Cardiopulmonary exercise testing has greater prognostic value than sarcopenia in oesophago-gastric cancer patients undergoing neoadjuvant therapy and surgical resection.

BACKGROUND: Sarcopenia (low skeletal muscle mass), myosteatosis (low skeletal muscle radiation-attenuation) and fitness are independently associated with postoperative outcomes in oesophago-gastric cancer. This study aimed to investigate (1) the effect of neoadjuvant therapy (NAT) on sarcopenia, myosteatosis and cardiopulmonary exercise testing (CPET), (2) the relationship between these parameters, and (3) their association with postoperative morbidity and survival. METHODS: Body composition analysis used single slice computed tomography (CT) images from chest (superior to aortic arch) and abdominal CT scans (third lumbar vertebrae). Oxygen uptake at anaerobic threshold (VO2 at AT) and at peak exercise (VO2 Peak) were measured using CPET. Measurements were performed before and after NAT and an adjusted regression model assessed their association. RESULTS: Of the 184 patients recruited, 100 underwent surgical resection. Following NAT skeletal muscle mass, radiation-attenuation and fitness reduced significantly (p < 0.001). When adjusted for age, sex, and body mass index, only pectoralis muscle mass was associated with VO2 Peak (p = 0.001). VO2 at AT and Peak were associated with 1-year survival, while neither sarcopenia nor myosteatosis were associated with morbidity or survival. CONCLUSION: Skeletal muscle and CPET variables reduced following NAT and were positively associated with each other. Cardiorespiratory function significantly contributes to short-term survival after oesophago-gastric cancer surgery.

Effects of dietary nitrate supplementation on microvascular physiology at 4559 m altitude - A randomised controlled trial (Xtreme Alps).

Native highlanders (e.g. Sherpa) demonstrate remarkable hypoxic tolerance, possibly secondary to higher levels of circulating nitric oxide (NO) and increased microcirculatory blood flow. As part of the Xtreme Alps study (a randomised placebo-controlled trial of dietary nitrate supplementation under field conditions of hypobaric hypoxia), we investigated whether dietary supplementation with nitrate could improve NO availability and microvascular blood flow in lowlanders. Plasma measurements of nitrate, nitrite and nitroso species were performed together with measurements of sublingual (sidestream dark-field camera) and forearm blood flow (venous occlusion plethysmography) in 28 healthy adult volunteers resident at 4559 m for 1 week; half receiving a beetroot-based high-nitrate supplement and half receiving an identically-tasting low nitrate 'placebo'. Dietary supplementation increased plasma nitrate concentrations 4-fold compared to the placebo group, both at sea level (SL; 19.2 vs 76.9 µM) and at day 5 (D5) of high altitude (22.9 vs 84.3 µM, p < 0.001). Dietary nitrate supplementation also significantly increased both plasma nitrite (0.78 vs. 0.86 µM SL, 0.31 vs. 0.41 µM D5, p = 0.03) and total nitroso product (11.3 vs. 19.7 nM SL, 9.7 vs. 12.3 nM D5, p < 0.001) levels both at sea level and at 4559 m. However, plasma nitrite concentrations were more than 50% lower at 4559 m compared to sea level in both treatment groups. Despite these significant changes, dietary nitrate supplementation had no effect on any measured read-outs of sublingual or forearm blood flow, even when environmental hypoxia was experimentally reversed using supplemental oxygen. In conclusion, dietary nitrate supplementation does not improve microcirculatory function at 4559 m.

Xtreme Everest 2: unlocking the secrets of the Sherpa phenotype?

Xtreme Everest 2 (XE2) was part of an ongoing programme of field, laboratory and clinical research focused on human responses to hypoxaemia that was conducted by the Caudwell Xtreme Everest Hypoxia Research Consortium. The aim of XE2 was to characterise acclimatisation to environmental hypoxia during a standardised ascent to high altitude in order to identify biomarkers of adaptation and maladaptation. Ultimately, this may lead to novel diagnostic and treatment strategies for the pathophysiological hypoxaemia and cellular hypoxia observed in critically ill patients. XE2 was unique in comparing participants drawn from two distinct populations: native ancestral high-altitude dwellers (Sherpas) and native lowlanders. Experiments to study the microcirculation, mitochondrial function and the effect that nitric oxide metabolism may exert upon them were focal to the scientific profile. In addition, the genetic and epigenetic (methylation and histone modification) basis of observed differences in phenotype was explored. The biological samples and phenotypic metadata already collected during XE2 will be analysed as an independent study. Data generated will also contribute to (and be compared with) the bioresource obtained from our previous observational high-altitude study, Caudwell Xtreme Everest (2007).

Everest 60 years on: what next?

On 29 May 1953, Sherpa Tenzing Norgay and Edmund Hilary stood on the 8,848 m (29,029 ft) summit of Mount Everest, finally demonstrating that humans could overcome the physical and mental challenges required to conquer the world's highest peak. The 60th anniversary of this event is sadly the first with no member of the original expedition alive, since the death of George Lowe on 20 March 2013 at the age of 89 The successful 1953 expedition followed seven British expeditions to the north side of Everest during the 1920s and 30s. Although unsuccessful, these early expeditions achieved impressive altitudes. On several occasions, climbers exceeded 8,000 m (26,246 ft) both with supplemental oxygen (1922, 8,320 m/27,300 ft) and without (1924, 8,570 m/28120 ft; 1938, 8,230 m/27,000 ft).