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.

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.

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.

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.

Lifelong exposure to high-altitude hypoxia in humans is associated with improved redox homeostasis and structural-functional adaptations of the neurovascular unit.

High-altitude (HA) hypoxia may alter the structural-functional integrity of the neurovascular unit (NVU). Herein, we compared male lowlanders (n = 9) at sea level (SL) and after 14 days acclimatization to 4300 m (chronic HA) in Cerro de Pasco (CdP), Péru (HA), against sex-, age- and body mass index-matched healthy highlanders (n = 9) native to CdP (lifelong HA). Venous blood was assayed for serum proteins reflecting NVU integrity, in addition to free radicals and nitric oxide (NO). Regional cerebral blood flow (CBF) was examined in conjunction with cerebral substrate delivery, dynamic cerebral autoregulation (dCA), cerebrovascular reactivity to carbon dioxide (CVRCO2 ) and neurovascular coupling (NVC). Psychomotor tests were employed to examine cognitive function. Compared to lowlanders at SL, highlanders exhibited elevated basal plasma and red blood cell NO bioavailability, improved anterior and posterior dCA, elevated anterior CVRCO2 and preserved cerebral substrate delivery, NVC and cognition. In highlanders, S100B, neurofilament light-chain (NF-L) and T-tau were consistently lower and cognition comparable to lowlanders following chronic-HA. These findings highlight novel integrated adaptations towards regulation of the NVU in highlanders that may represent a neuroprotective phenotype underpinning successful adaptation to the lifelong stress of HA hypoxia. KEY POINTS: High-altitude (HA) hypoxia has the potential to alter the structural-functional integrity of the neurovascular unit (NVU) in humans. For the first time, we examined to what extent chronic and lifelong hypoxia impacts multimodal biomarkers reflecting NVU structure and function in lowlanders and native Andean highlanders. Despite lowlanders presenting with a reduction in systemic oxidative-nitrosative stress and maintained cerebral bioenergetics and cerebrovascular function during chronic hypoxia, there was evidence for increased axonal injury and cognitive impairment. Compared to lowlanders at sea level, highlanders exhibited elevated vascular NO bioavailability, improved dynamic regulatory capacity and cerebrovascular reactivity, comparable cerebral substrate delivery and neurovascular coupling, and maintained cognition. Unlike lowlanders following chronic HA, highlanders presented with lower concentrations of S100B, neurofilament light chain and total tau. These findings highlight novel integrated adaptations towards the regulation of the NVU in highlanders that may represent a neuroprotective phenotype underpinning successful adaptation to the lifelong stress of HA 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.

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.

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.

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.

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.

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.

Dynamic and Static Vessel Malperfusion as a Consequence of Acute Type B Aortic Dissection.

BACKGROUND: Acute type B aortic dissection (TBAD) is relatively uncommon with an estimated incidence of up to 8 cases per 100,000 individuals annually. It can be classified based on presenting clinical and radiological features into complicated and uncomplicated. Following the initial tear, the direction and extent of the dissection flap is unpredictable, possibly propagating proximally or distally. One consequence of a dissection flap is the occurrence of organ malperfusion by occlusion of the origin of the branch vessel. The 2 types of malperfusion in TBAD are static and dynamic, with the latter being the more common mechanism. Thoracic endovascular aortic repair (TEVAR) has demonstrated its high safety and efficacy when used for TBAD and subsequent malperfusion. AIMS: This original study specifically examines patients diagnosed with acute TBAD and treated with TEVAR at a single vascular unit, focusing on those presenting with organ malperfusion. METHODS: Over 16 years, 28 TBAD patients were admitted to a single center and treated using TEVAR. After clinical examination, all patients underwent computed tomography of the thorax and abdomen/pelvis to confirm the diagnosis and classify the extent of the dissection proximally and distally. Once diagnosed, patients were transferred to the high dependency unit and started on blood pressure medication. Subsequent computed tomography scans were performed to classify patients, after which TEVAR was performed. RESULTS: Twenty five patients underwent TEVAR for TBAD, of which 8 (32%) had symptoms of organ malperfusion. The majority of cases presented with hypertension (89%), describing a sudden onset of upper/midthoracic pain. The origin of the left subclavian artery was occluded in 14 (56%) patients with 9 (64%) needing an extra-anatomical bypass. There was only a single mortality due to a posterior circulation stroke 2 days after TEVAR. Median (range) length of coverage of thoracic aorta by the stent-graft was 33 (15-35) cm. The true lumen (TL) perfused the celiac artery in 6/8 malperfusion patients, superior mesenteric artery in 7/8, right renal artery in 6/8, and, conversely, left renal artery in only 2/8. CONCLUSIONS: Complicated TBADs behave in an unpredictable manner as it seems the propagating intimal flap invariably maintains vital organ perfusion via the TL. Maintenance of abdominal vessels perfusion from the TL following TEVAR is vital to ensuring optimal results.

Cost Analysis of Thoracic Endovascular Aortic Repair in Type B Aortic Dissection: How Much Does Quality Cost?

BACKGROUND: Aortic dissection (AD) is a life-threatening medical emergency that affects an estimated 3-4 people per 100,000 annually, with 40% of cases classified as type B AD (TBAD). TBAD can be further classified as being complicated (co-TBAD) or uncomplicated (un-TBAD) based on the presence or absence of certain features such as malperfusion and rupture. TBAD can be managed conservatively with optimal medical therapy (OMT), or invasively with open surgical repair (OSR) or thoracic endovascular aortic repair (TEVAR), depending on several factors such as type of TBAD and its clinical acuity. The cost-effectiveness, or cost-benefit profile, of these strategies must be given equal consideration. However, TBAD studies featuring cost analyses are limited within the literature. This narrative review aims to address the gap in the literature on cost-effectiveness of TBAD treatments by providing an overview of cost analyses comparing OMT with TEVAR in un-TBAD and TEVAR with OSR in co-TBAD. Another aim is to provide a market analysis of the commercially available TEVAR devices. METHODS: A comprehensive literature search was performed using several search engines including PubMed, Ovid, Google Scholar, Scopus, and Embase to identify and extract relevant studies. RESULTS: Several TEVAR devices are available commercially on the global market costing $12,000-19,495. Nevertheless, the Terumo Aortic RELAY® stent graft seems to be the most cost-effective, yielding highly favourable clinical outcomes. Despite the higher initial cost of TEVAR, evidence in the literature strongly suggest that it is superior to OMT for un-TBAD on the long-term. In addition, TEVAR is well established in the literature as being gold-standard repair technique for co-TBAD, replacing OSR by offering a more optimal cost-benefit profile through lower costs and improved results. CONCLUSIONS: The introduction of TEVAR has revolutionized the field of aortovascular surgery by offering a highly efficacious and long-term cost-effective treatment for TBAD.

Fate and Consequences of the False Lumen After Thoracic Endovascular Aortic Repair in Type B Aortic Dissection.

BACKGROUND: Type B aortic dissection (TBAD) occurs due to an entry tear in the intimal layer of the aorta distal to the origin of the left subclavian artery where blood enters the newly formed false lumen (FL) and extends distally or proximally to form a dissection over an indeterminate length of the aorta which, over time, may eventually rupture. Thoracic endovascular aortic repair (TEVAR) aims to seal off the entry tear proximally with the stent-graft, occluding the origin of the dissection and excluding the FL. Nevertheless, in some cases, the perfusion to the FL is maintained, hindering the aortic remodelling process and increasing the risk of aneurysmal degeneration and rupture, particularly in the abdominal aorta where evidence suggest that remodelling is slower. This review examines the long-term effects of a patent or partially thrombosed FL on clinical outcomes following TEVAR in TBAD, also highlighting the pathological processes behind negative aortic remodelling. Another aim of this review is to provide an overview and appraisal of the currently available techniques for managing a patent or partially thrombosed FL to prevent long-term morbidity occurring. METHODS: A comprehensive literature search was performed using several search engines including PubMed, Ovid, Google Scholar, Scopus, and Embase to identify and extract relevant studies. RESULTS: Evidence in the literature show that a partially thrombosed FL is more dangerous than a patent FL due to the occlusion of the distal re-entry tears, impeding outflow and increasing mean arterial and diastolic pressures, whereas the latter is decompressed via distal re-entry sites. FL thrombosis and satisfactory remodelling is sometimes achieved in as few as 40% of patients after TEVAR due to the maintained perfusion of the FL either at the level of the thoracic or abdominal aorta. However, although the thoracic aorta is predominantly covered by the TEVAR stent-graft, poorer remodelling and more dilation is seen in the abdominal aorta. Several techniques are available to embolize the FL, including the Provisional Extension to Induce Complete Attachment, Stent Assisted Balloon Induced Intimal Disruption and Relamination in Aortic Dissection Repair, candy-plug, and Knickerbocker techniques. CONCLUSIONS: The management of TBAD is invariably TEVAR to seal off the proximal entry tear while extending the repair distally to completely exclude the FL. A risk of aortic wall dilatation distal to TEVAR stent-graft remains; hence, regular monitoring and accurate imaging are essential. At present, a patent FL can be treated using a range of different endovascular techniques.

Ethnic & Sex Disparities in Type B Aortic Dissection Patients Undergoing Thoracic Endovascular Aortic Repair: An International Perspective.

BACKGROUND: There has been a revolution in the management of type B aortic dissection (TBAD) over the last 2 decades due to the increasing development of endovascular techniques, with the prime example being thoracic endovascular aortic repair (TEVAR). However, many controversies concerning the use of TEVAR in TBAD exist. For instance, there is little available evidence suggesting any differences in demographics, disease characteristics, intervention technicalities, and clinical outcomes between males and females as well as different ethnicities when undergoing TEVAR for TBAD, both in the short and long term. Also, there is no risk prediction model/tool available. The objective of this international study is to describe and delineate the disparities between male and female patients of different ethnicities in terms of demographics, disease and interventional characteristics, and clinical outcomes. METHODS: Over 17 years a total of 58 TBAD patients were admitted to 2 tertiary vascular centres and treated using TEVAR. Mortality, postoperative complications and reintervention data were recorded for the first 30 days after the procedure as well as during follow-up. Follow-up for all patients lasted until the study endpoint or until a patient's death. Data were analysed retrospectively using IBM SPSS statistical package 26 for Windows. RESULTS: The mean age was similar between the 2 groups, with the majority of patients in both being Caucasian. More than half of the males had complicated TBAD, while the majority of females were classed as having uncomplicated disease. The most commonly utilized proximal and distal landing zone for the TEVAR stent graft was zone 2 and zone 4, respectively. The mean proximal stent diameter was significantly larger in males compared to females (P = 0.004). The difference in mean distal diameter between the 2 groups was insignificant (P = 0.721). The mean total stent coverage of the thoracic aorta was 251.3 mm in male patients compared to 291.2 mm in females (P = 0.203). A total of 32 patients underwent adjunctive procedures. Seven (17%) of the males had one or more postoperative complications compared to 2 (12%) females. Nine (22%) males underwent a reintervention procedure post TEVAR compared to only 1 (6%) female (P = 0.136). Overall, males had a mortality rate of 24% (n = 10) compared to 41% of females (n = 7) (P = 0.201). Estimated survival of males and females post TEVAR was 80.4 ± 9.6 months and 69.7 ± 14.4 months (P = 0.428). For the total population, the number of stent grafts was inversely correlated with mortality. CONCLUSIONS: Despite the favourable clinical outcomes achieved by TEVAR in TBAD, there remains a grey area concerning its management. Thus, it is important to perform risk stratification of individual patients using their demographics and comorbidities, particularly scrutinizing patient sex and ethnic origin, when considering intervention for TBAD to achieve optimum results.

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.

Nitric oxide contributes to cerebrovascular shear-mediated dilatation but not steady-state cerebrovascular reactivity to carbon dioxide.

Cerebrovascular CO2 reactivity (CVR) is often considered a bioassay of cerebrovascular endothelial function. We recently introduced a test of cerebral shear-mediated dilatation (cSMD) that may better reflect endothelial function. We aimed to determine the nitric oxide (NO)-dependency of CVR and cSMD. Eleven volunteers underwent a steady-state CVR test and transient CO2 test of cSMD during intravenous infusion of the NO synthase inhibitor NG -monomethyl-l-arginine (l-NMMA) or volume-matched saline (placebo; single-blinded and counter-balanced). We measured cerebral blood flow (CBF; duplex ultrasound), intra-arterial blood pressure and PaCO2${P_{{\rm{aC}}{{\rm{O}}_{\rm{2}}}}}$ . Paired arterial and jugular venous blood sampling allowed for the determination of trans-cerebral NO2- exchange (ozone-based chemiluminescence). l-NMMA reduced arterial NO2- by ∼25% versus saline (74.3 ± 39.9 vs. 98.1 ± 34.2 nM; P = 0.03). The steady-state CVR (20.1 ± 11.6 nM/min at baseline vs. 3.2 ± 16.7 nM/min at +9 mmHg PaCO2${P_{{\rm{aC}}{{\rm{O}}_{\rm{2}}}}}$ ; P = 0.017) and transient cSMD tests (3.4 ± 5.9 nM/min at baseline vs. -1.8 ± 8.2 nM/min at 120 s post-CO2 ; P = 0.044) shifted trans-cerebral NO2- exchange towards a greater net release (a negative value indicates release). Although this trans-cerebral NO2- release was abolished by l-NMMA, CVR did not differ between the saline and l-NMMA trials (57.2 ± 14.6 vs. 54.1 ± 12.1 ml/min/mmHg; P = 0.49), nor did l-NMMA impact peak internal carotid artery dilatation during the steady-state CVR test (6.2 ± 4.5 vs. 6.2 ± 5.0% dilatation; P = 0.960). However, l-NMMA reduced cSMD by ∼37% compared to saline (2.91 ± 1.38 vs. 4.65 ± 2.50%; P = 0.009). Our findings indicate that NO is not an obligatory regulator of steady-state CVR. Further, our novel transient CO2 test of cSMD is largely NO-dependent and provides an in vivo bioassay of NO-mediated cerebrovascular function in humans. KEY POINTS: Emerging evidence indicates that a transient CO2 stimulus elicits shear-mediated dilatation of the internal carotid artery, termed cerebral shear-mediated dilatation. Whether or not cerebrovascular reactivity to a steady-state CO2 stimulus is NO-dependent remains unclear in humans. During both a steady-state cerebrovascular reactivity test and a transient CO2 test of cerebral shear-mediated dilatation, trans-cerebral nitrite exchange shifted towards a net release indicating cerebrovascular NO production; this response was not evident following intravenous infusion of the non-selective NO synthase inhibitor NG -monomethyl-l-arginine. NO synthase blockade did not alter cerebrovascular reactivity in the steady-state CO2 test; however, cerebral shear-mediated dilatation following a transient CO2 stimulus was reduced by ∼37% following intravenous infusion of NG -monomethyl-l-arginine. NO is not obligatory for cerebrovascular reactivity to CO2 , but is a key contributor to cerebral shear-mediated dilatation.

'Fit for surgery': the relationship between cardiorespiratory fitness and postoperative outcomes.

NEW FINDINGS: What is the topic of this review? The relationships and physiological mechanisms underlying the clinical benefits of cardiorespiratory fitness (CRF) in patients undergoing major intra-abdominal surgery. What advances does it highlight? Elevated CRF reduces postoperative morbidity/mortality, thus highlighting the importance of CRF as an independent risk factor. The vascular protection afforded by exercise prehabilitation can further improve surgical risk stratification and postoperative outcomes. ABSTRACT: 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 (O2 ). Systemic O2 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 O2 demand, which if not met leads to O2 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.

Therapeutic benefits of proning to improve pulmonary gas exchange in severe respiratory failure: focus on fundamentals of physiology.

NEW FINDINGS: What is the topic of this review? The use of proning for improving pulmonary gas exchange in critically ill patients. What advances does it highlight? Proning places the lung in its 'natural' posture, and thus optimises the ventilation-perfusion distribution, which enables lung protective ventilation and the alleviation of potentially life-threatening hypoxaemia in COVID-19 and other types of critical illness with respiratory failure. ABSTRACT: The survival benefit of proning patients with acute respiratory distress syndrome (ARDS) is well established and has recently been found to improve pulmonary gas exchange in patients with COVID-19-associated ARDS (CARDS). This review outlines the physiological implications of transitioning from supine to prone on alveolar ventilation-perfusion ( V ̇ A -- Q ̇ ${\dot V_{\rm{A}}}\hbox{--}\dot Q$ ) relationships during spontaneous breathing and during general anaesthesia in the healthy state, as well as during invasive mechanical ventilation in patients with ARDS and CARDS. Spontaneously breathing, awake healthy individuals maintain a small vertical (ventral-to-dorsal) V ̇ A / Q ̇ ${\dot V_{\rm{A}}}/\dot Q$ ratio gradient in the supine position, which is largely neutralised in the prone position, mainly through redistribution of perfusion. In anaesthetised and mechanically ventilated healthy individuals, a vertical V ̇ A / Q ̇ ${\dot V_{\rm{A}}}/\dot Q$ ratio gradient is present in both postures, but with better V ̇ A -- Q ̇ ${\dot V_{\rm{A}}}\hbox{--}\dot Q$ matching in the prone position. In ARDS and CARDS, the vertical V ̇ A / Q ̇ ${\dot V_{\rm{A}}}/\dot Q$ ratio gradient in the supine position becomes larger, with intrapulmonary shunting in gravitationally dependent lung regions due to compression atelectasis of the dorsal lung. This is counteracted by proning, mainly through a more homogeneous distribution of ventilation combined with a largely unaffected high perfusion dorsally, and a consequent substantial improvement in arterial oxygenation. The data regarding proning as a therapy in patients with CARDS is still limited and whether the associated improvement in arterial oxygenation translates to a survival benefit remains unknown. Proning is nonetheless an attractive and lung protective manoeuvre with the potential benefit of improving life-threatening hypoxaemia in patients with ARDS and CARDS.

Malperfusion syndrome in acute type A aortic dissection: It's not what you know, it's what you can prove!

Organ malperfusion after type A aortic dissection represents a high-risk group for open surgical repair. This is particularly the case when mesenteric ischemia occurs. Central aortic repair should be considered for all presenting with malperfusion as many are due to dynamic obstruction. However, depending on imaging and clinical appearance many should be considered for adjunctive techniques including catheter-based endovascular and even open surgical revascularisation may be appropriate. This is due to as many as 20% with a static component to the malperfusion syndrome. Improving methods of ascertaining the type of malperfusion being treated and presenting symptoms requires a multidisciplinary team with access to a hybrid theater where all techniques can be accessed 24/7. This would only be achieved by centralization of vascular units whereby sufficient funding and organization are in place to deal with the consequences of this unpredictable and invariably deadly aortic pathology.