Clinical profile of anti-NXP-2 antibody-positive inflammatory myositis and outcome in an Indian population.

INTRODUCTION: Myositis-specific antibodies (MSA) play an important role in the clinical presentation and prognosis of patients with idiopathic inflammatory myositis (IIM). Anti-NXP-2 is one of the newly described MSA. OBJECTIVE: We aimed to describe various clinical presentations associated with anti-NXP2 antibodies and assess response to treatment. METHODS: In this retrospective study, the electronic medical records of all patients who tested positive for anti-NXP2 during June 2019 to April 2022 were screened. Details of demography, clinical presentation, and treatment data were recorded. The anti-NXP2 was tested using the Euro line test kit. Any patient who had an intensity of ≥1+ was considered testing positive. The diagnosis of IIM was reviewed after applying the 2017 European League of Rheumatology (EULAR)/American College of Rheumatology (ACR) criteria of myositis. RESULTS: Among the 660 suspected patients, 470 (71.2%) patients were positive for IIM, and 28 (5.95%) patients were positive for anti-NXP2. From anti-NXP2-antibody positive, 21/470 (4.46%) patients fulfilled criteria for IIM. Among 12 adult (57.14%) patients with IIM, 7 (58.33%) presented as polymyositis (PM) and 5 (41.6%) as dermatomyositis (DM) with median age at presentation of 45 (IQR: 25-58) years. Calcinosis and subcutaneous oedema were observed in 4 (19%) and 2 (9.52%), respectively; myalgia in 6 (28.6%); and distal muscle weakness in 5 (23.8%) patients. Malignancy at the time of diagnosis was observed in two adults with IIM (16.7%), one with DM (intraductal breast cancer), and another with PM (anaplastic large cell lymphoma). Remaining, 9 had juvenile dermatomyositis (JDM) with a median age of 4 (IQR: 3-8) years. Seven (77.8%) patients with JDM had skin rash specific for DM (heliotrope rash and Gottron's papule). None of the patients had cardiac and lung involvement, while GI symptoms, especially dysphagia, were present in 5 (23.8%) patients. During a median follow-up of 19 months (IQR: 12-26 months), 19/19 patients reported improvement and were in remission with treatment. CONCLUSION: The current study shows that adult DM patients with anti-NXP-2 autoantibodies have a unique clinical phenotype. Its presentation differs between adult and JDM, even in different parts of the world. Muscle weakness is mild and responds to treatment. Dysphagia needs more time and aggressive IS for improvement as compared to other muscle involvement. Key Points • Anti-NXP-2 antibody presentation varied from adult to child, as in different parts of the world. • In Indian adult patients, non-specific skin manifestations were more common, whereas in JDM, specific skin features were common. • There was less likely involvement of the lung and heart. But more risk of GI involvement requiring aggressive management. • Adult with anti-NXP-2 antibody should be screened for malignancy at the time of presentation.

Clinical and angiographic outcomes of Mycophenolate versus Methotrexate in South Asian patients of Takayasu arteritis: Results from an open-label, randomised controlled trial.

OBJECTIVE: To compare the clinical and angiographic responses of Mycophenolate Mofetil (MMF) versus Methotrexate (MTX) in Takayasu arteritis (TAK). METHODS: This was a open label, outcome assessor blinded trial. Adult patients of TAK with active disease were randomized 1:1 to MMF 1g twice daily or MTX 20 mg once weekly, by computer generated program. All patients were started on 0.5 mg/kg of steroids with a predetermined tapering protocol. Primary outcome was treatment response as defined by Indian Takayasu arteritis score at 9 months. Secondary end points included time to first failure and angiographic progression. RESULTS: A total of 52 patients (26 in each arm) were recruited. The rate of responders was 71.43% (15/21) in the MMF arm and 63.64% (14/22) in the MTX arm (p=0.58). The median time to 1st failure was 9 months (Range: 3-9) and 4.5 months (range: 3-9) in the MMF and MTX arm respectively (p=0.052). In both groups, 15 % of patients (n=3) had progressive disease in angiography. CONCLUSION: The results showed numerically better outcomes towards MMF, with a longer time to first failure than Methotrexate(9 months versus 4.5 months, p=0.052). No significant difference was seen in the angiographic outcomes.

N-hydroxypipecolic acid-induced transcription requires the salicylic acid signaling pathway at basal SA levels.

Systemic acquired resistance (SAR) is a plant immune response established in uninfected leaves after colonization of local leaves with biotrophic or hemibiotrophic pathogens. The amino acid-derived metabolite N-hydroxypipecolic acid (NHP) travels from infected to systemic leaves, where it activates salicylic acid (SA) biosynthesis through the isochorismate pathway. The resulting increased SA levels are essential for induction of a large set of SAR marker genes and full SAR establishment. In this study, we show that pharmacological treatment of Arabidopsis thaliana with NHP induces a subset of SAR-related genes even in the SA induction-deficient2 (sid2/isochorismate synthase1) mutant, which is devoid of NHP-induced SA. NHP-mediated induction is abolished in sid2-1 NahG plants, in which basal SA levels are degraded. The SA receptor NON-EXPRESSOR OF PATHOGENESIS-RELATED GENES1 (NPR1) and its interacting TGACG SEQUENCE-SPECIFIC BINDING PROTEIN (TGA) transcription factors are required for the NHP-mediated induction of SAR genes at resting SA levels. Isothermal titration analysis determined a KD of 7.9 ± 0.5 µM for the SA/NPR1 complex, suggesting that basal levels of SA would not bind to NPR1 unless yet unknown potentially NHP-induced processes increase the affinity. Moreover, the nucleocytoplasmic protein PHYTOALEXIN DEFICIENT4 is required for a slight NHP-mediated increase in NPR1 protein levels and NHP-induced expression of SAR-related genes. Our experiments have unraveled that NHP requires basal SA and components of the SA signaling pathway to induce SAR genes. Still, the mechanism of NHP perception remains enigmatic.

Mycophenolate in idiopathic inflammatory myositis: outcome data of a large South Asian cohort.

BACKGROUND: Consensus on treatment of idiopathic inflammatory myositis (IIM), particularly with regard to flares and interstitial lung disease (ILD), does not exist. We studied the long-term outcome and treatment response in our large, retrospective cohort of adult South-Asian patients exclusively with IIM. METHODOLOGY: Electronic records of IIM patients satisfying inclusion and exclusion criteria were studied longitudinally at presentation, at 3, 6, 12, 18 and 24 months and thereafter yearly till their last follow up (F/u) visit. Depending on clinical, imaging, and muscle enzyme profile during the F/u period, patients were categorised as complete (CR) and partial responders (PRs). Parameters favouring CR were assessed using multivariate logistic regression analysis. Outcome parameters and flares on immunosuppressants (IS) were then assessed in patients with/without ILD. RESULTS: Two hundred thirty-two patients with median F/u duration of 44.5 months (25-80.25) were included. ILD was seen in 40.1%. Patients with non-Jo1 anti-synthetase antibodies (n=26) were numerically more than those with Jo-1 antibody (n=24). CR status was attained by 50.9% patients. Absence of pericardial effusion (p=0.042, OR 4.223, 95% CI: 1.05-16.9) and presence of Gottron's rash (p=0.044, OR 1.78, 95% CI 1.017-3.121) at baseline predicted CR by multivariate regression. Majority received mycophenolate during the entire F/u period. Discontinuation of steroids was feasible in 51.7% after a median duration of 24 months (18-42). After excluding patients with ILD, flares were numerically lesser in patients only on mycophenolate compared with those only on methotrexate (p=0.06). Further flares were curtailed when switched from other agents to mycophenolate. CONCLUSION: Mycophenolate is an effective treatment option in IIM patients with and without co-existing ILD. Presence of Gottron's rash and absence of pericardial effusion were found to be predictors of favourable clinical outcome in this largest single-centre study.

Mycophenolate in scleroderma-associated interstitial lung disease: Real-world data from rheumatology and pulmonology clinics in South Asia.

Introduction: There is a paucity of real-world data on mycophenolate mofetil/mycophenolate sodium in systemic sclerosis-related interstitial lung disease. Aim: To study the efficacy of mycophenolate mofetil/ mycophenolate sodium in systemic sclerosis-related interstitial lung disease. Methods: In this single-centre study, clinical, laboratory and imaging details of consecutive patients with systemic sclerosis-related interstitial lung disease receiving mycophenolate mofetil/mycophenolate sodium from rheumatology and pulmonology clinics between January 2008 and March 2017 were retrospectively retrieved. The change in percentage of predicted normal forced vital capacity at last follow-up visit as compared with baseline was studied. In addition, high-resolution computed tomography scans at baseline and 2-year follow-up visit were scored as either stable/improved or worsened by experienced thoracic radiologists blinded to the clinical details of patients. Results: Altogether, 88 patients (85.2% females) with mean age (SD) of 33.8 years (± 11.3) and median (interquartile range) duration of disease since non-Raynaud's symptoms of 36 months (13.5-60) were studied. Diffuse systemic sclerosis comprised 85.2% of them. The mean baseline forced vital capacity was 61.2 ± 17.9% and median scores for ground glass opacities and fibrosis in high-resolution computed tomography were 0.5 (0-1.3) and 1 (0-1.3), respectively. At a median follow-up duration of 30 months (interquartile range = 16.5-49), the percentage of forced vital capacity improved by 1.8% (-3.82 to 9.07) as compared with baseline visit (p = 0.02). In the 2-year follow-up, the ground glass opacity and fibrosis scores in high-resolution computed tomography improved in 17.3% and 7.7% of patients and stabilized in 63.5% and 78.8% patients, respectively. Conclusion: Mycophenolate mofetil/mycophenolate sodium was efficacious in improving /stabilizing forced vital capacity irrespective of the baseline high-resolution computed tomography lung scores in our patients with systemic sclerosis-related interstitial lung disease during the ⩾ 2-year follow-up period.

Redox-active cysteines in TGACG-BINDING FACTOR 1 (TGA1) do not play a role in salicylic acid or pathogen-induced expression of TGA1-regulated target genes in Arabidopsis thaliana.

Salicylic acid (SA) is an important signaling molecule of the plant immune system. In Arabidopsis thaliana, SA biosynthesis is indirectly modulated by the closely related transcription factors TGACG-BINDING FACTOR 1 and 4 (TGA1 and TGA4, respectively). They activate expression of SYSTEMIC ACQUIRED RESISTANCE DEFICIENT1, the gene product of which regulates the key SA biosynthesis gene ISOCHORISMATE SYNTHASE 1. Since TGA1 interacts with the SA receptor NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1) in a redox-dependent manner and since the redox state of TGA1 is altered in SA-treated plants, TGA1 was assumed to play a role in the NPR1-dependent signaling cascade. Here, we identified 193 out of 2090 SA-induced genes that require TGA1/TGA4 for maximal expression after SA treatment. One robustly TGA1/TGA4-dependent gene encodes for the SA hydroxylase DOWNY MILDEW RESISTANT 6-LIKE OXYGENASE 1, suggesting an additional regulatory role of TGA1/TGA4 in SA catabolism. Expression of TGA1/TGA4-dependent genes in mock/SA-treated or Pseudomonas-infected plants was rescued in the tga1 tga4 double mutant after introduction of a mutant genomic TGA1 fragment encoding a TGA1 protein without any cysteines. Thus, the functional significance of the observed redox modification of TGA1 in SA-treated tissues remains enigmatic.

Clinical course of 602 patients with Takayasu's arteritis: comparison between Childhood-onset versus adult onset disease.

OBJECTIVES: To describe the clinical profile of Asian Indian patients with Takayasu's arteritis (TAK) and to compare clinical features and outcome of childhood-onset Takayasu's arteritis (cTAK) with adult-onset TAK (aTAK). METHODS: Data related to clinical features and response to treatment of patients with cTAK (age of onset <16 years) and aTAK from a large observational cohort in our tertiary care teaching hospital were noted and compared. RESULTS: Altogether, 602 patients (cTAK = 119; aTAK = 483) were studied. Patients with cTAK had a blunted female: male ratio; but fever, elevated acute phase reactants, involvement of abdominal aorta or its branches, hypertension, abdominal pain, elevated serum creatinine and cardiomyopathy were more common in cTAK as compared with aTAK. Patients with aTAK were more likely to have aortic-arch disease and claudication than cTAK. During follow-up, complete remission was more common in cTAK (87% vs 66%; P < 0.01), but subsequent relapses were equally common (30% vs 27%; P = 0.63). Independent associations of disease duration at presentation with disease extent [Disease Extent Index in TAK (DEI.Tak)] and damage [TAK Damage Score (TADS)] were observed (P ≤ 0.01). Moreover, 54% of patients with symptom duration of >5 years at presentation still continued to have elevated CRP suggesting continued and active inflammation warranting escalation or inititation of immunosuppression. CONCLUSION: Patients with cTAK are more likely to have arterial disease below the diaphragm, systemic inflammation and achieve remission. Disease of the aortic arch is more common in patients with aTAK. Longer duration of symptoms prior to initiation of immunosuppression, thereby leading to extensive disease and damage, reflects ongoing disease activity as the rule rather than exception in untreated TAK.

Derivation of an angiographically based classification system in Takayasu's arteritis: an observational study from India and North America.

OBJECTIVES: To develop and replicate, using data-driven methods, a novel classification system in Takayasu's arteritis based on distribution of arterial lesions. METHODS: Patients were included from four international cohorts at major academic centres: India (Christian Medical College Vellore); North America (National Institutes of Health, Vasculitis Clinical Research Consortium and Cleveland Clinic Foundation). All patients underwent whole-body angiography of the aorta and branch vessels, with categorization of arterial damage (stenosis, occlusion or aneurysm) in 13 territories. K-means cluster analysis was performed to identify subgroups of patients based on pattern of angiographic involvement. Cluster groups were identified in the Indian cohort and independently replicated in the North American cohorts. RESULTS: A total of 806 patients with Takayasu's arteritis from India (n = 581) and North America (n = 225) were included. Three distinct clusters defined by arterial damage were identified in the Indian cohort and replicated in each of the North American cohorts. Patients in cluster one had significantly more disease in the abdominal aorta, renal and mesenteric arteries (P < 0.01). Patients in cluster two had significantly more bilateral disease in the carotid and subclavian arteries (P < 0.01). Compared with clusters one and two, patients in cluster three had asymmetric disease with fewer involved territories (P < 0.01). Demographics, clinical symptoms and clinical outcomes differed by cluster. CONCLUSION: This large study in Takayasu's arteritis identified and replicated three novel subsets of patients based on patterns of arterial damage. Angiographic-based disease classification requires validation by demonstrating potential aetiological or prognostic implications.

Validation of new classification criteria of rheumatoid arthritis in an international multicentre study.

OBJECTIVES: Early identification of patients with rheumatoid arthritis (RA) is essential to allow prompt therapy. In this study, we aimed to evaluate the performance of the newly proposed ERA criteria, compared to the 1987 ACR and 2010 ACR/EULAR criteria in an international multicentre study. METHODS: A total of 606 patients with disease duration ≤2 years and age ≥16 years who were diagnosed as RA or non-RA were enrolled from China, Sweden and India. The clinical and laboratory parameters were recorded. We compared the sensitivity, specificity, predictive value, likelihood ratio (LR), and the area under the ROC curve (AUC) of three criteria in these cohorts. Concordance between the three criteria was calculated with the Kappa coefficient. RESULTS: Three hundred and twelve RA and 294 non-RA patients were included. The Early Rheumatoid Arthritis (ERA) criteria had significantly higher specificity compared to the 2010 ACR/ EULAR criteria (83.7% vs. 78.2%, p=0.02) and sensitivity were similar (79.2% vs. 78.5%, p=0.883). In comparison with the 1987 ACR criteria, the ERA criteria had higher sensitivity (79.2% vs. 54.5%, p<0.001) but lower specificity (83.7% vs. 89.1%, p<0.001), and the AUC of the ERA criteria (0.878) was comparable to the 2010 ACR/EULAR criteria (0.849) and higher than the 1987 ACR criteria (0.791, p<0.0001). Patients from the three countries, seronegative and very early arthritis cohorts yielded consistent results. CONCLUSIONS: The ERA criteria demonstrate a better performance across ethnics in early RA diagnosis, and is more feasible in daily practice.

Unique clinical and autoantibody profile of a large Asian Indian cohort of scleroderma-do South Asians have a more aggressive disease?

AIM AND METHODS: A single-centre retrospective study was conducted using electronic medical records (EMR) of inpatients and outpatients with the diagnosis of "scleroderma" or "systemic sclerosis" visiting our clinic over the preceding 5 years. RESULTS: A total of 327 patients' charts met our selection criteria; 301 were females. The median (IQR (inter quartile range)) age at onset of first non-Raynaud's symptom was 34.67 (27-43) years and median (IQR) disease duration prior to presentation to our department was 2.5 (1-5) years. Of these, 310 (94.8%) belonged to diffuse systemic sclerosis variety, 13 (4%) had limited systemic sclerosis, and 4 (1.2%) were of sine scleroderma type. A total of 289/302 (95.7%) patients were positive for ANA; of them, 245/327 (74.9%) were Scl-70 antibody-positive and 4% were CENP antibody-positive. Interstitial lung disease (ILD) was present in 288/327 (88.1%) patients. Among patients with available baseline forced vital capacity (FVC) data, 20% had a normal lung function and 28.4% had severe restriction. Pulmonary hypertension as assessed by echocardiography was present in 8.1% of patients. A significant association of Scl-70 antibody positivity with the presence of interstitial lung disease (ILD) (p = 0.000) and pulmonary hypertension (p = 0.035) was seen. On the other hand, presence of CENP antibody showed a protective trend against muscle weakness and/or muscle enzyme elevation (p = 0.052). Presence of arthritis was protective against development of digital ulceration (p = 0.021) and PAH (0.004). Patients younger than 40 years of age had significantly higher frequency of Scl-70 positivity (p = 0.038), whereas CENP antibody positivity was more likely in those aged > 40 years (p = 0.002). CONCLUSION: Younger age of onset and high prevalence of Scl-70 antibody are unique South Asian features common with large Indian, Thai, and Chinese series. High prevalence of ILD is a feature common to Indian and Chinese series. Strong correlation of Scl-70 antibody with younger age and pulmonary hypertension were unique features of our cohort. KEY POINTS: • Asian Indian scleroderma patients are younger by 2 decades compared to Caucasian series. • Higher prevalence of Scl-70 antibody, its association with young age, interstitial lung disease and pulmonary hypertension are features of our cohort. • High prevalence of interstitial lung disease (88.1%) was noted ; among those with baseline spirometry data (141/327), two thirds(66%) had moderate to severe restriction. • Younger age at onset, higher prevalence of Scl-70 antibody are features common to other Indian, Thai and Chinese series.

Balancing trade-offs between biotic and abiotic stress responses through leaf age-dependent variation in stress hormone cross-talk.

In nature, plants must respond to multiple stresses simultaneously, which likely demands cross-talk between stress-response pathways to minimize fitness costs. Here we provide genetic evidence that biotic and abiotic stress responses are differentially prioritized in Arabidopsis thaliana leaves of different ages to maintain growth and reproduction under combined biotic and abiotic stresses. Abiotic stresses, such as high salinity and drought, blunted immune responses in older rosette leaves through the phytohormone abscisic acid signaling, whereas this antagonistic effect was blocked in younger rosette leaves by PBS3, a signaling component of the defense phytohormone salicylic acid. Plants lacking PBS3 exhibited enhanced abiotic stress tolerance at the cost of decreased fitness under combined biotic and abiotic stresses. Together with this role, PBS3 is also indispensable for the establishment of salt stress- and leaf age-dependent phyllosphere bacterial communities. Collectively, our work reveals a mechanism that balances trade-offs upon conflicting stresses at the organism level and identifies a genetic intersection among plant immunity, leaf microbiota, and abiotic stress tolerance.

Study of serial serum myeloid-related protein 8/14 as a sensitive biomarker in Takayasu arteritis: a single centre study.

The aim of the study was to explore utility of serial serum myeloid-related protein 8/14 (MRP8/14) as a biomarker of clinical disease activity and angiographic progression in Takayasu arteritis (TA). Serum MRP8/14 levels were assayed by commercial ELISA for 85 TA patients and 24 healthy controls at baseline, and for 56 and 21 TA patients during follow-up visits R1 and R2, respectively. Disease was categorised as active, indeterminate and stable according to Indian Takayasu Arteritis score (ITAS 2010), ITAS-A(CRP) and angiography. Patients were divided into responders and non-responders/relapsers based on treatment response. Non-parametric tests were used for inter-group comparisons at baseline and during follow-up time points. Generalised Estimating Equation was used to study association between changes in serial MRP8/14 levels and disease activity. At baseline, median MRP8/14 levels were higher in patients with TA than healthy controls [7353 (4524 to11283) vs 4896 (3194 to 8474.5) ng/ml, p = 0.011]. Patients with active disease had higher levels [8552 (5463-12488)] than stable disease [5292.5 (3140.5-7310)], p = 0.002, and healthy controls [4896 (3194-8474.5)], p = 0.001. Changes in serial MRP8/14 level were associated with changes in disease activity, independent of steroid dose, p = 0.000. At R1, MRP 8/14 levels were lower than baseline in responders (n = 38) [9146.0 (6296.8-13693.8) vs 6501 (4314.8-8304.5), p = 0.004], but did not change in non-responders/relapsers (n = 14) [6693.5(4210.8-10516.3) vs 7755.0(5342-10741.0), p = 0.42]. Similar trend was observed at R2. MRP8/14 levels increased during follow-up in 66% and 26.3% of angiographic progressors and non-progressors, respectively. MRP8/14 in TA may act as a novel biomarker with prognostic implications.

C-reactive protein gene polymorphisms (rs1205) in Asian Indian patients with Takayasu arteritis: Associations and phenotype correlations.

BACKGROUND/PURPOSE: Normal C-reactive protein (CRP) in active Takayasu arteritis (TA) is a dilemma. We attempted to validate our pilot study finding of rs1205 in CRP gene being protective against TA. METHODS: Genomic DNA of 104 patients and 185 sex-matched healthy controls were genotyped for rs1205 by Taqman assay. Clinical details, demography, angiographic and activity scores (Indian Takayasu arteritis score 2010) were recorded prospectively at baseline and during follow-up visits for 12 months. Minor allele frequency (MAF) and genotype distribution between patients and controls as well as patient subgroups were compared using χ2 test with Bonferroni correction (pc ) and logistic regression was performed to determine independent associations. RESULTS: The majority of patients (n = 84) and controls (n = 166) were females. MAF of T allele of rs1205 was less frequent in patients (27%) as compared to controls (37.6%), P = 0.013, pc = 0.026 with an odds ratio of 0.632 irrespective of gender. Frequency of CC genotype was higher in cases (53.8%) than controls (37.3%), P = 0.006, pc = 0.018. A dominant model of genotype-phenotype association revealed CC to be associated with more frequent coronary arterial and ascending aorta involvement than the other genotypes clubbed together (P = 0.01 and P = 0.014, respectively). Blunted CRP response seems to be less frequent in patients with CC genotype (P = 0.064). CONCLUSION: T allele of rs1205 in CRP gene was less frequent in TA. CC genotype was associated with involvement of coronary arteries and ascending aorta. CC genotype was less commonly associated with blunted CRP response (CT + TT > CC).

Utility of CT imaging in differentiating sacroiliitis associated with spondyloarthritis from gouty sacroiliitis: a retrospective study.

Sacroiliitis is one of the criteria for classification as spondyloarthritis (SpA), though not unique to SpA. Other conditions including gout may be erroneously diagnosed as SpA due to sacroiliitis. The objective was to identify specific CT findings in sacroiliitis associated with SpA and gout. In this retrospective study, CT images of patients with sacroiliitis and clinical diagnosis of gout or SpA from 2010 to 2015 were independently reviewed by two radiologists, blinded to diagnosis. Axial and coronal oblique images were analyzed for characteristics of erosions. The receiver operator characteristic curve was constructed to analyze the discriminating ability of radiological findings. CT SI joint images of 11 patients with gout and 224 patients with SpA were re-analyzed. There was excellent agreement between the radiologists (ICC from 0.78 to 1). Erosions were more numerous in SpA. Erosions in gout were associated with tophi in 65.7% (73/111). Erosions in gout were para-articular and had sclerotic margins, overhanging edges, and multilobulated base (P < 0.0001 for all). Length and depth of erosions were more in gout as compared to SpA. AUCs for length, depth of erosions, and subchondral sclerosis were 0.665, 0.694, and 0.991, respectively. Subchondral sclerosis ≤ 4.5 mm had a sensitivity and specificity of 100 and 96%, respectively, for diagnosis of gout. In addition to known radiological features of gout, multilobulated base of erosions and absence of subchondral sclerosis could possibly distinguish sacroiliitis in SpA from gout. Our limited analysis suggests that CT imaging could help in differentiating the two.

Mycophenolate mofetil and deflazacort combination in neuropsychiatric lupus: a decade of experience from a tertiary care teaching hospital in southern India.

Mycophenolate mofetil (MMF) is an effective therapeutic agent with high safety profile in the management of lupus nephritis. This retrospective study was conducted to assess the efficacy and side effect profile of MMF as induction as well as maintenance therapeutic agent along with tapering steroids in neuropsychiatric lupus (NPSLE). Hospital electronic medical records of patients with SLE diagnosed by ACR 1990 and/or SLICC 2012 criteria between January 2005 and May 2015 were retrieved. Among them, patients fulfilling ACR 1999 criteria for NPSLE were identified. Data of NPSLE patients treated with MMF as upfront second line immunosuppressive agent, both for induction and maintenance, were analyzed. Of the 140 patients with NPSLE, 88 fulfilled the inclusion criteria. Mean age of the cohort was 25.51 ± 7.82 years with female to male ratio of 84:4. Median duration of follow-up was 33 months (3-129 months). Seizure was the most common NPSLE manifestation (n = 37, 42.05%). Of the 88 patients, 18 had NPSLE solely due to secondary antiphospholipid syndrome. Of the remaining 70 patients, 61 (87.1%) had improved, 7 remained unchanged with no worsening and 3 patients had worsening or developed new symptoms during follow up after 3 months from baseline. At last follow-up, 55 out of 57 patients (97.1%) with detailed data had improved, while 2 patients had relapsed. Side effects were significantly more common in patients on prednisolone as compared to those on deflazacort. In patients with NPSLE, MMF along with tapering steroids is an efficacious combo in inducing remission and preventing relapse of disease.

Serum amyloid A as a marker of disease activity and treatment response in Takayasu arteritis.

Assessment of disease activity in Takayasu arteritis (TA) is challenging. We aimed to study utility of serum amyloid A (SAA) to assess disease activity and its association with SAA gene polymorphisms, if any, in our TA patients. Serum of 99 consecutive adult TA patients and 40 healthy controls were assayed for SAA. Depending on the ITAS2010 and ITAS-CRP score, patients were designated as having active disease if ITAS2010 ≥ 2 or ITAS-CRP ≥ 3 and stable disease if ITAS2010 = 0 or ITAS-CRP is ≤1. Clinical ITAS of 0 with raised inflammatory markers scoring a ITAS-CRP of 2 was considered as indeterminate for disease activity assessment. Repeat SAA levels for active group was measured after 6 months from baseline. SAA levels between active and stable disease as well as serial levels were compared. DNA of 40 patients and controls were genotyped for SAA polymorphisms (rs12218, rs2468844) and the allele frequencies were compared. At baseline, SAA levels were higher in patients as compared to controls (137.4 vs 100.8 ng/ml, p = 0.001) and higher in patients with active disease (166.4 ng/ml) than those with stable disease (98.2 ng/ml), p = 0.001. SAA decreased during follow-up in treatment responders (189.9 ng/ml at baseline vs 119.0 ng/ml at follow-up, p = 0.008); in contrast, there was no significant change among non-responders during follow-up. Allelic frequencies of SAA gene polymorphisms did not differ between cases and controls. SAA may be a reliable biomarker to assess disease activity and treatment response in TA.

A Comparative Evaluation of the Influence of Command Set Methods on Microleakage of Glass Ionomer Cement: An In Vitro Study.

INTRODUCTION: A major challenge when using glass ionomer cement in clinical situation particularly in paediatric dentistry is to overcome the problem of microleakage. Fast or command setting of Type IX glass ionomer cement using external energy source enhances the setting reaction and results in improved initial physical and mechanical properties. AIM: To compare and evaluate the influence of ultrasonic activation, halogen light irradiation and combined effect of both on microleakage of enamel adjacent to Type IX glass ionomer restorations. MATERIALS AND METHODS: For forty premolar teeth, standard Class V cavities prepared were restored with GC Gold Label Type IX glass ionomer cement in vitro. The specimens were randomly divided into four groups: 1) Control group; 2) halogen group; 3) ultrasonic group; 4) ultrasonic with halogen group. The teeth were kept in distilled water for 24 hours. Teeth were exposed to 1500 thermocycles at temperature of 12°C ±2 and 60°C ±2 with alternate immersion in hot and cold water for one minute. First teeth were immersed in dye solution for four hours and then in developing solution for four hours. The samples were sectioned buccolingually through centre of the restorations and degree of dye penetration was assessed under stereomicroscope and scored. One-Way ANOVA model was constructed followed by post-hoc Tukey's test for multiple pair wise comparison of mean values. RESULTS: Statistically significant differences were found in microleakage among the four groups (p<0.001) with respect to dye penetration. Halogen group showed least microleakage followed by control but differences between them were statistically not significant (p>0.05). Similarly the differences between Ultrasonic plus halogen group and ultrasonic group were not significant (p>0.05). The differences between ultrasonic and halogen group were statistically significant (p<0.05). CONCLUSION: Halogen light decreases the microleakage of enamel adjacent to GC Type IX glass ionomer restorations, when used to accelerate the setting reaction of glass ionomers and can be used as command set method in paediatric dentistry.

TNFα blockers followed by continuation of sulfasalazine and methotrexate combination: a retrospective study on cost saving options of treatment in Spondyloarthritis.

High cost deters continuous use of tumor necrosis factor α blockers (TNFi) in developing countries. The objective of this study was to evaluate outcome and expenditure incurred in Spondyloarthritis (SpA) patients beyond a year of follow-up after receiving four doses of infliximab (IFX) over and above background therapy of methotrexate (MTX) and sulfasalazine (SSZ) combination. Electronic medical records were screened for patients with SpA satisfying the Assessment of Spondyloarthritis International Society (ASAS) criteria between 2008 and 2014. Patients who completed at least 1 year of follow-up after receiving four doses of IFX (5 mg/kg at 0, 2, 6, and 14 weeks) on a background therapy of MTX (10-25 mg/week) and SSZ (2-3 g/day) combination were enrolled after obtaining an informed consent. Primary outcome assessed was "time to disease flare". Changes in acute phase reactants, patient reported outcomes (BASDAI, BASFI), and cost were also assessed. Forty-five patients were enrolled. Mean (SD) duration of follow up after fourth IFX dose was 28.9 (18.7) months. Disease flare occurred in 33.3% (15/45) after a mean (SD) duration of 14.5 (10.8) months as compared to 4-6 months described in literature on discontinuing TNFi. Reduction in ESR, CRP, BASDAI and BASFI continued to be statistically significant at follow-up as compared to baseline. As compared to continuous IFX therapy, this treatment reduced cost by 57.1% for each patient-month of follow-up. Short course IFX dosing followed by continuation of MTX and SSZ combination can prolong time to disease flare and decrease requirement for additional IFX dose in SpA. This regimen could be a cost saving option for patients with SpA.

Serum Cytokine Profile in Asian Indian Patients with Takayasu Arteritis and its Association with Disease Activity.

BACKGROUND: Arterial inflammation Takayasu arteritis (TA) is an outcome of balance between pro- and anti-inflammatory cytokines. Comprehensive assessment of these cytokines is important for understanding pathogenesis and assessing disease activity. OBJECTIVE: To study pro- and anti-inflammatory cytokines representing different T-helper cell pathway in serum samples of Asian Indian patients with TA and to assess their association with disease activity. METHODS: Consecutive Indian patients with TA were assayed for serum interferon-γ, interleukin-6, interleukin-23, interleukin-17, interleukin-10 and transforming growth factor- ß levels at baseline and follow up visit. Patients were grouped into active and stable disease based on Indian Takyasu Arteritis clinical Activity Score-2010. Serum levels of these cytokines between active and stable disease and between baseline and follow up visits were compared by non-parametric tests. RESULTS: Among 32 patients enrolled, 15 were classified as active while 17 as stable disease at baseline. IFN-γ levels were significantly higher in active disease than stable disease (p=0.0129) while other cytokines did not differ significantly between 2 groups. Serum levels of none of the cytokines changed significantly over 2 visits in both responders and non-responders. IL23 levels positively correlate with disease duration ((r=0.999; p<0.005). Modest correlation was observed between IFN-γ and IL23 levels at both baseline and follow up and between IFN-γ and IL-6 and CRP at follow up. CONCLUSION: IFN-γ levels are raised in active disease in TA and correlates well with other biomarkers of disease activity and proinflammatory cytokines. There is also a direct correlation between Il-23 levels and disease duration.