Neuropsychiatric manifestations are associated with increased mortality in Indian patients with lupus: A single centre retrospective observational study.

OBJECTIVE: To study the prevalence of different NPSLE manifestations in our cohort and to compare clinical and immunological features and outcomes including mortality of patients with NPSLE and SLE controls without NP involvement. METHODS: This was a retrospective study in a tertiary care referral centre. All patients of SLE seen in the last 10 years and fulfilling the SLICC criteria with neuropsychiatric manifestations as per the ACR definitions were included. Patients of SLE without NP involvement were sequentially assigned as controls in a ratio of 1:2. RESULTS: Of the 769 patients diagnosed with SLE from Jan 2011 to December 2020, 128 (16.6%) had NPSLE manifestations as per the ACR definitions. The commonest NPSLE manifestation was seizures (6.5%) followed by cerebrovascular accident (3.9%). NPSLE manifestation occurred at the first presentation of SLE in 99/128 (77.3%) patients and 58 (45.3%) patients had more than one NPSLE manifestation. Lupus anticoagulant and anticardiolipin antibody were tested in 120 patients and were positive in 16 (13.3%) and 12 (10%), respectively. No difference was found in anti-ribosomal p, lupus anticoagulant and anticardiolipin antibodies between the cases and controls. Twenty-one (16.4%) deaths occurred in patients with NPSLE (median follow-up of 40 months) as compared to 13 (5%) in controls (median follow-up of 32 months) (p = <0.001). The cumulative survival of patients with NPSLE was lower as compared to controls (p < 0.001). Relapse of NPSLE was seen in 11(8.6%) patients and was associated with mortality (p = 0.017). CONCLUSIONS: Seizures and cerebrovascular accidents are the commonest NPSLE syndromes in our patients. The presence of NPSLE was associated with high mortality in Indian patients with lupus.

Magnetic Resonance Imaging evidence of Inflammation at Interphalangeal joint of Thumb - A distinct entity in psoriatic arthritis.

BACKGROUND: This study aimed to compare inflammation at the interphalangeal (IP) joint of thumb in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), undifferentiated inflammatory arthritis (UIA), and in psoriasis patients without clinical arthritis (PsO) using low-field magnetic resonance imaging (MRI). METHODS: Age-matched and disease duration-matched patients with inflammatory arthritis (RA, PsA, and UIA) and psoriasis patients without clinical arthritis (PsO), who had undergone MRI of hands were included in this study. The presence or absence of MRI inflammatory lesions including synovitis, tenosynovitis, and bone marrow edema was assessed by three independent readers. Agreement between the readers was assessed using the intraclass correlation coefficient. Risk ratio of MRI global inflammation around thumb IP joints among patients with PsA was compared with the other groups. RESULTS: Clinical parameters and MRI inflammation were studied in 161 patients (42 PsA, 28 RA, 29 UIA, and 62 PsO). Global MRI inflammation at the IP joint of the thumb was observed in 33.3% of PsA patients compared with 14.3% in RA, and 10.3% in UIA. Subclinical MRI inflammation was observed in 8.1% of patients with PsO. The risk ratios of MRI global inflammation at the IP joint of the thumb in PsA patients were 2.3 (95% confidence interval [CI] 0.86-6.36) and 3.2 (95% CI 1.02-10.21) compared with RA and UIA patients, respectively. CONCLUSION: Global MRI inflammation around the IP joint of the thumb is significantly more common in patients with PsA as compared to individuals with UIA.

Incidence of infection other than tuberculosis in patients with autoimmune rheumatic diseases treated with bDMARDs: a real-time clinical experience from India.

Biologic disease-modifying anti-rheumatic drugs (bDMARD) have transformed the treatment paradigm of chronic autoimmune rheumatic diseases (ARDs), but they are often associated with adverse drug reactions. The present study evaluated the frequency, characteristics and type of infections, other than tuberculosis (TB), in ARD patients receiving bDMARDs. The multicentre, cross-sectional, retrospective, observational study was conducted across 12 centers in Karnataka, India, between January to August 2016. The study included patients receiving bDMARD therapy for various ARDs. Outcome variables considered were any infection, minor infections and major infections, other than TB. Clinical variables were compared between infection and no infection group, and the increase in the likelihood of infection with respect to various clinical variables was assessed. The study involved 209 subjects with a median (range) age of 41 (16-84) years and male to female ratio of 0.97:1. A total of 29 (13.88%) subjects developed infection following bDMARD therapy, out of whom a majority had minor infection (n = 26). The likelihood of developing any infection was noted to be more in subjects receiving anti-TNF (golimumab, P = 0.03) and those on three or more conventional synthetic (cs) DMARDs (P < 0.01). Infection risk was higher in patients with systemic lupus erythematosus (P = 0.04), other connective tissue disease (P < 0.01) and in patients with comorbidities (P = 0.13). The risk of infection was associated with the use of anti-TNF therapy and more than three csDMARDs, co morbidities and Adds such as systemic lupus erythematosus and connective tissue disease.

Biologics and risk of tuberculosis in autoimmune rheumatic diseases: A real-world clinical experience from India.

AIM: Tuberculosis (TB) is one of the major adverse events of concern associated with the use of biologics for managing autoimmune inflammatory rheumatic diseases (AIRDs). The study presents the data on incidence of TB in relation to biologic used, screening test and TB prophylaxis in a real-world setting. METHODS: The cross-sectional, observational, retrospective study was conducted across 12 centres in Karnataka, India. The study included patients receiving biologics therapy for AIRDs, established based on the respective diagnostic criteria. The development of TB after receiving biologic therapy and other clinical variables and the predictability of the test performed for latent TB were evaluated. RESULTS: One hundred and ninety-five AIRDs patients with an average age of 41 years were initiated on biologic therapy. Twenty-one patients were latent TB positive and were given antitubercular prophylaxis, prior to biologics treatment. During follow-up, seven patients belonging to the negative test group (n = 174) developed TB. The negative predictive values noted for Mantoux test (n = 120) and quantiFERON TB gold test (n = 178) were 96.52% and 96.25%, respectively. Patients on anti-tumor necrosis factor were more likely to develop TB. Presence of comorbidities and steroid use increased the likelihood of developing TB by 1.5 and 4.6 times, respectively. CONCLUSION: Close monitoring of patients receiving biologics is essential for early identification of adverse events, especially in test negative patients. Prophylaxis can effectively reduce the risk of developing TB in patients positive for screening.

The age of skin cancers.

Cancer affects two major cell types in the human skin: epithelial cells and melanocytes. Aging and a previous history of ultraviolet light exposure are major risk factors for skin cancers, including basal and squamous cell carcinomas and melanomas. However, melanomas, which are the most deadly of the skin tumors, display two intriguing characteristics: The incidence is increased and the prognosis is worse in males over 60 years as compared with females of the same age. This Perspective discusses possible reasons for age and gender as melanoma risk factors, as well as the need for studies aimed at unraveling the molecular mechanism of such puzzling events.

Human neuroblastoma (SH-SY5Y) cell culture and differentiation in 3-D collagen hydrogels for cell-based biosensing.

Cell-based three-dimensional systems are desirable in the field of high throughput screening assays due to their potential similarity to in vivo environment. We have used SH-SY5Y human neuroblastoma cells cultured in 3-D collagen hydrogel, confocal microscopy and immunofluorescence staining, to assess the merit of the system as a functional, cell-based biosensor. Our results show differences between 2-D and 3-D resting membrane potential development profile upon differentiation. There was no statistically significant difference in SH-SY5Y proliferation rate between 2-D monolayer and 3-D collagen culture formats. A large percentage of cells (2-D, 91.30% and 3-D, 84.93%) did not develop resting membrane potential value equal to or lower than -40 mV; instead cells exhibited a heterogeneous resting membrane potential distribution. In response to high K(+) (50 mM) depolarization, 3-D cells were less responsive in terms of increase in intracellular Ca(2+), in comparison to 2-D cells, supporting the hypothesis that 2-D cell calcium dynamics may be exaggerated. L-Type Ca(2+) expression levels based on staining results was inconsistent with Bay K 8644 channel activation results, strongly suggesting that either the majority of the channels were non-functional or could not be activated by Bay K 8644. In general, the results in this study confirm the depolarization-induced differences in intracellular calcium release when cultured using a 2-D versus a 3-D matrix.

Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.