6 research outputs found

    Determinants of Reperfusion Injury in the Diabetic Heart

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    Ischaemic cardiac injury is a leading cause of morbidity and mortality. Recent advances in management of acute cardiac ischaemia have seen early mortality fall and increased survival of myocardial infarction. An increase in prevalence of left ventricular systolic dysfunction and congestive cardiac failure have accompanied increased survival of acute events. Chronic congestive cardiac failure confers high morbidity and late mortality from ischaemic disease. Given the correlation between infarct volume and likelihood of post-infarct heart failure, reduction of infarct size has emerged as an important therapeutic target. A range of experimental treatments collectively termed “preconditioning” have been shown to reduce vulnerability to experimental myocardial infarction in animals but reproducing these results in human cohorts suffering spontaneous myocardial infarction has proved challenging. One of the explanations advanced for lack of translation has been the high prevalence of diabetes in the human population undergoing myocardial infarction, and a direct interaction between the diabetic state and preconditioning treatments has been proposed. Here, I investigate if animal model of diabetes can be used to predict and overcome failure of preconditioning treatments in the diabetic population. Using a rat model of type 2 diabetes, alongside rat strains at lower risk of developing diabetes, the impact of blood insulin content and blood glucose content on susceptibility to myocardial infarction and amelioration by preconditioning treatments was quantified. Experimental infarction was induced by temporary coronary occlusion in an ex vivo Langendorff preparation; both direct and remote ischaemic preconditioning treatments were studied. A raised threshold for successful preconditioning in diabetes was confirmed for direct ischaemic preconditioning and identified for the first time in remote ischaemic preconditioning. Relationships between myocardial exposure to glucose and extent of ischaemia-reperfusion injury were described in both diabetic and non-diabetic animals, and the damage attributable to high glucose exposure in non-diabetic hearts rescued by partial blockade of cellular glucose uptake

    Randomized comparison of oesophageal protection with a temperature control device: results of the IMPACT study.

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    AIMS : Thermal injury to the oesophagus is an important cause of life-threatening complication after ablation for atrial fibrillation (AF). Thermal protection of the oesophageal lumen by infusing cold liquid reduces thermal injury to a limited extent. We tested the ability of a more powerful method of oesophageal temperature control to reduce the incidence of thermal injury. METHODS AND RESULTS : A single-centre, prospective, double-blinded randomized trial was used to investigate the ability of the ensoETM device to protect the oesophagus from thermal injury. This device was compared in a 1:1 randomization with a control group of standard practice utilizing a single-point temperature probe. In the protected group, the device maintained the luminal temperature at 4°C during radiofrequency (RF) ablation for AF under general anaesthesia. Endoscopic examination was performed at 7 days post-ablation and oesophageal injury was scored. The patient and the endoscopist were blinded to the randomization. We recruited 188 patients, of whom 120 underwent endoscopy. Thermal injury to the mucosa was significantly more common in the control group than in those receiving oesophageal protection (12/60 vs. 2/60; P = 0.008), with a trend toward reduction in gastroparesis (6/60 vs. 2/60, P = 0.27). There was no difference between groups in the duration of RF or in the force applied (P value range= 0.2-0.9). Procedure duration and fluoroscopy duration were similar (P = 0.97, P = 0.91, respectively). CONCLUSION : Thermal protection of the oesophagus significantly reduces ablation-related thermal injury compared with standard care. This method of oesophageal protection is safe and does not compromise the efficacy or efficiency of the ablation procedure

    Do not attempt CPR: how the pandemic changed perceptions and practice

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    In this article, the authors look at the current literature and studies around ‘Do Not Attempt Cardiopulmonary Resuscitation’ (DNACPR) discussions and decisions, and how the global coronavirus disease (COVID-19) pandemic brought increased focus on this area of practice. For patients with incurable, advancing illness, having discussions to ascertain their views about CPR, and suggesting and instituting advance care planning measures such as ‘Do Not Attempt CPR’ forms, is becoming part of normal practice in medical settings. Yet all decisions must be individualized to each patient. There was evidence of increased decision-making regarding DNACPR during the pandemic, with concerns raised in the press and on social media. Here, we discuss how this has changed with the global COVID-19 pandemic, where concerns about blanket decision-making and lack of candour in discussing DNACPR decisions with patients and those close to them were raised

    Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

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    © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research

    Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

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    © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit
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