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The aim of this study is to evaluate the agreement between three-dimensional (3D) transesophageal echocardiography (TEE) and multidetector computed tomography (MDCT) for assessing mitral annular (MA) dimensions. A total of 105 patients (79 ± 9 years old, 52% male) who underwent clinically indicated 3D TEE and MDCT feasible for MA geometrical assessment were included. Using dedicated semi-automated postprocessing software, MA geometry, including mitral annular area (MAA), perimeter, septal-lateral (SL) diameter, and inter-trigonal (TT) diameter, was evaluated using 3D TEE and MDCT. Compared to 3D TEE, MAA, perimeter, and SL distance measured on MDCT data were larger (9.9 ± 3.0 vs. 9.3 ± 3.1 cm2 for MAA, 115 ± 18 vs. 108 ± 18 mm for perimeter, and 35 ± 5 vs. 32 ± 5 cm for SL distance, all p &lt, 0.001). By contrast, the TT distance was comparable between MDCT and 3D TEE (26 ± 4 vs. 26 ± 4 cm, p = 0.258). The correlations of all the MA dimensions were good to excellent between the two modalities (R = 0.911 for MAA, 0.890 for perimeter, 0.739 for TT distance, and 0.857 for SL distance, respectively, all p &lt, 0.001). This study showed good agreement between 3D TEE- and MDCT-derived MA measurements although MDCT systematically provided larger MAA, perimeter, and SL distance compared with 3D TEE.

The development of transcatheter mitral valve replacement therapies requires accurate post-processing analysis tools to provide D-shaped mitral annulus dimensions from 3-dimensional (3D) data. The agreement between two semi-automated, software packages to process 3D transesophageal echocardiography (TEE) data for the measurement of the mitral valve annulus dimensions was evaluated. 3DTEE data of patients with moderate&ndash, severe mitral regurgitation (MR) were postprocessed with semi-automated, vendor-independent (VI) software and vendor-specific (VS) software. Both post-processing software provided key measurements for the selection of transcatheter valve prosthesis size: annulus area, annulus circumference and the septal-to-lateral distance of the annulus. The intertrigonal distance was provided only by the VS software. The inter- and intra-observer agreements were assessed with Bland&ndash, Altman analysis. Of 105 patients (63.8 &plusmn, 11 years, 66% male) with MR, 28 had secondary MR, 45 fibroelastic deficiency, and 32 Barlow&rsquo, s disease. Using VS software, the dimensions for the overall population were 16.1 &plusmn, 4.6 cm2 for annulus area, for circumference 14.4 &plusmn, 1.9 cm, intertrigonal distance 3.4 &plusmn, 0.5 cm and septal-to-lateral distance 3.8 &plusmn, 0.6 cm. Similar dimensions were obtained using VI software: 15.7 &plusmn, 4.6 cm2 for annulus area, 14.5 &plusmn, 2.0 cm for circumference, and 4.1 &plusmn, 0.6 cm for septal-to-lateral distance. The inter- and intra-observer agreement for both software programs was excellent. In conclusion, current post-processing software programs for 3DTEE data of the mitral valve annulus provide good reproducibility of key measurements to select the transcatheter prosthesis size.

Background Assessment of left ventricular (LV) function in patients with secondary mitral regurgitation (SMR) remains challenging because LV ejection fraction (LVEF) reflects changes in LV volume without taking into account the direction of the blood flow. LV global longitudinal strain better reflects active LV myocardial deformation but does not incorporate afterload. LV myocardial work derived from pressure-strain loops integrates speckle tracking echocardiography with non-invasive blood pressure measurement. Purpose To evaluate LV myocardial work components to better characterize LV function in patients with SMR. Methods 378 patients (72% men, median age 68 [range 60 to 74 years]) with various grades of SMR were retrospectively analysed. LV myocardial constructive work, wasted work and work efficiency were measured with speckle tracking echocardiography. Results 145 patients had mild SMR, 130 moderate SMR and 103 severe SMR. Patients with severe SMR had larger LV volumes, lower LVEF and more impaired LV GLS (Table 1). While LV constructive work was more impaired in patients with severe SMR, wasted work was lower as compared to mild SMR (Table 1). Consequently, patients with severe SMR had better myocardial work efficiency than patients with mild MR. This could reflect, the regurgitant volume which is pumped into a low pressure chamber (the left atrium) resulting in less myocardial wasted work and preservation of myocardial efficiency. Conclusion In patients with severe SMR, LVEF, LV GLS and myocardial constructive work are more impaired when compared to mild SMR. However, myocardial wasted work is lower, resulting in higher better LV myocardial work efficiency. Funding Acknowledgement Type of funding source: None

Background Left ventricular (LV) myocardial contractility evaluation is of crucial importance in patients with secondary mitral regurgitation (SMR). The most widespread echocardiographic tool, left ventricular ejection fraction (LVEF), might overestimate LV function, since it calculates the volume changes regardless of the flow direction. Global myocardial constructive work (GMCW) might be a more suitable tool, as LV myocardial work derived from pressure-strain loops obtained with speckle tracking echocardiography incorporates non-invasive blood pressure measurements. Purpose To evaluate the prognostic value of LV GMCW in patients with SMR. Methods 378 patients (72% men, median age 68 [range 60 to 74 years]) with various grades of SMR were retrospectively analysed. LV global myocardial constructive work, wasted work and work efficiency were measured with speckle tracking echocardiography. Results There were 145 patients with mild SMR, 130 with moderate SMR and 103 with severe SMR. Patients with severe SMR had larger LV volumes, lower LVEF and more impaired LV GLS. GMCW was more impaired in patients with severe SMR, compared with mild MR (678 mmHg% vs. 845 mmHg% p Conclusion Global myocardial constructive work ≤700 mmHg% is associated with worse long-term survival in patients with SMR. Kaplan-Meier survival curves Funding Acknowledgement Type of funding source: None

Remdesivir is a direct-acting nucleoside RNA polymerase inhibitor with activity against the novel severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virus used in the treatment of coronavirus disease 2019 (COVID-19) pneumonia. Here, we present two cases of suspected remdesivir-associated acute liver failure (ALF) in which the liver failure improved after continuous infusion acetylcysteine and withdrawal of remdesivir. Both patients had significant increases in transaminases between day 3 and day 10 of remdesivir therapy accompanied by coagulopathy and encephalopathy. After initiation of continuous infusion acetylcysteine, the transaminases of both patients rapidly improved. Ultimately, one patient fully recovered while the other died of suspected septic shock. Due to its novel nature and only recent widespread use, there are very little data on the risk of ALF from remdesivir. Additionally, the data for the use of acetylcysteine to manage non-acetaminophen-induced ALF are limited. It is important to consider the risk of remdesivir-associated ALF when weighing the risk versus benefits of use, and acetylcysteine may have a role in its management.

Catastrophic thrombotic syndrome, otherwise known as thrombotic storm (TS) is an extreme prothrombotic clinical syndrome that presents as rapid onset of multiple thromboembolic events affecting a large variety of vasculature. In recent studies, there has been a correlation of high plasma levels of factor VIII with thrombotic events. We present the case of a young man who exhibited multi-organ failure due to thrombotic storm. A 38-year-old male presented to the emergency department for progressive dyspnea and was diagnosed to have pulmonary embolism. The patient developed respiratory distress requiring intubation and was diagnosed with both an ST-elevation myocardial infarction and right cerebral infarction during the hospital course. The patient expired and autopsy revealed the cause of death to be myocardial, cerebral and renal infarction from widespread vascular thrombosis. Autopsy revealed cause of death to be elevated factor VIII associated thrombotic coagulopathy. Factor VIII level upon autopsy was 375% (55-200%). Although TS is rare, it can be lifethreatening if not recognized early. Survival depends on the prompt initiation and duration of anticoagulation.

Patient: Female, 38-year-old Final Diagnosis: Hypercalcemia resulting from necrotizing leiomyoma in pregnancy Symptoms: Pain Medication: — Clinical Procedure: Cesarean section Specialty: General and Internal Medicine • Obstetrics and Gynecology Objective: Rare disease Background: Hypercalcemic crisis is defined as a serum calcium level >14 mg/dL in a symptomatic patient. While severe hypercalcemia during pregnancy is rare, it poses a life-threatening risk to both mother and fetus. Hypercalcemia in association with a benign tumor such as a leiomyoma is exceedingly rare. Case Report: A 38-year-old primagravida at 31.2 week’s gestation conceived by in vitro fertilization presented to the emergency department for complaints of nausea, vomiting, and epigastric abdominal pain. Her fetal monitor strip was reassuring. A complete metabolic panel on admission was significant for severely elevated calcium of 15.9 mg/dL (8.6–10.3 mg/dL) and an elevated lipase of 1457U/L (11–82 U/L). She was started on aggressive intravenous fluid resuscitation, but became confused and lethargic, unarousable to verbal stimuli, as a result of hypercalcemia. Computed tomography (CT) scan of the abdomen and pelvis revealed a heterogeneously enhancing, placental-appearing soft tissue mass extending posteriorly and to the right that measured 2414 cm. The patient subsequently underwent planned low transverse cesarean delivery and exploratory laparotomy for myomectomy with removal of a 2834-g benign leiomyoma measuring 19.018.514.0 cm. Her serum parathyroid hormone-related protein (PTHrP) was elevated to 9.6 pmol/L (

Cardiac resynchronization therapy (CRT) is a well-established heart failure (HF) treatment and exerts its effects through restoration of synchronous ventricular contraction. Myocardial work (MW) is a novel semiautomatic echocardiographic method which characterizes the efficacy of the left

Valvular atrial fibrillation (AF) is defined as AF in the presence of mitral stenosis or mechanical valve prosthesis. However, there are patients with AF who have significant native valvular heart disease (VHD) others than mitral stenosis that are classified as nonvalvular AF. The characteristics and prognostic implications of these entities have not been extensively studied. Of 1,885 AF patients referred for electrical cardioversion (64 +/- 13years, 71% male), 171 (9.1%) had valvular AF (any grade of mitral stenosis or mechanical/biological valve prostheses) and 1,714 patients were identified as nonvalvular AF, of whom 329 (17.5%) had significant left-sided VHD. Patients with nonvalvular AF but with significant left-sided VHD were older, more frequently women and had more co-morbidities compared with the other groups. Furthermore, nonvalvular AF patients with significant left-sided VHD showed the worst left ventricular systolic function and largest left atrial volumes. During a median follow-up of 64 months (interquartile range: 33 to 96 months), 488 patients presented with the combined endpoint of all-cause mortality, heart failure hospitalization, and ischemic stroke. Patients with nonvalvular AF and with significant left-sided VHD had more events of heart failure whereas patients with valvular AF had higher all-cause mortality events. There were no differences in ischemic stroke events. Type of AF was not associated with outcomes after correcting for echocardiographic variables. In conclusion, the frequency of AF patients with significant VHD is relatively high. The consequences of VHD and AF on cardiac structure and function are more important determinants of adverse outcome than the type of AF. (C) 2020 Elsevier Inc. All rights reserved.

Background Preterm birth is associated with higher risk of death and severe neurodevelopmental impairment. There is an increased risk in extremely preterm infants, raising questions among ethicists and clinicians as to whether providing active care to infants born at the lower extreme is worth the outcomes, and if these outcomes are a source of decisional regrets for parents. Objectives Explore decisional regrets in parents of extremely preterm children. Design/Methods We consecutively recruited all parents of infants born Results Responses were obtained from 249 parents (98% participation rate). The following main themes emerged: (1) Nothing – I did what I could or was told to do: 53%; (2) Regrets about self-care: 31%; “I would listen to the nurses’ advice to sleep more” (3) Guilt related to the impression preterm labor could have been prevented by them or the medical team: 19%; “I would have pushed for better care and monitoring during pregnancy. I felt as though I wasn’t listened to when I thought I was in labour when sure enough I was” (4) Regrets about parental role in decision-making: 15%; “I would speak up more at the beginning of the hospitalisation”. None of the parents reported on regretting any life-and-death decisions they made at birth and in the neonatal unit. Conclusion In our cohort, more than half of parents of surviving preterm infants did not have any regrets associated to their NICU experience. However, lessons can be learned to improve parental support, self-care and solutions to improve their role as parents. Unlike what can be stated using “opinion-based medicine”, limiting or forgoing intensive care is not a solution to eliminate decisional regrets in parents.

Purpose The purpose of this paper is to obtain insights into Vietnamese consumers’ knowledge and relevance of as well as their reaction to modern food retailers (MFRs) responsible and irresponsible conduct. Design/methodology/approach Data were obtained from an online survey applying content analysis, uni- and multivariate tests and multivariate regression models. Findings In total, 60 percent of respondents are not aware of (ir)responsible conduct of MFR. Most of those aware of such behavior indicate that this has induced a change in their shopping behavior. This holds to a similar extent for those not aware but envisaging the (ir)responsible conduct of MFRs. The findings point to a negativity bias in that consumers’ reaction is more sensitive regarding irresponsible than responsible firm behavior. This bias is higher for consumers already knowledgeable about the (ir)responsible behavior of MFRs. The likelihood that consumers punish irresponsible conduct is influenced by the importance they attach to “food quality and safety” while those having high concerns for environmental, social and ethical’ issues are more likely to reward responsible firm actions. Research limitations/implications The negativity bias which implies that consumers react more sensitive regarding irresponsible than responsible firm behavior is likely underestimated in hypothetical studies. Practical implications Customer loyalty is at stake for MFRs behaving irresponsible while it can be strengthened by responsible firm conduct. Originality/value This research is the first to highlight the importance consumers in Vietnam attach to responsible firm conduct. It also points to a lack of awareness of such behavior.

Headache is a common source of pain in children after traumatic brain injury (TBI); however, relatively little is known about nonheadache pain in this pediatric population. The present review seeks to map the extant literature to determine the prevalence, characteristics, and impact of nonheadache pain in children post-TBI of all severities. We found that of 109 studies published on pain in children after a TBI, 95 (87%) were focused exclusively on headache pain and only 14 (13%) reported on nonheadache pain or overall pain, with half (n = 7) in the form of case studies. Overall, the level of evidence was low, with only three level 1 high-quality prospective studies. In one study, over half (57.1%) of adolescents who experienced persistent pain post-TBI reported pain in multiple body sites (e.g., back, lower limb, and neck).(1) For each additional noncephalic pain site, the risk for developing chronic migraine is also increased. Nevertheless, pain in body regions other than the head is often not assessed systematically in pediatric TBI research. Findings of the current review suggest that pain assessment in children post-TBI needs improvement, given that pain is linked to worse recovery, poorer quality of life, and can be long-lasting. More rigorous examination of nonheadache pain and its role in impeding recovery in children post-TBI is imperative and has the potential to improve the care and management of children with TBI. We conclude with recommendations for pain assessment, discuss gaps in the literature, and highlight directions for future research.

TOPIC: Critical Care TYPE: Original Investigations PURPOSE: In 2020, ELSO published guidelines to assist providers with patient selection for ECMO in COVID ARDS. A BMI > 40 was listed as a relative contraindication for ECMO support without any supporting data in this specific patient population. Two major reports on ECMO patients from France and the ELSO database that included a total of 1118 patients with COVID ARDS, all with BMIs of 40 to be ECMO candidates. We aim to demonstrate the outcomes and feasibility of using ECMO in ARDS patients with extreme obesity METHODS: Data was collected from the ELSO database outlining outcomes of patients cannulated at Advent Health-Orlando for ECMO due to COVID ARDS between March 2020 – April 2021. The data included only patients with a BMI > 40. Data collected included age, length of stay, survival, discharge disposition, and expiration RESULTS: We have cannulated a total of 33 morbidly obese patients (BMI >40). 19/33 (57%) have survived and transitioned to either home, long-term acute care facility, rehab, or original referring hospital. 11/33 (33%) expired while on ECMO, 1/33 (3%) expired post-ECMO, resulting in an overall mortality of (12/33) 36%. The average LOS for all patients was 39.9 days. The survival group had an average LOS of 46.1 days. The average age for our cohort was 41 years CONCLUSIONS: It is our experience at Advent Health Orlando, that providing ECMO support to patients with BMI >40 has similar outcomes to patients who are not morbidly obese, our 59% survival rate compares to 60% in the ELSO historical database. Our 36% mortality rate compared to a range of 31-37% reported in the recent literature for COVID ARDS. Based on our results, we suggest that BMI > 40 be removed as a relative contraindication to ECMO. We also urge other centers to re-consider denying morbidly obese patients ECMO support based on the assumption that they may have a worse outcome than the rest of the population CLINICAL IMPLICATIONS: Based on our data, we demonstrate patients with COVID-19 ARDS with BMI > 40 benefited from ECMO support. In order to effectively ventilate morbidly obese patients, higher plateau pressures are required and may result in barotrauma and hemodynamic compromise. Supporting obese patients with ECMO to maintain protective lung settings can ultimately lead to better long-term outcomes. More data is needed to fully assess the survivability and overall quality of life in morbidly obese patients who are placed on ECMO, however, while this information is collected, we hope that the medical community will start offering the same opportunities to all patients regardless of weight DISCLOSURES: No relevant relationships by Nicholas Cavarocchi, source=Web Response No relevant relationships by Sergio Ramirez, source=Web Response No relevant relationships by Mai Vo, source=Web Response

In this study, benzyladenine (BA) and α- naphthaleneacetic acid (NAA) are used to study the growth of pineapple fruit (Ananas comosus (L.) Merr.) in the early growth phase. Pineapple fruits are sprayed with BA or NAA at different concentrations (1, 5, 10, 20, 40 and 60 mg.L-1) at both 0 and 3 days after flowering (DAF, 50 % dried flowers). Fruits are sampled every 15 days from 0 to 75 days to survey to weight, size and qualities of pineaple fruit. Besides, fruits (which are sprayed with BA or NAA at concentration 20 mg.L-1) are sampled at 15 days for the cell size observation. The results showed that the treatments with three highest concentration of BA or NAA (20, 40 và 60 mg.L-1) significantly increased fruit weights and fruit sizes. Exogenous BA or NAA at the concentration 20 mg.L-1 increased the fruit weights by increasing the number of flesh cells without negative effects on fruit qualities.

Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity. Although the severity of neonatal outcomes is inversely correlated with gestational age, all PTBs can lead to potentially life-threatening neonatal outcomes and major lifelong health complications. Because advances in neonatal care have substantially decreased neonatal mortality, the incidence of PTB and its complications is unabatedly rising. PTB currently affects more than 10% of births worldwide, with similar numbers in developed countries. Correspondingly, improving neonatal outcome is a key objective of the World Health Organization. The recently approved (in Europe) tocolytics drug, Atosiban, used to prolong preterm gestation, has not been shown to improve neonatal outcome, nor have other tocolytic agents used in clinic. Thus, PTB remains an unmet medical need. Recent evidence shows that most, if not all, PTBs are associated with (overt or occult) inflammatory processes in gestational tissues, independent of infection. Pro- inflammatory cytokines are produced from maternal and fetal cells in response to sterile or infectious stressors. These seem to orchestrate a multi-tissue response including myometrial contractility, cervical ripening, and weakening/rupture of fetal membranes, leading to the onset of preterm labor. This integrated system might have been conserved through mammalian evolution due to increased maternal and/or fetal survival when gestation is terminated in specific settings, such as infection. Hence, inflammation may be a common pathway to the numerous aetiologies of PTB. Most importantly, recent evidence suggests that inflammation is transmitted to the fetus, thereby inducing organ injuries that may underlie the development of major neonatal diseases. Targeting inflammation prenatally instead of myometrial contraction could be a more successful and safe approach for the management of PTB, as suggested by recent animal studies. RésuméLa naissance prématurée est la principale cause de mortalité et de morbidité néonatale. Bien que la sévérité des issus néonataux soit inversement corrélée avec l’âge gestationnel à la naissance, toutes les naissances prématurées peuvent mener à des issus néonataux potentiellement mortels et à des complications avec répercussions s’échelonnant sur toute la vie. Étant donné que la mortalité néonatale a considérablement diminuée avec les récentes avancées en néonatalogie, l’incidence de la naissance prématurée et de ses complications sont en hausse. La naissance prématurée affecte présentement plus de 10% des naissances à travers le monde, avec des taux similaires dans les pays développés. Conséquemment, d’améliorer l’issu néonatal est un objectif clé de l’Organisation Mondiale de la Santé. Le tocolytique Atosiban récemment approuvé (en Europe) pour prolonger les gestations pré- maturées n’a pas démontré d’efficacité pour améliorer les issus néonataux, tout comme les autres tocolytiques utilisés en clinique, et la naissance prématurée demeure un besoin médical non-atteint. Des données récentes démontrent que la plupart, sinon toutes les naissances prématurées sont associées avec des processus inflammatoires (francs ou silencieux) dans les tissus gestationnels, indépendamment de l’infection. Les cytokines pro-inflammatoires sont produites dans les cellules maternelles et fœtales en réponse à des stresseurs stériles ou infectieux, et semblent orchestrer une réponse multi-tissulaire incluant la contractilité myométriale, la préparation cervicale, et l’affaiblissement/rupture des membranes fœtales, menant au commencement du travail préterme. Ce système intégré pourrait avoir été conservé durant l’évolution mammifère à cause d’une survie accrue de la mère et/ou du fœtus lorsque la gestation est terminée dans un contexte spécifique, comme l’infection. Donc, l’inflammation pourrait constituer une voie commune finale pour les nombreuses causes de la naissance prématurée. De façon importante, des données récentes sug- gèrent que cette inflammation est transmise au fœtus et en retour induit des dommages aux organes qui pourraient sous-tendre le développement de maladies néonatales majeures. De cibler l’inflammation en prénatal plutôt que les contractions myométriales pourrait constituer une approche sécuritaire et plus efficace, comme suggéré par de récentes études animales.

Despite displaying broad tropism in vivo, human cytomegalovirus (CMV) contained in bodily fluids replicates inefficiently in most cultured cell types except fibroblasts. As propagation in fibroblasts leads to the accumulation of genomic changes, a number of strains were generated by serial passaging on endothelial cells. One of these, TB40/E, was shown to contain a mixture of genetically distinct virus variants, and to retain tropism for fibroblasts, endothelial and epithelial cells. Cloning of an endotheliotropic subpopulation produced the TB40-BAC4 variant, extensively used in CMV tropism studies. Because TB40-BAC4 represents only one of the different variants comprising TB40/E, we generated a series of epithelial-cell adapted stocks derived from a TB40/E mixed stock, rather than from TB40-BAC4. Within two passages on ARPE-19 cells, virus populations were produced with the ability to enter and initiate replication with similar efficiencies in both epithelial cells and fibroblasts. Although the ability to release progeny also increased, cell-free virus yields from ARPE-19 cells remained consistently two to three-logs lower than from fibroblasts, hinting at the existence of a post-entry and post-genome synthesis block in epithelial cells. Multinucleated syncytia also rapidly appeared exclusively in ARPE-19 cell cultures, where their numbers and dimensions increased with virus passage. Irrespective of the number of infected nuclei comprising each syncytium, however, only one cytoplasmic virion assembly compartment was consistently observed, leading us to speculate that improvements in entry efficiency associated with ARPE-19 cell adaptation lead to the development of syncytia, which may negatively affect progeny release by limiting the amount of resources available to maturing virions.

Background The impact of left bundle branch block (LBBB) on left ventricular (LV) myocardial work may vary according to the specific definition of a LBBB. Quantification of the interplay between LV myocardial work and the underlying electrical dyssynchrony may improve our understanding of cardiac resynchronization therapy (CRT) response. Objective To evaluate the impact of LBBB, defined according to Strauss and ESC 2013 ECG criteria, as well as non-LBBB morphologies on different LV myocardial work indices and response to CRT. Methods LBBB was defined according to the Strauss criteria and ESC 2013 guidelines on heart failure. LV myocardial constructive and wasted work (CW and WW) were derived from pressure-strain loop analysis integrating valvular opening and closing times, speckle tracking strain echocardiography and noninvasive blood pressure measurement. LV myocardial work efficiency (WE) was calculated from the ratio of constructive work, divided by the sum of constructive and wasted work. CRT response was defined as a decrease in LV end-diastolic volume (EDV) ≥15% at 6 months' follow-up. Results Patients were divided into 3 groups: 1) LBBB according to Strauss criteria (group 1, n=109, age 64±10 years), 2) LBBB according to ESC 2013 criteria (group 2, n=22, age 64±10 years) and 3) non-LBBB (group 3, n=44, age 69±10 years). Patients from group 1 were 4.2 times more likely to respond to CRT than patients from group 3 (odds ratio [OR] 4.182; 95% confidence interval [CI], 1.999–8.750; p Conclusion Patients with a LBBB according to Strauss criteria had a higher probability of response to CRT, compared to those with a LBBB defined by ESC 2013 guidelines criteria or with non-LBBB morphology. This is reflected in a greater amount of wasted work and more impaired LV myocardial work efficiency at baseline in patients with LBBB satisfying Strauss criteria, compared to the other two groups, representing the substrate for CRT. Acknowledgement/Funding Study was supported by ESC Research grant 2018

Background Myocardial work, assessed by speckle tracking echocardiography, reflects mechanical efficiency of the left ventricle. In heart failure patients, characterization of acute changes in regional (septal and lateral) left ventricular (LV) myocardial walls after cardiac resynchronization therapy (CRT) may enhance understanding of CRT response. Objective To evaluate the interaction between CRT response and components of myocardial work of the lateral wall and septum in patients with heart failure. Methods Regional LV myocardial work was calculated by integrating non-invasive blood pressure measurements, timing of mitral and aortic valve opening and closure and speckle tracking-derived LV longitudinal strain. From pressure-strain loops, constructive work (CW) and wasted work (WW) were calculated. CRT response was defined as a decrease in LV end-systolic volume ≥15% at 6 months follow-up. Changes in CW and WW of the septal and lateral walls prior to (baseline) and within the first 5 days after CRT implantation were compared between CRT responders and non-responders. Results At baseline, measurement of regional CW and WW was performed in 168 patients treated with CRT (71% men, 66±10 years). At 6 months, 59% of patients were CRT responders. CRT responders more frequently had non-ischemic heart failure than non-responders (54% vs 36%; p=0.027). At baseline, CRT responders were characterized by a significantly higher septal WW (270.5 [160.0; 451.5] mmHg% vs. 210.5 [106.3; 336.5] mmHg%; p=0.038) and lateral CW (989.5 [574.0; 1439.0] mmHg% vs. 689.0 [463,3; 1140.0] mmHg%; p=0.005). On multivariable analysis, only CW of the lateral wall at baseline was independently associated with CRT response (HR 1.001; 95% CI, 1.000–1.001; p=0.048). Immediately after CRT implantation, measurement of regional CW and WW was feasible in 115 patients. CRT responders showed improvement in CW (433.0 [254.5; 686.5] mmHg% to 664.5 [424.5; 977.8] mmHg%; p Conclusion CRT responders are characterized by increased WW of the septum and CW of the lateral wall at baseline, which are corrected immediately after CRT implantation. Constructive work of the LV lateral wall at baseline is independently associated with CRT response. Acknowledgement/Funding Study was supported by ESC Research grant 2018

Preterm birth is associated with proinflammatory conditions and alterations in adult cardiac shape and function. Neonatal exposure to high oxygen, a rat model of prematurity-related conditions, leads to cardiac remodeling, fibrosis, and dysfunction. TLR (Toll-like receptor) 4 signaling is a critical link between oxidative stress, inflammation, and the pathogenesis of cardiovascular diseases. The current study sought to investigate the role of TLR4 signaling in neonatal oxygen-induced cardiomyopathy. Male Sprague-Dawley pups were kept in 80% oxygen or room air from day 3 to 10 of life and treated with TLR4 antagonist lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides (LPS-RS) or saline. Echocardiography was performed at 4, 7, and 12 weeks. At 12 weeks, intraarterial blood pressure was measured before euthanization for histological and biochemical analyses. At day 10, cardiac TLR4, Il (interleukin) 18, and Il1β expression were increased in oxygen-exposed compared with room air controls. At 4 weeks, compared with room air-saline, saline-, but not LPS-RS treated-, oxygen-exposed animals, exhibited increased left ventricle mass index, reduced ejection fraction, and cardiac output index. Findings were similar at 7 and 12 weeks. LPS-RS did not influence echocardiography in 12 weeks room air animals. Systolic blood pressure was higher in saline- but not LPS-RS treated-oxygen-exposed animals compared with room air-saline and -LPS-RS controls. LPS-RS prevented cardiac fibrosis and cardiomyocytes hypertrophy, the increased TLR4, Myd88, and Il18 gene expression, TRIF expression, and CD68+ macrophages infiltration associated with neonatal oxygen exposure, without impact in room air rats. This study indicates that neonatal exposure to high oxygen programs TLR4 activation, which contributes to cardiac remodeling and dysfunction.

INTRODUCTION: Remdesivir is a direct-acting nucleoside RNA polymerase inhibitor with activity against the novel SARS-CoV-2 virus used in the treatment of COVID-19 pneumonia Here we describe a case of suspected remdesivir-induced acute liver failure (ALF) successfully treated with intravenous acetylcysteine METHODS: A 68-year-old female was identified as COVID-19 positive while in the operating room undergoing multi-vessel cardiac bypass surgery While previously asymptomatic, she required intensive care unit admission for worsening oxygenation on post-operative day (POD) 2, and remdesivir was initiated On POD 3, amiodarone was initiated for new onset atrial fibrillation By POD 4 (remdesivir day 3, amiodarone day 2), the patient developed an AST/ALT of >5000 units/L each, a total bilirubin of 3 1 mg/dL, and an ammonia of 161 umol/L Remdesivir and amiodarone were discontinued and continuous infusion acetylcysteine was initiated using the 21-hour acetaminophen toxicity protocol of 150 mg/kg over 1 hour, 50 mg/kg over 4 hours, and 100 mg/kg over 16 hours By the end of the 21-hour infusion, the AST/ ALT had decreased to 1348/1861 units/L The patient's LFTs and total bilirubin returned to normal within 14 days of discontinuation of remdesivir (POD 18) The patient was discharged home with home health 4 days later (POD 22) RESULTS: Remdesivir has been reported in practice to cause transaminitis up to 5-10 times the upper limit of normal based on early clinical trials, and the Emergency Use Authorization (EUA) issued by the FDA requires ongoing monitoring of ALT throughout therapy Due to remdesivir only recently being widely used in clinical practice, the incidence of remdesivir-induced ALF is unclear Amiodarone was unlikely the cause of ALF due to very recent timing of initiation and the rapid resolution of symptoms once discontinued despite the long half-life of amiodarone While acetylcysteine is FDA approved only for acetaminophen overdose, there are small studies and case reports of its use in nonacetaminophen- induced liver failure The use of a novel, unapproved therapy through an EUA program may place patients at risk for unexpected adverse events and, in this case, the patient's acute liver failure resolved after treatment with acetylcysteine

Background Extremely preterm birth is associated with death and a higher risk of adverse long-term outcomes. Neurodevelopmental impairment (NDI) has become the focus of neonatal follow-up and outcome research, with classifications chosen by clinicians and researchers. However, parents were never consulted about this classification. Objectives To examine parental perspectives about the health of their ex-preterm infants. Design/Methods Over a one-year period, at Sainte-Justine University Hospital’s Neonatal Follow-Up Clinic, all parents of children born Results 249 parental responses were obtained (98% participation rate). On average, parents rated their child’s health to be 8/10 (range 3-10/10, median 8/10). Main themes invoked about areas for improvement were developmental outcomes (65%):“if he could talk and hold his head up himself”; respiratory heath and overall medical fragility (35%): “improve the health of her lungs”; and behavior/emotional issues (21%): “his anxiety”. Twenty-three percent did not wish to improve anything: “I am very happy with his health and development. I hope he continues on the same path.” When examining developmental outcomes more closely, the recurrent sub-themes for improvement were: language/communication (22%), motor/movement (17%) and cognitive/learning (16%): “improving her attention in school”. Conclusion When they come to neonatal follow-up, parents generally perceive the health of their extremely preterm children in a positive way. While some parents have no wishes for improvement in their children, many are concerned by their children’s NDI. On the other hand, several parent-important outcomes, such as lung health and overall medical fragility, are insufficiently investigated during follow-up at the present time.

Functional mitral regurgitation (FMR) and atrial fibrillation (AF) are frequent heart failure (HF) complications. Cardiac resynchronization therapy (CRT) can improve FMR; however, little is known about the influence of AF on FMR improvement.The purpose of this study was to investigate the mechanisms and impact of baseline AF on FMR improvement after CRT.CRT recipients with HF, AF, or sinus rhythm (SR) at baseline with moderate or severe FMR, were included from an ongoing registry. Left atrial (LA), mitral annular (MA), and left ventricular (LV) dimensions were evaluated echocardiographically. FMR improvement was defined as ≥1 grade decrease from baseline to 6-month follow-up. Clinical and echocardiographic measurements were performed at baseline and 6-month follow-up.A total of 419 patients (age 66 ± 8 years; 73% male) were analyzed. At 6-month follow-up, FMR improved in 145 patients (45.6%) with SR vs 31 of AF patients (30.7%) (P = .011). Despite similar LV reverse remodeling at 6 months after CRT (LV end-systolic volume decreased by 32.1 ± 43.2 mL in the SR group and by 27.7 ± 6.3 mL in those with AF; P = .353), patients with SR exhibited smaller LA volumes (63.0 ± 26.5 mL vs 103.1 ± 41.0 mL; P.001) and MA diameters (42.3 ± 5.6 mm vs 46.1 ± 5.8 mm; P.001) compared to AF patients.FMR improvement is more common in CRT recipients in SR vs AF, despite a similar degree of LV remodeling. LA volume and MA diameter are greater in the AF group, causing the negative impact of AF on FMR improvement in CRT, as well as indicating a potential therapeutic target (ie, AF rhythm control).

The factors influencing the results of transcatheter mitral valve repair using the MitraClip system for secondary mitral regurgitation (MR) are still controversial. We hypothesized that insufficient remodeling of the mitral leaflets relative to the annular dilatation may be associated with the