Exposure to postoperative hypothermia and its association with complications after major abdominal surgery: a retrospective cohort study.

Purpose: Many patients who undergo major abdominal surgery experience inadvertent hypothermia during the perioperative period. This study aimed to identify risk factors related to postoperative hypothermia and their association with postoperative complications. Methods: This retrospective cohort study used data from Seoul National University Bundang Hospital, a tertiary university medical center in South Korea, between January 1, 2018 and December 31, 2022. We included patients aged ≥18 years who underwent elective major abdominal surgery for more than 2 hours in the operating room. The patients were categorized into the hypothermia (body temperature <36.5℃) and non-hypothermia (body temperature ≥36.5℃) groups. Results: The study sample comprised 30,194 patients, and we classified 21,293 and 8,901 into the hypothermic and non-hypothermic groups, respectively. Some factors associated with the occurrence of postoperative hypothermia included the type of surgery. In the multivariable logistic regression model, the incidence of postoperative complications was 9% higher in the hypothermia group than in the non-hypothermic group (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.01-1.19; P = 0.040). Among postoperative complications, the hypothermic group showed a 14% higher incidence of acute kidney injury (OR, 1.14; 95% CI, 1.04-1.25; P = 0.007) than the non-hypothermic group. Conclusion: The appearance of postoperative hypothermia during the first 30 minutes of the recovery period was significantly associated with the appearance of postoperative complications, especially acute kidney injury. However, further studies are required to validate these findings.

Biomarker patterns and mechanistic insights into hypothermia from a postmortem metabolomics investigation.

Postmortem metabolomics holds promise for identifying crucial biological markers relevant to death investigations and clinical scenarios. We aimed to assess its applicability in diagnosing hypothermia, a condition lacking definitive biomarkers. Our retrospective analysis involved 1095 postmortem femoral blood samples, including 150 hypothermia cases, 278 matched controls, and 667 randomly selected test cases, analyzed using UHPLC-QTOF mass spectrometry. The model demonstrated robustness with an R2 and Q2 value of 0.73 and 0.68, achieving 94% classification accuracy, 92% sensitivity, and 96% specificity. Discriminative metabolite patterns, including acylcarnitines, stress hormones, and NAD metabolites, along with identified pathways, suggest that metabolomics analysis can be helpful to diagnose fatal hypothermia. Exposure to cold seems to trigger a stress response in the body, increasing cortisol production to maintain core temperature, possibly explaining the observed upregulation of cortisol levels and alterations in metabolic markers related to renal function. In addition, thermogenesis seems to increase metabolism in brown adipose tissue, contributing to changes in nicotinamide metabolism and elevated levels of ketone bodies and acylcarnitines, these findings highlight the effectiveness of UHPLC-QTOF mass spectrometry, multivariate analysis, and pathway identification of postmortem samples in identifying metabolite markers with forensic and clinical significance. The discovered patterns may offer valuable clinical insights and diagnostic markers, emphasizing the broader potential of postmortem metabolomics in understanding critical states or diseases.

Early automated classification of neonatal hypoxic-ischemic encephalopathy - An aid to the decision to use therapeutic hypothermia.

OBJECTIVE: The study aimed to address the challenge of early assessment of neonatal hypoxic-ischemic encephalopathy (HIE) severity to identify candidates for therapeutic hypothermia (TH). The objective was to develop an automated classification model for neonatal EEGs, enabling accurate HIE severity assessment 24/7. METHODS: EEGs recorded within 6 h of life after perinatal anoxia were visually graded into 3 severity groups (HIE French Classification) and quantified using 6 qEEG markers measuring amplitude, continuity and frequency content. Machine learning models were developed on a dataset of 90 EEGs and validated on an independent dataset of 60 EEGs. RESULTS: The selected model achieved an overall accuracy of 80.6% in the development phase and 80% in the validation phase. Notably, the model accurately identified 28 out of 30 children for whom TH was indicated after visual EEG analysis, with only 2 cases (moderate EEG abnormalities) not recommended for cooling. CONCLUSIONS: The combination of clinically relevant qEEG markers led to the development of an effective automated EEG classification model, particularly suited for the post-anoxic latency phase. This model successfully discriminated neonates requiring TH. SIGNIFICANCE: The proposed model has potential as a bedside clinical decision support tool for TH.

Knowledge and practices of neonatal intensive care unit nurses concerning hypothermia in preterm infants: A descriptive cross-sectional study.

AIM: To investigate the knowledge level and clinical practice of neonatal intensive care unit nurses on the whole process of hypothermia prevention in preterm infants. DESIGN: A polycentric descriptive cross-sectional study was conducted in 23 hospitals in Shandong province involving 254 neonatal intensive care unit nurses. METHODS: An evidence-based knowledge and clinical practice questionnaire on hypothermia prevention in preterm infants and a general information questionnaire were used to collect data. SPSS and EXCEL 24.0 database were used for data statistics and analysis. RESULTS: Nearly one-third of nurses were unclear about the definition of mild hypothermia and heat preservation measures during labour management and resuscitation. Knowledge about the correct rate of amniotic fluid evaporation was low. The higher the hospital level and nurses' education level, professional title, work experience, and position, the higher the knowledge level. The clinical practice of nurses differed in terms of body temperature assessment tools, measurement sites, and measurement frequency for premature infants. CONCLUSIONS: Nurses in neonatal intensive care units need to apply evidence-based knowledge and carry out practice interventions to ensure preterm infants' safe transition from the delivery room to the neonatal intensive care unit. IMPACT: There have been few studies evaluating neonatal nurses' knowledge and practices with regards to the preventing hypothermia of premature infants from delivery room to neonatal intensive care unit. The study identifies the deficiencies and problems in temperature management that can be attributed to the knowledge level of nurses. The findings will help improve the current curriculum, teaching strategies, and the nurses' knowledge levels, preventing premature hypothermia in infants. REPORTING METHOD: This study adhered to the STROBE statement for observational studies and obtained approval (KYLL-2023LW045) from the ethics committee of The Second Hospital of Shandong University. The other 22 third- and second-level hospitals, as our alliance members, recognized our chairperson status within the alliance and were willing to join our academic activities. Mutual responsibility for ethical filing between alliance units. PUBLIC CONTRIBUTION: 254 nurses were recruited from 23 tertiary and secondary public hospitals in Shandong province. No public or patient involvement. Members of the research group used the Questionnaire Star platform to prepare the electronic questionnaire, including obtaining informed consent, taking precautions for questionnaire completion, and using the aforementioned measurement tools. The project research team contacted the head nurses of 23 neonatal intensive care units in Shandong Province. After obtaining consent from the head nurses, they were asked to send the requirements and link of the electronic questionnaire to their WeChat management group. The nurses go through each question and make a choice which has two options of 'agree' or 'disagree.' Based on their answers, nurses were evaluated as having 'mastered' or 'not mastered' each item. Each 'mastered' item (correct answer) was given a score of 4; an item 'not mastered' (incorrect answer) was given a score of 0. The total score ranged from 0 to 100.

A clinical comparison of glycol and water-based heater-cooler systems for cardiopulmonary bypass.

INTRODUCTION: While newer heater-cooler technologies using ethylene glycol-based (GB) solutions during cardiothoracic surgery have become commercially available, there is a paucity of clinical data describing their effectiveness during cardiopulmonary bypass (CPB) support. This analysis aimed to compare clinical characteristics and procedural outcomes using water-based (WB) and GB heater-cooler systems. METHODS: A retrospective analysis was performed on consecutive adult patients undergoing CPB from June to October 2022 comparing WB or GB groups. The primary outcome was a composite of operative death or major morbidity. Secondary endpoints included transfusion requirements on CPB, patient cooling and warming rates, and vasoactive-inotropic scores (VIS) at case completion. P-control charts were used to monitor the weekly incidence of the composite outcome. A sub-analysis was performed to evaluate the primary outcome for cardiac surgery cases indexed by the Society of Thoracic Surgeons (STS). RESULTS: There were 167 patients included for analysis; 87 (52.1%) underwent CPB with a WB system and 80 (47.9%) with a GB system. GB procedure subjects were younger (p = .01), experienced longer CPB times (p = .034), and were more likely to receive thoracic transplant or aortic surgery (p = 0.015). The composite outcome of operative mortality or major morbidity occurred in 29.9% and 24% of the WB and GB groups, respectively (p = .372). P-control charts indicated a weekly mean incidence of 30% during WB practice, which decreased to 24% with GB practice. Among 106 STS-indexed cardiac surgery cases, mean composite outcome incidence decreased from 19% to 6% following our GB transition. Additionally, cooling, and warming rates indexed to patient BSA and VIS at case completion were not significantly different. CONCLUSION: Our analysis demonstrated a safe transition from WB to GB heater-cooler technologies in our practice. This early analysis suggests that GB heater coolers may be safely adopted to mitigate the risks of nontuberculous mycobacterium infections for cardiac surgical patients.

Intermittent hemodialysis as a rewarming strategy for severe hypothermia in patients without renal failure: a case report.

This case report highlights the effective use of intermittent hemodialysis (IHD) in warming a 71-year-old female patient with severe hypothermia who presented with a rectal temperature of 25 °C and signs of hemodynamic instability. The patient, found unconscious after prolonged exposure to cold exacerbated by alcohol consumption, initially showed some improvement in core temperature through active external rewarming methods. However, soon, her temperature plateaued at 27 °C. Patient was deemed unsuitable for extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass (CPB) due to her age, and urgent IHD was initiated. This approach resulted in a stable increase in core temperature at approximately 2.0 °C/hr, along with normalization of lactic acidosis, creatinine phosphokinase, and correction of electrolyte imbalances, culminating in her full recovery and discharge after seven days in the hospital.After reviewing this case alongside similar ones from before, this case report highlights the efficacy and safety of IHD as an efficient, readily available, and less invasive method for rewarming moderate to severe hypothermic patients who are hemodynamically unstable patients but do not have cardiac arrest or renal dysfunction. IHD is especially useful when less invasive cooling devices (Artic Sun/ CoolGard) are not available or more invasive extracorporeal life support options (ECMO/ CPB) are either not indicated or unavailable. IHD can also help improve concurrent electrolyte imbalances and/or toxin buildup. The report further emphasizes the necessity of monitoring for potential complications, such as post-dialysis hypophosphatemia and rebound hyperkalemia, following successful rewarming.

Prevalence of Pulmonary Hypertension During Therapeutic Hypothermia for Hypoxic Ischemic Encephalopathy and Evaluation of Short-Term Outcomes.

Infants with perinatal asphyxia and moderate-to-severe hypoxic ischemic encephalopathy (HIE) are currently treated with therapeutic hypothermia (TH) as part of a brain protective strategy. However, perinatal asphyxia is a risk factor for development of persistent pulmonary hypertension (PPHN). As such, the aim of this study was to quantify the risk of PPHN in infants undergoing TH and assess short-term outcomes in infants developing PPHN. All N = 59 infants undergoing TH for moderate-to-severe HIE over a period of 3 years (January 2020-December 2022) at a single center were included. PPHN was diagnosed in N = 10 (17%), with this deemed to have been exacerbated by TH in n = 6 (10%). Only 50% (5/10) with PPHN required inhaled nitric oxide, and none of the infants received extracorporeal membrane oxygenation. PPHN was not found to be significantly associated with short-term outcomes, including the extent of HIE on brain magnetic resonance imagings, in-hospital mortality or requirement for nasogastric feeding at discharge. In conclusion, TH appears to be a safe and effective treatment for moderate-to-severe HIE with or without PPHN.

Avalanche fatalities in Czech Republic: a 23-years retrospective study.

Avalanche fatalities are quite rare in the Czech Republic. Due to the presence of avalanche fields in the two Czech mountains, forensic pathologists at some forensic medicine departments may encounter this specific mechanism of accidental death. The authors summarize medicolegal aspects of deaths in avalanches in the territory of the Czech Republic for the twenty-three-year period between 1993-2015. Ten avalanche fatalities were recorded during study period. The studied group consisted of nine male and one female victims. The average age of the deceased was 27.9 years. Skiers or ski-alpinists died in the avalanche in five cases (50%), climbers in two cases (20%), snowboarders in one case (10%), cross-country skiers in one case (10%) and in one case it was a fatality of child playing on a snowy hill (10%). The cause of death was suffocation in four cases (40%), blunt trauma in four cases (40%), and in the remaining two cases it was the survival of trapped persons several hours after being rescued from the avalanche in the hospital; both victims subsequently died as a result of prolonged shock (20%) due to a combination of prolonged suffocation and hypothermia. The time interval from the fall of the avalanche to the rescue of the trapped person was in the range of minutes to 3 hours. The presence of alcohol or drugs was not detected in any studied case.

Early outcomes of experience warm surgery in children undergoing complete repair of tetralogy of Fallot in developing countries.

OBJECTIVES: While significant evidence supports the benefits of normothermic cardiopulmonary bypass (NCPB) over hypothermic techniques, many institutions in developing countries, including ours, continue to employ hypothermic methods. This study aimed to assess the early postoperative outcomes of normothermic cardiopulmonary bypass (NCPB) for complete surgical repair via the Tetralogy of Fallot (TOF) within our national context. METHODS: We conducted this study in the Pediatric Cardiac Intensive Care Unit (PCICU) at the University Children's Hospital. One hundred patients who underwent complete TOF repair were enrolled and categorized into two groups: the normothermic group (n = 50, temperature 35-37 °C) and the moderate hypothermic group (n = 50, temperature 28-32 °C). We evaluated mortality, morbidity, and postoperative complications in the PCICU as outcome measures. RESULTS: The demographic characteristics were similar between the two groups. However, the cardiopulmonary bypass (CPB) time and aortic cross-clamp (ACC) time were notably longer in the hypothermic group. The study recorded seven deaths, yielding an overall mortality rate of 7%. No significant differences were observed between the two groups concerning mortality, morbidity, or postoperative complications in the PCICU. CONCLUSIONS: Our findings suggest that normothermic procedures, while not demonstrably effective, are safe for pediatric cardiac surgery. Further research is warranted to substantiate and endorse the adoption of this technique.

An Implementation Science Study of a Heat-Producing Wrap to Complement KMC in Rwanda.

Background: Neonatal hypothermia is a major cause of preventable morbidity and mortality, especially among the world's poorest newborns. A heat-producing wrap is necessary when kangaroo mother care (KMC) is insufficient or unavailable, yet there is little published research on such wraps. The Dream Warmer is a wrap designed to complement KMC and has been extensively studied in formal research settings but not in real-world conditions. Objectives: We used implementation science methodology to understand the safety, effectiveness, and functionality of the Dream Warmer (hereafter, "Warmer"); its effect on clinical workflows; its interaction with other aspects of care such as KMC; and the Warmer's reception by healthcare providers (HCPs) and parents. Methods: We conducted a prospective, interventional, one-arm, open-label, mixed-methods study in 6 district hospitals and 84 associated health centers in rural Rwanda. Our intervention was the provision of the Warmer and an educational curriculum on thermoregulation. We compared pre and post intervention data using medical records, audits, and surveys. Findings: The Warmer raised no safety concerns. It was used correctly in the vast majority of cases. The mean admission temperature rose from slightly hypothermic (36.41 °C) pre, to euthermic (36.53 °C) post intervention (p = 0.002). Patients achieved a temperature ≥36.5 °C in 86% of uses. In 1% of audits, patients were hyperthermic (37.6-37.9 °C). Both HCPs and parents reported a generally positive experience with the Warmer. HCPs were challenged to prepare it in advance of need. Conclusions: The Warmer functions similarly well in research and real-world conditions. Ongoing education directed toward both HCPs and parents is critical to ensuring the provision of a continuous heat chain. Engaging families in thermoregulation could ease the burden of overtaxed HCPs and improve the skill set of parents. Hypothermia is a preventable condition that must be addressed to optimize neonatal survival and outcome.

STudy to ActivelY WARM trauma patients (STAY WARM): a pilot study assessing feasibility of self-warming blankets in patients requiring a massive hemorrhage protocol activation.

PURPOSE: Massively bleeding trauma patients often arrive to intensive care units hypothermic. Active warming blankets have shown promise in reducing hypothermia in the pre-hospital setting, but less is known about their in-hospital use. The aim of this pilot evaluation was to understand the feasibility of the Ready-Heat® blanket in a level 1 trauma centre to improve the management of hypothermia in massively bleeding trauma patients. METHODS: This was a prospective, observational, feasibility study of 15 patients performed at a single level 1 trauma centre. Patients were eligible for enrollment if they presented to the trauma bay and a massive hemorrhage protocol was activated. Primary outcome measures (feasibility) included: blanket applied to the patient; temperature recording in the trauma bay, and next phase or final phase of care; and blanket remaining on patient upon arrival to the subsequent phase of care.Secondary outcome measures (safety) included skin irritation and cold discomfort. Use of the Ready-Heat® blanket was considered feasible if 10 of 15 patients met all four criteria for feasibility. RESULTS: The Ready-Heat® blanket was placed on all patients with mean time to blanket application of 24 (± 13.4) minutes. Thirteen patients (86.7%) met all four criteria for feasibility. Initial challenges were identified in the first five patients including proper blanket application, keeping the blanket on the patient through subsequent phases of care, and failure to obtain temperature recordings. CONCLUSION: The Ready-Heat® blanket proves feasible for this patient population. A larger study focusing on hypothermia prevention and treatment is warranted. TRIAL REGISTRATION NUMBER: NCT04399902. DATE OF REGISTRATION: May 22, 2020.

Intraoperative zero-heat-flux thermometry overestimates nasopharyngeal temperature by 0.39 °C: an observational study in patients undergoing congenital heart surgery.

During surgery for congenital heart disease (CHD) temperature management is crucial. Vesical (Tves) and nasopharyngeal (TNPH) temperature are usually measured. Whereas Tves slowly responds to temperature changes, TNPH carries the risk of bleeding. The zero-heat-flux (ZHF) temperature monitoring systems SpotOn™ (TSpotOn), and Tcore™ (Tcore) measure temperature non-invasively. We evaluated accuracy and precision of the non-invasive devices, and of Tves compared to TNPH for estimating temperature. In this prospective observational study in pediatric and adult patients accuracy and precision of TSpotOn, Tcore, and Tves were analyzed using the Bland-Altman method. Proportion of differences (PoD) and Lin´s concordance correlation coefficient (LCC) were calculated. Data of 47 patients resulted in sets of matched measurements: 1073 for TSpotOn vs. TNPH, 874 for Tcore vs. TNPH, and 1102 for Tves vs. TNPH. Accuracy was - 0.39 °C for TSpotOn, -0.09 °C for Tcore, and 0.07 °C for Tves. Precisison was between - 1.12 and 0.35 °C for TSpotOn, -0.88 to 0.71 °C for Tcore, and - 1.90 to 2.05 °C for Tves. PoD ≤ 0.5 °C were 71% for TSpotOn, 71% for Tcore, and 60% for Tves. LCC was 0.9455 for TSpotOn, 0.9510 for Tcore, and 0.9322 for Tves. Temperatures below 25.2 °C (TSpotOn) or 27.1 (Tcore) could not be recorded non-invasively, but only with Tves. Trial registration German Clinical Trials Register, DRKS00010720.

Ultrafast Cooling With Total Liquid Ventilation Mitigates Early Inflammatory Response and Offers Neuroprotection in a Porcine Model of Cardiac Arrest.

BACKGROUND: Brain injury is one of the most serious complications after cardiac arrest (CA). To prevent this phenomenon, rapid cooling with total liquid ventilation (TLV) has been proposed in small animal models of CA (rabbits and piglets). Here, we aimed to determine whether hypothermic TLV can also offer neuroprotection and mitigate cerebral inflammatory response in large animals. METHODS AND RESULTS: Anesthetized pigs were subjected to 14 minutes of ventricular fibrillation followed by cardiopulmonary resuscitation. After return of spontaneous circulation, animals were randomly subjected to normothermia (control group, n=8) or ultrafast cooling with TLV (TLV group, n=8). In the latter group, TLV was initiated within a window of 15 minutes after return of spontaneous circulation and allowed to reduce tympanic, esophageal, and bladder temperature to the 32 to 34 °C range within 30 minutes. After 45 minutes of TLV, gas ventilation was resumed, and hypothermia was maintained externally until 3 hours after CA, before rewarming using heat pads (0.5 °C-1 °C/h). After an additional period of progressive rewarming for 3 hours, animals were euthanized for brain withdrawal and histological analysis. At the end of the follow-up (ie, 6 hours after CA), histology showed reduced brain injury as witnessed by the reduced number of Fluroro-Jade C-positive cerebral degenerating neurons in TLV versus control. IL (interleukin)-1ra and IL-8 levels were also significantly reduced in the cerebrospinal fluid in TLV versus control along with cerebral infiltration by CD3+ cells. Conversely, circulating levels of cytokines were not different among groups, suggesting a discrepancy between local and systemic inflammatory levels. CONCLUSIONS: Ultrafast cooling with TLV mitigates neuroinflammation and attenuates acute brain lesions in the early phase following resuscitation in large animals subjected to CA.

Parent-infant closeness and care practices during therapeutic hypothermia in Swedish neonatal intensive care units.

OBJECTIVES: The aim of this study was to investigate care practices among Neonatal Intensive Care Units (NICU) providing Therapeutic hypothermia (TH), and more specific to investigate staff's experiences of parental participation, presence, and possibilities of being close with their infant during TH. METHODS: A descriptive, qualitative, and quantitative study. All Swedish NICUs providing TH (n = 10) participated. Data were collected during January-April 2021 via a questionnaire followed by a semi-structured interview with the registered nurse and the neonatologist responsible for TH at each unit. Descriptive statistics were calculated, and a qualitative content analysis was performed. RESULTS: All NICUs allowed parents unlimited stay with their infants and were keen to support parental presence, which was a prerequisite for promoting parent-infant closeness. Standardized routines regarding the infants' care space and course of action were described as time-efficient and staff-saving, which freed up time to focus on the families. CONCLUSION: Standardized routines regarding the care space setup and the medical and caring approach, as well as the NICU environment and practices around the families, can promote or curb the possibilities of parent-infant closeness. Well-established care practices and good environmental conditions with flexibility regarding the family's needs are therefore required.

Reverse Therapy: Impact of Hyperthermia and Rewarming on Newborn Outcomes.

Therapeutic hypothermia is now well established to improve neurodevelopmental outcomes after hypoxic-ischemic encephalopathy (HIE). Although the overall principles of treatment are now well established, many smaller questions are unclear. The potential impact of reversal of hypothermia therapy and the effect of high temperatures on recovery of the neurovascular unit after therapeutic hypothermia for HIE has received relatively little attention. This article will address the effects of hypoxia-ischemia and rewarming and increased temperatures on the neurovascular unit in preclinical and clinical models.

Long-Term Outcomes Following Hypoxic Ischemic Encephalopathy.

Hypoxic ischemic encephalopathy (HIE) is the most common cause of neonatal encephalopathy and results in significant morbidity and mortality. Long-term outcomes of the condition encompass impairments across all developmental domains. While therapeutic hypothermia (TH) has improved outcomes for term and late preterm infants with moderate to severe HIE, trials are ongoing to investigate the use of TH for infants with mild or preterm HIE. There is no evidence that adjuvant therapies in combination with TH improve long-term outcomes. Numerous trials of various adjuvant therapies are underway in the quest to further improve outcomes for infants with HIE.

Communicating with Parents About Therapeutic Hypothermia and Hypoxic Ischemic Encephalopathy: Integrating a Palliative Care Approach into Practice.

Parents of newborns with hypoxic ischemic encephalopathy (HIE) can face communication challenges in the neonatal intensive care unit. Both specialty palliative care and primary palliative care trained clinicians can assist parents as they navigate traumatic experiences and uncertain prognoses. Using evidence-based frameworks, the authors provide samples of how to communicate with parents and promote parent well-being across the care trajectory. The authors demonstrate how to involve parents in a shared decision-making process and give special consideration to the complexities of hospital discharge and the transition home. Sustained investment to guide the development of effective communication skills is crucial to support families of infants with HIE.

A New Horizon for Understanding the Comparative Effectiveness for Cooling Prospectively Infants with Mild Encephalopathy.

The authors summarize the methodology for a new pragmatic comparative effectiveness research investigation, Cooling Prospectively Infants with Mild Encephalopathy (COOLPRIME), which uses sites' existing mild hypoxic-ischemic encephalopathy (HIE) treatment preference (hypothermia or normothermia) to assess hypothermia effectiveness and safety. COOLPRIME's primary aim is to determine the safety and effectiveness of hypothermia compared to normothermia in mild HIE. Engagement of Families and Community Affected by Hypoxic-Ischemic Encephalopathy strongly favored Effectiveness over Efficacy Trials leading to COOL PRIME design.

Key Inflammatory Biomarkers in Perinatal Asphyxia: A Comprehensive Review.

This article summarizes the current evidence regarding inflammatory biomarkers (placental and postnatal) and provides a comprehensive understanding of their roles: (1) diagnostic accuracy to predict the severity of hypoxic-ischemia encephalopathy (HIE), (2) value in assessing treatment responses, and (3) prediction of both short- and long-term neurodevelopmental outcomes. In the early critical stages of perinatal asphyxia, inflammatory biomarkers may guide clinical decision-making. Additional research is required to increase our understanding of the optimal utility of biomarkers to predict the severity, evolution, and developmental outcomes after exposure to HIE.

Pipeline to Neonatal Clinical Transformation: The Importance of Preclinical Data.

Historically, neonatal neuroscience boasted a robust and successful preclinical pipeline for therapeutic interventions, in particular for the treatment of hypoxic-ischemic encephalopathy (HIE). However, since the successful translation of therapeutic hypothermia (TH), several high-profile failures of promising adjunctive therapies, in addition to the lack of benefit of TH in lower resource settings, have brought to light critical issues in that same pipeline. Using recent data from clinical trials of erythropoietin as an example, the authors highlight several key challenges facing preclinical neonatal neuroscience for HIE therapeutic development and propose key areas where model development and collaboration across the field in general can ensure ongoing success in treatment development for HIE worldwide.