Prevalence, Predictors, and Prognosis of Serious Infections in Takayasu Arteritis: A Cohort Study.

OBJECTIVE: To describe the incidence, risk factors, and outcomes associated with serious infections in patients with Takayasu arteritis (TA). METHODS: Serious infections, defined as infections resulting in hospitalization or death or unusual infections like tuberculosis, were identified from a cohort of patients with TA. Corticosteroid and disease-modifying antirheumatic drug (DMARD) use at the time of serious infection was noted. Demographic characteristics, clinical presentation, angiography, and disease activity at presentation, and the use of DMARDs during follow-up were compared between patients with TA with or without serious infections. Mortality in patients with TA who developed serious infections was compared to those who did not using hazard ratios (HR; with 95% CI). RESULTS: Of 238 patients with TA, 38 (16%) had developed serious infections (50 episodes, multiple episodes in 8; 3 episodes resulted in death). Among the 38 initial episodes, 11/38 occurred in those not on corticosteroids and 14/38 in those not on DMARDs. Pneumonia (n = 19) was the most common infection, followed by tuberculosis (n = 12). Patients with TA who developed serious infections vs those who did not had higher disease activity at presentation (active disease 97.4% vs 69.5%, mean Indian Takayasu Arteritis Activity Score 2010 12.7 (SD 7.3) vs 10.2 (SD 7.0), mean Disease Extent Index in Takayasu Arteritis 11.2 (SD 6.1) vs 8.8 (SD 6.1) and were more frequently initiated on corticosteroids or DMARDs. HRs calculated using exponential parametric regression survival-time model revealed increased mortality rate in patients with TA who developed serious infections (HR 5.52, 95% CI 1.75-17.39). CONCLUSION: Serious infections, which occurred in the absence of immunosuppressive treatment in approximately one-fifth of patients with TA, were associated with increased mortality in patients with TA.

Validation of the 2022 American College of Rheumatology/EULAR classification criteria for Takayasu arteritis.

OBJECTIVES: The present study validates the 2022 ACR/European Alliance of Associations for Rheumatology (EULAR) classification criteria for Takayasu's arteritis (TAK), compared with the 1990 ACR TAK classification criteria. METHODS: The fulfilment of 2022 ACR/EULAR and 1990 ACR TAK criteria from four referral centres was assessed for TAK compared with extracranial giant cell arteritis (EC-GCA) and other controls. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio of a positive test (LR+) or negative test (LR-), and area under receiver operating characteristics curve (AUC) were calculated. RESULTS: Among 504 patients with TAK (404 females) and 222 controls (151 females, 144 patients with EC-GCA), the 2022 ACR/EULAR criteria had better sensitivity (95.83% vs 82.94%) and NPV, but poorer specificity (63.51% vs 90.54%), PPV, LR+, LR- and AUC at the pre-determined cut-offs than the 1990 ACR criteria. The 2022 ACR/EULAR criteria had greater specificity (76.06% vs 57.62%) and AUC (0.845 vs 0.771), with similar sensitivity (93% vs 96.53%) in males as in females. The 2022 ACR/EULAR criteria performed similarly with only EC-GCA as controls (sensitivity 95.83%, specificity 60.42%, AUC 0.781). Sensitivity remained similar, whereas specificity was higher for 40-60 years vs <40 years. Cut-offs of ≥6 (sensitivity 91.87%, specificity 82.88%) and ≥7 (sensitivity 86.71%, specificity 86.49%), or removing the point for female sex (sensitivity 92.64%, specificity 81.08%) greatly improved the balance between sensitivity and specificity. CONCLUSION: The poor specificity of the 2022 ACR/EULAR TAK criteria in real-life settings was improved by increasing the cut-off to 6 or 7, or removing the point for female sex.

Increased mortality rate in Takayasu arteritis is largely driven by cardiovascular disease-a cohort study.

OBJECTIVES: To analyze the risk, causes, and predictors of mortality in Takayasu arteritis (TAK). METHODS: Survival was assessed in a cohort of patients with TAK using Kaplan-Meier curves. Age- and sex-standardized mortality ratio (SMR = observed: expected deaths) for TAK were calculated by applying age- and sex-specific mortality rates for the local population to calculate expected deaths. Hazard ratios (HR with 95%CI) for predictors of mortality based on demographic characteristics, presenting features, baseline angiographic involvement, disease activity, number of immunosuppressive medications used, procedures related to TAK, and any serious infection were calculated using Cox regression or exponential parametric regression models. RESULTS: Among 224 patients with TAK (159 females, mean follow-up duration 44.36 months), survival at 1, 2, 5, and 10 years was 97.34%, 96.05%, 93.93%, and 89.23%, respectively. Twelve deaths were observed, most of which were due to cardiovascular disease (heart failure, myocardial infarction, stroke). Mortality risk was significantly higher with TAK (SMR 17.29, 95%CI 8.95-30.11) than the general population. Earlier age at disease onset (HR 0.90, 95%CI 0.83-0.98; or pediatric-onset vs adult-onset disease, HR 5.51, 95%CI 1.57-19.32), higher disease activity scores (ITAS2010: HR 1.15, 95%CI 1.05-1.25, DEI.TAK: HR 1.18, 95%CI 1.08-1.29), any serious infections (HR 5.43, 95%CI 1.72-17.12), heart failure (HR 7.83, 95%CI 2.17-28.16), or coeliac trunk involvement at baseline (HR 4.01, 95%CI 1.26-12.75) were associated with elevated mortality risk. CONCLUSION: Patients with TAK had an elevated risk of mortality as compared with the general population. Cardiovascular disease was the leading cause of death in TAK.

Clinical metabolomics by NMR revealed serum metabolic signatures for differentiating sarcoidosis from tuberculosis.

BACKGROUND: Pulmonary sarcoidosis (SAR) and tuberculosis (TB) are two granulomatous lung-diseases and often pose a diagnostic challenge to a treating physicians. OBJECTIVE: The present study aims to explore the diagnostic potential of NMR based serum metabolomics approach to differentiate SAR from TB. MATERIALS AND METHOD: The blood samples were obtained from three study groups: SAR (N = 35), TB (N = 28) and healthy normal subjects (NC, N = 56) and their serum metabolic profiles were measured using 1D 1H CPMG (Carr-Purcell-Meiboom-Gill) NMR spectra recorded at 800 MHz NMR spectrometer. The quantitative metabolic profiles were compared employing a combination of univariate and multivariate statistical analysis methods and evaluated for their diagnostic potential using receiver operating characteristic (ROC) curve analysis. RESULTS: Compared to SAR, the sera of TB patients were characterized by (a) elevated levels of lactate, acetate, 3-hydroxybutyrate (3HB), glutamate and succinate (b) decreased levels of glucose, citrate, pyruvate, glutamine, and several lipid and membrane metabolites (such as very-low/low density lipoproteins (VLDL/LDL), polyunsaturated fatty acids, etc.). CONCLUSION: The metabolic disturbances not only found to be well in concordance with various previous reports, these further demonstrated very high sensitivity and specificity to distinguish SAR from TB patients suggesting serum metabolomics analysis can serve as surrogate method in the diagnosis and clinical management of SAR.

Overlap syndrome of anti-aquaporin-4 positive neuromyelitis optica spectrum disorder and systemic lupus erythematosus: A systematic review of individual patient data.

BACKGROUND: Neurological involvement can occur in systemic lupus erythematosus (SLE) due to co-existing neuromyelitis optica spectrum disorder (NMOSD). The symptoms can mimic those of neuropsychiatric manifestations of SLE. Pathogenic anti-aquaporin-4 (AQP4) antibodies, commonly found in NMOSD, are responsible for the neuroinflammatory response and secondary demyelinating lesions. These anti-AQP4 antibodies can be the drivers of neuroinflammatory process in SLE patients, which is distinct from the immunopathogenesis seen in traditional neuropsychiatric SLE. The clinical course is often a relapsing one and is managed differently. In this review, we describe and outline the clinical course and outcomes of AQP4+ NMOSD/SLE overlap cases. METHODS: To investigate the co-existence of SLE with AQP4+NMOSD, we conducted a systematic review of individual patient data from case reports and case series reported in major databases. The study extracted clinic-demographic features, imaging and laboratory profiles, treatment approaches, and outcomes of these patients. Inclusion criteria for the review required patients to have positivity for AQP4 or NMO in the blood and/or cerebrospinal fluid (CSF) and exhibit at least one manifestation of both NMOSD and SLE. RESULTS: In this overlap between SLE and AQP4+NMOSD, a high female preponderance was observed, with 42 out of 46 patients (91.3%) being female. Nearly half of the NMOSD cases (47.8%) had onset after lupus, with a median of 5 years between the two diagnoses. Hematological manifestations were seen in the majority of patients (63%), as well as longitudinally extensive transverse myelitis (87%), and brainstem involvement on imaging (29.6%). Cerebrospinal fluid analysis showed a dominantly lymphocytic pleocytosis, with oligoclonal bands being reported scarcely. Although cyclophosphamide was the most common steroid sparing agent used for maintenance, robust evidence for both efficacy and safety in AQP4+NMOSD is available for mycophenolate mofetil, azathioprine, and rituximab. The majority of reported cases showed a relapsing course, while one patient had a monophasic course. CONCLUSION: AQP4+NMOSD in SLE patients is a relapsing and neurologically disabling disorder that can mimic neuropsychiatric manifestations, frequently occurs after the onset of lupus or may predate, responds to immunosuppressants, and necessitates indefinite treatment.

Paediatric-onset Takayasu's arteritis associates with worse survival than adult-onset Takayasu's arteritis. A matched retrospective cohort study.

OBJECTIVES: A subset of Takayasu's arteritis (TAK) begins in the paediatric age group (≤18 years). Differences in prognosis between paediatric-onset and adult-onset TAK are unclear. We compared the differences in the presentation and survival between paediatric-onset and adult-onset TAK in our cohort of TAK. METHODS: From a retrospective cohort of TAK, clinical presentation, angiographic features, treatments received, disease activity, and survival were compared between paediatric-onset and adult-onset TAK. Multivariable-adjusted logistic regression models were used to compute adjusted odds ratio (aOR) with 95% confidence intervals (95%CI) for paediatric-onset vs. adult-onset TAK. Hazard ratios (HR, with 95%CI) for mortality with paediatric-onset vs adult-onset TAK (crude, adjusted for prognostic covariates or differences in presentation) and propensity score-matched survival analyses were estimated. RESULTS: Among 56 paediatric-onset and 135 adult-onset TAK, chest pain (aOR 3.21, 95%CI 1.06-9.74), heart failure (aOR 3.16, 95%CI 1.05-9.53), headache (aOR 2.60, 95%CI 1.01-6.74), ascending aorta (aOR 3.02, 95%CI 1.04-8.80) and left renal artery involvement (aOR 2.45, 95%CI 1.04-5.80) were more frequent in paediatric-onset TAK. Despite similar longitudinal patterns of disease activity and glucocorticoid or disease-modifying antirheumatic drug (DMARD) use, mortality was higher for paediatric-onset TAK (HR, unadjusted 6.13, 95%CI 1.51-24.91; adjusted for prognostic covariates gender, diagnostic delay, baseline disease activity, number of conventional and biologic/targeted synthetic DMARDs used, 4.97, 95%CI 1.20-20.58; adjusted for differences between groups 5.54, 95%CI 1.22-25.09; after propensity-score matching for prognostic covariates, 54 pairs, log-rank p-value 0.026). CONCLUSIONS: Considering the greater mortality risk, greater vigilance is required while managing paediatric-onset TAK.

Overlap syndrome of anti-aquaporin 4 positive neuromyelitis optica spectrum disorder and primary Sjögren's syndrome: a systematic review of individual patient data.

Central nervous system (CNS) involvement can occur in primary Sjögren's syndrome (pSS) due to co-existing neuromyelitis optica spectrum disorder (NMOSD) which has a highly relapsing course requiring indefinite immunosuppression, and if not diagnosed early, damage accrual occurs over time leading to permanent disability and morbidity. In this review, we describe and outline the clinical course and outcomes of anti-aquaporin 4 (AQP4) antibody seropositive NMOSD with pSS overlap cases. To investigate the co-existence of AQP4 + NMOSD with pSS, we conducted a review of individual patient data from case reports and case series found in major databases. The study extracted clinico-demographic features, imaging and laboratory profiles, treatment approaches, and outcomes of these patients. Inclusion criteria for the review required patients to have positivity for anti-AQP4 or NMO-IgG autoantibodies in the blood and/or cerebrospinal fluid (CSF) and exhibit at least one manifestation of both pSS and NMOSD. In this overlap between AQP4 + NMOSD and pSS, 44 patients were included of whom 41 (93.2%) were females. The mean age of pSS onset was 44.8 ± 18.4 years and NMOSD onset was 43.2 ± 19.8 years. In 20 (45.5%) patients, NMOSD preceded pSS onset, 13 (29.5%) NMOSD occurred after pSS onset, and 11 (25%) patients had a simultaneous presentation. 31 (70.5%) patients experienced acute transverse myelitis, 21 (47.7%) optic neuritis, 14 (31.8%) cerebral syndrome, 10 (22.7%) acute brainstem syndrome, 5 (11.4%) area postrema syndrome, and 2 (4.5%) diencephalic clinical syndromes. For the treatment of acute phase, 40 (90.9%) patients received intravenous methylprednisolone, 15 (34.1%) received plasma exchange, and 10 (22.7%) received intravenous immunoglobulin; and for the induction/maintenance therapy, 16 (36.4%) patients received cyclophosphamide, 6 (13.6%) received rituximab, 16 (36.4%) received azathioprine, and 10 (22.7%) received mycophenolate mofetil. Disease course was monophasic in 2 (4.5%) and relapsing in 27 (61.4%) patients. At median (IQR) follow-up duration of 2.4 (6) years, 39 (88.6%) patients showed improvement, 3 (6.8%) showed stabilization and 2 (4.5%) showed worsening of their NMOSD manifestations. In this overlap syndrome of AQP4 + NMOSD and pSS, patients have a neurologically disabling disorder that can mimic neurological manifestations of pSS, frequently occurs prior to the onset of pSS, has a relapsing course, responds well to immunosuppressants, and necessitates indefinite treatment. Collaborative multicentre studies are needed to clarify the natural history and outcomes of this rare overlap syndrome.

Artificial intelligence-based preventive, personalized and precision medicine for cardiovascular disease/stroke risk assessment in rheumatoid arthritis patients: a narrative review.

The challenges associated with diagnosing and treating cardiovascular disease (CVD)/Stroke in Rheumatoid arthritis (RA) arise from the delayed onset of symptoms. Existing clinical risk scores are inadequate in predicting cardiac events, and conventional risk factors alone do not accurately classify many individuals at risk. Several CVD biomarkers consider the multiple pathways involved in the development of atherosclerosis, which is the primary cause of CVD/Stroke in RA. To enhance the accuracy of CVD/Stroke risk assessment in the RA framework, a proposed approach involves combining genomic-based biomarkers (GBBM) derived from plasma and/or serum samples with innovative non-invasive radiomic-based biomarkers (RBBM), such as measurements of synovial fluid, plaque area, and plaque burden. This review presents two hypotheses: (i) RBBM and GBBM biomarkers exhibit a significant correlation and can precisely detect the severity of CVD/Stroke in RA patients. (ii) Artificial Intelligence (AI)-based preventive, precision, and personalized (aiP3) CVD/Stroke risk AtheroEdge™ model (AtheroPoint™, CA, USA) that utilizes deep learning (DL) to accurately classify the risk of CVD/stroke in RA framework. The authors conducted a comprehensive search using the PRISMA technique, identifying 153 studies that assessed the features/biomarkers of RBBM and GBBM for CVD/Stroke. The study demonstrates how DL models can be integrated into the AtheroEdge™-aiP3 framework to determine the risk of CVD/Stroke in RA patients. The findings of this review suggest that the combination of RBBM with GBBM introduces a new dimension to the assessment of CVD/Stroke risk in the RA framework. Synovial fluid levels that are higher than normal lead to an increase in the plaque burden. Additionally, the review provides recommendations for novel, unbiased, and pruned DL algorithms that can predict CVD/Stroke risk within a RA framework that is preventive, precise, and personalized.

A systematic review and meta-analysis of mycobacterial infections in patients with idiopathic inflammatory myopathies.

OBJECTIVES: Infections including tuberculosis (TB) are a leading cause of morbidity and mortality in idiopathic inflammatory myopathies (IIM). We systematically reviewed the prevalence of mycobacterial infections in patients with IIM. METHODS: We screened PUBMED, EMBASE and SCOPUS databases and conference abstracts (2015-20) for original articles using Covidence. Pooled estimates of prevalence were calculated. RESULTS: Of 83 studies (28 cohort studies, two case control and 53 case reports), 19 were analysed. Of 14 043 IIM patients, DM (54.41%) was the most common subset among TB. Most studies were from Asia with high prevalence (5.86%, 2.33%-10.60%). Pooled prevalence of mycobacterial infections among IIM was 3.58% (95% CI: 2.17%, 5.85%, P < 0.01). Disseminated and extrapulmonary forms (46.58%; 95% CI: 39.02%, 54.31%, P = 1.00) were as common as pulmonary TB (49.07%; 95% CI: 41.43%, 56.75%, P =0.99) both for I2=0. Muscle involvement, an otherwise rare site, was frequently seen in case reports (24.14%). M. tuberculosis (28.84%) was the most common pathogen followed by Mycobacterium avium complex (3.25%). Non-tuberculous mycobacteria were less common overall (6.25; 95% CI: 3.49%, 10.93%) I2=0, P =0.94. Subgroup analysis and meta-regression based on high vs low TB regions found prevalence 6.61% (2.96%, 11.33%) in high TB regions vs 2.05% (0.90%, 3.56%) in low TB regions. While death due to TB was occasionally reported (P =0.82), successful anti-tubercular treatment was common (13.95%). CONCLUSION: TB is common in IIM, particularly in endemic regions though current data is largely heterogeneous. Extra-pulmonary forms and atypical sites including the muscle are frequent. Limited data suggests fair outcomes, although larger prospective studies may offer better understanding.

Tacrolimus induces remission in refractory and relapsing lupus nephritis by decreasing P-glycoprotein expression and function on peripheral blood lymphocytes.

P-glycoprotein (P-gp)-mediated efflux of corticosteroids (CS) may contribute to treatment unresponsiveness in Lupus Nephritis (LN) patients. Tacrolimus is a P-gp inhibitor and hence, may overcome this resistance. We aimed to study the response to tacrolimus, along with the expression and function of P-gp on peripheral blood lymphocytes (PBL) in patients with refractory and relapsing proliferative Lupus Nephritis. We enrolled 12 refractory/relapsing LN patients and treated them with corticosteroids and tacrolimus for 6 months. Expression and function of P-gp on PBL was measured by flow cytometry (as relative fluorescence index, RFI and Rhodamine dye efflux assay) before and 3 months after tacrolimus therapy. Renal response was assessed according to ACR response criteria after 3 and 6 months of tacrolimus therapy. 8 out of 12 refractory/relapsing LN patients achieved renal response (5 partial response, PR and 3 complete responses, CR) as early as 3 months, and 11 patients achieved renal response (7 PR and 4 CR) at 6 months from start of tacrolimus therapy. Proteinuria decreased from median urine protein creatinine ratio (UPCR) of 2.80 (2.00-3.40) at baseline to 1.20 (0.66-1.73) at 3 months (p < 0.001) and to 0.80 (0.19-1.30) at 6 months (p < 0.01). There was significant decrease in P-gp expression [RFI, 3.33 (2.87-4.97) vs 2.03 (1.25-3.86), p < 0.05) and P-gp function (RFI, 55.7 (29.7-84.1) vs 26.8 (16.1-37.0), p < 0.01) after 3 months of tacrolimus therapy. Tacrolimus achieves renal response in refractory/relapsing proliferative LN patients which may be partly related to overcoming P-glycoprotein mediated treatment unresponsiveness.

Clinical, radiologic and serologic profile of patients with interstitial pneumonia with autoimmune features: a cross-sectional study.

The current study aimed to characterize patients from a rheumatology referral center in north India, who satisfied the definition of interstitial pneumonia with autoimmune features (IPAF) as given by the American Thoracic Society and European Respiratory Society (ATS/ERS) consensus committee in 2015. Thirty-five adult patients aged 18 years and above, fulfilling the 2015 ATS/ERS criteria for IPAF were included in the study. The clinical and immunological profile, and radiologic findings on high-resolution computerized tomography thorax were noted. Antinuclear antibody (ANA) by indirect immunofluorescence at 1:320 titer and myositis-specific antibody (MSA) assays were performed. Non-parametric tests were used to compare variables between groups. The study cohort included predominantly female patients with a mean age of 50.6 ± 13 years and mean duration of disease of 38.8 ± 28.4 months. Majority of patients (49%) fulfilled the morphologic and serologic domains as per the IPAF consensus criteria and 31% patients had features in all three domains. Non-specific interstitial pneumonia was the most common pattern observed in 77% patients. Raynaud's phenomenon and inflammatory arthritis were the predominant autoimmune features. Pulmonary arterial hypertension was documented in 60% of patients on echocardiography. Positive ANA at 1:320 dilution was present in all 26 patients tested, whereas extractable nuclear antigen and MSA assays detected autoantibodies in 49% and 51% of patients respectively. IPAF predominantly affected females in the age group of 50 years and above, with varied autoimmune manifestations and autoantibody profile.

Statistical data presentation: a primer for rheumatology researchers.

Statistical presentation of data is key to understanding patterns and drawing inferences about biomedical phenomena. In this article, we provide an overview of basic statistical considerations for data analysis. Assessment of whether tested parameters are distributed normally is important to decide whether to employ parametric or non-parametric data analyses. The nature of variables (continuous or discrete) also determines analysis strategies. Normally distributed data can be presented using means with standard deviations (SD), whereas non-parametric measures such as medians (with range or interquartile range) should be used for non-normal distributions. While the SD provides a measure of data dispersion, the standard error provides estimates of the 95% confidence interval i.e. the actual mean in the population. Univariable analyses should be directed to denote effect sizes, as well as test a priori hypothesis (i.e. null hypothesis significance testing). Univariable analyses should be followed up by suitable adjusted multivariable analyses such as linear or logistic regression. Linear correlation statistics can help assess whether two variables change hand in hand. Concordance rather than correlation should be used to compare outcome measures of disease states. Prior sample size calculation to ensure adequate study power is recommended for studies which have analogues in the literature with SDs. Statistical considerations for systematic reviews should include appropriate use of meta-analysis, assessment of heterogeneity, publication bias assessment when there are more than ten studies, and quality assessment of studies. Since statistical errors are responsible for a significant proportion of retractions, appropriate statistical analysis is mandatory during study planning and data analysis.

Corticosteroid monotherapy for the management of Takayasu arteritis-a systematic review and meta-analysis.

We evaluated clinical response, normalization of inflammatory markers, angiographic stabilization (primary outcomes), relapses and adverse events (secondary outcomes) in Takayasu arteritis (TAK) patients following corticosteroid monotherapy. MEDLINE, EMBASE, Web of Science, Scopus, Pubmed Central, Cochrane library, clinical trial databases and major international Rheumatology conferences were searched for studies reporting outcomes in TAK following corticosteroid monotherapy (without language/date restrictions). Risk ratios were calculated for controlled studies. Proportions were pooled for uncontrolled studies. Heterogeneity was assessed using I2 statistic. Quality assessment of individual studies utilized the Newcastle-Ottawa scale. GRADE methodology ascertained certainty of individual outcomes across studies. Twenty-eight observational studies (1098 TAK) were identified. Twenty-three uncontrolled studies (580 TAK) were synthesized in meta-analysis. Clinical response was observed in 60% (95% CI 45-74%, 19 studies), normalization of inflammatory markers in 84% (95% CI 54-100%, 4 studies) and angiographic stabilization in 28% (95% CI 6-57%, 4 studies). Relapses occurred in 66% (95% CI 18-99%, 4 studies). Adverse events were reported in 51% (95% CI 2-99%, 4 studies). All pooled estimates had considerable heterogeneity, unexplained by subgroup analyses (time period, geographic location or number of patients). Two studies reported lesser restenosis following vascular surgery and fewer relapses when corticosteroids were combined with immunosuppressants compared with corticosteroid monotherapy. All outcomes had very low certainty. While corticosteroid monotherapy induces clinical response in most TAK patients, angiographic stabilization is observed in fewer than one-third. Most patients relapse following corticosteroid withdrawal. Preliminary evidence supports up-front addition of immunosuppressants to retard angiographic progression and reduce relapses (PROSPERO identifier CRD42021242910).

Poor maternal and foetal outcomes in women with systemic sclerosis: an interview-based study at a tertiary centre.

Poor obstetric outcomes are described in rheumatic diseases (RDs) such as systemic sclerosis (SSc). We assessed the effect of the disease in Indian women and compared with those in developed countries and other RDs. Women with SSc (ACR/EULAR 2013 criteria) registered at a tertiary care centre (2010-2016) were interviewed by teleconsultation. Pregnancies occurring after disease onset were compared with those occurring prior to it. Maternal complications included antepartum hemorrhage, postpartum hemorrhage, spontaneous abortion, preterm rupture of membrane, oligohydramnios, infection, prolonged labour, and foetal complications including low birth weight (LBW), intrauterine death (IUD), preterm delivery, and neonatal infection. Results were expressed as median (Interquartile range). Of 200 SSc, 75 patients aged 31 (22-38) years and disease duration 41 (32-50) months were interviewed. Diffuse cutaneous SSc was the most common (42.56%). 127 conceptions before the onset of SSc were compared with 15 after. Among post-diagnosis, 9 (60%) were live births, 3 (20%) spontaneous abortions 1 (6.7%) induced abortion, 2 (13.3%) IUD. Of the live births, 4 (26.7%) were preterm and 3 (20%) were LBW. Pregnancies after disease onset had a higher rate of maternal (OR - 4.9) and foetal (OR - 9.9) complications compared to pregnancies before SSc. Compared to the Italian cohort, Indian SSc patients had a higher abortion rate (OR - 5.8), frequent lower section ceaserean section (OR - 9.4) and lower live births (OR - 0.05). More frequent caesarean deliveries (OR - 93), preterm deliveries (OR - 20) when compared with lupus and favourable maternal outcomes (OR - 0.15), higher preterm deliveries (OR - 9.6) in comparison with Takayasu arteritis were noted. SSc incurs a higher risk of poor maternal as well as the foetal outcome.

Managing ANCA-associated vasculitis during the COVID-19 pandemic: results from an online survey.

Management of ANCA-associated vasculitis (AAV) during the COVID-19 pandemic poses unique therapeutic challenges. An online survey was conducted to understand physician's choices for treating AAV during the COVID-19 pandemic. Web-based survey featuring nineteen questions was circulated amongst physicians across various specialties. The responses regarding immunosuppressive therapy for remission induction and maintenance, COVID-19 testing, and preventive measures were recorded. A total of 304 responses were recorded. Most of the respondents were from India (83.9%) and comprised rheumatologists (66%) in practice for ≥ 5 years (71%). Though a majority preferred Rituximab or intravenous cyclophosphamide (CYC) as a remission induction agent, a significant proportion opted for oral CYC and mycophenolate mofetil (MMF) also. Only one-third wanted to test for COVID-19 before initiating immunosuppressive therapy in patients with organ/life-threatening manifestations. Rituximab was the most favored maintenance therapy (47%), followed by azathioprine, MMF, and methotrexate. The results of this focused survey of managing AAV patients depict the real-world dilemmas and physicians' choices in this setting.

Plagiarism in Non-Anglophone Countries: a Cross-sectional Survey of Researchers and Journal Editors.

BACKGROUND: Plagiarism is one of the most common violation of publication ethics, and it still remains an area with several misconceptions and uncertainties. METHODS: This online cross-sectional survey was conducted to analyze plagiarism perceptions among researchers and journal editors, particularly from non-Anglophone countries. RESULTS: Among 211 respondents (mean age 40 years; M:F, 0.85:1), 26 were scholarly journal editors and 70 were reviewers with a large representation from India (50, 24%), Turkey (28, 13%), Kazakhstan (25, 12%) and Ukraine (24, 11%). Rigid and outdated pre- and post-graduate education was considered as the origin of plagiarism by 63% of respondents. Paraphragiarism was the most commonly encountered type of plagiarism (145, 69%). Students (150, 71%), non-Anglophone researchers with poor English writing skills (117, 55%), and agents of commercial editing agencies (126, 60%) were thought to be prone to plagiarize. There was a significant disagreement on the legitimacy of text copying in scholarly articles, permitted plagiarism limit, and plagiarized text in methods section. More than half (165, 78%) recommended specifically designed courses for plagiarism detection and prevention, and 94.7% (200) thought that social media platforms may be deployed to educate and notify about plagiarism. CONCLUSION: Great variation exists in the understanding of plagiarism, potentially contributing to unethical publications and even retractions. Bridging the knowledge gap by arranging topical education and widely employing advanced anti-plagiarism software address this unmet need.

Formulating Hypotheses for Different Study Designs.

Generating a testable working hypothesis is the first step towards conducting original research. Such research may prove or disprove the proposed hypothesis. Case reports, case series, online surveys and other observational studies, clinical trials, and narrative reviews help to generate hypotheses. Observational and interventional studies help to test hypotheses. A good hypothesis is usually based on previous evidence-based reports. Hypotheses without evidence-based justification and a priori ideas are not received favourably by the scientific community. Original research to test a hypothesis should be carefully planned to ensure appropriate methodology and adequate statistical power. While hypotheses can challenge conventional thinking and may be controversial, they should not be destructive. A hypothesis should be tested by ethically sound experiments with meaningful ethical and clinical implications. The coronavirus disease 2019 pandemic has brought into sharp focus numerous hypotheses, some of which were proven (e.g. effectiveness of corticosteroids in those with hypoxia) while others were disproven (e.g. ineffectiveness of hydroxychloroquine and ivermectin).

A Review on Joint Carotid Intima-Media Thickness and Plaque Area Measurement in Ultrasound for Cardiovascular/Stroke Risk Monitoring: Artificial Intelligence Framework.

Cardiovascular diseases (CVDs) are the top ten leading causes of death worldwide. Atherosclerosis disease in the arteries is the main cause of the CVD, leading to myocardial infarction and stroke. The two primary image-based phenotypes used for monitoring the atherosclerosis burden is carotid intima-media thickness (cIMT) and plaque area (PA). Earlier segmentation and measurement methods were based on ad hoc conventional and semi-automated digital imaging solutions, which are unreliable, tedious, slow, and not robust. This study reviews the modern and automated methods such as artificial intelligence (AI)-based. Machine learning (ML) and deep learning (DL) can provide automated techniques in the detection and measurement of cIMT and PA from carotid vascular images. Both ML and DL techniques are examples of supervised learning, i.e., learn from "ground truth" images and transformation of test images that are not part of the training. This review summarizes (1) the evolution and impact of the fast-changing AI technology on cIMT/PA measurement, (2) the mathematical representations of ML/DL methods, and (3) segmentation approaches for cIMT/PA regions in carotid scans based for (a) region-of-interest detection and (b) lumen-intima and media-adventitia interface detection using ML/DL frameworks. AI-based methods for cIMT/PA segmentation have emerged for CVD/stroke risk monitoring and may expand to the recommended parameters for atherosclerosis assessment by carotid ultrasound.

Patient Perspectives on the Effect of the SARS-CoV-2 Pandemic on Patients With Systemic Sclerosis: An International Patient Survey.

BACKGROUND: The coronavirus disease (COVID-19) pandemic and its subsequent effects on health care systems have significantly impacted the management of chronic rheumatic diseases, including systemic sclerosis (SSc). METHODS: In this context, a 25-item anonymized e-survey was posted on the Twitter and Facebook e-groups and pages of various scleroderma organizations and patient communities to assess the problems faced by patients with SSc during the pandemic, with a focus on effects on the disease, drug procurance, continuity of medical care, and prevalent fears among patients. RESULTS: Of the 291 participants (median age of 55 [43.5-63] years, 93.8% females), limited systemic sclerosis was the most common diagnosis (42.3%). Many patients experienced problems attributable to the COVID-19 pandemic (119, 40.9%), of which 46 (38.7%) required an increase in medicines, and 12 (10.1%) of these needed hospitalizations for disease-related complications. More than one-third (36.4%) were on glucocorticoids or had underlying cardiovascular risks (39%) that would predispose them to severe COVID-19.A significant proportion (38.1%) faced hurdles in procuring medicines or experienced disruption in physiotherapy sessions (24.7%). One-quarter (24.1%) felt it was difficult to contact their specialist, whereas another 7.2% were unable to do so. Contracting COVID-19 was the most prevalent fear (71.5%), followed by infection in the family (61.9%), and a flare of the disease (45.4%). Most respondents preferred teleconsultations (55.7%) over hospital visits in the pandemic period. CONCLUSION: The results of the patient survey suggest that the COVID-19 pandemic has affected many patients with SSc and may translate to poorer outcomes in this population in the postpandemic period.

Integration of cardiovascular risk assessment with COVID-19 using artificial intelligence.

Artificial Intelligence (AI), in general, refers to the machines (or computers) that mimic "cognitive" functions that we associate with our mind, such as "learning" and "solving problem". New biomarkers derived from medical imaging are being discovered and are then fused with non-imaging biomarkers (such as office, laboratory, physiological, genetic, epidemiological, and clinical-based biomarkers) in a big data framework, to develop AI systems. These systems can support risk prediction and monitoring. This perspective narrative shows the powerful methods of AI for tracking cardiovascular risks. We conclude that AI could potentially become an integral part of the COVID-19 disease management system. Countries, large and small, should join hands with the WHO in building biobanks for scientists around the world to build AI-based platforms for tracking the cardiovascular risk assessment during COVID-19 times and long-term follow-up of the survivors.