107 research outputs found

    The HFE p.H63D (p.His63Asp) Polymorphism Is a Modifier of ALS Outcome in Italian and French Patients with SOD1 Mutations

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    Background: Data from published studies about the effect of HFE polymorphisms on ALS risk, phenotype, and survival are still inconclusive. We aimed at evaluating whether the p.H63D polymorphism is a modifier of phenotype and survival in SOD1-mutated patients. Methods: We included 183 SOD1-mutated ALS patients. Mutations were classified as severe or mild according to the median survival of the study population. Patients were screened for the HFE p.H63D polymorphism. Survival was calculated using the Kaplan-Meier modeling, and differences were measured by the log-rank test. Multivariable analysis was performed with the Cox proportional hazards model (stepwise backward). Results: SOD1 severe mutation carriers show more frequent familial history for ALS and shorter survival compared to mild mutation carriers. Carriers and non-carriers of the p.H63D polymorphism did not differ in terms of sex ratio, frequency of positive familial history, age at onset, and bulbar/spinal ratio. In univariate and in Cox multivariable analysis using sex, age at onset, site of onset, family history, country of origin, and mutation severity as covariates, p.H63D carriers had a longer survival (p = 0.034 and p = 0.004). Conclusions: We found that SOD1-mutated ALS patients carrying the p.H63D HFE polymorphism have a longer survival compared to non-carriers, independently of sex, age and site of onset, family history, nation of origin, and severity of mutations, suggesting a possible role as disease progression modifier for the p.H63D HFE polymorphism in SOD1-ALS

    Clinical and laboratory features associated with macrophage activation syndrome in Still's disease : data from the international AIDA Network Still's Disease Registry

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    Abstract: To characterize clinical and laboratory signs of patients with Still's disease experiencing macrophage activation syndrome (MAS) and identify factors associated with MAS development. Patients with Still's disease classified according to internationally accepted criteria were enrolled in the AutoInflammatory Disease Alliance (AIDA) Still's Disease Registry. Clinical and laboratory features observed during the inflammatory attack complicated by MAS were included in univariate and multivariate logistic regression analysis to identify factors associated to MAS development. A total of 414 patients with Still's disease were included; 39 (9.4%) of them developed MAS during clinical history. At univariate analyses, the following variables were significantly associated with MAS: classification of arthritis based on the number of joints involved (p = 0.003), liver involvement (p = 0.04), hepatomegaly (p = 0.02), hepatic failure (p = 0.01), axillary lymphadenopathy (p = 0.04), pneumonia (p = 0.03), acute respiratory distress syndrome (p < 0.001), platelet abnormalities (p < 0.001), high serum ferritin levels (p = 0.009), abnormal liver function tests (p = 0.009), hypoalbuminemia (p = 0.002), increased LDH (p = 0.001), and LDH serum levels (p < 0.001). At multivariate analysis, hepatomegaly (OR 8.7, 95% CI 1.9-52.6, p = 0.007) and monoarthritis (OR 15.8, 95% CI 2.9-97.1, p = 0.001), were directly associated with MAS, while the decade of life at Still's disease onset (OR 0.6, 95% CI 0.4-0.9, p = 0.045), a normal platelet count (OR 0.1, 95% CI 0.01-0.8, p = 0.034) or thrombocytosis (OR 0.01, 95% CI 0.0-0.2, p = 0.008) resulted to be protective. Clinical and laboratory factors associated with MAS development have been identified in a large cohort of patients based on real-life data

    Still's disease continuum from childhood to elderly : data from the international AIDA Network Still's disease registry

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    Abstract: Objective Still's disease is more frequently observed in the paediatric context, but a delayed onset is not exceptional both in the adulthood and in the elderly. However, whether paediatric-onset, adult-onset and elderly-onset Still's disease represent expressions of the same disease continuum or different clinical entities is still a matter of controversy. The aim of this study is to search for any differences in demographic, clinical features and response to treatment between pediatric-onset, adult-onset and elderly-onset Still's disease. Methods Subjects included in this study were drawn from the International AutoInflammatory Disease Alliance Network registry for patients with Still's disease. Results A total of 411 patients suffering from Still's disease were enrolled; the disease occurred in the childhood in 65 (15.8%) patients, in the adult 314 (76.4%) patients and in the elderly in 32 (7.8%) patients. No statistically significant differences at post-hoc analysis were observed in demographic features of the disease between pediatric-onset, adult-onset and elderly-onset Still's disease. The salmon-coloured skin rash (p=0.004), arthritis (p=0.009) and abdominal pain (p=0.007) resulted significantly more frequent among paediatric patients than in adult cases, while pleuritis (p=0.015) and arthralgia (p<0.0001) were significantly more frequent among elderly-onset patients compared with paediatric-onset subjects. Regarding laboratory data, thrombocytosis was significantly more frequent among paediatric patients onset compared with adult-onset subjects (p<0.0001), while thrombocytopenia was more frequent among elderly-onset patients although statistical significance was only bordered. No substantial differences were observed in the response to treatments. Conclusions Despite some minor difference between groups, overall, demographic, clinical, laboratory and treatments aspects of Still's disease were similarly observed in patients at all ages. This supports that pediatric-onset, adult-onset and elderly-onset Still's disease is the same clinical condition arising in different ages

    Fertility in Acromegaly: a single center experience on female patients during active disease and after disease remission

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    Context: Fertility represents a major concern in patients with acromegaly. Objective: Investigation of gonadal function and fertility rate in acromegalic women. Design: Retrospective study. Anthropometric, metabolic, hormonal parameters, and gynaecological ultrasound were evaluated at diagnosis and after disease control. Data about menstrual disturbances, pregnancy, and PCO-morphology (PCOM) were investigated at disease onset, diagnosis and after disease control. Setting: Referral center. Patients: 50 acromegalic women with disease onset within the reproductive age. Intervention: None. Main outcome measures: Prevalence of gonadal dysfunction and infertility. Results: At presumed disease onset, menstrual disturbances were reported in 32% of patients. Uterine leiomyoma, ovarian cysts and PCOM were diagnosed in 18%, 12% and 8%, respectively; 36.8% of patients were infertile. At diagnosis, menstrual disturbances were found in 58.1% (p‚ÄČ=‚ÄČ0.02), being significantly more prevalent in patients with higher IGF-I quartiles (Q) (p‚ÄČ=‚ÄČ0.03, Q1 vs Q4). Gynaecological ultrasound revealed uterine leiomyoma, ovarian cysts and PCOM in 39.1% (p‚ÄČ=‚ÄČ0.04), 28.2% (p‚ÄČ=‚ÄČ0.09), and 13% (p‚ÄČ=‚ÄČ0.55), respectively. The infertility rate was 100% (p‚ÄČ=‚ÄČ0.02). At disease control, menstrual disturbances (p‚ÄČ=‚ÄČ0.05), particularly amenorrhea (p‚ÄČ=‚ÄČ0.03), significantly persisted in patients with disease duration above than in those with disease duration below 5 years (median). Among patients with pregnancy desire, 73.3% conceived at least once, resulting infertility significantly decreased compared to diagnosis (26.7%, p‚ÄČ=‚ÄČ0.01). At-term, pre-term deliveries and spontaneous abortions were recorded in 86.7%, 3.3% and 10%, respectively. No neonatal malformations and/or abnormalities were recorded. Conclusions: Gonadal dysfunction and infertility are common in acromegalic women within the reproductive age, being directly influenced by the disease status and/or duration

    Clinical and laboratory features associated with macrophage activation syndrome in Still's disease: data from the international AIDA Network Still's Disease Registry

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    : To characterize clinical and laboratory signs of patients with still's disease experiencing macrophage activation syndrome (MAS) and identify factors associated with MAS development. patients with still's disease classified according to internationally accepted criteria were enrolled in the autoInflammatory disease alliance (AIDA) still's disease registry. clinical and laboratory features observed during the inflammatory attack complicated by MAS were included in univariate and multivariate logistic regression analysis to identify factors associated to MAS development. A total of 414 patients with Still's disease were included; 39 (9.4%) of them developed MAS during clinical history. At univariate analyses, the following variables were significantly associated with MAS: classification of arthritis based on the number of joints involved (p‚ÄČ=‚ÄČ0.003), liver involvement (p‚ÄČ=‚ÄČ0.04), hepatomegaly (p‚ÄČ=‚ÄČ0.02), hepatic failure (p‚ÄČ=‚ÄČ0.01), axillary lymphadenopathy (p‚ÄČ=‚ÄČ0.04), pneumonia (p‚ÄČ=‚ÄČ0.03), acute respiratory distress syndrome (p‚ÄČ&lt;‚ÄČ0.001), platelet abnormalities (p‚ÄČ&lt;‚ÄČ0.001), high serum ferritin levels (p‚ÄČ=‚ÄČ0.009), abnormal liver function tests (p‚ÄČ=‚ÄČ0.009), hypoalbuminemia (p‚ÄČ=‚ÄČ0.002), increased LDH (p‚ÄČ=‚ÄČ0.001), and LDH serum levels (p‚ÄČ&lt;‚ÄČ0.001). at multivariate analysis, hepatomegaly (OR 8.7, 95% CI 1.9-52.6, p‚ÄČ=‚ÄČ0.007) and monoarthritis (OR 15.8, 95% CI 2.9-97.1, p‚ÄČ=‚ÄČ0.001), were directly associated with MAS, while the decade of life at Still's disease onset (OR 0.6, 95% CI 0.4-0.9, p‚ÄČ=‚ÄČ0.045), a normal platelet count (OR 0.1, 95% CI 0.01-0.8, p‚ÄČ=‚ÄČ0.034) or thrombocytosis (OR 0.01, 95% CI 0.0-0.2, p‚ÄČ=‚ÄČ0.008) resulted to be protective. clinical and laboratory factors associated with MAS development have been identified in a large cohort of patients based on real-life data

    Clinical and laboratory features associated with macrophage activation syndrome in Still's disease: data from the international AIDA Network Still's Disease Registry (vol 18, pg 2231, 2023)

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    Development and Implementation of the AIDA International Registry for Patients with Non-Infectious Uveitis

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    Introduction: The aim of this paper is to point out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry for paediatric and adult patients with non-infectious uveitis (NIU). Methods: This is a physician-driven, population- and electronic-based registry implemented for both retrospective and prospective collection of real-world demographics, clinical, laboratory, instrumental and socioeconomic data of patients with uveitis and other non-infectious inflammatory ocular diseases recruited through the AIDA Network. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is thought to collect standardised information for real-life research and has been developed to change over time according to future scientific acquisitions and potentially communicate with other similar instruments. Security, data quality and data governance are cornerstones of this platform. Results: Ninety-five centres have been involved from 19 countries and four continents from 24&nbsp;March to 16&nbsp;November 2021. Forty-eight out of 95 have already obtained the approval from their local ethics committees. At present, the platform counts 259 users (95 principal investigators, 160 site investigators, 2 lead investigators, and 2 data managers). The AIDA Registry collects baseline and follow-up data using 3943 fields organised into 13 instruments, including patient's demographics, history, symptoms, trigger/risk factors, therapies and healthcare utilization for patients with NIU. Conclusions: The development of the AIDA Registry for patients with NIU will facilitate the collection of standardised data leading to real-world evidence and enabling international multicentre collaborative research through inclusion of patients and their families worldwide

    IL10 Secretion Endows Intestinal Human iNKT Cells with Regulatory Functions Towards Pathogenic T Lymphocytes

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    Background and aims: Invariant natural killer T [iNKT] cells perform pleiotropic functions in different tissues by secreting a vast array of pro-inflammatory and cytotoxic molecules. However, the presence and function of human intestinal iNKT cells capable of secreting immunomodulatory molecules such as IL-10 has never been reported so far. Here we describe for the first time the presence of IL10-producing iNKT cells [NKT10 cells] in the intestinal lamina propria of healthy individuals and of Crohn's disease [CD] patients. Methods: Frequency and phenotype of NKT10 cells were analysed ex vivo from intestinal specimens of Crohn's disease [n = 17] and controls [n = 7]. Stable CD-derived intestinal NKT10 cell lines were used to perform in vitro suppression assays and co-cultures with patient-derived mucosa-associated microbiota. Experimental colitis models were performed by adoptive cell transfer of splenic na√Įve CD4+ T cells in the presence or absence of IL10-sufficient or -deficient iNKT cells. In vivo induction of NKT10 cells was performed by administration of short chain fatty acids [SCFA] by oral gavage. Results: Patient-derived intestinal NKT10 cells demonstrated suppressive capabilities towards pathogenic CD4+ T cells. The presence of increased proportions of mucosal NKT10 cells associated with better clinical outcomes in CD patients. Moreover, an intestinal microbial community enriched in SCFA-producing bacteria sustained the production of IL10 by iNKT cells. Finally, IL10-deficient iNKT cells failed to control the pathogenic activity of adoptively transferred CD4+ T cells in an experimental colitis model. Conclusions: These results describe an unprecedentd IL10-mediated immunoregulatory role of intestinal iNKT cells in controlling the pathogenic functions of mucosal T helper subsets and in maintaining the intestinal immune homeostasis

    Sex-related differences in patients with coronavirus disease 2019: results of the Cardio-COVID-Italy multicentre study

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    Introduction: The role of sex compared to comorbidities and other prognostic variables in patients with coronavirus disease (COVID-19) is unclear. Methods: This is a retrospective observational study on patients with COVID-19 infection, referred to 13 cardiology units. The primary objective was to assess the difference in risk of death between the sexes. The secondary objective was to explore sex-based heterogeneity in the association between demographic, clinical and laboratory variables, and patients' risk of death. Results: Seven hundred and one patients were included: 214 (30.5%) women and 487 (69.5%) men. During a median follow-up of 15‚Äädays, deaths occurred in 39 (18.2%) women and 126 (25.9%) men. In a multivariable Cox regression model, men had a nonsignificantly higher risk of death vs. women (P = 0.07).The risk of death was more than double in men with a low lymphocytes count as compared with men with a high lymphocytes count [overall survival hazard ratio (OS-HR) 2.56, 95% confidence interval (CI) 1.72-3.81]. In contrast, lymphocytes count was not related to death in women (P‚Ää=‚Ää0.03).Platelets count was associated with better outcome in men (OS-HR for increase of 50‚Ää√ó‚Ää103 units: 0.88 95% CI 0.78-1.00) but not in women. The strength of association between higher PaO2/FiO2 ratio and lower risk of death was larger in women (OS-HR for increase of 50‚ÄämmHg/%: 0.72, 95% CI 0.59-0.89) vs. men (OS-HR: 0.88, 95% CI 0.80-0.98; P‚Ää=‚Ää0.05). Conclusions: Patients' sex is a relevant variable that should be taken into account when evaluating risk of death from COVID-19. There is a sex-based heterogeneity in the association between baseline variables and patients' risk of death

    Adult-onset Still's disease with elderly onset, results from a multicentre study

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    Objectives: In this study, we aimed at describing the clinical characteristics, life-threatening complications occurrence, and mortality of adult-onset Still's disease (AOSD) patients with elderly onset. Methods: A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was performed. Results: Out of 221 assessed patients, 37 (16.7%) had an onset of the disease aged over 60 years. When compared with younger patients, these were characterised by a higher prevalence of pericarditis (p=0.008), comorbidities (p<0.0001), and mortality (p=0.023). Age predicted the presence of serositis in both univariate (HR: 1.02, 95%CI: 1.01-1.03, p=0.007) and multivariate analyses (HR: 1.02, 95%CI: 1.01-1.04, p=0.007). Age was also a significant predictor of parenchymal lung disease in both univariate (HR: 1.03, 95%CI: 1.01-1.05, p=0.017) and multivariate analyses (HR: 1.03, 95%CI: 1.00-1.05, p=0.048). Furthermore, age resulted to be a negative predictor of polycyclic pattern only in univariate analysis (HR: 0.99, 95%CI: 0.97-1.00, p=0.048). Finally, age significantly predicted the mortality in both univariate (HR: 1.03, 95%CI: 1.00-1.06, p=0.034) and multivariate analyses (HR: 1.05, 95%CI: 1.01-1.08, p=0.012). Conclusions: Clinical features of AOSD patients in elderly were described in our cohort. Although the main clinical characteristics were similar comparing older and younger patients, patients aged over 60 years at disease onset were characterised by an increased prevalence of serositis, comorbidities, mostly cardiometabolic, and a higher mortality rate. Age predicted the presence of parenchymal lung disease and mortality, and it could be considered a negative prognostic factor in AOSD
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