Ankylosing spondylitis is associated with increased prevalence of valvular heart diseases: a cross-sectional population-based study.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory arthritis primarily affecting the sacroiliac joint and axial skeleton with associated extra-articular involvement including cardiovascular system disease including aortic valve disease with variable reported prevalence. The aim of this study is to determine the prevalence of heart valve disorders in AS patients. METHODS: This was a retrospective, population-based, cross-sectional study that retrieved data from the Clalit Health Services registry. Cases were defined as having AS, whereas controls were frequency matched by age and sex in a ratio of 5:1. The prevalence of valvular heart diseases was compared between the two groups; a multivariate logistic regression model was applied to estimate the association after controlling for potential confounders. RESULTS: We included 4082 AS patients and 20 397 controls frequency matched by age and sex. AS patients had a significantly higher prevalence of cardiovascular risk factors (P < .001) and a higher prevalence of valvular heart disease. In the multivariate logistic regression model, adjusting for multiple confounding factors, AS was independently associated with aortic stenosis [odds ratio (OR): 2.25, 95% confidence interval (CI): 1.57-3.23, P < 0.001], aortic insufficiency (OR: 2.44, 95% CI: 1.50-3.94, P < 0.001), and mitral insufficiency (OR: 1.75, 95% CI: 1.17-2.61, P < 0.001) but not mitral stenosis (OR: 1.31, 95% CI: 0.60-2.70, P = 0.47). CONCLUSIONS: Our study reports the increased risk of valvular heart diseases in patients with AS, possibly due to the inflammatory milieu associated with the disease process and the result of biomechanical stress affecting the enthesis-like valvular structures.

Vascular Reactivity of Adult-Onset Systemic Lupus Erythematosus Patients.

BACKGROUND: Cardiovascular disease (CVD) is more frequent in patients with systemic lupus erythematosus (SLE) compared with age- and sex-matched healthy subjects. SLE is an autoimmune disease that is more prevalent in women (9:1). Women tend to develop CVD in post-menopausal years; however, women with SLE may develop endothelial dysfunction and CVD at a younger age in the pre-menopausal years. OBJECTIVES: To study the endothelial function of adult-onset SLE patients from the north of Israel (the Galilee region) and to determine whether modern management (including biological treatments) changes the risk of developing CVD. METHODS: Thirteen females with adult-onset SLE without renal involvement were recruited to this prospective study. Clinical parameters (age, height, body mass index [BMI]), laboratory parameters (C-reactive protein [CRP] and hemoglobin level), and vascular responsiveness (flow mediated diameter percent change [FMD%]) were evaluated and compared to 11 age-matched healthy females. Student's t-test was used to find differences between the two groups. RESULTS: No difference was observed in adult-onset SLE female patients and their age- and sex-matched controls with regard to age (42.1 ± 11.8 years vs. 36.6 ± 10.8 years, P = NS), BMI (25 ± 1.8 kg/m2 vs. 25 ± 2.5 kg/m2, P = NS), and hemoglobin level (11.9 ± 0.9 gr% vs. 12.7 ± 1.2 gr%, P = NS). However, a significant difference was found in CRP (2.57 ± 2.2 mg vs. 0.60 ± 0.37 mg, P = 0.001), vascular responsiveness (0.94 ± 6.6 FMD% vs. 9.2 ± 8.1 FMD%, P = 0.012), and height (165.7 ± 4.5 cm vs. 171.6 ± 5.8 cm, P = 0.009). CONCLUSIONS: Adult-onset SLE females had impaired endothelial function even though they were treated by modern protocols.

Rheumatoid Arthritis and Atherosclerosis.

BACKGROUND: Inflammation is the basic mechanism leading to many pathological processes, including degenerative diseases, atherosclerosis, and cancer. We found an interesting link connecting rheumatoid arthritis and atherosclerosis that may explain the high cardiovascular event rate among patients with rheumatoid arthritis, but also may lead to a new way of thinking and a better understanding of atherosclerosis. Rheumatoid arthritis could serve as a model of accelerated atherosclerosis. Understanding the basic mechanisms of rheumatoid arthritis may solve some of the complexity of atherosclerosis.

Leveraging Google Trends, Twitter, and Wikipedia to Investigate the Impact of a Celebrity's Death From Rheumatoid Arthritis.

BACKGROUND: Technological advancements, such as patient-centered smartphone applications, have enabled to support self-management of the disease. Further, the accessibility to health information through the Internet has grown tremendously. This article aimed to investigate how big data can be useful to assess the impact of a celebrity's rheumatic disease on the public opinion. METHODS: Variable tools and statistical/computational approaches have been used, including massive data mining of Google Trends, Wikipedia, Twitter, and big data analytics. These tools were mined using an in-house script, which facilitated the process of data collection, parsing, handling, processing, and normalization. RESULTS: From Google Trends, the temporal correlation between "Anna Marchesini" and rheumatoid arthritis (RA) queries resulted 0.66 before Anna Marchesini's death and 0.90 after Anna Marchesini's death. The geospatial correlation between "Anna Marchesini" and RA queries resulted 0.45 before Anna Marchesini's death and 0.52 after Anna Marchesini's death. From Wikitrends, after Anna Marchesini's death, the number of accesses to Wikipedia page for RA has increased 5770%. From Twitter, 1979 tweets have been retrieved. Numbers of likes, retweets, and hashtags have increased throughout time. CONCLUSIONS: Novel data streams and big data analytics are effective to assess the impact of a disease in a famous person on the laypeople.

Seasonality and autoimmune diseases: The contribution of the four seasons to the mosaic of autoimmunity.

Autoimmune diseases (ADs) are a heterogeneous groups of diseases that occur as a results of loss of tolerance to self antigens. While the etiopathogeneis remain obscure, different environmental factors were suggested to have a role in the development of autoimmunity, including infections, low vitamin D levels, UV radiation, and melatonin. Interestingly, such factors possess seasonal variation patterns that could influence disease development, severity and progression. Vitamin D levels which reach a nadir during late winter and early spring is correlated with increased disease activity, clinical severity as well as relapse rates in several disease entities including multiple sclerosis (MS), non-cutaneous flares of systemic lupus erythematosus (SLE), psoriasis, and rheumatoid arthritis (RA). Additionally, immunomodulatory actions of melatonin secretion ameliorate the severity of several ADs including MS and SLE. Melatonin levels are lowest during spring, a finding that correlates with the highest exacerbation rates of MS. Further, melatonin is postulated to be involved in the etiopathogenesis of inflammatory bowel diseases (IBD) through it influence on adhesion molecule and therefore transcription factor expression. Moreover, infections can mount to ADs through pro-inflammatory cytokine release and human antigen mimicry. Seasonal patterns of infectious diseases are correlated with the onset and exacerbation of ADs. During the winter, increased incidence of Epstein-Barr virus (EBV) infectious are associated with MS and SLE flares/onset respectively. In addition, higher Rotavirus infections during the winter precedes type 1 diabetes mellitus onset (T1DM). Moreover, Escherichia coli (E. coli) infection prior to primary biliary cirrhosis (PBC) and T1DM disease onset subsequent to Coxachievirus infections are seen to occur during late summer, a finding that correlate with infectious agents' pattern of seasonality. In this review, the effects of seasonality on the onset, relapses and activity of various ADs were discussed. Consideration of seasonal variation patterns of ADs can possibly provide clues to diseases pathogenesis and lead to development of new approaches in treatment and preventative care.

On status epilepticus and pins: A systematic content analysis.

Status epilepticus (SE) can be defined as abnormally prolonged, persistent, or recurrent clinical and/or electrographic epileptic activity and, as such, is a challenging medical emergency requiring an aggressive treatment aimed at promptly terminating the seizures. It imposes a relevant clinical burden, both in terms of comorbidity and mortality. In the era of the Web 2.0, most people search the Web to obtain SE-related information. The current investigation aimed at qualitatively characterizing the pins related to SE: Pinterest, "the world's catalog of ideas", is a visual social networking site that enables users to freely upload visual material, to bookmark, and to share it (repin). Using SE as a keyword, 192 pins were extracted and analyzed on the basis of their content. Fifty-five were found to meet the inclusion criteria. Fifty-six point four percent of the pins reported at least one cause of SE, the most quoted of which being remote brain injuries (47.3% of the pins); 54.5% and 45.5% of the included pins reported SE symptoms and diagnosis, respectively; 72.7% and 40.0% of pins focused on SE treatment and on prognosis, respectively; and 50.9%, 30.9%, and 40.0% of the pins were intended for physicians, medical/nursing students, and lay people, respectively. Only 12.7% of pins were patient-centered and devoted to fund-raising and advocacy. In the field of neurological diseases, Pinterest, despite being a "pinstructive" tool, is too much overlooked and underused for advocacy purposes. Healthcare workers and stakeholders should be aware of the opportunities offered by Pinterest and exploit this visual social networking site for raising awareness of the life-threatening condition of SE, promoting fund-raising campaigns.

Autoimmunity in the Elderly: Insights from Basic Science and Clinics - A Mini-Review.

Advancements in the field of biomedicine, including the control of infectious diseases through antibiotics and vaccination practices and the prevention of chronic disorders, have led to reduced mortality, increased life expectancy and, as such, growth of the older population. Ageing is accompanied by profound morphological and physiological alterations. In particular, the immune system undergoes a complex series of remodeling/restructuring events, involving almost all compartments - both the innate and the adaptive system. This process is termed immunosenescence or immune dysregulation and, basically, includes 3 events: a reduction in immune response, an increase in the inflammatory and oxidation background (inflammaging and oxi-inflammaging), and a production of autoantibodies. While there is an increase in autoimmunity in the elderly, this does not always translate into an increase in autoimmune diseases, which represent an important cause of morbidity and mortality and affect 5-10% of the world population. Each disease involves a specific age group. Generally speaking, most autoimmune diseases have a decreased peak age of onset, except for very few diseases such as giant cell arteritis and primary biliary cirrhosis, which are more prevalent among the elderly, or inflammatory bowel disease, which has 2 peaks of onset, the first one in young subjects and the other in those older than 60 years. Autoimmune disorders in the elderly have unique clinical presentations, and insidious and atypical symptoms may constitute a challenge for the physician. They are generally milder than in adults and can be controlled by a proper therapeutic treatment. However, despite advancements both in basic and clinical sciences, further studies and investigations are warranted and should be carried out in order to dissect the molecular framework induced by ageing.

Readability of Wikipedia Pages on Autoimmune Disorders: Systematic Quantitative Assessment.

BACKGROUND: In the era of new information and communication technologies, the Internet is being increasingly accessed for health-related information. Indeed, recently published patient surveys of people with autoimmune disorders confirmed that the Internet was reported as one of the most important health information sources. Wikipedia, a free online encyclopedia launched in 2001, is generally one of the most visited websites worldwide and is often consulted for health-related information. OBJECTIVE: The main objective of this investigation was to quantitatively assess whether the Wikipedia pages related to autoimmune disorders can be easily accessed by patients and their families, in terms of readability. METHODS: We obtained and downloaded a list of autoimmune disorders from the American Autoimmune Related Diseases Association (AARDA) website. We analyzed Wikipedia articles for their overall level of readability with 6 different quantitative readability scales: (1) the Flesch Reading Ease, (2) the Gunning Fog Index, (3) the Coleman-Liau Index, (4) the Flesch-Kincaid Grade Level, (5) the Automated Readability Index (ARI), and (6) the Simple Measure of Gobbledygook (SMOG). Further, we investigated the correlation between readability and clinical, pathological, and epidemiological parameters. Moreover, each Wikipedia analysis was assessed according to its content, breaking down the readability indices by main topic of each part (namely, pathogenesis, treatment, diagnosis, and prognosis plus a section containing paragraphs not falling into any of the previous categories). RESULTS: We retrieved 134 diseases from the AARDA website. The Flesch Reading Ease yielded a mean score of 24.34 (SD 10.73), indicating that the sites were very difficult to read and best understood by university graduates, while mean Gunning Fog Index and ARI scores were 16.87 (SD 2.03) and 14.06 (SD 2.12), respectively. The Coleman-Liau Index and the Flesch-Kincaid Grade Level yielded mean scores of 14.48 (SD 1.57) and 14.86 (1.95), respectively, while the mean SMOG score was 15.38 (SD 1.37). All the readability indices confirmed that the sites were suitable for a university graduate reading level. We found no correlation between readability and clinical, pathological, and epidemiological parameters. Differences among the different sections of the Wikipedia pages were statistically significant. CONCLUSIONS: Wikipedia pages related to autoimmune disorders are characterized by a low level of readability. The onus is, therefore, on physicians and health authorities to improve the health literacy skills of patients and their families and to create, together with patients themselves, disease-specific readable sites, disseminating highly accessible health-related online information, in terms of both clarity and conciseness.

Artificial neural networks can be effectively used to model changes of intracranial pressure (ICP) during spinal surgery using different noninvasive ICP surrogate estimators.

BACKGROUND: Artificial intelligence (AI) techniques play a major role in anesthesiology, even though their importance is often overlooked. In the extant literature, AI approaches, such as artificial neural networks (ANNs), have been underutilized, being used mainly to model patient's consciousness state, to predict the precise number of anesthetic gases, the level of analgesia, or the need of anesthesiological blocks, among others. In the field of neurosurgery, ANNs have been effectively applied to the diagnosis and prognosis of cerebral tumors, seizures, low back pain, and also to the monitoring of intracranial pressure (ICP). METHODS: A multilayer perceptron (MLP), which is a feedforward ANN, with hyperbolic tangent as activation function in the input/hidden layers, softmax as activation function in the output layer, and cross-entropy as error function, was used to model the impact of prone versus supine position and the use of positive end expiratory pressure (PEEP) on ICP in a sample of 30 patients undergoing spinal surgery. Different noninvasive surrogate estimations of ICP have been used and compared: namely, mean optic nerve sheath diameter (ONSD), noninvasive estimated cerebral perfusion pressure (NCPP), Pulsatility Index (PI), ICP derived from PI (ICP-PI), and flow velocity diastolic formula (FVDICP). RESULTS: ONSD proved to be a more robust surrogate estimation of ICP, with a predictive power of 75%, whilst the power of NCPP, ICP-PI, PI, and FVDICP were 60.5%, 54.8%, 53.1%, and 47.7%, respectively. CONCLUSIONS: Our MLP analysis confirmed our findings previously obtained with regression, correlation, multivariate receiving operator curve (multi-ROC) analyses. ANNs can be successfully used to predict the effects of prone versus supine position and PEEP on ICP in patients undergoing spinal surgery using different noninvasive surrogate estimators of ICP.

The association between elevated serum interleukin-22 and the clinical diagnosis of axial spondyloarthritis: A retrospective study.

OBJECTIVE: There is an unmet need for a reliable biomarker for the differentiation of axial spondyloarthritis (AxSpA) from its mimickers. Serum levels of interleukin-22 (IL-22) have previously been found to be significantly elevated in patients with AxSpA compared with healthy individuals or persons with osteoarthritis. METHODS: Consecutive patients with established or suspected AxSpA were enrolled. The clinical data, as well as results of laboratory and imaging studies, were acquired from patients' charts. The final diagnosis of definite or probable SpA, or an alternative diagnosis, was determined, and the serum levels of IL-22 were examined by enzyme-linked immunosorbent immunoassay. RESULTS: Interleukin-22 levels were significantly higher in patients with definite AxSpA (29 patients) compared with patients with alternative diagnoses (14 patients) and healthy volunteers (16 individuals; P < 0.001 for both comparisons). The sensitivity and specificity of the serum IL-22 for the AxSpA diagnosis were 0.68 (95% CI 0.49-0.84) and 0.86 (95% CI 0.68-0.95), respectively, for the cut-off value of 5 pg/mL. In patients with AxSpA, serum IL-22 levels did not correlate with modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), or serum C-reactive protein. CONCLUSION: Serum IL-22 levels are elevated in patients with the clinical diagnosis of AxSpA and can potentially serve as an independent biomarker for the differentiation of AxSpA from its non-inflammatory mimickers.

RIPK1 mutations causing infantile-onset IBD with inflammatory and fistulizing features.

Purpose: Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important regulator of necroptosis and inflammatory responses. We present the clinical features, genetic analysis and immune work-up of two patients with infantile-onset inflammatory bowel disease (IBD) resulting from RIPK1 mutations. Methods: Whole exome and Sanger sequencing was performed in two IBD patients. Mass cytometry time of flight (CyTOF) was conducted for in-depth immunophenotyping on one of the patient's peripheral blood mononuclear cells, and compared to control subjects and patients with Crohn's disease. Results: The patients presented with severe colitis and perianal fistulas in the first months of life, without severe/atypical infections. Genetic studies identified pathogenic genetic variants in RIPK1 (Patient 1, A c.1934C>T missense mutation in Exon 11; Patient 2, c.580G>A missense mutation residing in Exon 4). Protein modeling demonstrated that the mutation in Patient 1 displaces a water molecule, potentially disrupting the local environment, and the mutation in Patient 2 may lead to disruption of the packing and conformation of the kinase domain. Immunofluorescence RIPK1 staining in rectal biopsies demonstrated no expression for Patient 1 and minimal expression for Patient 2, compared to controls and patients with active Crohn's disease. Using CyTOF unbiased clustering analysis, we identified peripheral immune dysregulation in one of these patients, characterized by an increase in IFNγ CD8+ T cells along with a decrease in monocytes, dendritic cells and B cells. Moreover, RIPK1-deficient patient's immune cells exhibited decreased IL-6 production in response to lipopolysaccharide (LPS) across multiple cell types including T cells, B cells and innate immune cells. Conclusions: Mutations in RIPK1 should be considered in very young patients presenting with colitis and perianal fistulas. Given RIPK1's role in inflammasome activation, but also in epithelial cells, it is unclear whether IL1 blockade or allogeneic hematopoietic stem cell transplantation can suppress or cure the hyper-inflammatory response in these patients. Additional studies in humans are required to better define the role of RIPK1 in regulating intestinal immune responses, and how treatment can be optimized for patients with RIPK1 deficiency.

Suicidal Behavior in Fibromyalgia Patients: Rates and Determinants of Suicide Ideation, Risk, Suicide, and Suicidal Attempts-A Systematic Review of the Literature and Meta-Analysis of Over 390,000 Fibromyalgia Patients.

Background: Suicide is a leading cause of death worldwide, affecting ~800,000 people every year. Fibromyalgia is an extremely prevalent rheumatic disease with a predisposition for comorbid anxiety and depression, which are known risk factors for suicidal behavior. Suicidality and relevant risk factors for suicidal behavior have not been thoroughly studied in patients with fibromyalgia. Objectives: To investigate the risk of suicidal ideation and attempts in patients with fibromyalgia. Methods: A systematic review and meta-analysis was conducted and reported according to the "Preferred Reporting Items for Systematic reviews and Meta-analyses" (PRISMA) standards. Also, the gray literature was extensively searched. Results: Thirteen studies were included in the present systematic review and meta-analysis, including 394,087 fibromyalgia patients. Sample size ranged from 44 to 199,739 subjects, mean age ranged from 45.8 to 54.5 years while the female percentage with fibromyalgia ranged from 17.1 to 100.0%. The overall suicide ideation prevalence was 29.57% (95%CI 1.84-72.07), with an OR 9.12 of (95%CI 1.42-58.77), ranging from 2.34 (95%CI 1.49-3.66) to 26.89 (95%CI 5.72-126.42). Pooled suicide attempt prevalence was 5.69% [95%CI 1.26-31.34], with an OR of 3.12 [95%CI 1.37-7.12]. Suicide risk was higher with respect to the general population with an OR of 36.77 (95%CI 15.55-96.94), as well as suicide events with an HR of 1.38 (95%CI 1.17-1.71). Determinants of suicidality were found to be: employment status, disease severity, obesity and drug dependence, chronic pain and co-morbidities, in particular depression, anxiety, poor sleep, and global mental health. However, in some cases, after adjusting for psychiatric conditions, the threshold of statistical significance was not achieved. Conclusion: Fibromyalgia patients are particularly prone to suicide, in terms of ideation, attempt, risk and events, warranting a pre-emptive screening of their mental health status. Given the few studies available, the high amount of heterogeneity, the evidence of publications bias and the lack of statistical significance when adjusting for underlying psychiatric co-morbidities, further high-quality studies should be conducted. Clinical Trial Registration: ClinicalTrial.gov, identifier 10.17605/OSF.IO/Y4BUE.

Think Melkersson-Rosenthal Syndrome: A Fissured Tongue With Facial Paralysis.

Melkersson-Rosenthal syndrome (MRS) was first described and named after E. Melkersson in 1928 and C. Rosenthal in 1931. MRS is a rare cause of recurrent facial nerve palsy and can manifest as facial paralysis, orofacial edema, and/or tongue fissuring. Presenting with the complete triad, it was scarcely reported in literature. However, the patient reported here had the complete triad. MRS should be considered when facial paralysis is recurrent or when it presents with orofacial edema, and/or tongue fissuring.

Rheumatoid arthritis (RA) and cardiovascular disease.

Patients with rheumatoid arthritis (RA) suffer cardiovascular events 1.5-2 fold than the general population, and cardiovascular (CV) events are leading cause of death in patients with RA. It is known that patients with RA have endothelial dysfunction, related with impaired function of endothelial progenitor cells (EPCs). The mechanistic pathways leading to endothelial function are complicated, but understanding these mechanisms may open new frontiers of management and therapies to patients suffering from atherosclerosis. Inflammation is a key factor in atherosclerosis, including endothelial function, plaque stabilization and post infarct remodeling; thus, inhibition of TNF-α may affect the inflammatory burden and plaque vulnerability leading to less cardiovascular events and myocardial infarctions. An aggressive management of inflammation may lead to a significant improvement in the clinical cardiovascular outcome of patients with RA. The clinical evidence that showed a reduced risk of CV events following treatment with anti-inflammatory agents may suggest a new approach to treat atherosclerosis, i.e., inhibition of inflammation using biological medications that were primarily aimed to treat the high scale inflammation of RA and other autoimmune-inflammatory diseases, but may be useful also to prevent progression of atherosclerosis.

Role of anti-DNA auto-antibodies as biomarkers of response to treatment in systemic lupus erythematosus patients: hypes and hopes. Insights and implications from a comprehensive review of the literature.

Introduction: Due to the polymorphic clinical presentations and manifestations of systemic lupus erythematosus (SLE), biomarkers with enough diagnostic and prognostic value are of paramount importance. Recently, anti-double stranded DNA (anti-dsDNA) auto-antibodies have been proposed to monitor the response to different therapies. It has also been suggested that they should be employed as entry markers in trial studies. However, their clinical use remains still debated and, sometimes, controversial, due to conflicting findings reported. Areas covered: Through an extensive literature review, we evaluated changes in anti-dsDNA auto-antibodies levels before and after the administration of the treatment (either biological or non-biological). Expert opinion: Anti-dsDNA auto-antibodies related findings are still difficult to compare mainly because of the different detecting methods employed, even though in most studies included in this review a consistent decreasing pattern after the treatment seems to emerge. Hence, if properly standardized, anti-dsDNA auto-antibody profile may be a reliable biomarker to monitor the effectiveness of biologics as well as of non-biological drugs, especially if grouped in composite outcomes scores, such as the 'Lupus Multivariable Outcome Score' (LUMOS) or measured with other biomarkers, such as anti-nucleosome auto-antibodies. We recommend the assessment of anti-dsDNA auto-antibodies levels in both daily practice and research settings.

Psychometric properties of the Brief Symptom Inventory in nomophobic subjects: insights from preliminary confirmatory factor, exploratory factor, and clustering analyses in a sample of healthy Italian volunteers.

BACKGROUND: The Brief Symptom Inventory (BSI), developed by Derogatis in 1975, represents an important standardized screening instrument that enables one to quantitatively assess psychological distress and psychiatric disorders. The BSI is a 53-item self-report scale, measuring nine dimensions that can be summed up to reflect three global indices, including the General Severity Index (GSI). In the era of new information and communication technologies, nomophobia ("no mobile phobia") is an emerging disorder, characterized by the fear of being out of mobile phone contact. Nothing is known, however, about the factor structure and reliability of the BSI in a population of nomophobic subjects. This study aimed at addressing this gap in knowledge. METHODS: A sample of 403 subjects aged 27.91±8.63 years (160 males, 39.7% of the entire sample, and 243 females, 60.3%), recruited via snowball sampling, volunteered to take part in the study. The Italian versions of the Nomophobia questionnaire and the BSI were administered. Exploratory factor analyses, confirmatory factor analyses, and clustering analysis were carried out together with correlation analysis, analysis of variance, and multivariate regression analysis. RESULTS: For each BSI subscale, scores were significantly higher than the norms. The nine subscales exhibited acceptable-to-good Cronbach's alpha coefficients, varying from 0.733 for psychoticism to 0.875 for depression. Overall, the reliability of the entire instrument proved to be excellent (alpha coefficient=0.972). Furthermore, all BSI subscales as well as BSI synthetic indexes correlated with nomophobia in a significant way. Stratifying the population according to the severity of nomophobia (mild, 206 individuals, 51.1% of the sample; moderate, 167 subjects, 41.4%; and severe, 30 individuals, 7.4%), the GSI score could distinguish (P<0.001) between mild and moderate (0.99±0.71 vs 1.32±0.81) and between mild and severe (0.99±0.71 vs 1.54±0.79) nomophobia, although not between moderate and severe nomophobia (P>0.05). Similar patterns could be found for the other subscales of the BSI. Finally, looking at the fit indexes, the second-order 9-factor model best fit the data compared with the Derogatis 1-factor model. CONCLUSION: The findings of our study show that the BSI is a reliable and valid instrument with acceptable psychometric properties, and can be administered to populations of nomophobic subjects.

FMF Is Associated With a Wide Spectrum of MHC Class I- and Allied SpA Disorders but Not With Classical MHC Class II-Associated Autoimmune Disease: Insights From a Large Cohort Study.

Objectives: To test the hypothesis that familial Mediterranean fever (FMF)-associated autoinflammation may exaggerate the tendency toward adaptive immunopathology or spondyloarthritis (SpA)-associated disorders including major histocompatibility complex (MHC) class I associated disorders but not classical MHC class II-associated disorders that exhibit transplacental autoimmunity including myasthenia gravis and pemphigus. Methods: Seven thousand seven hundred forty-seven FMF patients and 10,080 age- and sex-matched controls in the Clalit Health Services medical database were identified and compared in terms of prevalence of SpA-associated disorders. We also evaluated four classical and strong MHC class II-associated disorders, namely, pemphigus vulgaris, myasthenia gravis, sarcoidosis, and pernicious anemia, to ascertain whether such associations with SpA-spectrum disease were specific or merely reflected the non-specific consequences of innate immune system activation on driving divergent types of immunity. The diagnosis of FMF was based on the medical records and not genetically proven. Results: FMF showed a strong association with MHC class I-related diseases: odds ratio (OR) of 28.58 [95% confidence interval (95% CI), 6.93-117.87; p < 0.0001] for Behçet's disease, OR of 10.33 (95% CI, 4.09-26.09; p < 0.0001) for ankylosing spondylitis, and OR of 1.67 (95% CI, 1.19-2.33; p = 0.0029) for psoriasis. For weakly MHC class I-linked diseases, an OR of 3.76 (95% CI, 2.48-5.69; p < 0.0001) for Crohn's disease and OR of 2.64 (95% CI, 1.52-4.56; p = 0.0005) for ulcerative colitis were found. No association was found between FMF and the four MHC class II-associated autoimmune disorders. Conclusion: FMF patients are associated with increased risk of SpA-related disease diagnosis including MHC-I-opathies but not MHC-II-associated autoimmune diseases, suggesting that tissue-specific dysregulation of innate immunity share between FMF and SpA spectrum disorders may drive adaptive immune MHC class I-associated conditions.