Hyperlactatemia

By studying mutations in yeast and human cells, scientists say they have found that biochemical bonds between fats and proteins in the mitochondrion, the cell's powerhouse, play a crucial role in how our cells produce energy. By studying mutations in yeast and human cells, Johns Hopkins Medicine scientists say they have found that biochemical bonds between fats and proteins in the mitochondrion, the cell's powerhouse, play a crucial role in how our cells produce energy. The study results, published June 5 in The EMBO Journal, shed new light, researchers say, on the way the altered mitochondrial membranes found in people with metabolic diseases such as Barth syndrome, a rare genetic disorder that weakens the heart, fail to enable cellular power production. Metabolism is a set of biochemical reactions central to making energy to fuel life and to getting rid of substances a body no longer needs. Metabolic diseases include forms of high cholesterol that run in families. Approximately one in three adults have some form of a metabolic syndrome, according to the National Heart, Lung, and Blood Institute. Building on previous research, the Johns Hopkins scientists sought to better understand the interaction of two components in the mitochondrial membrane: cardiolipin, a fatty compound, or lipid, and proteins that transport the building blocks of adenosine triphosphate, or ATP, an energy molecule made by the mitochondria that fuels cell metabolism. "Down the line, a better understanding of protein-lipid interactions could help researchers find new therapeutic targets for a wide range of metabolic diseases, including Barth syndrome," says senior author Steven Claypool, Ph.D., professor of physiology at the Johns Hopkins University School of Medicine. He says previous studies suggested it's likely that protein-lipid interactions in mitochondrial membranes play an important role in regulating mitochondria's powerhouse activities. The researchers conducted their experiments in samples of yeast with mutations, or alterations, in a mitochondrial membrane protein called AAC and samples of human cells that modeled a person with a mutation of the protein ANT1 who was diagnosed with metabolic disease, symptoms of which include weakness in the heart and skeletal muscles, exercise intolerance and hyperlactatemia, or elevated lactate levels in the blood. The protein in yeast, AAC, is the equivalent of ANT in humans, Claypool says. Looking at three areas where cardiolipin binds to the AAC proteins in yeast, Claypool and his colleagues found that when they introduced mutations into AAC2 to disrupt these interactions, cardiolipin could no longer bond to the protein, which weakened its structure and lowered its function. Similarly, in the cell model of the person with mutations in ANT1, the protein's structure was weakened, limiting its ability to transport ATP across the mitochondrial membrane. "These findings indicate that when the interaction between cardiolipin and proteins break down, the entire process that makes mitochondria our powerhouse is disrupted," says first author Nanami Senoo, Ph.D., a postdoctoral fellow in Claypool's lab. Claypool says few studies have detailed individual protein-lipid interactions, and many more experiments will be needed to "understand the full complement of mechanisms and roles that these interactions have in the membrane." Mitochondrial membranes contain a lot of proteins, many of which associate with lipids. "This discovery opens up new possibilities for understanding the complexities of how our cells produce energy," Claypool says. "In the future, we plan to explore how other protein-lipid interactions contribute to energy production." Other scientists who contributed to the study are Matthew G. Baile, Oluwaseun B. Ogunbona, James A. Saba, Teona Munteanu, Yllka Valdez, Kevin Whited and Macie S. Sheridan of Johns Hopkins; Dinesh K. Chinthapalli, Bodhisattwa Saha, Abraham O. Oluwole, Dror Chorev and Carol V. Robinson of University of Oxford; Vinaya K. Golla, Nathan N. Alder and Eric R. May of University of Connecticut. Funding for this study was provided by the National Institutes of Health (R01HL108882, R01HL165729, R35GM119762, T32GM007445 and T32GM136577), the American Heart Association, the Uehara Memorial Foundation, the Barth Syndrome Foundation and the Royal Society Newton International Fellowship.

Studies presented at World Congress of Pediatric Cardiology and Cardiac Surgery show Etiometry’s clinical intelligence platform supports efficient escalation and safe de-escalation decisions to enhance patient outcomes and reduce length of stay BOSTON--(BUSINESS WIRE)-- Etiometry, the leader in clinical decision-support software, shares exciting new study results from ten hospitals, including Boston Children’s Hospital, Children’s of Alabama, Children’s National Hospital and St. Louis Children’s Hospital, that demonstrate the significant impact its platform has on outcomes for critically ill patients. Physician researchers presented their findings at the World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) in Washington, D.C. on Monday, Aug. 28, 2023. Key data highlights include: Etiometry utilization reduced time on mechanical ventilation by 22% and decreased hospital length of stay in these patients by 19%. Etiometry utilization reduced time on vasoactive medications by 18%. Etiometry’s Hyperlactatemia Index provides early warning for elevated lactic acid, alerting the care team to potentially impaired oxygen delivery. The studies utilized Etiometry’s FDA-cleared Risk Analytics, Automated Clinical Pathways and Quality Improvement App to address pressing challenges in critical care settings, which are often the most complex and expensive units in the hospital. Etiometry’s Risk Analytics provide an individualized assessment of the patient’s condition, bringing attention to patients who need it most and revealing insight into the cause of potential deterioration or improvement to a patient's state. When paired with the platform’s Clinical Pathway Automation, care teams can achieve the elusive balance of individualized and standardized care to support quality initiatives like ICU liberation. Mechanical Ventilation Management Extubation failure is associated with significant morbidity, including prolonged total ventilation time and longer hospital length of stay. Extubation readiness trials (ERTs) are used to guide clinicians when a patient is ready to extubate, and these manual workflows are cumbersome for staff. Etiometry automates this process, providing clinicians with alerts when a patient is eligible for an ERT, and automatically tracks performance throughout the spontaneous breathing trial. The study presented at WCPCCS analyzed before and after deployment of Etiometry’s automated ERT pathway on patients undergoing cardiopulmonary bypass surgery and found that using Etiometry reduced time on mechanical ventilation by 22%. Study Title: Automated Extubation Readiness Tool is Associated with Improved Outcomes Following Pediatric Cardiac Surgery 747 patients were included in the analysis Research led by Santiago Borasino MD, MPH, Donald M. James Chair in Pediatric Cardiac Critical Care Medicine, Professor of Pediatrics, and Section Head of Pediatric Cardiac Critical Care Medicine, Division of Cardiology, University of Alabama at Birmingham, and Medical Director, Cardiovascular Intensive Care Unit, of Children’s of Alabama Weaning of Vasoactive Medications Vasoactive medication is crucial for hemodynamic management after cardiac surgery, but its use carries risks of complications and requires close monitoring and individual patient management for appropriate care de-escalation. Until now, there have been no clinical trials exploring the use of algorithms in the safe de-escalation of care. Etiometry’s IDO2 Index™, a non-invasive algorithm that predicts the probability of inadequate oxygen delivery, was paired with Etiometry’s clinical pathway automation capability to evaluate its potential to prompt earlier weaning of vasoactive medication support. The findings reveal the new automated standardized workflow in Etiometry informed data-driven decisions leading to an 18% reduction of time with vasoactive infusions. Study Title: Use of a Risk Analytic Algorithm to Inform Weaning from Vasoactive Medication in Patients Following Pediatric Cardiac Surgery 851 patients enrolled Research led by Joshua Salvin, MD, MPH, Pediatric Cardiac Intensivist, Attending, Department of Cardiology of Boston Children’s Hospital and Associate Professor of Pediatrics, Harvard Medical School Early Warning of Hyperlactatemia Pediatric patients after cardiac surgery are predisposed to develop low cardiac output syndrome. Serum lactate is a well-defined marker of inadequate systemic oxygen delivery which can be a major risk for organ failure. Researchers utilized Etiometry’s HLA Index™ to monitor inadequate perfusion and identify risk of HLA or hyperlactatemia (elevated lactic acid). Etiometry’s HLA Index showed a strong positive association with elevated lactic acid, providing the bedside clinician with an early, non-invasive warning of impaired oxygen delivery. Study Title: A Near Real Time Risk Analytics Algorithm Predicts Elevated Lactate Levels in Pediatric Cardiac Critical Care Patients: 3,496 enrolled patients compared to 58,168 lactic acid test results Research led by Ahmed M. Asfari, MD, MSHA, Pediatric Cardiologist, Cardiac Critical Care at Children’s of Alabama and Assistant Professor, University of Alabama at Birmingham “We’re grateful to the physician researchers who’ve utilized our platform and our superb team of data scientists, engineers and clinical specialists to tackle key challenges of a stressful, high-acuity environment, such as the ICU. The data are compelling, especially in terms of how our clinical intelligence can enhance patient care,” said Shane Cooke, CEO of Etiometry. “We look forward to supporting many more research and quality improvement initiatives.” Etiometry continues to expand its capabilities. This year, the company announced two software releases with several customer-driven enhancements, achieved two FDA clearances for its risk algorithms and continues to enable collaboration among clinicians to support standardization of care with automated clinical pathways. “Through our tools, automated reporting and support, we are committed to not only deploying our clinical decision support system technology into care, but equally important - enabling the measurement of their performance,” said Evan Butler, Co-founder of Etiometry and Chief Operating Officer. “These studies are a testament to the unique capability we can provide our ICUs.” Through Thursday, Aug. 31, WCPCCS attendees have the opportunity to engage in person with Etiometry’s experts, delve into the platform’s functionalities and experience live demonstrations that showcase its transformative potential. Those not in attendance can request an online demo at Etiometry.com/GetYourView. About Etiometry Founded in 2010, Etiometry is the leader in clinical decision-support software designed to help clinicians in the intensive care setting make data-based decisions regarding their patients’ care and treatment. The company’s technologies provide valuable clinical insight and analysis to support early recognition of subtle changes in patients’ conditions to avoid complications and speed recovery. Etiometry has nine FDA clearances and four Health Canada approvals and CE markings. With roots in pediatric ICUs, Etiometry is utilized by some of the world’s top academic medical centers as well as leading children’s hospitals ranked by US News and World Report and Newsweek. Etiometry is committed to improving patient outcomes, increasing clinical efficiency, and lowering the cost of care through the more effective use of data. The Etiometry Platform is the only critical care software solution that reveals deep insights into patient physiology, helping critical care teams deliver standardized and individualized care - and provides the ability to automate care escalation and de-escalation decisions. It is designed to facilitate the use of all available data to support the anticipation and management of the dynamic condition of patients requiring intensive care. To learn more, visit .

BOSTON--( BUSINESS WIRE )-- Etiometry , the leader in clinical decision-support software for critical care, today provided a glimpse into its 2023 priorities as well as highlights from 2022, which marked a landmark year of growth for the company – including its database volume, which now exceeds 150 million hours of deidentified data signals. These patient-generated data are key to scaling Etiometry’s technology to serve additional populations and inform the company’s risk algorithms, which bolster the platform’s use as a safety net for clinicians caring for critically ill patients. On the heels of record growth in 2021, Etiometry harnessed the momentum moving into 2022, more than doubling sales over 2021, and also initiated its first adult hospital installations. On the regulatory front, Etiometry announced this month its eighth FDA clearance ; the IDO2 Index TM is now cleared for adult use. In 2022, the company doubled its FDA-cleared risk analytics portfolio to four indices, adding the HLA Index™ for hyperlactatemia, and ACD Index™ for acidemia, further strengthening its capability to track the fundamental pathways through which patients deteriorate under intensive care. In other markets, the company received CE Marking and Health Canada authorization for all four risk algorithms in pediatrics and the additional approval of the ID02 algorithm in adults in each geography. “Our regulatory success uniquely positions Etiometry for further developments in 2023 that will result in enhanced offerings benefiting patients and the care teams treating them,” said Shane Cooke, CEO of Etiometry. “We’ve also seen a substantial uptick in clinicians using the platform’s data for research.” Six peer-reviewed articles were published about the Etiometry platform in 2022, bringing the total to 12 journals and adding to the more than 120 ongoing research projects, which include 15 multi-center studies. As the body of research highlighting the clinical efficacy of the Etiometry platform continues to grow, so does the attention from industry stakeholders. Following its 2021 strategic partnership with Terumo, last year, Etiometry formed its second partnership with Radiometer, a medical device company specializing in acute care testing solutions to enhance neonatal intensive care outcomes. In October, clinicians from some of the nation’s top-ranked hospitals participated in Etiometry’s Guiding Patient Safety Summit to discuss how the platform can impact patient care and improve daily workflows. Capping off the year, Frost & Sullivan presented Etiometry with its Enabling Technology Leadership Award for critical care decision making. In 2023, Etiometry aims to maintain its regulatory tempo, add new customers across pediatric and adult hospital systems, and continue to expand its utilization footprint by installing the platform in more intensive care units, operating rooms, and emergency departments – a number that has already grown by a factor of four over the past two years. Etiometry also plans to add to its talent pool – which currently includes clinicians to inform product developments, as well as data science experts to expand the reach of the company’s AI-based platform. “Aside from the strides we’re making in enhancing our platform’s capabilities, it’s exciting to pique the interest of more and more hospital leaders. The driver is always about enhancing patient care while reducing length of stay and readmissions,” said Cooke, “But, I would add that by decreasing the cognitive burden of care teams, Etiometry provides a concrete way to alleviate clinician burnout, which we all know, is a persisting problem. There really hasn’t been a better time for our solution.” About Etiometry Founded in 2010, Etiometry is the leader in clinical decision-support software designed to help clinicians in the intensive care setting make data-based decisions regarding their patients’ care and treatment. The company’s technologies provide valuable clinical insight and analysis to support early recognition of subtle changes in patients’ conditions to avoid complications and speed recovery. Etiometry has eight FDA clearances and four Health Canada approvals and CE markings. With roots in pediatric ICUs, Etiometry’s software is utilized by some of the world’s top academic medical centers, 20 of the Best Children’s Hospitals, ranked by U.S. News & World Report , 4 out of 5 of the highest ranked children’s hospitals in Newsweek’s Top Specialty Hospitals in the World and a growing number of top adult hospitals. Etiometry is committed to improving patient outcomes, increasing clinical efficiency, and lowering the cost of care through the more effective use of data. The Etiometry Platform is an end-to-end data management software solution for the collection, analysis, visualization, and archiving of ICU clinical data. It is designed to facilitate the use of all available data to support the anticipation and management of the dynamic condition of patients requiring intensive care. To learn more, visit www.etiometry.com .