Early Immunological Effects of Ischemia-Reperfusion Injury: No Modulation by Ischemic Preconditioning in a Randomised Crossover Trial in Healthy Humans

Ischemic preconditioning (IPC) has been protective against ischemia-reperfusion injury (IRI), but the underlying mechanism is poorly understood. We examined whether IPC modulates the early inflammatory response after IRI. Nineteen healthy males participated in a randomised crossover trial with and without IPC before IRI. IPC and IRI were performed by cuff inflation on the forearm. IPC consisted of four cycles of five minutes followed by five minutes of reperfusion. IRI consisted of twenty minutes followed by 15 min of reperfusion. Blood was collected at baseline, 0 min, 85 min and 24 h after IRI. Circulating monocytes, T-cells subsets and dendritic cells together with intracellular activation markers were quantified by flow cytometry. Luminex measured a panel of inflammation-related cytokines in plasma. IRI resulted in dynamic regulations of the measured immune cells and their intracellular activation markers, however IPC did not significantly alter these patterns. Neither IRI nor the IPC protocol significantly affected the levels of inflammatory-related cytokines. In healthy volunteers, it was not possible to detect an effect of the investigated IPC-protocol on early IRI-induced inflammatory responses. This study indicates that protective effects of IPC on IRI is not explained by direct modulation of early inflammatory events

Remote ischaemic conditioning on recipients of deceased renal transplants, effect on immediate and extended kidney graft function: A multicentre, randomised controlled trial protocol (CONTEXT)

Introduction: Delayed graft function due to ischaemia-reperfusion injury is a frequent complication in deceased donor renal transplantation. Experimental evidence indicates that remote ischaemic conditioning (RIC) provides systemic protection against ischaemia-reperfusion injury in various tissues. Methods and analysis: 'Remote ischaemic conditioning in renal transplantation-effect on immediate and extended kidney graft function' (the CONTEXT study) is an investigator initiated, multicentre, randomised controlled trial investigating whether RIC of the leg of the recipient improves short and long-term graft function following deceased donor kidney transplantation. The study will include 200 kidney transplant recipients of organ donation after brain death and 20 kidney transplant recipients of organ donation after circulatory death. Participants are randomised in a 1:1 design to RIC or sham-RIC (control). RIC consists of four cycles of 5 min occlusion of the thigh by a tourniquet inflated to 250 mm Hg, separated by 5 min of deflation. Primary end point is the time to a 50% reduction from the baseline plasma creatinine, estimated from the changes of plasma creatinine values 30 days post-transplant or 30 days after the last performed dialysis post-transplant. Secondary end points are: need of dialysis post-transplant, measured and estimated-glomerular filtration rate (GFR) at 3 and 12 months after transplantation, patient and renal graft survival, number of rejection episodes in the first year, and changes in biomarkers of acute kidney injury and inflammation in plasma, urine and graft tissue. Ethics and dissemination: The study is approved by the local ethical committees and national data security agencies. Results are expected to be published in 2016

Organophosphate and carbamate insecticide exposure is related to lung function change among smallholder farmers: A prospective study

Introduction and aim: Exposure to some insecticides may cause airway obstruction, but existing evidence is limited by cross-sectional designs and inadequate confounder control. We investigated the relation between organophosphate and carbamate insecticides and pulmonary function in a prospective study accounting for important confounders. Methods: In a cohort of 364 smallholder farmers in Uganda (69% women), participants underwent pre-bronchodilator spirometry at baseline (September/October 2018) and at two follow-up visits (November/December 2018 and January/February 2019). Exposure to carbamate and organophosphate insecticides was assessed using haemoglobin-adjusted erythrocyte acetylcholinesterase (AChE/Hb). Less than 3% of participants were lost to follow-up. We calculated Z-scores for FEV1, FVC and FEV1/FVC using the Global Lung Function Initiative equations. Data were analysed in linear mixed and fixed effect models accounting for family relationships and repeated measures of exposure and outcome. Results: Low AChE/Hb was significantly associated with low FEV1 Z-score in both unadjusted and adjusted analyses. Compared with individuals with AChE/Hb 25.90 U/g (50th percentile, reference), those with lower AChE/Hb 24.50 U/g (35th percentile) had mean FEV1 Z-score 0.045 (0.003 to 0.087) lower, and persons with higher AChE/Hb 27.30 U/g (65th percentile) had a mean FEV1 Z-score 0.043 (-0.002 to 0.087) higher compared with the reference. Similar, but numerically smaller and statistically non-significant effects were seen for Z-scores of FVC and FEV1/FVC. Conclusion: Exposure to organophosphate and carbamate insecticides may lead to lung function decline. Our results add to the growing evidence of health effects in relation to exposure to organophosphate and carbamate insecticides, underlining the importance of minimising exposure

Intrapleural fibrinolysis and DNase versus video-assisted thoracic surgery (VATS) for the treatment of pleural empyema (FIVERVATS) : protocol for a randomised, controlled trial – surgery as first-line treatment

Introduction: Pleural empyema is a frequent disease with a high morbidity and mortality. Current standard treatment includes antibiotics and thoracic ultrasound (TUS)-guided pigtail drainage. Simultaneously with drainage, an intrapleural fibrinolyticum can be given. A potential better alternative is surgery in terms of video-assisted thoracoscopic surgery (VATS) as first-line treatment. The aim of this study is to determine the difference in outcome in patients diagnosed with complex parapneumonic effusion (stage II) and pleural empyema (stage III) who are treated with either VATS surgery or TUS-guided drainage and intrapleural therapy (fibrinolytic (Alteplase) with DNase (Pulmozyme)) as first-line treatment. Methods and analysis: A national, multicentre randomised, controlled study. Totally, 184 patients with a newly diagnosed community acquired complicated parapneumonic effusion or pleural empyema are randomised to either (1) VATS procedure with drainage or (2) TUS-guided pigtail catheter placement and intrapleural therapy with Actilyse and DNase. The total follow-up period is 12 months. The primary endpoint is length of hospital stay and secondary endpoints include for example, mortality, need for additional interventions, consumption of analgesia and quality of life. Ethics and dissemination: All patients provide informed consent before randomisation. The research project is carried out in accordance with the Helsinki II Declaration, European regulations and Good Clinical Practice Guidelines. The Scientific Ethics Committees for Denmark and the Danish Data Protection Agency have provided permission. Information about the subjects is protected under the Personal Data Processing Act and the Health Act. The trial is registered at www.clinicaltrials.gov, and monitored by the regional Good clinical practice monitoring unit. The results of this study will be published in peer-reviewed journals and presented at various national and international conferences. Trial registration number: NCT04095676