Enthesitis in a European registry-based cohort of patients with psoriatic arthritis treated with tumour necrosis factor inhibitors: clinical burden, patient-reported outcomes, and treatment response.

OBJECTIVE: To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment across 12 European registries, compare the disease burden and patient-reported outcomes (PROs) between patients with and without enthesitis, and assess the enthesitis treatment response. METHOD: Demographics, clinical characteristics, and PROs at first TNFi (TNFi-1) initiation (baseline) were assessed in patients with PsA, diagnosed by a rheumatologist, with versus without assessment of entheses and between those with versus without enthesitis. Enthesitis scores and resolution frequency were identified at follow-up. RESULTS: Of 10 547 patients in the European Spondyloarthritis (EuroSpA) Research Collaboration Network initiating TNFi, 1357 underwent evaluation for enthesitis. Eight registries included a validated scoring system for enthesitis. At baseline, 874 patients underwent entheses assessment [Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 485 patients, Spondyloarthritis Research Consortium of Canada (SPARCC) 389 patients]. Enthesitis was detected by MASES in 170/485 (35%, mean score ± sd 3.1 ± 2.4) and by SPARCC in 236/389 (61%, 4 ± 3.4). Achilles enthesitis was most frequent, by both MASES (unilateral/bilateral 28%/9%) and SPARCC (48%/18%). MASES/SPARCC baseline and follow-up scores for TNFi-1 were available for 100/105 patients. Of these, 63 patients (63%) (MASES) and 46 (43.8%) (SPARCC) achieved resolution of enthesitis. The site-specific enthesitis resolution was overall lower at SPARCC sites (peripheral; 63-80%) than at MASES sites (mainly axial; 82-100%) following TNFi-1. Disease activity and PROs were worse in patients with versus without enthesitis. CONCLUSION: Entheseal assessments are only registered in a minority of patients with PsA in routine care. When assessed, enthesitis was common, and a substantial proportion demonstrated resolution following treatment with TNFi-1.

Beta and theta oscillations track effort and previous reward in human basal ganglia and prefrontal cortex during decision making.

Choosing whether to exert effort to obtain rewards is fundamental to human motivated behavior. However, the neural dynamics underlying the evaluation of reward and effort in humans is poorly understood. Here, we investigate this with chronic intracranial recordings from prefrontal cortex (PFC) and basal ganglia (BG; subthalamic nuclei and globus pallidus) in people with Parkinson's disease performing a decision-making task with offers that varied in levels of reward and physical effort required. This revealed dissociable neural signatures of reward and effort, with BG beta (12-20 Hz) oscillations tracking subjective effort on a single trial basis and PFC theta (4-7 Hz) signaling previous trial reward. Stimulation of PFC increased overall acceptance of offers in addition to increasing the impact of reward on choices. This work uncovers oscillatory mechanisms that guide fundamental decisions to exert effort for reward across BG and PFC, as well as supporting a causal role of PFC for such choices.

Long-term outcomes to neoadjuvant pembrolizumab based on pathological response for patients with resectable stage III/IV cutaneous melanoma.

BACKGROUND: While neoadjuvant immunotherapy for melanoma has shown promising results, the data have been limited by a relatively short follow-up time, with most studies reporting 2-year outcomes. The goal of this study was to determine long-term outcomes for stage III/IV melanoma patients treated with neoadjuvant and adjuvant programmed cell death receptor 1 (PD-1) inhibition. PATIENTS AND METHODS: This is a follow-up study of a previously published phase Ib clinical trial of 30 patients with resectable stage III/IV cutaneous melanoma who received one dose of 200 mg IV neoadjuvant pembrolizumab 3 weeks before surgical resection, followed by 1 year of adjuvant pembrolizumab. The primary outcomes were 5-year overall survival (OS), 5-year recurrence-free survival (RFS), and recurrence patterns. RESULTS: We report updated results at 5 years of follow-up with a median follow-up of 61.9 months. No deaths occurred in patients with a major pathological response (MPR, <10% viable tumor) or complete pathological response (pCR, no viable tumor) (n = 8), compared to a 5-year OS of 72.8% for the remainder of the cohort (P = 0.12). Two of eight patients with a pCR or MPR had a recurrence. Of the patients with >10% viable tumor remaining, 8 of 22 patients (36%) had a recurrence. Additionally, the median time to recurrence was 3.9 years for patients with ≤10% viable tumor and 0.6 years for patients with >10% viable tumor (P = 0.044). CONCLUSIONS: The 5-year results from this trial represent the longest follow-up of a single-agent neoadjuvant PD-1 trial to date. Response to neoadjuvant therapy continues to be an important prognosticator with regard to OS and RFS. Additionally, recurrences in patients with pCR occur later and are salvageable, with a 5-year OS of 100%. These results demonstrate the long-term efficacy of single-agent neoadjuvant/adjuvant PD-1 blockade in patients with a pCR and the importance of long-term follow-up for these patients. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02434354.

Burden of osteoarthritis in India and its states, 1990-2019: findings from the Global Burden of disease study 2019.

OBJECTIVE: To describe the burden of osteoarthritis (OA) in India from 1990 to 2019. DESIGN: Data from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used. The burden of OA -knee OA, hip OA, hand OA, and other OA- was estimated for India and its states from 1990 to 2019 through a systematic analysis of prevalence, incidence, years lived with disability (YLD), and disability-adjusted life years (DALY) using methods reported in GBD 2019 study. RESULT: Around 23.46 million individuals in India had OA in 1990; this increased to 62.35 million in 2019. The age-standardised prevalence of OA increased from 4,895 (95% uncertainty interval (UI):4,420-5,447) in 1990-5313 (95%UI:4,799-5,898) in 2019, per 100,000 persons. Similarly, DALYs due to OA increased from 0.79 million (95%UI:0.40-1.55) to 2.12 million (95%UI:1.07-4.23); while age-standardised DALYs increased from 164 (95%UI:83-325) to 180 (95%UI:91-361) per 100,000 persons from 1990 to 2019. OA was the 20th most common cause of YLDs in India in 2019, accounting for 1.48% (95%UI:0.88-2.78) of all YLDs; increasing from 23rd most common cause in 1990 (1.25%(95%UI:0.74-2.34)). Knee OA was the most common form of OA, followed by hand OA. The prevalence, incidence, and DALYs for OA and knee OA were consistently higher in females than males. CONCLUSION: The burden and impact of OA in India are substantial and is increasing. Adopting suitable control and preventive community measures to reduce modifiable risk factors (obesity, injuries, occupational stress) are needed to reduce the current and future burden of OA in India.

Reliability and agreement of proton density-weighted vs. gadolinium-enhanced T1-weighted MRI in hand osteoarthritis. An OMERACT MRI special interest group reliability exercise.

OBJECTIVES: To compare reliabilities of assessing synovitis in hand osteoarthritis (OA) using Magnetic Resonance Imaging (MRI) with/without gadolinium (Gd). METHODS: Three readers scored synovitis on non-enhanced two-dimensional (2D) proton density (PD)-weighted MRI and Gd-enhanced (3D) MRI of hand joints in 20 patients. Inter-reader reliabilities were examined. RESULTS: Reliability was good for Gd-enhanced MRI, but poor for non-enhanced PD-weighted MRI (intraclass correlation coefficient 0.83 and 0.21, respectively). Agreement between the two sequences was poor (weighted kappa 0.18). CONCLUSION: Gd-enhanced MRI was more reliable than PD-weighted MRI for assessing synovitis. Gd-enhancement, but also resolution and tissue contrast, might have contributed to this.

Chikungunya Infection: a Global Public Health Menace.

Chikungunya virus (CHIKV) has been involved in epidemics in African and Asian subcontinents and, of late, has transcended to affect the Americas. Aedes aegypti and Aedes albopictus are the major vectors for CHIKV infection, which results in dissemination of virus to various vital organs. Entry of virus into these tissues causes infiltration of innate immune cells, monocytes, macrophages, neutrophils, natural killer cells, and adaptive immune cells. Macrophages bearing the replicating virus, in turn, secrete pro-inflammatory cytokines IL-1ß, TNF-α, and IL-17. Together, this pro-inflammatory milieu induces osteoclastogenesis, bone loss, and erosion. CHIKV is characterized by fever, headache, myalgia, rash, and symmetric polyarthritis, which is generally self-limiting. In a subset of cases, however, musculoskeletal symptoms may persist for up to 3-5 years. Viral culture and isolation from blood cells of infected patients are the gold standards for diagnosis of CHIKV. In routine practice, however, assays for anti-CHIKV IgM antibodies are used for diagnosis, as elevated levels in blood of infected patients are noted from 10 days following infection for up to 3-6 months. Early diagnosis of CHIKV is possible by nucleic acid detection techniques. Treatment of acute CHIKV is mainly symptomatic, with analgesics, non-steroidal anti-inflammatory agents (NSAIDs), and low-dose steroids. No vaccines or anti-viral medicines have been approved for clinical therapy in CHIKV as yet. Hydroxychloroquine and methotrexate have been used in chronic CHIKV infection with variable success.

Rheumatic-musculoskeletal pain and disorders in a naïve group of individuals 15 months following a Chikungunya viral epidemic in south India: a population based observational study.

BACKGROUND: Prospective community data on arthropathy following Chikungunya (CHIKV), a self-limiting, arboviral infection, causing debilitating arthropathy are lacking. The clinical profile of chronic rheumatic-musculoskeletal (RMSK) pain and disorders, captured inadvertently about 15 months following a CHIKV epidemic is described. MATERIALS AND METHODS: Patients with RMSK pain following the CHIKV epidemic in 2007 were identified from a randomly selected population of 5277 (Age > 15 years) in a village in south India, using a validated questionnaire-based house-to-house survey. Typical narration, records and serology were relied upon to classify CHIKV. Respondents who recorded active pain sites on a human mannequin were evaluated by Rheumatology physicians. RESULTS: A total of 1396 CHIKV infected individuals with painful MSKD were identified, of whom 437 patients (mean age: 48.37 ± 13.62 years; 71.6% women) who were naïve to RMSK pain prior to the epidemic were studied in detail. Incidence of RMSK pain and disorders in the naïve group was 8.3% (437/5277). Knee was the commonest self-reported pain site (83.3%). Majority of the patients (57%) had postviral non-specific polyarthralgia. Soft tissue rheumatism was very common (27.7%). Rheumatoid arthritis and seronegative spondyloarthritis were observed in 6 and 11 patients, respectively. CONCLUSIONS: Although a causal association could not be established, this study has unravelled a wide spectrum of unrecognised post-CHIKV chronic RMSK disorders. Aetiopathogenesis and risk factors of chronicity need to be studied further.

Perennial impression of an emerging arbovirus on the epidemiology of rheumatic diseases in south India: insights from the COPCORD study.

Are rheumatic musculoskeletal diseases (RMSD) given their due recognition by the medical fraternity and policy makers in India today? Focus on lifestyle diseases has taken away the importance of morbidity caused by musculoskeletal pain, which is one of the commonest ailments in the community. Poor awareness in general regarding the upcoming field of rheumatology and lack of proper data regarding these diseases in the country are the primary causes for this debacle. The epidemiology of RMSD in the country is fast changing, especially in the wake of viral epidemics, which leave their mark for months and years together. This view point emphasizes the burden of RMSD by highlighting the findings of two Community Oriented Programme for the Control of Rheumatic Diseases studies conducted to study the prevalence of RMSD in rural communities in the southern state of Kerala, which inadvertently captured the burden of RMSD following Chikungunya viral epidemics in the regions. Both the studies have reported a high prevalence of RMSD following the epidemics. The value of including RMSD in a national programme to combat the morbidity caused and to improve the health related quality of life of patients has been stressed upon, in the background of altering epidemiology of these disorders in the country.

The effect of butyrate on the healing of colonic anastomoses in rats.

BACKGROUND: Butyrate, a short-chain fatty acid (SCFA) formed by the fermentation of complex carbohydrates by the bacteria in the colon, is the main source of nutrition for colonocytes. The aim of this experiment was to investigate the effect of butyrate on the healing of colonic anastomosis in a rat model. MATERIALS AND METHODS: Forty male Wistar rats were fed a fibre-free diet for 2 days. They then underwent laparotomy, transection, and anastomosis of both left and right colon, with a defunctioning caecostomy. The animals were then randomly assigned to receive butyrate or saline enemas from the third postoperative day and underwent another laparotomy on the seventh postoperative day when the bursting pressures of both anastomoses were measured. RESULTS: Out of the 40 rats, 23 were available for the final data analysis. The mechanical strength of the anastomosis was measured by the bursting wall tension (BWT), which was calculated from the bursting pressure and the anastomotic circumference. The anastomoses in the butyrate arm showed a significantly higher BWT for both the right (48.9 s 64.71 dyne10(-3)/cm, p value .04) and the left (51.44 vs 72.38 dyne 10(-3)/cm, p value .01). CONCLUSION: This experiment suggests that butyrate has a significant role in increasing the mechanical strength of colonic anastomoses in rats.

Health-related quality of life in rheumatoid arthritis patients in South India.

INTRODUCTION: Assessment of health-related quality of life (HRQL) has been gaining much importance in the care of rheumatoid arthritis (RA). This study was aimed at assessing the HRQL of patients with RA in South India. METHODS: HRQL of consenting RA patients, on disease-modifying anti-rheumatoid drugs (DMARDs) and attending a rheumatology clinic, was assessed using a self-filled Malayalam version of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) version 4 questionnaire. RESULTS: 50 patients were assessed out of 58 responses. The mean duration of the disease was 7.29 years. 46 patients (79.3 percent) had tried complementary and alternative medicines (CAM). The HRQL score in patients who were put on DMARDs within six months of symptoms was significantly higher (p-value is equal to 0.008). CONCLUSION: HRQL in patients treated early by DMARDs is significantly higher in this region, where a good proportion of patients seek the CAM for treatment of RA.

Wegener's granulomatosis: a rare presentation.

Wegener's granulomatosis (WG) is a necrotizing granulomatous vasculitis involving the nose, paranasal sinuses, lungs, and kidneys. There are two types of WG-systemic, which is characterized by focal segmental necrotizing glomerulonephritis and limited in which the kidneys are spared. Without proper immunosuppression, WG can be aggressive and often fatal. There are very few reports on WG presenting as parotitis and lacrimal gland involvement. We report a lady who presented recurrent parotitis, focal segmental glomerulosclerosis, and orbital cellulitis, in whom the final diagnosis was revealed after an open lung biopsy.