Bilateral remote ischemic conditioning in children: A two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery.

Objective: The study objective was to determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for 2 common congenital heart defects with or without cyanosis. Methods: We performed a prospective, double-blind, randomized controlled trial at 2 centers in the United Kingdom. Children aged 3 to 36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analyzed by intention-to-treat. Right atrial biopsies were obtained in selected participants. Results: Between October 2016 and December 2020, 120 eligible children were randomized to receive bilateral preconditioning (n = 60) or sham intervention (n = 60). The primary outcome, area under the curve for high-sensitivity troponin-T, was higher in the preconditioning group (mean: 70.0 ± 50.9 µg/L/h, n = 56) than in controls (mean: 55.6 ± 30.1 µg/L/h, n = 58) (mean difference, 13.2 µg/L/h; 95% CI, 0.5-25.8; P = .04). Subgroup analyses did not show a differential treatment effect by oxygen saturations (pinteraction = .25), but there was evidence of a differential effect by underlying defect (pinteraction = .04). Secondary outcomes and myocardial metabolism, quantified in atrial biopsies, were not different between randomized groups. Conclusions: Bilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot. The routine use of remote ischemic preconditioning cannot be recommended for myocardial protection during pediatric cardiac surgery.

'Being with' or 'doing for'? How the role of an end-of-life volunteer befriender can impact patient wellbeing: interviews from a multiple qualitative case study (ELSA).

PURPOSE: To explore the perspectives of people anticipated to be in their last year of life, family carers, volunteers and staff on the impacts of receiving a volunteer-provided befriending service. Patient participants received up to 12 weeks of a volunteer-provided befriending intervention. Typically, this involved one visit per week from a trained volunteer. Such services complement usual care and are hoped to enhance quality of life. METHODS: Multiple case study design (n = 8). Cases were end-of-life befriending services in home and community settings including UK-based hospices (n = 6), an acute hospital (n = 1) and a charity providing support to those with substance abuse issues (n = 1). Data collection incorporated qualitative thematic interviews, observation and documentary analysis. Framework analysis facilitated within and across case pattern matching. RESULTS: Eighty-four people participated across eight sites (cases), including patients (n = 23), carers (n = 3), volunteers (n = 24) and staff (n = 34). Interview data are reported here. Two main forms of input were described-'being there' and 'doing for'. 'Being there' encapsulated the importance of companionship and the relational dynamic between volunteer and patient. 'Doing for' described the process of meeting social needs such as being able to leave the house with the volunteer. These had impacts on wellbeing with people describing feeling less lonely, isolated, depressed and/or anxious. CONCLUSION: Impacts from volunteer befriending or neighbour services may be achieved through volunteers taking a more practical/goal-based orientation to their role and/or taking a more relational and emotional orientation. Training of volunteers must equip them to be aware of these differing elements of the role and sensitive to when they may create most impact. TRIAL REGISTRATION: ISRCTN12929812.

Insulin--carcinogen or mitogen? Preclinical and clinical evidence from prostate, breast, pancreatic, and colorectal cancer research.

Diabetes mellitus is a chronic disease that affects > 23.6 million Americans, and occurs when the body is unable to produce or becomes resistant to endogenous insulin. This alteration of insulin's action reduces adequate utilization of glucose transporter type 4 (GLUT4) receptors, which are responsible for cellular glucose uptake. Thus, exogenous administration of human insulin and insulin analogs is an important modality used to reduce morbidity and mortality in both type 1 and type 2 diabetes. According to 2007 estimates, 27% of all patients with diabetes use some form of insulin therapy. The increasing utilization of insulin has become a cause for concern because findings from several observational trials have suggested an association with an increased risk of developing cancer. To help elucidate the potential interplay between insulin use and cancer, we searched PubMed and MEDLINE to identify articles that assessed the carcinogenic and/or mitogenic potential of diabetes treatments, focusing on insulin specifically. Data from our review suggest that insulin analogs, particularly insulin glargine, may play more of a mitogenic than a carcinogenic role in association with different types of cancer, suggesting an amplified rate of existing tumor growth in the presence of insulin analogs. Evidence for insulin-induced mitogenicity appears to be most prevalent in prostate, breast, pancreatic, and colorectal cancers. In conclusion, the positive effects of insulin therapy on reducing morbidity and mortality in diabetes greatly outweigh the risks at this time. However, clinicians must be diligent in both screening for new cancers in patients receiving insulin and in monitoring for tumor growth or maintenance of remission in patients with existing cancers.