MI Arrest Research Articles

Impact of heart failure on COVID-19 patients: An insight from nationwide inpatient sample

BackgroundPatients with COVID-19 have been reported to experience adverse cardiovascular outcomes, such as myocarditis, acute myocardial infarction, and heart failure. Among these complications, heart failure (HF) has emerged as the most common critical complication during exacerbations of COVID-19, potentially leading to increased mortality rates and poorer clinical outcomes. We aimed to investigate the in-hospital outcomes of COVID-19 patients with HF. MethodsWe analyzed the Nationwide Inpatient Sample (NIS) dataset to select COVID-19 patients aged over 18 years who were hospitalized between January 1, 2020, and December 31, 2020, using ICD-10. Based on the presence of acute HF, the patients were divided into two cohorts. The clinical outcomes and complications were assessed at index admissions using STATA v.17." Results1,666,960 COVID-19 patients were hospitalized in 2020, of which 156,755 (9.4%) had associated HF. COVID-19 patients with HF had a mean age of (72.38 ± 13.50) years compared to (62.3 ± 17.67) years for patients without HF. The HF patients had a higher prevalence of hypertension, hyperlipidemia, type 2 diabetes, smoking, and preexisting cardiovascular disease. Additionally, after adjusting for baseline demographics and comorbidities, COVID-19 patients with HF had higher rates of in-hospital mortality (23.86% vs. 17.63%, p<0.001), acute MI (18.83% vs. 10.91%, p<0.001), acute stroke (0.78% vs. 0.58%, p=0.004), cardiogenic shock (2.56% vs. 0.69%, p<0.001), and sudden cardiac arrest (5.54% vs. 3.41%, p<0.001) compared to those without HF. ConclusionCOVID-19 patients admitted with acute HF had worse clinical outcomes, such as higher mortality, myocardial infarction, cardiogenic shock, cardiac arrest, and a higher length of stay and healthcare than patients without HF.

Clinical impact of type 1 and type 2 diabetes mellitus in atrial fibrillation and the effect of severe hypoglycaemia: a nationwide cohort study

Abstract Background Both atrial fibrillation (AF) and diabetes mellitus (DM) are common chronic conditions associated with a significant disease burden. Diabetes increases the risk of AF and the presence of both diseases is associated with higher risk of all-cause mortality and complications. We aimed to compare prognosis individuals with type 1 (T1DM) and type 2 (T2DM) diabetes, against those without DM, in a nationwide cohort of patients with AF and second, to study the outcomes in cases of severe hypoglycaemia amongst those with DM. Methods Based on the France nationwide administrative hospital-discharge database, we collected information for all AF patients seen in French hospitals between 2014 and 2022. Among 3,311,634 patients identified with AF, 694,610 (21.0%) had diabetes: 37,218 (1.1%) with T1DM and 657,392 (19.9%) with T2DM. History of severe hypoglycaemia was defined as a primary or secondary hospital ICD-10 diagnosis of E16.0, E16.1, E16.2, E10.0, E11.0, E12.0, E13.0, or E14.0 and was identified in 22,717 patients (3.1% of those with T1DM and 3.3% of those with T2DM). Adverse outcomes were investigated during follow-up until 31 December 2022. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox model and were adjusted for age, sex and comorbidities (hypertension, obesity, smoking, alcohol abuse, coronary artery disease, heart failure, valve disease, presence of pacemaker or implantable cardioverter defibrillator, peripheral artery disease, stroke, chronic lung disease, chronic kidney disease, dementia and history of cancer). Results Using individuals without diabetes as reference, the adjusted HRs indicated an increased risk in patients T1DM and in those with T2DM for all-cause death, cardiovascular death, HF, MI, ischemic stroke, dementia, VT/VF and cardiac arrest (HRs ranging from 1.19 to 1.69 in T1DM and from 1.10 to 1.41 in T2DM, all p &amp;lt;0.0001, see Table 1). Among patients with diabetes, those with a history of severe hypoglycaemia had increased risks of all-cause death, dementia and cardiac arrest in case of T1DM and an increased risk of all-cause death, cardiovascular death, HF, MI, dementia and cardiac arrest in case of T2DM (see Table 2). Conclusion Presence of diabetes (regardless of type) is associated with an increased risk of premature death, cardiovascular events and dementia in patients with AF. This increase seems more pronounced in T1DM than in T2DM. A history of severe hypoglycaemia is associated with a much worse prognosis in patients with T1DM or T2DM.

Abstract 15750: Impact of Acute Heart Failure on COVID -19 Patients: An Insight From Nationwide Inpatient Sample

Introduction: Patients with COVID-19 had experienced adverse cardiovascular outcomes, such as myocarditis, MI, and Heart Failure (HF). Among them, HF has emerged as the most common critical complication during COVID-19 exacerbations, potentially leading to increased mortality rates and poorer clinical outcomes. However, there is a lack of available data to thoroughly investigate the consequences of acute HF in patients admitted with COVID-19. Methods: We analyzed the Nationwide Inpatient Sample (NIS) dataset to select COVID-19 patients over 18 years old who were hospitalized during 2020, in the United States (US) using ICD-10. Based on the presence of acute HF, patients were divided into two cohorts. Propensity score was used to match patients across various factors including age, race, sex, and comorbidities. Results: A total of 1,666,960 COVID-19 patients were hospitalized in 2020, of which 156,755 (9.4%) had associated HF. COVID-19 patients with HF had a mean age of (72.38±13.50) years compared to (62.3 ± 17.67) years for patients without HF. HF patients had a higher prevalence of HTN, hyperlipidemia, type 2 diabetes, smoking, and preexisting cardiovascular disease. After propensity matching, HF patients had higher rates of in-hospital mortality (23.86% vs 17.63%, p&lt;0.001), acute MI (18.83% vs 10.91%, p&lt;0.001), acute stroke (0.78% vs 0.58%, p=0.004), cardiogenic shock (2.56% vs 0.69%, p&lt;0.001), and sudden cardiac arrest (5.54% vs 3.41%, p&lt;0.001) compared to those without HF. Conclusions: COVID-19 patients admitted with acute HF had worse clinical outcomes and higher mortality rates. In addition to a higher length of stay and healthcare compared with patients without HF.

Phenotypic variability in two female siblings with oocyte maturation arrest due to a TUBB8 variant

Tubulin beta-8 (TUBB8) is expressed exclusively in the oocyte and early embryo, encoding a beta-tubulin polypeptide that participates in the assembly of microtubules. TUBB8 was first attributed to being responsible for oocyte MI arrest. Further studies have demonstrated that patients with different pathogenic variants have variable phenotypes. We report a TUBB8 variant (c.10 A > C) in two siblings who presented different clinical features of primary infertility. The younger sister showed severe oocyte maturation arrest with abnormal morphology, whereas a few mature oocytes and zygotes could be retrieved from the older sister, but no embryo was available for transfer. This variant was previously reported without in vitro functional assays. In the present study, RT‒qPCR and western blot analyses revealed that c.10 A > C reduces TUBB8 mRNA and protein levels; however, immunofluorescence demonstrated that this variant does not change the localization of the protein. These findings confirm the pathogenicity of the c.10 A > C variant and support the relationship between the variant and phenotype in the patients.

Chromatin Morphology in Human Germinal Vesicle Oocytes and Their Competence to Mature in Stimulated Cycles.

The search for simple morphological predictors of oocyte quality is an important task for assisted reproduction technologies (ARTs). One such predictor may be the morphology of the oocyte nucleus, called the germinal vesicle (GV), including the level of chromatin aggregation around the atypical nucleolus (ANu)-a peculiar nuclear organelle, formerly referred to as the nucleolus-like body. A prospective cohort study allowed distinguishing three classes of GV oocytes among 135 oocytes retrieved from 64 patients: with a non-surrounded ANu and rare chromatin blocks in the nucleoplasm (Class A), with a complete peri-ANu heterochromatic rim assembling all chromatin (Class C), and intermediate variants (Class B). Comparison of the chromatin state and the ability of oocytes to complete meiosis allowed us to conclude that Class B and C oocytes are more capable of resuming meiosis in vitro and completing the first meiotic division, while Class A oocytes can resume maturation but often stop their development either at metaphase I (MI arrest) or before the onset of GV breakdown (GVBD arrest). In addition, oocytes with a low chromatin condensation demonstrated a high level of aneuploidy during the resumption of meiosis. Considering that the degree of chromatin condensation/compaction can be determined in vivo under a light microscope, this characteristic of the GV can be considered a promising criterion for selecting the best-quality GV oocytes in IVM rescue programs.

PAK2 is essential for chromosome alignment in metaphase I oocytes

As a highly conserved and ubiquitously expressed serine/threonine kinase, p21-activated kinase 2 (PAK2) participates in diverse biologic events. However, its roles in mouse oocyte meiotic maturation remain unclear. The present study revealed that mouse oocytes depleted of Pak2 were unable to completely progress through meiosis and that a majority were arrested at metaphase I. Pak2 depletion thus prompted MI arrest and induced meiotic chromosome alignment defects in mouse oocytes, in part due to a reduction in polo-like kinase (PLK1). We demonstrated that PAK2’s interaction with PLK1 protected it from degradation by APC/CCdh1, and that it promoted meiotic progression and bipolar spindle formation. Our data collectively display critical functions for PAK2 in meiotic progression and chromosome alignment in mouse oocytes.

Mitochondrial E3 ubiquitin ligase MARCH5 is required for mouse oocyte meiotic maturation†.

As the most abundant organelles in oocytes, mitochondria play an important role in maintaining oocyte quality. Here, we report that March5, encoding a mitochondrial ubiquitin ligase that promotes mitochondrial elongation, plays a critical role in mouse oocyte meiotic maturation via regulating mitochondrial function. The subcellular localization of MARCH5 was similar to the mitochondrial distribution during mouse oocyte meiotic progression. Knockdown of March5 caused decreased ratios of the first polar body extrusion. March5-siRNA injection resulted in oocyte mitochondrial dysfunctions, manifested by increased reactive oxygen species, decreased ATP content as well as decreased mitochondrial membrane potential, leading to reduced ability of spindle formation and an increased ratio of kinetochore-microtubule detachment. Further study showed that the continuous activation of the spindle assembly checkpoint and the failure of Cyclin B1 degradation caused MI arrest and first polar body (PB1) extrusion failure in March5 knockdown oocytes. Taken together, our results demonstrated that March5 plays an essential role in mouse oocyte meiotic maturation, possibly via regulation of mitochondrial function and/or ubiquitination of microtubule dynamics- or cell cycle-regulating proteins.

Oocyte phenotype, genetic diagnosis, and clinical outcome in case of patients with oocyte maturation arrest.

oocyte maturation arrest (OMA) is currently one of the major causes of in vitro fertilization (IVF) failure, and several gene mutations were found to be associated with OMA. The purpose of this study was to identify the oocyte phenotype, genetic diagnosis, and clinical outcomes of patients with OMA and explore their possible interrelationships, thus providing a more individualized and efficient treatment strategy guidance accordingly. A retrospective study was conducted, involving 28 infertile women with OMA in the Reproductive Medicine Center of Tongji Hospital from 2018 to 2021. Whole-exome sequencing was performed for the detection of gene mutations. Patients were classified into three groups based on their oocyte phenotype, and for each group, the immature oocytes were cultured in vitro and mature oocytes were fertilized to evaluate both the maturation capacity and developmental potential. The clinical outcomes of OMA patients with different gene mutations or from different groups were further analyzed and compared. Twenty-eight women with OMA were evaluated in this study. According to the stage of OMA, 14 (50.0%) women were classified as OMA Type-1 (GV arrest), 5 (17.9%) were OMA Type-2 (MI arrest), and 9 (32.1%) were OMA Type-3 (with both GV and MI arrest). Immature oocytes from OMA patients exhibited significantly lower maturation rates even after IVM, compared to those in general patients. Seven patients (25.0%) were detected to have deleterious variations in two genes (PATL2 and TUBB8), known to be associated with the OMA phenotype. Patients with identified mutations were found to have little opportunity to obtain offspring with their own oocytes. Among the patients without mutations identified, those classified as OMA Type-1 or Type-3 still had a chance to obtain offspring through IVF or natural pregnancy, while all patients in the Type-2 group failed to obtain live birth. Three different phenotypes were observed in patients with OMA. The clinical outcomes of patients were associated with the presence of gene mutations and the classification of oocyte phenotype, thus a reasonable triage system was proposed to optimize the allocation of health care resources and maximize patient benefit.

Septin 9 controls CCNB1 stabilization via APC/CCDC20 during meiotic metaphase I/anaphase I transition in mouse oocytes.

The anaphase promoting complex/cyclosome (APC/C) and its cofactors CDH1 and CDC20 regulate the accumulation/degradation of CCNB1 during mouse oocyte meiotic maturation. Generally, the CCNB1 degradation mediated by APC/CCDC20 activity is essential for the transition from metaphase to anaphase. Here, by using siRNA and mRNA microinjection, as well as time-lapse live imaging, we showed that Septin 9, which mediates the binding of septins to microtubules, is critical for oocyte meiotic cell cycle progression. The oocytes were arrested at the MI stage and the connection between chromosome kinetochores and spindle microtubules was disrupted after Septin 9 depletion. As it is well known that spindle assembly checkpoint (SAC) is an important regulator of the MI-AI transition, we thus detected the SAC activity and the expression of CDC20 and CCNB1 which were the downstream proteins of SAC during this critical period. The signals of Mad1 and BubR1 still remained on the kinetochores of chromosomes in Septin 9 siRNA oocytes at 9.5h of in vitro culture when most control oocytes entered anaphase I. The expression of CCNB1 did not decrease and the expression of CDC20 did not increase at 9.5h in Septin 9 siRNA oocytes. Microinjection of mRNA encoding Septin 9 or CDC20 could partially rescue MI arrest caused by Septin 9 siRNA. These results suggest that Septin 9 is required for meiotic MI-AI transition by regulating the kinetochore-microtubule connection and SAC protein localization on kinetochores, whose effects are transmitted to APC/CCDC20 activity and CCNB1 degradation in mouse oocytes.

Abstract 11760: Depression Paradox for In-Hospital Cardiovascular Outcomes in Obstructive Sleep Apnea - A National Population-Level Analysis

Background: ​​Depression is a frequently encountered comorbidity in patients with Obstructive Sleep Apnea (OSA), with a higher prevalence than the general population. However, there is limited data on the impact of psychiatric comorbidities on the outcomes of OSA. Methods: We identified OSA hospitalizations using the National Inpatient Sample (2018) and relevant ICD-10 codes. After propensity score matching, demographics and comorbidities were compared between the two groups of OSA with (OSA-D+) vs without depression (OSA-D-). The odds of in-hospital outcomes between them were analysed using multivariable regression analyses. Results: Of the 2169730 OSA hospitalizations, 20.1% had comorbid depression. Matched cohorts included 846150 admissions in both groups - OSA-D+ and OSA-D-.The OSA-D+ cohort often consisted of younger (median age, 64 vs 65); females (55.5% vs 55.2%) with both cohorts predominantly including white, Medicare enrollees. The OSA-D+ cohort had significantly higher rates (all p&lt;0.001) of comorbidities such as Hypertension (68.6% vs 64.6%); Diabetes (48.4% vs 47.4%); Hyperlipidemia (59.2% vs 53.5%); Congestive Heart Failure (21.7% vs 20.6%); Peripheral Vascular Disease (6.7% vs 6.3%); Anemia (22.4% vs 19.7%); Smoking (44.6% vs 41.8%); Substance abuse, prior MI,TIA/Stroke and Venous Thromboembolism compared to the OSA-D- group. Paradoxically, there was decreased all-cause mortality (OR:0.79, 95%CI 0.73-0.86), major adverse cardiac and cerebrovascular events (OR:0.83, 95%CI 0.80-0.87), acute MI (OR:0.80, 95%CI 0.76-0.85), dysrhythmia/AF (OR:0.81, 95%CI 0.79-0.83) and cardiac arrest including VF (OR:0.65, 95%CI 0.73-0.82) in the OSA-D+ cohort cohort during hospitalization (p&lt;0.001). Conclusion: Despite having more comorbidities, OSA patients with depression were found to have better in-hospital outcomes. Further studies are required for a conclusive reason for this paradoxical effect of co-morbid depression.

Abstract 12809: Cirrhotic Cardiomyopathy Before Orthotropic Liver Transplantation is Associated With Major Adverse Cardiac Events at 13-Months Post Orthotropic Liver Transplantation

Background: Major adverse cardiac events (MACE) are a leading cause of morbidity and mortality after orthotopic liver transplantation (OLT). Cirrhotic cardiomyopathy (CCM) is relatively common and a source of MACE in patients after OLT. Initial diagnostic criteria based on transthoracic echocardiogram (TTE) were described in 2005 and revised in 2019 with echocardiographic advancements (Table 1). We sought to identify CCM related predictors of MACE at 13 months post-OLT. Methods: This is a retrospective study of adult patients who underwent OLT between 2009-2019. All patients had TTE’s within one year pre-OLT and one month to 13 months post-OLT. We excluded TTE’s within one-month post-OLT to reduce contributions from stress cardiomyopathy. Patients with a left ventricular ejection fraction less than 50% pre-OLT were excluded. MACE was defined as death, MI, CHF hospitalization, or cardiac arrest. Multivariable Cox regression was used to identify independent predictors of MACE. Results: Of 568 OLT patients screened, 131 met inclusion criteria for this study. There were 103 and 23 patients who met 2005 and 2019 criteria, respectively. During the 13 month follow up period, 42 patients had MACE. Compared to those without MACE, patients with MACE had more ascites (93 vs 70%, p 0.003), hepatorenal syndrome (HRS) (17 vs 4%, p 0.019), delayed OLT &gt;10 days after admission (19 vs 7%, p 0.033), pre-OLT CCM per 2005 criteria (90% vs 73%, p 0.023), and lower diastolic blood pressure (60.81 vs 66.88, p 0.014). There was no difference in pre-OLT CCM per 2019 criteria (19 vs 17%, p 0.758) or MELD-Na score (21.24 vs 19.40, p 0.166). In multi-variable cox regression analysis adjusted for diastolic blood pressure, HRS, ascites, and OLT timing during admission, CCM per 2005 criteria remained significant as seen in Figure 1 (Hazard Ratio = 3, p 0.038). Conclusion: CCM per 2005 criteria is an independent predictor of MACE at 13 months post-OLT while CCM per 2019 criteria is not.

Identification of TUBB8 Variants in 5 Primary Infertile Women with Multiple Phenotypes in Oocytes and Early Embryos

Tubulin beta 8 class VIII (TUBB8) is a β-tubulin isotype that is specifically expressed in human oocytes and early embryos. It has been identified as a disease-causing gene in primary female infertility by affecting oocyte maturation arrest. This study investigated the genetic cause of female infertility in five patients from four families. Five women with primary infertility were recruited. Medical-exome sequencing and Sanger sequencing were performed on the patients, and their family members to identify candidate genes that explained infertility. Additionally, the morphology of oocytes and zygotes from the patients and controls were assessed. We observed recurrent oocytes MI arrest, oocytes abnormal fertilization, uncleaved embryos, and embryo transfer failure in the patients. Heterozygous missense variants in TUBB8, c.538G > A (p.V180M), c.527C > G (p.S176W), c.124C > G (p.L42V), and c.628A > C (p.I210L), were verified in four unrelated families. This study expanded the mutational spectrum of TUBB8 by identifying three novel heterozygous missense variants. Screening for TUBB8 mutation demonstrated the diagnostic utility of female infertility.

Long-term follow-up of medically treated patients with spontaneous coronary artery dissection: a prospective, Swiss single-centre cohort study

Spontaneous coronary artery dissection (SCAD) is an increasingly diagnosed cause of acute myocardial infarction. However, there is still a limited number of larger cohorts with long-term follow-up. We report on the largest Swiss single-centre cohort to date, with follow-up of up to 22 years. We prospectively collected SCAD cases from June 1998 until December 2020. A strategy of systematic follow-up angiography was applied. Information on long-term follow-up was collected up to the end of 2020. Major cardiovascular events (MACE) were defined as all-cause death, non-fatal MI, and non-fatal cardiac arrest. We identified 105 SCAD patients (mean age 53 ± 11 years, 98 female, 5 peripartum). Presentation was myocardial infarction in all patients. In 102 patients, there was one contiguous dissection. Three patients had two (n = 2) or three (n = 1) non-contiguous dissections. In the majority of patients (n = 97), the primary treatment approach was conservative (dual antiplatelet therapy for 12 months in 90% of patients, statins in 91%). Seven patients were treated with percutaneous coronary intervention (PCI) and one patient underwent bypass surgery. Elective follow-up angiograms were performed in 73 asymptomatic patients after a median follow-up of 6.0 months (interquartile range [IQR] 5.5-6.5). These showed healing of the dissection (n = 65) or a good result after PCI (n = 5) in 70 patients. Three patients had a persistent dissection but conservative treatment was continued. After a median follow-up of 7.5 years (IQR 3.6-12.5) (longest follow-up: 22.5 years) there were 15 MACE. Five MACE occurred within 30 days of the index event: death following catastrophic peripartum left main SCAD (n = 1), out-of-hospital cardiac arrest with successful resuscitation 16 days after SCAD (n = 1), ST-segment elevation myocardial infarction due to occlusion of the dissected artery 10 hours after the index angiogram with subsequent PCI (n = 1), SCAD of a second vessel 8 days after the index SCAD (n = 1), and non-ST-segment elevation myocardial infarction with persistent, multisite SCAD 10 days after the index event (n = 1). There were 10 late MACE, including myocardial infarction and recurrent SCAD (different vessel/lesion) a median of 7.6 years (IQR 3.9-9.6) after the index event in eight patients and death with unclear cause in two patients. This SCAD series highlights its highly variable clinical course during the acute phase and in the long term. Although most SCAD patients can be treated conservatively with subsequent healing of the dissection and good clinical outcome, there are also patients with dramatic acute presentation or MACE several years after the initial presentation.

EFFECT OF ANTICOAGULATION AND ANTIPLATELET AGENTS ON HYPERCOAGULABILITY STATES IN PATIENTS WITH COVID-19

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: We retrospectively investigated COVID-19 patients on anticoagulation or antiplatelet medications as their home medication or used as inpatient treatment to evaluate if they exhibited lower levels of D-dimer and lower rates of embolic events and mortality. METHODS: This correlational retrospective study evaluated n=319 COVID-19 patients admitted to acute inpatient services across the Mercy Health Youngstown hospitals. A retrospective chart audit included home medications and admission medications, hospital and ICU length of stay, days on the ventilator, initial and follow-up labs (D-dimer), and thromboembolic events after diagnosis of COVID-19. We constructed a composite index for any embolic events occurring in inpatient: MI, DVT, PE, stroke, and cardiac arrest. The prevalence of these embolic events was 23.5% (n=75/319). For propensity modeling, comorbidities, initial D-dimer, demographics, days from a positive COVID-19 test result to admission, and a summative index of comorbidities were entered in a binary logistic regression model to predict embolic events. RESULTS: The rate of any embolic events among COVID inpatients was 23.5% (n=75/319). Initial D-dimer was 1648±1702 ng/mL among patients experiencing any embolic events and was lower among patients without embolic events, 1009±1205 ng/mL (t=3.638, p < 0.001). In iterative forward selection, logistic modeling retained in the model for embolic events were age, initial D-dimer, past medical history of ESRD, and ethnicity, which correctly classified 75% of embolic events in patients (AUC=0.702). The addition of home medications, antiplatelets and anticoagulants to the propensity model did not significantly improve AUC (0.704) which indicates that neither home use of anticoagulation nor antiplatelets was associated with inpatient embolic events in a propensity adjusted model. However, when inpatient anticoagulation therapy was initiated, statistically significant benefit in preventing embolic events was observed (AOR = 3.32 (95% CI 1.79-6.16); AUC 0.752 (p < 0.001)). Similarly, home use of antiplatelet and anticoagulation medications was not associated with mortality in COVID-19 patients, but in-hospital use of anticoagulation was statistically significant (p=0.036). CONCLUSIONS: Our study aimed to see if taking antiplatelet or anticoagulation medications as a home medication would have any effect on thromboembolic events and mortality in COVID-19 patients compared to when receiving antiplatelet or anticoagulation agents during hospitalization. We found that being on an antiplatelet or anticoagulation medication at home (before hospitalization) did not prevent COVID-19 patients from thromboembolic events or improve mortality. However, after adjusting for baseline risk of embolic events, in-hospital anticoagulation had a statistically significant benefit in preventing embolic events and mortality. CLINICAL IMPLICATIONS: It has been established that COVID-19 patients are at higher risk for embolic events that have been linked to increased mortality. In our current study using a composite index model to predict embolic events in COVID-19 patients, the use of anticoagulation agents during hospitalization revealed a significant reduction in embolic risks and mortality while patients on home antiplatelet or anticoagulation medications did not show benefits in reducing the same risks. DISCLOSURES: No relevant relationships by Omotooke Babalola, source=Web Response No relevant relationships by Timothy Barreiro, source=Web Response No relevant relationships by David Gemmel, source=Web Response No relevant relationships by Oyidiya Osoka, source=Web Response No relevant relationships by Jeannie Ur, source=Web Response

FBXO34 Regulates the G2/M Transition and Anaphase Entry in Meiotic Oocytes.

There are two important events in oocyte meiotic maturation, the G2/M transition and metaphase I progression. Thousands of proteins participate in regulating oocyte maturation, which highlights the importance of the ubiquitin proteasome system (UPS) in regulating protein synthesis and degradation. Skp1–Cullin–F-box (SCF) complexes, as the best characterized ubiquitin E3 ligases in the UPS, specifically recognize their substrates. F-box proteins, as the variable adaptors of SCF, can bind substrates specifically. Little is known about the functions of the F-box proteins in oocyte maturation. In this study, we found that depletion of FBXO34, an F-box protein, led to failure of oocyte meiotic resumption due to a low activity of MPF, and this phenotype could be rescued by exogenous overexpression of CCNB1. Strikingly, overexpression of FBXO34 promoted germinal vesicle breakdown (GVBD), but caused continuous activation of spindle assembly checkpoint (SAC) and MI arrest of oocytes. Here, we demonstrated that FBXO34 regulated both the G2/M transition and anaphase entry in meiotic oocytes.

Prevalence and predictors associated with in-hospital mortality in acute ST segment elevation myocardial infarction after reperfusion therapy in developing country.

The prevalence and predictors of in-hospital mortality in the unselected patients with ST-segment elevation myocardial infarction (STEMI) after reperfusion therapy with fibrinolytic or primary percutaneous coronary intervention (PCI) in developing country have not well established. We conducted a retrospective cohort study design. All admission records of acute ST elevation myocardial infarction at Suratthani Hospital between October 2015 and September 2017. The finding between October 2015 and September 2017, a total of 431 patients received reperfusion therapy and were included in the present study. Majority of the patient were male (80.5%), almost half of the population had anterior wall MI, 32 patients died (7.4%), and 399 survived during the index hospitalization. The prevalence of chronic kidney disease, anterior wall MI, cardiogenic shock and cardiac arrest in non-survived group was higher than the survived group. Echocardiogram was performed in 299 patient (69.4%) and the median left ventricular ejection fraction (LVEF) in overall population was 51%. After adjustment for baseline variables, LVEF (aOR 0.91, 95% CI, 0.83-0.98, P=0.02) and cardiac arrest at presentation (aOR 22, 95% CI, 1.22-410.05, P=0.036) were independently associated with in-hospital mortality. LVEF and cardiac arrest at presentation were independently associated with in-hospital mortality in STEMI patients receiving reperfusion therapy either fibrinolytic therapy or primary PCI.

Oocyte Maturation in Starfish.

Oocyte maturation is a process that occurs in the ovaries, where an immature oocyte resumes meiosis to attain competence for normal fertilization after ovulation/spawning. In starfish, the hormone 1-methyladenine binds to an unidentified receptor on the plasma membrane of oocytes, inducing a conformational change in the heterotrimeric GTP-binding protein α-subunit (Gα), so that the α-subunit binds GTP in exchange of GDP on the plasma membrane. The GTP-binding protein βγ-subunit (Gβγ) is released from Gα, and the released Gβγ activates phosphatidylinositol-3 kinase (PI3K), followed by the target of rapamycin kinase complex2 (TORC2) and 3-phosphoinositide-dependent protein kinase 1 (PDK1)-dependent phosphorylation of serum- and glucocorticoid-regulated kinase (SGK) of ovarian oocytes. Thereafter, SGK activates Na+/H+ exchanger (NHE) to increase the intracellular pH (pHi) from ~6.7 to ~6.9. Moreover, SGK phosphorylates Cdc25 and Myt1, thereby inducing the de-phosphorylation and activation of cyclin B–Cdk1, causing germinal vesicle breakdown (GVBD). Both pHi increase and GVBD are required for spindle assembly at metaphase I, followed by MI arrest at pHi 6.9 until spawning. Due to MI arrest or SGK-dependent pHi control, spawned oocytes can be fertilized normally

Novel homozygous mutations in PATL2 lead to female infertility with oocyte maturation arrest.

To identify the disease gene in 40 patients with female infertility due to oocyte maturation arrest. Genomic DNA was extracted from peripheral blood of 40 patients and their family members. Whole-exome sequencing was performed on the patients, and the PATL2 mutations were identified and confirmed by Sanger sequencing. Harmfulness of the mutations was analyzed by SIFT, Polyphen-2, Mutation Taster, and M-CAP software, and we used western immunoblotting analysis to check the effect of mutations on PATL2 protein expression in vitro. Two novel missense mutations c.1528C>A (p.Pro510Thr) and c.1376C>A (p.Ser459Tyr) in PATL2 were identified in three patients (7.5%) from two consanguineous families in our cohort. We found that mutations in PATL2 resulted in variable oocyte phenotypes, including GV arrest, MI arrest, and morphologic abnormalities. Western immunoblotting analysis showed that the expression levels of the two novel mutant PATL2 proteins decreased significantly. We identified two novel PATL2 mutations that caused oocyte maturation arrest and abnormal morphology, and variable phenotypes in patients.

KETAMINE VS ETOMIDATE FOR RAPID SEQUENCE INTUBATION IN THE CRITICALLY ILL POPULATION

SESSION TITLE: Endotracheal Intubation: Getting In and Getting Out SESSION TYPE: Original Investigations PRESENTED ON: 10/23/2019 10:45 AM - 11:45 AM PURPOSE: Etomidate and ketamine are both used for sedation in rapid sequence intubation (RSI). Early studies reported few adverse pulmonary or cardiovascular effects with etomidate use, but recent work describes potential increased mortality secondary to adrenal suppression, and possible hypotension with etomidate use in critically ill patients. Ketamine has, thus, been suggested as an alternative agent. Few studies have compared outcomes for ketamine vs. etomidate for RSI, and results are conflicting. Given the paucity of literature, and controversy over best agent, we compared outcomes with ketamine vs. etomidate for RSI in the critical care setting. METHODS: A multi-center retrospective cohort study was conducted on patients aged 18 and older who underwent rapid sequence intubation (RSI) between 1/1/2017 and 12/31/2017. Outcomes of interest included post-RSI hypotension, hospital length of stay, ventilator days, in-hospital death, and post-RSI cardiac events (MI, CVA, or cardiac arrest). RESULTS: Of 842 identified patients, 808 were exposed to etomidate and 34 to ketamine as part of RSI. There were no differences in patient characteristics or comorbidities between groups. Post-RSI hypotension was lower in those exposed to ketamine 41.2% vs. 57.0%, p = 0.078. After controlling for concurrent medications (propofol, fentanyl, versed, levophed, vasopressin, and steroid use), ketamine was less likely to cause clinical hypotension compared to etomidate in patients with non-sepsis (OR = 0.28, 95% CI 0.10-0.79, p = 0.017) and in general overall (OR = 0.36, 95% CI 0.15-0.85, p = 0.019). However, in just the sepsis group, ketamine was insignificant (OR = 0.66, 95% CI 0.13-3.42, p = 0.619). There were no differences in length of stay, ventilator days, in-hospital death or post-RSI cardiac events between groups. CONCLUSIONS: Though ketamine was associated with less clinical hypotension when used in RSI, this did not translate to differences in patient outcomes. CLINICAL IMPLICATIONS: Concerns have been raised regarding etomidate use in RSI for patients with sepsis because of etomidate’s effect on the adrenal axis and potential to increase mortality. However, we found no meaningful difference in hospital complications, length of stay, or mortality, even in those patients who had sepsis. Given the small number of patients in our study, additional work is required to evaluate for drug superiority, specifically in patients with sepsis. DISCLOSURES: No relevant relationships by Jordan Arends, source=Web Response No relevant relationships by John Elliott, source=Web Response No relevant relationships by Kim Jordan, source=Web Response No relevant relationships by Vincent Kang, source=Web Response No relevant relationships by Gabrielle Sabino, source=Web Response No relevant relationships by Steven Wu, source=Web Response

Tubastatin A inhibits HDAC and Sirtuin activity rather than being a HDAC6-specific inhibitor in mouse oocytes.

Tubastatin A (TubA) is a highly selective histone deacetylase 6 (HDAC6) inhibitor. As expected, mouse germinal vesicle oocytes fail to extrude the first polar body following TubA treatment. However, a previous study demonstrated that homozygous Hdac6 knockout (KO) mice can be viable and fertile. Therefore, we asked whether TubA is indeed a specific inhibitor of HDAC6 activity. RNA-sequencing and in silico analysis demonstrated that the TubA-treated group presented significant changes in the expression of Hdac subfamily genes such as Hdac6, 10, and 11, and Sirtuin 2, 5, 6, and 7. Additionally, gene expression related to the p53, MAPK, Wnt, and Notch signaling pathways in the TubA-treated group were increased significantly; in contrast, gene expression related to metabolism, DNA replication, and oxidative phosphorylation was decreased significantly. Furthermore, gene expression related to cell cycle, cell structure, pyrimidine metabolism, pentose phosphate pathway, mitochondrial activation, proteasome pathway, RNA polymerase, DNA replication, cyclin-dependent kinase, nucleolar activity, and MI arrest were significantly decreased, indicating that TubA-induced abnormal meiotic maturation and oocyte senescence may be due to the combined effects of HDAC and Sirtuin inhibition, and not HDAC6 inhibition alone. Thus, we believed that this system could provide a model for monitoring the effects of TubA on mouse oocytes.