Exploratory clinical subgroup clustering in systemic sclerosis: Results from the Indian Progressive Systemic Sclerosis Registry.

Objective: To conduct an exploratory cluster analysis of systemic sclerosis patients from the baseline data of the Indian systemic sclerosis registry. Methods: Patients satisfying American College of Rheumatology-European League Against Rheumatism classification criteria for systemic sclerosis were included. The clusters formed using clinical and immunological parameters were compared. Results: Of the 564 systemic sclerosis registry participants, 404 patients were included. We derived four clusters of which three were anti-topoisomerase I predominant and one was anti-centromere antibody 2 dominant. Cluster 1 (n-82 (20.3%)) had diffuse cutaneous systemic sclerosis patients with the most severe skin disease, anti-topoisomerase I positivity, males, younger age of onset and high prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 2 (n-141 (34.9%)) was also diffuse cutaneous systemic sclerosis and anti-topoisomerase I predominant but with less severe skin phenotype than cluster 1 and a lesser prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 3 (n-119 (29.5%)) had limited cutaneous systemic sclerosis patients with anti-topoisomerase I positivity along with other antibodies. The proximal muscle weakness was higher and digital pitting scars were lower, while other organ involvement was similar between clusters 2 and 3. Cluster 4 (n-62 (15.30%)) was the least severe group with limited cutaneous systemic sclerosis and anti-centromere antibody predominance. Age of onset was higher with low musculoskeletal disease and a higher presence of upper gastrointestinal features. The prevalence of interstitial lung disease was similar in the three anti-topoisomerase I predominant clusters. Conclusion: With exploratory cluster analysis, we confirmed the possibility of subclassification of systemic sclerosis along a spectrum based on clinical and immunological characteristics. We also corroborated the presence of anti-topoisomerase I in limited cutaneous systemic sclerosis and the association of interstitial lung disease with anti-topoisomerase I.

Pattern of disease expression in SLE patients with antiphospholipid antibodies: data from Indian Systemic Lupus Erythematosus Inception cohort (INSPIRE).

Antiphospholipid antibodies (APLA) are present in one-third of systemic lupus erythematosus (SLE) patients, and they are associated with both criteria and non-criteria manifestations. We studied the prevalence, clinical associations, and impact on mortality of APLA in SLE patients from India. Among the Indian SLE inception cohort (INSPIRE), patients who had data on all five routinely performed APLAs [lupus anticoagulant (LA), IgG and IgM anticardiolipin antibody (aCL) and anti-ß2-glycoprotein I(ß2GPI)] at enrolment were selected. Patients were divided into four categories based on the presence/absence of APLA associated manifestations and presence/absence of the APLA viz SLE-APS, SLE-APLA, SLE: events but no APLA, and SLE: no events, no APLA (reference group). 1035 SLE patients at least 1 APLA antibody was detected in 372 (35.9%). LA was present in 206 (19.9%), aCL in 126 (12.2%) and ß2-GPI in 178 (17.2%). There were 88 thrombotic events in 83 patients (8.0%); 73 (82.9%) being arterial; APLA positivity was present in 37 (44.6%) [AOR 1.70 (1.054, 2.76)]. SLE-APS patients were younger and had higher mortality [AOR 4.11 (1.51, 11.3)], neuropsychiatric and hematologic disease. SLE-APLA also had a higher mortality rate [AOR 2.94 (1.06, 8.22)] than the reference group. The mortality was highest in the subset of patients with thrombotic events in the presence of APLA [AOR 7.67 (1.25, 46.9)]. The mere presence of APLA also conferred higher mortality even in the absence of thrombotic events [AOR 3.51 (1.43, 8.63)]. Hematologic manifestations (36.1%) were the most common non-criteria-manifestation. One-third of SLE patients have APLA and its presence is associated with non-criteria hematologic manifestations, arterial thrombosis and higher mortality rate.

Gastrointestinal Manifestations in Systemic Lupus Erythematosus: Data from an Indian Multi-institutional Inception (INSPIRE) Cohort.

OBJECTIVES: To study the prevalence, correlates, and outcomes of GI manifestations in a prospectively enrolled nationwide cohort of SLE in India (INSPIRE). METHODS: It is an observational cohort study with analysis of the baseline database of the INSPIRE cohort with early outcomes assessed till April 10, 2023. Cases with GI manifestations as per the BILAG index were selected, pertinent clinical and laboratory data were retrieved for analysis. Patients with GI manifestations were compared with the rest of the cohort and factors associated with death were determined. RESULTS: Of the 2503 patients with SLE enrolled in the INSPIRE cohort, 243(9.7%) had GI manifestations observed early in the disease course(1,0-3 months). Ascites(162,6.5%), followed by enteritis(41,1.6%), pancreatitis(35,1.4%) and hepatitis(24,0.9%) were the most prevalent manifestations.All patients received immunosuppressive therapy, and four patients required surgery. Twenty-nine patients died(11.9%), with uncontrolled disease activity(17,58.6%) and infection(6,20.7%) accounting for the majority of deaths. Low socioeconomic class[lower(Hazard Ratio (95% Confidence intervals- CI) 2.8(1.1-7.9); upper lower 7.5(2-27.7); reference as upper class] and SLEDAI 2K[1.06(1.02-1.11)] were associated with death in the GI group.GI manifestations were significantly associated with age[Odds Ratio & 95% CI 0.97(0.96-0.99)], pleural effusion[4.9(3.6-6.7)], thrombocytopenia[1.7(1.2-2.4)], myositis[1.7(1.1-2.7)], albumin[0.7(0.5-0.8)], alkaline phosphatase(ALP)[1.01(1.0-1.002)], low C3[1.9(1.3-2.5)], total bilirubin[1.2(1.03-1.3)], alopecia[0.62(0.5-0.96], elevated anti-dsDNA[0.5(0.4-0.8)], and anti-U1RNP antibody[0.8(0.5-0.7)] in model one; and age[0.97(0.96-0.99)], creatinine[1.2(1.03-1.4)], total bilirubin[1.2(1.03-1.3)], ALP[1.01(1.0-1.002)], albumin[0.6(0.5-0.7)], andanti-U1RNP antibody[0.6(0.5-0.8)] in model two in multivariate analysis compared with patients without GI features. The mortality was higher in the GI group(11.9% and 6.6%, p= 0.01) as compared with controls. CONCLUSION: GI manifestations were observed in 9.7% of the cohort and were always associated with systemic disease activity and had higher mortality.

Transcarpal Motor Conduction Velocity: Repeatability and Application in Carpal Tunnel Syndrome.

Background: Conduction velocity of the short segment of the median motor nerve, across wrist (transcarpal motor conduction velocity (TCMCV)), has been used to increase diagnostic yield in carpal tunnel syndrome (CTS). However, repeatability of this parameter has not been studied till date. It has not been used as an indicator of response to treatment. Using surface stimulation techniques, it is difficult to localize the sites of stimulation of transcarpal segment of median nerve in palm. As a result, small errors in measurements of TCMCV can be magnified and variability of TCMCV may occur on successive measurements. Despite this possible variation, TCMCV can be a useful tool for assessing response to therapy, if its repeatability is assessed and a cut-off value determined for a significant change in nerve conduction velocity. Purpose: In this study, it was determined whether TCMCV is repeatable. If found to be repeatable, we show a method to determine the cut-off value of the change in this parameter for it to be considered significant. Methods: Difference between values of TCMCV on successive measurements was obtained in hands of 26 controls. Repeatability of this parameter was determined in this control population following criteria of British Standards Institution. In 19 patients of CTS, treated with intracarpal steroid injection, pre-treatment and post-treatment values of TCMCV, and of symptom severity scale (SSS) and functional status scale (FSS), were obtained at 1, 2, and 3 months after treatment. Results: Repeat measurements of TCMCV were made in each hand of all controls. After applying criteria of British Standards Institution, to such recordings, TCMCV was found to be repeatable and the cut-off value for significant change determined. According to this cut-off value, 4 patients of CTS showed improvement in TCMCV, with consistent improvement in SSS and FSS. Change in TCMCV corroborated qualitatively with changes in SSS and FSS. Conclusion: Repeatability of TCMCV can be assessed by criteria of British Standards Institution and a cut-off value determined to use it as an indicator of response to treatment in CTS.

Clusters based on demography, disease phenotype, and autoantibody status predicts mortality in lupus: data from Indian lupus cohort (INSPIRE).

OBJECTIVES: SLE is associated with significant mortality, and data from South Asia is limited. Thus, we analysed the causes and predictors of mortality and hierarchical cluster-based survival in the Indian SLE Inception cohort for Research (INSPIRE). METHODS: Data for patients with SLE was extracted from the INSPIRE database. Univariate analyses of associations between mortality and a number of disease variables were conducted. Agglomerative unsupervised hierarchical cluster analysis was undertaken using 25 variables defining the SLE phenotype. Survival rates across clusters were assessed using non-adjusted and adjusted Cox proportional-hazards models. RESULTS: Among 2072 patients (with a median follow-up of 18 months), there were 170 deaths (49.2 deaths per 1000 patient-years) of which cause could be determined in 155 patients. 47.1% occurred in the first 6 months. Most of the mortality (n = 87) were due to SLE disease activity followed by coexisting disease activity and infection (n = 24), infections (n = 23), and 21 to other causes. Among the deaths in which infection played a role, 24 had pneumonia. Clustering identified four clusters, and the mean survival estimates were 39.26, 39.78, 37.69 and 35.86 months in clusters 1, 2, 3 and 4, respectively (P < 0.001). The adjusted hazard ratios (HRs) (95% CI) were significant for cluster 4 [2.19 (1.44, 3.31)], low socio-economic-status [1.69 (1.22, 2.35)], number of BILAG-A [1.5 (1.29, 1.73)] and BILAG-B [1.15 (1.01, 1.3)], and need for haemodialysis [4.63 (1.87,11.48)]. CONCLUSION: SLE in India has high early mortality, and the majority of deaths occur outside the health-care setting. Clustering using the clinically relevant variables at baseline may help identify individuals at high risk of mortality in SLE, even after adjusting for high disease activity.

Refractory Takayasu arteritis with recurrent pyoderma gangrenosum: a therapeutic challenge with case-based review.

Takayasu arteritis (TA) is an uncommon chronic granulomatous large-vessel vasculitis affecting the aorta and its branches. Pyoderma gangrenosum (PG) is a chronic neutrophilic dermatosis characterized by rapidly developing painful ulcers. The association of PG with TA is relatively uncommon. We report a case of a 22-year-old lady with a history of recurrent pyoderma lesions for 4 months following which she developed right upper limb claudication. She underwent contrast-enhanced magnetic resonance angiography of the aorta and its branches and was initially diagnosed with type IIb TA. She was put on prednisolone and methotrexate but had a major relapse with new-onset lower limb claudication despite an appropriate course of immunosuppression. She was planned for tocilizumab infusion 8 mg/kg intravenous every 4 weeks. Following the first dose of tocilizumab, her vascular symptoms improved but she had a flare of PG. This was followed by another flare after the second dose. She was switched to tofacitinib which led to sustained remission of her TA activity and healing of her skin lesions, and the prednisolone dose could be reduced to 5 mg daily over the next 1 year. Various immunosuppressives were used to date for treating PG in TA. However, tofacitinib is being reported for the first time in literature for treating PG and controlling TA activity. The paradoxical flare of PG with tocilizumab is quite uncommon and is also reported in our case with literature review.

Validation of antioxidant, antiproliferative, and in vitro anti-rheumatoid arthritis activities of epigallo-catechin-rich bioactive fraction from Camellia sinensis var. assamica, Assam variety white tea, and its comparative evaluation with green tea fraction.

The epigallocatechin-rich polyphenolic fraction of Assam variety white tea, traditionally used for the management of diverse inflammatory ailments and health drink, was investigated through eco-friendly green aqueous extraction, TLC, and HPLC characterization, phytochemical screening, in vitro DPPH assay, anti-proteinase, MTT assay on synovial fibroblast and colon cancer cells, apoptotic FACS analysis, cytokine ELISA, p-STAT3 western blotting, and in silico docking analysis. HPLC-TLC standardized white tea fraction (WT-F) rendered higher extractive-yield (21%, w/w), than green tea fraction(GT-F) (12%, w/w). WT-F containing flavonoids and non-hydrolysable polyphenols showed better antioxidant activity, rather than equivalent GT-F. WT-F demonstrated remarkable anti-rheumatoid-arthritis activity via killing of synovial fibroblast cells (66.1%), downregulation of TNF-α (93.33%), IL-6 (87.97%), and p-STAT3 inhibition (77.75%). Furthermore, WT-F demonstrated better anti-proliferative activity against colon cancer cells (HCT-116). Collectively, our study revealed that the white tea fraction has boundless potential as anti-rheumatoid arthritis and anti-proliferative agent coupled with apoptotic, antioxidant anti-proteinase, and anti-inflammatory properties. PRACTICAL APPLICATIONS: Our eco-friendly extracted bioactive aqueous fraction of white tea, characterized by TLC-HPLC study and phytochemical screening have demonstrated remarkable anti-rheumatoid arthritis property and anti-proliferative action on colon cancer cells including potential anti-oxidant, anti-inflammatory, and anti-proteinase efficacy. The test WT-F sample has shown impressive safety on normal mammalian cells. WT-F has demonstrated better efficacy against rheumatoid arthritis and cancer model compared to equivalent green tea fraction. Traditionally, it is extensively used for boosting immunity, and energy, with cosmetic, and agricultural applications by the native inhabitants. So, the aqueous fraction of WT is suggested to be used as a prophylactic nutraceutical supplement and or therapeutic agent in commercial polyherbal formulation to attenuate and management of auto-inflammatory rheumatoid arthritis and carcinogenesis of colon. It is additionally suggested to establish in vivo rheumatoid arthritis animal and clinical study to validate their pharmacokinetic stability and dose optimization coupled with anti-inflammatory, cytotoxicity, and anti-oxidant property.

Role of oxidative stress in induction of trans-differentiation of neutrophils in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disorder whose etiopathology involves an interplay between genetic and environmental factors, with oxidative stress being a key contributory factor. This study aimed to establish the impact, if any, of an oxidative, pro-inflammatory milieu upon trans-differentiation of neutrophils and disease progression. In the synovial fluid (SF) and peripheral blood sourced from patients with RA (n = 40) along with healthy controls (n = 25), the proportion of neutrophil-dendritic (N-DC) cell hybrids, i.e. CD66b+/CD83+ was characterized in terms of their antigen presentation (HLA-DR, CD80, andCD86) and cell adhesion and migration (ICAM-1, VCAM-1, and CD62L) properties, along with their ability to generate reactive oxygen species (ROS). In the SF of RA cases, the raised levels of circulating and intra-neutrophilic pro-inflammatory cytokines/chemokines were accompanied by an enhanced proportion of CD66b+ neutrophils, that co-expressed features of antigen presenting cells (APCs) namely CD83, HLA-DR, CD80, CD86, ICAM-1, VCAM-1, and decreased CD62L. These N-DCs as compared to canonical neutrophils demonstrated a higher generation of ROS, and their frequency positively correlated with disease activity score (DAS28). An ex-vivo functional assay validated that oxidative stress supported trans-differentiation and could be attenuated by a free radical scavenger. Taken together, the pro-inflammatory microenvironment in the SF of patients with RA coupled with a higher generation of ROS promoted the trans-differentiation of neutrophils into N-DCs, suggesting the inclusion of anti-oxidants as an add-on therapeutic strategy to limit trans-differentiation.

Evaluation of Subclinical Hand Joint Synovitis by Ultrasonography in Patients with Psoriatic Arthritis and Cutaneous Psoriasis: A Case-Control Study.

Objectives: To find the frequency of subclinical hand joint synovitis (SS) in patients with psoriatic arthritis (PsA) and cutaneous psoriasis (PsC) compared to healthy controls (HC), and correlation of SS with disease activity. Methods: PsA patients (n= 52), without any past/current history of hand joint arthritis, PsC patients (n= 48), and 45 HC were recruited. Grey-scale and power Doppler Ultrasonography of bilateral hand joints were performed. The proportions of hand joints with SS were estimated in each group. A wrist-ray score was devised. Correlations were obtained between the number of joints with SS and disease activity parameters. Results: Higher proportion of PsA patients (55.8%) had SS than PsC (29.2%, p= 0.007), and HC (22.2%, p=0.001). Proportion of joints with SS was higher in PsA patients (5.38%) compared to PsC (2.92%, [p=0.0008]), and HC (1.11%, [p=0.0007]). Compared to HC, PsA patients had significantly higher bilateral ray 3 (p=0.002 and 0.01 for left and right ray 3, respectively), and right ray 4 involvement (p=0.037) and PsC patients had higher left ray 3 involvement (p=0.03). Wrist-ray score above 2.5 could distinguish patients of PsC with significant subclinical synovitis compared to controls (area under curve: 0.857, 95% confidence interval: 0.71-1.00). There was a significant correlation of SS with ESR in PsA group (p-value: 0.044), and with CRP in PsC group (p-value: 0.003), but not with other disease activity indices. Conclusion: SS was noted in approximately half of PsA and 1/3rd of PsC patients. Both PsA and PsC patients had a significantly higher number of hand joint SS than HC. Ray pattern of hand joint SS could be present in both PsA and PsC.

Evaluation of levels of oxidative stress as a potential biomarker in patients with rheumatoid arthritis.

OBJECTIVES: One of the most prevalent autoimmune disease globally, rheumatoid arthritis (RA) is caused by interplay of multiple inflammatory mediators in specific joints. Altered redox balance is one of the key factors in pathophysiology of RA. This study aims to find whether oxidative stress in peripheral blood neutrophil correlates with the disease activity and disability associated with it. METHODS: Ten healthy controls and 29 RA patients with moderate to severe disease activity (DAS28 score >3.2) were recruited and reactive oxygen species (ROS) level in peripheral blood neutrophil was measured using flow cytometry at baseline visit and after 6 months follow-up. Functional status of RA patients was measured using Health Assessment Questionnaire Disability Index (HAQ-DI). RESULTS: RA patients showed significantly higher level of ROS in compared to healthy control. DAS28 correlated well with ROS at baseline visit (Pearson's r = +0.63) as well as follow-up visit (Pearson's r = +0.75). HAQ-DI showed weak positive correlation at baseline visit (Pearson's r = 0.1) but it was negative at follow-up visit (Pearson's r = -0.19). CONCLUSIONS: Oxidative stress mirrors the disease activity in RA and can be considered as a biomarker, but it is not related with functional ability of the patients.

Clinical and psychosocioeconomic impact of COVID-19 pandemic on patients of the Indian Progressive Systemic Sclerosis Registry (IPSSR).

OBJECTIVES: The aim was to determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on access to health care among patients with scleroderma and to analyse the economic and psychosocial impacts and the infection prevention measures taken by them during the pandemic. METHODS: A 25-item questionnaire designed to assess the components of the objectives was tele-administered between October 2020 and January 2021 to the patients enrolled in the Indian Progressive Systemic Sclerosis Registry. RESULTS: Of the 428 patients in the registry, 336 took part in the study. A scheduled outpatient visit was missed by 310 (92.3%) patients, and 75 (22.3%) skipped prescription drugs. During the pandemic, 75 (22.3%) had a family member lose a job. Financial difficulties were reported by 155 (46.1%), with 116 (34.5%) patients having to spend an additional INR 4000 (2000-10 000) [USD 54.9 (27.0-137.4)] to continue treatment. Although 35 patients (10.4%) had at least one symptom suggestive of COVID-19, infection was confirmed in only 4. None of them needed hospitalization or had adverse outcomes. Worsening of scleroderma was seen in 133 (39.6%) individuals, with 15 (4.5%) requiring hospitalization. Most (96%) of the patients were aware of infection prevention measures, and 91 (27.1%) had taken unproven prophylactic medications. CONCLUSION: Individuals with scleroderma in India have been affected during the pandemic owing to closure of hospital services, lack of transport, loss of jobs and the additional financial burden. Health-care providers should continue to educate patients to stay on their medications and encourage them to be vaccinated for COVID-19.

Phenotypic characterization of circulating endothelial cells induced by inflammation and oxidative stress in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic auto-immune disease, affecting the spine, sacroiliac, and sometimes peripheral joints. It is also involved with cardio-vascular risk factors due to accelerated atherosclerosis. Oxidative burst, systemic inflammation coupled with endothelial dysfunction (ED), resulting in reduced bioavailability of the vasodilator nitric oxide (NO) and an increased number of circulating endothelial cells (CECs) may correlate with disease activity and its sustenance. Hence, the study was aimed to detect and quantify CECs and assess the oxidative stress and inflammatory status in AS patients vis-à-vis healthy controls, as well as relate these parameters with AS disease activity and atherosclerotic markers in patients. Our study showed an increased frequency of endothelial cells in peripheral blood of AS patients in pro-inflammatory conditions. In AS patient population, they showed significant reduction of flow-mediated dilatation (%FMD) (p < 0.05), and increased soluble adhesion molecules such as sICAM-1 (p < 0.01) and sVCAM-1 (p < 0.05) compared to healthy controls. A marked increase in pro-inflammatory markers such as TNF-α (p < 0.01) and IL-1ß (p < 0.001) and reactive free radicals (p < 0.05) along with reduced serum nitrite in AS, provided a strong pro-inflammatory milieu which positively correlated with Bath ankylosing spondylitis disease activity and functional indices (BASDAI and BASFI). The observed significant upregulation in CECs (CD45-/CD31+/CD105+/CD144+) in patients compared to healthy controls positively correlated with disease activity and duration as well as with markers of oxidative stress. Thus, chronic inflammation and oxidative burst induce loss of NO bioavailability, leading to ED. This may cause the derangement of CECs that may be considered as a prognostic biomarker for ED.

Indian SLE Inception cohort for Research (INSPIRE): the design of a multi-institutional cohort.

Systemic lupus erythematosus (SLE) cohorts across the world have allowed better understanding of SLE, including its bimodal mortality, and the impact of social factors and ethnicity on outcomes. The representation of patients from South Asia has been poor in the existing SLE cohorts across the world. Hence, we planned to initiate an inception cohort to understand the diversity of lupus in India. Indian SLE Inception cohort for REsearch (INSPIRE), planned over 5 years is a multi-centric cohort of adult and childhood lupus patients of Indian origin, fulfilling the SLICC-2012 classification criteria, with an aim to provide cross-sectional information on demography, ethnicity, socio-economic status, standard disease variables, quality of life, and prospective information on new events like hospitalization, infections, pregnancies, changes in disease activity, and damage. One of the other deliverables of this project is the establishment of a biorepository. The instruments to be used for each variable and outcome were finalized, and a web-enabled case report form was prepared to encompass SLEDAI, BILAG, SLICC damage scores, and Lupus quality-of-life index.Ten centers located in different geographic areas of India would enroll patients who are seen for the first time after the start of the study. In the first 8 months, 476 patients (63 children, 36 males) have been enrolled with a median disease duration of 10 (IQR 4-17) months and mucocutaneous features being the most prevalent clinical manifestations. INSPIRE is the first prospective Indian SLE cohort to study the diversity of Indian patients.

High-resolution ultrasonography in carpal tunnel syndrome: role of ancillary criteria in diagnosis and response to steroid injection.

OBJECTIVES: (1) Development and validation of a composite ultrasound score (cUSS) for the diagnosis of carpal tunnel syndrome (CTS). (2) To predict treatment response after local corticosteroid injection. METHODS: Wrists of CTS patients and controls were evaluated with high-resolution ultrasound and cross-sectional area of median nerve at carpal tunnel inlet (CSAp) and outlet (CSAd) and bowing of flexor retinaculum (FRB), flexor tenosynovitis, and intraneural vascularity and echogenicity changes were noted. Patients were prospectively followed after ultrasound-guided corticosteroid injection. RESULTS: We studied 479 wrists of 141 patients and 99 controls. Optimal cut-offs for diagnosing CTS were 9.5 mm2 and 10.5 mm2, respectively, for CSAp and CSAd. A cUSS consisting of the following parameters was developed: age, CSAp, CSAd, FRB, and flexor tenosynovitis and echogenicity changes. External validation of cUSS yielded sensitivity, specificity, and diagnostic accuracy of 91.7%, 87.1%, and 89.8%, respectively. Treatment responses from 88 injections (median duration of follow-up of 6 months) were available with satisfactory initial responses in 69.32% (61/88) and relapses in 30.86% (25/81). Median time to relapse was 2 months. Initial response was predicted by FRB (odds ratio (OR): 5.43, 95% confidence interval (CI): 1.45-20.3, p = 0.012). Relapse was predicted by age (hazard ratio (HR) 1.168, 95% CI: 1.076-1.268, p = 0.0002), male gender (HR: 8.1.02, 95% CI: 2.394-27.422, p = 0.0007), FRB, (HR: 46.982, 95% CI: 5.048-437.293, p = 0.0008), and higher body mass index (HR: 0.238, 95% CI: 0.064-0.892, p = 0.0332). CONCLUSIONS: The developed cUSS has a diagnostic accuracy of 88% for diagnosing CTS. Ultrasound parameters could predict both initial treatment response and relapse. KEY POINTS: • Anatomical ultrasound parameters in addition to nerve cross-sectional area is important for diagnosis of CTS. • A composite US score for diagnosis of CTS was developed with accuracy 88.6%. • Bowing of flexor retinaculum predicts short and long term response to local steroid injection.

Osteoarthritis: Prognosis and emerging therapeutic approach for disease management.

Osteoarthritis (OA), a disorder of joints, is prevalent in older age. The contemporary cure for OA is aimed to confer symptomatic relief, consisting of temporary pain and swelling relief. In this paper, we discuss various modalities responsible for the onset of OA and associated with its severity. Inhibition of chondrocytes receptors such as DDR2, SDF-1, Asporin, and CXCR4 by specific pharmacological inhibitors attenuates OA, a critical step for finding potential disease modifying drugs. We critically analyzed recent OA studies with an emphasis on intermediate target molecules for OA intervention. We also explored some novel and safe treatments for OA by considering disease prognosis crosstalk with cellular signaling pathways.

Rituximab in the treatment of systemic sclerosis-related interstitial lung disease: a systematic review and meta-analysis.

OBJECTIVES: To assess the effect of rituximab (RTX) on the lung function parameters in SSc interstitial lung disease (SSc-ILD) patients. METHODS: PubMed and Embase were searched to identify studies on SSc-ILD treated with RTX, confined to a predefined inclusion and exclusion criteria. A systematic review and meta-analysis were performed on the included studies on changes in forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) from baseline to 6 and 12 months of follow-up. RESULTS: A total of 20 studies (2 randomized controlled trials, 6 prospective studies, 5 retrospective studies and 7 conference abstracts) were included (n = 575). RTX improved FVC from baseline by 4.49% (95% CI 0.25, 8.73) at 6 months and by 7.03% (95% CI 4.37, 9.7) at 12 months. Similarly, RTX improved DLCO by 3.47% (95% CI 0.99, 5.96) at 6 months and 4.08% (95% CI 1.51, 6.65) at 12 months. In the two studies comparing RTX with other immunosuppressants, improvement of FVC by 6 months in the RTX group was 1.03% (95% CI 0.11, 1.94) greater than controls. At the 12 month follow-up, RTX treatment was similar to controls in terms of both FVC and DLCO. Patients treated with RTX had a lower chance of developing infections compared with controls [odds ratio 0.256 (95% CI 0.104, 0.626), I2 = 0%, P = 0.47). CONCLUSIONS: Treatment with RTX in SSc-ILD was associated with a significant improvement of both FVC and DLCO during the first year of treatment. RTX use was associated with lower infectious adverse events.

Quantification of health-related quality of life among patients with rheumatoid arthritis: An institution-based study in Kolkata, West Bengal.

CONTEXT: Rheumatoid arthritis (RA) is a known chronic debilitating disease accounting for a large percentage of disability globally. Pain and stiffness, decreased work function, depression and emotional state alteration, fatigue, disability, and social handicaps are some patient reported outcomes, which if considered with priority the health-related quality of life (HRQOL) of patients with RA could improve. AIMS: This study was conducted with the aim to assess the HRQOL of the patients with RA and the determinants related to it. SETTINGS AND DESIGN: This was a cross-sectional study conducted at Rheumatology Department of a tertiary care hospital, Kolkata. SUBJECTS AND METHODS: A total of 252 patients with RA were selected in this study through systematic random sampling. STATISTICAL ANALYSIS USED: Data were analyzed using appropriate statistical measures with Statistical Package for the Social Sciences(SPSS) version 16.0 (Armonk, NY: IBM Corporation) software program, version 16.0. Univariate and multivariable logistic regression were carried out. RESULTS: In the study, the mean age of the patients was 43.1 years (mean age ±SD: 43.05±10.63 years). The proportion of female subjects was 84.5%. Unsatisfactory QOL was found in 59.9% study participants. In multivariable logistic regression unsatisfactory quality of life was significantly associated to moderate to high functional disability [AOR: 6.04, CI: 2.86, 12.78], disease activity moderate to high [AOR: 5.41, CI: 1.87, 15.69], presence of comorbidity [AOR: 2.90, CI: 1.39, 6.04], extra-articular manifestations [AOR: 3.14, CI: 1.41, 6.96] and delay in starting Disease-Modifying Anti-Rheumatoid Drugs (DMARDs) [AOR: 1.24, CI: 1.08, 1.42]. CONCLUSION: Findings of this study clearly indicate the presence of high proportion of unsatisfactory QOL among the patients with RA. Early identification and prompt referral are the key strategies to prevent any permanent damage. Regular follow-up of the patients should be carried out to prevent or delay the disability progression and provide high-quality physical and mental health.

Role of redox imbalance and cytokines in mediating oxidative damage and disease progression of patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disorder wherein the contributory role of oxidative stress has been established in the synovial fluid. As availability of synovial fluid is limited, this study aimed to evaluate in the peripheral blood of patients with RA, the relationship if any, between the extent of oxidative stress in terms of generation of reactive oxygen species (ROS) in neutrophils, plasma NADPH oxidase and myeloperoxidase activity with markers of oxidative damage, circulating cytokines and disease activity score (DAS28). In patients with RA, neutrophils in peripheral blood demonstrated an enhanced generation of ROS, coupled with depletion of free radical scavenging activity. Furthermore, the NADPH oxidase and myeloperoxidase activity was enhanced as were markers of damage. There was a positive correlation between the DAS 28 and generation of ROS, NADPH oxidase and myeloperoxidase activity as also with oxidative stress mediated protein carbonylation. Patients with RA demonstrated an increase in proinflammatory (IL-17, IL-23, and IFN-γ) and some anti-inflammatory (IL-4, IL-5, and TGF-ß) cytokines. Although the levels of IL-17 correlated positively with generation of ROS, myeloperoxidase, markers of protein damage and DAS28, IL-23 correlated positively only with protein damage, and negatively with free radical scavenging activity. Importantly, incubation of neutrophils from healthy donors with plasma or SF from patients with RA translated into an enhanced generation of ROS, along with an elevation of intracellular proinflammatory cytokines. Taken together, in patients with RA, circulating neutrophils mediated a shift in the oxidant/antioxidant balance favouring the former, which translated into protein damage and contributed towards disease progression.

Quality of life among female patients with systemic lupus erythematosus in remission.

The objective is to assess quality-of-life (QoL) parameters among Indian female systemic lupus erythematosus (SLE) patients with durable remission. Indian female SLE patients in remission determined by the European consensus criteria and age-matched female control participants were included in the study. All included participants underwent measurements of QoL [Medical Outcomes Study Short-Form-12 (SF12)], Fatigue Severity Scale, and structured interview with a clinical psychologist. The population comprised of 126 female SLE patients [median age: 27.5 years [interquartile range (IQR): 11]; median disease duration: 36 months (IQR 26)] and 110 female controls [median age 30 years (IQR 9)]. Clinical remission was seen in 65.9% (83/126) and complete remission in 34.1% (43/126). Significant fatigue was present in 18.3% (23/126). Both SF-12 physical component summary (PCS) and mental component summary (MCS) were similar between SLE patients and controls [median PCS: 50.3 (IQR: 16.2) vs. 48.6 (IQR: 11.6); median MCS: 57.2 (IQR: 4.8) vs. 57.9 (IQR: 7.6)]. In generalised linear modelling, PCS was associated with fatigue [odd's ratio (OR) 0.012, 95% confidence interval (CI) 0.006-0.025, p < 0.001], disease duration ≥ 5 years (OR 23.16, 95% CI 1.548-346.58, p = 0.023), and complete remission (OR 33.16, 95% CI 4.43-248.15, p = 0.001); MCS with fatigue (OR 0.53, 95% CI 0.34-0.84, p = 0.007) and absence of depression (OR 3.65, 95% CI 1.07-12.44, p = 0.038). Patients with SLE in remission report significant fatigue in 18.3% of subjects. Both PCS and MCS scores are similar to healthy controls. Better PCS was associated with less fatigue, longer disease duration, and complete remission. Better MCS was associated with less fatigue and absence of depression.

Discoidin domain receptor 2: An emerging pharmacological drug target for prospective therapy against osteoarthritis.

Discoidin domain receptor2 (DDR2), a cell membrane tyrosine kinase on chondrocytes surface plays main role in cell-ECM interaction during the progressive degeneration of articular cartilage in osteoarthritis. The degraded component of ECM, type II collagen upon DDR2 binding provokes synthesis of matrix metalloproteinases (MMPs), responsible for severe destruction of joint tissues. DDR2 knockout has been investigated to decline the expression of MMP-1 and 13. Previously, various molecules were effective in preclinical level against different targets in OA, but found to be collapsed in clinical trial due to insufficient target specificity and clinical toxicity. Review emphasizes the role of DDR2 in the degeneration of cartilage in osteoarthritis (OA) and its blocking by DDR2 antagonist attenuates the disease severity. DDR2 in chondrocytes contributes paramount role in degradation of cartilage at early stage of osteoarthritis via collagen 2 binding through the felicitation of TGF-ß signaling molecule and other triggering factors. DDR2 involvement in regulation of matrix metalloproteinase (MMP), cross talking interaction in maintenance of ECM-chondrocytes, bone developments, interference RNA and designing the DDR2 antagonists have been critically investigated. The exploration may conclude that the DDR2 could be the novel pharmacological target to prevent the progression of osteoarthritis at early stage because of over expression of DDR2 and MMP which further promotes severe cartilage degeneration. Owing to pharmacological specificity of DDR2 in OA as drug target, it is to be hypothesized that development of safe molecules as DDR2 antagonist could be the good option in the treatment of OA with promising landmark.