Publications by authors named "Vikas Agarwal"

269 Publications

Th17.1 lymphocytes: emerging players in the orchestra of immune-mediated inflammatory diseases.

Clin Rheumatol 2022 May 11. Epub 2022 May 11.

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow-226014, India.

It is now well established that Th17 lymphocytes associate with myriad immune-mediated inflammatory diseases. Over the past one and a half decades, a subset of Th17 lymphocytes viz. Th17.1 lymphocytes has been identified in pre-clinical and clinical models of inflammatory rheumatic diseases. These lymphocytes secrete IL-17A (signature cytokine of Th17 lymphocytes) as well as IFN-γ (the signature cytokine of Th1 lymphocytes). They express the chemokine markers for Th1 (CXCR3) as well as Th17 (CCR6) lymphocytes. Th17.1 lymphocytes also express the drug efflux protein p-glycoprotein, which associates with resistance to corticosteroids and other immunosuppressive drugs. This narrative review overviews the evidence regarding Th17.1 lymphocytes in different inflammatory rheumatic diseases. It is now recognized that Th17.1 lymphocytes are increased in the synovial fluid of affected joints in rheumatoid arthritis (RA) and associate with poor treatment response to abatacept. Th17.1 lymphocytes from synovial fluid of RA are less responsive to immunosuppression than those from the peripheral blood. In sarcoidosis, Th17.1 lymphocytes are concentrated in mediastinal lymph nodes and alveolar lining. Such Th17.1 lymphocytes in sarcoidosis are the predominant source of IFN-γ in the sarcoid lung. Th17.1 lymphocytes are elevated in lupus and Takayasu arteritis and associate with disease activity. Future studies should evaluate isolated Th17.1 lymphocytes from peripheral blood or sites of pathology such as synovial fluid and assess their modulation with immunosuppressive therapy in vitro. The analysis of gene expression signature of isolated Th17.1 lymphocytes might enable the identification of newer therapeutic strategies specifically targeting these cell populations in inflammatory rheumatic diseases. Key Points • Th17.1 lymphocytes are a subset of Th17 lymphocytes secreting both IFN-γ and IL-17 • Th17.1 lymphocytes drive neutrophilic inflammation, granuloma formation, and corticosteroid resistance • Th17.1 lymphocytes are elevated in rheumatoid arthritis and sarcoidosis at sites of inflammation • Increased circulating Th17.1 lymphocytes have been identified in lupus and Takayasu arteritis and associate with active disease.
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http://dx.doi.org/10.1007/s10067-022-06202-2DOI Listing
May 2022

Anti-mitochondrial antibodies in Indian patients with idiopathic inflammatory myopathies.

Int J Rheum Dis 2022 Apr 6. Epub 2022 Apr 6.

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Aims: Anti-mitochondrial antibodies (AMAs) are associated with distinct clinical phenotypes including cardiac and hepatic manifestations in idiopathic inflammatory myopathies (IIMs). This article studies the prevalence, clinical characteristics and outcomes of AMA in Indian patients with IIM.

Methods: Patients (97: 81 adult, 16 juvenile) clinically diagnosed with polymyositis or antibody-negative IIM were retrieved from the MyoCite bio-archive. They were tested for myositis-specific autoantibodies / myositis autoantibodies (MSAs/MAAs) using line immunoassay and antinuclear antibodies and AMAs using immunofluorescence assay (IFA). Patients were also screened for cardiac biomarkers (cardiac troponin I [c-TnI] and N terminal-pro brain natriuretic peptide [NT-pro-BNP] using immunometric immunoassay technique and enhanced chemiluminescence assay testing respectively) and hepatic manifestations using AMA testing. Results were formulated after carrying out analytical tests.

Results: Of the cohort, 5 adults (6.2%) (M:F 0:1) with a median age and disease duration of 37 years and 2 months respectively, tested AMA+ while the children tested negative. Dermatomyositis was the commonest phenotype, with amyopathic forms being common, often with MSA positivity. Cancer-associated myositis and polymyositis were also seen. AMA positivity is associated with Gottron's sign and calcinosis. Comparable levels of C-TnI and NT-pro-BNP and AMA testing in patients help to rule out subclinical cardiac and hepatic involvement respectively.

Conclusion: Anti-mitochondrial antibodies are rare (6.2%) in different subtypes of IIM in the Indian population, and often coexist with MSAs. Their negative association with cardiac and hepatic involvement and probable association with Gottron's sign and calcinosis merit further investigation and long-term follow-up to understand the entire spectrum of the disease.
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http://dx.doi.org/10.1111/1756-185X.14320DOI Listing
April 2022

Novel Th17 Lymphocyte Populations, Th17.1 and PD1+Th17, are Increased in Takayasu Arteritis, and Both Th17 and Th17.1 Sub-Populations Associate with Active Disease.

J Inflamm Res 2022 1;15:1521-1541. Epub 2022 Mar 1.

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India.

Purpose: We evaluated T helper lymphocyte profile, including novel Th17 subsets Th17.1 (secrete IFN-γ, associate with corticosteroid resistance) and PD1+Th17 (secrete TGF-β1, implicated in fibrosis), and related cytokines in peripheral blood of Takayasu arteritis (TAK).

Materials And Methods: We evaluated circulating Th1, Th2, Th17, Th17.1, PD1+CD4+ T lymphocytes, PD1+Th17, and Treg lymphocytes, inflammatory (IFN-γ, IL-4, IL-6, IL-17A, IL-23, IL-1β, TNF-α) and regulatory (IL-10, TGF-β1) cytokines in peripheral blood of TAK (n = 57; median age 35 (interquartile range 26-45) years; 40 females) in a cross-sectional design. We studied inflammatory and regulatory cytokines in culture supernatant of peripheral blood mononuclear cells (PBMCs) from TAK following stimulation with anti-CD3/anti-CD28 and their modulation by tacrolimus (immunosuppressive) with/without tadalafil (anti-fibrotic). Furthermore, we followed up immunosuppressive-naïve active TAK (n = 16) and compared T helper lymphocyte populations and cytokines before and after immunosuppressive therapy. Healthy controls (HC, n = 21) and sarcoidosis (disease control, n = 11) were compared against TAK.

Results: TAK had higher Th17, Th17.1 and PD1+Th17 lymphocytes than HC (p < 0.001), and higher PD1+CD4+ T lymphocytes than sarcoidosis (p < 0.001). Th17 lymphocytes associated with active TAK after multivariable-adjusted logistic regression (p = 0.008). TAK had greater cytokine secretion from PBMCs (IFN-γ, IL-17A, IL-10 versus HC; IL-6, TNF-α, IL-1β versus HC or sarcoidosis) (p < 0.05). In-vitro, PBMCs from TAK showed reduced secretion of all inflammatory cytokines with tacrolimus, with synergistic reduction in IL-17A, IL-6, IL-1β and IL-10 following addition of tadalafil to tacrolimus. Serial follow-up of immunosuppressive-naïve TAK (n = 16) showed reduction in serum IL-6 and TGF-β1 (p < 0.05) and IL-6 in culture supernatant (p < 0.05) following immunosuppressive therapy.

Conclusion: Novel Th17 sub-populations (Th17.1 and PD1+Th17) are elevated in TAK. Th17 lymphocytes associate with active TAK. In-vitro experiments on cultured PBMCs suggest promise for further evaluation of a combination of immunosuppressive tacrolimus with anti-fibrotic tadalafil (or other anti-fibrotic therapies) in clinical trials of TAK.
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http://dx.doi.org/10.2147/JIR.S355881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8898181PMC
March 2022

Neglected tropical rheumatic diseases.

Clin Rheumatol 2022 May 10;41(5):1293-1304. Epub 2022 Feb 10.

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow-226014, India.

The complexities of dealing with rheumatic diseases in tropical countries are diverse and likely due to limited health care infrastructure, lack of diagnostic and therapeutic facilities, impact of dominant prevailing diseases, and the challenges of differentiating from infectious and non-infectious disease mimics. Several tropical diseases present with musculoskeletal and rheumatic manifestations and often pose a diagnostic dilemma to rheumatologists. The diagnosis is often delayed or the disease is misdiagnosed, leading to poor patient outcomes. Endemic tropical diseases like tuberculosis and leprosy have myriad rheumatic presentations and remain important differentials to consider in patients with rheumatic manifestations. Infection with human immunodeficiency virus is a great masquerade and can mimic manifestations of multiple diseases. The role of viral infections in triggering and perpetuating autoimmunity is well known and chikungunya arthritis is a classic example of the same. This review highlights the rheumatic manifestations of tropical diseases and aims to create awareness among the caregivers. Key Points • It is crucial to be aware and identify infectious diseases presenting with rheumatic manifestations in the tropics. • Presentations akin to classic rheumatic syndromes such as rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus and vasculitis are common.
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http://dx.doi.org/10.1007/s10067-022-06090-6DOI Listing
May 2022

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

Mediterr J Rheumatol 2021 Dec 27;32(4):338-344. Epub 2021 Dec 27.

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.

Objectives: Understanding of Juvenile reactive arthritis (jReA) and other spondyloarthritides of childhood (jSpA) is limited to small case series. Since most of them have speculated pathogenic origins in the gut, we compared and contrasted jReA with other jSpA -Enthesitis-related arthritis (ERA) and undifferentiated SpA (jUSpA).

Methods: A record-based medical data review of jReA, and jUSpA was compared with cohort data of ERA collected for other studies. Data are presented as median (interquartile range) and non-parametric tests used for analysis.

Results: Of 179 juvenile SpA (61 jReA; 101 ERA; and 17 jUSpA), 61 had jReA [M:F-52:9; 15.5 (12-18) years] with a disease duration of 2.75(1-36) months. Inflammatory backache IBP (32%), dactylitis (21%) and enthesitis (29%) were common. A significant proportion (14 of 17, 82.3% at >6 months follow-up) had a chronic course. 101 ERA [M:F-93:7; age-16(14-20) years] had a longer disease duration (45 vs 2.75 months, p<0.001), as compared with jReA. Enthesitis and IBP was more common in ERA (OR-2.3 and 3.4 respectively). jUSpA (n=17) had a similar clinico-laboratory profile and exhibited significant (7 of 17, 58.3%) chronicity over 9.5(4.8-37) months follow-up.

Conclusion: jReA and jSpA exhibit similar features apart from varying disease duration, suggesting that jspA may form a continuum with similar clinico-laboratory profiles plausibly due to shared pathogenesis.
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http://dx.doi.org/10.31138/mjr.32.4.338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8802200PMC
December 2021

Tuberculosis in Children with Rheumatic Diseases Treated with Biologic Disease-Modifying Anti-Rheumatic Drugs.

Mediterr J Rheumatol 2021 Dec 27;32(4):290-315. Epub 2021 Dec 27.

Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Chronic rheumatic diseases entail the use of biologics in children. Immunosuppressive effects of drug therapy put children at risk of various infections including tuberculosis (TB). Even though TB is a major concern among individuals on biological DMARDs, the incidence and distribution among children on these drugs is not known. Hence, we performed a literature search to ascertain the prevalence of tuberculosis amongst children with rheumatic disorders treated with biological agents. Articles available on MEDLINE and SCOPUS published on or after January 1, 2010 to 1 October 2019 were reviewed and collated. We found that published data on TB infections in children with rheumatic disorders on biologics is scant even from regions with highest TB burden. Tuberculosis was reported on occasion (0-5 cases per country) in the developed world with most reports being from Turkey. While most of the retrospective studies suggest that TB risk is minimal in the paediatric rheumatology patients, prospective studies suffer from a short observation period. Most registries focus on response to therapy rather than complications. In this review we have then discussed about the variation in screening strategies for latent TB and the role of bacille Calmette-Guerin (BCG) vaccination. Based on the dearth of data and inconsistency in data collection, we propose a way forward in the form of establishing well-designed long-term prospective national registries from countries with high background prevalence of TB with focus not only on treatment efficacy but also on adverse events and infections.
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http://dx.doi.org/10.31138/mjr.32.4.290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8802205PMC
December 2021

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

Rheumatology (Oxford) 2022 Feb 1. Epub 2022 Feb 1.

Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

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, 2 case-control and 53 case reports), 19 were analysed. Of 14043 IIM patients, Dermatomyositis (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 & 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 &atypical sites including the muscle are frequent. Limited data suggests fair outcomes, although larger prospective studies may offer better understanding.
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http://dx.doi.org/10.1093/rheumatology/keac041DOI Listing
February 2022

The ADVICER Template for Faculty Reviewer Letters for Promotion and Appointment.

Acad Radiol 2022 Jan 27. Epub 2022 Jan 27.

Department of Radiology (V.A.), University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Department of Radiology and Imaging Sciences (M.E.M.), Emory University and Emory Healthcare, Atlanta, Georgia; Department of Diagnostic Imaging (M.B.M.), The Warren Alpert Medical School of Brown University, Providence, Rhode Island; Department of Radiological Sciences (R.D.S.), David Geffen School of Medicine at University of California, Los Angeles, California; Department of Radiology, Division of Breast Imaging at Penn State Health (A.L.C.), Hershey Medical Center, Hershey, Pennsylvania; Department of Radiology and OBGYN, Dartmouth-Hitchcock Medical Center (P.J.L.), Geisel School of Medicine at Dartmouth, 1, Medical Center Drive, Lebanon, New Hampshire 03756. Electronic address:

Rationale And Objectives: Promotion is an important milestone in the career of academic radiologists. Appointments, Promotion and Tenure (APT) committees require multiple letters of support from both internal and external referees. Traditional narrative letters are highly subjective, have high inter-reader variability, are time-intensive, and vulnerable to gender and other biases. The Alliance of Directors and Vice Chairs of Education in Radiology (ADVICER) recognized the need for a standardized template to assist academic faculty, letter writers, and APT committees.

Materials And Methods: An ADVICER ad hoc committee of six educators with experience serving as external referees was convened to create a standardized template. Committee members performed a search of the relevant literature and internet sites, spoke with stakeholders such as APT chairs, and ultimately developed a template for faculty reviewer letters using the common clinician-educator pathway as a focal point.

Results: An open source, modifiable, standardized, template was produced. The template has been made available to ADVICER members and is available on the Association of University Radiologists (AUR) website at: https://www.aur.org/resources/Template-for-Faculty-Reviewer-Letters-for-Promotion-and-Appointment CONCLUSION: This external referee template has the potential to reduce subjectivity, eliminate bias, and provide a flexible, modifiable, comprehensive faculty review letter template which will be useful for academic faculty, letter writers, and promotions committees.
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http://dx.doi.org/10.1016/j.acra.2021.12.027DOI Listing
January 2022

Prevalent Drug Usage Practices in Adults and Children With Idiopathic Inflammatory Myopathies: Registry-Based Analysis From the MyoCite Cohort.

J Clin Rheumatol 2022 03;28(2):89-96

Department of Medicine, University of Pittsburgh, Pittsburgh, PA.

Background: Idiopathic inflammatory myopathies (IIMs) form a heterogeneous group of disorders with a deficit of quality evidence regarding its management. Therefore, we aimed to explore the prevalent treatment practices in the MyoCite cohort from India.

Methods: Drug usage patterns, their predictors, drug retention rates, efficacy, and adverse drug reactions were analyzed for adults and children newly diagnosed with IIM (2017-2020) and followed prospectively and compared with real-world data by performing a medical records review. GraphPad Prism version 8.4.2 was used for statistical analysis.

Results: Of 181 adults (male-to-female ratio, 1:4.6) and 30 children (M:F, 1.3:1), dermatomyositis (41% adults, 93% children) was the most common subtype. Methotrexate (MTX) was the drug of choice (67% adult, 90% children) followed by azathioprine (AZA) and mycophenolate mofetil (MMF). The MMF, AZA, cyclophosphamide, and rituximab (RTX) were preferred for those with antisynthetase syndrome (ASSD) and those with lung involvement, whereas MTX was avoided in them. Functional class and family income did not determine drug preferences. Glucocorticoids were initiated at a lower dose in overlap myositis (45% vs 80%, p = 0.001), and the time to achieve the lowest dose of glucocorticoids was longer than 24 months for ASSD (77% vs 14%, p = 0.002).Over a median of 35 months, the overall retention rate was the highest for RTX (75%) followed by MTX (58%). Relapse-free survival was the highest for RTX followed by MTX. The most common reasons for discontinuation were adverse drug reactions for MTX and MMF, inefficacy for AZA, and cost for RTX.

Conclusions: In this first analysis of drug usage and retention in patients with IIM in Northern India, MTX emerged as the most preferred drug in both adults and children, with the exception of those with ASSD or lung disease. Organ involvement and subtype of IIM are key determinants of drug preference. Overall, RTX and MTX were well-tolerated with high retention rates, followed by AZA and MMF.
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http://dx.doi.org/10.1097/RHU.0000000000001813DOI Listing
March 2022

Role of blood oxygen level-dependent magnetic resonance imaging in studying renal oxygenation changes in renal artery stenosis.

Abdom Radiol (NY) 2022 03 20;47(3):1112-1123. Epub 2022 Jan 20.

Department of Biostatistics and Health Informatics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raibareli Road, Lucknow, U.P., 226014, India.

Aim: Primary objective of this study was to compare R2* value of the post-stenotic kidney with contralateral kidney, kidneys of essential hypertensive patients, and healthy subjects using blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) technique. The secondary objective was to study the effect of severity of stenosis and viability of kidneys on R2* value.

Methods: We compared 4 groups of kidneys including 92 with renal artery stenosis, 37 normal contralateral kidneys of unilateral renal artery stenosis patients, 62 kidneys of essential hypertensive patients, and 40 kidneys of healthy controls using BOLD MRI. Deoxyhemoglobin level represented by R2* was calculated before and after giving furosemide and was compared among different groups.

Results: Baseline means cortical R2* value did not differ between groups. Response to furosemide was reduced in stenotic kidneys as compared to essential hypertensive and healthy control groups (p < 0.001). The mean R2* value of the contralateral normal kidney group was not significantly different from the stenotic group. Baseline R2* value and delta R2* values did not differ between different degrees of stenosis. Higher mean cortical R2* was seen in stenotic kidneys which were small (< 7 cm) in size (24.27 ± 5.65 vs 21.7 ± 3.88; p value 0.02) or with poor corticomedullary differentiation (24.64 ± 5.8 vs 20.74 ± 3.34; p value 0.006) as compared to other stenotic kidneys. Similarly, the delta R2* value was also blunted in these small shrunken kidneys (p value < 0.001).

Conclusion: R2* values on BOLD MRI are significantly different between kidneys with and without renal artery stenosis and can potentially also predict the utility of revascularization.
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http://dx.doi.org/10.1007/s00261-022-03408-5DOI Listing
March 2022

The prevalence and clinical characteristics of anti-HMGCR (anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase) antibodies in idiopathic inflammatory myopathy: an analysis from the MyoCite registry.

Rheumatol Int 2022 Jan 15. Epub 2022 Jan 15.

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

This study aimed to determine the prevalence and clinical characteristics of anti-HMGCR antibodies in idiopathic inflammatory myositis (IIM) at a tertiary care centre in northern India. Data (adult and children) were retrieved from the MyoCite dataset, identifying patients with polymyositis, dermatomyositis, and antibody-negative IIM whilst fulfilling the ACR/EULAR criteria. SLE, sarcoidosis, and systemic sclerosis were included for comparison as disease controls. The baseline clinical profile, laboratory tests, and muscle biopsies were retrieved and analysed. Descriptive statistics and non-parametric statistics were used for comparison. Among 128 IIM (112 adults, 16 children, M:F 1:2.8) of age 37 (24-47) years and 6 (3-17) months disease duration, 4 (3.6%) young adults tested positive for anti-HMGCR antibodies. All children and disease control tested negative for the antibody. Anti-HMGCR + IIM exhibited higher muscle enzymes [AST (367 vs 104 IU/L, p = 0.045), ALT (502 vs 78 IU/L, p = 0.004), and CPK (12,242 vs 699 IU/L, p = 0.001] except lactate dehydrogenase with less frequent systemic features such as fatigue than antibody-negative IIM. One young girl presented with a Limb-girdle muscular dystrophy (LGMD) with chronic pattern. None of the patients exhibited rashes, statin exposure, or cancer, though one had anti-Ro52 and mild disease. Our observations depict a younger population while affirming previous literature, including NM-like presentation, and chronic LGMD-like pattern of weakness in one case. Although a small number of children were included, ours is one of the few paediatric studies that evaluated HMGCR antibodies thus far. Further investigations in a larger Indian cohort are warranted to substantiate our findings.
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http://dx.doi.org/10.1007/s00296-021-05063-3DOI Listing
January 2022

Obstetric outcomes in systemic sclerosis: learning to walk before running.

Rheumatol Int 2022 05 13;42(5):923-924. Epub 2022 Jan 13.

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.

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http://dx.doi.org/10.1007/s00296-022-05093-5DOI Listing
May 2022

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

Rheumatol Int 2022 Jan 7. Epub 2022 Jan 7.

Department of Clinical Immunology & Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India.

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.
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http://dx.doi.org/10.1007/s00296-021-05057-1DOI Listing
January 2022

Formulating Hypotheses for Different Study Designs.

J Korean Med Sci 2021 Dec 27;36(50):e338. Epub 2021 Dec 27.

Departments of Rheumatology and Research and Development, Dudley Group NHS Foundation Trust (Teaching Trust of the University of Birmingham, UK), Russells Hall Hospital, Dudley, UK.

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).
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http://dx.doi.org/10.3346/jkms.2021.36.e338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728594PMC
December 2021

COVLIAS 1.0 vs. MedSeg: Artificial Intelligence-Based Comparative Study for Automated COVID-19 Computed Tomography Lung Segmentation in Italian and Croatian Cohorts.

Diagnostics (Basel) 2021 Dec 15;11(12). Epub 2021 Dec 15.

Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.

(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 AtheroPoint, 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 <2.5%, meeting the standard of equivalence. The average running times for COVLIAS and MedSeg on a single lung CT slice were ~4 s and ~10 s, respectively. (4) Conclusions: The performances of COVLIAS and MedSeg were similar. However, COVLIAS showed improved computing time over MedSeg.
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http://dx.doi.org/10.3390/diagnostics11122367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699928PMC
December 2021

Nutrition, atherosclerosis, arterial imaging, cardiovascular risk stratification, and manifestations in COVID-19 framework: a narrative review.

Front Biosci (Landmark Ed) 2021 11;26(11):1312-1339

Department of Cardiology, Indraprastha APOLLO Hospitals, 110001 New Delhi, India.

: Atherosclerosis is the primary cause of the cardiovascular disease (CVD). Several risk factors lead to atherosclerosis, and altered nutrition is one among those. Nutrition has been ignored quite often in the process of CVD risk assessment. Altered nutrition along with carotid ultrasound imaging-driven atherosclerotic plaque features can help in understanding and banishing the problems associated with the late diagnosis of CVD. Artificial intelligence (AI) is another promisingly adopted technology for CVD risk assessment and management. Therefore, we hypothesize that the risk of atherosclerotic CVD can be accurately monitored using carotid ultrasound imaging, predicted using AI-based algorithms, and reduced with the help of proper nutrition. : The review presents a pathophysiological link between nutrition and atherosclerosis by gaining a deep insight into the processes involved at each stage of plaque development. After targeting the causes and finding out results by low-cost, user-friendly, ultrasound-based arterial imaging, it is important to (i) stratify the risks and (ii) monitor them by measuring plaque burden and computing risk score as part of the preventive framework. Artificial intelligence (AI)-based strategies are used to provide efficient CVD risk assessments. Finally, the review presents the role of AI for CVD risk assessment during COVID-19. : By studying the mechanism of low-density lipoprotein formation, saturated and trans fat, and other dietary components that lead to plaque formation, we demonstrate the use of CVD risk assessment due to nutrition and atherosclerosis disease formation during normal and COVID times. Further, nutrition if included, as a part of the associated risk factors can benefit from atherosclerotic disease progression and its management using AI-based CVD risk assessment.
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http://dx.doi.org/10.52586/5026DOI Listing
November 2021

Inter-Variability Study of COVLIAS 1.0: Hybrid Deep Learning Models for COVID-19 Lung Segmentation in Computed Tomography.

Diagnostics (Basel) 2021 Nov 1;11(11). Epub 2021 Nov 1.

AtheroPoint LLC, Roseville, CA 95611, USA.

: 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. : 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. : 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. : The AI models were clinically robust and stable during the inter-variability analysis on the CT lung segmentation on COVID-19 patients.
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http://dx.doi.org/10.3390/diagnostics11112025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625039PMC
November 2021

ACR Appropriateness Criteria® Suspected Spine Infection.

J Am Coll Radiol 2021 11;18(11S):S488-S501

Specialty Chair, Atlanta VA Health Care System and Emory University, Atlanta, Georgia.

Spine infection is both a clinical and diagnostic imaging challenge due to its relatively indolent and nonspecific clinical presentation. The diagnosis of spine infection is based upon a combination of clinical suspicion, imaging evaluation and, when possible, microbiologic confirmation performed from blood cultures or image-guided percutaneous or open spine biopsy. With respect to the imaging evaluation of suspected spine infection, MRI without and with contrast of the affected spine segment is the initial diagnostic test of choice. As noncontrast MRI of the spine is often used in the evaluation of back or neck pain not responding to conservative medical management, it may show findings that are suggestive of infection, hence this procedure may also be considered in the evaluation of suspected spine infection. Nuclear medicine studies, including skeletal scintigraphy, gallium scan, and FDG-PET/CT, may be helpful in equivocal or select cases. Similarly, radiography and CT may be appropriate for assessing overall spinal stability, spine alignment, osseous integrity and, when present, the status of spine instrumentation or spine implants. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
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http://dx.doi.org/10.1016/j.jacr.2021.09.001DOI Listing
November 2021

ACR Appropriateness Criteria® Plexopathy: 2021 Update.

J Am Coll Radiol 2021 11;18(11S):S423-S441

Specialty Chair, Atlanta VA Health Care System and Emory University, Atlanta, Georgia.

Plexopathy may be caused by diverse pathologies, including trauma, nerve entrapment, neoplasm, inflammation, infection, autoimmune disease, hereditary disease, and idiopathic etiologies. For patients presenting with brachial or lumbosacral plexopathy, dedicated plexus MRI is the most appropriate initial imaging modality for all clinical scenarios and can identify processes both intrinsic and extrinsic to the nerves. Other imaging tests may be appropriate for initial imaging depending on the clinical scenario. This document addresses initial imaging strategies for brachial and lumbosacral plexopathy in the following clinical situations: nontraumatic plexopathy with no known malignancy, traumatic plexopathy (not perinatal), and plexopathy occurring in the context of a known malignancy or posttreatment syndrome. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
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http://dx.doi.org/10.1016/j.jacr.2021.08.014DOI Listing
November 2021

ACR Appropriateness Criteria® Low Back Pain: 2021 Update.

J Am Coll Radiol 2021 11;18(11S):S361-S379

Specialty Chair, Atlanta VA Health Care System and Emory University, Atlanta, Georgia.

In the United States, acute low back pain, with or without radiculopathy, is the leading cause of years lived with disability and the third ranking cause of disability-adjusted life-years. Uncomplicated acute low back pain and/or radiculopathy is a benign, self-limited condition that does not warrant any imaging studies. Imaging is considered in those patients who have had up to 6 weeks of medical management and physical therapy that resulted in little or no improvement in their back pain. It is also considered for those patients presenting with red flags, raising suspicion for a serious underlying condition, such as cauda equina syndrome, malignancy, fracture, or infection. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
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http://dx.doi.org/10.1016/j.jacr.2021.08.002DOI Listing
November 2021

Validation of two simple patient-centered outcome measures for virtual monitoring of patients with idiopathic inflammatory myositis.

Clin Rheumatol 2022 Mar 17;41(3):765-772. Epub 2021 Nov 17.

Department of Clinical Immunology and Rheumatology, SGPGIMS, Raebareli Road, Lucknow, 226014, India.

Background: Telemedicine has changed the landscape of patient care with wider use of patient-centered outcome measures (PCOMs). We evaluated two novel task-based PCOMs namely ten times arm lift (AL) test and two-minute walk distance (2MWD) in idiopathic myositis (IIM).

Methods: This was a cross-sectional observational study with the enrolment of adult IIM (ACR/EULAR criteria) patients with active/inactive disease. Active disease was defined as any two of increase in immunosuppression within 3 months, elevated muscle enzymes, physician VAS ≥ 2, worsened cutaneous disease, or fall in MMT8 < 76. Standard myositis core set measures (CSMs) were evaluated and test-retest validity [Cronbach's alfa (CA)], construct validity (Pearson's correlation), and discriminant validity (between active/inactive IIM) were assessed. The results were further validated in a separate tele-rheumatology cohort.

Results: Among 22 IIM patients (68%-female) of age 30.5(19-62) years, AL and 2MWD showed excellent test-retest reliability (CA-0.987, 0.99). AL exhibited moderate-strong correlation with all CSMs except CK levels and MDI. In contrast, 2MWD values were highly variable without CSM correlation. A higher AL time discriminated active and inactive myositis (16.6 vs 11 s, p = 0.006) with an AUC of 0.882 (p = 0.006). AL > 12.8 s had 94% negative predictive value (NPV) for active muscle disease. In the validation cohort (47 patient visits among 26 patients), AL significantly differentiated between active vs. inactive disease with an NPV of 95%.

Conclusions: AL test exhibits pilot evidence of construct and discriminant validity in patients with IIM requiring further evaluation. 2MWD was not a good test for outcome evaluation of IIM patients. Key Points • Novel task-based patient-centered outcome measures were evaluated for remote monitoring of muscle strength in IIM. • Ten times arm lift (AL) test showed strong test-retest reliability as well as provide pilot evidence of construct and discriminant validity in patients with IIM unlike 2-min walk distance. • This provides preliminary evidence to further evaluate the role of AL as patient-centered outcome measure in patients with IIM for virtual clinical trials.
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http://dx.doi.org/10.1007/s10067-021-05990-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8598218PMC
March 2022

Fibroblast Growth Factor 23 Level and Cardiovascular Parameters in Children with Chronic Kidney Disease.

Indian J Pediatr 2021 Nov 12. Epub 2021 Nov 12.

Center of Biostatistics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

Objective: To find out the serum fibroblast growth factor 23 (FGF-23) levels in different grades of CKD, and the prevalence of abnormal left ventricular mass index (LVMI), carotid intima-medial thickness (cIMT), and central pulse wave velocity (cPWV) and the risk factors including FGF-23 for these abnormalities.

Methods: Fifty-nine patients of CKD with G2 to G5, aged 2-18 y were included. The LVMI, cIMT, and cPWV were measured using standard techniques, and serum intact FGF-23 levels were estimated at enrollment.

Results: Median FGF-23 levels were significantly raised in all the grades of CKD than controls (p < 0.001), and also in G4 and G5 in comparison to G2&3 and in G5D than G5. Increased LVMI in 42 (71.2%), elevated cIMT in 30 (57.7%), and cPWV in 14 (26.9%) patients were found. The FGF-23 showed significant negative correlation with eGFRcr and positive with serum iPTH, phosphate and alkaline phosphatase levels, but had no correlations with LVMI, cIMT SDS, and cPWV SDS. Only systolic BP SDS (odds ratio 1.5, 95% CI 1.008-2.231, p = 0.046) was observed as a significant predictor for increased cIMT, while no variables had any association with abnormal LVMI and cPWV.

Conclusions: Serum FGF-23 showed higher levels with increasing grades of CKD, but no significant association with cardiovascular parameters. Systolic BP SDS was found as a significant risk factor for increased cIMT in children with CKD.
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http://dx.doi.org/10.1007/s12098-021-03927-xDOI Listing
November 2021

A systematic review of clinical and preclinical evidences for Janus kinase inhibitors in large vessel vasculitis.

Clin Rheumatol 2022 Jan 3;41(1):33-44. Epub 2021 Nov 3.

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, 226014, India.

Corticosteroid-sparing disease-modifying anti-rheumatic drugs are an area of active exploration in large vessel vasculitis (LVV), i.e., Takayasu arteritis (TAK) and Giant Cell Arteritis (GCA). The role of Janus kinase (JAK) inhibitors has been recently identified in different inflammatory rheumatic diseases. We conducted a systematic review of the use of JAK inhibitors in LVV across MEDLINE, Scopus, Web of Science, EMBASE, PubMed Central, Cochrane database of controlled trials, clinicaltrials.gov, and major recent international conferences. We identified four cohort studies and ten case reports. The JAK inhibitors used in these studies were tofacitinib, baricitinib, and ruxolitinib. A cohort study in TAK compared 27 patients treated with tofacitinib with 26 others treated with methotrexate, with better clinical outcomes with tofacitinib but similar angiographic stabilization, relapses, corticosteroid-sparing effect, and adverse events in both groups. Most of the other studies favored clinical responses with JAK inhibitors in LVV but with a paucity of data on other outcomes. Most of the included studies were of moderate quality. Evidence from pre-clinical models of LVV as well as limited in vivo data in patients with TAK appears to suggest that JAK inhibition reduces adventitial fibrosis, intimal proliferation, and inflammatory T lymphocyte infiltration in the media as well as reduces resident memory T cells in the vascular wall (which are otherwise resistant to corticosteroids). Ongoing clinical trials of tofacitinib, baricitinib, and upadacitinib in LVV shall help to further clarify the potential promise of JAK inhibitors for LVV (PROSPERO registration number CRD42021273359). KEY POINTS : •Tofacitinib appeared to associate with better clinical outcomes than methotrexate in TAK. •JAKinibs reduce adventitial fibrosis, intimal proliferation, and inflammatory vascular infiltrate in pre-clinical models of LVV. •Tofacitinib downregulates resident memory vascular T lymphocytes in pre-clinical models of LVV.
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http://dx.doi.org/10.1007/s10067-021-05973-4DOI Listing
January 2022

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

J Korean Med Sci 2021 Oct 11;36(39):e247. Epub 2021 Oct 11.

Departments of Rheumatology and Research and Development, Dudley Group NHS Foundation Trust (Teaching Trust of the University of Birmingham, UK), Russells Hall Hospital, Dudley, West Midlands, UK.

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.
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http://dx.doi.org/10.3346/jkms.2021.36.e247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506419PMC
October 2021

Utility of neutrophil CD64 in distinguishing bacterial infection from inflammation in severe alcoholic hepatitis fulfilling SIRS criteria.

Sci Rep 2021 10 5;11(1):19726. Epub 2021 Oct 5.

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, 226014, India.

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 < 0.05], as was their mean fluorescence intensity [MFI; 1431 (229-1828) vs. 853 (20-968) vs. 99.5 (54.7-140.7), p < 0.05]. Using a cut-off of 27%, the sensitivity and specificity of nCD64% to diagnose bacterial infection was 94% and 81%, respectively, with area under curve (AUC) of 0.95. At a cut-off value of 0.261 ng/ml, the sensitivity and specificity of serum procalcitonin was 83% and 72%, respectively, with AUC of 0.86. Serum CRP, total leukocyte count, NLR had AUCs of 0.78, 0.63 and 0.64, respectively. Quantitative measurement of nCD64 can better distinguish systemic bacterial infection and inflammation in SAH as compared to traditional biomarkers.
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http://dx.doi.org/10.1038/s41598-021-99276-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492738PMC
October 2021

MRI and Sonography of the Knee in Acute Reactive Arthritis: An Observational Cohort Study.

J Clin Rheumatol 2022 03;28(2):e511-e516

From the Departments of Clinical Immunology and Rheumatology.

Introduction: Reactive arthritis (ReA) is a unique subgroup of spondyloarthritis with acute presentation and tendency to develop chronicity. Magnetic resonance imaging (MRI) has enabled identification of sensitive markers of response to therapy.

Methods: A longitudinal pilot study of acute ReA with knee joint involvement satisfying the Braun's criteria was undertaken. Magnetic resonance imaging of the knee was assessed at baseline, and agreement with ultrasonography was assessed. Clinical details were recorded using a detailed and structured case record form. Patients were followed up, and MRI predictors of transition to chronic arthritis were looked for.

Results: In 25 patients with ReA, synovial thickening was the most common feature. Enthesitis was observed on MRI in 20%. Urethritis-related and HLA-B27-positive ReA had higher synovial thickening scores (p = 0.007). Agreement was poor between MRI and ultrasonography (synovial hypertrophy: k = 0.04). On follow-up, 34% (n = 7/21 for >12 months) continued to have active disease. None of the clinical or radiological features were predictive of chronicity.

Conclusions: Posturethritis and B27-positive ReA was more severe than postenteritis ReA and RA on MRI. One third develop chronic disease on follow-up. Magnetic resonance imaging is superior to sonography, although baseline imaging is not predictive of chronicity. The results of this pilot exploratory study argue for larger studies on MRI in ReA.
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http://dx.doi.org/10.1097/RHU.0000000000001785DOI Listing
March 2022

Highly cited papers in Takayasu arteritis on Web of Science and Scopus: cross-sectional analysis.

Clin Rheumatol 2022 Jan 4;41(1):129-135. Epub 2021 Sep 4.

Clinical Immunology and Rheumatology Services, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.

Background: Takayasu arteritis (TAK) is a large vessel vasculitis affecting relatively younger population. Since literature on bibliometric analysis of TAK is scarce, we analyzed top-cited articles in TAK to address this knowledge gap.

Methods: We analyzed the top hundred cited articles in TAK on Web of Science and Scopus for time of publication, article type, country of origin, source journal, and authors. Furthermore, we conducted univariable- and multivariable-adjusted linear regression analyses to explore associations of rank of cited articles, mean number of annual citations, and total citations with traditional (journal impact factor, CiteScore) and alternative (PlumX) metrics.

Results: Concordance between databases was 76%. Most top-cited articles were from the USA, Japan, or the UK, and published in Annals of the Rheumatic Diseases, Arthritis and Rheumatism, and Circulation and Rheumatology (Oxford). Original articles comprised a majority of these top-cited articles. Articles describing criteria or disease management recommendations received the highest mean number of citations. Performing multivariable-adjusted linear regression analyses, years of publication associated with mean annual citations on Web of Science as well as total citations across databases (p < 0.01). The 2-year JIF significantly associated with mean annual citations on Web of Science (p = 0.047). On Scopus, the number of captures denoted under PlumX metrics consistently associated with citations (p < 0.001).

Conclusion: Both traditional and alternative metrics associate with higher citations in TAK. Development of disease assessment and clinical practice guidelines and conduct and reporting of randomized controlled trials to guide TAK management are important research areas. The key points themselves are all right. Key Points • A majority of top-cited papers in TAK are original articles. • Both traditional and alternative metrics associate with number of citations for these papers. • Recommendations for disease assessment or clinical practice and clinical trials are important research agenda in TAK.
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http://dx.doi.org/10.1007/s10067-021-05901-6DOI Listing
January 2022

High Prevalence of Active Tuberculosis in Adults and Children with Idiopathic Inflammatory Myositis as Compared with Systemic Lupus Erythematosus in a Tuberculosis Endemic Country: Retrospective Data Review from a Tertiary Care Centre in India.

Mediterr J Rheumatol 2021 Jun 30;32(2):134-142. Epub 2021 Jun 30.

Department of Clinical Immunology & Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Aim: Infections are the leading cause of morbidity and mortality in idiopathic inflammatory myositis (IIM) with India being endemic for Tuberculosis (TB). We compared and contrasted the prevalence, clinical profile and outcomes of active TB in IIM with systemic lupus erythematosus (SLE).

Methods: Medical records were reviewed for adults and children with IIM (Bohan and Peter criteria) and SLE (ACR criteria) at a tertiary care hospital in India from January 2015 to October 2017. Follow-up was recorded until February 2020 for all those who had developed active TB.

Results: Of 167 (132 adults and 35 juvenile) IIM and 280 (131 adults and 149 juvenile) SLE, active TB occurred in 24 (14.4%) IIM (22 (16.7% of 132) adults; 2 (5.71% of 35) juvenile) and 18 (6.4%) SLE [(8 (6.1% of 131) adults; 10 (6.7% of 149) juvenile, p-value < 0.01]. Patients with IIM had higher odds of developing TB as compared with SLE [OR 2.24 (CI 1.5-5.5), p=0.007]. The risk of developing active TB was 68-fold and 30.4-fold higher in patients with IIM and SLE, respectively, as compared with the general population. Extrapulmonary forms were more common (14/24). Nearly half developed TB during active IIM, at a glucocorticoid dose of 0.25 (0-1.5) mg/kg/day. Over a follow-up duration of 27 months (8-184), all were cured of TB, though prolonged course of anti-tuberculous treatment was required in 25%, and five IIM relapsed during treatment.

Conclusion: Patients with IIM have increased risk of active TB, with common extrapulmonary forms, slow response, and relapses during treatment.
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http://dx.doi.org/10.31138/mjr.32.2.134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369275PMC
June 2021

COVLIAS 1.0: Lung Segmentation in COVID-19 Computed Tomography Scans Using Hybrid Deep Learning Artificial Intelligence Models.

Diagnostics (Basel) 2021 Aug 4;11(8). Epub 2021 Aug 4.

Vascular Screening and Diagnostic Centre, University of Nicosia Medical School, Nicosia 2408, Cyprus.

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 , and (-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 . On benchmarking against the National Institute of Health (NIH) segmentation method, the proposed model demonstrated a and improvement in ResNet-SegNet, and improvement in VGG-SegNet for lung area, and lung long axis, respectively. The PE statistics performance was in the following order: . The HDL runs in <1 s on test data per image.

Conclusions: The COVLIAS 1.0 system can be applied in real-time for radiology-based clinical settings.
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http://dx.doi.org/10.3390/diagnostics11081405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392426PMC
August 2021
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