Search

Anti-synthetase syndrome (ASSD) is a heterogeneous autoimmune disease characterised by multi-system involvement with a wide variety of manifestations. Validated classification criteria are necessary to improve recognition and prevent misclassification, especially given the lack of reliable and standardised autoantibody testing. We systematically reviewed the literature to analyse proposed ASSD criteria, characteristics, and diagnostic performance. Methods We searched PubMed and Embase databases (01/01/1984 to 06/11/2018) and the ACR and EULAR meeting abstracts (2017-2018). Sensitivities, specificities, positive, negative likelihood ratios and risk of bias were calculated for ASSD criteria and key variables reported in the literature. We performed meta-analysis when appropriate. Results We retrieved 4,358 studies. We found 85 proposed ASSD criteria from a total of 82 studies. All but one study included anti-synthetase autoantibody (ARS) positivity in the ASSD criteria. Most studies required only one ASSD feature plus anti-ARS to define ASSD (n=64, 78%), whereas 16 studies required more than one ASSD variable plus anti-ARS. The only criteria not including anti-ARS positivity required 5 ASSD clinical features. We found limited data and wide variability in the diagnostic performance of each variable and definition proposed in the literature. Given these limitations we only meta-analysed the performance of individual muscle biopsy and clinical variables in diagnosing ASSD, which performed poorly. Conclusion The current ASSD criteria include a variety of serological, clinical, and histological features with wide variability amongst proposed definitions and the performance of these definitions has not been tested. This systematic literature review suggests the need for additional data and consensus-driven classification criteria for ASSD.

Calcinosis, insoluble calcium compounds deposited in skin and other tissues, is a crippling sequela of dermatomyositis. Prolonged disease associated with ongoing inflammation, ischemia, repetitive trauma, and certain autoantibodies are associated with calcinosis. Herein, we describe potential pathogenic mechanisms including the role of mitochondrial calcification. There are no widely effective treatments for calcinosis. We review available pharmacologic therapies for calcinosis including those targeting calcium and phosphorus metabolism; immunosuppressive/anti-inflammatory therapies; and vasodilators. Mounting evidence supports the use of various formulations of sodium thiosulfate in the treatment of calcinosis. Although the early institution of aggressive immunosuppression may prevent calcinosis in juvenile dermatomyositis, only limited data support improvement once it has developed. Minocycline can be useful particularly for lesions associated with surrounding inflammation. Powerful vasodilators, such as prostacyclin analogs, may have promise in the treatment of calcinosis, but further studies are necessary. Surgical removal of lesions when amenable is our treatment of choice.

Objective Cigarette smoking is associated with immune-mediated disorders. We explored the contribution of smoking to polymyositis (PM) and dermatomyositis (DM) phenotypes and attempted to determine whether cigarette smoking effects differ by race and genotype. Methods Associations of tobacco smoking with disease features, autoantibodies, HLA types, and race were evaluated using multiple logistic regressions in 465 patients. Results Caucasian ever-smokers (n = 140) were more likely to have PM (adjusted OR = 2.24, 95% CI: 1.41\x963.57), anti-synthetase (adjusted OR = 1.93, 95% CI: 1.12\x963.34) and anti-Jo-1 autoantibodies (adjusted OR = 1.94, 95% CI: 1.08\x963.46) and less likely to have anti-p155/140 autoantibodies (adjusted OR = 0.36, 95% CI: 0.14\x960.92). In Caucasians, ever-smokers had a greater interstitial lung disease (ILD) frequency than never-smokers, while in African-Americans this relationship was inverted, but neither trend reached statistical significance. Pack-years of cigarette smoking showed significant positive associations with PM (adjusted OR = 1.02, 95% CI: 1.002\x961.04) and ILD (adjusted OR = 1.02, 95% CI: 1.001\x961.03) and was inversely associated with anti-p155/140 autoantibodies (adjusted OR = 0.93, 95% CI: 0.87\x960.99) in Caucasians. Caucasian heavy smokers (=20 pack-years) were more likely to have PM (adjusted OR = 2.52, 95% CI: 1.25\x965.09), ILD (adjusted OR = 2.48, 95% CI: 1.23\x965.00) and anti-Jo-1 autoantibodies (adjusted OR = 2.65, 95% CI: 1.16\x966.08) than never-smokers. In Caucasians, compared to never-smokers without HLA-DRB1*03:01 allele, ever-smokers with HLA-DRB1*03:01 allele had the highest odds of PM, ILD, ASA, and anti-Jo-1 autoantibodies. Risks for those with only one of these two factors were intermediate. An inverse pattern was observed regarding anti-p155/140 autoantibodies. Conclusion Tobacco smoking was associated with clinical and autoantibody phenotypes in Caucasians. Our findings also suggest possible interactions among HLA-DRB1*03:01 and smoking on the risk of PM and ILD, as well as, anti-synthetase, anti-Jo-1, and anti-p155/140 autoantibodies in Caucasians.

Vitamin D deficiency, common in the population with irritable bowel syndrome (IBS), can induce the main factors that lead to IBS clinical symptoms, such as depression, anxiety, and inflammation. Serotonin (5-HT) plays an important role in the pathophysiology of IBS, and its production and secretion are increased from the lumen due to stress and inflammation. The aim of this study was to evaluate the effect of vitamin D3 supplementation on the pathogenesis of diarrhea-predominant IBS (IBS-D). Seventy-four IBS-D patients (age: 18-65 y) participated in a randomized, double-blind, placebo-controlled trial study from February 2017 to May 2018, at Rasoul-e-Akram Hospital, Tehran, Iran. Subjects were allocated into two groups receiving 50,000 IU/week of vitamin D3 or placebo for 9 weeks. IBS severity score system (IBS-SSS), IBS-quality of life questionnaire (QoL), hospital anxiety and depression Scale (HADs), visceral sensitivity index (VSI) and serum 25(OH) vitamin D3, serotonin, 5-hydroxy-indole acetic acid and ratio of 5-HIAA/5-HT were evaluated before and after the interventions. Symptoms severity, QoL, HADs-depression, and VSI score improved significantly in the vitamin D group as compared to the placebo group (P-values, EXCLI Journal;Vol. 19. 2020, p. 652-667

Vitamin D deficiency, common in the population with irritable bowel syndrome (IBS), can induce the main factors that lead to IBS clinical symptoms, such as depression, anxiety, and inflammation. Serotonin (5-HT) plays an important role in the pathophysiology of IBS, and its production and secretion are increased from the lumen due to stress and inflammation. The aim of this study was to evaluate the effect of vitamin D3 supplementation on the pathogenesis of diarrhea-predominant IBS (IBS-D). Seventy-four IBS-D patients (age: 18-65 y) participated in a randomized, double-blind, placebo-controlled trial study from February 2017 to May 2018, at Rasoul-e-Akram Hospital, Tehran, Iran. Subjects were allocated into two groups receiving 50,000 IU/week of vitamin D3 or placebo for 9 weeks. IBS severity score system (IBS-SSS), IBS-quality of life questionnaire (QoL), hospital anxiety and depression Scale (HADs), visceral sensitivity index (VSI) and serum 25(OH) vitamin D3, serotonin, 5-hydroxy-indole acetic acid and ratio of 5-HIAA/5-HT were evaluated before and after the interventions. Symptoms severity, QoL, HADs-depression, and VSI score improved significantly in the vitamin D group as compared to the placebo group (P-values, EXCLI Journal; 19:Doc652; ISSN 1611-2156

Background Antisynthetase syndrome (ASSD) lacks of established clinico-serological classification criteria. A taskforce by EULAR and ACR is working on to develop and validate classification criteria for ASSD. Objectives To systematically upraise literature to retrieve the available definitions of ASSD and to evaluate their diagnostic performance. Methods This systematic review followed a pre-specified protocol. Two research questions (Q1: how is ASSD defined; Q2: what is the diagnostic performance of the definitions) were rephrased into PICOs terms to create search strategies. Studies on patients with suspect or confirmed ASSD, including a definition of the disease with any study design, excluding case-reports and narrative reviews, were eligible for inclusion. The diagnostic performance had to be tested against the reference standard of expert opinion. PubMed and Embase were searched from 01/01/1984 to 06/11/2018. Moreover, the ACR and EULAR congress abstracts (2017-2018) were hand searched. The titles and abstracts of the retrieved studies were screened by pairs of reviewers, the full-text of studies fulfilling the inclusion criteria was assessed to confirm eligibility. The references of the included studies were also evaluated in search of additional studies. Data from primary studies were extracted into a pre-specified extraction form and, if possible, 2x2 tables to assess diagnostic performance were completed. Sensitivities, specificities, positive and negative likelihood ratios (LR) were calculated for each study. If the diagnostic performance of a definition or variable was assessed in at least 4 studies, a meta-analysis of diagnostic performance was undertaken. The risk of bias (RoB) was assessed using the most appropriate tool depending on study design. Results After the exclusion of duplicates, the searches retrieved 4358 studies, of which 375 suitable for full-text review. Finally, 77 studies were included, along with 1 additional study from hand search and 3 congress abstracts. 72 studies were included in Q1 and 9 in both Q1 and 2. The presence of antisynthetase antibodies (70 studies), mainly anti-Jo1 (57 studies); myositis (51 studies), mainly defined clinically (32 studies); and interstitial lung disease (38 studies) were the variables most frequently used to define ASSD. Other variables, such as arthritis (19 studies), Raynaud’s phenomenon and skin manifestations (10 studies each) were included less frequently. Most commonly, ASSD was defined by a combination of clinical and serological variables. However, no study evaluated the diagnostic performance of such combined definitions. Most of the studies included in Q2 (6) evaluated specific variables of muscle biopsy, one evaluated MRI and 2 clinical variables, with a wide variability in the performance of each item. It was possible to meta-analyze data only to assess the performance of perifascicular necrosis/atrophy: pooled sensitivity (95%CI) was 0.53 (0.33,0.72) and specificity 0.63 (0.47,0.76), pooled LR+ 1.45 (0.72,2.89) and LR- 0.73 (0.40,1.34). Conclusion ASSD is defined according to a variety of combinations of serological, clinical and histological variables. The performance of these combined definitions however has not been tested, and from the limited evidence available single muscle biopsy variable (perifascicular necrosis/atrophy) seem to perform poorly. The systematic review confirms the need of data and consensus driven classification criteria for ASSD. Disclosure of Interests Giovanni Zanframundo: None declared, Sara Faghihi Kashani: None declared, Lorenzo Cavagna: None declared, Rohit Aggarwal: None declared, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Sanofi, Genzyme, Lilly, MSD, Pfizer, UCB, Carlo Alberto Scire: None declared, Garifallia Sakellariou: None declared

Background Curcumin (diferuloylmethane) has been associated with the inhibition of angiogenesis, as well as the prevention of cancers and inflammatory processes. The aim of this study was to assess the efficacy of curcumin in suppressing angiogenesis in the cultured endothelial cells of rat aortic rings. Methods Eight-week-old male Wistar rats were randomized into five groups each with a different treatment and cell culturing paradigm: controls cultured in the absence of VEGF (vascular endothelial growth factor) (C), controls cultured in the presence of VEGF (C-V), controls treated with curcumin and then cultured in media lacking VEGF (C-TC), diabetics cultured in media supplemented with VEGF (D-V) and diabetics treated with curcumin and then cultured in media supplemented with VEGF (D-V-TC). Each group consisted of 8 animals. Diabetes was induced in by streptozotocin (STZ; 60 mg/kg body weight, IV). After 8 weeks, animals were sacrificed and their aortas were excised. Ring-shaped explants were embedded in a 96-well culture plate. Angiogenesis response was measured by counting the number of primary microtubules in each well. Results Optic microscopy revealed that the D-V group had the highest number of microvessels, while angiogenesis was not observed in the C or C-TC groups. The number of primary microtubules was significantly lower in the D-V-TC group compared to the D-V group (P, Graphical abstract

The objective of present study was to assess the safety and efficacy of nanocurcumin as an anti-inflammatory and antioxidant agent in adults with amyotrophic lateral sclerosis (ALS). We conducted a 12-month, double-blind, randomized, placebo-controlled trial at a neurological referral center in Iran. Eligible patients with a definite or probable ALS diagnosis were randomly assigned to receive either nanocurcumin (80 mg daily) or placebo in a 1:1 ratio. A computerized random number generator was used to prepare the randomization list. All patients and research investigators were blinded to treatment allocation. The primary outcome was survival, and event was defined to be death or mechanical ventilation dependency. Analysis was by intention-to-treat and included all patients who received at least one dose of study drug. A total of 54 patients were randomized to receive either nanocurcumin (n = 27) or placebo (n = 27). After 12 months, events occurred in 1 patient (3.7%) in the nanocurcumin group and in 6 patients (22.2%) in the placebo group. Kaplan–Meier analysis revealed a significant difference between the study groups regarding their survival curves (p = 0.036). No significant between-group differences were observed for any other outcome measures. No serious adverse events or treatment-related deaths were detected. No patients withdrew as a result of drug adverse events. The results suggest that nanocurcumin is safe and might improve the probability of survival as an add-on treatment in patients with ALS, especially in those with existing bulbar symptoms. Future studies with larger sample sizes and of longer duration are needed to confirm these findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-018-0606-7) contains supplementary material, which is available to authorized users.

To investigate in a pilot study the safety and efficacy of infliximab in patients with refractory dermatomyositis (DM) and polymyositis (PM).A randomized, double-blind, placebo-controlled trial including subjects with active DM or PM. Participants had stable doses of immunosuppressive medication and prednisone (≤0.5mg/kg/day), and exhibited clinical signs of muscle weakness for at least 4 weeks prior to study entry. Participants received infusions of either placebo or infliximab 5mg/kg at 0, 2, 6, and 14 weeks in blinded manner. The primary outcome was a ≥15% manual muscle strength (MMT) improvement at week 16 compared to week 0. The secondary outcome measures were improvement defined by the International Myositis Assessment and Clinical Studies Group (IMACS) criteria. At week 16, responders in each arm had the option of either continuing the same treatment or changing to the non-responder treatment for that study arm. Non-responders in the 5mg/kg infliximab arm were increased to infliximab 7.5mg/kg for weeks 22, 30, and 38. Non-responders in the placebo arm at week 16 received infliximab 5mg/kg at weeks 16, 18, 22, 30, and 38. Outcomes were reassessed at week 40.Twelve subjects completed the study to week 16. Six of the 12 subjects received infliximab treatment at the dose of 5mg/kg with only one subject meeting the responder criteria at that dose. Of the remaining five subjects on infliximab, three crossed over to the infliximab 7.5mg/kg dose. One of those three subjects responded. All six patients in the placebo arm crossed over to the 5mg/kg dosing regimen after week 16, and two of those responded to infliximab.Infliximab therapy for patients with refractory PM and DM was well tolerated and may benefit a subset of patients.

Epilepsy is one of the most common neurological disorders. Studies have demonstrated that genetic factors have a strong role in etiology of epilepsy. Mutations in genes encoding ion channels, neurotransmitters and other proteins involved in the neuronal biology have been recognized in different types of this disease. Moreover, some chromosomal aberration including ring chromosomes will result in epilepsy. In this review, we intend to highlight the role of molecular genetic in etiology of epilepsy syndromes, inspect the most recent classification of International League against Epilepsy and discuss the role of genetic counseling and genetic testing in management of epilepsy syndromes. Furthermore, we emphasize on collaboration of neurologists and geneticists to improve diagnosis and management.

Administration of filgrastim (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) (Neupogen) in healthy donors to mobilize hematopoietic stem cells (HSCs) is a widespread practice in adults. Application of peripheral blood stem cell (PBSC) collection in normal pediatric donors is scarce due to ethical issues. Hence, there are insufficient data on the long-term impact of PBSC procedure in healthy children. This retrospective study aimed to evaluate the early and late adverse effects of PBSC donation in pediatric donors. Bone marrow and PBSC procedures and known adverse events of each technique were completely explained to parents and when applicable to children and written informed consent was obtained. rhG-CSF was administered for 4 days. HSCs were collected on the fifth day through continuous-flow apheresis and donors were followed for 30 days. Manual chart review was performed to collect short-term complications. Donors' health status was assessed via a questionnaire. A total of 145 healthy pediatric donors with a median age of 10 years at the time of donation (2 to 15 years) were followed for a median of 4.8 years (range, 1.2 to 14.2 years). The most frequent symptoms of rhG-CSF administration were fatigue (5%) and headache (3%). Thirty-five (24%) donors experienced hypocalcaemia during apheresis procedure that quickly responded to treatment. Two pregnancies occurred after rhG-CSF administration that resulted in normal births. We did not encounter any serious adverse events, including neoplastic disorders and death in this study. rhG-CSF and leukophresis procedure were well-tolerated in this study and all children completed the donation process without interruption or reduction of rhG-CSF dosage. Our results suggest that rhG-CSF is a safe drug in healthy children for the purpose of HSC mobilization.

Reduced-intensity conditioning (RIC) has offered many primary immunodeficiency disorder (PID) patients who are ineligible for myeloablative regimens a chance of cure. However, the beneficial role of RIC was questioned following reports suggesting higher chance of rejection and lower symptom resolution rate in mixed chimerism settings. Forty-five children affected by PIDs with a median age of 21 months underwent allogeneic hematopoietic stem cell transplantation in our institute from 2007 to 2013. All patients received an identical RIC regimen. Forty-one patients had successful primary engraftment (91%). Of the successful engraftments, 80% (n=33) had stable full donor chimerism at last contact. Overall, eleven transplant-related mortalities were reported including five patients due to sepsis, three children due to grade IV acute GvHD, two due to chronic GvHD and one patient due to sepsis after primary graft failure. The median post-transplantation follow-up of deceased patients was 55 days. Five-year overall survival and disease-free survival was 75.6% and 68.89%, respectively. All surviving patients with successful engraftment became disease free, regardless of having full or mixed chimerism. Our study suggests that RIC regimen provides satisfactory rates of successful engraftment and full chimerism. Furthermore, patients with mixed chimerism were stable in long-term follow-up and this chimerism status offered the potential to resolve symptoms of immunodeficiency.

Background: Good knowledge, attitude and practice (KAP) of the physicians allow them to handle their patients in such a way that they prevent themselves from contracting, and their patients from spreading, the infection. However, the Iranian standardized KAP questionnaire of physicians about viral hepatitis is not available. So, we developed a standard questionnaire. Objectives: The purpose of this study was to provide a standard questionnaire as a basic tool for assessment of the present situation of the KAP of clinicians. It can also be used for evaluating educational programs and interventions on physicians in addition to any trends in their KAP about viral hepatitis. Patients and Methods: In order to design and standardize a 29-item self-administered questionnaire, we developed a cross sectional pilot study on 60 Iranian physicians. Ten experts in the field of liver diseases and/or designing the questionnaire answered questions about its validity. Cronbach's Alpha (on 60 physicians that participated in a congress) and factor analysis (on 370 persons; participants of two viral hepatitis congresses in Tehran and Zanjan and physicians of two university hospitals in Ahvaz) were used in the analysis. Results: Reliability was 0.7 according to Cronbach's Alpha score. Face validity was higher than 80%. Content validity of the whole parts of the questionnaire was 96.25% for clarity, 91.56% for relevancy, 96.25% for simplicity and 98.44% for consistency of each question with the questions' set. Factor analysis showed that 13 components account for 67.4% of the total variance. Conclusions: This study provided evidence that our questionnaire is a feasible, valid and reliable measure of physicians' KAP status in Iran. The factor analysis did not reveal a strong cluster structure. This questionnaire should be interpreted as a one-dimensional element by the sum of all items, rather than a multi-dimensional instrument.

Background and Aims Health care workers (HCWs) are at risk of contracting and spreading hepatitis B virus (HBV) and hepatitis C virus (HCV) to others. The aim of this study was to evaluate knowledge, attitudes and behavior of physicians concerning HBV and HCV. Methods A 29-item questionnaire (reliability coefficient = 0.7) was distributed at two national/regional congresses and two university hospitals in Iran. Five medical groups (dentists, general practitioners, paraclinicians, surgeons and internists) received 450 questionnaires in 2009, of which 369 questionnaires (82%) were filled out. Results Knowledge about routes of transmission of HBV and HCV, prevalence rate and seroconversion rates secondary to a needlestick injury was moderate to low. Concern about being infected with HBV and HCV was 69.4±2.1 and 76.3±2 (out of 100), respectively. Complete HBV vaccination was done on 88.1% of the participants. Sixty percent had checked their hepatitis B surface antibody (anti-HBs), and 83.8% were positive. Only 24% of the surgeons often used double gloves and 28% had reported a needlestick. There was no significant correlation between the different specialties and: concern about HBV and HCV; the underreporting of needlestick injuries; and correct knowledge of post-needlestick HBV infection. Conclusions Although our participants were afraid of acquiring HBV and HCV, knowledge about routes of transmission, prevalence, protection and post-exposure seroconversion rates was unsatisfactory. By making physicians aware of possible post-exposure prophylaxis, the underreporting of needlestick injuries could be eliminated. Continuous training about HBV and HCV transmission routes, seroconversion rates, protection, as well as hepatitis B vaccination and checking the anti-HBs level, is a matter of necessity.