Genetic factors associated with exercise performance in atmospheric hypoxia.

Background And Objective: 'Natural selection' has been shown to have enriched the genomes of high-altitude native populations with genetic variants of advantage in this hostile hypoxic environment. In lowlanders who ascend to altitude, genetic factors may also contribute to the substantial interindividual variation in exercise performance noted at altitude. We performed a systematic literature review to identify genetic variants of possible influence on human hypoxic exercise performance, commenting on the strength of any identified associations.

Cardiopulmonary exercise testing, prehabilitation, and Enhanced Recovery After Surgery (ERAS).

Purpose: This review evaluates the current and future role of cardiopulmonary exercise testing (CPET) in the context of Enhanced Recovery After Surgery (ERAS) programs.

Principal Findings: There is substantial literature confirming the relationship between physical fitness and perioperative outcome in general. The few small studies in patients undergoing surgery within an ERAS program describe less fit individuals having a greater incidence of morbidity and mortality.

Systemic oxygen extraction during exercise at high altitude.

Background: Classic teaching suggests that diminished availability of oxygen leads to increased tissue oxygen extraction yet evidence to support this notion in the context of hypoxaemia, as opposed to anaemia or cardiac failure, is limited.

Methods: At 75 m above sea level, and after 7-8 days of acclimatization to 4559 m, systemic oxygen extraction [C(a-v)O2] was calculated in five participants at rest and at peak exercise. Absolute [C(a-v)O2] was calculated by subtracting central venous oxygen content (CcvO2) from arterial oxygen content [Formula: see text] in blood sampled from central venous and peripheral arterial catheters, respectively.

The effect of neoadjuvant chemoradiotherapy on whole-body physical fitness and skeletal muscle mitochondrial oxidative phosphorylation in vivo in locally advanced rectal cancer patients--an observational pilot study.

Background: In the United Kingdom, patients with locally advanced rectal cancer routinely receive neoadjuvant chemoradiotherapy. However, the effects of this on physical fitness are unclear. This pilot study is aimed to investigate the effect of neoadjuvant chemoradiotherapy on objectively measured in vivo muscle mitochondrial function and whole-body physical fitness.

Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome.

Background: Acute respiratory distress syndrome (ARDS) is a life-threatening critical illness, characterised by qualitative and quantitative surfactant compositional changes associated with premature airway collapse, gas-exchange abnormalities and acute hypoxic respiratory failure. The underlying mechanisms for this dysregulation in surfactant metabolisms are not fully explored. Lack of therapeutic benefits from clinical trials, highlight the importance of detailed in-vivo analysis and characterisation of ARDS patients according to patterns of surfactant synthesis and metabolism.

Changes in muscle proteomics in the course of the Caudwell Research Expedition to Mt. Everest.

This study employed differential proteomic and immunoassay techniques to elucidate the biochemical mechanisms utilized by human muscle (vastus lateralis) in response to high altitude hypoxia exposure. Two groups of subjects, participating in a medical research expedition (A, n = 5, 19 d at 5300 m altitude; B, n = 6, 66 d up to 8848 m) underwent a ≈ 30% drop of muscular creatine kinase and of glycolytic enzymes abundance. Protein abundance of most enzymes of the tricarboxylic acid cycle and oxidative phosphorylation was reduced both in A and, particularly, in B.

King of the mountains: Tibetan and Sherpa physiological adaptations for life at high altitude.

Anecdotal evidence surrounding Tibetans' and Sherpas' exceptional tolerance to hypobaric hypoxia has been recorded since the beginning of high-altitude exploration. These populations have successfully lived and reproduced at high altitude for hundreds of generations with hypoxia as a constant evolutionary pressure. Consequently, they are likely to have undergone natural selection toward a genotype (and phenotype) tending to offer beneficial adaptation to sustained hypoxia.

Metabolic monitoring in the intensive care unit: a comparison of the Medgraphics Ultima, Deltatrac II, and Douglas bag collection methods.

Background: The accuracy of oxygen consumption measurement by indirect calorimeters is poorly validated in mechanically ventilated intensive care patients where multiple confounders exist. This study sought to compare the Medgraphics Ultima (MGU) and Deltatrac II (DTII) devices, and the Douglas bag (DB) technique in mechanically ventilated patients at rest.

Methods: Prospective comparison of oxygen consumption measurement using three indirect calorimetry techniques in stable, resting mechanically ventilated patients at rest.

Perceptions of diagnosis and management of patients with acute respiratory distress syndrome: a survey of United Kingdom intensive care physicians.

Background: Acute respiratory distress syndrome (ARDS) is a potentially devastating refractory hypoxemic illness with multi-organ involvement. Although several randomised controlled trials into ventilator and fluid management strategies have provided level 1 evidence to guide supportive therapy, there are few, established guidelines on how to manage patients with ARDS. In addition, and despite their continued use, pharmacotherapies for ARDS disease modulation have no proven benefit in improving mortality.

Effect of prehabilitation on objectively measured physical fitness after neoadjuvant treatment in preoperative rectal cancer patients: a blinded interventional pilot study.

Background: Patients requiring surgery for locally advanced rectal cancer often additionally undergo neoadjuvant chemoradiotherapy (NACRT), of which the effects on physical fitness are unknown. The aim of this feasibility and pilot study was to investigate the effects of NACRT and a 6 week structured responsive exercise training programme (SRETP) on oxygen uptake [Formula: see text] at lactate threshold ([Formula: see text]) in such patients.

Methods: We prospectively studied 39 consecutive subjects (27 males) with T3-4/N+ resection margin threatened rectal cancer who completed standardized NACRT.

Survival after postoperative morbidity: a longitudinal observational cohort study.

Background: Previous studies have suggested that there may be long-term harm associated with postoperative complications. Uncertainty exists however, because of the need for risk adjustment and inconsistent definitions of postoperative morbidity.

Methods: We did a longitudinal observational cohort study of patients undergoing major surgery.

Cardiopulmonary exercise testing for the prediction of morbidity risk after rectal cancer surgery.

Background: This study investigated the relationship between objectively measured physical fitness variables derived by cardiopulmonary exercise testing (CPET) and in-hospital morbidity after rectal cancer surgery.

Methods: Patients scheduled for rectal cancer surgery underwent preoperative CPET (reported blind to patient characteristics) with recording of morbidity (recorded blind to CPET variables). Non-parametric receiver operating characteristic (ROC) curves and logistic regression were used to assess the relationship between CPET variables and postoperative morbidity.

Effect of a perioperative, cardiac output-guided hemodynamic therapy algorithm on outcomes following major gastrointestinal surgery: a randomized clinical trial and systematic review.

Importance: Small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm.

Objective: To evaluate the clinical effectiveness of a perioperative, cardiac output-guided hemodynamic therapy algorithm.

Design, Setting, And Participants: OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom.

Permissive hypoxaemia versus normoxaemia for mechanically ventilated critically ill patients.

Background: Permissive hypoxaemia describes a concept in which a lower level of arterial oxygenation (PaO2) than usual is accepted to avoid the detrimental effects of high fractional inspired oxygen and invasive mechanical ventilation. Currently however, no specific threshold is known that defines permissive hypoxaemia, and its use in adults remains formally untested. The importance of this systematic review is thus to determine whether any substantial evidence is available to support the notion that permissive hypoxaemia may improve clinical outcomes in mechanically ventilated critically ill patients.

The effects of neoadjuvant chemoradiotherapy on physical fitness and morbidity in rectal cancer surgery patients.

Background: Neoadjuvant chemoradiotherapy (NACRT) followed by surgery for resectable locally advanced rectal cancer improves outcome compared with surgery alone. Our primary hypothesis was that NACRT impairs objectively-measured physical fitness. We also wished to explore the relationship between fitness and postoperative outcome.

Effects of prolonged exposure to hypobaric hypoxia on oxidative stress, inflammation and gluco-insular regulation: the not-so-sweet price for good regulation.

Objectives: The mechanisms by which low oxygen availability are associated with the development of insulin resistance remain obscure. We thus investigated the relationship between such gluco-insular derangements in response to sustained (hypobaric) hypoxemia, and changes in biomarkers of oxidative stress, inflammation and counter-regulatory hormone responses.

Methods: After baseline testing in London (75 m), 24 subjects ascended from Kathmandu (1,300 m) to Everest Base Camp (EBC;5,300 m) over 13 days.

The effect of neoadjuvant chemotherapy on physical fitness and survival in patients undergoing oesophagogastric cancer surgery.

Background: Neoadjuvant chemotherapy (NAC) followed by surgery for resectable oesophageal or gastric cancer improves outcome when compared with surgery alone. However NAC has adverse effects. We assess here whether NAC adversely affects physical fitness and whether such an effect is associated with impaired survival following surgery.

Oral Coenzyme Q10 supplementation does not prevent cardiac alterations during a high altitude trek to everest base cAMP.

Exposure to high altitude is associated with sustained, but reversible, changes in cardiac mass, diastolic function, and high-energy phosphate metabolism. Whilst the underlying mechanisms remain elusive, tissue hypoxia increases generation of reactive oxygen species (ROS), which can stabilize hypoxia-inducible factor (HIF) transcription factors, bringing about transcriptional changes that suppress oxidative phosphorylation and activate autophagy. We therefore investigated whether oral supplementation with an antioxidant, Coenzyme Q10, prevented the cardiac perturbations associated with altitude exposure.

Phospholipid composition and kinetics in different endobronchial fractions from healthy volunteers.

Background: Alterations in surfactant phospholipid compositions are a recognized feature of many acute and chronic lung diseases. Investigation of underlying mechanisms requires assessment of surfactant phospholipid molecular composition and kinetics of synthesis and turnover. Such studies have recently become possible in humans due to the development of stable isotope labelling combined with advances in analytical methods in lipidomics.

Association between preoperative haemoglobin concentration and cardiopulmonary exercise variables: a multicentre study.

Background: Preoperative anaemia and low exertional oxygen uptake are both associated with greater postoperative morbidity and mortality. This study reports the association among haemoglobin concentration ([Hb]), peak oxygen uptake (V˙O2 peak) and anaerobic threshold (AT) in elective surgical patients.

Methods: Between 1999 and 2011, preoperative [Hb] and cardiopulmonary exercise tests were recorded in 1,777 preoperative patients in four hospitals.