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Andrea Doria

Publications and source records attributed to Andrea Doria.

At least 19 recordsLinked to original sources
PubMed2025

Genetic Architecture of Idiopathic Inflammatory Myopathies From Meta-Analyses.

OBJECTIVE: Idiopathic inflammatory myopathies (IIMs, myositis) are rare systemic autoimmune disorders that lead to muscle inflammation, weakness, and extramuscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis data set to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes. METHODS: We performed association analyses on 14,903 individuals (3,206 patients and 11,697 controls) with genotypes and imputed data from the Trans-Omics for Precision Medicine reference panel. Fine-mapping and expression quantitative trait locus colocalization analyses in myositis-relevant tissues indicated potential causal variants. Functional annotation and network analyses using the random walk with restart (RWR) algorithm explored underlying genetic networks and drug repurposing opportunities. RESULTS: Our analyses identified novel risk loci and susceptibility genes, such as FCRLA, NFKB1, IRF4, DCAKD, and ATXN2 in overall IIMs; NEMP2 in polymyositis; ACBC11 in dermatomyositis; and PSD3 in myositis with anti-histidyl-transfer RNA synthetase autoantibodies (anti-Jo-1). We also characterized effects of HLA region variants and the role of C4. Colocalization analyses suggested putative causal variants in DCAKD in skin and muscle, HCP5 in lung, and IRF4 in Epstein-Barr virus (EBV)-transformed lymphocytes, lung, and whole blood. RWR further prioritized additional candidate genes, including APP, CD74, CIITA, NR1H4, and TXNIP, for future investigation. CONCLUSION: Our study uncovers novel genetic regions contributing to IIMs, advancing our understanding of myositis pathogenesis and offering new insights for future research.

Humans↗
PubMed2006

MRI of traumatic patellar dislocation in children.

BACKGROUND: Traumatic patellar dislocations (TPD) are common injuries in children, and MRI is useful in evaluation of pediatric musculoskeletal injuries. However, no pediatric studies on the MR features of TPD have been reported. OBJECTIVE: To review the injuries after TPD in children. MATERIALS AND METHODS: Patients with clinical or radiological recognition of TPD and those with suggestive MR findings were selected. Bone, cartilage and soft-tissue injuries and patellofemoral relationships were assessed. RESULTS: A total of 26 patients (age range 10-18 years) were identified. The following injuries were seen: bone bruising of the inferomedial patella (81% of patients) and the lateral femoral condyle (81% of patients), cartilage injuries of the inferomedial patella (38% of patients) and the lateral femoral condyle (38% of patients), osteochondral fragments (42% of patients) and injuries of the medial patellar restraints (81% of patients). CONCLUSION: Pediatric manifestations of TPD seen on MRI are similar to those in adults. TPD is often occult in children. Early recognition of bone bruising of the patella and lateral femoral condyle, associated osteochondral injuries, and medial patellar stabilizer injury is important for timely diagnosis.

Adolescent↗
PubMed2006

Influence of coping skills on health-related quality of life in patients with systemic lupus erythematosus.

OBJECTIVE: To identify coping strategies used by patients with systemic lupus erythematosus (SLE), and to assess the influence of main clinical and coping variables on health-related quality of life (HRQOL). METHODS: We administered the Coping Orientation to Problems Experienced and the Short Form 36 questionnaire to a group of 144 patients with SLE and a group of 129 healthy controls. At the time of the psychological assessment, all patients underwent a complete clinical and laboratory evaluation. RESULTS: SLE patients had higher scores in acceptance (P < 0.001) and turning to religion (P = 0.05) and lower scores in planning (P = 0.001), suppression of competing activities (P = 0.010), restraint coping (P = 0.031), focusing on and venting of emotion (P = 0.009), and strategies focused on problem (P = 0.012) compared with controls. By means of linear regression analysis, HRQOL in SLE patients seemed to be influenced positively by restraint coping and positive reinterpretation and growth, and negatively by focusing on and venting of emotion, behavioral disengagement, and mental disengagement. When clinical variables were added to the multivariate analysis for coping strategies, more significant regression models that included joint pain were obtained. CONCLUSION: In facing stressful situations, patients with SLE tend to use coping skills that are generally adopted for events perceived as nonmodifiable. Strategies that show a passive attitude and joint pain seem to impair these patients' HRQOL.

Adaptation, Psychological↗
PubMed2006

Long-term outcomes in difficult-to-treat patients with recurrent pericarditis.

Patients with many recurrences of acute pericarditis are commonly alarmed by the fear of constriction. We studied their long-term outcome and the possible presence of systemic diseases. Sixty-one Italian patients (36 men) were followed for an average of 8.3 years according to a predefined protocol, including testing for autoimmune diseases and familial Mediterranean fever. Symptomatic pericarditis lasted from 1 to 43 years (mean 5.4 years). Fifty-two patients had been referred to us after failure of previous therapies, including steroids. We observed 378 attacks with a mean of 1.6 per patient per year and 156 hospital admissions. Thirteen patients had a post-cardiac injury syndrome. In 43 (70.5%), the pericarditis remained idiopathic, whereas we made a new diagnosis of rheumatoid arthritis in 1 and of Sjogren's syndrome in 4 patients, but in these patients pericarditis represented the dominant clinical manifestation. Cardiac tamponade occurred during the initial attacks in 4 patients (6.5%) but never recurred. Pleural effusions were present during the first attack in 22 patients (36.0%) and liver involvement in 5 (8%). No patients developed constrictive pericarditis. Echocardiographic examination produced no evidence of chronic myocardial disease. Response to therapy was good. Thirty-one patients (50.8%) are in sustained remission, without any therapy; their total observation period has averaged 10.3 years. In idiopathic patients, antinuclear antibodies were present in 56.2% and anti-Ro/SSA in 8.3%. Mutations linked to familial Mediterranean fever were absent. In conclusion, in this large series of difficult patients with recurrent acute pericarditis and a very long follow-up, the long-term prognosis is good.

Acute Disease↗
PubMed2006

Th2 immune deviation induced by pregnancy: the two faces of autoimmune rheumatic diseases.

One of the most important immunological modifications during pregnancy is the Th1/Th2 shift, due to the progressive increase of progesterone and estrogens during pregnancy, which reach their peak-level in the third trimester of gestation. At high levels, estrogens seem mainly to suppress Th1 cytokines and stimulate Th2-mediated immunological responses as well as antibody production. For this reason Th1-mediated diseases, like rheumatoid arthritis (RA), tend to improve and Th2-mediated disease, like systemic lupus erythematosus (SLE), tend to worsen during pregnancy. SLE is the autoimmune rheumatic disease in which pregnancy most frequently occurs because it predominantly affects young females in their childbearing age. Other autoimmune rheumatic diseases, including RA, are less frequently observed during pregnancy due to their low female-to-male ratio and peak onset after the age of 40. This review is focused on the disease course, gestational outcome and management of patients with SLE and RA during pregnancy.

Adrenal Cortex Hormones↗
PubMed2006

Anti-inflammatory and immunosuppressive drugs and reproduction.

Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given.

Adult↗
PubMed2006

Accuracy of anti-ribosomal P protein antibody testing for the diagnosis of neuropsychiatric systemic lupus erythematosus: an international meta-analysis.

OBJECTIVE: To quantitatively evaluate the diagnostic accuracy of antibodies to ribosomal P proteins (anti-P) for neuropsychiatric systemic lupus erythematosus (NPSLE) in general, for psychosis, mood disorder, or both, and for other diffuse manifestations. METHODS: This international meta-analysis combined standardized data from 1,537 lupus patients contributed by 14 research teams. Weighted estimation of sensitivity and specificity with fixed-effects and random-effects models, as well as summary receiver operating characteristic (SROC) curve analysis, was used to summarize test performance. The robustness of the overall estimates was examined in sensitivity analyses that included additional studies published up to November 1, 2004 in the Medline, EMBase, and Cochrane databases. RESULTS: Combining the data from the 14 teams, the weighted sensitivity and specificity estimates for the diagnosis of NPSLE were 26% (95% confidence interval [95% CI] 15-42%) and 80% (95% CI 74-85%), respectively. For psychosis, mood disorder, or both, the sensitivity and specificity were 27% (95% CI 14-47%) and 80% (95% CI 74-85%), respectively. For other diffuse manifestations, the sensitivity was 24% (95% CI 12-42%), and the specificity was 80% (95% CI 73-85%). The proportion of patients with anti-P antibodies did not vary markedly across different presentations of NPSLE. Between-study heterogeneity was substantial, but the SROC curves were consistent with the weighted estimates. In further analyses that included another 24 published studies, only the sensitivity for psychosis and/or mood disorder was slightly improved, but it was still suboptimal (42% [95% CI 30-53%]); the specificity remained essentially the same (81% [95% CI 76-85%]). CONCLUSION: Anti-P antibody testing has limited diagnostic value for NPSLE, and it is not helpful in differentiating among various disease phenotypes.

Antibodies↗
PubMed2006

Long-term prognosis and causes of death in systemic lupus erythematosus.

PURPOSE: We studied survival rate, prognostic factors, and causes of death in patients with systemic lupus erythematosus (SLE), particularly focusing on the influence of disease severity. PATIENTS AND METHODS: A cohort of 207 consecutive Italian patients with SLE were prospectively studied. All prominent clinical and serologic parameters were evaluated and considered as prognostic risk factors. Causes of death were defined on the basis of clinical data and, when available, postmortem examination. Survival was calculated from the time of diagnosis by Kaplan-Meier method. RESULTS: A total of 17 of 207 patients died; causes of death were active disease manifestations in 35.3% of cases and complication of the disease or its treatment in 64.7% of cases. The survival rates at 5, 10, and 15 years after the diagnosis were 96%, 93% and 76%, respectively. By multivariate analysis of the risk factors, a predictive model consisting of male gender, positive lupus anticoagulant, and "severe" SLE was identified. The survival curve of the patients with severe disease was similar to that of patients with mild disease until 10 to 15 years from the diagnosis. Thereafter the two curves tended to diverge, showing a clear survival decline in patients with severe disease. CONCLUSIONS: Our study confirms the increase of short- and medium-term survival in patients with SLE, but long-term prognosis remains poor in patients with severe SLE manifestations.

Adolescent↗
PubMed2006

Polymyositis-dermatomyositis and infections.

In genetically predisposed individuals, viruses, bacteria, or parasitic infectious agents are suspected to induce autoimmunity and/or to exacerbate the disease once the self-tolerance is broken. Although direct evidence for this association is still lacking, numerous data from animal models as well as from humans support the hypothesis of a direct contribution of pathogens to the induction of several autoimmune diseases. This review focused on the possible role of infectious agents as triggers of autoimmunity in polymyositis (PM) and dermatomyositis (DM). Epidemiological studies, clinical and experimental findings that support the hypothesis of infection-induced PM and DM are summarized and discussed. In addition, immune response abnormalities and immunosuppressive medications may be responsible for the high percentage of infectious complications in PM and DM patients. In this review, the increased risk of developing infections in these patients is also underlined and published data are reported.

Animals↗
PubMed2006

Increased neural sympathetic activation in fibromyalgia syndrome.

Fibromyalgia (FM) is a syndrome characterized by widespread musculoskeletal pain, although the mechanisms underlying the pain have not been fully elucidated. FM patients describe a number of nonspecific symptoms, such as anxiety, depression, fatigue, unrefreshing sleep, and gastrointestinal complaints, which appear after a flu-like illness, or after physical or emotional trauma in half of the patients, and are often exacerbated by exertion, stress, lack of sleep, and weather changes. There may also be symptoms of orthostatic intolerance, which suggests underlying abnormalities in cardiovascular neural regulation. Research suggests that various components of the central nervous system are involved, including the hypothalamic-pituitary-adrenal (HPA) axis, pain-processing pathways, and the autonomic nervous system (ANS). This review discusses the general aspects of the altered HPA and ANS, sympathetic overactivity, and alterations in cardiovascular autonomic responses to gravitational stimuli.

Fibromyalgia↗
PubMed2006

Estrogens in pregnancy and systemic lupus erythematosus.

Successful pregnancy depends on an adaptation of the maternal immune system that becomes tolerant to fetal antigens of paternal origin. The altered immune regulation induced by pregnancy occurs predominantly at the maternal-fetal interface, but it has also been observed in the maternal circulation. Th1/Th2 shift is one of the most important immunologic changes during gestation. It is due to the progressive increase of estrogens, which reach peak level in the third trimester of pregnancy. At these high levels, estrogens suppress the Th1-mediated responses and stimulate Th2-mediated immunologic responses. For this reason Th1-mediated diseases, such as rheumatoid arthritis, tend to improve, while Th2-mediated diseases, such as systemic lupus erythematosus (SLE) tend to worsen during pregnancy. However, in some recent studies SLE flare-ups were less frequently observed in the third trimester of gestation in comparison to the second trimester and postpartum period. These data are apparently in contrast to the Th2 immune-response polarization expected during pregnancy due to the progressive increase of estrogens. Some further data suggest that in SLE patients estradiol serum levels are surprisingly lower than expected during the third trimester of pregnancy, probably due to a placental compromise. This occurrence could lead to a lower-than-expected increase of IL-6, accounting for the low humoral immune response and the low disease activity observed in the third trimester of pregnancy in such patients.

Animals↗
PubMed2006

Cell stress response in skeletal muscle myofibers.

Cells respond to conditions that impair homeostasis through ex novo synthesis of stress proteins, which differ in subcellular localization and biological function and whose differential expression depends on the type of the stressing stimulus and on the involvement of the specific stress-response signaling cascade. The biological significance of such an event is the increased resistance against further perturbations of cell homeostasis, and thus, enhanced survival. We will review briefly the available evidence concerning stress response of skeletal muscle cells, including recent results indicating the involvement of endoplasmic reticulum stress response and proteins in skeletal muscle cell differentiation and in progression of muscle diseases.

Animals↗
PubMed2005

Five-year follow-up by transesophageal echocardiographic studies in primary antiphospholipid syndrome.

This prospective study describes valvular abnormalities assessed by transesophageal echocardiography (TEE) in patients with primary antiphospholipid syndrome (APLS) over a 5-year follow-up. Of the 56 patients with APLS evaluated at baseline, 47 (84%) had repeat TEE examinations, including 3 patients who died before the end of the follow-up. The first TEE study showed cardiac involvement (thickening or vegetations and embolic sources) in 34 subjects (61%), with mitral valve thickening, the most common abnormality, present in 30 patients (54%). Embolic sources were found in 14 patients (25%; 9 severe spontaneous echocardiographic contrast, 5 Libman-Sacks endocarditis), associated with mitral valve thickening or stenosis in 10 patients. Over the 5-year follow-up, cardiac involvement was unchanged in 30 subjects (64%). New cardiac abnormalities were observed in 17 patients (36%), 15 (88%) with high immunoglobulin-G (IgG) anticardiolipin antibody (aCL) titers and 2 (12%) with low IgG aCL titers. In conclusion, this study showed that mitral valve thickening and embolic sources are frequently observed in patients with APLS. Anticoagulant and/or antiplatelet treatment was ineffective in terms of valvular lesion regression. New appearances of cardiac involvement are significantly related to high IgG aCL titers.

Adult↗
PubMed2005

2nd conference on heart, rheumatism and autoimmunity, Pescara, Italy, May 19-20, 2005.

Systemic autoimmune diseases, which comprise a family of conditions which share common pathogenetic mechanisms, are frequently associated to cardiac involvement and to a high prevalence of ischemic coronary events often occurring at a younger age than in normal population. A large increase in mortality is related to premature atherosclerosis with coronary artery disease and stroke in patients with connective tissue diseases. Coronary heart disease is responsible for 40-50% of the death of patients with rheumatoid arthritis. Moreover, a growing body of evidence supports the view that autoimmune mechanisms are involved in the pathogenesis of cardiovascular disease. Inflammatory heart disease is a rising concern worldwide. Similar mechanisms link autoimmune diseases, including the association of increased disease with proinflammatory cytokines and the importance of regulatory mechanisms in the control of chronic inflammation. The role of the immune system in modulating atherosclerosis has recently been well documented. Studies have revealed that cellular and humoral immunity plays crucial roles in atherogenic plaque formation. This includes macrophages, CD4+ T cells and dendritic cells as well as autoantigens such as oxidized low-density lipoprotein (oxLDL), heat shock proteins and beta2-glycoprotein I. The inflammatory component is not localized to the "culprit" plaque, but it is diffused to the entire coronary vascular bed, and involves also the myocardium. The aim of the conference (2nd conference on heart, rheumatism and autoimmunity) was to focus the attention of the participants on some pathogenetic, clinical and therapeutic aspects at the boundary between cardiology and rheumatology and to encourage the debate among clinicians and basic researchers with different backgrounds and experiences.

Autoimmunity↗
PubMed2005

Thrombotic risk factors in primary antiphospholipid syndrome: a 5-year prospective study.

BACKGROUND AND PURPOSE: Because thromboembolic events are frequently observed in primary antiphospholipid syndrome (PAPS), we assessed the risk factors for new thrombotic episodes. METHODS: Fifty-six PAPS patients (mean age, 37+/-10 years) were prospectively studied for 5 years. The preliminary Sapporo classification criteria for antiphospholipid syndrome (APS; a medium-high anticardiolipin antibody [aCL] titer and/or a positive lupus anticoagulant [LA] test in the presence of vascular thrombosis and/or pregnancy morbidity) were used to confirm the diagnosis. Thrombotic episodes or pregnancy losses before a diagnosis of PAPS were considered events, and any new disease manifestation other than thrombocytopenia was considered a recurrent event. Only patients with objectively verified thrombotic events were included in the study. RESULTS: Twenty-one new thrombotic events were observed in 15 subjects (26.8%), including 3 (5.4%) who died during the follow-up. The patients with IgG aCL levels of >40 IgG phospholipid unit (GPL-U) showed a higher incidence of new thrombotic events (43.3%) than those with levels of < or =40 GPL-U (7.7%). Univariate analysis identified a history of recurrent clinical events (P=0.004), a highly positive aCL titer (P=0.007), and the presence of cardiac abnormalities (P=0.036) as significant risk factors for new thrombotic events. A multivariate regression model confirmed that an IgG aCL titer of >40 GPL-U was an independent risk factor for thrombosis (odds ratio, 9.17; 95% confidence interval, 1.83 to 46.05). CONCLUSIONS: A high IgG aCL titer is the strongest predictor of new thrombotic events in PAPS patients.

Abortion, Spontaneous↗
PubMed2005

Pregnancy and autoimmunity: maternal treatment and maternal disease influence on pregnancy outcome.

If a woman suffers from autoimmune disease (AD), several factors can affect pregnancy or neonatal outcome: repeated spontaneous pregnancy losses (frequently related to antiphospholipid antibodies (aPL)), neonatal lupus with complete congenital heart block (CHB) (linked to transplacental passage of IgG anti Ro/SS-A antibodies) and the disease activity itself that can affect the mother, the pregnancy and fetal outcome. If appropriately managed, the antiphospholipid syndrome (APS) is "one of the few tractable causes of pregnancy losses." A recent case control study, on babies from APS-mothers and healthy mothers, did not show any difference in the occurrence of neonatal complications. There are few data about the long-term outcome of babies born to patients with AD. We recently reported increased occurrence of learning disabilities in children born to aPL positive mothers with systemic lupus erythematosus (SLE). The modern management of pregnancy in patients with AD includes the treatment of disease flares, using drugs effective but safe for fetus. Corticosteroids and some immunosuppressive drugs can be used in pregnancy to control maternal disease. A prolonged fetal exposure to dexamethasone was reported to impair cerebral development, but we recently studied 6 children, born to patients treated with dexamathasone because of CHB, showing a normal intelligence quotient. The last 10-year experience shows that fetal exposure to antimalarial drugs should not be regarded as an important risk factor for gestational nor neonatal complications. However, information about long-term outcome of children exposed to immunosuppressive drugs "in utero" are still lacking and more efforts are needed in this research area.

Autoimmune Diseases↗
PubMed2005

Potential cost-effectiveness of a preventive hepatitis C vaccine in high risk and average risk populations in Canada.

Hepatitis C virus (HCV) vaccine development remains at an early stage. We explored the economic and health consequences of potential HCV vaccines by comparing universal vaccination with a hepatitis C vaccine to no vaccination in two groups: (1) injecting drug users (IDU); (2) all 12 year olds, using a Markov cohort simulation. Among IDUs, vaccination would avert 248 cases of HCV infection and 89 HCV-related deaths per 1000 individuals, and reduce costs. In average risk cohorts, vaccination did not reduce costs but was reasonably cost effective. These results provide encouragement to vaccine developers that a vaccine that is moderately effective and reasonably priced should not face economic barriers to implementation and will be attractive to third party payers.

Canada↗