Targeting the mitochondria in chronic respiratory diseases.

Mitochondria are one of the basic essential components for eukaryotic life survival. It is also the source of respiratory ATP. Recently published studies have demonstrated that mitochondria may have more roles to play aside from energy production. There is an increasing body of evidence which suggest that mitochondrial activities involved in normal and pathological states contribute to significant impact to the lung airway morphology and epithelial function in respiratory diseases such as asthma, COPD, and lung cancer. This review summarizes the pathophysiological pathways involved in asthma, COPD, lung cancer and highlights potential treatment strategies that target the malfunctioning mitochondria in such ailments. Mitochondria are responsive to environmental stimuli such as infection, tobacco smoke, and inflammation, which are essential in the pathogenesis of respiratory diseases. They may affect mitochondrial shape, protein production and ultimately cause dysfunction. The impairment of mitochondrial function has downstream impact on the cytosolic components, calcium control, response towards oxidative stress, regulation of genes and proteins and metabolic activities. Several novel compounds and alternative medicines that target mitochondria in asthma and chronic lung diseases have been discussed here. Moreover, mitochondrial enzymes or proteins that may serve as excellent therapeutic targets in COPD are also covered. The role of mitochondria in respiratory diseases is gaining much attention and mitochondria-based treatment strategies and personalized medicine targeting the mitochondria may materialize in the near future. Nevertheless, more in-depth studies are urgently needed to validate the advantages and efficacy of drugs that affect mitochondria in pathological states.

Frail patients having vascular surgery during the early COVID-19 pandemic experienced high rates of adverse perioperative events and amputation.

BACKGROUND: Frailty predicts adverse perioperative outcomes and increased mortality in patients having vascular surgery. Frailty assessment is a potential tool to inform resource allocation, and shared decision-making about vascular surgery in the resource constrained COVID-19 pandemic environment. This cohort study describes the prevalence of frailty in patients having vascular surgery and the association between frailty, mortality and perioperative outcomes. METHODS: The COVID-19 Vascular Service in Australia (COVER-AU) prospective cohort study evaluates 30-day and six-month outcomes for consecutive patients having vascular surgery in 11 Australian vascular units, March-July 2020. The primary outcome was mortality, with secondary outcomes procedure-related outcomes and hospital utilization. Frailty was assessed using the nine-point visual Clinical Frailty Score, scores of 5 or more considered frail. RESULTS: Of the 917 patients enrolled, 203 were frail (22.1%). The 30 day and 6 month mortality was 2.0% (n = 20) and 5.9% (n = 35) respectively with no significant difference between frail and non-frail patients (OR 1.68, 95%CI 0.79-3.54). However, frail patients stayed longer in hospital, had more perioperative complications, and were more likely to be readmitted or have a reoperation when compared to non-frail patients. At 6 months, frail patients had twice the odds of major amputation compared to non-frail patients, after adjustment (OR 2.01; 95% CI 1.17-3.78), driven by a high rate of amputation during the period of reduced surgical activity. CONCLUSION: Our findings highlight that older, frail patients, experience potentially preventable adverse outcomes and there is a need for targeted interventions to optimize care, especially in times of healthcare stress.

The prescription of best medical therapy following infrainguinal bypass grafting in Australia and New Zealand: a multicentre Australasian audit.

BACKGROUND: The benefits of best medical therapy (BMT) for secondary prevention of cardiovascular events in patients with peripheral arterial disease are well established. Guidelines recommend prescription of BMT should consist of anti-platelet, statins and angiotensin-converting enzyme inhibitor or angiotensin receptor blocking therapy, with evidence this regimen reduces cardiovascular mortality following vascular surgery and improves vascular bypass graft patency. This multicentre study examines the BMT prescription on discharge after infrainguinal bypass (IIB) in Australia and New Zealand (ANZ). Primary outcome measure was discharge prescription of three BMT pharmacological agents, defined for study purposes as an anti-platelet/anti-coagulant, a lipid-lowering agent, and an anti-hypertensive medication if hypertension was diagnosed. METHODS: This study retrospectively examined discharge prescriptions and summaries of all patients discharged following IIB in five ANZ hospitals, between January 2015 and April 2018. RESULTS: A total of 688 admissions for IIB were included (76.9% male; mean age 67.8 ± 12.0). A total of 72.4% of procedures were for chronic limb ischaemia, compared to acute limb ischaemia (12.6%), and aneurysmal disease (15%). The primary outcome of adherence with complete BMT prescription occurred in 66.9% of admissions. Anti-thrombotic agents were most frequently prescribed (96.4%), followed by anti-lipidaemic agents (82.1%). Of the patients with documented hypertension, 43.8% were not prescribed an angiotensin-converting enzyme inhibitor/angiotensin receptor blocking, while 19.2% were discharged without any anti-hypertensive medications. CONCLUSION: Almost one third of patients were not prescribed complete BMT following IIB. There is potential to improve the outcomes after IIB in ANZ through a focus on risk-factor control and BMT prescription.