‘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 (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

Retroperitoneal Compared to Transperitoneal Approach for Open Abdominal Aortic Aneurysm Repair Is Associated with Reduced Systemic Inflammation and Postoperative Morbidity

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

Subjective assessment underestimates surgical risk: On the potential benefits of cardiopulmonary exercise testing for open thoracoabdominal repair

BACKGROUND: Initial clinical evaluation (ICE) is traditionally considered a useful screening tool to identify frail patients during the preoperative assessment. However, emerging evidence supports the more objective assessment of cardiorespiratory fitness (CRF) via cardiopulmonary exercise testing (CPET) to improve surgical risk stratification. Herein, we compared both subjective and objective assessment approaches to highlight the interpretive idiosyncrasies. METHODS: As part of routine preoperative patient contact, patients scheduled for major surgery were prospectively “eyeballed” (ICE) by two experienced clinicians before more detailed history taking that also included the American Society of Anesthesiologists score classification. Each patient was subjectively judged to be either “frail” or “not frail” by ICE and “fit” or “unfit” from a thorough review of the medical notes. Subjective data were compared against the more objective validated assessment of postoperative outcomes using established CPET “cut‐off” metrics incorporating peak pulmonary oxygen uptake, V̇O(2PEAK) at the anaerobic threshold (V̇O(2)‐AT), and ventilatory equivalent for carbon dioxide that collectively informed risk stratification. These data were retrospectively extracted from a single‐center prospective National Health Service database. Data were analyzed using the Chi‐square automatic interaction detection decision tree method. RESULTS: A total of 127 patients were examined that comprised 58% male and 42% female patients aged 69 ± 10 years with a body mass index of 29 ± 7 kg/m(2). Patients were poorly conditioned with a V̇O(2PEAK) almost 20% lower than predicted for age, sex‐matched healthy controls with 35% exhibiting a V̇O(2)‐AT < 11 ml/kg/min. Disagreement existed between the subjective assessments of risk with ∼34% of patients classified as not frail on ICE were considered unfit by notes review (p < .0001). Furthermore, ∼35% of patients considered not frail on ICE and ∼31% of patients considered fit by notes review exhibited a V̇O(2)‐AT < 11 ml/kg/min, and of these, ∼28% and ∼19% were classified as intermediate to high risk. CONCLUSIONS: These findings highlight the interpretive limitations associated with the subjective assessment of patient frailty with surgical risk classification underestimated in up to a third of patients compared to the validated assessment of CRF. They reinforce the benefits of a more objective and integrated approach offered by CPET that may help us to improve perioperative risk assessment and better direct critical care provision in patients scheduled for “high‐stakes” surgery including open thoracoabdominal aortic aneurysm repair

Cardiopulmonary fitness predicts postoperative major morbidity after esophagectomy for patients with cancer

Surgery for radical treatment of esophageal cancer (EC) carries significant inherent risk. The objective identification of patients who are at high risk of complications is of importance. In this study the prognostic value of cardiopulmonary fitness variables (CPF) derived from cardiopulmonary exercise testing (CPET) was assessed in patients undergoing potentially curative surgery for EC within an enhanced recovery program. OC patients underwent preoperative CPET using automated breath‐by‐breath respiratory gas analysis, with measurements taken during a ramped exercise test on a bicycle. The prognostic value of urn:x-wiley:2051817X:media:phy214174:phy214174-math-0001, Anaerobic Threshold (AT) and VE/VCO2 derived from CPET were studied in relation to post‐operative morbidity, which was collected prospectively, and overall survival. Consecutive 120 patients were included for analysis (median age 65 years, 100 male, 75 neoadjuvant therapy). Median AT in the cohort developing major morbidity (Clavien–Dindo classification >2) was 10.4 mL/kg/min compared with 11.3 mL/kg/min with no major morbidity (P = 0.048). Median urn:x-wiley:2051817X:media:phy214174:phy214174-math-0002 in the cohort developing major morbidity was 17.0 mL/kg/min compared with 18.7 mL/kg/min in the cohort (P = 0.009). urn:x-wiley:2051817X:media:phy214174:phy214174-math-0003 optimum cut‐off was 17.0 mL/kg/min (sensitivity 70%, specificity 53%) and for AT was 10.5 mL/kg/min (sensitivity 60%, specificity 44%). Multivariable analysis revealed urn:x-wiley:2051817X:media:phy214174:phy214174-math-0004 to be the only independent factor to predict major morbidity (OR 0.85, 95% CI 0.75–0.97, P = 0.018). Cumulative survival was associated with operative morbidity severity (χ2 = 4.892, df = 1, P = 0.027). These results indicate that urn:x-wiley:2051817X:media:phy214174:phy214174-math-0005 as derived from CPET is a significant predictor of major morbidity after oesophagectomy highlighting the physiological importance of cardiopulmonary fitness

GWAS of Suicide Attempt in Psychiatric Disorders Identifies Association With Major Depression Polygenic Risk Scores

Objective: Over 90% of suicide attempters have a psychiatric diagnosis, however twin and family studies suggest that the genetic etiology of suicide attempt (SA) is partially distinct from that of the psychiatric disorders themselves. Here, we present the largest genome-wide association study (GWAS) on suicide attempt using major depressive disorder (MDD), bipolar disorder (BIP) and schizophrenia (SCZ) cohorts from the Psychiatric Genomics Consortium. Method: Samples comprise 1622 suicide attempters and 8786 non-attempters with MDD, 3264 attempters and 5500 non-attempters with BIP and 1683 attempters and 2946 non-attempters with SCZ. SA GWAS were performed by comparing attempters to non-attempters in each disorder followed by meta-analyses across disorders. Polygenic risk scoring was used to investigate the genetic relationship between SA and the psychiatric disorders. Results: Three genome-wide significant loci for SA were found: one associated with SA in MDD, one in BIP, and one in the meta-analysis of SA in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with SA in MDD (R2=0.25%, P=0.0006), BIP (R2=0.24%, P=0.0002) and SCZ (R2=0.40%, P=0.0006). Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size hold potential to robustly identify genetic associations and gain biological insights into the etiology of suicide attempt

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Artificial cell research as a field that connects chemical, biological and philosophical questions

This review article discusses the interdisciplinary nature and implications of artificial cell research. It starts from two historical theories: Gánti's chemoton model and the autopoiesis theory by Maturana and Varela. They both explain the transition from chemical molecules to biological cells. These models exemplify two different ways in which disciplines of chemistry, biology and philosophy can profit from each other. In the chemoton model, conclusions from one disciplinary approach are relevant for the other disciplines. In contrast, the autopoiesis model itself (rather than its conclusions) is transferred from one discipline to the other. The article closes by underpinning the relevance of artificial cell research for philosophy with reference to the on-going philosophical debates on emergence, biological functions and biocentrism