A Novel Non-Psychoactive Fatty Acid from a Marine Snail, Conus inscriptus, Signals Cannabinoid Receptor 1 (CB1) to Accumulate Apoptotic C16:0 and C18:0 Ceramides in Teratocarcinoma Cell Line PA1.

The cannabinoid-type I (CB1) receptor functions as a double-edged sword to decide cell fate: apoptosis/survival. Elevated CB1 receptor expression is shown to cause acute ceramide accumulation to meet the energy requirements of fast-growing cancers. However, the flip side of continual CB1 activation is the initiation of a second ceramide peak that leads to cell death. In this study, we used ovarian cancer cells, PA1, which expressed CB1, which increased threefold when treated with a natural compound, bis(palmitoleic acid) ester of a glycerol (C2). This novel compound is isolated from a marine snail, Conus inscriptus, using hexane and the structural details are available in the public domain PubChem database (ID: 14275348). The compound induced two acute ceramide pools to cause G0/G1 arrest and killed cells by apoptosis. The compound increased intracellular ceramides (C:16 to 7 times and C:18 to 10 times), both of which are apoptotic inducers in response to CB1 signaling and thus the compound is a potent CB1 agonist. The compound is not genotoxic because it did not induce micronuclei formation in non-cancerous Chinese hamster ovarian (CHO) cells. Since the compound induced the cannabinoid pathway, we tested if there was a psychotropic effect in zebrafish models, however, it was evident that there were no observable neurobehavioral changes in the treatment groups. With the available data, we propose that this marine compound is safe to be used in non-cancerous cells as well as zebrafish. Thus, this anticancer compound is non-toxic and triggers the CB1 pathway without causing psychotropic effects.

Neurologic Statistical Prognostication and Risk Assessment for Kids on Extracorporeal Membrane Oxygenation-Neuro SPARK.

This study presents Neuro-SPARK, the first scoring system developed to assess the risk of neurologic injury in pediatric and neonatal patients on extracorporeal membrane oxygenation (ECMO). Using the extracorporeal life support organization (ELSO) registry, we applied robust machine learning methodologies and clinical expertise to a 10 years dataset. We produced separate models for veno-venous (V-V ECMO) and veno-arterial (V-A ECMO) configurations due to their different risk factors and prevalence of neurologic injury. Our models identified 14 predictor variables for V-V ECMO and 20 for V-A ECMO, which demonstrated moderate accuracy in predicting neurologic injury as defined by the area under the receiver operating characteristic (AUROC) (V-V = 0.63, V-A = 0.64) and good calibration as measured by the Brier score (V-V = 0.1, V-A = 0.15). Furthermore, our post-hoc analysis identified high- and low-risk groups that may aid clinicians in targeted neuromonitoring and guide future research on ECMO-associated neurologic injury. Despite the inherent limitations, Neuro-SPARK lays the foundation for a risk-assessment tool for neurologic injury in ECMO patients, with potential implications for improved patient outcomes.

Survival and neurobehavioral outcomes following out-of-hospital cardiac arrest in pediatric patients with pre-existing morbidity: An analysis of the THAPCA out-of-hospital arrest data.

AIM: Pre-arrest morbidity in adults who suffer out-of-hospital cardiac arrest (OHCA) is associated with increased mortality and poorer neurologic outcomes. The objective of this study was to determine if a similar association is seen in pediatric patients. METHODS: We performed a secondary analysis of data from the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital trial. Study sites included 36 pediatric intensive care units across the United States and Canada. The study enrolled children between the ages of 48 hours and 18 years following an OHCA between September 1, 2009 and December 31, 2012. For our analysis, patients with (N = 151) and without (N = 142) pre-arrest comorbidities were evaluated to assess morbidity, survival, and neurologic function following OHCA. RESULTS: No significant difference in 28-day survival was seen between groups. Dependence on technology and neurobehavioral outcomes were assessed among survivors using the Vineland Adaptive Behavior Scales-Second Edition (VABS-II), Pediatric Cerebral Performance Category (PCPC) and Pediatric Overall Performance Category (POPC). Children with pre-existing comorbidities maintained worse neurobehavioral function at twelve months, evidenced by poorer scores on POPC (p = 0.016), PCPC (p = 0.044), and VABS-II (p = 0.020). They were more likely to have a tracheostomy at hospital discharge (p = 0.034), require supplemental oxygen at three months (p = 0.039) and twelve months (p = 0.034), and be mechanically ventilated at twelve months (p = 0.041). CONCLUSIONS: There was no difference in survival to 28 days following OHCA in children with pre-existing comorbidity compared to previously healthy children. The group with pre-existing comorbidity was more reliant on technology following arrest and exhibited worse neurobehavioral outcomes.

Neuromonitoring of Pediatric and Adult Extracorporeal Membrane Oxygenation Patients: The Importance of Continuous Bedside Tools in Driving Neuroprotective Clinical Care.

Extracorporeal membrane oxygenation (ECMO) is a form of temporary cardiopulmonary bypass for patients with acute respiratory or cardiac failure refractory to conventional therapy. Its usage has become increasingly widespread and while reported survival after ECMO has increased in the past 25 years, the incidence of neurological injury has not declined, leading to the pressing question of how to improve time-to-detection and diagnosis of neurological injury. The neurological status of patients on ECMO is clinically difficult to evaluate due to multiple factors including illness, sedation, and pharmacological paralysis. Thus, increasing attention has been focused on developing tools and techniques to measure and monitor the brain of ECMO patients to identify dynamic risk factors and monitor patients' neurophysiological state as a function in time. Such tools may guide neuroprotective interventions and thus prevent or mitigate brain injury. Current means to continuously monitor and prevent neurological injury in ECMO patients are rather limited; most techniques provide indirect or postinsult recognition of irreversible brain injury. This review will explore the indications, advantages, and disadvantages of standard-of-care, emerging, and investigational technologies for neurological monitoring on ECMO, focusing on bedside techniques that provide continuous assessment of neurological health.

Pediatric Highlights From the Extracorporeal Life Support Organization Registry: 2017-2022.

The Extracorporeal Life Support Organization (ELSO) registry which collects data from hundreds of participating centers supports research in ECMO to help improve patient outcomes. The ELSO Scientific Oversight Committee, an international and diverse group of ECMOlogists ( https://www.elso.org/registry/socmembers.aspx ), selected the most impactful and innovative research articles on pediatric ECMO emerging from ELSO data. Here they present brief highlights of these publications.

Clinical Guidelines for Routine Neuromonitoring in Neonatal and Pediatric Patients Supported on Extracorporeal Membrane Oxygenation.

DISCLAIMER: These guidelines for routine neuromonitoring in neonatal and pediatric patients supported on extracorporeal membrane oxygenation (ECMO) are intended for educational use to build the knowledge of physicians and other health professionals in assessing the conditions and managing the treatment of patients undergoing extracorporeal life support (ECLS)/ECMO and describe what are believed to be useful and safe practice for ECLS and ECMO but these are not necessarily consensus recommendations. The aim of clinical guidelines was to help clinicians to make informed decisions about their patients. However, adherence to a guideline does not guarantee a successful outcome. Healthcare professionals must make their own treatment decisions about care on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge, and expertise. These guidelines do not take the place of physicians' and other health professionals' judgment in diagnosing and treatment of patients. These guidelines are not intended to and should not be interpreted as setting a standard of care or being deemed inclusive of all proper methods of care nor exclusive of other methods of care directed at obtaining the same results. The ultimate judgment must be made by the physician and other health professionals and the patient considering all the circumstances presented by the individual patient, and the known variability and biologic behavior of the clinical condition. These guidelines reflect the data at the time the guidelines were prepared; the results of subsequent studies or other information may cause revisions to the recommendations in these guidelines to be prudent to reflect new data, but ELSO is under no obligation to provide updates. In no event will ELSO be liable for any decision made or action taken in reliance upon the information provided through these guidelines.

Association Between Disrupted Cerebral Autoregulation and Radiographic Neurologic Injury for Children on Extracorporeal Membrane Oxygenation: A Prospective Pilot Study.

Validation of a real-time monitoring device to evaluate the risk or occurrence of neurologic injury while on extracorporeal membrane oxygenation (ECMO) may aid clinicians in prevention and treatment. Therefore, we performed a pilot prospective cohort study of children under 18 years old on ECMO to analyze the association between cerebral blood pressure autoregulation as measured by diffuse correlation spectroscopy (DCS) and radiographic neurologic injury. DCS measurements of regional cerebral blood flow were collected on enrolled patients and correlated with mean arterial blood pressure to determine the cerebral autoregulation metric termed DCSx. The primary outcome of interest was radiographic neurologic injury on eligible computed tomography (CT) or magnetic resonance imaging (MRI) scored by a blinded pediatric neuroradiologist utilizing a previously validated scale. Higher DCSx scores, which indicate disruption of cerebral autoregulation, were associated with higher radiographic neurologic injury score (slope, 11.0; 95% confidence interval [CI], 0.29-22). Patients with clinically significant neurologic injury scores of 10 or more had higher median DCSx measures than patients with lower neurologic injury scores (0.48 vs . 0.13; p = 0.01). Our study indicates that obtaining noninvasive DCS measures for children on ECMO is feasible and disruption of cerebral autoregulation determined from DCS is associated with higher radiographic neurologic injury score.

Hypothermia after extracorporeal cardiopulmonary resuscitation not associated with improved neurologic complications or survival in children: An analysis of the ELSO registry.

AIM: To analyze the association between hypothermia and neurologic complications among children who were treated with extracorporeal cardiopulmonary resuscitation (ECPR) using the Extracorporeal Life Support Organization (ELSO) international registry. METHODS: We conducted a retrospective, multicenter, database study utilizing ELSO data for ECPR encounters from January 1, 2011, through December 31, 2019. Exclusion criteria included multiple ECMO runs and lack of variable data. The primary exposure was hypothermia under 34 °C for greater than 24 hours. The primary outcome, determined a priori, was a composite of neurologic complications defined by ELSO registry including brain death, seizures, infarction, hemorrhage, diffuse ischemia. Secondary outcomes were mortality on ECMO and mortality prior to hospital discharge. Multivariable logistic regression determined the odds of neurologic complications, mortality on ECMO or prior to hospital discharge associated with hypothermia after adjustment for available pertinent covariables. RESULTS: Of the 2,289 ECPR encounters, no difference in odds of neurologic complications were found between the hypothermia and non-hypothermia groups (AOR 1.10, 95% CI 0.80-1.51). However, hypothermia exposure was associated with decreased odds of mortality on ECMO (AOR 0.76, 95% CI 0.59-0.97), but no difference in mortality prior to hospital discharge (AOR 0.96, 95% CI 0.76-1.21) CONCLUSION: Analysis of a large, multicenter, international dataset demonstrates that hypothermia for greater than 24 hours among children who undergo ECPR is not associated with decreased neurologic complications or mortality benefit at time of hospital discharge.

Expert consensus statement on venovenous extracorporeal membrane oxygenation ECMO for COVID-19 severe ARDS: an international Delphi study.

BACKGROUND: The high-quality evidence on managing COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support is insufficient. Furthermore, there is little consensus on allocating ECMO resources when scarce. The paucity of evidence and the need for guidance on controversial topics required an international expert consensus statement to understand the role of ECMO in COVID-19 better. Twenty-two international ECMO experts worldwide work together to interpret the most recent findings of the evolving published research, statement formulation, and voting to achieve consensus. OBJECTIVES: To guide the next generation of ECMO practitioners during future pandemics on tackling controversial topics pertaining to using ECMO for patients with COVID-19-related severe ARDS. METHODS: The scientific committee was assembled of five chairpersons with more than 5 years of ECMO experience and a critical care background. Their roles were modifying and restructuring the panel's questions and, assisting with statement formulation in addition to expert composition and literature review. Experts are identified based on their clinical experience with ECMO (minimum of 5 years) and previous academic activity on a global scale, with a focus on diversity in gender, geography, area of expertise, and level of seniority. We used the modified Delphi technique rounds and the nominal group technique (NGT) through three face-to-face meetings and the voting on the statement was conducted anonymously. The entire process was planned to be carried out in five phases: identifying the gap of knowledge, validation, statement formulation, voting, and drafting, respectively. RESULTS: In phase I, the scientific committee obtained 52 questions on controversial topics in ECMO for COVID-19, further reviewed for duplication and redundancy in phase II, resulting in nine domains with 32 questions with a validation rate exceeding 75% (Fig. 1). In phase III, 25 questions were used to formulate 14 statements, and six questions achieved no consensus on the statements. In phase IV, two voting rounds resulted in 14 statements that reached a consensus are included in four domains which are: patient selection, ECMO clinical management, operational and logistics management, and ethics. CONCLUSION: Three years after the onset of COVID-19, our understanding of the role of ECMO has evolved. However, it is incomplete. Tota14 statements achieved consensus; included in four domains discussing patient selection, clinical ECMO management, operational and logistic ECMO management and ethics to guide next-generation ECMO providers during future pandemic situations.

Predicting Cardiac Arrest in Children with Heart Disease: A Novel Machine Learning Algorithm.

BACKGROUND: Children with congenital and acquired heart disease are at a higher risk of cardiac arrest compared to those without heart disease. Although the monitoring of cardiopulmonary resuscitation quality and extracorporeal resuscitation technologies have advanced, survival after cardiac arrest in this population has not improved. Cardiac arrest prevention, using predictive algorithms with machine learning, has the potential to reduce cardiac arrest rates. However, few studies have evaluated the use of these algorithms in predicting cardiac arrest in children with heart disease. METHODS: We collected demographic, laboratory, and vital sign information from the electronic health records (EHR) of all the patients that were admitted to a single-center pediatric cardiac intensive care unit (CICU), between 2010 and 2019, who had a cardiac arrest during their CICU admission, as well as a comparator group of randomly selected non-cardiac-arrest controls. We compared traditional logistic regression modeling against a novel adaptation of a machine learning algorithm (functional gradient boosting), using time series data to predict the risk of cardiac arrest. RESULTS: A total of 160 unique cardiac arrest events were matched to non-cardiac-arrest time periods. Using 11 different variables (vital signs and laboratory values) from the EHR, our algorithm's peak performance for the prediction of cardiac arrest was at one hour prior to the cardiac arrest (AUROC of 0.85 [0.79,0.90]), a performance that was similar to our previously published multivariable logistic regression model. CONCLUSIONS: Our novel machine learning predictive algorithm, which was developed using retrospective data that were collected from the EHR and predicted cardiac arrest in the children that were admitted to a single-center pediatric cardiac intensive care unit, demonstrated a performance that was similar to that of a traditional logistic regression model. While these results are encouraging, future research, including prospective validations with multicenter data, is warranted prior to the implementation of this algorithm as a real-time clinical decision support tool.

Early Changes in Arterial Partial Pressure of Carbon Dioxide and Blood Pressure After Starting Extracorporeal Membrane Oxygenation in Children: Extracorporeal Life Support Organization Database Study of Neurologic Complications.

OBJECTIVE: Neurologic complications in pediatric patients supported by extracorporeal membrane oxygenation (ECMO) are common and lead to morbidity and mortality; however, few modifiable factors are known. DESIGN: Retrospective study of the Extracorporeal Life Support Organization registry (2010-2019). SETTING: Multicenter international database. PATIENTS: Pediatric patients receiving ECMO (2010-2019) for all indications and any mode of support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We investigated if early relative change in Pa co2 or mean arterial blood pressure (MAP) soon after starting ECMO was associated with neurologic complications. The primary outcome of neurologic complications was defined as a report of seizures, central nervous system infarction or hemorrhage, or brain death. All-cause mortality (including brain death) was used as a secondary outcome.Out of 7,270 patients, 15.6% had neurologic complications. Neurologic complications increased when the relative Pa co2 decreased by greater than 50% (18.4%) or 30-50% (16.5%) versus those who had a minimal change (13.9%, p < 0.01 and p = 0.046). When the relative MAP increased greater than 50%, the rate of neurologic complications was 16.9% versus 13.1% those with minimal change ( p = 0.007). In a multivariable model adjusting for confounders, a relative decrease in Pa co2 greater than 30% was independently associated with greater odds of neurologic complication (odds ratio [OR], 1.25; 95% CI, 1.07-1.46; p = 0.005). Within this group, with a relative decrease in Pa co2 greater than 30%, the effects of increased relative MAP increased neurologic complications (0.05% per BP Percentile; 95% CI, 0.001-0.11; p = 0.05). CONCLUSIONS: In pediatric patients, a large decrease in Pa co2 and increase in MAP following ECMO initiation are both associated with neurologic complications. Future research focusing on managing these issues carefully soon after ECMO deployment can potentially help to reduce neurologic complications.

Early Changes in Near-Infrared Spectroscopy Are Associated With Cardiac Arrest in Children With Congenital Heart Disease.

Background: The association of near-infrared spectroscopy (NIRS) with various outcomes after pediatric cardiac surgery has been studied extensively. However, the role of NIRS in the prediction of cardiac arrest (CA) in children with heart disease has yet to be evaluated. We sought to determine if a model utilizing regional cerebral oximetry (rSO2c) and somatic oximetry (rSO2s) could predict CA in children admitted to a single-center pediatric cardiac intensive care unit (CICU). Methods: We retrospectively reviewed 160 index CA events for patients admitted to our pediatric CICU between November 2010 and January 2019. We selected 711 control patients who did not have a cardiac arrest. Hourly data was collected from the electronic health record (EHR). We previously created a machine-learning algorithm to predict the risk of CA using EHR data. Univariable analysis was done on these variables, which we then used to create a multivariable logistic regression model. The outputs from the model were presented by odds ratio (OR) and 95% confidence interval (CI). Results: We created a multivariable model to evaluate the association of CA using five variables: arterial saturation (SpO2)- rSO2c difference, SpO2-rSO2s difference, heart rate, diastolic blood pressure, and vasoactive inotrope score. While the SpO2-rSO2c difference was not a significant contributor to the multivariable model, the SpO2-rSO2s difference was. The average SpO2-rSO2s difference cutoff with the best prognostic accuracy for CA was 29% [CI 26-31%]. In the multivariable model, a 10% increase in the SpO2-rSO2s difference was independently associated with increased odds of CA [OR 1.40 (1.18, 1.67), P < 0.001] at 1 h before CA. Our model predicted CA with an AUROC of 0.83 at 1 h before CA. Conclusion: In this single-center case-control study of children admitted to a pediatric CICU, we created a multivariable model utilizing hourly data from the EHR to predict CA. At 1 h before the event, for every 10% increase in the SpO2-rSO2s difference, the odds of cardiac arrest increased by 40%. These findings are important as the field explores ways to capitalize on the wealth of data at our disposal to improve patient care.

Extracorporeal Life Support Organization Guidelines for the Provision and Assessment of Nutritional Support in the Neonatal and Pediatric ECMO Patient.

DISCLAIMER: This guideline is intended for educational use to build the knowledge of physicians and other health professionals in assessing the conditions and managing the treatment of patients undergoing extracorporeal life support (ECLS)/extracorporeal membrane oxygenation (ECMO) and describe what are believed to be useful and safe practice for extracorporeal life support (ECLS, ECMO) but these are not necessarily consensus recommendations. The aim of clinical guidelines are to help clinicians to make informed decisions about their patients. However, adherence to a guideline does not guarantee a successful outcome. Ultimately, healthcare professionals must make their own treatment decisions about care on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge, and expertise. These guidelines do not take the place of physicians' and other health professionals' judgment in diagnosing and treatment of particular patients. These guidelines are not intended to and should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment must be made by the physician and other health professionals and the patient in light of all the circumstances presented by the individual patient, and the known variability and biologic behavior of the clinical condition. These guidelines reflect the data at the time the guidelines were prepared; the results of subsequent studies or other information may cause revisions to the recommendations in these guidelines to be prudent to reflect new data, but Extracorporeal Life Support Organization (ELSO) is under no obligation to provide updates. In no event will ELSO be liable for any decision made or action taken in reliance upon the information provided through these guidelines.

Routine Neuroimaging: Understanding Brain Injury in Pediatric Extracorporeal Membrane Oxygenation.

OBJECTIVES: This project aims to describe brain injuries on routine neuroimaging in a large single-center neonatal and pediatric cohort supported by extracorporeal membrane oxygenation. The study also aims to examine the association of these injuries with neurocognitive outcomes in survivors and identify laboratory findings associated with neurologic injury. DESIGN: Retrospective observational single-center cohort study. SETTING: Tertiary care PICU. PATIENTS: Pediatric patients with noncardiac indications for extracorporeal membrane oxygenation supported by venoarterial or venovenous extracorporeal membrane oxygenation, with on-extracorporeal membrane oxygenation brain CT or postextracorporeal membrane oxygenation brain CT/MRI. INTERVENTIONS: Extracorporeal membrane oxygenation support. MEASUREMENTS AND MAIN RESULTS: Occurrence of brain injury on CT and MRI was reviewed; injuries were scored. Clinical and laboratory results associated with injury were identified. Survivor neurocognitive outcomes were obtained using the Pediatric Overall Performance Category scale and Pediatric Cerebral Performance Category scale. Of 132 imaged patients, 98 (74%) had radiological evidence of brain injury. Mean injury score was 6.5 (± 3.8). Head ultrasounds and clinician suspicion performed poorly in suspecting the presence of injury. Of 104 respondents to neurodevelopmental assessments, 61 (59%) had normal scores; 12.5%, 17%, and 11.5% had mild, moderate, or severe disability. A neuroimaging score greater than 10 was associated with an unfavorable outcome on the Pediatric Cerebral Performance Category (odds ratio, 3.4; p < 0.01) and Pediatric Overall Performance Category (odds ratio, 1.7; p < 0.05). Ischemic injury correlated with worse neurodevelopmental outcome. Preextracorporeal membrane oxygenation lactate, Vasoactive-Inotropic Scores, transaminitis, elevated bilirubin and creatinine levels, and thrombocytopenia were associated with injury occurrence. CONCLUSIONS: Brain injury is frequent in extracorporeal membrane oxygenation patients, although the majority of survivors have favorable neurocognitive outcomes. More research is needed in order to understand the etiology of such injuries. Head ultrasound and clinician suspicion are not sensitive in detecting extracorporeal membrane oxygenation-related brain injuries. Protocolizing postextracorporeal membrane oxygenation imaging with brain MRI allows the identification of injuries and provision of timely neurocognitive intervention.

Extracorporeal membrane oxygenation in children receiving haematopoietic cell transplantation and immune effector cell therapy: an international and multidisciplinary consensus statement.

Use of extracorporeal membrane oxygenation (ECMO) in children receiving haematopoietic cell transplantation (HCT) and immune effector cell therapy is controversial and evidence-based guidelines have not been established. Remarkable advancements in HCT and immune effector cell therapies have changed expectations around reversibility of organ dysfunction and survival for affected patients. Herein, members of the Extracorporeal Life Support Organization (ELSO), Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network (HCT and cancer immunotherapy subgroup), the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT), the supportive care committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC), and the Pediatric Intensive Care Oncology Kids in Europe Research (POKER) group of the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) provide consensus recommendations on the use of ECMO in children receiving HCT and immune effector cell therapy. These are the first international, multidisciplinary consensus-based recommendations on the use of ECMO in this patient population. This Review provides a clinical decision support tool for paediatric haematologists, oncologists, and critical care physicians during the difficult decision-making process of ECMO candidacy and management. These recommendations can represent a base for future research studies focused on ECMO selection criteria and bedside management.

Review of acute kidney injury and continuous renal replacement therapy in pediatric extracorporeal membrane oxygenation.

PURPOSE: To review the relevant literature of acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) as it relates to pediatric extracorporeal membrane oxygenation (ECMO). METHODS: Available online relevant literature. RESULTS: ECMO is a therapeutic modality utilized to support patients with refractory respiratory and/or cardiac failure. AKI and fluid overload (FO) are frequently observed in this patient population. There are multiple modalities that can be utilized for AKI and FO which include the following: diuretics, in-line hemofiltration, and CRRT. There are multiple considerations when using CRRT with ECMO including access, CRRT flows, hemolysis, anticoagulation, and CRRT termination. CONCLUSION: While each ECMO center has its own set of equipment, experiences, and practices, it is imperative that the international ECMO community continues to work together to provide an evidence-based approach to address the morbidity and mortality associated with AKI and FO.

3-Hydroxypropane-1,2-Diyl Dipalmitoleate-A Natural Compound with Dual Roles (CB1 Agonist/FAAH1 Blocker) in Inhibiting Ovarian Cancer Cell Line.

Though it was once known that upregulated Cannabinoid Receptor (CB1) and downregulated Fatty Acid Amide Hydrolase (FAAH1) are associated with tumour aggressiveness and metastasis, it is now clear that upregulated CB1 levels more than a certain point cause accumulation of ceramide and directs cells to apoptosis. Hence, CB1 analogues/FAAH1 blockers are explored widely as anticancer drugs. There are reports on CB1-agonists and FAAH1-blockers separately, however, dual activities along with ovarian cancer-specific links are not established for any natural compound. With this setting, we describe for the first time the isolation of 3-hydroxypropane-1,2-diyl dipalmitoleate (564.48 Da) from a marine snail, Conus inscriptus, which binds to both CB1 and FAAH1 (glide energies: -70.61 and -30.52 kcal/mol, respectively). MD simulations indicate stable compound-target interaction for a minimum of 50 nanoseconds with relative invariabilities in Rg. The compound inhibited ovarian cancer cell line, PA1 at 1.7 µM. Structural and chemical interpretation of the compound (C2) was done using FT-IR, GC-MS, ESI-MS, 1H and 13C-NMR (1 and 2D). Furthermore, a probable route for gram-scale synthesis of C2 is hinted herein. With the available preliminary data, molecular mechanisms involving dual roles for this potent molecule must be elucidated to understand the possibilities of usage as an anticancer drug.

Extracorporeal Life Support Organization (ELSO): Guidelines for Pediatric Cardiac Failure.

These guidelines are applicable to neonates and children with cardiac failure as indication for extracorporeal life support. These guidelines address patient selection, management during extracorporeal membrane oxygenation, and pathways for weaning support or bridging to other therapies. Equally important issues, such as personnel, training, credentialing, resources, follow-up, reporting, and quality assurance, are addressed in other Extracorporeal Life Support Organization documents or are center-specific.

Extracorporeal Membrane Oxygenation for COVID-19: Updated 2021 Guidelines from the Extracorporeal Life Support Organization.

DISCLAIMER: This is an updated guideline from the Extracorporeal Life Support Organization (ELSO) for the role of extracorporeal membrane oxygenation (ECMO) for patients with severe cardiopulmonary failure due to coronavirus disease 2019 (COVID-19). The great majority of COVID-19 patients (>90%) requiring ECMO have been supported using venovenous (V-V) ECMO for acute respiratory distress syndrome (ARDS). While COVID-19 ECMO run duration may be longer than in non-COVID-19 ECMO patients, published mortality appears to be similar between the two groups. However, data collection is ongoing, and there is a signal that overall mortality may be increasing. Conventional selection criteria for COVID-19-related ECMO should be used; however, when resources become more constrained during a pandemic, more stringent contraindications should be implemented. Formation of regional ECMO referral networks may facilitate communication, resource sharing, expedited patient referral, and mobile ECMO retrieval. There are no data to suggest deviation from conventional ECMO device or patient management when applying ECMO for COVID-19 patients. Rarely, children may require ECMO support for COVID-19-related ARDS, myocarditis, or multisystem inflammatory syndrome in children (MIS-C); conventional selection criteria and management practices should be the standard. We strongly encourage participation in data submission to investigate the optimal use of ECMO for COVID-19.