively applying the SLE/SLICC criteria, 44 patients already satisfied this set of criteria for SLE. During the follow-up 23 new patients reached the SLE/SLICC criteria and 14 patients met the ACR criteria with a stable rate of progression to SLE over time. Acute or subacute skin rash, antiphospholipid antibody (aPL) positivity and serositis were the variables correlated to the evolution to SLE. Conclusions In our UCTD population, the application of SLICC classification criteria for SLE at disease onset allowed identification of a proportion of otherwise missed SLE cases; during follow-up, and compared with ACR criteria, SLICC criteria expanded the number of patients classifiable as SLE otherwise classified as UCTD.


Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , Doença Mista do Tecido Conjuntivo/classificação , Adulto , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença
16.
J Autoimmun ; 74: 41-72, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27427403

RESUMO

Neuropsychiatric (NP) involvement in Systemic Lupus Erythematosus (SLE), can be a severe and troubling manifestation of the disease that heavily impacts patient's health, quality of life and disease outcome. It is one of the most complex expressions of SLE which can affect central, peripheral and autonomous nervous system. Complex interrelated pathogenetic mechanisms, including genetic factors, vasculopathy, vascular occlusion, neuroendocrine-immune imbalance, tissue and neuronal damage mediated by autoantibodies, inflammatory mediators, blood brain barrier dysfunction and direct neuronal cell death can be all involved. About NPSLE a number of issues are still matter of debate: from classification and burden of NPSLE to attribution and diagnosis. The role of neuroimaging and new methods of investigation still remain pivotal and rapidly evolving as well as is the increasing knowledge in the pathogenesis. Overall, two main pathogenetic pathways have been recognized yielding different clinical phenotypes: a predominant ischemic-vascular one involving large and small blood vessels, mediated by aPL, immune complexes and leuko-agglutination which it is manifested with more frequent focal NP clinical pictures and a predominantly inflammatory-neurotoxic one mediated by complement activation, increased permeability of the BBB, intrathecal migration of autoantibodies, local production of immune complexes and pro-inflammatory cytokines and other inflammatory mediators usually appearing as diffuse NP manifestations. In the attempt to depict a journey throughout NPSLE from diagnosis to a reasoned therapeutic approach, classification, epidemiology, attribution, risk factors, diagnostic challenges, neuroimaging techniques and pathogenesis will be considered in this narrative review based on the most relevant and recent published data.


Assuntos
Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/terapia , Biomarcadores , Gerenciamento Clínico , Eletroencefalografia , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/epidemiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/etiologia , Imagem Multimodal/métodos , Neuroimagem/métodos , Testes Neuropsicológicos , Fatores de Risco
17.
Lupus ; 25(2): 193-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26405021

RESUMO

OBJECTIVES: The objectives of this report are to assess the occurrence of microembolic signals (MES) detected by transcranial Doppler ultrasound (TCD) in systemic lupus erythematosus (SLE) patients with (NPSLE) and without (SLE) neuropsychiatric involvement, and to verify the correlation between MES, clinical characteristics, especially the patent foramen ovale (PFO), and the presence of punctuate T2-hyperintense white matter lesions (WMHLs) detected by conventional magnetic resonance imaging (cMRI). METHODS: A TCD registration to detect MES from the middle cerebral artery was carried out in SLE and NPSLE patients after exclusion of aortic and/or carotid atheromatous disease. In all patients conventional brain magnetic resonance imaging (cMRI) and transesophageal echocardiography were performed. Patients were stratified in two groups, with and without WMHLs, and compared. RESULTS: Twenty-three SLE patients (16 NPSLE and seven SLE) were enrolled in the study. Overall MES were detected in 12 patients (52.1%), WHMLs were detectable in 15 patients (13 NPSLE and two SLE) while eight patients had normal cMRI (three NPSLE and five SLE). Matching TCD ultrasound and neuroimaging data, MES were detected in 10 (nine NPSLE and one SLE) out of 15 patients with WHMLs and in only two out of eight patients (two NPSLE and six SLE) with normal cMRI, both with NP involvement. A PFO was confirmed in all cases of MES detection. CONCLUSION: MES are frequent findings in SLE patients, especially in those with focal WMHLs detected by cMRI and correlating with PFO. These findings should be taken into account and suggest caution in the interpretation of cMRI pictures along with a careful evaluation of MES in patients with cMRI abnormalities that should be included in the workup of SLE patients.


Assuntos
Embolia Intracraniana/diagnóstico , Embolia Intracraniana/patologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/patologia , Adulto , Encéfalo/patologia , Feminino , Forame Oval Patente/diagnóstico , Forame Oval Patente/diagnóstico por imagem , Forame Oval Patente/patologia , Humanos , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/psicologia , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/psicologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/patologia , Neuroimagem , Ultrassonografia Doppler Transcraniana/métodos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
18.
Oncogene ; 35(8): 977-89, 2016 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-25961931

RESUMO

Many drugs currently used in chemotherapy work by hindering the process of ribosome biogenesis. In tumors with functional p53, the inhibition of ribosome biogenesis may contribute to the efficacy of this treatment by inducing p53 stabilization. As the level of stabilized p53 is critical for the induction of cytotoxic effects, it seems useful to highlight those cancer cell characteristics that can predict the degree of p53 stabilization following the treatment with inhibitors of ribosome biogenesis. In the present study we exposed a series of p53 wild-type human cancer cell lines to drugs such as actinomycin D (ActD), doxorubicin, 5-fluorouracil and CX-5461, which hinder ribosomal RNA (rRNA) synthesis. We found that the amount of stabilized p53 was directly related to the level of ribosome biogenesis in cells before the drug treatment. This was due to different levels of inactivation of the ribosomal proteins-MDM2 pathway of p53 digestion. Inhibition of rRNA synthesis always caused cell cycle arrest, independent of the ribosome biogenesis rate of the cells, whereas apoptosis occurred only in cells with a high rDNA transcription rate. The level of p53 stabilization induced by drugs acting in different ways from the inhibition of ribosome biogenesis, such as hydroxyurea (HU) and nutlin-3, was independent of the level of ribosome biogenesis in cells and always lower than that occurring after the inhibition of rRNA synthesis. Interestingly, in cells with a low ribosome biogenesis rate, the combined treatment with ActD and HU exerted an additive effect on p53 stabilization. These results indicated that (i) drugs inhibiting ribosome biogenesis may be highly effective in p53 wild-type cancers with a high ribosome biogenesis rate, as they induce apoptotic cell death, and (ii) the combination of drugs capable of stabilizing p53 through different mechanisms may be useful for treating cancers with a low ribosome biogenesis rate.


Assuntos
Antineoplásicos/farmacologia , Biogênese de Organelas , RNA Ribossômico/efeitos dos fármacos , Ribossomos/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Apoptose , Humanos , Estabilidade Proteica/efeitos dos fármacos , RNA Ribossômico/biossíntese , Ribossomos/metabolismo , Transcrição Gênica/efeitos dos fármacos , Células Tumorais Cultivadas
19.
Reumatismo ; 66(4): 285-303, 2015 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-25829189

RESUMO

Golimumab is an anti-TNF monoclonal antibody administred subcutaneously once a month and produced with an innovative technology that minimizes immunogenicity. This paper reviews and updates the main studies on the efficacy, safety and pharmacoeconomic aspects of treatment with golimumab of psoriatic arthritis, ankylosing spondylitis and rheumatoid arthritis.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Espondilite Anquilosante/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
20.
Reumatismo ; 67(4): 138-48, 2015 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-27215179

RESUMO

Diet and lifestyles modification are core aspects of the non-pharmacological management of gout, but a poor consistency with suggested guidelines is reported. This study aimed to investigate dietary and lifestyle habits of patients with gout followed in rheumatology settings. Data were retrieved from the baseline dataset of the KING study, a multicentre cohort study of patients with gout followed in rheumatology settings. Dietary habits were assessed with the Italian National Institute of Statistics (ISTAT) food-frequency questionnaire and compared with reported data about general population. The relative increase of exposure was estimated by standardized prevalence ratios adjusted for gender, age and geographical distribution. The study population included 446 patients, with a mean age of 63.9 years and a M/F ratio of 9:1. Compared to the Italian population, gouty patients showed a higher prevalence of obesity [1.82 (1.52-2.18)] and a higher consumption of wine [1.85 (1.48-2.32)] and beer [2.21 (1.68-2.90)], but a lower prevalence of smoking and a lower intake of liquor. They showed a lower intake of red meat [0.80 (0.71-0.91)], but a similar intake of other tested dietary factors. Gouty patients' lifestyle is still partially different from the recommended.


Assuntos
Comportamento Alimentar , Gota/complicações , Gota/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Estilo de Vida , Obesidade/complicações , Obesidade/prevenção & controle , Reumatologia , Animais , Cerveja/estatística & dados numéricos , Índice de Massa Corporal , Estudos de Coortes , Feminino , Peixes , Gota/epidemiologia , Gota/etiologia , Fidelidade a Diretrizes , Humanos , Itália/epidemiologia , Masculino , Carne/estatística & dados numéricos , Pessoa de Meia-Idade , Avaliação Nutricional , Obesidade/epidemiologia , Obesidade/etiologia , Prevalência , Carne Vermelha/estatística & dados numéricos , Fatores de Risco , Fumar/epidemiologia , Inquéritos e Questionários , Vinho/estatística & dados numéricos
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