Physiolometrics and the puzzle of methodical acumen'It is of the highest importance in the art of detection to be able to recognize, out of a number of facts, which are incidental and which vital!' These words, spoken by Sherlock Holmes in The Adventure of the Reigate Squire (later also known as The Adventure of the Reigate Puzzle) published in the June issue of The Strand Magazine in 1893, resonate with our quest as physiologists for methodological rigor to this day.

Surgery accounts for 7.7% of all deaths globally and the number of procedures is increasing annually. A patient's 'fitness for surgery' describes the ability to tolerate a physiological insult, fundamental to risk assessment and care planning. We have evolved as obligate aerobes that rely on oxygen (O 2 ). Systemic O 2 consumption can be measured via cardiopulmonary exercise testing (CPET) providing objective metrics of cardiorespiratory fitness (CRF). Impaired CRF is an independent risk factor for mortality and morbidity. The perioperative period is associated with increased O 2 demand, which if not met leads to O 2 deficit, the magnitude and duration of which dictates organ failure and ultimately death. CRF is by far the greatest modifiable risk factor, and optimal exercise interventions are currently under investigation in patient prehabilitation programmes. However, current practice demonstrates potential for up to 60% of patients, who undergo preoperative CPET, to have their fitness incorrectly stratified. To optimise this work we must improve the detection of CRF and reduce potential for interpretive error that may misinform risk classification and subsequent patient care, better quantify risk by expressing the power of CRF to predict mortality and morbidity compared to traditional cardiovascular risk factors, and improve patient interventions with the capacity to further enhance vascular adaptation. Thus, a better understanding of CRF, used to determine fitness for surgery, will enable both clinicians and exercise physiologists to further refine patient care and management to improve survival.

Voluntary asphyxia imposed by static apnea challenges blood-brain barrier (BBB) integrity in humans through transient extremes of hypertension, hypoxemia and hypercapnia. In the present study, ten ultra-elite breath-hold divers performed two maximal dry apneas preceded by normoxic normoventilation (NX: severe hypoxemia and hypercapnia) and hyperoxic hyperventilation (HX: absence of hypoxemia with exacerbating hypercapnia) with measurements obtained before and immediately after apnea. Transcerebral exchange of NVU proteins (ELISA, Single Molecule Array) were calculated as the product of global cerebral blood flow (gCBF, duplex ultrasound) and radial arterial to internal jugular venous concentration gradients. Apnea duration increased from 5 m 6 s in NX to 15 m 59 s in HX ( P = <0.001) resulting in marked elevations in gCBF and venous S100B, glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase-L1 and total tau (all P < 0.05 vs. baseline). This culminated in net cerebral output reflecting mildly increased BBB permeability and increased neuronal-gliovascular reactivity that was more pronounced in NX due to more severe systemic and intracranial hypertension ( P < 0.05 vs. HX). These findings identify the hemodynamic stress to which the apneic brain is exposed, highlighting the critical contribution of hypoxemia and not just hypercapnia to BBB disruption.

New Findings What is the central question of this study?What are the molecular, cerebrovascular and cognitive biomarkers of retired rugby union players with concussion history? What is the main finding and its importance?Retired rugby players compared with matched controls exhibited lower systemic nitric oxide bioavailability accompanied by lower middle cerebral artery velocity and mild cognitive impairment. Retired rugby players are more susceptible to accelerated cognitive decline. Abstract Following retirement from sport, the chronic consequences of prior‐recurrent contact are evident and retired rugby union players may be especially prone to accelerated cognitive decline. The present study sought to integrate molecular, cerebrovascular and cognitive biomarkers in retired rugby players with concussion history. Twenty retired rugby players aged 64 ± 5 years with three (interquartile range (IQR), 3) concussions incurred over 22 (IQR, 6) years were compared to 21 sex‐, age‐, cardiorespiratory fitness‐ and education‐matched controls with no prior concussion history. Concussion symptoms and severity were assessed using the Sport Concussion Assessment Tool. Plasma/serum nitric oxide (NO) metabolites (reductive ozone‐based chemiluminescence), neuron specific enolase, glial fibrillary acidic protein and neurofilament light‐chain (ELISA and single molecule array) were assessed. Middle cerebral artery blood velocity (MCAv, doppler ultrasound) and reactivity to hyper/hypocapnia (CVRCO2hyper${\mathrm{CVR}}_{{\mathrm{CO}}_{\mathrm{2}}{\mathrm{hyper}}}$/CVRCO2hypo${\mathrm{CVR}}_{{\mathrm{CO}}_{\mathrm{2}}{\mathrm{hypo}}}$) were assessed. Cognition was determined using the Grooved Pegboard Test and Montreal Cognitive Assessment. Players exhibited persistent neurological symptoms of concussion (U = 109(41), P = 0.007), with increased severity compared to controls (U = 77(41), P < 0.001). Lower total NO bioactivity (U = 135(41), P = 0.049) and lower basal MCAv were apparent in players (F2,39 = 9.344, P = 0.004). This was accompanied by mild cognitive impairment (P = 0.020, 95% CI, −3.95 to −0.34), including impaired fine‐motor coordination (U = 141(41), P = 0.021). Retired rugby union players with history of multiple concussions may be characterised by impaired molecular, cerebral haemodynamic and cognitive function compared to non‐concussed, non‐contact controls.

Background In the United Kingdom, the most common surgical approach for repair of open abdominal aortic aneurysms (AAAs) is transperitoneal (TP). However, retroperitoneal (RP) approach is favored in those with more complex vascular anatomy often requiring a cross-clamp on the aorta superior to the renal arteries. This study compared these approaches in patients matched on all major demographic, comorbid, anatomic, and physiological variables. Methods Fifty-seven patients (TP: n = 24; RP: n = 33) unsuitable for endovascular aneurysm repair underwent preoperative cardiopulmonary exercise testing prior to open AAA repair. The surgical approach undertaken was dictated by individual surgeon preference. Postoperative mortality, complications, and length of hospital stay (LoS) were recorded. Patients were further stratified according to infrarenal (IR) or suprarenal/supraceliac (SR/SC) surgical clamping. Systemic inflammation (C-reactive protein) and renal function (serum creatinine and estimated glomerular filtration rate) were recorded. Results Twenty-three (96%) of TP patients only required an IR clamp compared with 12 (36%) in the RP group. Postoperative systemic inflammation was lower in RP patients (p = 0.002 vs. TP) and fewer reported pulmonary/gastrointestinal complications whereas renal impairment was more marked in those receiving SR/SC clamps (p < 0.001 vs. IR clamp). RP patients were defined by lower LoS (p = 0.001), while mid-/long-term mortality was low/comparable with TP, resulting in considerable cost savings. Conclusion Despite the demands of more complicated vascular anatomy, the clinical and economic benefits highlighted by these findings justify the more routine adoption of the RP approach for complex AAA repair.