The performance of large language models in intercollegiate Membership of the Royal College of Surgeons examination.

INTRODUCTION: Large language models (LLM), such as Chat Generative Pre-trained Transformer (ChatGPT) and Bard utilise deep learning algorithms that have been trained on a massive data set of text and code to generate human-like responses. Several studies have demonstrated satisfactory performance on postgraduate examinations, including the United States Medical Licensing Examination. We aimed to evaluate artificial intelligence performance in Part A of the intercollegiate Membership of the Royal College of Surgeons (MRCS) examination. METHODS: The MRCS mock examination from Pastest, a commonly used question bank for examinees, was used to assess the performance of three LLMs: GPT-3.5, GPT 4.0 and Bard. Three hundred mock questions were input into the three LLMs, and the responses provided by the LLMs were recorded and analysed. The pass mark was set at 70%. RESULTS: The overall accuracies for GPT-3.5, GPT 4.0 and Bard were 67.33%, 71.67% and 65.67%, respectively (p = 0.27). The performances of GPT-3.5, GPT 4.0 and Bard in Applied Basic Sciences were 68.89%, 72.78% and 63.33% (p = 0.15), respectively. Furthermore, the three LLMs obtained correct answers in 65.00%, 70.00% and 69.17% of the Principles of Surgery in General questions (p = 0.67). There were no differences in performance in the overall and subcategories among the three LLMs. CONCLUSIONS: Our findings demonstrated satisfactory performance for all three LLMs in the MRCS Part A examination, with GPT 4.0 the only LLM that achieved the pass mark set.

Multi-omic analysis of the effects of low frequency ventilation during cardiopulmonary bypass surgery.

BACKGROUND: Heart surgery with cardio-pulmonary bypass (CPB) is associated with lung ischemia leading to injury and inflammation. It has been suggested this is a result of the lungs being kept deflated throughout the duration of CPB. Low frequency ventilation (LFV) during CPB has been proposed to reduce lung dysfunction. METHODS: We used a semi-biased multi-omic approach to analyse lung biopsies taken before and after CPB from 37 patients undergoing coronary artery bypass surgery randomised to both lungs left collapsed or using LFV for the duration of CPB. We also examined inflammatory and oxidative stress markers from blood samples from the same patients. RESULTS: 30 genes were induced when the lungs were left collapsed and 80 by LFV. Post-surgery 26 genes were significantly higher in the LFV vs. lungs left collapsed, including genes associated with inflammation (e.g. IL6 and IL8) and hypoxia/ischemia (e.g. HIF1A, IER3 and FOS). Relatively few changes in protein levels were detected, perhaps reflecting the early time point or the importance of post-translational modifications. However, pathway analysis of proteomic data indicated that LFV was associated with increased "cellular component morphogenesis" and a decrease in "blood circulation". Lipidomic analysis did not identify any lipids significantly altered by either intervention. DISCUSSION: Taken together these data indicate the keeping both lungs collapsed during CPB significantly induces lung damage, oxidative stress and inflammation. LFV during CPB increases these deleterious effects, potentially through prolonged surgery time, further decreasing blood flow to the lungs and enhancing hypoxia/ischemia.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) mimics: the knot unravelled by cardiovascular MRI.

AIM: To assess the role of cardiovascular magnetic resonance imaging (CMRI) in patients referred for suspected arrhythmogenic right ventricular cardiomyopathy (ARVC), its ability to identify ARVC mimics, and subsequent clinical impact. MATERIALS AND METHODS: The CMRI registry of the year 2014 was analysed to identify all consecutive patients referred for suspected ARVC. A comprehensive CMRI protocol that included anatomy, bi-ventricular function modules, and late gadolinium enhancement (LGE) was performed in all patients. RESULTS: Out of 2,481 CMRI performed, 124 patients (5%) were referred for suspected ARVC. A pathological substrate was identified at CMRI in 36 patients (29%): five patients (4%) had ischaemic heart disease (IHD) and 10 (8%) non-IHD; five patients (4%) met CMRI criteria for ARVC and 16 (13%) were ARVC mimics. right ventricular end-diastolic volume (RVEDV) and right ventricular stroke volume (RVSV) were significantly higher in patients with ARVC mimics (RVEDV p=0.007, RVSV p=0.012) and ARVC (RVEDV p=0.013, RVSV p=0.013), as compared to those with structurally normal hearts. CMRI was superior to echocardiography in the identification of ARVC mimics (13% versus 1%, p=0.01). CONCLUSIONS: CMRI was able to identify 16 (13%) ARVC mimics, from congenital abnormalities to acquired heart disease. CMRI was superior in identifying ARVC mimics compared to echocardiography, and overall provided a change in diagnosis in 22% of patients.

Carotid artery ligation induced intimal thickening and proliferation is unaffected by ageing.

Following interventions to treat atherosclerosis, such as coronary artery bypass graft surgery, restenosis occurs in approximately 40% of patients. Identification of proteins regulating intimal thickening could represent targets to prevent restenosis. Our group previously demonstrated that in a murine model of vascular occlusion, Wnt4 protein expression and ß-catenin signalling was upregulated which promoted vascular smooth muscle cell (VSMC) proliferation and intimal thickening. In this study, the effect of age on VSMC proliferation, intimal hyperplasia and Wnt4 expression was investigated. In vitro proliferation of VSMCs isolated from young (2 month) or old (18-20 month) C57BL6/J mice was assessed by immunocytochemistry for EdU incorporation. As previously reported, 400 ng/mL recombinant Wnt4 protein increased proliferation of VSMCs from young mice. However, this response was absent in VSMCs from old mice. As our group previously reported reduced intimal hyperplasia in Wnt4+/- mice compared to wildtype controls, we hypothesised that impaired Wnt4 signalling with age may result in reduced neointimal formation. To investigate this, carotid artery ligation was performed in young and old mice and neointimal area was assessed 21 days later. Surprisingly, neointimal area and percentage lumen occlusion were not significantly affected by age. Furthermore, neointimal cell density and proliferation were also unchanged. These data suggest that although Wnt4-mediated proliferation was impaired with age in primary VSMCs, carotid artery ligation induced neointimal formation and proliferation were unchanged in old mice. These results imply that Wnt4-mediated proliferation is unaffected by age in vivo, suggesting that therapeutic Wnt4 inhibition could inhibit restenosis in patients of all ages.

Randomized trial of near-infrared spectroscopy for personalized optimization of cerebral tissue oxygenation during cardiac surgery.

BACKGROUND: We assessed whether a near-infrared spectroscopy (NIRS)-based algorithm for the personalized optimization of cerebral oxygenation during cardiopulmonary bypass combined with a restrictive red cell transfusion threshold would reduce perioperative injury to the brain, heart, and kidneys. METHODS: In a randomized controlled trial, participants in three UK centres were randomized with concealed allocation to a NIRS (INVOS 5100; Medtronic Inc., Minneapolis, MN, USA)-based 'patient-specific' algorithm that included a restrictive red cell transfusion threshold (haematocrit 18%) or to a 'generic' non-NIRS-based algorithm (standard care). The NIRS algorithm aimed to maintain cerebral oxygenation at an absolute value of > 50% or at > 70% of baseline values. The primary outcome for the trial was cognitive function measured up to 3 months postsurgery. RESULTS: The analysis population comprised eligible randomized patients who underwent valve or combined valve surgery and coronary artery bypass grafts using cardiopulmonary bypass between December 2009 and January 2014 ( n =98 patient-specific algorithm; n =106 generic algorithm). There was no difference between the groups for the three core cognitive domains (attention, verbal memory, and motor coordination) or for the non-core domains psychomotor speed and visuo-spatial skills. The NIRS group had higher scores for verbal fluency; mean difference 3.73 (95% confidence interval 1.50, 5.96). Red cell transfusions, biomarkers of brain, kidney, and myocardial injury, adverse events, and health-care costs were similar between the groups. CONCLUSIONS: These results do not support the use of NIRS-based algorithms for the personalized optimization of cerebral oxygenation in adult cardiac surgery. CLINICAL TRIAL REGISTRATION: http://www.controlled-trials.com , ISRCTN 23557269.

Out of hospital cardiac arrest survivors with inconclusive coronary angiogram: Impact of cardiovascular magnetic resonance on clinical management and decision-making.

BACKGROUND: Non-traumatic out of hospital cardiac arrest (OHCA) is the leading cause of death worldwide, mainly due to acute coronary syndromes. Urgent coronary angiography with view to revascularisation is recommended in patients with suspected acute coronary syndrome. Diagnosis and management of patients with inconclusive coronary angiogram (unobstructed coronaries or unidentified culprit lesion) is challenging. We sought to assess the role of Cardiovascular Magnetic Resonance (CMR) in the diagnosis and management of OHCA survivors with an inconclusive coronary angiogram. METHODS AND RESULTS: This is a retrospective multicentre CMR registry analysis of OHCA survivors with an inconclusive angiogram. Clinical, ECG and multi-modality imaging data were analysed. Clinical impact of CMR was defined as a change in diagnosis or management. Out of 174 OHCA survivors referred for CMR, 110 patients (63%, 84 male, median age 58) had an inconclusive angiogram. CMR identified a pathologic substrate in 76/110 patients (69%): ischemic heart disease was found in 45 (41%) and non-ischemic heart disease in 31 (28%). A structurally normal heart was found in 25 patients (23%) and non-specific findings in 9 (8%). As compared to trans-thoracic echocardiogram, CMR proved to be superior in identifying a pathologic substrate (69% vs 54%, p=0.018). The CMR study carried a clinical impact in 70% of patients, determining a change in diagnosis in 25%, in management in 29% and a change in both in 16%. CONCLUSIONS: CMR showed a promising role in the diagnostic work-up of OHCA survivors with inconclusive angiogram and its wider use should be considered.

Are lower levels of red blood cell transfusion more cost-effective than liberal levels after cardiac surgery? Findings from the TITRe2 randomised controlled trial.

OBJECTIVE: To assess the incremental cost and cost-effectiveness of a restrictive versus a liberal red blood cell transfusion threshold after cardiac surgery. DESIGN: A within-trial cost-effectiveness analysis with a 3-month time horizon, based on a multicentre superiority randomised controlled trial from the perspective of the National Health Service (NHS) and personal social services in the UK. SETTING: 17 specialist cardiac surgery centres in UK NHS hospitals. PARTICIPANTS: 2003 patients aged >16 years undergoing non-emergency cardiac surgery with a postoperative haemoglobin of <9 g/dL. INTERVENTIONS: Restrictive (transfuse if haemoglobin <7.5 g/dL) or liberal (transfuse if haemoglobin <9 g/dL) threshold during hospitalisation after surgery. MAIN OUTCOME MEASURES: Health-related quality of life measured using the EQ-5D-3L to calculate quality-adjusted life years (QALYs). RESULTS: The total costs from surgery up to 3 months were £17 945 and £18 127 in the restrictive and liberal groups (mean difference is -£182, 95% CI -£1108 to £744). The cost difference was largely attributable to the difference in the cost of red blood cells. Mean QALYs to 3 months were 0.18 in both groups (restrictive minus liberal difference is 0.0004, 95% CI -0.0037 to 0.0045). The point estimate for the base-case cost-effectiveness analysis suggested that the restrictive group was slightly more effective and slightly less costly than the liberal group and, therefore, cost-effective. However, there is great uncertainty around these results partly due to the negligible differences in QALYs gained. CONCLUSIONS: We conclude that there is no clear difference in the cost-effectiveness of restrictive and liberal thresholds for red blood cell transfusion after cardiac surgery. TRIAL REGISTRATION NUMBER: ISRCTN70923932; Results.

Inflammation, oxidative stress and postoperative atrial fibrillation in cardiac surgery.

Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery that occurs in up to 60% of patients. POAF is associated with increased risk of cardiovascular mortality, stroke and other arrhythmias that can impact on early and long term clinical outcomes and health economics. Many factors such as disease-induced cardiac remodelling, operative trauma, changes in atrial pressure and chemical stimulation and reflex sympathetic/parasympathetic activation have been implicated in the development of POAF. There is mounting evidence to support a major role for inflammation and oxidative stress in the pathogenesis of POAF. Both are consequences of using cardiopulmonary bypass and reperfusion following ischaemic cardioplegic arrest. Subsequently, several anti-inflammatory and antioxidant drugs have been tested in an attempt to reduce the incidence of POAF. However, prevention remains suboptimal and thus far none of the tested drugs has provided sufficient efficacy to be widely introduced in clinical practice. A better understanding of the cellular and molecular mechanisms responsible for the onset and persistence of POAF is needed to develop more effective prediction and interventions.

Remote ischaemic preconditioning: is it a flag on the field?

Ischaemic preconditioning is one of several different techniques that have been proposed to render the heart more resistant to ischaemia/reperfusion injuries. A significant reduction of troponin release is 'proof of concept', however, whether ischaemic preconditioning leads to improved clinical outcomes is still to be proven. Moreover, the exact mechanism of action still remains unknown since very few studies have investigated the signal transmission in humans.

Arterial blood pressure and vascular function in human saphenous vein.

Hypertension is a risk factor for accelerated saphenous vein (SV) graft disease and endothelial dysfunction in a number of vascular territories. We examined the relationship between blood pressure (BP) and vascular function in SV from 94 male patients undergoing coronary artery bypass grafting (CABG). Patients were pretreated with respect to cholesterol (3.4±1.2 mmol/L) and BP (systolic 139±22 mmHg, diastolic 74±13 mmHg). All patients were taking aspirin, 85% statins, 50% angiotensin-converting enzyme inhibitors and 70% beta-blockers. We demonstrate in human SV rings ex vivo that increased BP has no effect on acetylcholine-mediated vasodilatation (p=0.58), nor on the constrictor response to L-NMMA (p=0.98), but has a positive association with the constrictor response to phenylephrine (p=0.008) and a negative correlation with the vasodilator response to sodium nitroprusside (p=0.03). These results may provide further explanation for the high incidence of early vein graft failure after CABG in hypertensive patients and support an aggressive approach to optimize BP before surgery.

Dynamic output and control of the hypothalamic-pituitary-adrenal axis in critical illness and major surgery.

The hypothalamic-pituitary-adrenal (HPA) axis is a neuro-endocrine system that regulates circulating levels of glucocorticoid hormones. These hormones are vital for normal homeostasis and play a pivotal role in the response to stress. Levels of cortisol fluctuate throughout the day in a diurnal rhythm, underlying which is an ultradian rhythm of approximately hourly pulses, and this pulsatility directly affects transcriptional outcomes. Pulsatility is not the result of a 'pulse generator', but is inherent within the system as a result of negative feedback. These patterns of secretion change in both acute and chronic illness as a result of inflammatory mediators, splanchnic nerve output, and central nervous system control. Levels of cortisol in both normal and illness states are highly dynamic and so previously used static assessment tools for diagnosing corticosteroid related critical illness insufficiency (CRCI) are not likely to be useful. Therapeutic regimens have also failed so far, to take secretory patterns into account. In this review we look at the dynamic control and effects of glucocorticoids and frame in this context the current evidence surrounding steroid use in critical care and major surgery.

Pericardial neo-aorta to bridge long segment defects after infected aortic reconstructions.

Aortic prosthetic graft infection is a rare, potentially fatal complication. Surgical explantation of the infected native and prosthetic material with sufficient debridement has sometimes been limited by the lack of a suitable conduit to bridge the residual long segment defect. We describe the implantation of a bovine pericardial fashioned neo-aorta to manage this problem.

Cardioplegic strategies to protect the hypertrophic heart during cardiac surgery.

Cardioplegic arrest and cardiopulmonary bypass are key triggers of myocardial injury during aortic valve surgery. Cardioplegic ischaemic arrest is associated with disruption to metabolic and ionic homeostasis in cardiomyocytes. These changes predispose the heart to reperfusion injury caused by elevated intracellular reactive oxygen species and calcium. Cardiopulmonary bypass is associated with an inflammatory response that can generate systemic oxidative stress which, in turn, provokes further damage to the heart. Techniques of myocardial protection are routinely applied to all hearts, irrespective of their pathology, although different cardiomypathies respond differently to ischaemia and reperfusion injury. In particular, the efficacy of cardioprotective interventions used to protect the hypertrophic heart in patients with aortic valve disease remains controversial. This review will describe key cellular changes in hypertrophy, response to ischaemia and reperfusion and cardioplegic arrest and highlight the importance of optimising cardioprotective strategies to suit hypertrophic hearts.

Folic acid administration reduces neointimal thickening, augments neo-vasa vasorum formation and reduces oxidative stress in saphenous vein grafts from pigs used as a model of diabetes.

AIMS/HYPOTHESIS: There is evidence that plasma homocysteine augments vein graft failure and that it augments both micro- and macro-angiopathy in patients with diabetes mellitus. It is therefore suggested that homocysteine may augment vein graft thickening, a major cause of vein graft failure, in diabetic patients, as well as impairing adaptive growth of a new vasa vasorum, possibly through overproduction of superoxide. In order to test these proposals, the effect of folic acid administration, which lowers plasma homocysteine, on vein graft thickening and microvessel density was studied in pigs used as a model of diabetes. METHODS: Non-ketotic hyperglycaemia was induced in Landrace pigs by intravenous injection of streptozotocin, and folic acid was fed daily for 1 month. Vein grafts were excised and the thickness of the neointima and media and microvessel density were assessed by planimetry and superoxide formation. RESULTS: Plasma total homocysteine was significantly reduced by folic acid in both control and diabetic pigs, whereas glucose was unchanged. Compared with controls, diabetic pigs showed increased neointimal thickness and superoxide formation and decreased adventitial microvessel density. Folic acid reduced neointimal thickness and superoxide formation and augmented microvessel density in diabetic but not in control pigs. CONCLUSIONS: Folic acid administration reduces neointimal thickening, augments vasa vasorum neoformation and reduces oxidative stress in saphenous vein grafts from diabetic pigs. Folic acid may therefore be particularly effective in reducing vein graft failure in diabetic patients.

The importance of myocardial amino acids during ischemia and reperfusion in dilated left ventricle of patients with degenerative mitral valve disease.

Taurine, glutamine, glutamate, aspartate, and alanine are the most abundant intracellular free amino acids in human heart. The myocardial concentration of these amino acids changes during ischemia and reperfusion due to alterations in metabolic and ionic homeostasis. We hypothesized that dilated left ventricle secondary to mitral valve disease has different levels of amino acids compared to the right ventricle and that such differences determine the extent of amino acids' changes during ischemia and reperfusion. Myocardial concentration of amino acids was measured in biopsies collected from left and right ventricles before cardioplegic arrest (Custodiol HTK) and 10 min after reperfusion in patients undergoing mitral valve surgery. The dilated left ventricle had markedly higher (P < 0.05) concentrations (nmol/mg wet weight) of taurine (17.0 +/- 1.5 vs. 10.9 +/- 1.5), glutamine (20.5 +/- 2.4 vs. 12.1 +/- 1.2), and glutamate (18.3 +/- 2.2 vs. 11.4 +/- 1.5) when compared to right ventricle. There were no differences in the basal levels of alanine or aspartate. Upon reperfusion, a significant (P < 0.05) fall in taurine and glutamine was seen only in the left ventricle. These changes are likely to be due to transport (taurine) and/or metabolism (glutamine). There was a marked increase in the alanine to glutamate ratio in both ventricles indicative of ischemic stress which was confirmed by global release of lactate during reperfusion. This study shows that in contrast to the right ventricle, the dilated left ventricle had remodeled to accumulate amino acids which are used during ischemia and reperfusion. Whether these changes reflect differences in degree of cardioplegic protection between the two ventricles remain to be investigated.

H2S-donating sildenafil (ACS6) inhibits superoxide formation and gp91phox expression in arterial endothelial cells: role of protein kinases A and G.

BACKGROUND AND PURPOSE: Superoxide (O(2)(*-)), derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, is associated with acute respiratory distress syndrome (ARDS). NADPH oxidase activity and expression are blocked by nitric oxide (NO) and sildenafil. As another gas, hydrogen sulphide (H(2)S) is formed by blood vessels, the effect of sodium hydrosulphide (NaHS) and the H(2)S-donating derivative of sildenafil, ACS6, on O(2)(*-) formation and the expression of gp91(phox) (a catalytic subunit of NADPH oxidase) in porcine pulmonary arterial endothelial cells (PAECs) was investigated. EXPERIMENTAL APPROACH: PAECs were incubated with 10 ng mL(-1) tumour necrosis factor-alpha (TNFalpha) (+/-NaHS or ACS6), both of which released H(2)S, for 2 h or 16 h. O(2)(*-) was measured. Expression of gp91(phox) was measured by western blotting and the role of cyclic AMP (cAMP) and/or cyclic GMP was assessed using protein kinase inhibitors. KEY RESULTS: After either 2- or 16-h incubations, O(2)(*-) formation by PAECs was inhibited by NaHS or ACS6, with IC(50) values of about 10 nM and less than 1 nM, respectively. Both 100 nM NaHS and 1 nM ACS6 completely inhibited gp91(phox) expression induced by TNFalpha. The effects of NaHS were blocked by the inhibition of protein kinase A (PKA), but not PKG, and not by the inhibition of guanylyl cyclase. Effects of ACS6 were blocked by inhibition of both PKA and PKG. Both NaHS and ACS6 augmented cAMP formation. CONCLUSION AND IMPLICATIONS: H(2)S inhibited O(2)(*-) formation and upregulation of NADPH oxidase in PAECs through the adenylyl cyclase-PKA pathway. ACS6 may be effective in treating ARDS through both elevation of cAMP and inhibition of phosphodiesterase type 5 activity.

Inadequate blood glucose control is associated with in-hospital mortality and morbidity in diabetic and nondiabetic patients undergoing cardiac surgery.

BACKGROUND: Derangement of glucose metabolism after surgery is not specific to patients with diabetes mellitus. We investigated the effect of different degrees of blood glucose control (BGC) on clinical outcomes after cardiac surgery. METHODS AND RESULTS: We analyzed 8727 adults operated on between April 1996 and March 2004. The highest blood glucose level recorded over the first 60 hours postoperatively was used to classify patients as having good (<200 mg/dL), moderate (200 to 250 mg/dL), or poor (>250 mg/dL) BGC; 7547 patients (85%) had good, 905 (10%) had moderate, and 365 (4%) had poor BGC. Patients with inadequate BGC were more likely to present with advanced New York Heart Association class, congestive heart failure, hypertension, renal dysfunction, and ejection fraction <50% (P0

Superoxide from NADPH oxidase upregulates type 5 phosphodiesterase in human vascular smooth muscle cells: inhibition with iloprost and NONOate.

BACKGROUND AND PURPOSE: To determine whether there is an association between vascular NADPH oxidase (NOX), superoxide, the small GTPase Rac(1) and PDE type 5 (PDE5) in human vascular smooth muscle cell (hVSMCs). EXPERIMENTAL APPROACH: hVSMCs were incubated with xanthine-xanthine oxidase (X-XO; a superoxide generating system) or the thromboxane A(2) analogue, U46619 (+/-superoxide dismutase (SOD) or apocynin) for 16 h. The expression of PDE5 and NOX-1 was assessed using Western blotting and superoxide measured. The role of Rac(1) in superoxide generation was assessed by overexpressing either the dominant-negative or constitutively active Rac isoforms. The effects of iloprost, DETA-NONOate and the Rho-kinase inhibitor, Y27632, on PDE5 and NOX-1 expression were also studied. KEY RESULTS: Following 16 h incubation, U46619 and X-XO promoted the expression of PDE5 and NOX-1, an effect blocked by SOD or apocynin when co-incubated over the same time course. X-XO and U46619 both promoted the formation of superoxide. Overexpression of dominant-negative Rac(1) or addition of iloprost, DETA-NONOate or Y27632 completely blocked both superoxide release and PDE5 protein expression and activity. CONCLUSIONS AND IMPLICATIONS: These data demonstrate that superoxide derived from NOX upregulates the expression of PDE5 in human VSMCs. As PDE5 hydrolyses cyclic GMP, this effect may blunt the vasculoprotective actions of NO.