Neuronal inhibition of the autophagy nucleation complex extends life span in post-reproductive C. elegans.

Autophagy is a ubiquitous catabolic process that causes cellular bulk degradation of cytoplasmic components and is generally associated with positive effects on health and longevity. Inactivation of autophagy has been linked with detrimental effects on cells and organisms. The antagonistic pleiotropy theory postulates that some fitness-promoting genes during youth are harmful during aging. On this basis, we examined genes mediating post-reproductive longevity using an RNAi screen. From this screen, we identified 30 novel regulators of post-reproductive longevity, including pha-4 Through downstream analysis of pha-4, we identified that the inactivation of genes governing the early stages of autophagy up until the stage of vesicle nucleation, such as bec-1, strongly extend both life span and health span. Furthermore, our data demonstrate that the improvements in health and longevity are mediated through the neurons, resulting in reduced neurodegeneration and sarcopenia. We propose that autophagy switches from advantageous to harmful in the context of an age-associated dysfunction.

Single arterial access closure of post-infarction ventricular septal defect: A case series.

BACKGROUND: Post-infarction ventricular septal defect (PIVSD) carries a very poor prognosis. Surgical repair offers reasonable outcomes in patients who survive the initial healing period. Percutaneous device implantation remains a potentially effective earlier alternative. METHODS AND RESULTS: From March 2018 to May 2022, 11 trans-arterial PIVSD closures were attempted in 9 patients from two centers (aged 67.2 ± 11.1 years; 77.8% male). Two patients had a second procedure. Myocardial infarction was anterior in four patients (44.5%) and inferior in five cases (55.5%). Devices were successfully implanted in all patients. There were no major immediate procedural complications. Immediate shunt grade postprocedure was significant (11.1%), minimal (77.8%), or none (11.1%). Median length of stay after the procedure was 14.8 days. Five patients (55%) survived to discharge and were followed up for a median of 605 days, during which time no additional patients died. CONCLUSION: Single arterial access for percutaneous closure of PIVSD is a good option for these extremely high-risk patients, in the era of effective large-bore arterial access closure. Mortality remains high, but patients who survive to discharge do well in the longer term.

Intravascular lithotripsy in the treatment of coronary artery calcification in a high-risk real world population.

BACKGROUND: The DISRUPT-CAD study series demonstrated feasibility and safety of intravascular lithotripsy (IVL) in selected patients, but applicability across a broad range of clinical scenarios remains unclear. AIMS: This study aims to evaluate the procedural and clinical outcomes of IVL in a high-risk real-world cohort, compared to a regulatory approval cohort. METHODS: Consecutive patients treated with IVL and percutaneous coronary intervention at our center from May 2016 to April 2020 were included. Comparison was made between those enrolled in the DISRUPT-CAD series of studies to those with calcified lesions but an exclusion criteria. RESULTS: Among 177 patients treated with IVL, 142 were excluded from regulatory trials due to acute coronary syndrome presentation (47.2%), left ventricular ejection fraction <40% (22.5%), chronic renal failure (12.0%), or use of mechanical circulatory support (8.5%). This clinical cohort had a higher SYNTAX score (22.6 ± 12.1 vs. 17.4 ± 9.9, p = 0.019), and more treated ACC/AHA C lesions (56.3% vs. 37.1%, p = 0.042). Rates of device success (93.7% vs. 100.0%, p = 0.208), procedural success (96.5% vs. 100.0%, p = 0.585), and minimal lumen area gain (221.2 ± 93.7% vs. 198.6 ± 152.0%, p = 0.807) were similar in both groups. The DISRUPT-CAD cohort had no in-hospital mortality, 30-day major adverse cardiac events (MACE), or 30-day target vessel revascularization (TVR). The clinical cohort had an in-hospital mortality of 4.2%, 30-day MACE of 7.8%, and 30-day TVR of 1.5%. There was no difference in 12-month TVR (2.9% vs. 2.2%; p = 0.825). Twelve-month MACE was higher in the clinical cohort (21.1% vs. 8.6%, p = 0.03). CONCLUSION: IVL use remains associated with high clinical efficacy, procedural success, and low complication rates in a real-world population previously excluded from regulatory approving trials.

A machine learning algorithm to predict a culprit lesion after out of hospital cardiac arrest.

BACKGROUND: We aimed to develop a machine learning algorithm to predict the presence of a culprit lesion in patients with out-of-hospital cardiac arrest (OHCA). METHODS: We used the King's Out-of-Hospital Cardiac Arrest Registry, a retrospective cohort of 398 patients admitted to King's College Hospital between May 2012 and December 2017. The primary outcome was the presence of a culprit coronary artery lesion, for which a gradient boosting model was optimized to predict. The algorithm was then validated in two independent European cohorts comprising 568 patients. RESULTS: A culprit lesion was observed in 209/309 (67.4%) patients receiving early coronary angiography in the development, and 199/293 (67.9%) in the Ljubljana and 102/132 (61.1%) in the Bristol validation cohorts, respectively. The algorithm, which is presented as a web application, incorporates nine variables including age, a localizing feature on electrocardiogram (ECG) (≥2 mm of ST change in contiguous leads), regional wall motion abnormality, history of vascular disease and initial shockable rhythm. This model had an area under the curve (AUC) of 0.89 in the development and 0.83/0.81 in the validation cohorts with good calibration and outperforms the current gold standard-ECG alone (AUC: 0.69/0.67/0/67). CONCLUSIONS: A novel simple machine learning-derived algorithm can be applied to patients with OHCA, to predict a culprit coronary artery disease lesion with high accuracy.

Post-infarction ventricular septal defect: percutaneous or surgical management in the UK national registry.

AIMS: Post-infarction ventricular septal defect (PIVSD) is a mechanical complication of acute myocardial infarction (AMI) with a poor prognosis. Surgical repair is the mainstay of treatment, although percutaneous closure is increasingly undertaken. METHODS AND RESUTS: Patients treated with surgical or percutaneous repair of PIVSD (2010-2021) were identified at 16 UK centres. Case note review was undertaken. The primary outcome was long-term mortality. Patient groups were allocated based upon initial management (percutaneous or surgical). Three-hundred sixty-two patients received 416 procedures (131 percutaneous, 231 surgery). 16.1% of percutaneous patients subsequently had surgery. 7.8% of surgical patients subsequently had percutaneous treatment. Times from AMI to treatment were similar [percutaneous 9 (6-14) vs. surgical 9 (4-22) days, P = 0.18]. Surgical patients were more likely to have cardiogenic shock (62.8% vs. 51.9%, P = 0.044). Percutaneous patients were substantially older [72 (64-77) vs. 67 (61-73) years, P < 0.001] and more likely to be discussed in a heart team setting. There was no difference in long-term mortality between patients (61.1% vs. 53.7%, P = 0.17). In-hospital mortality was lower in the surgical group (55.0% vs. 44.2%, P = 0.048) with no difference in mortality after hospital discharge (P = 0.65). Cardiogenic shock [adjusted hazard ratio (aHR) 1.97 (95% confidence interval 1.37-2.84), P < 0.001), percutaneous approach [aHR 1.44 (1.01-2.05), P = 0.042], and number of vessels with coronary artery disease [aHR 1.22 (1.01-1.47), P = 0.043] were independently associated with long-term mortality. CONCLUSION: Surgical and percutaneous repair are viable options for management of PIVSD. There was no difference in post-discharge long-term mortality between patients, although in-hospital mortality was lower for surgery.

Outcomes following PCI in CABG candidates during the COVID-19 pandemic: The prospective multicentre UK-ReVasc registry.

OBJECTIVES: To describe outcomes following percutaneous coronary intervention (PCI) in patients who would usually have undergone coronary artery bypass grafting (CABG). BACKGROUND: In the United Kingdom, cardiac surgery for coronary artery disease (CAD) was dramatically reduced during the first wave of the COVID-19 pandemic. Many patients with "surgical disease" instead underwent PCI. METHODS: Between 1 March 2020 and 31 July 2020, 215 patients with recognized "surgical" CAD who underwent PCI were enrolled in the prospective UK-ReVasc Registry (ReVR). 30-day major cardiovascular event outcomes were collected. Findings in ReVR patients were directly compared to reference PCI and isolated CABG pre-COVID-19 data from British Cardiovascular Intervention Society (BCIS) and National Cardiac Audit Programme (NCAP) databases. RESULTS: ReVR patients had higher incidence of diabetes (34.4% vs 26.4%, P = .008), multi-vessel disease with left main stem disease (51.4% vs 3.0%, P < .001) and left anterior descending artery involvement (94.8% vs 67.2%, P < .001) compared to BCIS data. SYNTAX Score in ReVR was high (mean 28.0). Increased use of transradial access (93.3% vs 88.6%, P = .03), intracoronary imaging (43.6% vs 14.4%, P < .001) and calcium modification (23.6% vs 3.5%, P < .001) was observed. No difference in in-hospital mortality was demonstrated compared to PCI and CABG data (ReVR 1.4% vs BCIS 0.7%, P = .19; vs NCAP 1.0%, P = .48). Inpatient stay was half compared to CABG (3.0 vs 6.0 days). Low-event rates in ReVR were maintained to 30-day follow-up. CONCLUSIONS: PCI undertaken using contemporary techniques produces excellent short-term results in patients who would be otherwise CABG candidates. Longer-term follow-up is essential to determine whether these outcomes are maintained over time.

16S rDNA PCR for the aetiological diagnosis of culture-negative infective endocarditis.

INTRODUCTION: Culture-negative infective endocarditis (IE) accounts for 7-31% of all cases. Metagenomics has contributed to improving the aetiological diagnosis of IE patients undergoing valve surgery. We assessed the impact of 16S ribosomal DNA gene polymerase chain reaction (16S rDNA PCR) in the aetiological diagnosis of culture-negative IE. METHODS: Between January 2016 and January 2020, clinical data from culture-negative IE patients were reviewed retrospectively. Identification of bacteria was performed using 16S rDNA PCR in heart valve specimens. RESULTS: 36 out of 313 patients (12%) with culture-negative IE had their valve tissue specimens submitted for 16S rDNA PCR. 16S rDNA PCR detected and identified bacterial nucleic acid in heart valve tissue significantly more frequently compared to valve culture alone 25(70%) vs 5(12%); p < 0.05. Mean age was 57 years (SD 18) and 80% were male. Native and aortic valve were involved in 76% and 52% of cases, respectively. Streptococcus spp. (n 15) were the most commonly detected organisms, followed by bacteria of the HACEK group (Haemophilus parainfluenzae 2, Aggregatibacter actinomycetemcomitans 1), nutritionally variant streptococci (Abiotrophia defectiva 2), and one each of Staphylococcus aureus, Corynebacterium pseudodiphtheriticum, Helcococcus kunzii, Neisseria gonorrhoeae, Tropheryma whipplei. CONCLUSION: 16S rDNA PCR may be a useful diagnostic tool for the identification of the causative organism in culture-negative IE. Efforts towards a shorter turnaround time for results should be consider and further studies assessing the clinical impact of this technique in culture-negative IE are needed.

Contemporary Evidence-Based Diagnosis and Management of Severe Coronary Artery Calcification.

Percutaneous treatment of heavily calcified coronary lesions remains a challenge for interventional cardiologists with increased risk of incomplete lesion preparation, suboptimal stent deployment, procedural complications, and a higher rate of acute and late stent failure. Adequate lesion preparation through calcium modification is crucial in optimising procedural outcomes. Several calcium modification devices and techniques exist, with rotational atherectomy the predominant treatment for severely calcified lesions. Novel technologies such as intravascular lithotripsy are now available and show promise as a less technical and highly effective approach for calcium modification. Emerging evidence also emphasises the value of detailed characterisation of calcification severity and distribution especially with intracoronary imaging for appropriate device selection and individualised treatment strategy. This review aims to provide an overview of the non-invasive and invasive evaluation of coronary calcification, discuss calcium modification techniques and propose an algorithm for the management of calcified coronary lesions.

SCAI cardiogenic shock classification after out of hospital cardiac arrest and association with outcome.

OBJECTIVES: We aimed to validate the Society for Cardiovascular Angiography and Interventions (SCAI) classification to evaluate association with outcome in a real-world population and effect of invasive therapies. BACKGROUND: Cardiogenic shock is common after Out of Hospital Cardiac Arrest (OOHCA) but is often multifactorial and challenging to stratify. METHODS: The SCAI shock grade was applied to an observational registry of OOHCA patients on admission to our center between 2012 and 2017. The primary end-point was 30-day mortality and secondary end-points were mode of death and 12-month mortality. Provision of early CAG and mechanical circulatory support (MCS) was evaluated by SCAI shock grade using logistic regression. RESULTS: Three hundred and ninety-three patients (median age 64.3 years (24.9% females) were included. One hundred and seven patients (27.2%) were in Grade A, 94 (23.9%) in Grade B, 66 (16.8%) in Grade C, 91 (23.2%) in Grade D, and 35 (8.9%) in Grade E. There was a step-wise significant increase in 30-day mortality with increasing shock grade (A 28.9% vs. B 33.0% vs. C 54.5% vs. D 59.3% vs. E 82.9%; p < .0001). With worsening shock grade, requirement for renal replacement therapy and mortality from multiorgan dysfunction syndrome and cardiogenic causes increased. Early CAG was performed equally in all groups but was significantly associated with reduced mortality in SCAI grade D only (OR 0.26 [CI 0.08-0.91], p = .036). CONCLUSIONS: Increasing SCAI shock grade after OOHCA is associated with 30-day mortality, requirement for renal replacement therapy and mortality attributed to multiorgan dysfunction syndrome and cardiac etiology death.

Interdisciplinary Communication Needs to Become a Core Scientific Skill.

As scientific research has advanced so too has the complexity of the questions addressed. Cross-disciplinary collaborations are often the most efficient route to managing that complexity and require effective communication across boundaries. To continue driving science forward and be able to tackle global challenges, the art of good interdisciplinary communication needs to become a core skill in a scientist's portfolio.

A practical risk score for early prediction of neurological outcome after out-of-hospital cardiac arrest: MIRACLE2.

AIMS: The purpose of this study was to develop a practical risk score to predict poor neurological outcome after out-of-hospital cardiac arrest (OOHCA) for use on arrival to a Heart Attack Centre. METHODS AND RESULTS: From May 2012 to December 2017, 1055 patients had OOHCA in our region, of whom 373 patients were included in the King's Out of Hospital Cardiac Arrest Registry (KOCAR). We performed prediction modelling with multivariable logistic regression to identify predictors of the primary outcome to derive a risk score. This was externally validated in two independent cohorts comprising 473 patients. The primary endpoint was poor neurological outcome at 6-month follow-up (Cerebral Performance Category 3-5). Seven independent predictors of outcome were identified: missed (unwitnessed) arrest, initial non-shockable rhythm, non-reactivity of pupils, age (60-80 years-1 point; >80 years-3 points), changing intra-arrest rhythms, low pH <7.20, and epinephrine administration (2 points). The MIRACLE2 score had an area under the curve (AUC) of 0.90 in the development and 0.84/0.91 in the validation cohorts. Three risk groups were defined-low risk (MIRACLE2 ≤2-5.6% risk of poor outcome); intermediate risk (MIRACLE2 of 3-4-55.4% of poor outcome); and high risk (MIRACLE2 ≥5-92.3% risk of poor outcome). The MIRACLE2 score had superior discrimination than the OHCA [median AUC 0.83 (0.818-0.840); P < 0.001] and Cardiac Arrest Hospital Prognosis models [median AUC 0.87 (0.860-0.870; P = 0.001] and equivalent performance with the Target Temperature Management score [median AUC 0.88 (0.876-0.887); P = 0.092]. CONCLUSIONS: The MIRACLE2 is a practical risk score for early accurate prediction of poor neurological outcome after OOHCA, which has been developed for simplicity of use on admission.

Leveraging Deep Learning for Visual Odometry Using Optical Flow.

In this paper, we study deep learning approaches for monocular visual odometry (VO). Deep learning solutions have shown to be effective in VO applications, replacing the need for highly engineered steps, such as feature extraction and outlier rejection in a traditional pipeline. We propose a new architecture combining ego-motion estimation and sequence-based learning using deep neural networks. We estimate camera motion from optical flow using Convolutional Neural Networks (CNNs) and model the motion dynamics using Recurrent Neural Networks (RNNs). The network outputs the relative 6-DOF camera poses for a sequence, and implicitly learns the absolute scale without the need for camera intrinsics. The entire trajectory is then integrated without any post-calibration. We evaluate the proposed method on the KITTI dataset and compare it with traditional and other deep learning approaches in the literature.

A contemporary and complete treatment solution for a high-risk patient with critical aortic stenosis, left ventricular thrombus, severe left ventricular dysfunction, and calcified left main stem disease.

The combination of severe coronary disease, significant valvular dysfunction and impaired ventricular function pose patients at a very high procedural risk. In addition, the presence of left ventricular thrombus can complicate ventricular instrumentation increasing embolic risk. Contemporary techniques and devices have now become available to overcome these challenges to reduce risk and allow safer, more efficient procedures. We describe the feasibility of using Impella CP™ with cerebral protection to facilitate complete revascularisation and percutaneous valve replacement in a patient with critical aortic stenosis, severe left ventricular (LV) impairment, LV thrombus and a calcified left main stem disease.

Efficient Star Identification Using a Neural Network.

The required precision for attitude determination in spacecraft is increasing, providing a need for more accurate attitude determination sensors. The star sensor or star tracker provides unmatched arc-second precision and with the rise of micro satellites these sensors are becoming smaller, faster and more efficient. The most critical component in the star sensor system is the lost-in-space star identification algorithm which identifies stars in a scene without a priori attitude information. In this paper, we present an efficient lost-in-space star identification algorithm using a neural network and a robust and novel feature extraction method. Since a neural network implicitly stores the patterns associated with a guide star, a database lookup is eliminated from the matching process. The search time is therefore not influenced by the number of patterns stored in the network, making it constant (O(1)). This search time is unrivalled by other star identification algorithms. The presented algorithm provides excellent performance in a simple and lightweight design, making neural networks the preferred choice for star identification algorithms.

A Survey of Lost-in-Space Star Identification Algorithms since 2009.

The lost-in-space star identification algorithm is able to identify stars without a priori attitude information and is arguably the most critical component of a star sensor system. In this paper, the 2009 survey by Spratling and Mortari is extended and recent lost-in-space star identification algorithms are surveyed. The covered literature is a qualitative representation of the current research in the field. A taxonomy of these algorithms based on their feature extraction method is defined. Furthermore, we show that in current literature the comparison of these algorithms can produce inconsistent conclusions. In order to mitigate these inconsistencies, this paper lists the considerations related to the relative performance evaluation of these algorithms using simulation.

An Evaluation of Low-Cost Vision Processors for Efficient Star Identification.

Star trackers are navigation sensors that are used for attitude determination of a satellite relative to certain stars. A star tracker is required to be accurate and also consume as little power as possible in order to be used in small satellites. While traditional approaches use lookup tables for identifying stars, the latest advances in star tracking use neural networks for automatic star identification. This manuscript evaluates two low-cost processors capable of running a star identification neural network, the Intel Movidius Myriad 2 Vision Processing Unit (VPU) and the STM32 Microcontroller. The intention of this manuscript is to compare the accuracy and power usage to evaluate the suitability of each device for use in a star tracker. The Myriad 2 VPU and the STM32 Microcontroller have been specifically chosen because of their performance on computer vision algorithms alongside being cost-effective and low power consuming devices. The experimental results showed that the Myriad 2 proved to be efficient and consumed around 1 Watt of power while maintaining 99.08% accuracy with an input including false stars. Comparatively the STM32 was able to deliver comparable accuracy (99.07%) and power measurement results. The proposed experimental setup is beneficial for small spacecraft missions that require low-cost and low power consuming star trackers.

Transcatheter Valve-in-Valve Therapy Using a Balloon Expanding Valve for Treatment of Aortic Paravalvular Leakage.

Aortic paravalvular leakage (PVL) is a recognised complication of surgically replaced valves which is often treated using vascular plugs. Whilst transcatheter valve-in-valve therapy has been increasingly used for failed surgical bioprostheses, it is not considered as a treatment option for aortic PVL. However, the newer design of transcatheter aortic valves has a fabric skirt to create a more effective seal around the annulus. To our best knowledge, for the first time, we report successful adoption of the valve-in-valve therapy for the treatment of PVL in surgical bioprosthetic aortic valves such that the fabric skirt is placed immediately below the regurgitant orifice resulting in significant reduction in the PVL.

3DTEE imaging of a descending aorta floating thrombus in a patient with calciphylaxis.

We present a case of a 68-year-old man with calciphylaxis, who was found to have a floating thrombus in the descending aorta on a transesophageal echocardiogram. The use of 3D echocardiography demonstrated nicely the free motion of the thrombus, emerging from an atherosclerotic plaque in the descending aorta. Anticoagulation was started for thromboembolism prevention.

Optimized Outcomes Using a Standardized Approach for the Treatment of Patients with Carcinoid Heart Disease.

BACKGROUND: Carcinoid heart disease (CHD) is common in patients with carcinoid syndrome (CS). Surgical treatment improves the poor prognosis of CHD, although the reported peri-operative mortality is high (∼17%). We attempted to improve outcomes by implementation of a protocol for the management of patients with CHD at a UK Neuroendocrine Centre of Excellence and report our experience. METHODS: All patients treated for CHD between 2008 and 2015 were included. Peri-operative treatment included surgical features such as invasive pulmonary valve (PV) inspection and preservation of the tricuspid subvalvular apparatus. RESULTS: A total of 11 patients were treated; the median age was 63 years (IQR: 56-70). Ten patients underwent both pulmonary valve replacement (PVR) and tricuspid valve replacement (TVR); 1 patient underwent isolated TVR. One patient had additional aortic valve replacement (AVR), another one coronary artery bypass grafting. Bioprostheses (BP) were used in all patients, stented for TVR and AVR, stentless for PVR. Invasive PV inspection caused unplanned PVR in 3 cases (27.3%). All patients were discharged home. One patient (9.1%), who had had previous TVR by another surgeon, had right heart failure (RHF) during follow-up. One death occurred due to progression of CS (day 346). The carcinoids' primary was resected in 5 patients (45.5%) 10 months (4.5-19.5) after cardiac surgery. CONCLUSION: Excellent results were achieved in patients with CHD. PV stenosis can be underestimated by echocardiography; therefore, intraoperative inspection is recommended. Right ventricular geometry should be respected to prevent RHF. BP should be used, as these patients are likely to undergo future non-cardiac surgeries.