Long-standing and poorly controlled disease in juvenile dermatomyositis is associated with calcinosis: a real-world experience from a low-middle income country.

To study the prevalence and predictors of calcinosis in Juvenile Dermatomyositis (JDM). Medical records over 20 years at a tertiary care rheumatology center in Northern India were reviewed to identify patients with JDM and clinical details were recorded. The frequency of calcinosis, predictors, specific treatment, and its outcomes were studied. Data are expressed as median and interquartile range. In eighty-six patients (median age 10) of JDM, the frequency of calcinosis was 18.2% (8.5% at presentation). Younger age at presentation, longer follow-up, heliotrope rash [Odds Ratio (95% confidence interval), 11.4 (1.4-92.12)], chronic or polycyclic course [4.4 (1.2-15.5)] and cyclophosphamide use [8.2 (1.6-41.9)] were associated with calcinosis. Dysphagia [0.14 (0.02-1.2)] and elevated muscle enzymes [0.14 (0.04-0.5)] were negatively associated with calcinosis. Treatment with pamidronate had a good to moderate response to calcinosis in five of seven children. Calcinosis in JDM is associated with long-standing, poorly controlled disease, and the use of bisphosphonates like pamidronate offer promise in the future for its treatment.

Tuberculosis remains a leading contributor to morbidity due to serious infections in Indian patients of SLE.

INTRODUCTION: Infections are a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). We assessed the incidence and risk factors for major infections in SLE in India. METHODS: A retrospective review of a cohort of 1354 patients of adult SLE (ACR 1997 criteria) seen between 2000 and 2021 at a single center was conducted. Serious infections (need for hospitalisation, prolonged intravenous antibiotics, disability, or death) were recorded. Cox regression was used to determine factors associated with serious infection and the effects of serious infection on survival and damage. RESULTS: Among the 1354 patients (1258 females, mean age of 30.3 years, follow-up of 7127.89 person-years), there were 439 serious infections in 339 patients (61.6 per 1000 person-years follow-up). Bacterial infections (N = 226) were the most common infection followed by mycobacterial infections (n = 81), viral (n = 35), and then invasive fungal infections (N = 13). Mycobacterium tuberculosis was the single most common microbiologically confirmed organism with incidence of 1136.4/100,000 person-years with 72.8% of them being extrapulmonary. Infection free survival at 1 year and 5 years was 82.9% and 73.8%. There were 119 deaths with infection attributable mortality in 65 (54.6%). On multivariable Cox regression analysis, higher baseline activity (HR 1.02, 1.01-1.05), gastrointestinal involvement (HR 2.75, 1.65-4.69), current steroid dose (HR 1.65, 1.55-1.76), and average cumulative steroid dose per year (HR 1.007, 1.005-1.009) were associated with serious infection and higher albumin (HR 0.65, 0.56-0.76) was protective. Serious infections led to greater damage accrual (median SLICC damage index of 1 vs. 0) and mortality (HR was 18.2, 32.7 and 81.6 for the first, second, and third infections). CONCLUSION: Serious infections remain a major cause of mortality and damage accrual in SLE and higher disease activity, gastrointestinal involvement, hypoalbuminemia, current steroid dose, and cumulative steroid dose are the risk factors for it.

Peripheral T helper subset profiling in idiopathic inflammatory myositis: Proof of concept.

INTRODUCTION: There is a dearth of biomarkers in Idiopathic Inflammatory Myopathies (IIM) to recognize ongoing muscle inflammation and distinguish damage from activity. Since IIM is an autoantibody-mediated disease with tertiary lymphoid organogenesis reported in the diseased muscles, we aimed to study the peripheral blood T helper (Th) subset profiling as a plausible reflection of ongoing muscle inflammation. METHODS: Fifty-six patients of IIM were compared with 21 healthy controls (HC) and 18 patients with sarcoidosis. Th1, Th17, Th17.1, and Treg cells were identified after stimulation assays (BD Biosciences). Myositis autoantibodies were tested by line immunoassay (Euroimmune, Germany). RESULTS: All Th subsets were elevated in IIM as compared with HC. As compared to HC, PM had elevated Th1 and Treg while Th17 and Th17.1 populations were higher in OM. Patients with sarcoidosis had higher Th1 and Treg but lower Th17 population as compared to IIM {Th1(69.1% vs 49.65%, p<0.0001), {Treg (12.05% vs 6.2%, p<0.0001), {Th17 (2.49% vs 4.4%, p<0.0001)}. Similar results were obtained when sarcoidosis ILD was compared with IIM ILD with a higher Th1 and Treg population but lower Th17 population in the former. No difference in T cell profile was observed after stratification for MSA positivity, type of MSA, clinical features of IIM and disease activity. CONCLUSION: Th subsets in IIM are distinct from sarcoidosis and HC with a TH17 predominant paradigm, creating a case of exploring Th17 pathway and IL-17 blockers for the treatment of IIM. However, cell profiling cannot distinguish active from inactive disease limiting its predictive potential as a biomarker of activity in IIM.

Peripheral T helper subset profiling in idiopathic inflammatory myositis: Proof of concept / Perfil de subconjunto auxiliar T periférico en miositis inflamatoria idiopática: prueba de concepto

Introduction: There is a dearth of biomarkers in Idiopathic Inflammatory Myopathies (IIM) to recognize ongoing muscle inflammation and distinguish damage from activity. Since IIM is an autoantibody-mediated disease with tertiary lymphoid organogenesis reported in the diseased muscles, we aimed to study the peripheral blood T helper (Th) subset profiling as a plausible reflection of ongoing muscle inflammation. Methods: Fifty-six patients of IIM were compared with 21 healthy controls (HC) and 18 patients with sarcoidosis. Th1, Th17, Th17.1, and Treg cells were identified after stimulation assays (BD Biosciences). Myositis autoantibodies were tested by line immunoassay (Euroimmune, Germany). Results: All Th subsets were elevated in IIM as compared with HC. As compared to HC, PM had elevated Th1 and Treg while Th17 and Th17.1 populations were higher in OM. Patients with sarcoidosis had higher Th1 and Treg but lower Th17 population as compared to IIM {Th1(69.1% vs 49.65%, p<0.0001), {Treg (12.05% vs 6.2%, p<0.0001), {Th17 (2.49% vs 4.4%, p<0.0001)}. Similar results were obtained when sarcoidosis ILD was compared with IIM ILD with a higher Th1 and Treg population but lower Th17 population in the former. No difference in T cell profile was observed after stratification for MSA positivity, type of MSA, clinical features of IIM and disease activity. Conclusion: Th subsets in IIM are distinct from sarcoidosis and HC with a TH17 predominant paradigm, creating a case of exploring Th17 pathway and IL-17 blockers for the treatment of IIM. However, cell profiling cannot distinguish active from inactive disease limiting its predictive potential as a biomarker of activity in IIM.(AU)

Introducción: Hay una escasez de biomarcadores en las miopatías inflamatorias idiopáticas (MII) para reconocer la inflamación muscular en curso y distinguir el daño de la actividad. Dado que la MII es una enfermedad mediada por autoanticuerpos con organogénesis linfoide terciaria informada en los músculos enfermos, nuestro objetivo fue estudiar el perfil del subconjunto de linfocitos T helpers (Th) de sangre periférica como un reflejo plausible de la inflamación muscular en curso. Métodos: Se compararon 56 pacientes de MII con 21 controles sanos (CS) y 18 pacientes con sarcoidosis. Las células Th1, Th17, Th17.1 y Treg se identificaron después de los ensayos de estimulación (BD Biosciences). Los autoanticuerpos de miositis se analizaron mediante inmunoanálisis en línea (Euroimmune, Alemania). Resultados: Todos los subconjuntos de Th estaban elevados en las MII en comparación con los CS. En comparación con los CS, PM tenía Th1 y Treg elevados, mientras que las poblaciones de Th17 y Th17.1 eran más altas en OM. Los pacientes con sarcoidosis tenían una población Th1 y Treg más alta pero una población Th17 más baja en comparación con MII {Th1 (69,1% frente a 49,65%, p<0,0001), {Treg (12,05% frente a 6,2%, p<0,0001), {Th17 (2,49% frente a 4,4%, p<0,0001)}. Se obtuvieron resultados similares cuando se comparó la EPI de sarcoidosis con la EPI de las MII con una mayor población Th1 y Treg pero menor población Th17 en la primera. No se observaron diferencias en el perfil de células T después de la estratificación por positividad de MSA, tipo de MSA, características clínicas de las MII y actividad de la enfermedad. Conclusión: Los subconjuntos de Th en las MII son distintos de la sarcoidosis y los CS con un paradigma predominante TH17, lo que crea un caso de exploración de la vía Th17 y los bloqueadores de IL-17 para el tratamiento de las MII...(AU)

Renal involvement in Sjogren's syndrome: predictors and impact on patient outcomes.

Renal disease in primary Sjogren's Syndrome(pSS) occurs as tubulointerstitial nephritis(TIN) or glomerulonephritis(GN). Data from India on pSS are sparse and even less on nephritis.We studied the prevalence and impact of renal disease on patient outcomes. We reviewed 179 (F:M 12.7:1, age 41.7 ± 12.9 years) patients of pSS from records at a single centre from 2000 to 2020. Data on nephritis, clinical and laboratory variables were collected from baseline visit. Outcomes studied were chronic kidney disease(CKD) and death. We identified predictors of nephritis and rising creatinine on follow-up.Fifty-four (30.17%) patients had nephritis. Their mean age was 40.19 ± 13.28 years with 157.3 person-years follow-up. Vasculitis (OR 2.33, 1.02-5.3), fatigue (OR 3.29, 1.63-6.65), ANA positivity (OR 7.79, 1-60.62), anti-Ro52 (OR 2.74, 1.18-6.39), anti-La (OR 2.13, 1.1-4.14), both Ro and La (OR 2.4, 1.23-4.69) and lymphopenia (OR 2.27, 1.16-4.41) predicted nephritis on univariate analysis. On multivariate analysis, only fatigue (OR 2.83, 1.22-6.57) and an interaction between polyarthritis and vasculitis (OR 9.17, 1.15-72.96) was associated with nephritis. Creatinine at one (1.6 ± 1.17 mg/dL vs. 0.8 ± 0.2 mg/dL) and 2 years (1.62 ± 1.19 mg/dL vs. 0.8 ± 0.2 mg/dL) follow-up was higher in the nephritis group. Baseline haematuria, leukocyturia, 24 h urinary protein and thrombocytopenia were independent predictors of rising creatinine. Six patients died and 10 developed CKD. Event-free (death or CKD) survival was 89.1% at 5 years. Patients with nephritis had worse event-free survival.Our cohort had a younger age of onset of Sjogren's syndrome and a higher prevalence of nephritis than previously reported. Fatigue, polyarthritis and vasculitis at baseline predicted the development of nephritis. Nephritis was associated with a higher probability of death or CKD.

Multimodality carotid plaque tissue characterization and classification in the artificial intelligence paradigm: a narrative review for stroke application.

Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality in the United States of America and globally. Carotid arterial plaque, a cause and also a marker of such CVD, can be detected by various non-invasive imaging modalities such as magnetic resonance imaging (MRI), computer tomography (CT), and ultrasound (US). Characterization and classification of carotid plaque-type in these imaging modalities, especially into symptomatic and asymptomatic plaque, helps in the planning of carotid endarterectomy or stenting. It can be challenging to characterize plaque components due to (I) partial volume effect in magnetic resonance imaging (MRI) or (II) varying Hausdorff values in plaque regions in CT, and (III) attenuation of echoes reflected by the plaque during US causing acoustic shadowing. Artificial intelligence (AI) methods have become an indispensable part of healthcare and their applications to the non-invasive imaging technologies such as MRI, CT, and the US. In this narrative review, three main types of AI models (machine learning, deep learning, and transfer learning) are analyzed when applied to MRI, CT, and the US. A link between carotid plaque characteristics and the risk of coronary artery disease is presented. With regard to characterization, we review tools and techniques that use AI models to distinguish carotid plaque types based on signal processing and feature strengths. We conclude that AI-based solutions offer an accurate and robust path for tissue characterization and classification for carotid artery plaque imaging in all three imaging modalities. Due to cost, user-friendliness, and clinical effectiveness, AI in the US has dominated the most.

Rheumatology education in India: a survey-based cross sectional study.

This study aimed at understanding the perception and perspectives of rheumatology trainees about specialist training in India. Rheumatology trainees (Doctorate of Medicine, Diplomate of National Board) in Indian universities (2010 onwards) were contacted to complete a validated e-survey consisting of 41 questions to evaluate the current rheumatology training in India. Of 53 respondents (M:F 3.4:1, mean age 37 years ± 12.7), 81.1% trained at government hospitals, and 15.1% trained at private hospitals. During training period, 37.5% respondents were exposed to 6-7 h of didactics/week. They treated nearly 175 patients (175 ± 35.4) per week and reported a reasonable level of independence in management of patients with common rheumatic diseases (RDs) during their training (7.5 ± 0.7 SD). However, nearly one-third of the trainees were not exposed to basic immunology and laboratory techniques. Similarly, placement in the radiology department was not a part of the curriculum for nearly half of the trainees, 80% were not confident to manage paediatric RDs and soft tissue rheumatism. Almost 60% did not feel comfortable in addressing ancillary care including patient counselling as they had not received formal training. Among the participants, 59% were not satisfied by the current system of assessment, 86.8% suggested for multiple time point-based assessment systems and 45.3% preferred objective and subjective assessment in final examinations. Rheumatology training in India offers notable exposure to patients and independence in managing cases. However, there is an unmet need for improvement in training in the field of laboratory, radiology and ancillary care, and to overhaul assessment system by including objective evaluation.

Spectrum of Myelitis in Systemic Lupus Erythematosus: Experience from a Single Tertiary Care Centre over 25 Years.

BACKGROUND: Inflammatory myelitis rarely occurs in Systemic Lupus Erythematosus (SLE). METHODS: Medical records from a tertiary care centre in India (1989-2018) were reviewed to identify patients with myelitis in SLE and their clinical characteristics and outcomes were compared with two matching comparators drawn from adjacent hospital registration numbers in the SLE database. RESULTS: Ten patients had myelitis from a cohort of 1768 patients with SLE. Myelitis was the first manifestation of lupus in 7 (70%). Cervicothoracic cord was most frequent site of involvement. ANA was negative at onset in 2 cases. One of 4 was positive for Anti-Aquaporin 4 antibody. Four had relapsing disease (16 events) with a median time to relapse of 0.65 years (0.3- 7 years). All cases received steroid sparing agents over the follow-up duration (78.5 patient years). Lupus nephritis (20% vs. 75%, p=0.004) and haematologic manifestations (0 vs. 25%, p=0.02) were less common. Higher frequency of anti-Ro antibodies was noted in the group with myelitis (p=0.05). CONCLUSION: Myelitis can be a presenting feature of SLE with lupus nephritis and hematologic involvement being rare. Relapses are common that mandate long-term immunosuppression.

Patient-Reported Outcome Measures in Takayasu Arteritis: A Systematic Review and Meta-Analysis.

INTRODUCTION: We conducted a systematic review of patient-reported outcome measures (PROMs) regarding quality of life, disability, mood abnormalities (anxiety, depression), fatigue, illness perceptions and fibromyalgia in Takayasu arteritis (TAK). Wherever available, comparisons with healthy controls, disease controls or longitudinal changes in PROMs were noted. METHODS: MEDLINE, EMBASE, Scopus, Web of Science and Pubmed Central databases, major recent international rheumatology conference abstracts, clinical trial databases and the Cochrane library were searched for relevant articles. Wherever possible, outcome measures across studies were pooled using the restricted maximum likelihood model. Inter-group differences were pooled and compared using standardized mean differences (SMD) with 95% confidence intervals (95% CI). Heterogeneity was assessed using the I2 statistic. Quality of randomized controlled trials was assessed using the Cochrane risk of bias tool. For cross-sectional and cohort studies, the Joana Briggs Institute checklist and Newcastle-Ottawa scale were used, respectively. GRADE methodology was used to determine the certainty of evidence for outcomes. RESULTS: Twenty-one studies (all but one observational) involving 1311 patients with TAK and 308 healthy controls were identified. Ten studies (559 TAK patients, 182 healthy controls were synthesized in a meta-analysis. Patients with TAK had worse quality of life (pooled SMD - 6.66, 95% CI - 10.08 to - 3.23 for individual domains; - 0.64, 95% CI - 1.19 to - 0.09 for pooled physical and mental component scores of 36-item Short Form Survey), depression (SMD 0.26, 95% 0.05-0.47) and anxiety (SMD 0.34, 95% CI - 0.06 to 0.75) scores and higher disability (SMD 0.64, 95% CI 0.43-0.84) than healthy controls. Patients with active TAK had worse quality of life, depression and work impairment when compared with those with inactive disease. Included studies were of moderate to high quality. Certainty of evidence for individual outcomes was low to very low. CONCLUSION: Literature on PROMs in TAK, albeit sparse, appears to indicate worse scores in patients with TAK compared to healthy individuals. These results, however, require cautious interpretation. Development of a TAK-specific PROM is an important focus of the research agenda.

Clinical spectrum of active tuberculosis in patients with systemic lupus erythematosus.

INTRODUCTION: There is paucity of data on tuberculosis in Indian patients with systemic lupus erythematosus (SLE). We retrospectively studied clinical features and outcome of tuberculosis in SLE. METHODS: Medical records of patients who developed tuberculosis simultaneous or after the diagnosis of SLE were retrospectively reviewed. All patients fulfilled 1997 ACR and/or SLICC 2012 classification criteria for SLE. A diagnosis of tuberculosis required bacteriological, histopathological or CT/MRI suggestive of tuberculosis and initiation of four drug antituberculous therapy. Baseline parameters were compared with the rest of cohort to identify predictors of tuberculosis. RESULTS: In our cohort of 1335 SLE patients, 48 (3.6%) developed tuberculosis. Incidence of tuberculosis was calculated to be 733 per 100,000 patient years and occurred after a mean disease duration of 3.0 ± 4.1 years. Extrapulmonary tuberculosis (n = 37) was commoner than pulmonary tuberculosis (n =11). Most common radiological pattern in pulmonary tuberculosis was miliary and musculoskeletal TB was most common extrapulmonary TB. A microbiological diagnosis was obtained in 52.1% patients. Male gender was associated with higher risk of tuberculosis [OR 3.30 (1.55-7.05)]. Mortality was 14.5% and all patients who died had either disseminated (n = 5) or central nervous system (CNS) tuberculosis (n = 2). CONCLUSION: Incidence of tuberculosis in SLE is higher than general population and is associated with different phenotype and higher mortality. Male gender was associated with increased risk of tuberculosis in SLE.

Macrophage activation syndrome in systemic lupus erythematosus and systemic-onset juvenile idiopathic arthritis: a retrospective study of similarities and dissimilarities.

Macrophage activation syndrome (MAS) is a serious complication of rheumatic diseases. Fever and hyperferritinemia are common in active systemic-onset juvenile idiopathic arthritis (sJIA) and cytopenia in active systemic lupus erythematosus (SLE), thus recognizing MAS in them is a challenge. We compared clinical and laboratory parameters, various classification criteria, and outcomes of MAS in SLE and sJIA. Clinical and laboratory data were extracted from case records of patients with clinician diagnosed cases of SLE-MAS (adult and pediatric) and sJIA-MAS, admitted (2004-2018) at a tertiary care hospital. Ravelli, International consensus, HLH-2004, and criteria proposed by Parodi et al. were applied and compared. Among 33 patients (18 females) with MAS, 19 had SLE (7, childhood-onset SLE) and 14 had sJIA. MAS was more likely to be the presenting manifestation of disease in SLE (p < 0.05). There were no differences in the clinical features among them. Patients with SLE-MAS had lower baseline total leucocyte and platelet counts (p < 0.01), whereas patients with sJIA-MAS had significantly higher median CRP (p = 0.002), fall in TLC (p = 0.012), delta ESR/CRP ratio (p = 0.02), and lower fibrinogen level (p = 0.006). Neutrophil-to-lymphocyte ratio, ferritin/CRP ratio, and the number of patients with ferritin/ESR > 80 were similar. Only 6/33(18%) fulfilled the HLH criteria. Criteria meant for sJIA-MAS or SLE-MAS performed well for both diseases and the majority of patients could be diagnosed using them. Two patients died in each group. MAS in SLE and sJIA is more similar than dissimilar in clinical features and outcome. Criteria meant for MAS in sJIA or SLE-MAS performed equally well in both diseases.

Infections Are Leading Cause of In-Hospital Mortality in Indian Patients With Inflammatory Myopathy.

OBJECTIVES: We explored causes of in-hospital mortality in patients with inflammatory myositis at a tertiary care center in Northern India. METHODS: Records of adults and children diagnosed with dermatomyositis (DM), polymyositis, or anti-synthetase syndrome (ASSD) who died between 2000 and 2018 were reviewed, and causes of death were determined. RESULTS: Of the 38 patients, 20 had DM (including 2 clinically amyopathic DM), 4 juvenile DM, 12 polymyositis, whereas 2 had ASSD. Median age at death was 42.0 (interquartile range, 32.8-52.5) years. Median disease duration at death was 18.5 (interquartile range, 2.0-23.5) months. Twenty-four (63.2%) had infection as the primary cause of death. Other causes of death included pharyngeal muscle weakness and aspiration (n = 6), myocarditis (n = 2), respiratory failure (n = 2), cerebral bleed (n = 2), and pulmonary embolism (n = 1). One patient succumbed to rapidly progressive interstitial lung disease, whereas another patient with ASSD died following respiratory distress after rituximab infusion. In post hoc analysis, although thrombocytopenia appeared to be a risk factor for early mortality (odds ratio, 13.3; 95% confidence interval, 1.4-123.8; p = 0.01), this was not supported in the multivariate analysis. CONCLUSIONS: Infections are the most common cause of in-hospital mortality in myositis patients.

Juvenile Reactive Arthritis and other Spondyloarthritides of Childhood: A 28-year Experience from India.

OBJECTIVES: Understanding of Juvenile reactive arthritis (jReA) and other spondyloarthritides of childhood (jSpA) is limited to small case series. Since most of them have speculated pathogenic origins in the gut, we compared and contrasted jReA with other jSpA -Enthesitis-related arthritis (ERA) and undifferentiated SpA (jUSpA). METHODS: A record-based medical data review of jReA, and jUSpA was compared with cohort data of ERA collected for other studies. Data are presented as median (interquartile range) and non-parametric tests used for analysis. RESULTS: Of 179 juvenile SpA (61 jReA; 101 ERA; and 17 jUSpA), 61 had jReA [M:F-52:9; 15.5 (12-18) years] with a disease duration of 2.75(1-36) months. Inflammatory backache IBP (32%), dactylitis (21%) and enthesitis (29%) were common. A significant proportion (14 of 17, 82.3% at >6 months follow-up) had a chronic course. 101 ERA [M:F-93:7; age-16(14-20) years] had a longer disease duration (45 vs 2.75 months, p<0.001), as compared with jReA. Enthesitis and IBP was more common in ERA (OR-2.3 and 3.4 respectively). jUSpA (n=17) had a similar clinico-laboratory profile and exhibited significant (7 of 17, 58.3%) chronicity over 9.5(4.8-37) months follow-up. CONCLUSION: jReA and jSpA exhibit similar features apart from varying disease duration, suggesting that jspA may form a continuum with similar clinico-laboratory profiles plausibly due to shared pathogenesis.

In-hospital mortality and its predictors in a cohort of SLE from Northern India.

BACKGROUND: Mortality in SLE has a bimodal peak with early deaths mainly related to disease activity and infection. Although mortality has reduced over years, it is still two to three folds compared to the general population. In India due to increased burden of infection and limited access to health care, the causes may be different. METHODS: Retrospective, review of records of all adult SLE patients fulfilling ACR 1997 criteria, who died in hospital between 2000-2019 at a teaching hospital in India was done. In addition, baseline clinical features were extracted for all adult SLE patients seen during this period.Infections were either bacteriologically proven or based on clinicradiological or serologic evidence. Active disease was defined as SLEDAI 2k ≥ 5. Logistic regression was performed to ascertain risk factors for mortality. RESULTS: A total of 1337 (92% females) patient records were reviewed .The mean age at presentation was 29.9 ± 9 years.60-75% of patients had fever, mucocutaneous disease and arthritis, while nephritis, hematologic, serositis and neurologic involvement was seen in 48.6%, 43.2%, 16% and 10.3% respectively as presenting mainfestations. There were 80 in hospital deaths .Infection was the most common cause of death, with 37 due to infection alone and in 24 disease activity also contributed. Only 18 deaths were due to active disease. Among bacterial infections lung was the most common site and gram negative organism were the most common pathogens. There were 10 deaths due to Tuberculosis(TB) and half of them had disseminated disease. Patients with disease activity had a SLEDAI of 14.8 ± 6.4, with neurological, renal and cardiovascular involvement being the major contributors to mortality in 11, 7 and 6 cases respectively. Higher age at onset, male gender, fever, myositis, neurological, cardiovascular, gastrointestinal involvement, vasculitis, elevated serum creatinine at baseline were independent predictors of death. CONCLUSION: Infections are the most common cause of in-hospital mortality in SLE and TB still accounts for 15% of deaths related to infection. Vasculitis, myositis, cardiovascular and gastrointestinal involvement emerged as novel predictors of mortality in our cohort.

3-D optimized classification and characterization artificial intelligence paradigm for cardiovascular/stroke risk stratification using carotid ultrasound-based delineated plaque: Atheromatic™ 2.0.

BACKGROUND AND PURPOSE: Atherosclerotic plaque tissue rupture is one of the leading causes of strokes. Early carotid plaque monitoring can help reduce cardiovascular morbidity and mortality. Manual ultrasound plaque classification and characterization methods are time-consuming and can be imprecise due to significant variations in tissue characteristics. We report a novel artificial intelligence (AI)-based plaque tissue classification and characterization system. METHODS: We hypothesize that symptomatic plaque is hypoechoic due to its large lipid core and minimal collagen, as well as its heterogeneous makeup. Meanwhile, asymptomatic plaque is hyperechoic due to its small lipid core, abundant collagen, and the fact that it is often calcified. We designed a computer-aided diagnosis (CADx) system consisting of three kinds of deep learning (DL) classification paradigms: Deep Convolutional Neural Network (DCNN), Visual Geometric Group-16 (VGG16), and transfer learning, (tCNN). DCNN was 3-D optimized by varying the number of CNN layers and data augmentation frameworks. The DL systems were benchmarked against four types of machine learning (ML) classification systems, and the CADx system was characterized using two novel strategies consisting of DL mean feature strength (MFS) and a bispectrum model using higher-order spectra. RESULTS: After balancing symptomatic and asymptomatic plaque classes, a five-fold augmentation process was applied, yielding 1000 carotid scans in each class. Then, using a K10 protocol (trained to test the ratio of 90%-10%), tCNN and DCNN yielded accuracy (area under the curve (AUC)) pairs of 83.33%, 0.833 (p < 0.0001) and 95.66%, 0.956 (p < 0.0001), respectively. DCNN was superior to ML by 7.01%. As part of the characterization process, the MFS of the symptomatic plaque was found to be higher compared to the asymptomatic plaque by 17.5% (p < 0.0001). A similar pattern was seen in the bispectrum, which was higher for symptomatic plaque by 5.4% (p < 0.0001). It took <2 s to perform the online CADx process on a supercomputer. CONCLUSIONS: The performance order of the three AI systems was DCNN > tCNN > ML. Bispectrum-based on higher-order spectra proved a powerful paradigm for plaque tissue characterization. Overall, the AI-based systems offer a powerful solution for plaque tissue classification and characterization.

Insights into the knowledge, attitude and practices for the treatment of idiopathic inflammatory myopathy from a cross-sectional cohort survey of physicians.

The idiopathic inflammatory myopathies (IIM) are heterogeneous and lead to high morbidity and mortality. Knowledge deficits among healthcare professionals could be detrimental to clinical care. Identifying areas of deficient Knowledge, Attitude and Practice (KAP) of IIM can improve physician education and patient outcomes. To assess the proportion of physicians treating IIM with poor KAP and identify the key areas of deficit. An anonymised and validated e-survey (57 questions) was circulated among physicians treating IIM (purposive sampling). Responses were evaluated using the Likert scale for good (> 70% correct response), poor (> 20% chose > 2 answers) and the rest as intermediate consensus. Descriptive statistics were used. Intergroup comparisons were done using non-parametric tests. Of 80 (9.1% of 883) respondents, 90% were rheumatologists and 37.5% academicians. The knowledge base of treating physicians was good in specific domains such as triggers (80-90%), clinical presentation (MDA5, statin myositis, steroid myopathy, anti-synthetase syndrome) (82-92%), IIM mimics (41-89%), investigations (23-92%) and risk of osteoporosis in IIM (79%). There is also an intermediate knowledge base/consensus for outcome measures (30-56%) and response criteria (30-53%). There was poor knowledge and consensus on trials (27-34%), EULAR/ACR criteria (31%) and exercise-based interventions (17-62%). While 90% agree on the need for muscle biopsy to diagnose polymyositis, only one-third advocated it for juvenile and adult DM. Physicians have a good understanding of the triggers, clinical presentation and mimics of IIM. Poor to intermediate knowledge and consensus exists regarding muscle biopsy, outcome measures, response criteria and exercise-based interventions, which could be addressed through future focussed educational initiatives.

Circulatory Glutamine/Glucose ratio for evaluating disease activity in Takayasu arteritis: A NMR based serum metabolomics study.

Quantitative assessment of disease activity is important for effective care of patients with Takayasu arteritis (TA). Activated glutaminolysis and reduced glycolytic flux is the hallmark of active inflammation. Based on this, we hypothesize that the circulatory Glutamine/Glucose ratio (QGR) can serve as an indicant of active inflammation in TA. To probe this hypothesis, the serum samples were collected from 45 active and 53 inactive TA patients fulfilling American College of Rheumatology (ACR) criteria and assessed for disease activity according to Indian Takayasu Clinical Activity Score (ITAS) using acute phase reactant-erythrocyte sedimentation rate [ITAS-A (ESR)]. The quantitative profiles of circulatory metabolites implicated in glutaminolysis (Glutamine and Glutamate) and those which estimate glycolytic flux (i.e. glucose and lactate) were measured using high field (800 MHz) NMR spectroscopy. The recorded spectra were analyzed using CHENOMX NMR Suite and the estimated concentration profiles were compared and evaluated for their diagnostic potential using Metaboanalyst. Compared to inactive-TA patients, the sera of active-TA patients were characterized by significantly decreased serum levels of glutamine and lactate suggesting that these patients exhibit activated glutaminolysis and reduced glycolytic activity. This is further supported by significantly decreased QGR and lactate to glucose ratio (LGR) levels in active compared to inactive TA patients. The receiver operating characteristic (ROC) curve analysis revealed satisfactory accuracy, sensitivity and specificity for QGR [with area under ROC curve (AUROC) = 0.76 and 95% confidence interval (CI) = 0.66-0.84) compared to that for LGR (with AUROC = 0.67 and CI = 0.561-0.77). Therefore, we believe that the circulatory QGR has the potential to serve as surrogate marker for the assessment of disease activity in TA patients. However, the use of this ratio in clinical settings will require future studies on large patient cohorts and procedural optimization as well to improve accuracy.

Folyl polyglutamate synthethase (FPGS) gene polymorphisms may influence methotrexate adverse events in South Indian Tamil Rheumatoid Arthritis patients.

The aim of the study was to look for the association of FPGS 2752 G > A (rs1544105), FPGS 1994 A > G (rs10106), and GGH 452 C > T (rs 11545078), GGH -401C > T (rs 3758149) gene polymorphisms with methotrexate (MTX) treatment response and MTX-induced adverse events in South Indian Tamil patients with rheumatoid arthritis (RA). Further the influence of these gene polymorphisms on MTX polyglutamate levels was analyzed. A total of 330 patients with RA were investigated. FPGS gene polymorphisms were analyzed by TaqMan 5'nuclease assay and GGH gene polymorphisms were analyzed by PCR-RFLP. Methotrexate polyglutamates (nmol/L of packed erythrocytes) were measured by liquid chromatography mass spectrometry (LCMS/MS) method. We found that the heterozygous genotype of FPGS rs1544105 [p = 0.02, OR 1.93, 95% CI (1.15-3.35)] and FPGS rs10106 AG genotype [p = 0.01, OR 2.11, 95% CI (1.20-3.71)] were associated with MTX adverse events. FPGS rs1544105 and GGH -401C > T SNPs influenced the polyglutamate levels. None of the investigated SNPs seems to be associated with MTX treatment outcome.

Vasculitis research: Current trends and future perspectives.

We discuss recent and prospective research in small and large vessel vasculitis. Large cohorts of Takayasu arteritis (TA) have been recently published from across the world, clarifying our understanding of this uncommon disease. Novel open-ended approaches like large-scale genotyping, proteomics and metabolomics have helped gain novel insights into TA, giant cell arteritis (GCA) and anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Recent advances in the imaging of TA and GCA offer promise for earlier diagnosis and better monitoring of response to therapy. Although two randomized controlled trials of abatacept and tocilizumab failed to meet their primary end-points, successful large-scale studies of abatacept and tocilizumab in GCA hold promise for better disease control. While cyclophosphamide has revolutionized the management of AAV, increasing use of rituximab as an alternative induction regimen, as well as use of novel approaches involving reduced or no corticosteroid use for AAV and alternative agents such as avacopan (a complement 5a receptor antagonist) hold promise for lesser toxic induction regimens in the future. Increasingly, the risk of cardiovascular events and comorbidities such as osteoporosis are being recognized as factors affecting long-term prospects of patients with vasculitis. There is a shift in emphasis to utilize patient-reported outcomes to more accurately gauge the impact of vasculitides and their treatment.