Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial.

BACKGROUND: The International Liaison Committee on Resuscitation has called for a randomised trial of delivery to a cardiac arrest centre. We aimed to assess whether expedited delivery to a cardiac arrest centre compared with current standard of care following resuscitated cardiac arrest reduces deaths. METHODS: ARREST is a prospective, parallel, multicentre, open-label, randomised superiority trial. Patients (aged ≥18 years) with return of spontaneous circulation following out-of-hospital cardiac arrest without ST elevation were randomly assigned (1:1) at the scene of their cardiac arrest by London Ambulance Service staff using a secure online randomisation system to expedited delivery to the cardiac catheter laboratory at one of seven cardiac arrest centres or standard of care with delivery to the geographically closest emergency department at one of 32 hospitals in London, UK. Masking of the ambulance staff who delivered the interventions and those reporting treatment outcomes in hospital was not possible. The primary outcome was all-cause mortality at 30 days, analysed in the intention-to-treat (ITT) population excluding those with unknown mortality status. Safety outcomes were analysed in the ITT population. The trial was prospectively registered with the International Standard Randomised Controlled Trials Registry, 96585404. FINDINGS: Between Jan 15, 2018, and Dec 1, 2022, 862 patients were enrolled, of whom 431 (50%) were randomly assigned to a cardiac arrest centre and 431 (50%) to standard care. 20 participants withdrew from the cardiac arrest centre group and 19 from the standard care group, due to lack of consent or unknown mortality status, leaving 411 participants in the cardiac arrest centre group and 412 in the standard care group for the primary analysis. Of 822 participants for whom data were available, 560 (68%) were male and 262 (32%) were female. The primary endpoint of 30-day mortality occurred in 258 (63%) of 411 participants in the cardiac arrest centre group and in 258 (63%) of 412 in the standard care group (unadjusted risk ratio for survival 1·00, 95% CI 0·90-1·11; p=0·96). Eight (2%) of 414 patients in the cardiac arrest centre group and three (1%) of 413 in the standard care group had serious adverse events, none of which were deemed related to the trial intervention. INTERPRETATION: In adult patients without ST elevation, transfer to a cardiac arrest centre following resuscitated cardiac arrest in the community did not reduce deaths. FUNDING: British Heart Foundation.

Computed tomography derived anatomical predictors of vascular access complications following transfemoral transcatheter aortic valve implantation: A systematic review.

BACKGROUND: Vascular complications after percutaneous transfemoral transcatheter aortic valve implantation (TAVI) are associated with adverse clinical outcomes and remain a significant challenge. AIMS: The purpose of this review is to synthesize the existing evidence regarding the iliofemoral artery features predictive of vascular complications after TAVI on pre-procedural contrast-enhanced multidetector computed tomography (MDCT). METHODS: A systematic search was performed in Embase and Medline (Pubmed) databases. Studies of patients undergoing transfemoral TAVI with MDCT were included. Studies with only valve-in-valve TAVI, planned surgical intervention and those using fluoroscopic assessment were excluded. Data on study cohort, procedural characteristics and significant predictors of vascular complications were extracted. RESULTS: We identified 23 original studies involving 8697 patients who underwent TAVI between 2006 and 2020. Of all patients, 8514 (97.9%) underwent percutaneous transfemoral-TAVI, of which 8068 (94.8%) had contrast-enhanced MDCT. The incidence of major vascular complications was 6.7 ± 4.1% and minor vascular complications 26.1 ± 7.8%. Significant independent predictors of major and minor complications related to vessel dimensions were common femoral artery depth (>54 mm), sheath-to-iliofemoral artery diameter ratio (>0.91-1.19), sheath-to-femoral artery diameter ratio (>1.03-1.45) and sheath-to-femoral artery area ratio (>1.35). Substantial iliofemoral vessel tortuosity predicted 2-5-fold higher vascular risk. Significant iliofemoral calcification predicted 2-5-fold higher risk. The iliac morphology score was the only hybrid scoring system with predictive value. CONCLUSIONS: Independent iliofemoral predictors of access-site complications in TAVI were related to vessel size, depth, calcification and tortuosity. These should be considered when planning transfemoral TAVI and in the design of future risk prediction models.

Clinical outcomes following single access transfemoral transcatheter aortic valve implantation.

OBJECTIVES: We describe the first experience using calcification of anatomical landmarks to obviate the need for transcatheter aortic valve implantation (TAVI) alignment aortography and secondary TAVI access. BACKGROUND: TAVI alignment conventionally involves secondary femoral access for contrast aortography using a second catheter. Secondary femoral access accounts for up to 25% of all vascular complications. Heavily calcified aortic leaflets are often visible fluoroscopically and can act as markers for TAVI alignment. METHODS: We considered 100 consecutive patients for transfemoral TAVI. The first group was considered for a conventional dual access technique and the subsequent group was considered for a single access technique. Relevant baseline, and procedural and outcome measures were recorded. RESULTS: Baseline characteristics were comparable between groups. Balloon-expandable transcatheter heart valves (THV) were used in all cases. THV implantation was successful in 100% of cases with no procedural or in-hospital mortality. Procedural time and contrast use were lower in the single access group. There were no Valve Academic Research Consortium (VARC)-2 major vascular complications with the single access technique. CONCLUSIONS: This is the first study describing the use of calcification of anatomical landmarks to obviate the need for secondary TAVI access. Notable observations included successful device implantation in all cases, no VARC-2 major vascular complications, comparable rates of paravalvular leak and permanent pacemaker requirement, shorter procedural times, and lower contrast use. Single access TAVI is a viable alternative technique to minimize vascular access, contrast use, and procedural duration in experienced centers and with selected patients, allowing successful device implantation and low complication rates while further streamlining TAVI workflow.

Physiology of Angina and Its Alleviation With Nitroglycerin: Insights From Invasive Catheter Laboratory Measurements During Exercise.

BACKGROUND: The mechanisms governing exercise-induced angina and its alleviation by the most commonly used antianginal drug, nitroglycerin, are incompletely understood. The purpose of this study was to develop a method by which the effects of antianginal drugs could be evaluated invasively during physiological exercise to gain further understanding of the clinical impact of angina and nitroglycerin. METHODS: Forty patients (mean age, 65.2±7.6 years) with exertional angina and coronary artery disease underwent cardiac catheterization via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual nitroglycerin was administered to half the patients, and all patients continued to exercise for 2 minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity and central aortic pressure were recorded with sensor wires. RESULTS: Patients continued to exercise after nitroglycerin administration with less ST-segment depression (P=0.003) and therefore myocardial ischemia. Significant reductions in afterload (aortic pressure, P=0.030) and myocardial oxygen demand were seen (tension-time index, P=0.024; rate-pressure product, P=0.046), as well as an increase in myocardial oxygen supply (Buckberg index, P=0.017). Exercise reduced peripheral arterial wave reflection (P<0.05), which was not further augmented by the administration of nitroglycerin (P=0.648). The observed increases in coronary pressure gradient, stenosis resistance, and flow velocity did not reach statistical significance; however, the diastolic velocity-pressure gradient relation was consistent with a significant increase in relative stenosis severity (k coefficient, P<0.0001), in keeping with exercise-induced vasoconstriction of stenosed epicardial segments and dilatation of normal segments, with trends toward reversal with nitroglycerin. CONCLUSIONS: The catheterization laboratory protocol provides a model to study myocardial ischemia and the actions of novel and established antianginal drugs. Administration of nitroglycerin causes changes in the systemic and coronary circulation that combine to reduce myocardial oxygen demand and to increase supply, thereby attenuating exercise-induced ischemia. Designing antianginal therapies that exploit these mechanisms may provide new therapeutic strategies.

Rationale and design of: A Randomized tRial of Expedited transfer to a cardiac arrest center for non-ST elevation out-of-hospital cardiac arrest: The ARREST randomized controlled trial.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a global public health issue. There is wide variation in both regional and inter-hospital survival rates from OHCA and overall survival remains poor at 7%. Regionalization of care into cardiac arrest centers (CAC) improves outcomes following cardiac arrest from ST elevation myocardial infarction (STEMI) through concentration of services and greater provider experience. The International Liaison Committee on Resuscitation (ILCOR) recommends delivery of all post-arrest patients to a CAC, but that randomized controlled trials are necessary in patients without ST elevation (STE). METHODS/DESIGN: Following completion of a pilot randomized trial to assess safety and feasibility of conducting a large-scale randomized controlled trial in patients following OHCA of presumed cardiac cause without STE, we present the rationale and design of A Randomized tRial of Expedited transfer to a cardiac arrest center for non-ST elevation OHCA (ARREST). In total 860 patients will be enrolled and randomized (1:1) to expedited transfer to CAC (24/7 access to interventional cardiology facilities, cooling and goal-directed therapies) or to the current standard of care, which comprises delivery to the nearest emergency department. Primary outcome is 30-day all-cause mortality and secondary outcomes are 30-day and 3-month neurological status and 3, 6 and 12-month mortality. Patients will be followed up for one year after enrolment. CONCLUSION: Post-arrest care is time-critical, requires a multi-disciplinary approach and may be more optimally delivered in centers with greater provider experience. This trial would help to demonstrate if regionalization of post-arrest care to CACs reduces mortality in patients without STE, which could dramatically reshape emergency care provision.

A feasibility and safety study of intracoronary hemodilution during primary coronary angioplasty in order to reduce reperfusion injury in myocardial infarction.

OBJECTIVES: We designed a pilot study to evaluate safety and feasibility of an inexpensive and simple approach to intracoronary hemodilution during primary angioplasty (PPCI) to reduce reperfusion injury. INTRODUCTION: Early revascularization in acute myocardial infarction decreases infarct size and improves outcomes. However, abrupt restoration of coronary flow results in myocardial reperfusion injury and increased final infarct size. Dilution of coronary blood during revascularization may help reduce this damage. If proved effective, such an approach would need to be simple and suitable for widespread adoption. METHODS: Ten patients presenting with STEMI underwent intracoronary dilution with room temperature Hartmann's solution delivered through the guiding catheter during primary angioplasty (PPCI). Infusion of perfusate began prior to crossing the occluded artery with the guidewire, continuing until 10 min after completion of the balloon and stenting procedure. Infusion was briefly interrupted for contrast injection and pressure monitoring. The outcome measures were safety, including intracoronary temperature reduction and volume of intracoronary perfusate infused, and technical feasibility. RESULTS: There were no significant symptomatic, hemodynamic, ECG ST/T segment or rhythm changes observed during perfusate administration. The median (interquartile range) volume of perfusate administered was 550 mL (350-725 mL) and the median intracoronary temperature reduction observed was 3.4°Celsius. Myocardial salvage was 0.54 (0.43-0.65). CONCLUSIONS: Transcatheter intracoronary hemodilution with room temperature perfusate during PPCI is feasible and appears safe. Such a strategy is simple and inexpensive, with potential to be widely applied. Further mechanistic and subsequent outcome powered studies are required to evaluate whether this strategy can reduce reperfusion injury in STEMI.

Non-nutritive sucking for increasing physiologic stability and nutrition in preterm infants.

BACKGROUND: Non-nutritive sucking (NNS) is used during gavage feeding and in the transition from gavage to breast/bottle feeding in preterm infants to improve the development of sucking behavior and the digestion of enteral feedings. OBJECTIVES: To assess the effects of non-nutritive sucking on physiologic stability and nutrition in preterm infants. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1), MEDLINE via PubMed (1966 to 25 February 2016), Embase (1980 to 25 February 2016), and CINAHL (1982 to 25 February 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised trials that compared non-nutritive sucking versus no provision of non-nutritive sucking in preterm infants. We excluded cross-over trials. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and undertook data extraction independently. We analysed the treatment effects in the individual trials and reported mean differences (MD) for continuous data, with 95% confidence intervals (CIs). We used a fixed-effect model in meta-analyses. We did not perform subgroup analyses because of the small number of studies related to the relevant outcomes. We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: We identified 12 eligible trials enrolling a total of 746 preterm infants. Meta-analysis, though limited by data quality, demonstrated a significant effect of NNS on transition from gavage to full oral feeding (MD -5.51 days, 95% CI -8.20 to -2.82; N = 87), transition from start of oral feeding to full oral feeding (MD -2.15 days, 95% CI -3.12 to -1.17; N = 100), and the length of hospital stay (MD -4.59 days, 95% CI -8.07 to -1.11; N = 501). Meta-analysis revealed no significant effect of NNS on weight gain. One study found that the NNS group had a significantly shorter intestinal transit time during gavage feeding compared to the control group (MD -10.50 h, 95% CI -13.74 to -7.26; N = 30). Other individual studies demonstrated no clear positive effect of NNS on age of infant at full oral feeds, days from birth to full breastfeeding, rates and proportion of infants fully breastfeeding at discharge, episodes of bradycardia, or episodes of oxygen desaturation. None of the studies reported any negative outcomes. These trials were generally small and contained various methodological weaknesses including lack of blinding of intervention and outcome assessors and variability on outcome measures. The quality of the evidence on outcomes assessed according to GRADE was low to very low. AUTHORS' CONCLUSIONS: Meta-analysis demonstrated a significant effect of NNS on the transition from gavage to full oral feeding, transition from start of oral feeding to full oral feeding, and length of hospital stay. None of the trials reported any adverse effects. Well-designed, adequately powered studies using reliable methods of randomisation, concealment of treatment allocation and blinding of the intervention and outcome assessors are needed. In order to facilitate meta-analysis of these data, future research should involve outcome measures consistent with those used in previous studies.

The early childhood oral health program: a qualitative study of the perceptions of child and family health nurses in South Western Sydney, Australia.

BACKGROUND: Early childhood caries affects nearly half the population of Australian children aged 5 years and has the potential to negatively impact their growth and development. To address this issue, an Early Childhood Oral Health (ECOH) program, facilitated by Child and Family Health Nurses (CFHNs), commenced in 2007 in New South Wales, Australia. This study builds on the previous evaluation of the program. It aims to explore the perceptions of CFHNs regarding the implementation of the ECOH program in South Western Sydney and the challenges and barriers related to its sustainability. METHODS: A descriptive qualitative design was used in this study. Two focus groups were conducted with 22 CFHNs who were sampled from two Community Health Centres in South Western Sydney, Australia. Data were transcribed verbatim and thematic analysis was undertaken. RESULTS: Most CFHNs acknowledged the importance of early childhood oral health promotion and were providing education, oral assessments and referrals during child health checks. Many stressed the need for collaboration with other health professionals to help broaden the scope of the program. Some barriers to implementing the program included confusion regarding the correct referral process, limited feedback from dental services and the lack of oral health awareness among parents. CONCLUSION: The study findings suggest that the ECOH program is being sustained and effectively implemented into practice by CFHNs. Improvement in the referral and feedback process as well as enhancing parental knowledge of the importance of infant and child oral health could further strengthen the effectiveness of the program. Expanding oral health education opportunities into general practice is advocated, while regular on-line training for CFHNs is preferred. Future research should include strategies to reduce non-attendances, and an assessment of the impact on the prevalence of childhood caries of the ECOH program.

Cardiac myosin-binding protein C: a potential early biomarker of myocardial injury.

Cardiac troponins are released and cleared slowly after myocardial injury, complicating the diagnosis of early, and recurrent, acute myocardial infarction. Cardiac myosin-binding protein C (cMyC) is a similarly cardiac-restricted protein that may have different release/clearance kinetics. Using novel antibodies raised against the cardiac-specific N-terminus of cMyC, we used confocal microscopy, immunoblotting and immunoassay to document its location and release. In rodents, we demonstrate rapid release of cMyC using in vitro and in vivo models of acute myocardial infarction. In patients, with ST elevation myocardial infarction (STEMI, n = 20), undergoing therapeutic ablation of septal hypertrophy (TASH, n = 20) or having coronary artery bypass surgery (CABG, n = 20), serum was collected prospectively and frequently. cMyC appears in the serum as full-length and fragmented protein. Compared to cTnT measured using a contemporary high-sensitivity commercial assay, cMyC peaks earlier (STEMI, 9.3 ± 3.1 vs 11.8 ± 3.4 h, P < 0.007; TASH, 9.7 ± 1.4 vs 21.6 ± 1.4 h, P < 0.0001), accumulates more rapidly (during first 4 h after TASH, 25.8 ± 1.9 vs 4.0 ± 0.4 ng/L/min, P < 0.0001) and disappears more rapidly (post-CABG, decay half-time 5.5 ± 0.8 vs 22 ± 5 h, P < 0.0001). Our results demonstrate that following defined myocardial injury, the rise and fall in the serum of cMyC is more rapid than that of cTnT. We speculate that these characteristics could enable earlier diagnosis of myocardial infarction and reinfarction in suspected non-STEMI, a population not included in this early translational study.

Advanced cutaneous squamous cell carcinoma: Impact of age on the safety and efficacy of cemiplimab and the prognostic significance of blood biomarkers.

INTRODUCTION: Age-related differences in the safety profile of cemiplimab for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) have not been well described. We investigated the association of increasing age with immune related adverse events (irAE) from cemiplimab, efficacy outcomes, and the prognostic significance of pre-treatment blood biomarkers in contemporary practice. MATERIALS AND METHODS: Patients starting first-line cemiplimab for locally advanced or metastatic cSCC at British Columbia Cancer between April 2019 and January 2023 were identified. Landmark four-month logistic regression analysis compared the odds of developing irAE or sequelae amongst patients aged <75 years to those aged 75-84 or ≥ 85. Objective responses were determined using Response Evaluation Criteria in Solid Tumors version 1.1. Univariable Cox proportional hazard (PH) regression modelling of factors associated with overall survival (OS) was performed. RESULTS: Of 106 patients, the proportions aged <75, 75-84, and ≥ 85 years were 34%, 45%, and 21%, respectively. Overall, the proportion of patients with irAE ≥ grade 3, cemiplimab discontinuation, and hospitalization for immune toxicity was 27.4%, 31.1%, and 11.3%, respectively. There was no clear association between age and the odds of high grade irAE. However, increased odds of cemiplimab discontinuation was observed in patients aged 75-84 years (p = 0.05). Patients ≥85 years had increased hospitalizations due to irAE (OR = 5.00, 95% CI = 0.97-37.52) with two treatment-related deaths. Objective responses were similar across age cohorts (50.0%, 60.4%, and 54.5%) but progressive disease was higher in the age ≥ 85 group (22.2%, 18.8%, and 31.8%). On Cox PH regression analysis, age ≥ 85 years (vs. <75), Eastern Cooperative Oncology Group performance status 2-3 (vs. 0-1), and neutrophil to lymphocyte ratio (NLR) ≥7.80 (vs. <7.80) were associated with shorter survival. DISCUSSION: While the odds of high grade irAE were similar across age groups, significant age-related differences in treatment discontinuation and hospitalization due to immune toxicity were observed. Despite a higher incidence of primary progression and shorter OS in the oldest cohort, cemiplimab yielded robust objective responses regardless of age. Higher pre-treatment NLR was associated with shorter survival and the cut-point identified requires further study.

Tricuspid Regurgitation: From Imaging to Clinical Trials to Resolving the Unmet Need for Treatment.

Tricuspid regurgitation (TR) is a highly prevalent and heterogeneous valvular disease, independently associated with excess mortality and high morbidity in all clinical contexts. TR is profoundly undertreated by surgery and is often discovered late in patients presenting with right-sided heart failure. To address the issue of undertreatment and poor clinical outcomes without intervention, numerous structural tricuspid interventional devices have been and are in development, a challenging process due to the unique anatomic and physiological characteristics of the tricuspid valve, and warranting well-designed clinical trials. The path from routine practice TR detection to appropriate TR evaluation, to conduction of clinical trials, to enriched therapeutic possibilities for improving TR access to treatment and outcomes in routine practice is complex. Therefore, this paper summarizes the key points and methods crucial to TR detection, quantitation, categorization, risk-scoring, intervention-monitoring, and outcomes evaluation, particularly of right-sided function, and to clinical trial development and conduct, for both interventional and surgical groups.

Impact of the COVID-19 Pandemic on Global TAVR Activity: The COVID-TAVI Study.

BACKGROUND: The COVID-19 pandemic adversely affected health care systems. Patients in need of transcatheter aortic valve replacement (TAVR) are especially susceptible to treatment delays. OBJECTIVES: This study sought to evaluate the impact of the COVID-19 pandemic on global TAVR activity. METHODS: This international registry reported monthly TAVR case volume in participating institutions prior to and during the COVID-19 pandemic (January 2018 to December 2021). Hospital-level information on public vs private, urban vs rural, and TAVR volume was collected, as was country-level information on socioeconomic status, COVID-19 incidence, and governmental public health responses. RESULTS: We included 130 centers from 61 countries, including 65,980 TAVR procedures. The first and second pandemic waves were associated with a significant reduction of 15% (P < 0.001) and 7% (P < 0.001) in monthly TAVR case volume, respectively, compared with the prepandemic period. The third pandemic wave was not associated with reduced TAVR activity. A greater reduction in TAVR activity was observed in Africa (-52%; P = 0.001), Central-South America (-33%; P < 0.001), and Asia (-29%; P < 0.001). Private hospitals (P = 0.005), urban areas (P = 0.011), low-volume centers (P = 0.002), countries with lower development (P < 0.001) and economic status (P < 0.001), higher COVID-19 incidence (P < 0.001), and more stringent public health restrictions (P < 0.001) experienced a greater reduction in TAVR activity. CONCLUSIONS: TAVR procedural volume declined substantially during the first and second waves of the COVID-19 pandemic, especially in Africa, Central-South America, and Asia. National socioeconomic status, COVID-19 incidence, and public health responses were associated with treatment delays. This information should inform public health policy in case of future global health crises.

Residual tricuspid regurgitation after tricuspid transcatheter edge-to-edge repair: Insights into the EuroTR registry.

AIMS: Data on the prognostic impact of residual tricuspid regurgitation (TR) after tricuspid transcatheter edge-to-edge repair (T-TEER) are scarce. The aim of this analysis was to evaluate 2-year survival and symptomatic outcomes of patients in relation to residual TR after T-TEER. METHODS AND RESULTS: Using the large European Registry of Transcatheter Repair for Tricuspid Regurgitation (EuroTR registry) we investigated the impact of residual TR on 2-year all-cause mortality and New York Heart Association (NYHA) functional class at follow-up. The study further identified predictors for residual TR ≥3+ using a logistic regression model. The study included a total of 1286 T-TEER patients (mean age 78.0 ± 8.9 years, 53.6% female). TR was successfully reduced to ≤1+ in 42.4%, 2+ in 40.0% and 3+ in 14.9% of patients at discharge, while 2.8% remained with TR ≥4+ after the procedure. Residual TR ≥3+ was an independent multivariable predictor of 2-year all-cause mortality (hazard ratio 2.06, 95% confidence interval 1.30-3.26, p = 0.002). The prevalence of residual TR ≥3+ was four times higher in patients with higher baseline TR (vena contracta >11.1 mm) and more severe tricuspid valve tenting (tenting area >1.92 cm2). Of note, no survival difference was observed in patients with residual TR ≤1+ versus 2+ (76.2% vs. 73.1%, p = 0.461). The rate of NYHA functional class ≥III at follow-up was significantly higher in patients with residual TR ≥3+ (52.4% vs. 40.5%, p < 0.001). Of note, the degree of TR reduction significantly correlated with the extent of symptomatic improvement (p = 0.012). CONCLUSIONS: T-TEER effectively reduced TR severity in the majority of patients. While residual TR ≥3+ was associated with worse outcomes, no differences were observed for residual TR 1+ versus 2+. Symptomatic improvement correlated with the degree of TR reduction.

Cardiac arrest centres: What do they add?

There are wide regional variations in outcome following resuscitated out of hospital cardiac arrest. These geographical differences appear to be due to hospital infrastructure and provider experience rather than baseline characteristics. It is proposed that post-arrest care be delivered in a systematic fashion by concentrating services in Cardiac Arrest Centres, with greater provider experience, 24-hour access to diagnostics, and specialist treatment to minimise the impact of ischaemia-reperfusion injury and treat the causative pathology. These cardiac arrest centres would provide access to targeted critical care, acute cardiac care, radiology services and appropriate neuro-prognostication. However implementation of cardiac arrest networks with specialist receiving hospitals is complex and requires alignment of pre-hospital care services with those delivered in hospital. Furthermore there are no randomised trial data currently supporting pre-hospital delivery to a Cardiac Arrest Centre and definitions are heterogeneous. In this review article, we propose a universal definition of a Cardiac Arrest Centre and review the current observational data evidence and the potential impact of the ARREST trial.

Management of coronary artery disease in patients with aortic stenosis.

Aortic stenosis (AS) is the most common valvular heart disorder in the elderly population. As a result of the shared pathophysiological processes, AS frequently coexists with coronary artery disease (CAD). These patients have traditionally been managed through surgical aortic valve replacement (SAVR) and coronary artery bypass grafting. However, increasing body of evidence supports transcatheter aortic valve implantation (TAVI) as an alternative treatment for severe AS across the spectrum of operative risk. This has created the potential for treating AS and concurrent CAD completely percutaneously. In this review we consider the evidence guiding the optimal management of patients with severe AS and CAD. While invasive coronary angiography plays a central role in detecting CAD in patients with AS undergoing surgery or TAVI, the benefits of complementary functional assessment of coronary stenosis in the context of AS have not been fully established. Although the indications for revascularisation of significant proximal CAD in SAVR patients have not recently changed, routine revascularisation of all significant CAD before TAVI in patients with minimal angina is not supported by the latest evidence. Several ongoing trials will provide new insights into physiology-guided revascularisation in TAVI recipients. The role of the heart team remains essential in this complex patient group, and if revascularisation is being considered careful evaluation of clinical, anatomical and procedural factors is essential for individualised decision-making.

Conventional aortic root vs valve-sparing root replacement surgery in aortic dilatation syndromes: a comparison of mortality and postoperative complications.

INTRODUCTION: Conventional aortic root and valve-sparing root replacement surgery are two current surgical treatments for aortic dilatation syndromes. This review article aims to review the current literature surrounding these two established techniques. AREAS COVERED: This review article will address the current indications for valve-sparing root replacement surgery, technical considerations in surgical planning and a comparison of clinical outcomes between these two surgical techniques. EXPERT OPINION: Valve-sparing root replacement surgery is a safe and established treatment for aortic syndromes. Valve-sparing surgery procedure avoids the inherent risk of prosthetic valve dysfunction and prosthesis infection by preserving the native aortic valve compared to conventional aortic root surgery. This has been demonstrated in various observational studies and should be considered in clinically and anatomically appropriate patients. Other technical considerations, such as reimplantation versus remodeling technique and aortic cusp repair in select patients, may impact in short-term procedural and long-term clinical success with valve-sparing surgery.

Safety and efficacy of pembrolizumab for advanced nonsmall cell lung cancer: before and during the COVID-19 pandemic.

PURPOSE: The COVID-19 pandemic changed diagnostic and treatment pathways in oncology. We compared the safety and efficacy of pembrolizumab amongst advanced nonsmall cell lung cancer (NSCLC) patients with a PD-L1 tumor proportion score (TPS) ≥ 50% before and during the pandemic. METHODS: Advanced NSCLC patients initiating pembrolizumab between June 2015 and December 2019 ("pre-pandemic cohort") and between March 2020 and March 2021 ("pandemic cohort") at BC Cancer were identified retrospectively. Multivariable logistic regression evaluated risk factors for immune-related adverse events (irAE) ≥ grade 3 at the 6 week, 3 month, and 6 month landmarks. Cox regression models of overall survival (OS) were constructed. RESULTS: The study population comprised 417 patients in the pre-pandemic cohort and 111 patients in the pandemic cohort. Between March and May 2020, 48% fewer advanced NSCLC cases with PD-L1 TPS ≥ 50% were diagnosed compared to similar intervals in 2018-2019. Telemedicine assessment [new patient consultations (p < 0.001) and follow-up (p < 0.001)] and extended interval pembrolizumab dosing (p < 0.001) were more common in the pandemic cohort. Patients initiating pembrolizumab after February 2020 (vs. before January 2020) experienced similar odds of developing severe irAE. 2/111 (1.8%) patients receiving pembrolizumab during the pandemic tested positive for COVID-19. On multivariable analysis, no association between pembrolizumab treatment period (before vs. during the COVID-19 pandemic) and OS was observed (p = 0.18). CONCLUSION: Significant changes in healthcare delivery in response to the pandemic did not result in increased high grade toxicity or lower survival outcomes in patients with advanced NSCLC treated with pembrolizumab.