High Events Research Articles

Predictors of vessel quantitative flow ratio loss in patients with severely calcified lesions after rotational atherectomy.

Previous studies have established that moderately to severely calcified lesions (MSCL) are associated with high rates of major adverse cardiovascular events, even when drug-eluting stents are implanted after rotational atherectomy (RA). Yet, the changes in coronary function indexes during follow-ups have never been investigated. The quantitative flow ratio (QFR), a novel coronary function index, has been increasingly adopted in daily practice in recent years. A total of 111 MSCL patients were retrospectively enrolled in this study. The vessel QFR (QFRv) loss was defined as post-percutaneous coronary intervention QFRv minus follow-up QFRv. The study subjects were divided into high QFRv loss (n = 51) and low QFRv loss (n = 60) groups according to the binary method. The obtained predictors of QFRv loss were then analyzed. The results showed that the final burr-to-vessel ratio (B to V ratio) in the high QFRv loss group decreased significantly compared to the low QFRv loss group (p < 0.01). The univariate and multivariate regression analyses indicated that the final B to V ratio was an excellent predictor of QFRv loss. The cut-off value of the final B to V ratio for QFRv loss prediction was 0.50 (sensitivity: 50.98%, specificity: 68.33%, and area under the curve: 0.627 [95% confidence interval: 0.530-0.717], p < 0.05). Additionally, the target vessel failure incidence in the high QFRv loss group was higher than in the low QFRv loss group (p < 0.01). An increased burr-to-vessel ratio can prevent QFRv loss in patients with MSCLs after RA, an effect that might be closely associated with a low target vessel failure incidence.

PD-1/PD-L1 immune checkpoint inhibitors in metastatic triple-negative breast cancer: a systematic review and meta-analysis.

PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have been controversial in the treatment of metastatic triple negative breast cancer (mTNBC). We collected randomized controlled trials in accordance with the study and carried out meta-analysis to comprehensively evaluate the efficacy and safety of immune checkpoint inhibitors in mTNBC. To systematically evaluate the efficacy and safety of PD-1/PD-L1 ICIs (hereinafter referred to as ICIs) in the treatment of mTNBC. As of 2023.2.5, Medline, PubMed, Embase, Cochrane library database and Web of Science were searched to determine the study in accordance with the trial of ICIs in the treatment of mTNBC. The assessment endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Meta-analysis of the included studies was performed using Revman 5.4. A total of six trials with 3172 patients were included in this meta-analysis. The ORR of ICIs combined with chemotherapy was significantly improved compared with chemotherapy (HR=0.88, 95%CI: 0.81-0.94, I2=0%). For PFS, the experimental group were better than the control group in both intention-to-treat (ITT) population and PD-L1 positive population, showing statistical significance (ITT: HR=0.81, 95%CI: 0.74-0.89, P<0.05, I2=0%; PD-L1 positive: HR=0.72, 95%CI: 0.63-0.82, P<0.05, I2=18%); For OS, in the ITT population, no statistical difference was observed in either ICIs combined with chemotherapy(HR=0.92, 95%CI: 0.83-1.02, P=0.10)or immune monotherapy(HR=0.78, 95%CI: 0.44-1.36, P=0.37), in the PD-L1 positive population, ICIs group had better OS than chemotherapy group (HR=0.83, 95%CI: 0.74-0.93, P < 0.05); In safety, serious adverse event (SAE) was no statistically significant difference between the ICIs group and the chemotherapy group; however, the incidence of immune-related adverse event (irAE) was significantly higher in the ICIs group than in the chemotherapy group (HR=2.15, 95%CI: 1.45-3.19, P < 0.05). ICIs combined with chemotherapy significantly improved the PFS of mTNBC, however, ICIs only improved the OS in PD-L1 positive people, and no statistical difference was observed in ITT population; while benefiting from ICIs, we found that irAE in ICIs group increased significantly, and its high rate of adverse events still needs to be taken seriously.

Time to clinical improvement: an appropriate surrogate endpoint for pulmonary arterial hypertension medication trials.

Many retrospective studies suggest that risk improvement may be a suitable efficacy surrogate endpoint for pulmonary arterial hypertension (PAH) medication trials. This prospective multicenter study assessed the efficacy of domestic ambrisentan in Chinese PAH patients and observed risk improvement and time to clinical improvement (TTCI) under ambrisentan treatment. Eligible patients with PAH were enrolled for a 24-week treatment with ambrisentan. The primary efficacy endpoint was 6-min walk distance (Δ6MWD). The exploratory endpoints were risk improvement and TTCI, defined as the time from initiation of treatment to the first occurrence of risk improvement. A total of 83 subjects were enrolled. After ambrisentan treatment, Δ6MWD was significantly increased at week 12 (42.2 m, P < 0.0001) and week 24 (53.4 m, P < 0.0001). Within 24 weeks, risk improvement was observed in 53 (64.6%) subjects (P < 0.0001), which is higher than WHO-FC (30.5%) and TAPSE/PASP (32.9%). Kaplan-Meier analysis of TTCI showed a median improvement time of 131 days and a cumulative improvement rate of 75.1%. Also, TTCI is consistent across different baseline risk status populations (log-rank P = 0.51). The naive group had more risk improvement (P = 0.043) and shorter TTCI (log-rank P = 0.008) than the add-on group, while Δ6MWD did not show significant differences between the two groups. Domestic ambrisentan significantly improved the exercise capacity and risk status of Chinese PAH patients. TTCI has a relatively high positive event rate within 24-week treatment duration. Compared to Δ6MWD, TTCI is not affected by baseline risk status. Additionally, TTCI could identify better improvements in patients, which Δ6MWD does not detect. TTCI is an appropriate composite surrogate endpoint for PAH medication trials. NCT No. [ClinicalTrials.gov], identifier [NCT05437224].

Association of intravascular enhancement sign detected on high-resolution vessel wall imaging with ischaemic events in middle cerebral artery occlusion

PurposePatients with intracranial artery occlusion have high rates of ischaemic events and recurrence. Early identification of patients with high-risk factors is therefore beneficial for prevention. Here we assessed the association between the intravascular enhancement sign (IVES) on high-resolution vessel wall imaging (HR-VWI) and acute ischaemic stroke (AIS) in a population with middle cerebral artery (MCA) occlusion. MethodWe retrospectively analysed the records of 106 patients with 111 MCA occlusions, including 60 with and 51 without AIS, who had undergone HR-VWI and computed tomography angiography (CTA) examinations from November 2016 to February 2023. Numbers of IVES vessels were counted and compared to the CTA findings. Statistical analyses of demographic and medical data were also performed. ResultsOccurrence rates and numbers of IVES vessels were significantly higher in the AIS than the non-AIS group (P < 0.05), and most vessels were detected on CTA. Numbers of vessels positively correlated with AIS occurrence (rho = 0.664; P < 0.0001). A multivariable ordinal logistic regression model adjusted for age, degree of wall enhancement, hypertension, and heart status identified the number of IVES vessels as an independent predictor for AIS (odds ratio = 1.6; 95% CI, 1.3–1.9; P < 0.0001). ConclusionNumber of IVES vessels is an independent risk factor for AIS events, and may represent poor cerebral blood flow status and collateral compensation level. It thus provides cerebral haemodynamic information for patients with MCA occlusion for clinical use.

A FPGA-Based Architecture for Real-Time Cluster Finding in the LHCb Silicon Pixel Detector

This article describes a custom VHDL firmware implementation of a two-dimensional cluster-finder architecture for reconstructing hit positions in the new vertex pixel detector (VELO) that is part of the LHCb Upgrade. This firmware has been deployed to the existing FPGA cards that perform the readout of the VELO, as a further enhancement of the DAQ system, and will run in real time during physics data taking, reconstructing VELO hits coordinates on-the-fly at the LHC collision rate. This pre-processing allows the first level of the software trigger to accept a 11% higher rate of events, as the ready-made hits coordinates accelerate the track reconstruction and consumes significantly less electrical power. It additionally allows the raw pixel data to be dropped at the readout level, thus saving approximately 14% of the DAQ bandwidth. Detailed simulation studies have shown that the use of this real-time cluster finding does not introduce any appreciable degradation in the tracking performance in comparison to a full-fledged software implementation. This work is part of a wider effort aimed at boosting the real-time processing capability of HEP experiments by delegating intensive tasks to dedicated computing accelerators deployed at the earliest stages of the data acquisition chain.

MONOCYTE DERIVED CYTOKINES INDUCE ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH PRIMARY ALDOSTERONISM

Objective: Due to aldosterone excess and its pleotropic effects patients with primary aldosteronism (PA) are exposed to high rates of cardiovascular events. Endothelial dysfunction, as a part of vascular disease, is one of the earliest changes related to high cardiovascular risk and monocytes are the main immune cells participating in the development of vascular wall damage. Therefore, we ought to compare endothelial function between PA patients and healthy controls. Next, we wanted to estimate, if monocytes are able to induce endothelial dysfunction solely by their secretome. Design and method: 13 healthy controls and 42 PA patients received flow mediated dilation measurements (FMD). Later, monocytes were isolated from 8 PA patients and 6 healthy individuals and placed in cell culture. 24 hours later supernatants were collected for cytokine measurements using Human Cytokine 17-plex Assay (Bio-rad). Effects of monocyte derived cytokines on endothelial function were assessed using wire Myograph (Danish Myo Technology). Pre-contraction was induced by norepinephrine (1μM) (Sigma) followed by cumulative concentration response curve to carbachol (0.3μM-300μM) (Sigma). Results: FMD was significantly lower among PA patients (6.3(3.8-8.1)% vs 10.5 ± 3%, p &lt; 0.05). Furthermore, monocytes from patients with PA secreted significantly higher concentrations of following cytokines and growth factors than healthy controls: G-CSF, IFN-gamma, TNF-alfa, IL-6, IL-10, IL-8, IL-17, and MCP-1. Especially concentrations of IL-6 (388 (351-580)pg/ml vs 36(4-268)pg/ml, p &lt; 0.05) and TNF-alfa (95(48-135)pg/ml vs 17(5-41)pg/ml, p &lt; 0.05) were much higher among PA patients. Incubation of mouse thoracic aorta with this monocyte secretome for 24 hours revealed stronger vascular contraction than using supernatant from healthy controls. In pre-constricted murine aortas, maximal dilation of 87.9 ± 11% was reached using aortas incubated in PA monocyte secretome whereas a dilation of 90.9 ± 9.1% was reached in controls. Indeed, carbachol EC50 for aortas incubated in monocyte secretome derived from healthy controls was 1.0mkM and 1.9mkM for PA patients. Conclusions: PA patients demonstrate endothelial dysfunction measured by FMD. Moreover, monocytes isolated from these patients are characterized by high secretion of pro-inflammatory cytokines which induce endothelial dysfunction, one of mechanisms triggering vascular dysfunction among these patients.

COMPLEX ANKLE FUSION WITH CIRCULAR FRAMES: FACTORS INFLUENCING OUTCOMES, COMPLICATIONS, AND PATIENT SATISFACTION

IntroductionCircular frames for ankle fusion are usually reserved for complex clinical scenarios. Current literature is heterogenous and difficult to interpret. We aimed to study the indications and outcomes of this procedure in detail.Materials &amp; MethodsA retrospective cohort study was performed based on a prospective database of frame surgeries performed in a tertiary institution. Inclusion criteria were patients undergoing complex ankle fusion with circular frames between 2005 and 2020, with a minimum 12-month follow up. Data were collected on patient demographics, surgical indications, comorbidities, surgical procedures, external fixator time (EFT), length of stay (LOS), radiological and clinical outcomes, and adverse events. Factors influencing radiological and clinical outcomes were analysed.Results47 patients were included, with a mean follow-up of three years. The mean age at time of surgery was 63.6 years. Patients had a median of two previous surgeries. The median LOS was 8.5 days, and median EFT was 237 days. Where simultaneous limb lengthening was performed, the average lengthening was 2.9cm, increasing the EFT by an average of 4 months. Primary and final union rates were 91.5% and 95.7% respectively. At last follow-up, ASAMI bone scores were excellent or good in 87.2%. ASAMI functional scores were good in 79.1%. Patient satisfaction was 83.7%. 97.7% of patients experienced adverse events, most commonly pin-site related, with major complications in 30.2% and re-operations in 60.5%. There were 3 amputations. Adverse events were associated with increased age, poor soft tissue condition, severe deformities, subtalar fusions, peripheral neuropathy, peripheral vascular disease, and prolonged EFT.ConclusionsComplex ankle fusion using circular frames can achieve good outcomes in complicated clinical scenarios, however patients can expect a prolonged time in the frame and high rates of adverse events. Multiple risk factors were identified for poorer outcomes, which should be considered in patient counselling and prognostication.

Transnasal Humidified Rapid Insufflation Ventilatory Exchange in children requiring emergent intubation (Kids THRIVE): a statistical analysis plan for a randomised controlled trial

The placement of an endotracheal tube for children with acute or critical illness is a low-frequency and high-risk procedure, associated with high rates of first-attempt failure and adverse events, including hypoxaemia. To reduce the frequency of these adverse events, the provision of oxygen to the patient during the apnoeic phase of intubation has been proposed as a method to prolong the time available for the operator to insert the endotracheal tube, prior to the onset of hypoxaemia. However, there are limited data from randomised controlled trials to validate the efficacy of this technique in children. The technique known as transnasal humidified rapid insufflation ventilatory exchange (THRIVE) uses high oxygen flow rates (approximately 2 L/kg/min) delivered through nasal cannulae during apnoea. It has been shown to at least double the amount of time available for safe intubation in healthy children undergoing elective surgery. The technique and its application in real time have not previously been studied in acutely ill or injured children presenting to the emergency department or admitted to an intensive care unit. The Kids THRIVE trial is a multicentre, international, randomised controlled trial (RCT) in children less than 16 years old undergoing emergent intubation in either the intensive care unit or emergency department of participating hospitals. Participants will be randomised to receive either the THRIVE intervention or standard care (no apnoeic oxygenation) during their intubation. The primary objective of the trial is to determine if the use of THRIVE reduces the frequency of oxygen desaturation and increases the frequency of first-attempt success without hypoxaemia in emergent intubation of children compared with standard practice. The secondary objectives of the study are to assess the impact of the use of THRIVE on the rate of adverse events, length of mechanical ventilation and length of stay in intensive care. In this paper, we describe the detailed statistical analysis plan as an update of the previously published protocol.

Prophylactic rivaroxaban in the early post-discharge period reduces the rates of hospitalization for atrial fibrillation and incidence of sudden cardiac death during long-term follow-up in hospitalized COVID-19 survivors.

Introduction: While acute Coronavirus disease 2019 (COVID-19) affects the cardiovascular (CV) system according to recent data, an increased CV risk has been reported also during long-term follow-up (FU). In addition to other CV pathologies in COVID-19 survivors, an enhanced risk for arrhythmic events and sudden cardiac death (SCD) has been observed. While recommendations on post-discharge thromboprophylaxis are conflicting in this population, prophylactic short-term rivaroxaban therapy after hospital discharge showed promising results. However, the impact of this regimen on the incidence of cardiac arrhythmias has not been evaluated to date. Methods: To investigate the efficacy of this therapy, we conducted a single center, retrospective analysis of 1804 consecutive, hospitalized COVID-19 survivors between April and December 2020. Patients received either a 30-day post-discharge thromboprophylaxis treatment regimen using rivaroxaban 10mg every day (QD) (Rivaroxaban group (Riva); n = 996) or no thromboprophylaxis (Control group (Ctrl); n = 808). Hospitalization for new atrial fibrillation (AF), new higher-degree Atrioventricular-block (AVB) as well as incidence of SCD were investigated in 12-month FU [FU: 347 (310/449) days]. Results: No differences in baseline characteristics (Ctrl vs Riva: age: 59.0 (48.9/66.8) vs 57 (46.5/64.9) years, p = n.s.; male: 41.5% vs 43.7%, p = n.s.) and in the history of relevant CV-disease were observed between the two groups. While hospitalizations for AVB were not reported in either group, relevant rates of hospitalizations for new AF (0.99%, n = 8/808) as well as a high rate of SCD events (2.35%, n = 19/808) were seen in the Ctrl. These cardiac events were attenuated by early post-discharge prophylactic rivaroxaban therapy (AF: n = 2/996, 0.20%, p = 0.026 and SCD: n = 3/996, 0.30%, p < 0.001) which was also observed after applying a logistic regression model for propensity score matching (AF: χ 2-statistics = 6.45, p = 0.013 and SCD: χ 2-statistics = 9.33, p = 0.002). Of note, no major bleeding complications were observed in either group. Conclusion: Atrial arrhythmic and SCD events are present during the first 12months after hospitalization for COVID-19. Extended prophylactic Rivaroxaban therapy after hospital discharge could reduce new onset of AF and SCD in hospitalized COVID-19 survivors.

Patient profiles in heart failure with reduced ejection fraction: prevalence, characteristics, treatments and outcomes in a real-world heart failure population.

The Heart Failure Association of the European Society of Cardiology has recently proposed to optimize guidelines-directed medical treatments according to patient's profiles. Aim of this analysis was to investigate prevalence/characteristics/treatments/outcomes for individual profiles. Patients with heart failure with reduced ejection fraction (HFrEF) enrolled in the Swedish Heart Failure Registry (SwedeHF) between 2013-2021 were considered. Among 108 profiles generated by combining different strata of renal function (by estimated glomerular filtration rate, eGFR), systolic blood pressure (sBP), heart rate, atrial fibrillation (AF) status and presence of hyperkalaemia, 93 were identified in our cohort. Event rates for a composite of cardiovascular (CV) mortality or first HF hospitalization were calculated for each profile. The 9 most frequent profiles accounting for 70.5% of the population had eGFR 30-60 or ≥60 mL/min/1.73m2 , sBP 90-140mmHg and no hyperkalaemia. Heart rate and AF were evenly distributed. The highest risk of CV mortality/first HF hospitalization was observed in those with concomitant eGFR 30-60 mL/min/1.73m2 and AF. We also identified 9 profiles with the highest event rates, representing only 5% of the study population, characterized by no hyperkalaemia, even distribution among the sBP strata, predominance of eGFR <30mL/min/1.73m2 and AF. The 3 profiles with eGFR 30-60mL/min/1.73m2 also showed sBP <90mmHg. In a real-world cohort most patients fit in a few easily identifiable profiles; the 9 profiles at highest risk of mortality/morbidity accounted for only 5% of the population. Our data might contribute to identifying profile-tailored approaches to guide drugs´ implementation and follow-ups. This article is protected by copyright. All rights reserved.

Familial predisposition to cardiovascular disease and death in patients with an out-of-hospital cardiac arrest

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Rigshospitalet Introduction Familial predisposition to cardiovascular disease (CVD) and death among patients with out-of-hospital cardiac arrest (OHCA), is sparsely described in current literature. A higher rate of events in first-degree relatives might imply an increased risk of future cardiac arrest and could provide vital improvements in prevention of sudden cardiac death. Therefore, investigation of CVD and death in family of OHCA-victims is needed. Purpose Determine familial predisposition to CVD and death in patients with OHCA. Methods This study used the nationwide Danish Cardiac Arrest Registry to identify all patients with OHCA (probands) of presumed cardiac origin from 2001-2014 and &amp;lt;70 years of age at time of OHCA. First-degree relatives were identified using the Danish Family Relations Database. We included probands with at least one identifiable first-degree relative. Date of OHCA was defined as index for first-degree relatives. The probands were stratified in age groups (0-18, 19-29, 30-49, and 50-69 years at OHCA) and CVD and death among first-degree relatives was assessed in each group. CVD was defined as diagnosis with any ICD-10 I00-I51 code (hypertension (I10-I14) excluded) and CVD-death defined as death with CVD being the main cause. Probands were matched with a background population (1:4) on age and sex. First-degree relatives of the background population were identified and stratified similarly to those of probands. Rates of familial predisposition to CVD and death in probands was compared to the background population. Results We identified 5,443 probands (75% male, median age 51 years) with 16,260 first-degree relatives; 10,207 parents (48.2% fathers, median age 71 years) and 6,053 full siblings (52.7% brothers, median age 47.2 years). Parents to probands had a higher rate of CVD (27.5% vs. 21.9%), a higher mortality rate (51.4% vs. 38.4%) and death more often caused by CVD (39.9% vs. 34.1%) compared to parents of the background population (p&amp;lt;0.001 for all). Stratified by age groups, probands in groups 19-29, 30-49 and 50-69 all had a higher rate of mortality among their parents compared to corresponding groups in the background population (bar diagram in fig.1). Siblings to probands also had a higher rate of CVD (4.9% vs. 2.9%, p&amp;lt;0.001), a higher rate of mortality (3.5% vs. 2.0%, p&amp;lt;0.001), and death more often caused by CVD (16.9% vs. 12.4%, p=0.19) compared to siblings of the background population. Stratified by age group, probands in groups 30-49 and 50-69 both had a higher mortality rate among their siblings compared to corresponding groups in the background population (bar diagram in fig.2). Conclusion Familial predisposition to both cardiovascular disease and death is more prevalent in patients with an out-of-hospital cardiac arrest compared to the background population. These results indicate that, cardiovascular disease and death of first-degree relatives is important risk factors for sudden cardiac arrest in the family.

WONDER-01: immediate necrosectomy vs. drainage-oriented step-up approach after endoscopic ultrasound-guided drainage of walled-off necrosis—study protocol for a multicentre randomised controlled trial

BackgroundWith the increasing popularity of endoscopic ultrasound (EUS)-guided transmural interventions, walled-off necrosis (WON) of the pancreas is increasingly managed via non-surgical endoscopic interventions. However, there has been an ongoing debate over the appropriate treatment strategy following the initial EUS-guided drainage. Direct endoscopic necrosectomy (DEN) removes intracavity necrotic tissue, potentially facilitating early resolution of the WON, but may associate with a high rate of adverse events. Given the increasing safety of DEN, we hypothesised that immediate DEN following EUS-guided drainage of WON might shorten the time to WON resolution compared to the drainage-oriented step-up approach.MethodsThe WONDER-01 trial is a multicentre, open-label, superiority, randomised controlled trial, which will enrol WON patients aged ≥ 18 years requiring EUS-guided treatment in 23 centres in Japan. This trial plans to enrol 70 patients who will be randomised at a 1:1 ratio to receive either the immediate DEN or drainage-oriented step-up approach (35 patients per arm). In the immediate DEN group, DEN will be initiated during (or within 72 h of) the EUS-guided drainage session. In the step-up approach group, drainage-based step-up treatment with on-demand DEN will be considered after 72–96 h observation. The primary endpoint is time to clinical success, which is defined as a decrease in a WON size to ≤ 3 cm and an improvement of inflammatory markers (i.e. body temperature, white blood cell count, and C-reactive protein). Secondary endpoints include technical success, adverse events including mortality, and recurrence of the WON.DiscussionThe WONDER-01 trial will investigate the efficacy and safety of immediate DEN compared to the step-up approach for WON patients receiving EUS-guided treatment. The findings will help us to establish new treatment standards for patients with symptomatic WON.Trial registrationClinicalTrials.gov NCT05451901, registered on 11 July 2022. UMIN000048310, registered on 7 July 2022. jRCT1032220055, registered on 1 May 2022.

Changing Concepts in Treatment of ST-Segment Elevation Myocardial

ST-Segment Elevation Myocardial (STEMI) is a lifethreatening condition that requires emergent, complex, well-coordinated treatment. Although the primary goal of treatment is simple to describe, reperfusion as quickly as possible- the management process is complicated and is affected by multiple factors including location, patient and practitioners’ characteristics. Indeed, treatment of acute STEMI has progressed considerably over the past 100 years, from the early stages of bed rest and development of thrombolytics and myocardial reperfusion, to today’s current strategy with a variety of mechanical and pharmacologic modalities. But the debate continues regarding optimal antithrombotic/anticoagulant and interventional strategies employed. Given the scientific and technological advantages, treatment strategies can be catered to better suit the patient and their presentation. Fibrinolytic therapy did save the lives compared to placebo, but at best restored Thrombolysis in Myocardial Infarction (TIMI) 3 Flow in 55-70% cases with increased incidence of recurrent ischaemia and infarction and intracranial haemorrhage. From Primary Angioplasty in Myocardial Infarction (PAMI) to 23 RCTs of Thrombolysis in Myocardial Infarction (TIMI) Vs Lysis showed that there is significant reduction in death (7.0% Vs 9.3%), Re-infarction (2.5% Vs 6.8%), haemorrhagic stroke (0.1% Vs 1.0%) and total stroke (1.0%) in Percutaneous Coronary Intervention (PCI) group. STEMI success has plateaued because of suboptimal salvage of myocardium and high rates of non-culprit lesion related events and reperfusion injury. Promising approaches should be further explored like hypothermia, stem cell and super-saturated oxygen therapy and PiCSO to enhance myocardial recovery and reduce infarct size. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 182

Thrombotic or Thromboembolic Events in COVID-19: A Literature Review

Context: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as a novel virus infection, was first detected in China in 2019 and has quickly spread as a pandemic leading to a high mortality rate and unprecedented challenges for healthcare systems. Although the SARS-CoV-2 clinical spectrum is different, acute failure of respiratory function and coagulopathy as a common manifestation can be observed in cases with severe coronavirus disease 2019 (COVID-19). Methods: This literature review was conducted based on standard guidelines to evaluate related-to-title information about thrombotic or thromboembolic events in COVID-19. Keywords were combined and included as “thrombotic event”, “thromboembolic events”, “diagnosis”, “management”, “SARS-CoV-2”, “COVID-19”, and “literature review”. Results: Lung tissue is a serious target of the COVID-19 virus leading to acute respiratory distress syndrome related to a thromboinflammatory condition. The storm of cytokines, pulmonary tropism, and thromboinflammation are bases of tissue damage leading to acute failure of the respiratory system and extended infection, which can lead to different organ failure and death. The thrombogenicity of this condition has been shown by the high prevalence rate of thromboembolic events observed in SARS-CoV-2 cases treated with anticoagulation. Enhanced D-dimers, as a biomarker reflecting the activation of fibrinolysis and hemostasis, and thrombocytopenia have a relationship with a higher mortality rate in COVID-19 cases. Conclusions: Based on the finding, the inflammation phase of COVID-19 can induce thromboinflammation and lead to thromboembolic events.

An HMM-DNN-Based System for the Detection and Classification of Low-Frequency Acoustic Signals from Baleen Whales, Earthquakes, and Air Guns off Chile

Marine passive acoustic monitoring can be used to study biological, geophysical, and anthropogenic phenomena in the ocean. The wide range of characteristics from geophysical, biological, and anthropogenic sounds sources makes the simultaneous automatic detection and classification of these sounds a significant challenge. Here, we propose a single Hidden Markov Model-based system with a Deep Neural Network (HMM-DNN) for the detection and classification of low-frequency biological (baleen whales), geophysical (earthquakes), and anthropogenic (air guns) sounds. Acoustic data were obtained from the Preparatory Commission for the Comprehensive Nuclear-Test-Ban Treaty Organization station off Juan Fernandez, Chile (station HA03) and annotated by an analyst (498 h of audio data containing 30,873 events from 19 different classes), and then divided into training (60%), testing (20%), and tuning (20%) subsets. Each audio frame was represented as an observation vector obtained through a filterbank-based spectral feature extraction procedure. The HMM-DNN training procedure was carried out discriminatively by setting HMM states as targets. A model with Gaussian Mixtures Models and HMM (HMM-GMM) was trained to obtain an initial set of HMM target states. Feature transformation based on Linear Discriminant Analysis and Maximum Likelihood Linear Transform was also incorporated. The HMM-DNN system displayed good capacity for correctly detecting and classifying events, with high event-level accuracy (84.46%), high weighted average sensitivity (84.46%), and high weighted average precision (89.54%). Event-level accuracy increased with higher event signal-to-noise ratios. Event-level metrics per class also showed that our HMM-DNN system generalized well for most classes but performances were best for classes that either had a high number of training exemplars (e.g., generally above 50) and/or were for classes of signals that had low variability in spectral features, duration, and energy levels. Fin whale and Antarctic blue whale song and air guns performed particularly well.

Bionic pancreas in children and adults with type 1 diabetes

Journal of Paediatrics and Child HealthEarly View Heads UpFree Access Bionic pancreas in children and adults with type 1 diabetes First published: 08 May 2023 https://doi.org/10.1111/jpc.16426 edited by Craig Mellis ([email protected]) AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Unlike currently available semi-automated insulin delivery systems, which require individualised settings and carbohydrate counting, bionic pancreas allows for automated insulin delivery based on body weight and ‘meal announcements’. The Bionic Pancreas Research Group randomised 326 persons with type 1 diabetes aged 6–79 years to insulin-only bionic pancreas treatment (n = 219) or standard care with any insulin-delivery method and unblinded continuous glucose monitoring (n = 107).1 After 13 weeks, the bionic pancreas group saw an HbA1c improving from 7.9% at baseline to 7.3% at follow-up, while standard-treatment group saw no change. Additionally, in the bionic pancreas group, mean sensor glucose improved and time in range (TIR) increased by 11% (Fig. 1). These effects were greater in participants with higher HbA1c and on multiple daily injections or non-automated pump systems. There was no difference in hypoglycaemia (sensor glucose <3 mmol/L). A high rate of adverse events occurred in the bionic pancreas group: hyperglycaemia occurred in 95 participants, predominantly due to infusion-set failures. However, such adverse events were not reported in the standard-treatment group. Of the bionic pancreas group, 19 participants stopped using the intervention prior to completion of the study and two children required additional insulin glargine for hyperglycaemia despite maximal insulin delivery based on the device algorithm. Fig. 1Open in figure viewerPowerPoint (a) Median glucose level over 24 h. Solid circles indicate the hourly median values of the participants' mean glucose levels, and shaded regions indicate the interquartile range; dashed curves indicate the 10th and 90th percentiles. (b) Cumulative distribution plot of the percentage of sensor glucose level in range (3.9–10 mmol/L). (), Standard care; (), bionic pancreas. In conclusion, insulin-only bionic pancreas resulted in lower HbA1c, improved TIR and lower mean sensor glucose level than standard care without increased hypoglycaemia. Further development and optimisation of insulin sets and the insulin delivery algorithm (especially for children) would reduce the risk of adverse events seen in this trial. Reference 1 Bionic Pancreas Research Group et al. Multicenter, randomized trial of a bionic pancreas in type 1 diabetes. N. Engl. J. Med. 2022; 387: 1161– 72. Reviewers: Lara E. Graves, [email protected], The Children's Hospital at Westmead, Sydney; Jessica Sandy, [email protected], The Children's Hospital at Westmead, Sydney Early ViewOnline Version of Record before inclusion in an issue FiguresReferencesRelatedInformation

PO-05-058 PROGNOSTIC EVALUATION OF PATIENTS WITH ICD IN A LATIN AMERICAN TERTIARY CENTER.

Despite advances in ICD, SCD remains a public health problem. Chagas disease, still prevalent in Brazil, is associated with higher VT and VF events and SCD when compared to other cardiopathies. Data are conflicting in correlating mortality reduction in chagasic patients and the ICD implantation. We aimed to evaluate the ICD receivers mortality after structuring arrhythmia service in a Latin American tertiary center. Evaluate if the mortality and VT/VF events decrease when patients who received ICD at different periods of time (2007-2010, 2011-2014, 2015-2018) are compared in a tertiary center; compare the prognosis of chagasic to non-chagasic patients in different periods. Retrospective observational study of patients with ICD implanted in the Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG) between October 2007 and December 2018. The primary outcome was mortality, evaluated in the total sample and in each period. The secondary outcomes were the VT/VF events and the combined outcome of death and/or VT/VF, evaluated in the total sample and in each period. A total of 885 patients were included, 31% chagasic. Out of these, 254 (28%) died, 127 (14%) had VT/VF and 329 (37%) died and/or had VT/VF. The Kaplan-Meier curves showed that period 3 vs. 1 was the only variable associated with better death-free survival, p=0.007. For the VT/VF and the combined outcome free survival curves, Chagas disease was the only variable associated with higher rate of events; p<0.001 and p=0.009, respectively. In the cox's analysis adjusted for age, sex and Chagas, period 2 vs. 1 was protective for death (HR 0.715, 95%CI 0.539-0.948) and combined outcome (HR 0.713, 95%CI 0.537-0.945); period 3 vs. 1 was protective for death (HR 0.516, 95%CI 0.351-0.759) and combined outcome (HR 0.530, 95%CI 0.361-0.780). After adjusting for age and gender, Chagas was associated with VT/VF in periods 1 (HR 2.531, 95%CI 1.469-4.360) and 2 (HR 3.247, 95%CI 1.735-6.076). There was a gradual reduction in mortality and combined outcome for ICD receivers at periods 2011-2014 and 2015-2018 compared to the initial period 2007-2010. Chagas was associated with a higher VT/VF events in ICD receivers only in the first two periods. The improvement of results was concomitant with the incorporation of new modalities and technologies to treat patients with ICD. The better organization of care may be associated with reduction of overall mortality and arrhythmic events in this population.

PO-03-107 MYOCARDIAL SCAR CHARACTERISTICS BY 3D-LGE CANNOT FULLY EXPLAIN DIFFERENT ARRHYTHMIC EVENT RATES IN PRIMARY AND SECONDARY PREVENTION OF SUDDEN CARDIAC DEATH

There is a noticeable difference in the incidence of ventricular arrythmias among patients receiving defibrillator devices (ICD or CRT-D) for primary vs. secondary prevention of sudden cardiac death (SCD). The underlying reasons for this difference remain to be fully explained. To assess for differences in myocardial scar characteristics between patients who had defibrillator devices implanted in primary vs. secondary prevention scenarios, and their correlation with arrhythmic events. In this single center retrospective study, patients who underwent late gadolinium enhancement (LGE) cardiac MRI for clinical purposes before the implantation of an ICD or CRT-D were included. Patients with channelopathies (n=2) or inappropriate imaging quality (n=7) were excluded. We used ADAS software to perform myocardial scar characterization in 3D-LGE datasets in all but 16 patients, in which 2D datasets were used. The primary endpoint was a composite of appropriate ICD therapy (appropriate shock or ATP), sustained ventricular tachycardia or SCD. A total of 116 patients (mean age 66±14 years, 81% male) were included, 40 (35%) with devices implanted in secondary prevention. During a median follow-up of 28 months (IQR 16-24), 23 events were identified (18 appropriate ICD therapy, 9 shocks and 9 ATP; 2 SCD; 3 sustained VT), 7 of which (30.4%) in the primary prevention group, and 16 (69.6%) in the secondary prevention group. The event rate was significantly higher in the secondary prevention setting (15.0 events per 100 persons-year [95% CI 7.7 – 22.4] vs. 4.1 events per 100 persons-year [95% CI 1.1 – 7.1]; p < 0.001). Despite a higher LVEF in the secondary prevention group (41 ± 14% vs. 30 ± 13%; p-value < 0.001), no statistically significant differences were found regarding scar tissue characteristics, namely scar and borderzone (BZ) mass, total channel mass, largest channel mass, number of channels and scar heterogeneity (BZ mass / scar mass ratio) – Table. Despite the higher event rate in patients receiving defibrillator devices in secondary vs. prevention, no differences in myocardial scar characteristics were found between both groups. These findings suggest that arrhythmic risk is unlikely to be explained solely by the anatomical substrate, and support a greater role for the interplay between substrate and transient triggers.Tabled 1Primary PreventionSecondary Preventionp-valueScar + BZ mass (g)26.2 (IQR 13.3 - 35.0)23.7 (IQR 11.4 - 33.4)p = 0.322Scar + BZ percentage (%)18.0 (IQR 11.0 – 27.0)17.0 (IQR 9.0 - 26.0)p = 0.545BZ mass (g)17.7 (IQR 11.1 - 24.2)14.8 (IQR 8.8 - 22.0)p = 0.350BZ percentage (%)13.0 (IQR 8.0 - 18.0)11.0 (IQR 6.0 - 17.0)p = 0.677Scar mass (g)6.6 (IQR 3.4 - 11.0)6.9 (IQR 2.0 - 10.3)p = 0.693Scar percentage (%)4.0 (IQR 2.0 - 9.0)5.0 (IQR 1.0 - 8.0)p = 0.695Scar heterogeneity2.4 (IQR 1.7 - 3.9)2.7 (IQR 1.5 - 4.4)p = 0.797Total channels mass (g)3.0 (IQR 0.7 - 4.9)1.8 (IQR 0.0 - 5.0)p = 0.215Biggest channel mass (g)1.4 (IQR 0.5 - 2.5)0.8 (IQR 0.0 - 3.0)p = 0.163Number of channels3.0 (IQR 1.0 - 5.0)3.0 (IQR 0.0 - 5.0)p = 0.520BZ, Borderzone Open table in a new tab

CO-induced TTP improves efficacy through resetting tumor-associated macrophages toward M1 phenotype in combined CTLA-4 and PD-1 blockade immunotherapy

Abstract Combined immune checkpoint blockade (CICB) targeting CTLA-4 and PD-1 has improved the prognosis for many malignancies, but also occurred a high rate of immune-related adverse events (irAEs). The manifestation of these toxicities is an important limiting factor for the successful implementation of CICB, restraining its anti-tumor efficacy. Carbon monoxide (CO), a pivotal endogenous signaling molecule, is able to maintain cell and tissue homeostasis and could be used as a therapeutic regimen. In our previous reports, CO could be useful therapeutics for the regulation of various inflammatory diseases through the increase of tristetraprolin (TTP) that binds to the AU-rich elements in target mRNA. In this study, we observed that CO-induced TTP activation ameliorated colitis and hepatitis, and improved anti-tumor efficacy in CICB treatment. We found that the colitis and hepatitis in TTP deficient mice were further exacerbated by CICB treatment. Moreover, CO increases CICB efficacy through TAM to M1 polarization together with diminishes irAEs through TTP enhancement in several irAEs target organ. Thus, we suggest that CO might be efficiently decouples anti-tumor efficacy and toxicity of CICB through TTP enhancement.

Endovascular embolization of visceral artery aneurysm: a retrospective study

To assess the safety and efficacy of endovascular embolization techniques, we compared the short- to medium-term prognosis of coil embolization for symptomatic visceral aneurysms (SVAA) and asymptomatic visceral aneurysms (ASVAA) to identify risk factors associated with 30-day mortality. Explore the symptom profile and intrinsic associations of SVAA. A retrospective study of 66 consecutive patients at two tertiary care hospitals from 2010 to 2020 compared the short- to mid-term outcomes of 22 symptomatic VAAs and 44 asymptomatic VAAs treated with coil embolization. Univariate and log-rank tests were used to analyze the prognostic impact of SVAA and ASVAA. SVAA group had significantly higher 30-day mortality than ASVAA group (2(9.1%) vs 0, P = 0.042), both patients who died had symptomatic pseudoaneurysms. Perioperative complications such as end-organ ischemia (P = 0.293) and reintervention (P = 1) were similar in both groups. No difference in event-free survival was identified between the two groups (P = 0.900), but we found that the majority of pseudoaneurysms were SVAA (4/5) and that they had a much higher event rate than true aneurysms. In addition, dyslipidemia may be an influential factor in the development of VAA (P = 0.010). Coil embolization is a safe and effective method of treatment for VAA. Most pseudoaneurysms have symptoms such as abdominal pain and bleeding, and in view of their risk, more attention should be paid to symptomatic patients and the nature of the aneurysm should be determined as soon as possible to determine the next stage of treatment.