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Objectives Chronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease activity and inflammatory markers on long-term cardiovascular risk in RA.Methods We studied 4370 participants without cardiovascular disease in a 10-country observational cohort of patients with RA. Endpoints were (1) major adverse cardiovascular events (MACE) encompassing myocardial infarction, stroke and cardiovascular death; and (2) any ischaemic cardiovascular events (iCVE) including MACE plus revascularisation, angina, transient ischaemic attack and peripheral arterial disease.Results Over 26 534 patient-years, 239 MACE and 362 iCVE occurred. The interaction between 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and bDMARD use was significant for MACE (p=0.017), suggesting the effect of DAS28-CRP on MACE risk differed among bDMARD users (n=515) and non-users (n=3855). DAS28-CRP (per unit increase) is associated with MACE risk in bDMARD non-users (HR 1.21 (95% CI 1.07 to 1.37)) but not users (HR 0.69 (95% CI 0.40 to 1.20)). The interaction between CRP (per log unit increase) and bDMARD use was also significant for MACE (p=0.011). CRP associated with MACE risk in bDMARD non-users (HR 1.16 (95% CI 1.04 to 1.30)), but not users (HR 0.65 (95% CI 0.36 to 1.17)). No interaction was observed between bDMARD use and DAS28-CRP (p=0.167) or CRP (p=0.237) for iCVE risk.Conclusions RA activity and inflammatory markers associated with risk of MACE in bDMARD non-users but not users suggesting the possibility of biological-specific benefits locally on arterial wall independently of effects on systemic inflammation.

Arterial wall damage in Takayasu arteritis (TAK) can progress despite immunosuppressive therapy. Vascular fibrosis is more prominent in TAK than in giant cell arteritis (GCA). The inflamed arterial wall in TAK is infiltrated by M1 macrophages [which secrete interleukin-6 (IL-6)], which transition to M2 macrophages once the inflammation settles. M2 macrophages secrete transforming growth factor beta (TGF-β) and glycoprotein non-metastatic melanoma protein B (GPNMB), both of which can activate fibroblasts in the arterial wall adventitia. Mast cells in the arterial wall of TAK also activate resting adventitial fibroblasts. Th17 lymphocytes play a role in both TAK and GCA. Sub-populations of Th17 lymphocytes, Th17.1 lymphocytes [which secrete interferon gamma (IFN-γ) in addition to interleukin-17 (IL-17)] and programmed cell death 1 (PD1)-expressing Th17 (which secrete TGF-β), have been described in TAK but not in GCA. IL-6 and IL-17 also drive fibroblast activation in the arterial wall. The Th17 and Th1 lymphocytes in TAK demonstrate an activation of mammalian target organ of rapamycin 1 (mTORC1) driven by Notch-1 upregulation. A recent study reported that the enhanced liver fibrosis score (derived from serum hyaluronic acid, tissue inhibitor of metalloproteinase 1, and pro-collagen III amino-terminal pro-peptide) had a moderate-to-strong correlation with clinically assessed and angiographically assessed vascular damage. In vitro experiments suggest the potential to target arterial wall fibrosis in TAK with leflunomide, tofacitinib, baricitinib, or mTORC1 inhibitors. Since arterial wall inflammation is followed by fibrosis, a strategy of combining immunosuppressive agents with drugs that have an antifibrotic effect merits exploration in future clinical trials of TAK.

Publication metrics enable the assessment of the performance of citations or utilization of published work. Journal-level metrics depend on the database whose citations are analyzed. Publication metrics from the Web of Science include the widely-used journal impact factor (JIF) and other indices such as Journal Citation Impact, Eigenfactor, normalized Eigenfactor, and Article Influence Score. Metrics from Scopus include the CiteScore, Source Normalized Impact Factor, and SCImago Journal Rank. Author-level metrics such as total citations, h-index, i10-index, and g-index inevitably increase with time and can be inflated by self-citations. Article-level metrics such as total citations and online attention scores derived from Scopus (PlumX Metrics) or Altmetric indicate the extent of utilization and discussion in scientific circles of a particular article. Publication metrics are useful to provide a bird's eye view of how well an individual journal or article has been cited or used. They do not necessarily reflect article quality. As an example, some of the articles with the highest Altmetric Attention Scores are actually retracted publications that attained high scores due to the negative debate that they elicited. Journal-level metrics such as the JIF are fluid and prone to historical fluctuations from year to year, most recently observed by increases in the JIF of journals which published a lot of coronavirus disease 19-related content. Research assessment of individual scientists often misuses publication metrics such as the JIF, when they should instead rely on a critical appraisal of research articles by assessors.

Background: Confinement and economic uncertainty, along with disease-specific issues such as pain and suffering may uniquely impact rheumatology patients, putting non-COVID morbidity at par with COVID-related losses. Methods: We conducted a review of records to explore the clinical profile and interventions in rheumatology patients at a tertiary care center in Northern India to identify the potential problems and propose direction for the future. Results: In our experience spanning 5 weeks, among 508 rheumatology patients who sought teleconsultations, rheumatoid arthritis was the most common diagnosis (35.2'), and 43' were asked to continue the same treatment over tele consults, whereas investigations were awaited for another 16'. Nearly one-third (29.9') required an intervention, though this largely consisted of dose titrations (104 of 152, 68.4'). Certain diseases such as myositis were under-represented among consults (1.2') but over-represented (33.3') among admissions. Among the 54 patients who were asked to rate their teleconsultation experience, the voice and consultation quality were rated and average of 9.9 each, and 88.9' (48/54) said they would prefer teleconsultations until the pandemic is over. Conclusion: A sizeable proportion of rheumatology patients can be managed with teleconsultations, with some requiring greater assistance, calling for a triage protocol for the times ahead. With propositions for a deliberate transition into the realm of virtual consulting, chronic caregivers can hope to reach an optimal balance between e-consults and in-person visits.

Background: Epigenetic factors play an essential role in regulating the action of steroids in asthma. Steroids suppress inflammation by recruiting histone deacetylase-2 (HDAC-2), which removes the acetyl group of the nuclear factor kappa B-enabled inflammatory gene complex and disables its action. P-glycoprotein (P-gp)/Multidrug resistance-associated protein 1 (MRP-1), the energy-dependent efflux pumps, reduces the bioavailability of steroids in the cell by pumping it out. The expression of P-gp/MRP-1 and HDAC-2 has been linked to regulating the action of steroids in asthma. Therefore, the use of HDAC-2 inducer like theophylline might improve asthma control by improving steroid responsiveness. Objective: HDAC-2 inducer, theophylline, can improve glucocorticoid responsiveness in severe uncontrolled asthma (UA). Materials and Methods: We classified subjects into severe UA (n = 7, age: 52.36 ± 11.94 years), controlled asthma (CA) (n = 23, age: 50.65 ± 16.11 years), and treatment-naïve patients (n = 10, age: 50.60 ± 14.38 years). Peripheral blood mononuclear cells (PBMCs) were isolated and treated with theophylline (1 μM) and Trichostatin-A (TSA) (0.8 μM) for 48 h, for induction/suppression of HDAC-2, respectively. The messenger RNA (mRNA) expression extracted from PBMCs was studied for HDAC-2and P-gp/MRP-1 by quantitative real-time polymerase chain reaction. Results: The mRNA expression of P-gp/MRP-1 was higher, whereas HDAC-2 mRNA levels were significantly lower in UA at baseline. Exposure to theophylline reduced mRNA expression of P-gp/MRP-1 (fold change: 2.57/2.15 in UA; 1.27/1.26 in CA, respectively, P < 0.0001), but the HDAC-2 mRNA expression increased (fold change: 5.56 in UA; 6.85 in CA, respectively, P < 0.0001). However, TSA treatment resulted in higher mRNA levels for P-gp/MRP-1 (fold change: 7.45/7.26 in UA; 3.34/3.29 in CA, respectively, P < 0.0001), whereas it significantly lowered expression for HDAC-2(fold change: 1.39 in UA; 2.46 in CA, respectively, P < 0.0001). Conclusion: HDAC-2 inducer theophylline has a potential to induce response against steroid resistance in severe UA.

Abstract To assess utility of neutrophilCD64 (nCD64) expression in differentiating bacterial infection from inflammation in patients with severe alcoholic hepatitis (SAH) fulfilling systemic inflammatory response syndrome criteria. Patients with SAH and infection (n = 58), SAH without infection (n = 70), and healthy controls (n = 20) were included. Neutrophil CD64 expression by flowcytometry, serum Procalcitonin (ELISA) and C-reactive protein (Nephelometry) and neutrophil–lymphocyte ratio (NLR) were studied. Percentage of neutrophils with CD64 expression (nCD64%) was significantly higher in patients with SAH and infection than in those without infection and controls [76.2% (56.9–86.5) vs. 16% (12.6–23.1) vs. 7.05% (1.4–9.5), p

MY LIFE AS A RESEARCHER AND EDITOR

Systematic reviews are considered as the highest rung in the ladder of evidence-based medicine. They are bound by a pre-defined structure and requirement for extensive literature searches, when compared with the more liberal format of narrative reviews. Systematic review protocols should ideally be pre-registered to avoid duplication or redundancy. After defining clear review question(s), thorough literature searches form the basis of systematic reviews. Presentation of results should be qualitative or quantitative (meta-analysis) if the data is homogenous enough to permit pooling across multiple studies. Quality of individual studies by Cochrane risk of bias 2 tool for interventional studies and other suitable scales for observational studies, as well as appropriate assessment of publication bias are recommended. Certainty of outcomes should be assessed by the GRADE profiler. Finally, systematic reviews should conclude with recommendations for future research, based on their findings.

Background/Objectives: The use of hydroxychloroquine (HCQ) for COVID-19 has raised concerns for adverse effects. We aimed to understand the practice, perceptions, and experience of adverse drug reactions (ADRs) with HCQ use for COVID-19 and other indications. Methods: A validated e-survey with 30 questions was circulated among rheumatologists and other specialists using SurveyMonkey. Responses from rheumatologists were compared with other doctors (odds ratio [OR], median, interquartile range), and ADRs encountered based on their indications. Results: Among 410 respondents (71.2% rheumatologists, 27% academicians) with a lifetime experience of 17886 (4884–52074) patients over 12 (7–20) years, and 148 (48–349) prescription of HCQ per month, one-third (135) were managing COVID-19 with 10 (0–60) prescriptions per physician. Electrocardiograms were seldom ordered preprescription (5%), but visual scans were requested by one-thirds, especially by rheumatologists (OR-1.9). Agreement on the safety of HCQ for non-COVID indications was nearly unanimous (99%), but only two-third (64%) perceived it to be safe for COVID-19, with most (72%) being uncomfortable using HCQ with macrolides. ADRs were most often encountered after middle-age with skin pigmentation (554 [123–2063]) being the most frequent, followed by gastrointestinal intolerance (222 [42–980] per million prescriptions). Cardiac toxicity was rarely reported. ADRs other than cutaneous and visual were noted more frequently by nonrheumatologists. Rheumatologists were less likely to consider HCQ unsafe (OR-0.04) and reportedly faced a greater challenge in drug procurance (OR-2.6) during the pandemic. Conclusions: Most ADRs are rare with HCQ use in our respondent population with a large user experience. HCQ use was considered unsafe by one-thirds in the setting of COVID-19 but not outside it, lesser so by rheumatologists.

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 AIbased platforms for tracking the cardiovascular risk assessment during COVID-19 times and long-term follow-up of the survivors.

A hypothesis is a statement of the expected outcome of a research study, generally based on analysis of prior published knowledge, or with reference to the previous work of the investigators. The hypothesis forms the foundation of a research proposal. A study based, and planned, on a sound hypothesis may have a greater likelihood of meaningfully contributing to science. After the generation of a hypothesis, it is equally important to appropriately design and adequately power a study (by ensuring a sufficient sample size) in order to test the hypothesis. Adhering to principles discussed forthwith shall help young researchers to generate and test their own hypotheses, and these are best learnt with experience.

Abstract Introduction Takayasu’s arteritis (TA) affects young women in the childbearing age group. We studied obstetric outcomes in these patients before and after disease onset. Methods Women aged more than 18 years with Takayasu’s arteritis (ACR 1990 criteria) were included. Demographic data, clinical features, disease activity using Indian Takayasu Arteritis clinical score (ITAS), Disease Extent Index for TA (DEI.TaK) and damage assessment using TA Damage score (TA), history of conception and maternal and fetal outcomes were recorded from hospital records and telephonic interview. Results are in median and IQR. Results Of the 64 women interviewed, aged 29 (24–38) years and disease duration 5 (4–10) years, 74 and 38 pregnancies had occurred before and after disease diagnosis in 29 and 20 women respectively. In eight, the diagnosis was made during pregnancy. Age at disease onset was 22 (18–30) years. Type 5 disease was the most common (n = 32, 59.3%), and an equal number of patients had Ishikawa’s class I and II disease (n = 26, 40.6%). Median ITAS (n = 44) was 13 (7–16), DEI.Tak 12.5 (9–16.75) and TADS 8 (6.5–10). Twenty-five patients wanted to get pregnant, of which 8 (32%) did not do so because of their disease. Fifteen were unmarried of whom 6 did not marry due to disease. Obstetric outcomes were poorer in pregnancies that occurred after the onset of disease as compared with those before it (RR = 1.5, p = 0.01). Pregnancies after the onset of TA carried a very high risk of maternal [RR3.9 (1.8–8.5), P

Takayasu arteritis is an enigmatic granulomatous large vessel vasculitis more common in the Indian scenario than in the West. Takayasu arteritis associates with impaired quality of life and also increases the risk of dying. Takayasu arteritis can present to virtually any medical or surgical specialty. In this editorial, we overview emerging concepts in the evaluation and management of Takayasu arteritis.

The present study compares disease characteristics, imaging modalities used, and patterns of treatment in two large cohorts of Takayasu arteritis (TAK) from Italy and India. Clinic files were retrospectively reviewed to retrieve information about initial choices of vascular imaging and immunosuppressive therapies. Unpaired t-tests compared means, and proportions were compared using Fisher’s exact test or Chi square test [Odds ratios (OR) with 95% confidence intervals (95%CI) calculated where appropriate]. The cohorts comprised 318 patients [Italy (n = 127), India (n = 191)] with similar delays to diagnosis. Ultrasound (OR Italy vs. India 9.25, 95%CI 5.02–17.07) was more frequently used in Italy and CT angiography in India (OR 0.32, 95%CI 0.20–0.51). Corticosteroid use was more prevalent and for longer duration in Italy. TAK from Italy had been more often treated with methotrexate, leflunomide or azathioprine, as opposed to tacrolimus in TAK from India (p < 0.05). Biologic or targeted synthetic disease-modifying agents were almost exclusively used in Italy. Survival on first immunosuppressive agent was longer from Italy than from India (log rank test p value 0.041). Considerable differences in the choice of initial vascular imaging modality and therapies for TAK from Italy and India could relate to prevalent socio-economic disparities. These should be considered while developing treatment recommendations for TAK.

Background: P-glycoprotein (P-gp) overexpression in peripheral blood mononuclear cells (PBMCs) has been reported in patients with steroid-resistant nephrotic syndrome (SRNS). Glucocorticoids suppress NFκB-associated coactivator activity by deacetylation of histone by enzyme histone deacetylase (HDAC)-2. Interaction between HDAC2 activity and P-gp expression in childhood NS patients is not clear. Aim: This study aims to evaluate the role of HDAC2 and P-gp expression on PBMCs and steroid responsiveness in patients with childhood NS. Materials and Methods: Thirty-one patients were recruited at baseline (n = 31) (before initiating steroid therapy); after 6 weeks of steroid therapy, 24 patients achieved remission (steroid-sensitive NS [SSNS] n = 24 mean age, 7.96 ± 3.90), whereas seven patients were resistant to steroids (SRNS, n = 7, mean age 10.00 ± 3.55). mRNA expression of HDAC2 and P-gp and functional analysis of P-gp and enzymatic activity of HDAC2 were analyzed at baseline, and at 6 weeks of steroid treatment and at the time of relapse. Results: The expression of P-gp mRNA was significantly lower in individuals (n = 24) who achieved remission at 6-week steroid therapy as compared to baseline and those who were resistant (n = 7) to steroids (P < 0.005). Similarly, the expression of HDAC2 mRNA was significantly higher at baseline and at remission following 6-week steroid therapy as compared to their expression in those who were resistant to steroids (P < 0.005). The function of P-gp was significantly lower in NS patients who achieved remission after 6-week steroid therapy compared to baseline (P < 0.005), whereas it was not significant in resistant patients (P = 0.37). The enzymatic activity of HDAC2 was significantly higher in SSNS patients as compared SRNS patients at 6-week steroid therapy (P < 0.005). Conclusion: The expression and function of P-gp and HDAC2 may affect steroid response in NS patients. Combined therapy of steroids with P-gp inhibitor and/or HDAC2 inducers may have a rationale in management of SRNS patients.

Background: We surveyed rheumatology consultants regarding their perceptions about rheumatology practice and training in India. Materials and Methods: A structured questionnaire was administered during two national rheumatology meetings to evaluate practice settings and demographic characteristics of patients seen. We also assessed perceptions regarding junior doctors, auxiliary health professionals (AHPs), ancillary facilities (daycare, intra-articular injections, musculoskeletal ultrasound [MSKUS]), and possible government-driven strategies for improving rheumatology care delivery. Results: The response rate was 56% (70/125); 68 complete responses were further analyzed. Most respondents were in the private sector (56/68), had been in practice for a mean of 11.5 (±8.4) years, attended to a mean of 150 (±91) patients every week, a majority of whom were educated upto intermediate level and belonged to the middle class. About 60% had junior doctors to assist them in care delivery; 82.5% (52/63) felt that junior doctors had limited competence in managing rheumatic diseases. More than 90% felt the need for AHPs in the clinic, although less than one-half had access to such personnel. Most utilized ancillary services like intra-articular injections (97%), daycare facilities for infusions (92%), and MSKUS (71%). More than 90% respondents felt that government-funded programs for the management of rheumatic diseases, coupled with a structured referral system, would be useful. Conclusion: Rheumatology practice in India may improve by better training junior doctors in skills related to rheumatology at the undergraduate and postgraduate internal medicine levels. The development of specialist AHPs may help enhance service delivery. Government programs for community management of rheumatic diseases and management guidelines suited to the needs of a developing economy majorly reliant on out-of-pocket expenditure for healthcare are significant areas for development.

Takayasu arteritis (TAK) could cause a stroke or transient ischemic attack (TIA) in young individuals due to inflammatory vascular occlusion or intracerebral hemorrhage. We compared the clinical presentation, angiographic features, longitudinal patterns of disease activity, medical treatments, and survival in 34 TAK patients with stroke/TIA and 157 without stroke/TIA from a single-center retrospective cohort. TAK patients with stroke/TIA were older (p = 0.044) with a greater proportion of males (p = 0.022), more frequent vision loss (odds ratio (OR) for stroke/TIA vs. without stroke TIA 5.21, 95% CI 1.42–19.14), and less frequent pulse or blood pressure inequality (OR 0.43, 95% CI 0.19–0.96) than TAK patients without stroke/TIA. Hata’s angiographic type IIa was more common in TAK patients with stroke/TIA (OR 11.00, 95%CI 2.60–46.58) and type V in TAK patients without stroke/TIA (OR 0.27, 95% CI 0.12–0.58). Cyclophosphamide was used more often in TAK patients with stroke/TIA (p = 0.018). Disease activity at baseline, 6, 12, and 24 months of follow-up was mostly similar for both groups. Risk of mortality was similar in TAK patients with or without stroke/TIA (hazard ratio unadjusted 0.76, 95% CI 0.15–3.99; adjusted for gender, age of disease onset, delay to diagnosis, baseline disease activity, and the number of conventional or biologic/targeted synthetic immunosuppressants used 1.38, 95% CI 0.19–10.20) even after propensity score-matched analyses. Stroke or TIA does not appear to affect survival in TAK patients adversely.

Takayasu arteritis (TAK) is a less common large vessel vasculitis where histopathology of involved arteries is difficult to access except during open surgical procedures. Assessment of disease activity in TAK, therefore, relies on surrogate measures. Clinical disease activity measures such as the National Institutes of Health (NIH) score, the Disease Extent Index in TAK (DEI.TAK) and the Indian TAK Clinical Activity Score (ITAS2010) inconsistently associate with acute phase reactants (APRs). Computerized tomographic angiography (CTA), magnetic resonance angiography (MRA), or color Doppler Ultrasound (CDUS) enables anatomical characterization of stenosis, dilatation, and vessel wall characteristics. Vascular wall uptake of 18-fluorodeoxyglucose or other ligands using positron emission tomography computerized tomography (PET-CT) helps assess metabolic activity, which reflects disease activity well in a subset of TAK with normal APRs. Angiographic scoring systems to quantitate the extent of vascular involvement in TAK have been developed recently. Erythrocyte sedimentation rate and C-reactive protein have a moderate performance in distinguishing active TAK. Numerous novel biomarkers are under evaluation in TAK. Limited literature suggests a better assessment of active disease by combining APRs, PET-CT, and circulating biomarkers. Validated damage indices and patient-reported outcome measures specific to TAK are lacking. Few biomarkers have been evaluated to reflect vascular damage in TAK and constitute important research agenda.

Aim The objective was to examine the prevalence of atherosclerotic cardiovascular disease (ASCVD) and its risk factors among patients with RA with diabetes mellitus (RA-DM) and patients with RA without diabetes mellitus (RAwoDM), and to evaluate lipid and blood pressure (BP) goal attainment in RA-DM and RAwoDM in primary and secondary prevention.Methods The cohort was derived from the Survey of Cardiovascular Disease Risk Factors in Patients with Rheumatoid Arthritis from 53 centres/19 countries/3 continents during 2014–2019. We evaluated the prevalence of cardiovascular disease (CVD) among RA-DM and RAwoDM. The study population was divided into those with and without ASCVD, and within these groups we compared risk factors and CVD preventive treatment between RA-DM and RAwoDM.Results The study population comprised of 10 543 patients with RA, of whom 1381 (13%) had DM. ASCVD was present in 26.7% in RA-DM compared with 11.6% RAwoDM (p

The SARS-CoV-2 virus has caused a pandemic, infecting nearly 80 million people worldwide, with mortality exceeding six million. The average survival span is just 14 days from the time the symptoms become aggressive. The present study delineates the deep-driven vascular damage in the pulmonary, renal, coronary, and carotid vessels due to SARS-CoV-2. This special report addresses an important gap in the literature in understanding (i) the pathophysiology of vascular damage and the role of medical imaging in the visualization of the damage caused by SARS-CoV-2, and (ii) further understanding the severity of COVID-19 using artificial intelligence (AI)-based tissue characterization (TC). PRISMA was used to select 296 studies for AI-based TC. Radiological imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound were selected for imaging of the vasculature infected by COVID-19. Four kinds of hypotheses are presented for showing the vascular damage in radiological images due to COVID-19. Three kinds of AI models, namely, machine learning, deep learning, and transfer learning, are used for TC. Further, the study presents recommendations for improving AI-based architectures for vascular studies. We conclude that the process of vascular damage due to COVID-19 has similarities across vessel types, even though it results in multi-organ dysfunction. Although the mortality rate is ~2% of those infected, the long-term effect of COVID-19 needs monitoring to avoid deaths. AI seems to be penetrating the health care industry at warp speed, and we expect to see an emerging role in patient care, reduce the mortality and morbidity rate.

Background: The previous COVID-19 lung diagnosis system lacks both scientific validation and the role of explainable artificial intelligence (AI) for understanding lesion localization. This study presents a cloud-based explainable AI, the “COVLIAS 2.0-cXAI” system using four kinds of class activation maps (CAM) models. Methodology: Our cohort consisted of ~6000 CT slices from two sources (Croatia, 80 COVID-19 patients and Italy, 15 control patients). COVLIAS 2.0-cXAI design consisted of three stages: (i) automated lung segmentation using hybrid deep learning ResNet-UNet model by automatic adjustment of Hounsfield units, hyperparameter optimization, and parallel and distributed training, (ii) classification using three kinds of DenseNet (DN) models (DN-121, DN-169, DN-201), and (iii) validation using four kinds of CAM visualization techniques: gradient-weighted class activation mapping (Grad-CAM), Grad-CAM++, score-weighted CAM (Score-CAM), and FasterScore-CAM. The COVLIAS 2.0-cXAI was validated by three trained senior radiologists for its stability and reliability. The Friedman test was also performed on the scores of the three radiologists. Results: The ResNet-UNet segmentation model resulted in dice similarity of 0.96, Jaccard index of 0.93, a correlation coefficient of 0.99, with a figure-of-merit of 95.99%, while the classifier accuracies for the three DN nets (DN-121, DN-169, and DN-201) were 98%, 98%, and 99% with a loss of ~0.003, ~0.0025, and ~0.002 using 50 epochs, respectively. The mean AUC for all three DN models was 0.99 (p < 0.0001). The COVLIAS 2.0-cXAI showed 80% scans for mean alignment index (MAI) between heatmaps and gold standard, a score of four out of five, establishing the system for clinical settings. Conclusions: The COVLIAS 2.0-cXAI successfully showed a cloud-based explainable AI system for lesion localization in lung CT scans.

Background and Motivation: Parkinson’s disease (PD) is one of the most serious, non-curable, and expensive to treat. Recently, machine learning (ML) has shown to be able to predict cardiovascular/stroke risk in PD patients. The presence of COVID-19 causes the ML systems to become severely non-linear and poses challenges in cardiovascular/stroke risk stratification. Further, due to comorbidity, sample size constraints, and poor scientific and clinical validation techniques, there have been no well-explained ML paradigms. Deep neural networks are powerful learning machines that generalize non-linear conditions. This study presents a novel investigation of deep learning (DL) solutions for CVD/stroke risk prediction in PD patients affected by the COVID-19 framework. Method: The PRISMA search strategy was used for the selection of 292 studies closely associated with the effect of PD on CVD risk in the COVID-19 framework. We study the hypothesis that PD in the presence of COVID-19 can cause more harm to the heart and brain than in non-COVID-19 conditions. COVID-19 lung damage severity can be used as a covariate during DL training model designs. We, therefore, propose a DL model for the estimation of, (i) COVID-19 lesions in computed tomography (CT) scans and (ii) combining the covariates of PD, COVID-19 lesions, office and laboratory arterial atherosclerotic image-based biomarkers, and medicine usage for the PD patients for the design of DL point-based models for CVD/stroke risk stratification. Results: We validated the feasibility of CVD/stroke risk stratification in PD patients in the presence of a COVID-19 environment and this was also verified. DL architectures like long short-term memory (LSTM), and recurrent neural network (RNN) were studied for CVD/stroke risk stratification showing powerful designs. Lastly, we examined the artificial intelligence bias and provided recommendations for early detection of CVD/stroke in PD patients in the presence of COVID-19. Conclusion: The DL is a very powerful tool for predicting CVD/stroke risk in PD patients affected by COVID-19.

Background: The private medical sector is a resource that must be estimated for efficient inclusion into public healthcare during pandemics.Methods: A survey was conducted among private healthcare workers to ascertain their views on the potential resources that can be accessed from the private sector and methods to do the same.Results: There were 213 respondents, 80% of them being doctors. Nearly half (47.4%) felt that the contribution from the private medical sector has been suboptimal. Areas suggested for improved contributions by the private sector related to patient care (71.8%) and provision of equipment (62.4%), with fewer expectations (39.9%) on the research front. Another area of deemed support was maintaining continuity of care for non-COVID patients using virtual consultation services (77.4%), tele-consultation being the preferred option (60%). 58.2% felt that the Government had not involved the private sector adequately; and 45.1% felt they should be part of policy-making.Conclusion: A streamlined pathway to facilitate the private sector to join hands with the public sector for a national cause is the need of the hour. Through our study, we have identified gaps in the current contribution by the private sector and identified areas in which they could contribute, by their own admission.

Vascular injury due to drugs is recognized as a distinct entity under the Chapel Hill Consensus Conference 2012 definitions for vasculitis. Drug-induced vasculitis (DIV) may affect various types of vessels. Isolated cutaneous leukocytoclastic vasculitis is most commonly seen in association with antibiotics and nonsteroidal anti-inflammatory drugs. Drug-induced antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis has been classically associated with cocaine (alone or contaminated with levamisole), antithyroid drugs (propylthiouracil, methimazole, carbimazole) and hydralazine; minocycline often mimics medium-vessel vasculitis, with ANCA positivity. Drug-induced large-vessel vasculitis remains rare; however, it has been reported with anticancer agents targeting immune pathways, including immune checkpoint inhibitors. Cerebral vasculitis has been associated with oral or topical sympathomimetic drug use. Operational pathogenetic mechanisms in DIV include immune complex deposition, abnormal generation of neutrophil extracellular traps, and bypassing of normal immune checkpoints like that between programmed cell death ligand 1 on dendritic cells and programmed cell death 1 on T-lymphocytes. DIV can have an unpredictable course, and a significant proportion of patients require immunosuppressive therapy in addition to drug withdrawal.

The prognosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has remarkably improved from an almost uniformly fatal disease about three decades back, to a chronic manageable disease with survival rates in excess of 80%. Induction of remission largely relies on cyclophosphamide or rituximab-based regimens, although emerging data suggest some potential role of mycophenolate mofetil (MMF), especially in milder disease phenotypes. Recent emphasis has shifted to exploration of treatment regimens minimizing dosage and duration of corticosteroid exposure, or replacing corticosteroids altogether with agents like avacopan, in an effort to ameliorate risks due to glucocorticoids as well as minimize damage accrual. Maintenance regimens traditionally have used azathioprine, methotrexate, or less commonly, MMF. However, rituximab is emerging as a useful maintenance agent, with the advantage of single-dose administration 6 monthly. Dosing interval for rituximab maintenance is another area of active research, with emerging literature suggesting the effectiveness of a dosing schedule based on B-cell repopulation or rise in ANCA titers. Long-term considerations for patients with AAV include the risk of infections (which can be minimized with alternate-day cotrimoxazole therapy), hypogammaglobulinemia in patients on rituximab, and accrual of damage, including drug-related damage (such as diabetes and osteoporosis) and malignancies. Ongoing clinical trials attempt to decipher the role of plasma exchange, as well as delineate the exact role of newer steroid-sparing therapeutic modalities such as avacopan. Recent clinical guidelines for the management of AAV from multiple societies, including the European League against Rheumatism and the British Society for Rheumatology, provide common treatment recommendations for AAV management.

Background: Sarcoidosis is a multisystem, chronic granulomatous disease of unknown etiology. The clinical course of sarcoidosis is punctuated with remission and relapses, which is unpredictable. Materials and Methods: This was a retrospective observational study in which case records of all patients with a confirmed diagnosis of sarcoidosis attending the outpatient department of pulmonary medicine department between January 2014 and December 2018 were evaluated. The diagnosis of sarcoidosis was confirmed by demonstration of noncaseating granuloma in cytopathology or histopathology along with a compatible clinical picture. Mantoux test, serum angiotensin-converting enzyme (ACE) levels, serum calcium, and 24-h urinary calcium were done. Results: Sarcoidosis was found to be more common in females. Cough, breathlessness, fever, and fatigue were the predominant symptoms. Mantoux was negative in 95.83%, raised serum ACE was seen in 65.83%, hypercalcemia in 10.83%, and hypercalciuria in 30.0% of patients, respectively. Chest radiograph revealed that 14.17% of patients presented with Stage 1, 52.50% of patients with Stage 2, 15.83% of patients with Stage 3, and 17.50% of patients with Stage 4. Mediastinal lymphadenopathy was seen in contrast-enhanced computed tomography chest in 93.33%, septal thickening with nodularity in 61.67% and fibrosis in 25.83%. Corticosteroids were started in 97.5% patients and 24.17% patients relapsed after stopping or tapering corticosteroids. Conclusion: Sarcoidosis is a common cause of bilateral hilar lymphadenopathy and interstitial lung diseases. Relapses are frequent after stopping corticosteroids, so patients should be followed up actively after stopping treatment.

Background: Evaluating the fertility and obstetric outcomes in women with rare rheumatic diseases is challenging as it needs to take into account various influencing factors. Aims and Objectives: The aim is to draft a structured case record form (CRF) for collating obstetric outcomes in rheumatic diseases Materials and Methods: Clinical CRFs were designed for inflammatory myositis, ANCA associated vasculitis, Takayasu arteritis and systemic sclerosis with the objectives in mind, taking into account disease characteristics, drugs administered, and the changes related to the pregnant state. The forms underwent four rounds of revision by two rheumatologists with trial runs on three patients each. The form was scrutinized for face validity, ambiguity and were designed to ease filling them in a busy outpatient setup. Results: The CRF forms for obstetric outcomes in patients were labelled as version 10.0, 11.0, 12.0, and 13.0 for myositis, AAV, TA, and SSc. Conclusion: Beginning with a well-designed CRF is the first step in collating proper data for research. This paper details the steps involved in the same for collating obstetric outcomes in tfour rare rheumatic illnesses.

Diabetes is one of the main causes of the rising cases of blindness in adults. This microvascular complication of diabetes is termed diabetic retinopathy (DR) and is associated with an expanding risk of cardiovascular events in diabetes patients. DR, in its various forms, is seen to be a powerful indicator of atherosclerosis. Further, the macrovascular complication of diabetes leads to coronary artery disease (CAD). Thus, the timely identification of cardiovascular disease (CVD) complications in DR patients is of utmost importance. Since CAD risk assessment is expensive for low-income countries, it is important to look for surrogate biomarkers for risk stratification of CVD in DR patients. Due to the common genetic makeup between the coronary and carotid arteries, low-cost, high-resolution imaging such as carotid B-mode ultrasound (US) can be used for arterial tissue characterization and risk stratification in DR patients. The advent of artificial intelligence (AI) techniques has facilitated the handling of large cohorts in a big data framework to identify atherosclerotic plaque features in arterial ultrasound. This enables timely CVD risk assessment and risk stratification of patients with DR. Thus, this review focuses on understanding the pathophysiology of DR, retinal and CAD imaging, the role of surrogate markers for CVD, and finally, the CVD risk stratification of DR patients. The review shows a step-by-step cyclic activity of how diabetes and atherosclerotic disease cause DR, leading to the worsening of CVD. We propose a solution to how AI can help in the identification of CVD risk. Lastly, we analyze the role of DR/CVD in the COVID-19 framework.

Background: COVID-19 is a disease with multiple variants, and is quickly spreading throughout the world. It is crucial to identify patients who are suspected of having COVID-19 early, because the vaccine is not readily available in certain parts of the world. Methodology: Lung computed tomography (CT) imaging can be used to diagnose COVID-19 as an alternative to the RT-PCR test in some cases. The occurrence of ground-glass opacities in the lung region is a characteristic of COVID-19 in chest CT scans, and these are daunting to locate and segment manually. The proposed study consists of a combination of solo deep learning (DL) and hybrid DL (HDL) models to tackle the lesion location and segmentation more quickly. One DL and four HDL models—namely, PSPNet, VGG-SegNet, ResNet-SegNet, VGG-UNet, and ResNet-UNet—were trained by an expert radiologist. The training scheme adopted a fivefold cross-validation strategy on a cohort of 3000 images selected from a set of 40 COVID-19-positive individuals. Results: The proposed variability study uses tracings from two trained radiologists as part of the validation. Five artificial intelligence (AI) models were benchmarked against MedSeg. The best AI model, ResNet-UNet, was superior to MedSeg by 9% and 15% for Dice and Jaccard, respectively, when compared against MD 1, and by 4% and 8%, respectively, when compared against MD 2. Statistical tests—namely, the Mann–Whitney test, paired t-test, and Wilcoxon test—demonstrated its stability and reliability, with p < 0.0001. The online system for each slice was Lesion lesion locator passed the intervariability test.

(1) Background: COVID-19 computed tomography (CT) lung segmentation is critical for COVID lung severity diagnosis. Earlier proposed approaches during 2020–2021 were semiautomated or automated but not accurate, user-friendly, and industry-standard benchmarked. The proposed study compared the COVID Lung Image Analysis System, COVLIAS 1.0 (GBTI, Inc., and AtheroPointTM, Roseville, CA, USA, referred to as COVLIAS), against MedSeg, a web-based Artificial Intelligence (AI) segmentation tool, where COVLIAS uses hybrid deep learning (HDL) models for CT lung segmentation. (2) Materials and Methods: The proposed study used 5000 ITALIAN COVID-19 positive CT lung images collected from 72 patients (experimental data) that confirmed the reverse transcription-polymerase chain reaction (RT-PCR) test. Two hybrid AI models from the COVLIAS system, namely, VGG-SegNet (HDL 1) and ResNet-SegNet (HDL 2), were used to segment the CT lungs. As part of the results, we compared both COVLIAS and MedSeg against two manual delineations (MD 1 and MD 2) using (i) Bland–Altman plots, (ii) Correlation coefficient (CC) plots, (iii) Receiver operating characteristic curve, and (iv) Figure of Merit and (v) visual overlays. A cohort of 500 CROATIA COVID-19 positive CT lung images (validation data) was used. A previously trained COVLIAS model was directly applied to the validation data (as part of Unseen-AI) to segment the CT lungs and compare them against MedSeg. (3) Result: For the experimental data, the four CCs between COVLIAS (HDL 1) vs. MD 1, COVLIAS (HDL 1) vs. MD 2, COVLIAS (HDL 2) vs. MD 1, and COVLIAS (HDL 2) vs. MD 2 were 0.96, 0.96, 0.96, and 0.96, respectively. The mean value of the COVLIAS system for the above four readings was 0.96. CC between MedSeg vs. MD 1 and MedSeg vs. MD 2 was 0.98 and 0.98, respectively. Both had a mean value of 0.98. On the validation data, the CC between COVLIAS (HDL 1) vs. MedSeg and COVLIAS (HDL 2) vs. MedSeg was 0.98 and 0.99, respectively. For the experimental data, the difference between the mean values for COVLIAS and MedSeg showed a difference of

Background: Laboratory tests evaluating autoantibodies form a key part of rheumatology practice, yet this remains the least emphasized part of rheumatology training. Methods: We conducted a single-day autoantibody workshop to train young rheumatologists in the principles of autoantibody testing as well as provide hands-on exposure to conduct these tests. We assessed the efficacy of this workshop by pretest and posttest questionnaires evaluating three domains – Antigen–antibody interactions and laboratory techniques other than immunofluorescence (Domain 1); immunofluorescence (Domain 2); and clinical relevance of autoantibodies (Domain 3). In addition, we also sought unstructured feedback from participants. Results: There was a baseline knowledge deficit regarding autoantibody estimation and evaluation among the participants. Comparison of pre- and posttest questionnaires revealed that the 1-day workshop was effective in improving overall knowledge about autoantibody testing as well as in Domain 1 and 2 but not Domain 3. Hands-on exposure and basic level discussion of laboratory techniques were appreciated by attendees. Conclusion: A single-day workshop is effective in enhancing knowledge of attendees about autoantibody testing. In-depth discussions about these laboratory techniques in rheumatology, the immune mechanisms involved and association with clinical scenarios require workshops of longer duration.

Background: Writing a scientific manuscript is an important skill to acquire for junior doctors considering the mandatory requirement of research publications during post-graduate training and for career advancement in India. Methods: We conducted a one-day workshop on scientific writing and publication at Udaipur in November 2017, comprising both didactic lectures as well as hands-on evaluation of a dummy manuscript, and evaluated structured questionnaires filled pre- and post-workshop. Results: There were 120 attendees, most of whom were junior doctors with little or no prior experience in writing a scientific paper. A significant baseline knowledge deficit regarding the principles and processes of scientific writing (ranging from 20.9% to 77.3% participants for the different questions asked) could be identified before the workshop. This knowledge deficit was significantly improved in most areas as assessed after the workshop. We identified the need to discuss predatory publishing in greater detail in subsequent workshops, as 20.8% of respondents after the workshop professed that they might consider publishing in a predatory journal. As expressed in participant feedback, longer, more-specialized or advanced level workshops on scientific writing in the future could also consider including more details on appropriate statistical presentation and pictorial representation of data as well as longer time spent on hands-on exercises. Conclusion: There remains a need to conduct more scientific writing workshops by national societies and journals all over the country.

Background: Ankylosing Spondylitis (AS) is a chronic inflammatory disease that leads to significant disability. We sought to study the impact of the disease activity and functional impairment on QoL in Indian patients with AS. Methods: World Health Organization- Quality of Life-BREF (WHOQoL-BREF) questionnaire was used to measure quality of life (QoL) in 99 adults with AS (modified Rome criteria), 72 healthy individuals, and 20 rheumatoid arthritis patients. Apart from demographic variable such as age, gender, clinical manifestations, and treatment received, disease activity parameters such as duration of early morning stiffness, BASDAI, swollen and tender joint count, Erythrocyte Sedimentation Rate (ESR) and C Reactive Protein (CRP) were also recorded. Presence of damage was assessed using spinal radiographs. All values are in median (IQR). Results: Out of the 99 patients, 5 were females and 5 had juvenile onset AS. Median age was 32 (26-42) years and median disease duration was 6 (1.25-10) years. Forty-three had peripheral arthritis and 18 had enthesitis. Syndesmophytes were present on spinal radiographs in 54 cases. BASDAI correlated negatively with the physical, psychological and environmental domains (P < 0.05), while BASFI and BASMI did not. In all 4 domains of WHO-BREF, scores for AS were significantly less as compared to healthy controls [P < 0.0001] or even to rheumatoid arthritis [P < 0.01]. Conclusion: Indian AS patients have poorer quality of life than patients with rheumatoid arthritis and healthy individuals, possibly due to poor control of disease activity.

Introduction: Microparticles (MPs) are submicron sized heterogeneous membrane-bound vesicles released from cells undergoing cell activation or apoptosis. Elevated platelet-derived MPs (PMPs) are reported in rheumatic diseases. We profiled Annexin-V+ MPs and CD61+ MPs in plasma and synovial fluid of patients with rheumatoid arthritis (RA) and their clinical correlates. Methods: Twenty-three newly diagnosed disease-modifying anti-rheumatic drug naïve patients with RA, 17 with osteoarthritis (OA) and 22 healthy controls (HC) were enrolled. Five milliliters of synovial fluid from the knee joint of patients with RA and OA was collected; 5 ml of peripheral blood was collected from patients with RA, OA, and HC. Cell-free synovial fluid and platelet poor plasma samples were stained with Annexin-V-APC and Anti-CD61-BV510 antibodies followed by flow cytometry analysis (FACSAria III) (results expressed as the mean ± standard deviation of % population). Results: Significantly greater levels of synovial fluid MPs (Annexin-V+ MPs) were observed in RA versus OA (P < 0.0001), significantly higher synovial fluid PMPs (Annexin V+ CD61+ MPs) levels in RA compared to HC (P = 0.0472). MPs other than those of platelet origin (Annexin V+ CD61− MPs) were also increased in the synovial fluid of RA patients compared to OA (P < 0.0001). Kruskal–Wallis test revealed the significant difference in the levels of plasma MPs (Annexin-V+), PMPs (Annexin V+ CD61+ MPs), and MPs other than those of platelet origin (Annexin V+ CD61− MPs) between RA, OA, and HC groups (P < 0.0001) with a higher percentage in RA group. Conclusions: Higher levels of Annexin-V+ MPs in both plasma and synovial fluid of RA suggest a role for MPs in the pathogenesis of RA. Elevated plasma PMPs (Annexin V+ CD61+ MPs) in RA may suggest their role in systemic involvement. Furthermore, increased levels of MPs other than those of platelet origin (Annexin V+ CD61− MPs) indicate the necessity to study the MPs from other cell lineages.

Background: For COVID-19 lung severity, segmentation of lungs on computed tomography (CT) is the first crucial step. Current deep learning (DL)-based Artificial Intelligence (AI) models have a bias in the training stage of segmentation because only one set of ground truth (GT) annotations are evaluated. We propose a robust and stable inter-variability analysis of CT lung segmentation in COVID-19 to avoid the effect of bias. Methodology: The proposed inter-variability study consists of two GT tracers for lung segmentation on chest CT. Three AI models, PSP Net, VGG-SegNet, and ResNet-SegNet, were trained using GT annotations. We hypothesized that if AI models are trained on the GT tracings from multiple experience levels, and if the AI performance on the test data between these AI models is within the 5% range, one can consider such an AI model robust and unbiased. The K5 protocol (training to testing: 80%:20%) was adapted. Ten kinds of metrics were used for performance evaluation. Results: The database consisted of 5000 CT chest images from 72 COVID-19-infected patients. By computing the coefficient of correlations (CC) between the output of the two AI models trained corresponding to the two GT tracers, computing their differences in their CC, and repeating the process for all three AI-models, we show the differences as 0%, 0.51%, and 2.04% (all < 5%), thereby validating the hypothesis. The performance was comparable; however, it had the following order: ResNet-SegNet > PSP Net > VGG-SegNet. Conclusions: The AI models were clinically robust and stable during the inter-variability analysis on the CT lung segmentation on COVID-19 patients.

Background: Reduced HDACs levels have been reported in steroid resistant chronic obstructive pulmonary disease and bronchial asthma patients. P-glycoprotein (P-gp) over expression in peripheral blood mononuclear cells (PBMCs) has been reported in patients with steroid resistant nephrotic syndrome (NS). Whether and how HDACs and P-gp are linked with each other is not clear, especially in NS patients.Aim: To evaluate mRNA expression of P-gp/MRP-1 and HDAC2 in PBMCs of steroid sensitive (SSNS) and steroid resistant nephrotic syndrome (SRNS) patients, and determine the relationship between expression of HDAC2 and P-gp/ MRP-1in NS patients.Methods: Twenty subjects (10 in each group), SSNS (mean age 7.54 ± 3.5 years), and SRNS (mean age 8.43 ± 3.8 years) were recruited. mRNA expression of HDAC2 and P-gp/MRP-1 was studied by quantitative real time PCR. PBMCs were treated with Theophylline, 1 μM, and Trichostatin A, 0.8 μM, for 48 h for induction and suppression of HDAC2, respectively.Results: At baseline, expression of P-gp (4.79 ± 0.10 vs. 2.13 ± 0.12, p < 0.0001) and MRP-1 (3.99 ± 0.08 vs. 1.99 ±0.11, p < 0.0001) on PBMCs were increased whereas, HDAC2 mRNA levels (2.97 ± 0.15 vs. 6.02 ± 0.13, p < 0.0001) were significantly decreased in SRNS as compared to that of SSNS patients. Compared to baseline, theophylline reduced mRNA expression of P-gp and MRP-1 (fold change 2.65 and 2.21, *p < 0.0001 in SRNS) (fold change 1.25, 1.24, *p < 0.0001 in SSNS), respectively. However, it increased the expression of HDAC2 (fold change 5.67, *p < 0.0001 in SRNS) (fold change 6.93, *p < 0.0001 in SSNS). Compared to baseline, TSA treatment increased mRNA levels of P-gp and MRP-1 (fold change 7.51, 7.31, *p < 0.0001 in SRNS) and (fold change 3.49, 3.35, *p < 0.0001 in SSNS), respectively. It significantly decreased the level of HDAC2 (fold change 1.50, *p < 0.0001 in SRNS) (fold change 2.53, *p < 0.0001 in SSNS) patients.Conclusion: Reduced HDAC2 and increased P-gp/MRP-1 activity may play a role in response to steroids in childhood NS. HDAC2 and P-gp/MRP-1 are in reciprocal relationship with each other.

Background: COVID-19 lung segmentation using Computed Tomography (CT) scans is important for the diagnosis of lung severity. The process of automated lung segmentation is challenging due to (a) CT radiation dosage and (b) ground-glass opacities caused by COVID-19. The lung segmentation methodologies proposed in 2020 were semi- or automated but not reliable, accurate, and user-friendly. The proposed study presents a COVID Lung Image Analysis System (COVLIAS 1.0, AtheroPoint™, Roseville, CA, USA) consisting of hybrid deep learning (HDL) models for lung segmentation. Methodology: The COVLIAS 1.0 consists of three methods based on solo deep learning (SDL) or hybrid deep learning (HDL). SegNet is proposed in the SDL category while VGG-SegNet and ResNet-SegNet are designed under the HDL paradigm. The three proposed AI approaches were benchmarked against the National Institute of Health (NIH)-based conventional segmentation model using fuzzy-connectedness. A cross-validation protocol with a 40:60 ratio between training and testing was designed, with 10% validation data. The ground truth (GT) was manually traced by a radiologist trained personnel. For performance evaluation, nine different criteria were selected to perform the evaluation of SDL or HDL lung segmentation regions and lungs long axis against GT. Results: Using the database of 5000 chest CT images (from 72 patients), COVLIAS 1.0 yielded AUC of ~0.96, ~0.97, ~0.98, and ~0.96 (p-value < 0.001), respectively within 5% range of GT area, for SegNet, VGG-SegNet, ResNet-SegNet, and NIH. The mean Figure of Merit using four models (left and right lung) was above 94%. On benchmarking against the National Institute of Health (NIH) segmentation method, the proposed model demonstrated a 58% and 44% improvement in ResNet-SegNet, 52% and 36% improvement in VGG-SegNet for lung area, and lung long axis, respectively. The PE statistics performance was in the following order: ResNet-SegNet > VGG-SegNet > NIH > SegNet. The HDL runs in

Phosphodiesterases (PDE) are a group of ubiquitously present enzymes involved in regulation of various cellular pathways. PDE5 acts to metabolize cyclic guanosine monophosphate (GMP). The various PDE5 inhibitors available are sildenafil, tadalafil, vardenafil, and mirodenafil. We shall discuss the roles of various PDE5 inhibitors in rheumatic diseases. PDE5 inhibitors prevent degradation of cyclic GMP; hence, they have vasodilatory properties which render them useful in the management of secondary Raynaud's phenomenon. They have also demonstrated efficacy in the healing of digital ulcers in systemic sclerosis and potentially prevent the formation of new digital ulcers. Their vasodilatory property has also been utilized in the management of pulmonary arterial hypertension, wherein their ability to favorably affect hemodynamics of a pressure-overloaded right heart is beneficial. Recent evidences have suggested a potential antifibrotic role of these agents, and studies in idiopathic pulmonary fibrosis and systemic sclerosis-associated interstitial lung disease hold promise for future exploration of these agents for these indications.