Autosomal-dominant spinocerebellar ataxia (ADCA) due to intronic GAA repeat expansion in FGF14 (SCA27B) is a recent, relatively common form of late-onset ataxia.BACKGROUNDAutosomal-dominant ...spinocerebellar ataxia (ADCA) due to intronic GAA repeat expansion in FGF14 (SCA27B) is a recent, relatively common form of late-onset ataxia.Here, we aimed to: (1) investigate the relative frequency of SCA27B in different clinically defined disease subgroups with late-onset ataxia collected among 16 tertiary Italian centers; (2) characterize phenotype and diagnostic findings of patients with SCA27B; (3) compare the Italian cohort with other cohorts reported in recent studies.OBJECTIVEHere, we aimed to: (1) investigate the relative frequency of SCA27B in different clinically defined disease subgroups with late-onset ataxia collected among 16 tertiary Italian centers; (2) characterize phenotype and diagnostic findings of patients with SCA27B; (3) compare the Italian cohort with other cohorts reported in recent studies.We screened 396 clinically diagnosed late-onset cerebellar ataxias of unknown cause, subdivided in sporadic cerebellar ataxia, ADCA, and multisystem atrophy cerebellar type. We identified 72 new genetically defined subjects with SCA27B. Then, we analyzed the clinical, neurophysiological, and imaging features of 64 symptomatic cases.METHODSWe screened 396 clinically diagnosed late-onset cerebellar ataxias of unknown cause, subdivided in sporadic cerebellar ataxia, ADCA, and multisystem atrophy cerebellar type. We identified 72 new genetically defined subjects with SCA27B. Then, we analyzed the clinical, neurophysiological, and imaging features of 64 symptomatic cases.In our cohort, the prevalence of SCA27B was 13.4% (53/396) with as high as 38.5% (22/57) in ADCA. The median age of onset of SCA27B patients was 62 years. All symptomatic individuals showed evidence of impaired balance and gait; cerebellar ocular motor signs were also frequent. Episodic manifestations at onset occurred in 31% of patients. Extrapyramidal features (17%) and cognitive impairment (25%) were also reported. Brain magnetic resonance imaging showed cerebellar atrophy in most cases (78%). Pseudo-longitudinal assessments indicated slow progression of ataxia and minimal functional impairment.RESULTSIn our cohort, the prevalence of SCA27B was 13.4% (53/396) with as high as 38.5% (22/57) in ADCA. The median age of onset of SCA27B patients was 62 years. All symptomatic individuals showed evidence of impaired balance and gait; cerebellar ocular motor signs were also frequent. Episodic manifestations at onset occurred in 31% of patients. Extrapyramidal features (17%) and cognitive impairment (25%) were also reported. Brain magnetic resonance imaging showed cerebellar atrophy in most cases (78%). Pseudo-longitudinal assessments indicated slow progression of ataxia and minimal functional impairment.Patients with SCA27B in Italy present as an adult-onset, slowly progressive cerebellar ataxia with predominant axial involvement and frequent cerebellar ocular motor signs. The high consistency of clinical features in SCA27B cohorts in multiple populations paves the way toward large-scale, multicenter studies.CONCLUSIONPatients with SCA27B in Italy present as an adult-onset, slowly progressive cerebellar ataxia with predominant axial involvement and frequent cerebellar ocular motor signs. The high consistency of clinical features in SCA27B cohorts in multiple populations paves the way toward large-scale, multicenter studies.
Adipose tissue is an attractive source of stem cells due to its wide availability. They contribute to the stromal vascular fraction (SVF), which is composed of pre-adipocytes, tissue-progenitors, and ...pericytes, among others. Because its direct use in medical applications is increasing worldwide, new quality control systems are required. We investigated the ability of the Non-Equilibrium Earth Gravity Assisted Dynamic Fractionation (NEEGA-DF) method to analyze and separate cells based solely on their physical characteristics, resulting in a fingerprint of the biological sample. Adipose tissue was enzymatically digested, and the SVF was analyzed by NEEGA-DF. Based on the fractogram (the UV signal of eluting cells versus time of analysis) the collection time was set to sort alive cells. The collected cells (F-SVF) were analyzed for their phenotype, immunomodulation ability, and differentiation potential. The SVF profile showed reproducibility, and the alive cells were collected. The F-SVF showed intact adhesion phenotype, proliferation, and differentiation potential. The methodology allowed enrichment of the mesenchymal component with a higher expression of mesenchymal markers and depletion of debris, RBCs, and an extracellular matrix still present in the digestive product. Moreover, cells eluting in the last minutes showed higher circularity and lower area, proving the principles of enrichment of a more homogenous cell population with better characteristics. We proved the NEEGA-DF method is a "gentle" cell sorter that purifies primary cells obtained by enzymatic digestion and does not alter any stem cell function.
Objective
We aimed to investigate the impact of applying the 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for ...systemic lupus erythematosus (SLE) in a previously described cohort of women with undifferentiated connective tissue disease (UCTD).
Methods
This study included 133 women with UCTD. At the time of inclusion into the study, none of the patients met any classification criteria for other defined systemic connective tissue disease.
Results
When applying the 2019 EULAR/ACR classification criteria to the cohort, 22 patients (17%) fulfilled the classification criteria for SLE. Patients classified as having SLE had significantly higher frequencies of mucocutaneous manifestations (23% versus 5%; P = 0.007), arthritis (59% versus 17%; P < 0.001), isolated urine abnormalities (18% versus 1%; P < 0.001), and highly specific antibodies (50% versus 15%; P < 0.001) compared to the other patients with UCTD. At follow‐up, these patients were statistically significantly more likely to also meet the 1997 ACR revised SLE criteria and the Systemic Lupus International Collaborating Clinics (SLICC) criteria (18.2% versus 1.8%; P < 0.001) compared to the other UCTD patients.
Patients who were diagnosed as having SLE according to the ACR 1997 update of the SLE revised criteria and the SLICC criteria during the follow‐up scored higher on outcome measures when classified as having SLE according to the new 2019 EULAR/ACR classification criteria when compared to the other patients with UCTD (mean ± SD score 8.3 ± 3.7 versus 4.5 ± 4; P < 0.05).
Conclusion
When applying the 2019 EULAR/ACR criteria for SLE in a cohort of patients with UCTD, we observed that in up to 17% of cases the original classification could be challenged. New implementation will help to identify earlier patients at higher risk of developing more severe CTD manifestations.
ObjectivesTo investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it.MethodsPregnant women with different ARD were enrolled ...for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018–2023). Maternal and infant information were collected in a web-based database.ResultsWe analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress.ConclusionsMultiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.
BACKGROUND
Autologous blood transfusion (ABT) is a performance‐enhancing method prohibited in sport; its detection is a key issue in the field of anti‐doping. Among novel markers enabling ABT ...detection, microRNAs (miRNAs) might be considered a promising analytical tool.
STUDY DESIGN AND METHODS
We studied the changes of erythroid‐related microRNAs following ABT, to identify novel biomarkers. Fifteen healthy trained males were studied from a population of 24 subjects, enrolled and randomized into a Transfusion (T) and a Control (C) group. Seriated blood samples were obtained in the T group before and after the two ABT procedures (withdrawal, with blood refrigerated or cryopreserved, and reinfusion), and in the C group at the same time points. Traditional hematological parameters were assessed. Samples were tested by microarray analysis of a pre‐identified set of erythroid‐related miRNAs.
RESULTS
Hematological parameters showed moderate changes only in the T group, particularly following blood withdrawal. Among erythroid‐related miRNAs tested, following ABT a pool of 7 miRNAs associated with fetal hemoglobin and regulating transcriptional repressors of gamma‐globin gene was found stable in C and differently expressed in three out of six T subjects in the completed phase of ABT, independently from blood conservation. Particularly, two or more erythropoiesis‐related miRNAs within the shortlist constituted of miR‐126‐3p, miR‐144‐3p, miR‐191‐3p, miR‐197‐3p, miR‐486‐3p, miR‐486‐5p, and miR‐92a‐3p were significantly upregulated in T subjects after reinfusion, with a person‐to‐person variability but with congruent changes.
CONCLUSIONS
This study describes a signature of potential interest for ABT detection in sports, based on the analysis of miRNAs associated with erythroid features.
ObjectiveIt is still a matter of debate whether low-dose acetylsalicylic acid (LDASA) should be prescribed to all patients with SLE during pregnancy. This study aimed at investigating the impact of ...LDASA on pregnancy outcomes in patients with SLE without history of renal involvement and without antiphospholipid antibodies (aPL).MethodsThis is a retrospective analysis of prospectively monitored pregnancies at seven rheumatology centres. Previous/current renal involvement and aPL positivity were the exclusion criteria. Adverse pregnancy outcome (APO) is the composite outcome of the study and included proteinuric pre-eclampsia, preterm delivery <37 weeks, small-for-gestational age infant, low birth weight <2500 g, intrauterine growth restriction and intrauterine fetal death after 12 weeks of gestation of a morphologically normal fetus.Results216 pregnancies in 187 patients were included; 82 pregnancies (38.0%) were exposed to LDASA treatment. No differences in terms of age at conception, disease duration, clinical manifestations, comorbidities and disease flare during pregnancy were observed between patients taking LDASA and those who did not take LDASA during pregnancy. APO was observed in 65 cases (30.1%), including 13 cases (6.1%) of pre-eclampsia. The incidence of all complications was similar in the two groups. However, it is interesting to note that pre-eclampsia had lower frequency in patients taking LDASA versus those not taking LDASA (2.4% vs 8.3%, p=0.14).ConclusionsIn pregnant patients with SLE without renal involvement and were aPL-negative, there is a low risk of severe obstetric complications, such as early pre-eclampsia. LDASA treatment does not provide a statistically significant advantage over these complications. However, a careful individual risk–benefit balance is warranted.
The objectives of this study were to present data on the presence of Salmonella enterica subsp. enterica and on the enumeration of Escherichia coli and faecal coliforms respectively in different ...species of bivalve molluscs and seawater and to conduct a retrospective evaluation to assess the capacity of E. coli in molluscs and faecal coliforms and S. enterica subsp. enterica in sea and brackish water to predict the presence of S. enterica subsp. enterica in bivalve molluscs, and therefore, the risk of exposure for consumers. Data were collected from 4972 seawater samples and 5785 live bivalve molluscs samples (2877 Ruditapes philippinarum, 2177 Mytilus galloprovincialis, 256 Chamelae gallina and 475 C. gigas and O. edulis) collected in the molluscs production area of Ferrara, Northern Italy, from 1997 to 2015. An overall S. enterica subsp. enterica occurrence of 2.2% was reported in water and molluscs, with percentages varying depending on the type of sample and on the classification areas. All the 237 Salmonella strains were identified as genus Salmonella and a total of 53 different serovars were observed. Significant associations between the fecal indicators and presence of S. enterica subsp. enterica were observed both applying EU and USA criteria, but, it should be noted that the EU approach seems to be more stringent achieving the goal of identifying the most critical batches (94 out of the 100) whereas, following the USA approach, a not negligible and higher number of batches compliant for faecal coliforms but contaminated by S. enterica subsp. enterica has to be mentioned. In any case, the faecal indicators E. coli in molluscs and faecal coliforms in seawaters reflect only in part the presence of S. enterica subsp. enterica in molluscs and the consequent potential risk for consumers. Microbiological evaluation of seawaters seems to have a minor impact into the prediction of S. enterica subsp. enterica presence in molluscs.
•The presence of Salmonella in 10 757 molluscs and water samples was presented.•An higher Salmonella prevalence in R. philippinarum has been observed.•Faecal indicators reflected only in part the presence of Salmonella in molluscs.•Seawaters’ analysis seems to not adequately predict Salmonella presence in molluscs.
Alveolar haemorrhage (AH) is considered an important cause of morbidity and early mortality in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV).
The aim of this study was ...to identify predictors of outcome in patients with AH-AAV and to evaluate outcome and causes of death in this subset.
A multicenter retrospective study was conducted in 29 Italian Centers. Clinicians were asked to recruit all patients diagnosed with AAV-associated AH during the last 10 years, from 2007 to 2016. Univariate and multivariable analysis were performed.
One-hundred and six patients were included (median age at onset of 55 years IQR 42–67). The majority were ANCA-positive (PR3 57.1%, MPO 33.7%) and 72.6% had also renal involvement. At presentation, anaemia was shown in 97 (92.4%) patients, hemoptysis in 54 (51.9%), respiratory failure in 68 (66.7%), of whom 48 (70.6%), requiring respiratory support. At the end of the 37 months IQR 13–77 follow-up, 19/106 (17.9%) patients were dead. The main causes of death were active disease and infections. By stepwise regression analysis, age >65 years (HR 3.66 95% CI 1.4–9.51, p = 0.008) and the need for respiratory support (HR 4.58 95% CI 1.51–13.87, p = 0.007) at AH onset were confirmed to be predictive of mortality.
Predictors of outcome in AAV-AH were determined. Factors related to the patient's performance status and the severity of the lung involvement strongly influenced the outcome. Balancing harms and benefits for the individual patient in induction and maintenance treatment strategies is crucial.
•This is the largest clinical description of alveolar haemorrhage in ANCA-associated vasculitis.•Unexplained progressive anaemia in AAV should arise the suspicion of AH in AAV.•Consider respiratory failure, age and cardiovascular comorbidity to manage AH in AAV in the short and long term.
Abstract Genetic and environmental factors contribute to disease Multiple Sclerosis (MS) susceptibility, the most prevalent neurological pathology affecting young individuals in Western countries. We ...focused our attention on HSP70-2, an inducible chaperon induced under stress conditions. Genotype analysis of HSP70-2 (+ 1267 A/G) polymorphism revealed a significant association between the minor allele G and presence of MS (OR:1.31, 95% CI: 1.02–1.69, P = 0.039). In addition, Hsp70-2 protein content in vitro from PBMC was significantly lower in MS patients with GG genotype compared to AA genotype, indicating an implication of the G allele of HSP70-2 gene polymorphism in the development of MS.
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