Enteral nutritional strategy during therapeutic hypothermia: who? when? what?

Background: There are no guidelines regarding enteral feeding (EF) of infants with hypoxic-ischemic encephalopathy (HIE) during and shortly after therapeutic hypothermia; consequently, clinical practice is, to date, still variable. The objective of this study is to assess whether a minimal EF strategy during therapeutic hypothermia may be associated with a shorter time to full EF of infants with HIE and to identify the clinical variables that independently affect the time to full EF. Methods: A retrospective study, covering the period from 1 January 2015 to 30 June 2022 was performed at the Neonatal Intensive Care Unit of the Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, which compared infants with HIE who received minimal EF during therapeutic hypothermia with those who did not. Results: Seventy-eight infants received minimal EF during therapeutic hypothermia, while 75 did not. Infants who were fed reached full EF significantly faster than those who were not. Moreover, they received parenteral nutrition and maintained central venous lines for a shorter time. A multivariate analysis, taking into account the variable of clinical severity, confirmed that minimal EF is an independent beneficial factor for reaching full EF in a shorter time and mechanical ventilation and seizures are independent factors for a longer time to full EF. Conclusions: Minimal EF during therapeutic hypothermia is associated with a shorter time to full EF in stable infants with HIE. Further prospective studies are needed to better define the enteral nutrition strategy for infants during therapeutic hypothermia, regardless of the severity of clinical conditions.

Fatal asphyxia due to large laryngeal granuloma.

Laryngeal granuloma, vocal process granuloma, or post-intubation granuloma are benign, inflammatory lesions of the arytenoid cartilage vocal process. The etiology of laryngeal granulomas is multifactorial, such as chronic irritation due to endotracheal intubation, vocal cord injury or trauma, and gastroesophageal reflux disease. They can arise postoperatively after mucosal injury due to orotracheal intubation. Clinical manifestations include voice change and dyspnea, which may start one to four months after extubation and may rarely lead to asphyxia. We presented a case of death due to glottic granuloma occurring after a surgical procedure to remove a laryngeal polyp attributed to previous laryngeal injuries by multiple intubations.

Amorfrutin B Compromises Hypoxia/Ischemia-induced Activation of Human Microglia in a PPARγ-dependent Manner: Effects on Inflammation, Proliferation Potential, and Mitochondrial Status.

Amorfrutin B is a selective PPARγ modulator that we demonstrated to be a promising neuroprotective compound in cellular models of stroke and perinatal asphyxia. Although neuronal mechanisms of amorfrutin B-evoked neuroprotection have been identified, none of them reflects the actions of the compound on microglia, which play a pivotal role in brain response to hypoxia/ischemia. Here, we provide evidence for amorfrutin B-induced effects on human microglia subjected to hypoxia/ischemia; the compound counteracts inflammation, and influences mitochondrial status and proliferation potential in a PPARγ-dependent manner. Post-treatment with amorfrutin B decreased the IBA1 fluorescence intensity, reduced caspase-1 activity, and downregulated IL1B/IL-1ß and TNFA but not IL10/IL-10 expression, which was upregulated. Amorfrutin B also stimulated PPARγ signaling, as evidenced by increased mRNA and/or protein levels of PPARγ and PGC1α. In addition, amorfrutin B reversed the hypoxia/ischemia-evoked effects on mitochondria-related parameters, such as mitochondrial membrane potential, BCL2/BCL2 expression and metabolic activity, which were correlated with diminished proliferation potential of microglia. Interestingly, the inhibitory effect of amorfrutin B on the proliferation potential and mitochondrial function of microglia is opposite to the stimulatory effect of amorfrutin B on mouse neuronal survival, as evidenced by increased neuronal viability and reduced neurodegeneration. In summary, this study showed for the first time that amorfrutin B compromises hypoxia/ischemia-induced activation of human microglia in a PPARγ-dependent manner, which involves inhibiting inflammation, normalizing mitochondrial status, and controlling proliferation potential. These data extend the protective potential of amorfrutin B in the pharmacotherapy of hypoxic/ischemic brain injury, targeting not only neurons but also activated microglia.

Short-term outcomes of asphyxiated neonates depending on requirement for transfer in the first 24 hours of life.

IMPORTANCE: In neonates with birth asphyxia (BA) and hypoxic-ischemic encephalopathy, therapeutic hypothermia (TH), initiated within six hours, is the only safe and established neuroprotective measure to prevent secondary brain injury. Infants born outside of TH centers have delayed access to cooling. OBJECTIVE: To compare in-hospital mortality, occurrence of seizures, and functional status at discharge in newborns with BA depending on postnatal transfer for treatment to another hospital within 24 hours of admission (transferred (TN) versus non-transferred neonates (NTN)). DESIGN: Nationwide retrospective cohort study from a comprehensive hospital dataset using codes of the International Classification of Diseases, 10th modification (ICD-10). Clinical and outcome information was retrieved from diagnostic and procedural codes. Hierarchical multilevel logistic regression modeling was performed to quantify the effect of being postnatally transferred on target outcomes. SETTING: All discharges from German hospitals from 2016 to 2021. PARTICIPANTS: Full term neonates with birth asphyxia (ICD-10 code: P21) admitted to a pediatric department on their first day of life. EXPOSURES: Postnatal transfer to a pediatric department within 24 hours of admission to an external hospital. MAIN OUTCOMES: In-hospital death; secondary outcomes: seizures and pediatric complex chronic conditions category (PCCC) ≥ 2. RESULTS: Of 11,703,800 pediatric cases, 25,914 fulfilled the inclusion criteria. TNs had higher proportions of organ dysfunction, TH, organ replacement therapies, and neurological sequelae in spite of slightly lower proportions of maternal risk factors. In TNs, the adjusted odds ratios (OR) for death, seizures, and PCCC ≥ 2 were 4.08 ((95 % confidence interval 3.41 - 4.89), 2.99 (2.65 - 3.38), and 1.76 (1.52 - 2.05), respectively. A subgroup analysis among infants receiving TH (n = 3,283) found less pronounced adjusted ORs for death (1.67 (1.29 - 2.17)) and seizures (1.26 (1.07 - 1.48)) and inverse effects for PCCC ≥ 2 (0.81 (0.64 - 1.02)) in TNs. Conclusion and relevance This comprehensive nationwide study found increased odds for adverse outcomes in neonates with BA who were transferred to another facility within 24 hours of hospital admission. Closely linking obstetrical units to a pediatric department and balancing geographical coverage of different levels of care facilities might help to minimize risks for postnatal emergency transfer and optimize perinatal care.

Accidental compression of the thoracic wall. Mechanical asphyxia rather than trauma is the main culprit.

We present three cases of traumatic asphyxia after thoracic compression. All victims were Caucasian males aged 22-50 years. One man was crushed by a truck trailer, another was crushed by an overturned vehicle, and the last was crushed by a large heavy stone slab. None of the patients survived the accident. There was no evidence of trauma or only minor trauma from the bones or vital organs of the thoracic cavity and abdomen.

Incidence and predictors of acute kidney injury among asphyxiated neonates in comprehensive specialized hospitals, northwest Ethiopia, 2023.

Acute kidney injury (AKI) is characterized by a sudden decline in the kidneys' abilities to remove waste products and maintain water and electrolyte homeostasis. This study aims to determine the incidence and predictors of acute kidney injury among neonates with perinatal asphyxia admitted at the neonatal intensive care unit of West Amhara Comprehensive Specialized Hospital, Northwest Ethiopia, 2023. Multicentred institution-based retrospective follow-up study was conducted from October 1, 2021, to September 30, 2023, among 421 perinatal asphyxia neonates. A simple random sampling technique was used. The data were collected using a data extraction checklist from the medical registry of neonates. The collected data were entered into EPI-DATA V.4.6.0.0. and analyzed using STATA V.14. The Kaplan-Meier failure curve and log-rank test were employed. Bivariable and multivariable Cox regression was carried out to identify predictors of Acute kidney injury. Statistical significance was declared at a p ≤ 0.05. The overall incidence of AKI was 54 (95% CI 47.07-62.51) per 100 neonate days. C/S delivery (AHR = 0.64; (95% CI 0.43-0.94), prolonged labor (AHR = 1.43; 95% CI 1.03-1.99) low-birth weight times (AHR = 1.49; (95% CI 1.01-2.20), stage three HIE(AHR: 1.68; (95% CI (1.02-2.77), No ANC follow up (AHR = 1.43; 95% CI 1.9 (1.07-3.43) and Hyperkalemia (AHR = 1.56; 95% CI 1.56 (1.05-2.29); 95% CI) were significant predictors. The incidence rate of acute kidney injury was higher than in other studies conducted on other groups of neonates. Cesarean section delivery, prolonged low birthweight, no Anc follow-up, stage 3 HIE, and neonatal hyperkalemia were predictors of acute kidney injury. However, it needs further prospective study. Therefore, the concerned stakeholders should give due attention and appropriate intervention to these predictors.

The effect of continuous electronic fetal monitoring on mode of delivery and neonatal outcome among low-risk laboring mothers at Debre Markos comprehensive specialized hospital, Northwest Ethiopia.

Background: Electronic fetal heart rate monitoring (EFM) has been widely used in obstetric practice for over 40 years to improve perinatal outcomes. Its popularity is growing in Ethiopia and other sub-Saharan African countries to reduce high perinatal morbidity and mortality rates. However, its impact on delivery mode and perinatal outcomes in low-risk pregnancies remains controversial. This study aimed to assess the effect of continuous EFM on delivery mode and neonatal outcomes among low-risk laboring mothers at Debre Markos Comprehensive Specialized Hospital, Northwest Ethiopia. Methods: A prospective follow-up study was conducted from November 20, 2023, to January 10, 2024. All low-risk laboring mothers meeting the inclusion criteria were included. Data were collected via pretested structured questionnaires and observation, then analyzed using Epi-data 4.6 and SPSS. The incidences of cesarean delivery and continuous EFM were compared using the chi-squared test and Fisher's exact test. Results: The study found higher rates of instrumental-assisted vaginal delivery (7% vs. 2.4%) and cesarean sections (16% vs. 2%) due to unsettling fetal heart rate patterns in the continuous EFM group compared to the intermittent auscultation group. However, there were no differences in immediate neonatal outcomes between the groups. Conclusion: When compared to intermittent auscultation with a Pinard fetoscope, the routine use of continuous EFM among low-risk laboring mothers was associated with an increased risk of cesarean sections and instrumental vaginal deliveries, without significantly improving immediate newborn outcomes. However, it is important to note that our study faced significant logistical constraints due to the limited availability of EFM devices, which influenced our ability to use EFM comprehensively. Given these limitations, we recommend avoiding the routine use of continuous EFM for low-risk laboring mothers to help reduce the rising number of operative deliveries, particularly cesarean sections. Our findings should be interpreted with caution, and further research with adequate resources is needed to draw definitive conclusions.

Dyskinetic Cerebral Palsy in Children: Clinical Perspectives on Common Comorbidities and Health-Related Quality of Life.

BACKGROUND: The data on specific comorbidities in children with dyskinetic cerebral palsy (DCP) is limited. We evaluated the pattern of comorbidities and health related quality of life (HRQOL) in these children and compared them between etiological and motor impairment subgroups. METHODOLOGY: This cross-sectional study was conducted over 18 months in children with DCP of both sex, and age between one and 14 years. Comorbidities were assessed using standardized scales such as gross motor functioning scale (GMFCS), developmental profile-3 (DP-3), developmental behaviour checklist, sleep behaviour questionnaire (SBQ), and caregiver questionnaire. RESULTS: Sixty-five children with DCP were evaluated (hyperbilirubinemia n = 43, 66% and perinatal asphyxia n = 19, 29%). The majority of children were severely affected in gross motor functioning (level IV 29.2% and level V 53.8%). Epilepsy was seen in 21.5% of cases (19% in hyperbilirubinemia and 32% in asphyxia, p = 0.4). The mean age of onset of seizures was 15.4 + 20.6 months (range 2-72). Visual problems were seen in 54% of cases and included upgaze palsy, squint, refractive error, optic atrophy and cortical blindness. A significant proportion of children with hyperbilirubinemia had upgaze palsy as compared to those with perinatal asphyxia (70% vs. 32%, p 0.01). Rest of the visual problems were not significantly different between the two etiological subgroups. Drooling (87.6%), protein-energy malnutrition (66.6%), and reflux (57%) were the most common gastrointestinal problems in children with DCP. Children with DCP showed problems in social relating (33.8%), anxiety (26.2%), and self-absorbed behaviour (7.7%). However, there were no statistically significant differences between the etiological, motor impairment and age-based subgroups. Children with DCP had high scores on SBQ, suggesting sleep problems. Sleep scores were similar in the hyperbilirubinemia and perinatal asphyxia subgroups. Greater sleep problems were noted in children aged < 4y (70.6 + 10.1 vs. 56.5 + 11.3, p < 0.05 as compared to children above 4y of age) and severe motor impairments (68.2 + 11.3 vs. 57.2 + 13.1, p 0.008 as compared to mild-moderate motor impairment). Poor overall developmental scores were seen in 61.5% children and were significantly associated with GMFCS (p 0.04). The majority of children showed impairments in physical (58.5%), adaptive behaviour (58.5%), social-emotional (50.8%), cognitive (60%) and communication (52%) subscales of DP-3. Cognitive impairment was similar in the etiological (hyperbilirubinemia vs. perinatal asphyxia, p = 0.3), and motor impairment (mild-moderate vs. severe, p = 0.9) subgroups. HRQOL was significantly affected by motor impairment in positioning-transfer (p value 0.0001), and interaction-communication domains (p value 0.0001), however, there was no difference based on the etiology of hyperbilirubinemia and asphyxia. CONCLUSION: Children with DCP demonstrate several comorbidities and impaired quality of life. These are similar in hyperbilirubinemia and perinatal asphyxia cohorts, expect for significant proportion of upgaze palsy in DCP secondary to hyperbilirubinemia. Younger children have more problematic behaviour and impaired sleep quality. Severe motor disability influences the developmental outcomes, cognition, sleep and HRQOL in children with DCP.

Neonatal therapeutic hypothermia in a regional swedish cohort: Adherence to guidelines, transport and outcomes.

AIM: Swedish guidelines for therapeutic hypothermia (TH) after perinatal asphyxia were established in 2007, following several randomised studies that demonstrated improved outcomes. We assessed the implementation of hypothermia treatment in a mid-Swedish region with a sizeable proportion of outborn infants. METHOD: A population-based TH cohort from 2007 to 2015 was scrutinised for adherence to national guidelines, interhospital transport, including the use of a cooling mattress made of phase change material for thermal management, and outcomes. RESULTS: Of 136 admitted infants, 99 (73 %) were born outside the hospital. Ninety-eight percent fulfilled the criteria for postnatal depression/acidosis, and all patients had moderate-to-severe encephalopathy. Treatment was initiated within 6 h in 85 % of patients; amplitude-integrated electroencephalography/electroencephalography was recorded in 98 %, cranial ultrasound in 78 %, brain magnetic resonance imaging in 79 %, hearing tests in all, and follow-up was performed in 93 %. Although target body temperature was attained later (p < 0.01) in outborn than in inborn infants, at a mean (standard deviations) age of 6.2 (3.2) h vs 4.4 (2.6) h, 40 % of those transported using the cooling mattress were already within the therapeutic temperature range on arrival, and few were excessively cooled. The mortality rate was 23 %, and 38 % of the survivors had neurodevelopmental impairment at a median of 2.5 years. CONCLUSION: The regionalisation of TH, including interhospital transport, was feasible and resulted in outcomes comparable to those of randomised controlled studies.

Risk factors for neonatal hypoxic ischemic encephalopathy and therapeutic hypothermia: a matched case-control study.

BACKGROUND: Peripartum asphyxia is one of the main causes of neonatal morbidity and mortality. In moderate and severe cases of asphyxia, a condition called hypoxic-ischemic encephalopathy (HIE) and associated permanent neurological morbidities may follow. Due to the multifactorial etiology of asphyxia, it may be difficult prevent, but in term neonates, therapeutic cooling can be used to prevent or reduce permanent brain damage. The aim of this study was to assess the significance of different antenatal and delivery related risk factors for moderate and severe HIE and the need for therapeutic hypothermia. METHODS: We conducted a retrospective matched case-control study in Helsinki University area hospitals during 2013-2017. Newborn singletons with moderate or severe HIE and the need for therapeutic hypothermia were included. They were identified from the hospital database using ICD-codes P91.00, P91.01 and P91.02. For every newborn with the need for therapeutic hypothermia the consecutive term singleton newborn matched by gender, fetal presentation, delivery hospital, and the mode of delivery was selected as a control. Odds ratios (OR) between obstetric and delivery risk factors and the development of HIE were calculated. RESULTS: Eighty-eight cases with matched controls met the inclusion criteria during the study period. Maternal and infant characteristics among cases and controls were similar, but smoking was more common among cases (aOR 1.46, CI 1.14-1.64, p = 0.003). The incidence of preeclampsia, diabetes and intrauterine growth restriction in groups was equal. Induction of labour (aOR 3.08, CI 1.18-8.05, p = 0.02) and obstetric emergencies (aOR 3.51, CI 1.28-9.60, p = 0.015) were more common in the case group. No difference was detected in the duration of the second stage of labour or the delivery analgesia. CONCLUSIONS: Smoking, induction of labour and any obstetric emergency, especially shoulder dystocia, increase the risk for HIE and need for therapeutic hypothermia. The decisions upon induction of labour need to be carefully weighed, since maternal smoking and obstetric emergencies can hardly be controlled by the clinician.

8-oxoguanine DNA glycosylase-1 may serve as biomarker of mechanical asphyxia.

AIM: To identify mtDNA and OGG1 as potential biomarker candidates for mechanical asphyxia. METHOD: The human tissues are divided into experimental group (hanging and strangulation) and control groups (hemorrhagic shock, brain injury group, and poisoning group). Detected the expression of OGG1 and integrity of mtDNA in cardiac tissue of each group. We used over-OGG1 vector and siRNA-OGG1 transfecting H9C2 cell line to observe the function of OGG1 in hypoxic cells. RESULTS: 1. mtDNA integrity decreased in the mechanical asphyxia group, OGG1 expression increased in mechanical asphyxia groups. They can be biomarkers for mechanical asphyxia. 2. OGG1 increased first and decreased in hypoxia-induced H9C2 cells. OGG1 upregulated the TFAM, NRF1, and Bcl2 in hypoxia-induced H9C2. OGG1 downregulated cleaved-Caspase3 in hypoxia-induced H9C2 cells. 3. In the normoxia condition, NAC maintained mtDNA integrity and decreased the mitochondrial membrane potential and amount of ATP. CONCLUSION: mtDNA integrity and OGG1 expression can be biomarkers for mechanical asphyxia. OGG1 can maintain mtDNA integrity and maintain the stability of the mitochondrial membrane.

Effect of dimethyl fumarate on mitochondrial metabolism in a pediatric porcine model of asphyxia-induced in-hospital cardiac arrest.

Neurological and cardiac injuries are significant contributors to morbidity and mortality following pediatric in-hospital cardiac arrest (IHCA). Preservation of mitochondrial function may be critical for reducing these injuries. Dimethyl fumarate (DMF) has shown potential to enhance mitochondrial content and reduce oxidative damage. To investigate the efficacy of DMF in mitigating mitochondrial injury in a pediatric porcine model of IHCA, toddler-aged piglets were subjected to asphyxia-induced CA, followed by ventricular fibrillation, high-quality cardiopulmonary resuscitation, and random assignment to receive either DMF (30 mg/kg) or placebo for four days. Sham animals underwent similar anesthesia protocols without CA. After four days, tissues were analyzed for mitochondrial markers. In the brain, untreated CA animals exhibited a reduced expression of proteins of the oxidative phosphorylation system (CI, CIV, CV) and decreased mitochondrial respiration (p < 0.001). Despite alterations in mitochondrial content and morphology in the myocardium, as assessed per transmission electron microscopy, mitochondrial function was unchanged. DMF treatment counteracted 25% of the proteomic changes induced by CA in the brain, and preserved mitochondrial structure in the myocardium. DMF demonstrates a potential therapeutic benefit in preserving mitochondrial integrity following asphyxia-induced IHCA. Further investigation is warranted to fully elucidate DMF's protective mechanisms and optimize its therapeutic application in post-arrest care.

Feasibility Analysis of ECG-Based pH Estimation for Asphyxia Detection in Neonates.

Birth asphyxia is a potential cause of death that is also associated with acute and chronic morbidities. The traditional and immediate approach for monitoring birth asphyxia (i.e., arterial blood gas analysis) is highly invasive and intermittent. Additionally, alternative noninvasive approaches such as pulse oximeters can be problematic, due to the possibility of false and erroneous measurements. Therefore, further research is needed to explore alternative noninvasive and accurate monitoring methods for asphyxiated neonates. This study aims to investigate the prominent ECG features based on pH estimation that could potentially be used to explore the noninvasive, accurate, and continuous monitoring of asphyxiated neonates. The dataset used contained 274 segments of ECG and pH values recorded simultaneously. After preprocessing the data, principal component analysis and the Pan-Tompkins algorithm were used for each segment to determine the most significant ECG cycle and to compute the ECG features. Descriptive statistics were performed to describe the main properties of the processed dataset. A Kruskal-Wallis nonparametric test was then used to analyze differences between the asphyxiated and non-asphyxiated groups. Finally, a Dunn-Sidák post hoc test was used for individual comparison among the mean ranks of all groups. The findings of this study showed that ECG features (T/QRS, T Amplitude, Tslope, Tslope/T, Tslope/|T|, HR, QT, and QTc) based on pH estimation differed significantly (p < 0.05) in asphyxiated neonates. All these key ECG features were also found to be significantly different between the two groups.

Comparison of maternal 25 (OH) vitamin D levels between premature infants with/without asphyxia.

OBJECTIVES: Perinatal asphyxia is the main risk factor for mortality and morbidity in neonates and neurological disorders in survived infants. We compared the neonatal and maternal 25 (OH) vitamin D levels in neonates with/without asphyxia. MATERIALS AND METHODS: This cross-sectional research was done on 229 neonates (including 158 neonates [69%] without asphyxia [control group] and 71 neonates [31%] with asphyxia [case group]) from 2020 to 2023 using the available sampling method. 25 (OH) Vit D levels in mothers and neonates were assessed and compared in the 2 groups. The data collection instrument was a researcher-made checklist, containing the maternal and neonatal characteristics and laboratory evaluations. Data were analyzed by SPSS 23 using the t-test. RESULTS: The mean maternal 25 (OH) Vit D levels in the case and control groups were 16.34±11.87 and 22.80±12.67 ng/mL, respectively. The mean neonatal 25 (OH) Vit D levels in the case and control groups were respectively 12.13±8.62 and 19.55±11.62 ng/mL (P = 0.002). The case group showed severer maternal and neonatal 25 (OH) Vit D deficiency (P = 0.000) compared to the control group. CONCLUSIONS: Neonatal and maternal 25 (OH) Vit D deficiency can increase the risk of perinatal asphyxia. Therefore, administration of 25 (OH) Vit D supplements to pregnant mothers may reduce the incidence of asphyxia.

Ischemic Post-Conditioning in a Rat Model of Asphyxial Cardiac Arrest.

BACKGROUND: Ischemic post-conditioning (IPoC) has been shown to improve outcomes in limited pre-clinical models. As down-time is often unknown, this technique needs to be investigated over a range of scenarios. As this tool limits reperfusion injury, there may be limited benefit or even harm after short arrest and limited ischemia-reperfusion injury. METHODS: Eighteen male Wistar rats underwent 7 min of asphyxial arrest. Animals randomized to IPoC received a 20 s pause followed by 20 s of compressions, repeated four times, initiated 40 s into cardiopulmonary resuscitation. If return of spontaneous circulation (ROSC) was achieved, epinephrine was titrated to mean arterial pressure (MAP) of 70 mmHg. Data were analyzed using t-test or Mann-Whitney test. Significance set at p ≤ 0.05. RESULTS: The rate of ROSC was equivalent in both groups, 88%. There was no statistically significant difference in time to ROSC, epinephrine required post ROSC, carotid flow, or peak lactate at any timepoint. There was a significantly elevated MAP with IPoC, 90.7 mmHg (SD 13.9), as compared to standard CPR, 76.7 mmHg (8.5), 2 h after ROSC, p = 0.03. CONCLUSIONS: IPoC demonstrated no harm in a model of short arrest using a new arrest etiology for CPR based IPoC intervention in a rat model.

Oxytocin Exhibits Neuroprotective Effects on Hippocampal Cultures under Severe Oxygen-Glucose Deprivation Conditions.

Perinatal asphyxia (PA) and hypoxic-ischemic encephalopathy can result in severe, long-lasting neurological deficits. In vitro models, such as oxygen-glucose deprivation (OGD), are used experimentally to investigate neuronal response to metabolic stress. However, multiple variables can affect the severity level of OGD/PA and may confound any measured treatment effect. Oxytocin (OXT) has emerged as a potential neuroprotective agent against the deleterious effects of PA. Previous studies have demonstrated OXT's potential to enhance neuronal survival in immature hippocampal cultures exposed to OGD, possibly by modulating gamma-aminobutyric acid-A receptor activity. Moreover, OXT's precise impact on developing hippocampal neurons under different severities of OGD/PA remains uncertain. In this study, we investigated the effects of OXT (0.1 µM and 1 µM) on 7-day-old primary rat hippocampal cultures subjected to 2 h OGD/sham normoxic conditions. Cell culture viability was determined using the resazurin assay. Our results indicate that the efficacy of 1 µM OXT treatment varied according to the severity of the OGD-induced lesion, exhibiting a protective effect (p = 0.022) only when cellular viability dropped below 49.41% in non-treated OGD cultures compared to normoxic ones. Furthermore, administration of 0.1 µM OXT did not yield significant effects, irrespective of lesion severity (p > 0.05). These findings suggest that 1 µM OXT treatment during OGD confers neuroprotection exclusively in severe lesions in hippocampal neurons after 7 days in vitro. Further research is warranted to elucidate the mechanisms involved in OXT-mediated neuroprotection.

The benefit of active management in true knot of the umbilical cord: a retrospective study.

PURPOSE: To compare perinatal outcomes between active and routine management in true knot of the umbilical cord (TKUC). METHODS: A retrospective study of singletons born beyond 22 6/7 weeks with TKUC. Active management included weekly fetal heart rate monitoring(FHRM) ≥ 30 weeks and labor induction at 36-37 weeks. Outcomes in active and routine management were compared, including composite asphyxia-related adverse outcome, fetal death, labor induction, Cesarean section (CS) or Instrumental delivery due to non-reassuring fetal heart rate (NRFHR), Apgar5 score < 7, cord Ph < 7, neonatal intensive care unit (NICU) admission and more. RESULTS: The Active (n = 59) and Routine (n = 1091) Management groups demonstrated similar rates of composite asphyxia-related adverse outcome (16.9% vs 16.8%, p = 0.97). Active Management resulted in higher rates of labor induction < 37 weeks (22% vs 1.7%, p < 0.001), CS (37.3% vs 19.2%, p = 0.003) and NICU admissions (13.6% vs 3%, p < 0.001). Fetal death occurred exclusively in the Routine Management group (1.8% vs 0%, p = 0.6). CONCLUSION: Compared with routine management, weekly FHRM and labor induction between 36 and 37 weeks in TKUC do not appear to reduce neonatal asphyxia. In its current form, active management is associated with higher rates of CS, induced prematurity and NICU admissions. Labor induction before 37 weeks should be avoided.

Digital biomarkers: 3PM approach revolutionizing chronic disease management - EPMA 2024 position.

Non-communicable chronic diseases (NCDs) have become a major global health concern. They constitute the leading cause of disabilities, increased morbidity, mortality, and socio-economic disasters worldwide. Medical condition-specific digital biomarker (DB) panels have emerged as valuable tools to manage NCDs. DBs refer to the measurable and quantifiable physiological, behavioral, and environmental parameters collected for an individual through innovative digital health technologies, including wearables, smart devices, and medical sensors. By leveraging digital technologies, healthcare providers can gather real-time data and insights, enabling them to deliver more proactive and tailored interventions to individuals at risk and patients diagnosed with NCDs. Continuous monitoring of relevant health parameters through wearable devices or smartphone applications allows patients and clinicians to track the progression of NCDs in real time. With the introduction of digital biomarker monitoring (DBM), a new quality of primary and secondary healthcare is being offered with promising opportunities for health risk assessment and protection against health-to-disease transitions in vulnerable sub-populations. DBM enables healthcare providers to take the most cost-effective targeted preventive measures, to detect disease developments early, and to introduce personalized interventions. Consequently, they benefit the quality of life (QoL) of affected individuals, healthcare economy, and society at large. DBM is instrumental for the paradigm shift from reactive medical services to 3PM approach promoted by the European Association for Predictive, Preventive, and Personalized Medicine (EPMA) involving 3PM experts from 55 countries worldwide. This position manuscript consolidates multi-professional expertise in the area, demonstrating clinically relevant examples and providing the roadmap for implementing 3PM concepts facilitated through DBs.

Perinatal asphyxia leads to acute kidney damage and increased renal susceptibility in adulthood.

Perinatal asphyxia (PA) poses a significant threat to multiple organs, particularly the kidneys. Diagnosing PA-associated kidney injury remains challenging and treatment options are inadequate. Furthermore, there is a lack of long-term follow-up data regarding the renal implications of PA. In this study, 7-day-old male Wistar rats were exposed to PA using a gas mixture (4% O2; 20% CO2 in N2 for 15 minutes) to investigate molecular pathways linked to renal tubular damage, hypoxia, angiogenesis, heat-shock response, inflammation, and fibrosis in the kidney. In a second experiment, adult rats with a history of PA were subjected to moderate renal ischemia-reperfusion (IR) injury to test the hypothesis that PA exacerbates renal susceptibility. Our results revealed an increased gene expression of renal injury markers (KIM-1, NGAL), hypoxic- and heat shock factors (HIF-1α, HSF-1, HSP-27), pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, MCP-1), and fibrotic markers (TGF-ß, CTGF, Fibronectin) promptly after PA. Moreover, a machine learning model was identified through Random Forest analysis, demonstrating an impressive classification accuracy (95.5%) for PA. Post-PA rats showed exacerbated functional decline and tubular injury and more intense hypoxic-, heat-shock-, pro-inflammatory-, and pro-fibrotic response after renal IRI compared to controls. In conclusion, PA leads to subclinical kidney injury, which may increase the susceptibility to subsequent renal damage later in life. Additionally, the parameters identified through Random Forest analysis provide a robust foundation for future biomarker research in the context of PA.

The Impact of Time to Initiate Therapeutic Hypothermia on Short-Term Neurological Outcomes in Neonates with Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Therapeutic hypothermia is the standard treatment for neonates with hypoxic-ischemic encephalopathy. Preclinical evidence indicates that the time to initiate therapeutic hypothermia correlates with its therapeutic success. This study aims to explore whether there is a correlation between the early initiation of therapeutic hypothermia and improved short-term neurological outcomes in cooled asphyxiated newborns. METHODS: A retrospective analysis was conducted, involving 68 neonates from two different neonatal intensive care units. The impact of time to initiate treatment, time to reach the target temperature, and time between initiation and target temperature was correlated with short-term outcomes on MRI. RESULTS: We did not find a significant difference between outcomes regarding the time to start treatment and the time to achieve the target temperature. Interestingly, neonates with a poor outcome were treated on average earlier than neonates with a favorable outcome but required more time to reach the target temperature. Additionally, the study results did not support the hypothesis that a shorter time to initiate treatment would lead to shorter times to achieve the target temperature. CONCLUSION: Based on our findings, it is recommended to prioritize a thorough evaluation of neonatal encephalopathy before initiating therapeutic hypothermia. Early initiation of treatment should be balanced with the time required for precise assessment to ensure better outcomes.