Association between psoas major muscle mass and CPET performance and long-term survival following major colorectal surgery: A retrospective cohort study.

OBJECTIVES: To evaluate whether computed tomography (CT)-derived psoas major muscle measurements could predict preoperative cardiopulmonary exercise testing (CPET) performance and long-term mortality in patients undergoing major colorectal surgery and to compare predictive performance of psoas muscle measurements using 2D approach and 3D approach. METHODS: A retrospective cohort study compliant with STROCSS standards was conducted. Consecutive patients undergoing major colorectal surgery between January 2011 and January 2017 following CPET as part of their preoperative assessment were included. Regression analyses were modelled to investigate association between the CT-derived psoas major muscle mass variables [total psoas muscle area (TPMA), total psoas muscle volume (TPMV) and psoas muscle index (PMI)] and CPET performance and mortality (1-year and 5-year). Discriminative performances of the variables were evaluated using Receiver Operating Characteristic (ROC) curve analysis. RESULTS: A total of 457 eligible patients were included. The median TPMA and TPMV were 21 â€‹cm2 (IQR: 15-27) and 274 â€‹cm3 (IQR: 201-362), respectively. The median PMI measured via 2D and 3D approaches were 7 â€‹cm2/m2 (IQR: 6-9) and 99 â€‹cm3/m2 (IQR: 76-120), respectively. The risks of 1-year and 5-year mortality were 7.4% and 27.1%, respectively. Regression analyses showed TPMA, TPMV, and PMI can predict preoperative CPET performance and long-term mortality. However, ROC curve analyses showed no significant difference in predictive performance amongst TPMA, TPMV, and PMI. CONCLUSION: Radiologically-measured psoas muscle mass variables may predict preoperative CPET performance and may be helpful with informing more objective selection of patients for preoperative CPET and prehabilitation.

Cognition is selectively impaired in males with spinal pain: A retrospective analysis of data from the Longitudinal Study of Ageing Danish Twins.

Cognitive decline and spinal pain (back pain [BP] and neck pain [NP]) represent a major public health challenge, yet the potential relationship between them remains elusive. A retrospective analysis of the Longitudinal Study of Ageing Danish Twins was performed to determine any potential relationships between BP/NP and cognitive function adjusting for age, sex, educational and socioeconomic status. A total of 4731 adults (2788 females/1943 males) aged 78 ± 6 (SD) years were included in the analysis. We observed a 1-month prevalence of 25% with BP, 21% with NP and 11% for combined BP/NP. While there were no differences in cognition scores for males and females reporting combined BP/NP, compared to those without combined BP/NP (34.38 points [95% confidence interval (CI) = 31.88, 36.88] vs. 35.72 points [95% CI = 35.19, 36.26]; P = 0.180; and 35.72 points [95% CI = 35.19, 36.26] vs. 35.85 points [95% CI = 35.39, 36.31]; P = 0.327; for male and females, respectively), an adjusted analysis revealed that males with combined BP/NP presented with lower cognitive scores compared to males without combined BP/NP (81.26 points [95% CI = 73.80, 88.72] vs. 79.48 points [95% CI = 70.31, 88.66]; P = 0.043). The findings of this hypothesis-generating study may highlight a potential sex-specific association between spinal pain and later-life neurodegeneration.

Severe hypoxaemic hypercapnia compounds cerebral oxidative-nitrosative stress during extreme apnoea: Implications for cerebral bioenergetic function.

We examined the extent to which apnoea-induced extremes of oxygen demand/carbon dioxide production impact redox regulation of cerebral bioenergetic function. Ten ultra-elite apnoeists (six men and four women) performed two maximal dry apnoeas preceded by normoxic normoventilation, resulting in severe end-apnoea hypoxaemic hypercapnia, and hyperoxic hyperventilation designed to ablate hypoxaemia, resulting in hyperoxaemic hypercapnia. Transcerebral exchange of ascorbate radicals (by electron paramagnetic resonance spectroscopy) and nitric oxide metabolites (by tri-iodide chemiluminescence) were calculated as the product of global cerebral blood flow (by duplex ultrasound) and radial arterial (a) to internal jugular venous (v) concentration gradients. Apnoea duration increased from 306 ± 62 s during hypoxaemic hypercapnia to 959 ± 201 s in hyperoxaemic hypercapnia (P ≤ 0.001). Apnoea generally increased global cerebral blood flow (all P ≤ 0.001) but was insufficient to prevent a reduction in the cerebral metabolic rates of oxygen and glucose (P = 0.015-0.044). This was associated with a general net cerebral output (v > a) of ascorbate radicals that was greater in hypoxaemic hypercapnia (P = 0.046 vs. hyperoxaemic hypercapnia) and coincided with a selective suppression in plasma nitrite uptake (a > v) and global cerebral blood flow (P = 0.034 to <0.001 vs. hyperoxaemic hypercapnia), implying reduced consumption and delivery of nitric oxide consistent with elevated cerebral oxidative-nitrosative stress. In contrast, we failed to observe equidirectional gradients consistent with S-nitrosohaemoglobin consumption and plasma S-nitrosothiol delivery during apnoea (all P ≥ 0.05). Collectively, these findings highlight a key catalytic role for hypoxaemic hypercapnia in cerebral oxidative-nitrosative stress. KEY POINTS: Local sampling of blood across the cerebral circulation in ultra-elite apnoeists determined the extent to which severe end-apnoea hypoxaemic hypercapnia (prior normoxic normoventilation) and hyperoxaemic hypercapnia (prior hyperoxic hyperventilation) impact free radical-mediated nitric oxide bioavailability and global cerebral bioenergetic function. Apnoea generally increased the net cerebral output of free radicals and suppressed plasma nitrite consumption, thereby reducing delivery of nitric oxide consistent with elevated oxidative-nitrosative stress. The apnoea-induced elevation in global cerebral blood flow was insufficient to prevent a reduction in the cerebral metabolic rates of oxygen and glucose. Cerebral oxidative-nitrosative stress was greater during hypoxaemic hypercapnia compared with hyperoxaemic hypercapnia and coincided with a lower apnoea-induced elevation in global cerebral blood flow, highlighting a key catalytic role for hypoxaemia. This applied model of voluntary human asphyxia might have broader implications for the management and treatment of neurological diseases characterized by extremes of oxygen demand and carbon dioxide production.

Aortic Arch Debranching and Thoracic Endovascular Aortic Repair (TEVAR) for Type B Aortic Dissection.

BACKGROUND: Since its introduction, thoracic endovascular aortic repair (TEVAR) has revolutionized the treatment of type B aortic dissections (TBADs). However, the proximal aspect of the aortic pathology treated may infringe on the origin of the left subclavian artery or even more proximally. Hence, to ensure durable outcomes, the origin of these vessels needs to be covered, but an extra-anatomical bypass is required to perfuse vital branches, known as aortic arch debranching. This series aims to describe and delineate the disparities of aortic arch debranching during TEVAR for TBAD. METHODS: A retrospective review and analysis of a multicenter international database was conducted to identify patients with TBAD treated with TEVAR between 2005 and 2021. Data analyzed included patient demographics, disease characteristics, operative characteristics, and postoperative outcomes with follow-up on mortality and reintervention. All statistical analyses were carried out using IBM SPSS 26. Patient survival was calculated using a Kaplan-Meier survival analysis, and a P value of less than 0.05 was considered statistically significant. RESULTS: A total of 58 patients were included in the analysis, of which 27 (46.6%) presented with complicated disease and 31 were uncomplicated, of which 10 (17.2%) were classed as high risk and 21 (36.2%) low risk. Zone 2 was the most common proximal landing zone for the stent graft. Left subclavian artery bypass was performed selectively (26%), with 1 stroke occurring, likely due to embolic reasons. A further 6 underwent more proximal aortic debranching before TEVAR (10%) and was a significant risk factor for mortality and the number of stents deployed. The overall rates of reintervention and mortality were 17.2% (n = 10) and 29.3% (n = 17). CONCLUSIONS: Aortic arch debranching and TEVAR for TBAD is associated with significant mortality. Future developments to treat aortic arch pathology could incorporate branched graft devices, eliminating the need for debranching, improving stroke rates, and reducing future reinterventions.

Acute hypoxia impairs posterior cerebral bioenergetics and memory in man.

Hypoxia has the potential to impair cognitive function; however, it is still uncertain which cognitive domains are adversely affected. We examined the effects of acute hypoxia (∼7 h) on central executive (Go/No-Go) and non-executive (memory) tasks and the extent to which impairment was potentially related to regional cerebral blood flow and oxygen delivery (CDO2 ). Twelve male participants performed cognitive tasks following 0, 2, 4 and 6 h of passive exposure to both normoxia and hypoxia (12% O2 ), in a randomized block cross-over single-blinded design. Middle cerebral artery (MCA) and posterior cerebral artery (PCA) blood velocities and corresponding CDO2 were determined using bilateral transcranial Doppler ultrasound. In hypoxia, MCA DO2 was reduced during the Go/No-Go task (P = 0.010 vs. normoxia, main effect), and PCA DO2 was attenuated during memorization (P = 0.005 vs. normoxia) and recall components (P = 0.002 vs. normoxia) in the memory task. The accuracy of the memory task was also impaired in hypoxia (P = 0.049 vs. normoxia). In contrast, hypoxia failed to alter reaction time (P = 0.19 vs. normoxia) or accuracy (P = 0.20 vs. normoxia) during the Go/No-Go task, indicating that selective attention and response inhibition were preserved. Hypoxia did not affect cerebral blood flow or corresponding CDO2 responses to cognitive activity (P > 0.05 vs. normoxia). Collectively, these findings highlight the differential sensitivity of cognitive domains, with memory being selectively vulnerable in hypoxia. NEW FINDINGS: What is the central question of this study? We sought to examine the effects of acute hypoxia on central executive (selective attention and response inhibition) and non-executive (memory) performance and the extent to which impairments are potentially related to reductions in regional cerebral blood flow and oxygen delivery. What is the main finding and its importance? Memory was impaired in acute hypoxia, and this was accompanied by a selective reduction in posterior cerebral artery oxygen delivery. In contrast, selective attention and response inhibition remained well preserved. These findings suggest that memory is selectively vulnerable to hypoxia.

Selective elevation in external carotid artery flow during acute gravitational transition to microgravity during parabolic flight.

This study sought to determine to what extent acute exposure to microgravity (0 G) and related increases in central blood volume (CBV) during parabolic flight influence the regional redistribution of intra and extra cranial cerebral blood flow (CBF). Eleven healthy participants performed during two parabolic flights campaigns aboard the Airbus A310-ZERO G aircraft. The response of select variables for each of the 15 parabolas involving exposure to both 0 G and hypergravity (1.8 G) were assessed in the seated position. Mean arterial blood pressure (MAP) and heart rate (HR) were continuously monitored and used to calculate stroke volume (SV), cardiac output ([Formula: see text]), and systemic vascular resistance (SVR). Changes in CBV were measured using an impedance monitor. Extracranial flow through the internal carotid, external carotid, and vertebral artery ([Formula: see text]ICA, [Formula: see text]ECA, and [Formula: see text]VA), and intracranial blood velocity was measured by duplex ultrasound. When compared with 1-G baseline condition, 0 G increased CBV (+375 ± 98 mL, P = 0.004) and [Formula: see text] (+16 ± 14%, P = 0.024) and decreased SVR (-7.3 ± 5 mmHg·min·L-1, P = 0.002) and MAP (-13 ± 4 mmHg, P = 0.001). [Formula: see text]ECA increased by 43 ± 46% in 0 G (P = 0.030), whereas no change was observed for CBF, [Formula: see text]ICA, or [Formula: see text]VA (P = 0.102, P = 0.637, and P = 0.095, respectively).NEW & NOTEWORTHY Our findings demonstrate that in microgravity there is a selective increase in external carotid artery blood flow whereas global and regional cerebral blood flow remained preserved. To what extent this reflects an adaptive, neuroprotective response to counter overperfusion remains to be established.

Lower systemic nitric oxide bioactivity, cerebral hypoperfusion and accelerated cognitive decline in formerly concussed retired rugby union players.

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 ( CVR CO 2 hyper ${\mathrm{CVR}}_{{\mathrm{CO}}_{\mathrm{2}}{\mathrm{hyper}}}$ / CVR CO 2 hypo ${\mathrm{CVR}}_{{\mathrm{CO}}_{\mathrm{2}}{\mathrm{hypo}}}$ ) 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.

Correlative effect between sac regression and clinical outcomes following endovascular repair in abdominal aortic aneurysm: fact or myth?

INTRODUCTION: Endovascular aneurysm repair (EVAR) has rapidly become the preferred management of abdominal aortic aneurysm (AAA). Sac regression status post-EVAR has been linked to clinical outcomes as well as the choice of EVAR device. The aim of this narrative review is to investigate the relationship between sac regression and clinical outcomes post-EVAR in AAA. Another aim is to compare sac regression achieved with the main EVAR devices. AREAS COVERED: We carried out a comprehensive literature search on multiple electronic databases. Sac regression was usually defined as a decrease in the sac diameter (>10 mm) over follow-up. This revealed that individuals who had sac regression post-EVAR had significantly lower mortality, and higher event-free survival rates. Further, lower rates of endoleak and reintervention were observed in patients with regressing aneurysm sacs. Sac regression patients also had significantly lower odds of rupture compared to counterparts with stable or expanded sacs. The choice of EVAR device was also shown to impact regression, with the Fenestrated Anaconda showing favorable results. EXPERT OPINION: Sac regression post-EVAR in AAA is an important prognostic factor as it translates to improved mortality and morbidity. Therefore, this relationship must be seriously taken into consideration during follow-up.

Impact of patient demographics and intraoperative characteristics on abdominal aortic aneurysm sac following endovascular repair.

BACKGROUND: Endovascular aortic repair (EVAR) has become the preferred treatment for abdominal aortic aneurysm (AAA). Its main aim is to seal the perfusion of the aneurysmal sac and, thus, induce sac regression and subsequent aortic remodelling. Aneurysmal sac regression has been linked to the short- and long-term clinical outcomes post-EVAR. It has also been shown to be influenced by endograft device choice, with several of these available commercially. This review summarises and discusses current evidence on the influence of pre- and intraoperative factors on sac regression. Additionally, this review aims to highlight the device-specific variations in sac regression to provide an overall holistic approach to treating AAAs with EVAR. METHODS: A comprehensive literature search was conducted using multiple electronic databases to identify and extract relevant data. RESULTS: Female sex, >70 mm original sac diameters, higher pre-procedural fibrinogen levels, smoking and low intra-aneurysmal pressure were found to positively impact sac regression. Whereas renal impairment, ischemic heart disease, high intra-aneurysmal pressure and aneurysm neck thrombus negatively influenced sac regression. Patent lumbar arteries, age, statins and hypercholesterolaemia displayed conflicting evidence regarding sac regression. Regarding the EVAR endografts compared, newer generation devices such as the Anaconda mainly showed the most optimal results. CONCLUSION: Sac regression following EVAR in AAA is an important prognostic factor for morbidity and mortality. Nevertheless, several pre- and intraoperative factors can have an influence on sac regression. Therefore, it is necessary to take them into account when assessing AAA patients for EVAR to optimise outcomes. The choice of EVAR stent-graft can also affect sac regression, with evidence suggesting that the Fenestrated Anaconda is associated with the most favourable results.

Myths and methodologies: Cardiopulmonary exercise testing for surgical risk stratification in patients with an abdominal aortic aneurysm; balancing risk over benefit.

The extent to which patients with an abdominal aortic aneurysm (AAA) should exercise remains unclear, given theoretical concerns over the perceived risk of blood pressure-induced rupture, which is often catastrophic. This is especially pertinent during cardiopulmonary exercise testing, when patients are required to perform incremental exercise to symptom-limited exhaustion for the determination of cardiorespiratory fitness. This multimodal metric is being used increasingly as a complementary diagnostic tool to inform risk stratification and subsequent management of patients undergoing AAA surgery. In this review, we bring together a multidisciplinary group of physiologists, exercise scientists, anaesthetists, radiologists and surgeons to challenge the enduring 'myth' that AAA patients should be fearful of and avoid rigorous exercise. On the contrary, by appraising fundamental vascular mechanobiological forces associated with exercise, in conjunction with 'methodological' recommendations for risk mitigation specific to this patient population, we highlight that the benefits conferred by cardiopulmonary exercise testing and exercise training across the continuum of intensity far outweigh the short-term risks posed by potential AAA rupture.

Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent and S-nitrosothiol mediated signal transduction.

Cerebral hypoxic vasodilation is poorly understood in humans, which undermines the development of therapeutics to optimize cerebral oxygen delivery. Across four investigations (total n = 195) we investigated the role of nitric oxide (NO) and hemoglobin-based S-nitrosothiol (RSNO) and nitrite (NO2-) signaling in the regulation of cerebral hypoxic vasodilation. We conducted hemodilution (n = 10) and NO synthase inhibition experiments (n = 11) as well as hemoglobin oxygen desaturation protocols, wherein we measured cerebral blood flow (CBF), intra-arterial blood pressure, and in subsets of participants trans-cerebral release/uptake of RSNO and NO2-. Higher CBF during hypoxia was associated with greater trans-cerebral RSNO release but not NO2-, while NO synthase inhibition reduced cerebral hypoxic vasodilation. Hemodilution increased the magnitude of cerebral hypoxic vasodilation following acute hemodilution, while in 134 participants tested under normal conditions, hypoxic cerebral vasodilation was inversely correlated to arterial hemoglobin concentration. These studies were replicated in a sample of polycythemic high-altitude native Andeans suffering from excessive erythrocytosis (n = 40), where cerebral hypoxic vasodilation was inversely correlated to hemoglobin concentration, and improved with hemodilution (n = 6). Collectively, our data indicate that cerebral hypoxic vasodilation is partially NO-dependent, associated with trans-cerebral RSNO release, and place hemoglobin-based NO signaling as a central mechanism of cerebral hypoxic vasodilation in humans.

Uncomplicated Type B Aortic Dissection: Challenges in Diagnosis and Categorization.

BACKGROUND: Acute type B aortic dissection (TBAD) is a rare disease that is likely under-diagnosed in the UK. As a progressive, dynamic clinical entity, many patients initially diagnosed with uncomplicated TBAD deteriorate, developing end-organ malperfusion and aortic rupture (complicated TBAD). An evaluation of the binary approach to the diagnosis and categorisation of TBAD is needed. METHODS: A narrative review of the risk factors predisposing patients to progression from unTBAD to coTBAD was undertaken. RESULTS: Key high-risk features predispose the development of complicated TBAD, such as maximal aortic diameter > 40 mm and partial false lumen thrombosis. CONCLUSION: An appreciation of the factors that predispose to complicated TBAD would aid clinical decision-making surrounding TBAD.

Assessing cardiorespiratory fitness relative to sex improves surgical risk stratification.

BACKGROUND: To what extent sex-related differences in cardiorespiratory fitness (CRF) impact postoperative patient mortality and corresponding implications for surgical risk stratification remains to be established. METHODS: To examine this, we recruited 640 patients (366 males vs. 274 females) who underwent cardiopulmonary exercise testing prior to elective colorectal surgery. Patients were defined high risk if peak oxygen uptake was <14.3 mL kg-1  min-1 and ventilatory equivalent for carbon dioxide at 'anaerobic threshold' >34. Between-sex CRF and mortality was assessed, and sex-specific CRF thresholds predictive of mortality was calculated. RESULTS: Seventeen percent of deaths were attributed to sub-threshold CRF, which was higher than established risk factors for cardiovascular disease (CVD). The group (independent of sex) exhibited a 5-fold higher mortality (high vs. low risk patients hazard ratio = 4.80, 95% confidence interval 2.73-8.45, p < 0.001). Females exhibited 39% lower CRF (p < 0.001) with more classified high risk than males (36 vs. 23%, p = 0.001), yet mortality was not different (p = 0.544). Upon reformulation of sex-specific CRF thresholds, lower cut-offs for mortality were observed in females, and consequently, fewer (20%) were stratified with sub-threshold CRF compared to the original 36% (p < 0.001). CONCLUSIONS: Low CRF accounted for more deaths than traditional CVD risk factors, and when CRF was considered relative to sex, the disproportionate number of females stratified unfit was corrected. These findings support clinical consideration of 'sex-specific' CRF thresholds to better inform postoperative mortality and improve surgical risk stratification.

Personal protective equipment-induced systemic hypercapnic hypoxaemia: translational implications for impaired cognitive-clinical functional performance.

BACKGROUND: Personal protective equipment (PPE) adversely affects pulmonary gas exchange and may result in systemic hypercapnic hypoxaemia and headache. This study aimed to determine what extent PPE affects cerebral symptoms, global cerebral blood flow, and cognitive functional performance. METHODS: Higher surgical trainees participated in a randomized, repeated-measures, crossover study, completing 60 min of laparoscopic surgical simulation in both standard operating attire and type 3 PPE. Measurements were collected at baseline and after 60 min of simulation. The primary outcome measure was headache. Headache was examined using the validated visual analogue scale (VAS) and Environmental Symptoms Questionnaire C (ESQ-C), global cerebral blood flow with duplex ultrasonography, and visuospatial and executive gross/fine motor function with grooved peg board (GPB) and laparoscopic bead (LSB) board tasks. RESULTS: Thirty-one higher surgical trainees (20 men, 11 women) completed the study. Compared with standard operating attire, PPE increased headache assessment scores (mean(s.d.) VAS score 3.5(5.6) versus 13.0(3.7), P < 0.001; ESQ-C score 1.3(2.0) versus 5.9(5.1), P < 0.001) and was associated with poorer completion times for GPB-D (61.4(12.0) versus 71.1(12.4) s; P = 0.034) and LSB (192.5(66.9) versus 270.7(135.3) s; P = 0.025) tasks. Wearing PPE increased heart rate (82.5(13.6) versus 93.5(13.0) beats/min; P = 0.022) and skin temperature (36.6(0.4) versus 37.1(0.5)°C; P < 0.001), but decreased peripheral oxygen saturation (97.9(0.8) versus 96.8(1.0) per cent; P < 0.001). Female higher surgical trainees exhibited higher peripheral oxygen saturation across all conditions. No differences were observed in global cerebral blood flow as a function of attire, time or sex. CONCLUSION: Despite no marked changes in global cerebral blood flow, type 3 PPE was associated with increased headache scores and cerebral symptoms (VAS and ESQ-C) alongside impaired executive motor function highlighting the clinical implications of PPE-induced impairment for cognitive-clinical performance.