Pankaj Kumar Mishra

Bone marrow-derived mesenchymal stem cells for treatment of heart failure: is it all paracrine actions and immunomodulation?

Despite significant advances in medical and surgical management of heart failure, mostly of ischaemic origin, the mortality and morbidity associated with it continue to be high. Pluripotent stem cells are being evaluated for treatment of heart failure. Bone marrow-derived mesenchymal stem cells (MSCs) have been extensively studied. Emerging evidence suggests that locally delivered MSCs can lead to an improvement in ventricular function, but the cellular and molecular mechanisms involved remain unclear. Myocardial regeneration, as proposed by many researchers as the underlying mechanism, has failed to convince the scientific community. Recently some authors have ascribed improvement in ventricular function to paracrine actions of MSCs. A lot has been written about the host immune response triggered by embryonic stem cells and the consequent need for immunosuppression. Not enough work has been done on immune interactions involving allogeneic bone marrow cells. Full potential of stem cell therapy can be realised only when we are able to use allogeneic cells. The potential use of MSCs in cellular therapy has recently prompted researchers to look into their interaction with the host immune response. MSCs have immunomodulatory properties. They cause suppression of proliferation of alloreactive T cells in a dose-dependent manner. Tissue injury causes inflammation and release of several chemokines, cytokines and growth factors. They can cause recruitment of bone marrow-derived MSCs to the injured area. We review the literature on paracrine actions and immune interactions of allogeneic MSCs.

Informed consent in cardiac surgery: is it truly informed?

Objective To develop a validated questionnaire to measure how informed patients are when giving consent for elective coronary artery bypass grafting. Methods We developed a questionnaire covering the domains described in the consent guidelines published by the General Medical Council. The questionnaire was developed for use in face-to-face interviews as opposed to a self-administered questionnaire. Interviews were conducted after the patients had given consent for surgery. A total of 41 patients were interviewed. To validate the questionnaire we tested the interobserver reliability by using four different interviewers and the construct validity by comparing it with area deprivation index and with predicted intelligence quotient scores obtained from the National Adult Reading Test. Results The correlation of the ranking of the questions between the interviewers was satisfactory (Spearmans rank correlation coefficient, rs = 0.84–0.89). The total questionnaire scores correlated well with predicted intelligence quotient scores (rs = 0.48) but not with area deprivation index (rs = 0.01). Questions with the worst scores were those related to mortality, morbidity, alternative treatment options and their relative success rates and risks. Conclusions We have developed a validated questionnaire which tests patients level of knowledge with respect to surgical myocardial revascularisation. Our study identified areas of informed consent where the minimal level of knowledge is below the recommended level. The questionnaire could be used in audits and clinical trials in patients undergoing coronary artery bypass grafting. It could be used as a tool to measure the effectiveness of patient education programmes. With appropriate changes, this instrument could also be applied in other fields of medical intervention, which require patients to give informed consent.