Withholding methotrexate after vaccination with ChAdOx1 nCov19 in patients with rheumatoid or psoriatic arthritis in India (MIVAC I and II): results of two, parallel, assessor-masked, randomised controlled trials.

Background: There is a necessity for an optimal COVID-19 vaccination strategy for vulnerable population groups, including people with autoimmune inflammatory arthritis on immunosuppressants such as methotrexate, which inhibit vaccine-induced immunity against SARS-CoV-2. Thus, we aimed to assess the effects of withholding methotrexate for 2 weeks after each dose of ChAdOx1 nCov-19 (Oxford-AstraZeneca) vaccine (MIVAC I) or only after the second dose of vaccine (MIVAC II) compared with continuation of methotrexate, in terms of post-vaccination antibody titres and disease flare rates. Methods: MIVAC I and II were two parallel, independent, assessor-masked, randomised trials. The trials were done at a single centre (Dr Shenoy's Centre for Arthritis and Rheumatism Excellence; Kochi, India) in people with either rheumatoid arthritis or psoriatic arthritis with stable disease activity, who had been on a fixed dose of methotrexate for the preceding 6 weeks. Those with previous COVID-19 or who were positive for anti-SARS-CoV-2 nucleocapsid antibodies were excluded from the trials. People on high-dose corticosteroids and rituximab were also excluded, whereas other disease-modifying antirheumatic drugs were allowed. In MIVAC I, participants were randomly assigned (1:1) to stop methotrexate treatment for 2 weeks after each vaccine dose or to continue methotrexate treatment. In MIVAC II, participants who had continued methotrexate during the first dose of vaccine were randomly assigned (1:1) to withhold methotrexate for 2 weeks after the second dose of vaccine or to continue to take methotrexate. The treating physician was masked to the group assignments. The primary outcome for both MIVAC I and MIVAC II was the titre (absolute value) of anti-receptor binding domain (RBD) antibody measured 4 weeks after the second dose of vaccine. All analyses were done per protocol. The trials were registered with the Clinical Trials Registry- India, number CTRI/2021/07/034639 (MIVAC I) and CTRI/2021/07/035307 (MIVAC II). Findings: Between July 6 and Dec 15, 2021, participants were recruited to the trials. In MIVAC I, 250 participants were randomly assigned and 158 completed the study as per the protocol (80 in the methotrexate hold group and 78 in the control group; 148 [94%] were women and 10 [6%] were men). The median post-vaccination antibody titres in the methotrexate hold group were significantly higher compared with the control group (2484·0 IU/mL, IQR 1050·0-4388·8 vs 1147·5 IU/mL, 433·5-2360·3; p=0·0014). In MIVAC II, 178 participants were randomly assigned and 157 completed the study per protocol (76 in the methotrexate hold group and 81 in the control group; 135 [86%] were women and 22 [14%] were men). The methotrexate hold group had higher post-vaccination antibody titres compared with the control group (2553·5 IU/ml, IQR 1792·5-4823·8 vs 990·5, 356·1-2252·5; p<0·0001). There were no reports of any serious adverse events during the trial period. Interpretation: Withholding methotrexate after both ChAdOx1 nCov-19 vaccine doses and after only the second dose led to higher anti-RBD antibody titres compared with continuation of methotrexate. However, withholding methotrexate only after the second vaccine dose resulted in a similar humoral response to holding methotrexate after both vaccine doses, without an increased risk of arthritis flares. Hence, interruption of methotrexate during the second dose of ChAdOx1 nCov-19 vaccine appears to be a safe and effective strategy to improve the antibody response in patients with rheumatoid or psoriatic arthritis. Funding: Indian Rheumatology Association.

A Kerala model for cardiovascular research?

India's contribution to cardiovascular research has been dismal with a share of only 1% of total number of papers published in the world during the period 1999-2008. Based on two recent studies published from Kerala, the Kerala ACS Registry and the CSI Kerala CRP Study and four other studies being undertaken in Kerala, we think that a Kerala model for cardiovascular research can be conceptualized. This model which consists of funding by professional organization of cardiologists with wide participation of cardiologists, physicians, health workers, nurses, and in some situations general public, logistics looked after by a central coordinator and study design by panel of experts or institutions of repute in the region and carried out at low cost can be considered for implementation in rest of India. Studies based on such a model may change practice pattern of cardiovascular diseases in India.

Successful autologous hematopoietic stem cell transplantation for a patient with rapidly progressive localized scleroderma.

Autologous hematopoietic stem cell transplant (HSCT) for rapidly progressive disease has not been reported in localized scleroderma. Our patient, a 16-year-old girl had an aggressive variant of localized scleroderma, mixed subtype (linear-generalized) with Parry Romberg syndrome, with no internal organ involvement, that was unresponsive to immunosuppressive therapy and was causing rapid disfigurement. She was administered autologous HSCT in June 2011 and has maintained drug-free remission with excellent functional status at almost 3.5 years of follow-up.

Double ventricular rupture after acute myocardial infarction: A rare case report.

A previously asymptomatic 53-year-old male presented 5 days after an acute anterior wall myocardial infarction, who was fibrinolytic naïve, with worsening dyspnea. Transthoracic echocardiographic evaluation revealed rupture of the interventricular septum and pseudoaneurysm of the left ventricle, confirmed by angiography. Coronary angiogram revealed multivessel disease. The patient underwent successful closure of ventricular septal rupture with repair of pseudoaneurysm and saphenous vein grafts to posterior descending branch of right coronary artery and obtuse marginal branch of left circumflex artery. Double ventricular ruptures following acute myocardial infarction are very rare with a reported incidence of 0.3% from various series in the revascularization era. They are also associated with exceedingly high mortality rates reaching up to 50%, even when intervened emergently.

A change in QRS morphology in right ventricular apical pacing: is it a red flag sign?

A 74-year-old man with symptomatic complete heart block underwent right ventricular apical permanent pacemaker implantation. The postoperative ECG showed, as expected, completely paced left bundle branch block QRS morphology. However, at the 2-month follow-up examination, his ECG showed paced right bundle branch block (RBBB) QRS morphology, although the patient was asymptomatic. On evaluation, pacemaker functioning was normal with no evidence of lead displacement. This case report highlights that RBBB morphology of paced QRS complex is not always a red flag sign.

Malignant Arrhythmia with Benign Tumour: Fibrolipoma of the Left Ventricle

We report a case of young male referred for evaluation of recent onset recurrent syncope. Inhospital electrocardiogram revealed an episode of ventricular flutter which reverted spontaneously to sinus rhythm. Transthoracic echocardiogram showed hyperechoic mass in the left ventricle. For further tissue characterization a cardiac magnetic resonance imaging was done which revealed a left ventricular mass with predominant fat content. The tumor was surgically resected. Histopathological examination confirmed the diagnosis of cardiac fibrolipoma. The patient recovered and is currently asymptomatic.