Blocking vicious cycle of cardiac dysfunction by external cardiopulmonary resuscitation is the key to rescue acute aluminium phosphide poisoning

Aluminium phosphide (ALP) and aluminium zinc phosphide (ZnP), the two main ingredients of fumigation drugs, are commonly used to kill insects or rodents in grain. When exposed to water, highly toxic phosphine gas is released and absorbed through the respiratory or digestive tract. Phosphine gas could non-selectively block cytochrome oxidase, inhibit electron transfer and suppress oxidative phosphorylation, leading to cellular hypoxia and organ dysfunction. The characteristic clinical manifestations are refractory shock and metabolic acidosis with high mortality. However, patients with ALP poisoning have a chance to be cured. Here, we report a case of oral ALP poisoning that was successfully treated by extracorporeal membrane oxygenation (ECMO) combined with continuous renal replacement therapy (CRRT) during frequent ventricular fibrillation and cardiac dysfunction.

THE INFLUENCE OF CLINICAL AND LABORATORY FACTORS ON THE DEVELOPMENT OF HEMODYNAMIC COMPLICATIONS DURING ANESTHESIA IN CARDIAC SURGERY

Background. Currently, cardioanesthesiology is one of the most actively developing areas of modern medicine. Thanks to new methods of treatment, the contingent of patients for whom it became possible to undergo cardiac surgery has significantly expanded. The main problems that lead to hemodynamic complications are endothelial dysfunction and cellular hypoxia. Purpose. To present data on the influence of clinical and laboratory factors of endothelial dysfunction and cellular hypoxia on the development of hemodynamic complications during anesthesia in cardiac surgery. Material and methods. The review and analysis of literature data from 49 sources is presented. Results. The laboratory markers of endothelial dysfunction leading to the development of major hemodynamic complications in cardiovascular diseases are MPC-1, CRP, NO, TNF-α, IL-6, homocysteine. Conclusion. The data obtained indicate a significant effect of cell markers (MPC-1, CRP, NO, TNF-A, IL-6, homocysteine) as well as clinical and laboratory factors of endothelial dysfunction not only on the development of major diseases of the cardiovascular system, but also on their complications. An early study of these markers can improve anesthesia during cardiac surgery as well as reduce complications in the postoperative period.

THE INFLUENCE OF CLINICAL AND LABORATORY FACTORS ON THE DEVELOPMENT OF HEMODYNAMIC COMPLICATIONS DURING ANESTHESIA IN CARDIAC SURGERY

Background. Currently, cardioanesthesiology is one of the most actively developing areas of modern medicine. Thanks to new methods of treatment, the contingent of patients for whom it became possible to undergo cardiac surgery has significantly expanded. The main problems that lead to hemodynamic complications are endothelial dysfunction and cellular hypoxia. Purpose. To present data on the influence of clinical and laboratory factors of endothelial dysfunction and cellular hypoxia on the development of hemodynamic complications during anesthesia in cardiac surgery. Material and methods. The review and analysis of literature data from 49 sources is presented. Results. The laboratory markers of endothelial dysfunction leading to the development of major hemodynamic complications in cardiovascular diseases are MPC-1, CRP, NO, TNF-α, IL-6, homocysteine. Conclusion. The data obtained indicate a significant effect of cell markers (MPC-1, CRP, NO, TNF-A, IL-6, homocysteine) as well as clinical and laboratory factors of endothelial dysfunction not only on the development of major diseases of the cardiovascular system, but also on their complications. An early study of these markers can improve anesthesia during cardiac surgery as well as reduce complications in the postoperative period.

450 Cellular Energy Monitoring for Diagnosis and Management of Therapy for Sleep Disordered Breathing

Introduction Polysomnogram (PSG) monitoring, including pulse oximetry, is the current diagnostic standard in sleep medicine. However, potentially confounding aspects of PSG testing include: test site other than the subject’s normal bed, distracting sensors and wires, subjective interpretation of complex recorded signals, and limited sensitivity to relevant phenomena. There is currently an unmet need for a sleep test that is more clinically effective than PSG, and that can be administered in the subject’s normal sleeping environment. Additionally, confirmation that home therapy has been optimized cannot be achieved by PSG titration. Methods A recent proof of concept (POC) study of the armband-wearable Reveal Cellular Energy Monitor (CE monitor) directly compared its data product, Cellular Energy Index (CEi), with PSG data. Scoring methods were adapted from AASM guidance for interpretation of PSG data. At-home recording with the CE monitor was also performed prior to and following PSG studies. At-home incremental adjustment of APAP settings and mask selection was documented with CE monitoring and compared with the information recorded by the home APAP machine. Results The comparison of the POC data consistently found the CE monitor to be more sensitive and responsive to hypoxic stress than the PSG pulse oximeter during primary snoring. Obstructive and central apnea events were detected by both, but the CE monitor provided finer resolution of the breath-by-breath effort of breathing compared with PSG RIP and nasal sensors. At-home CE monitor optimization of therapy was documented to often differ from the settings and mask selection determined by PSG titration, and resulted in ‘normal’ sleep breathing data. Conclusion All diagnostically-relevant physiologic responses detected by PSG were also detected by the CE monitor. Evidence of cellular hypoxia in the skin, by CE monitor, was consistently recorded during prolonged periods of ‘primary snoring;’ i.e., SpO2 is less sensitive to hypoxic stress during sleep than CEi. Breath-by-breath effort is detected by the CE monitor. Support (if any) The POC study costs at UCSF were paid by Reveal Biosensors, Inc.

Micronutrients in Sepsis and COVID-19: A Narrative Review on What We Have Learned and What We Want to Know in Future Trials

Sepsis remains the leading cause of mortality in hospitalized patients, contributing to 1 in every 2–3 deaths. From a pathophysiological view, in the recent definition, sepsis has been defined as the result of a complex interaction between host response and the infecting organism, resulting in life-threatening organ dysfunction, depending on microcirculatory derangement, cellular hypoxia/dysoxia driven by hypotension and, potentially, death. The high energy expenditure driven by a high metabolic state induced by the host response may rapidly lead to micronutrient depletion. This deficiency can result in alterations in normal energy homeostasis, free radical damage, and immune system derangement. In critically ill patients, micronutrients are still relegated to an ancillary role in the whole treatment, and always put in a second-line place or, frequently, neglected. Only some micronutrients have attracted the attention of a wider audience, and some trials, even large ones, have tested their use, with controversial results. The present review will address this topic, including the recent advancement in the study of vitamin D and protocols based on vitamin C and other micronutrients, to explore an update in the setting of sepsis, gain some new insights applicable to COVID-19 patients, and to contribute to a pathophysiological definition of the potential role of micronutrients that will be helpful in future dedicated trials.

Molecular factors predicting steroid resistance in pediatric nephrotic syndrome

Objectives: the objective of this paper was to study the levels of cellular hypoxia, apoptosis controlling factors in children with steroid-sensitive and steroid-resistant nephrotic syndrome. Background: patients with steroid-resistant nephrotic syndrome (SRNS) represent a challenging subset of patients with nephrotic syndrome who often fail standard immunosuppression and have a higher likelihood of progressing to end-stage renal disease. The search of the biochemical markers undergoing the steroid-resistance is under urgent need. Methods: an examination of kidney biopsies and blood of 56 patients (aged 10 to 15 years) with nephrotic syndrome was done. Conventional clinical investigations, immunohistochemistry, immunoblotting were used in this study. Results: patients with steroid-resistant nephrotic syndrome show an increased level of HIF-1 alfa (a marker of cellular hypoxia) as compared to the control group and children with steroid-sensitive nephrotic syndrome. Patients with steroid-resistant nephrotic syndrome show a down-regulation of anti-apoptotic marker BcL-xL as compared to the control group and children with steroid-sensitive nephrotic syndrome. Conclusion: hypoxia-induces disorders and apoptosis activation markers are considered to be included in the complex scheme predicting steroid-resistance in nephrotic children.

HACE1 blocks HIF1α accumulation under hypoxia in a RAC1 dependent manner

Uncovering the mechanisms that underpin how tumor cells adapt to microenvironmental stress is essential to better understand cancer progression. The HACE1 (HECT domain and ankyrin repeat-containing E3 ubiquitin-protein ligase) gene is a tumor suppressor that inhibits the growth, invasive capacity, and metastasis of cancer cells. However, the direct regulatory pathways whereby HACE1 confers this tumor-suppressive effect remain to be fully elucidated. In this report, we establish a link between HACE1 and the major stress factor, hypoxia-inducible factor 1 alpha (HIF1α). We find that HACE1 blocks the accumulation of HIF1α during cellular hypoxia through decreased protein stability. This property is dependent on HACE1 E3 ligase activity and loss of Ras-related C3 botulinum toxin substrate 1 (RAC1), an established target of HACE1 mediated ubiquitinylation and degradation. In vivo, genetic deletion of Rac1 reversed the increased HIF1α expression observed in Hace1–/– mice in murine KRasG12D-driven lung tumors. An inverse relationship was observed between HACE1 and HIF1α levels in tumors compared to patient-matched normal kidney tissues, highlighting the potential pathophysiological significance of our findings. Together, our data uncover a previously unrecognized function for the HACE1 tumor suppressor in blocking HIF1α accumulation under hypoxia in a RAC1-dependent manner.

Is Serum Lactate a Good Predictor of Mortality in Children Aged 2 Months to 5 Years With Pneumonia in Central Vietnam

Pneumonia is a major cause of morbidity and mortality in children globally. Lactate, a product of anaerobic cellular metabolism, has been used as an indicator of poor tissue oxygenation and cellular hypoxia. Our objective was to determine whether serum lactate concentration at hospital admission predicted mortality in children aged 2 months to 5 years with pneumonia. Two hundred and eighty-one pediatric patients admitted to the Department of Pediatrics of a provincial hospital with WHO-defined pneumonia and severe pneumonia were included; of whom, 8 died during hospital stay. The median serum lactate concentration was 4.8 mmol/l (IQR 2.6-6.9) among children who died and 3.6 mmol/l (IQR 2.8-4.3) among children who survived ( P > .05); 4.1 mmol/l (IQR 2.7-4.7) among children with severe pneumonia and 3.5 mmol/l (IQR 2.8-4.3) among children with pneumonia ( P > .05). Serum lactate concentration had a low value in predicting pneumonia-related mortality (AUC 0.68, 95% CI 0.62-0.73); and the concentration cut-off of >4.06 mmol/l had the best sensitivity and specificity (75% and 68.9%, respectively) with a 2.4-fold risk of death (LR+ 2.4; 95% CI 1.6-3.7). Although hyperlactatemia was associated with severity and mortality in children 2 months to 5 years of age with pneumonia, its benefit was unclear.

Abstract 14708: Temporal Relationship Between Erythropoietin Administration and Mitochondrial Dysfunction in Cardiac Ischemia/reperfusion Injury

Introduction: Acute myocardial infarction remains a leading cause of mortality. Rapid restoration of coronary blood flow is the cornerstone of treatment. Paradoxically, it leads to a condition known as ischemia/reperfusion (I/R) injury which precipitates more injuries to the heart. Erythropoietin (EPO), a hormone produced by the kidneys in response to cellular hypoxia, reportedly provides cardioprotection following cardiac I/R injury in many preclinical experiments. Unfortunately, clinical trials failed to demonstrate cardioprotection when EPO was given after reperfusion. Therefore, we aim to determine the temporal influences on administering EPO in cardiac I/R injury. Hypothesis: Administration of EPO at different time points provides varying efficacy in reducing arrhythmias, LV and cardiac mitochondrial dysfunction after cardiac I/R injury. Methods: Male Wistar rats were divided into sham-operated and cardiac I/R group. In I/R group, rats were subdivided into 4 groups (n=10/group): vehicle, EPO pretreatment (P-EPO), EPO given during ischemia (I-EPO), and EPO given at reperfusion onset (R-EPO). EPO was intravenously given to the rats (5000 unit/kg). Rats underwent 30-min LAD ligation followed by 120-min reperfusion. Arrhythmia scores and LV function were recorded throughout the protocol. Then, rats were sacrificed to determine infarct size and mitochondrial function. Results: Cardiac I/R injury induced arrhythmias, LV and mitochondrial dysfunction (Fig . Administration of EPO before or during ischemia, but not at the onset of reperfusion, significantly attenuated LV dysfunction and infarct size. However, EPO did not reduce arrhythmia scores. Although EPO given at all time points reduced mitochondrial reactive oxygen species, EPO given at reperfusion failed to prevent mitochondrial swelling (Fig) . Conclusions: Acute EPO treatment before or during ischemia, but not at the onset of reperfusion, exerted cardioprotection against I/R injury.