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, V̇O2PEAK at the anaerobic threshold (V̇O2 -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/m2 . Patients were poorly conditioned with a V̇O2PEAK almost 20% lower than predicted for age, sex-matched healthy controls with 35% exhibiting a V̇O2 -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 V̇O2 -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.

Probenecid Increases the Concentration of 7-Chlorokynurenic Acid Derived from the Prodrug 4-Chlorokynurenine within the Prefrontal Cortex.

Recent advances in the understanding of depression have led to increasing interest in ketamine and the role that N-methyl-d-aspartate (NMDA) receptor inhibition plays in depression. l-4-Chlorokynurenine (4-Cl-KYN, AV-101), a prodrug, has shown promise as an antidepressant in preclinical studies, but this promise has not been realized in recent clinical trials. We sought to determine if transporters in the CNS could be playing a role in this clinical response. We used radiolabeled uptake assays and microdialysis studies to determine how 4-Cl-KYN and its active metabolite, 7-chlorokynurenic acid (7-Cl-KYNA), cross the blood-brain barrier (BBB) to access the brain and its extracellular fluid compartment. Our data indicates that 4-Cl-KYN crosses the blood-brain barrier via the amino acid transporter LAT1 (SLC7A5) after which the 7-Cl-KYNA metabolite leaves the brain extracellular fluid via probenecid-sensitive organic anion transporters OAT1/3 (SLC22A6 and SLC22A8) and MRP4 (ABCC4). Microdialysis studies further validated our in vitro data, indicating that probenecid may be used to boost the bioavailability of 7-Cl-KYNA. Indeed, we found that coadministration of 4-Cl-KYN with probenecid caused a dose-dependent increase by as much as an 885-fold increase in 7-Cl-KYNA concentration in the prefrontal cortex. In summary, our data show that 4-Cl-KYN crosses the BBB using LAT1, while its active metabolite, 7-Cl-KYNA, is rapidly transported out of the brain via OAT1/3 and MRP4. We also identify a hitherto unreported mechanism by which the brain extracellular concentration of 7-Cl-KYNA may be increased to produce significant boosting of the drug concentration at its site of action that could potentially lead to an increased therapeutic effect.

Translational Sciences in Cardiac Failure Secondary to Arteriovenous Fistula in Hemodialysis Patients.

High-output cardiac failure is a rare form of heart failure associated with the formation of arteriovenous fistula (AVF) in hemodialysis patients. The pathophysiology underlying the HOCF is complex and multifactorial. Presence of AVF can cause long term hemodynamic changes that ultimately lead to increased cardiac output and consequently cardiac failure. A number of risk factors have been associated with the development of HOCF post-AVF construction, including male sex, a proximally located AVF and a state of volume overload. Dysregulation of tissue inhibitor of matrix metalloproteinase 4, Sirtuin-1 and Sirtuin-3 gene expression have been associated with the development of heart failure. The differences observed between genders have been attributed to altered activity of the ß-adrenoceptor system. Numerous biomarkers including cardiac troponin T and I, atrial natriuretic peptide, brain natriuretic peptide among others have shown both prognostic and diagnostic potential; however further research is needed to establish their utility in clinical practice for patients with AVF associated HOCF. In recent years risk stratification models have been developed to help identify patients at the highest risk of developing HOCF post AVF which could be revolutionary in its identification and management. Potential options for managing HOCF post-AVF include AVF ligation, banding and anastoplasty however these procedures are not without their own associated risks. In this review, we discuss the pathophysiology, risk stratification and management of patients with AVF associated HOCF.

From ER to OR-Type A aortic dissection delay dilemma.

BACKGROUND AND AIM OF STUDY: Aortic dissection (AD) remains a life-threatening and time-critical condition. The classical presentation involves sudden onset, sharp "tearing" chest pain radiating to the back. However, it can present with a myriad of symptoms, leading to a high occurrence of misdiagnosis and delay in treatment. METHODS AND RESULTS: A review of the available literature published on AD and diagnostic delays. A systematic review of the literature performed via PubMed and Google scholar using key search terms such as "type A," "aortic dissection," "delay," "misdiagnosis," and synonyms. The Boolean operator used to narrow results specifically to diagnostic elements of AD. A current lack of data collection has impeded the systematic analysis and review of this condition making it difficult to assess reasons for delay. A review of the literature showed a large variation in the presentation of those that have acute AD. Often the presentation mimics other more common conditions such as acute coronary syndrome. Lack of awareness amongst clinicians means that it is often not considered as a differential. Furthermore, the lack of a discriminator for patients being triaged leads to diagnostic delay; this is exacerbated by limited accessibility to diagnostic tests such as CT. CONCLUSION: Based on the current literature, collaborative data collection, regular audit, national guidance, and communication between Royal Colleges will improve awareness, reduce diagnostic delays, and shine greater light on the issue.

Pernicious pregnancy: Type B aortic dissection in pregnant women.

BACKGROUND: Type B aortic dissection (TBAD) occurs seldomly, particularly in pregnancy, but has disastrous consequences for both mother and fetus. The focus of immediate surgical repair of type A aortic dissection due to higher mortality of patients is less clear in its counterpart, TBAD, in which management is controversial and debated. This article collates knowledge so far on this rare event during pregnancy. METHODS: A comprehensive literature search was performed in PubMed, Scopus, Google Scholar, Embase, and Medline. Key search terms included "type B aortic dissection," "pregnancy," and corresponding synonyms. Non-English papers were excluded. RESULTS: Risk factors for TBAD include aortic wall stress due to hypertension, previous cardiac surgery, structural abnormalities (bicuspid aortic valve, aortic coarctation), and connective tissue disorders. In pregnancy, pre-eclampsia is a cause of increased aortic wall stress. Management of this condition is often conservative, but this is dependent on a number of factors, including gestation, cardiovascular stability of the patient, and symptomology. In most cases, a cesarean section before intervention is carried out unless certain indications are present. CONCLUSIONS: Due to a scarce number of cases across the decades, it is difficult to determine which management is optimal. The gold-standard management of TBAD has traditionally been the medical treatment for uncomplicated cases and open surgery for those needing urgent intervention, but with the advent of techniques, such as thoracic endovascular aortic repair, the management of these group of patients continues to develop.

Acute aortic dissection during pregnancy: Trials and tribulations.

BACKGROUND: Type A acute aortic dissection (TAAD) during pregnancy is a life-threatening event for both the mother and the unborn baby. Pregnancy has been recognized as an independent risk factor for TAAD, postulated to be due to physiological changes that cause hyperdynamic circulation. This review seeks to outline the current controversies around this unique group. METHODS: A comprehensive literature search was carried out across large databases to assimilate relevant papers regarding acute aortic dissection in pregnant women. RESULTS: The presentation can be atypical in many cases and further concern from clinicians of fetal radiation exposure can result in missed or delayed diagnoses. Investigation via the quickest form of imaging, whether computed tomography, magnetic resonance imaging, or transesophageal echocardiography, should be carried out promptly due to the high risk of mortality. Surgical management of TAAD in pregnancy revolves primarily around the decision to deliver the fetus concomitantly or to perform the aortic repair with the fetus in utero. CONCLUSIONS: Management of this group includes rapid and dynamic assessment without delay. From conception to postpartum, there are multiple stages in which to manage these women. Challenges in carrying out management in the form of operative techniques and cardiopulmonary bypass place the fetus at risk and must be approached with caution, particularly as there is little evidence-base for many of these decisions. Further research into reducing maternal and fetal mortality is necessary.

Aortic Valve Repair: Where Are We Now?

The advent of aortic valve repair alongside the well-established technique of valve replacement changed the landscape of cardiac surgery, as well as the lives of patients suffering from valvular disease. Repair represents a novel option in those unfit for replacement and avoids the burden of lifelong anticoagulation in younger patients. Despite this, the associated risk of persistence of aortic insufficiency, and therefore reoperation, with valvular repair renders clinical decision making between the two techniques difficult. Unlike the burden of evidence supporting mitral valve repair over replacement, the debate surrounding aortic valve surgery continues. This article aims to explore the development of operative techniques underlying aortic valve repair as well as summarising existing research into short- and long-term patient outcomes in both aortic valve repair and replacement.

The automaton as a surgeon: the future of artificial intelligence in emergency and general surgery.

BACKGROUND: Artificial intelligence (AI) is a field involving computational simulation of human intelligence processes; these applications of deep learning could have implications in the specialty of emergency surgery (ES). ES is a rapidly advancing area, and this review will outline the most recent advances. METHODS: A literature search encompassing the uses of AI in surgery was conducted across large databases (Pubmed, OVID, SCOPUS). Two doctors (LR, CH) both collated relevant papers and appraised them. Papers included were published within the last 5 years, and a "snowball effect" used to collate further relevant literature. RESULTS: AI has been shown to provide value in predicting surgical outcomes and giving personalised patient risks based on inputted data. Further to this, image recognition technology within AI has showed success in fracture identification and breast cancer diagnosis. Regarding theatre presence, supervised robots have carried out suturing and anastomosis of bowel in controlled environments to a high standard. CONCLUSION: AI has potential for integration across surgical services, from diagnosis to treatment, and aiding the surgeon in key decision-making for risks per patient. Fully automated surgery may be the future, but at present, AI needs human supervision.

'It's always in the back of my mind': understanding the psychological impact of recovery following pancreaticoduodenectomy for cancer: a qualitative study.

OBJECTIVES: Ten per cent of patients diagnosed with pancreatic cancer undergo pancreaticoduodenectomy. There is limited previous research focusing on psychological well-being; unmet support needs impact negatively on quality of life. This paper reports the psychological impact of a pancreatic cancer diagnosis and subsequent pancreaticoduodenectomy, exploring how patients' lives alter following surgery and how they seek support. DESIGN: Inductive qualitative study involving in-depth semistructured interviews with 20 participants who had undergone pancreaticoduodenectomy for pancreatic or distal biliary duct cancer. Interviews were audiorecorded, transcribed and anonymised, and thematic analysis used principles of constant comparison. SETTING: Single National Health Service Trust in Northwest England. PARTICIPANTS: Patients were eligible for inclusion if they had had pancreaticoduodenectomy for head of pancreas cancer, periampullary cancer or distal cholangiocarcinoma between 6 months and 6 years previously, and had completed adjuvant chemotherapy. RESULTS: Analysis identified the following main themes: diagnosis and decision making around surgery; recovery from surgery and chemotherapy; burden of monitoring and ongoing symptoms; adjusting to 'a new normal'; understanding around prognosis; support-seeking. Participants seized the chance to have surgery, often without seeming to absorb the risks or their prognosis. They perceived that they were unable to control their life trajectory and, although they valued close monitoring, experienced anxiety around their appointments. Participants expressed uncertainty about whether they would be able to return to their former activities. There were tensions in their comments about support-seeking, but most felt that emotional support should be offered proactively. CONCLUSIONS: Patients should be made aware of potential psychological sequelae, and that treatment completion may trigger the need for more support. Clinical nurse specialists (CNSs) were identified as key members of the team in proactively offering support; further training for CNSs should be encouraged. Understanding patients' experience of living with cancer and the impact of treatment is crucial in enabling the development of improved support interventions.

"Proximalization is Advancement"-Zone 3 Frozen Elephant Trunk vs Zone 2 Frozen Elephant Trunk: A Literature Review.

Over the decades, the Frozen Elephant Trunk (FET) technique has gained immense popularity allowing simplified treatment of complex aortic pathologies. FET is frequently used to treat aortic conditions involving the distal aortic arch and the proximal descending aorta in a single stage. Surgical preference has recently changed from FET procedures being performed at Zone 3 to Zone 2. There are several advantages of Zone 2 FET over Zone 3 FET including reduction in spinal cord injury, visceral ischemia, neurological and cardiovascular sequelae. In addition, Zone 2 FET is a technically less complicated procedure. Literature on the comparison between Zone 3 and Zone 2 FET is scarce and primarily observational and anecdotal. Therefore, further research is warranted in this paradigm to substantiate current surgical treatment options for complex aortic pathologies. In this review, we explore literature surrounding FET and the reasons for the shift in surgical preference from Zone 3 to Zone 2.

Immunological therapeutics in acute aortic syndrome.

Acute aortic syndrome is a group of interlinked conditions with common presenting symptoms, including aortic dissection, penetrating atherosclerotic ulcer, and intramural hematoma. Pharmacological management of acute aortic syndrome is a growing area, with key themes to address the underlying inflammatory pathways believed to be the cause. Research into interleukins, matrix metalloproteinases, and granulocyte macrophage colony-stimulating factor are just some of the many immunological properties being investigated and translated into medical therapies. Stem cell experiments may indicate further advances in the pathologies of acute aortic syndrome. The study of pharmacogenomics to improve treatment across different genomes is also a novel area outlined in this paper.

Could Cerebrospinal Fluid Biomarkers Offer Better Predictive Value for Spinal Cord Ischaemia Than Current Neuromonitoring Techniques During Thoracoabdominal Aortic Aneurysm Repair - A Systematic Review.

OBJECTIVE: Cerebrospinal fluid (CSF) drainage is a technique that has significantly reduced the incidence of spinal cord ischaemia (SCI). We present results of a systematic review to assess the literature on this topic in relation to thoracoabdominal aortic aneurysm repair (TAAR). METHODS: Major medical databases were searched to identify papers related to CSF biomarkers measured during TAAAR. RESULTS: Fifteen papers reported measurements of CSF biomarkers with 265 patients in total. CSF biomarkers measured included S-100ß, neuron-specific endolase (NSE), lactate, glial fibrillary acidic protein A (GFPa), Tau, heat shock protein 70 and 27 (HSP70, HSP27), and proinflammatory cytokines. Lactate and S-100ß were reported the most, but did not correlate with SCI, which was also the case with NSE and TAU. GFPa showed significant CSF level rises, both intra and postoperative in patients who suffered SCI and warrants further investigation, similar results were seen with HSP70, HSP27 and IL-8. CONCLUSIONS: Although there is significant interest in this topic, there still remains a significant lack of high-quality studies investigating CSF biomarkers during TAAR to detect SCI. A large and multicentre study is required to identify the significant role of each biomarker.

Stented Versus Stentless Aortic Valve Replacement in Patients With Small Aortic Root: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of the study was to compare hemodynamic and perioperative outcomes of stented against stentless aortic valve replacement in patients with small aortic root (21 mm or less). METHODS: A comprehensive search was undertaken among the four major databases (PubMed, Embase, Scopus, and Ovid) to identify all randomized and nonrandomized controlled trials comparing stentless to stented bioprosthetic valves in small aortic root patients. Odds ratios, weighted mean differences, or standardized mean differences and their 95% confidence intervals were analyzed. RESULTS: A total of seven studies with a total of 965 patients fulfilled the inclusion criteria. There was no significant difference in preoperative baselines including mean age between both groups (P = 0.08), peak aortic valve gradient (P = 0.06), and effective orifice area (P = 0.28), whereas higher mean aortic valve gradient in the stented group (P = 0.007). No difference in cardiopulmonary bypass time (P = 0.74), aortic cross-clamp times (P = 0.88), intensive care unit stay (P = 0.13), and stroke rate (P = 0.56) were noted. However, stented group of patients showed higher rate of patient prosthesis mismatch (P = 0.0001) and longer total hospital stay (P = 0.002). Postoperatively, stentless group showed lower peak and mean aortic valve gradient (P = 0.003 and P = 0.008, respectively) with a better effective orifice area (P < 0.00001) at 6 months of follow-up. Mortality rates while in-hospital and at 1 year were similar in both groups (P = 0.94 and P = 0.86, respectively). CONCLUSIONS: Stentless aortic valves offer superior short-term hemodynamic outcomes in patients with small aortic root when compared with stented aortic valves. Although both groups have similar perioperative complications rates, stentless valves bring about a shorter hospital stay. A further large multicenter randomized controlled trial should address the longer-term benefit of stentless aortic valve over stented valve.

Is There Any Benefit of Neuromonitoring During Descending and Thoracoabdominal Aortic Aneurysm Repair?

OBJECTIVE: Paraplegia remains the most feared and a devastating complication after descending and thoracoabdominal aneurysm operative repair (DTA and TAAAR). Neuromonitoring, particularly use of motor-evoked potentials (MEPs), for this surgery has gained popularity. However, ambiguity remains regarding its use and benefit. We systematically reviewed the literature to assess the benefit and applicability of neuromonitoring in DTA and TAAAR. METHODS: Electronic searches were performed on 4 major databases from inception until February 2014 to identify relevant studies. Eligibility decisions, method quality, data extraction, and analysis were performed according to predefined clinical criteria and end points. RESULTS: Among the studies matching our inclusion criteria, 1297 patients had MEP monitoring during DTA and TAAAR. In-hospital mortality was low (6.9% ± 3.6). Immediate neurological deficit was low (3.5% ± 2.6). In one third of patients (30.4% ± 14.2), the MEPs dropped below threshold, which were 30.4% and 29.4% with threshold levels of 75% and 50%, respectively. A range of surgical techniques were applied after reduction in MEPs. Most patients whose MEPs dropped and remained below threshold had immediate permanent neurological deficit (92.0% ± 23.6). Somatosensory-evoked potentials were reported in one third of papers with little association between loss of somatosensory-evoked potentials and permanent neurological deficit (16.7% ± 28.9%). CONCLUSIONS: We demonstrate that MEPs are useful at predicting paraplegia in patients who lose their MEPs and do not regain them intraoperatively. To date, there is no consensus regarding the applicability and use of MEPs. Current evidence does not mandate or support MEP use.

The History of Deep Hypothermic Circulatory Arrest in Thoracic Aortic Surgery.

Depending on the extent of aortic disease and surgical repair required, thoracic aortic surgery often involves periods of reduced cerebral perfusion. Historically, this resulted in detrimental neurological dysfunction, and high risk of mortality and morbidity. Over the last half century, rapid improvements have revolutionized aortic surgery. Among these, deep hypothermic circulatory arrest (DHCA) has drastically reduced the risk of mortality and morbidity following surgery on the thoracic aorta. This progress was facilitated by experimental pioneers such as Bigelow, who studied reduced oxygen expenditure consequent on induction of hypothermia in dogs. These encouraging findings led to trials in human cardiac surgery by Lewis in 1952 and further made possible the first successful aortic arch replacement by Denton Cooley and Michael De Bakey. Modern day surgery has come a long way from the use of immersion of the patient in ice baths and other primitive techniques previously described. This paper explores the development of deep hypothermic circulatory arrest from its origins to the present.

Could cerebrospinal fluid biomarkers offer better predictive value for spinal cord ischaemia than current neuromonitoring techniques during thoracoabdominal aortic aneurysm repair - a systematic review

Abstract Objective: Cerebrospinal fluid (CSF) drainage is a technique that has significantly reduced the incidence of spinal cord ischaemia (SCI). We present results of a systematic review to assess the literature on this topic in relation to thoracoabdominal aortic aneurysm repair (TAAR). Methods: Major medical databases were searched to identify papers related to CSF biomarkers measured during TAAAR. Results: Fifteen papers reported measurements of CSF biomarkers with 265 patients in total. CSF biomarkers measured included S-100ß, neuron-specific endolase (NSE), lactate, glial fibrillary acidic protein A (GFPa), Tau, heat shock protein 70 and 27 (HSP70, HSP27), and proinflammatory cytokines. Lactate and S-100ß were reported the most, but did not correlate with SCI, which was also the case with NSE and TAU. GFPa showed significant CSF level rises, both intra and postoperative in patients who suffered SCI and warrants further investigation, similar results were seen with HSP70, HSP27 and IL-8. Conclusions: Although there is significant interest in this topic, there still remains a significant lack of high-quality studies investigating CSF biomarkers during TAAR to detect SCI. A large and multicentre study is required to identify the significant role of each biomarker.

A Perspective on Natural History and Survival in Nonoperated Thoracic Aortic Aneurysm Patients.

There are many questions that remain unanswered in the understanding of the natural history of thoracic aortic aneurysm (TAA). This review will critically appraise the current published evidence on the natural history of TAA in nonoperated patients and their present rates of survival.

Imaging of Thoracic Intercostal Artery Rupture during the Propagation of a Type B Acute Aortic Syndrome.

The natural history of an intramural hematoma (IMH) has not been completely defined. This is a case report of a 63-year-old woman, in whom imaging reveals intercostal artery rupture during the process of expansion of an IMH in a Type B acute aortic syndrome. This case demonstrates that intercostal artery rupture may act as a precursor for the transformation of IMH to a classical dissection. Interestingly, complete resolution of this condition is achieved through medical management.