Correlation Study on the Prognostic Value of miR-21 and S-100B Protein Levels in Neonatal Hypoxic-Ischemic Encephalopathy Undergoing Hypothermia Therapy.

OBJECTIVE: To evaluate the variations in serum levels of microRNA-21 (miR-21) and S-100B protein in neonates with hypoxic-ischemic encephalopathy (HIE) after receiving hypothermia therapy and explore the correlation of these biomarkers with the neurodevelopmental prognosis of the infants. METHODS: This retrospective analysis included 90 neonatal HIE patients diagnosed and treated between January 2019 and December 2022. Real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA) methods were used to measure miR-21 and S-100B protein levels. Neurodevelopmental assessments were conducted at one year, and follow-up was performed using the Bayley Scales of Infant and Toddler Development third edition. Statistical analysis was carried out using SPSS software, with t-tests for continuous variables, chi-square tests for categorical data, Pearson correlation coefficient for correlation analysis, and multivariate regression analysis to adjust for confounding factors. RESULTS: After hypothermia therapy, the observation group showed a significant decrease in miR-21 and S-100B protein levels (P < 0.001), and neurodevelopmental scores were significantly higher than the control group (P < 0.05). Correlation analysis indicated a negative correlation between miR-21 and neurodevelopmental scores (r=-0.62, P < 0.001), as well as a negative correlation between S-100B protein levels (r=-0.76, P < 0.001). Multivariate regression analysis demonstrated that miR-21 levels and S-100B protein levels maintained independent negative correlations with neurodevelopmental scores (P < 0.001). CONCLUSION: Hypothermia therapy significantly reduces serum levels of miR-21 and S-100B protein in neonatal HIE patients and may be associated with better prognosis. miR-21 and S-100B serve as prognostic biomarkers, aiding in predicting and improving the treatment outcomes and long-term prognosis of neonatal HIE.

Detailed statistical analysis plan for ALBINO: effect of Allopurinol in addition to hypothermia for hypoxic-ischemic Brain Injury on Neurocognitive Outcome - a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III).

BACKGROUND: Despite therapeutic hypothermia (TH) and neonatal intensive care, 45-50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants. Allopurinol - a xanthine oxidase inhibitor - reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult. This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE. METHODS/DESIGN: The ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE. Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years. RESULTS: The primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and ."will be stratified for the two treatment groups. DISCUSSION: The statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT03162653. Registered on 22 May 2017.

Inflammatory and Hematologic Liver and Platelet (HALP) Scores in Hypothermia-Treated Hypoxic-Ischemic Encephalopathy (HIE).

OBJECTIVE: This study examined systemic inflammatory indices and "Hemoglobin, Albumin, Lymphocyte, Platelet (HALP) scores" in neonates with hypoxic-ischemic encephalopathy (HIE). METHODS: A total of 43 neonates with moderate-to-severe HIE at 36 weeks' gestation were assessed. Systemic inflammatory markers were measured before HT commenced within 0-6 h after birth and between 60 and 72 h during and after therapy or before adjusting for hypothermia. RESULTS: Platelet counts, hemoglobin levels, and platelet indices in the HIE group were significantly lower at both time points (p = 0.001). Both the neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) decreased in the HIE group after hypothermia therapy (p = 0.001). Seizures, PVL, and kidney injuries were associated with higher HALP scores. The AUCs of NLR, PLR, MLR, SII, SIRI, and platelet, neutrophil, monocyte, and lymphocyte Index (PIV) showed significant sensitivity and specified HIE, with area under the curve (AUC) values of 0.654, 0.751, 0.766, 0.700, 0.722, and 0.749, respectively. CONCLUSIONS: A significant difference in systemic inflammatory markers was found between the HIE and control groups after hypothermia treatment, with significant reductions in the MLR and NLR. These markers, particularly MLR, were significant predictors of adverse clinical outcomes including seizures, PVL, and kidney damage.

GPR30 agonist G1 combined with hypothermia alleviates cognitive impairment and anxiety-like behavior after subarachnoid hemorrhage in rats.

INTRODUCTION: This study aimed to investigate the treatment effect of G protein-coupled receptor 30 (GPR30) agonist G1 combined with hypothermia (HT) on cognitive impairment and anxiety-like behavior after subarachnoid hemorrhage (SAH) in rats. METHODS: Fifty male rats were randomly assigned to one of five groups: Sham group, SAH group, SAH + G1 group, SAH + HT group, and SAH + G1 + HT group. The SAH rat model was established by modified endovascular puncture in all groups except the Sham group. Neurological function after the operation was assessed by Garcia scoring. The degree of rat cerebral edema was determined using dry-wet weighing method on the 28th day after operation. Moreover, the behavioral test was performed on rats on the 4th and 28th days after operation. RESULTS: Compared with Sham group, the Garcia score of each SAH rat model group decreased significantly on the first day and thereafter increased gradually. However, the recovery rate of each treatment group was higher than the SAH group (no treatment), and the Garcia score of SAH + G1 + HT group was much higher than the SAH group on the seventh day after operation. In addition, each treatment group could obviously reduce the cerebral edema degree of SAH rats, among which rats in SAH + G1 + HT group had lower cerebral edema degree than SAH + G1 group and SAH + HT group. Behavioral test results showed that the combination of GPR30 agonist G1 and HT markedly improved the learning and memory ability of SAH rats, alleviated their anxiety- and emotion-related behavior, and enhanced their social interaction. CONCLUSION: GPR30 agonist G1 combined with HT reduces cognitive impairment and anxiety-like behavior in rats with SAH.

Brain Hypothermia Therapy and Targeted Temperature Management for Acute Encephalopathy in Children: Status and Prospects.

In adult intensive care, brain hypothermia therapy (BHT) was reported to be effective in neuroprotection after resuscitation and cardiac arrest. By contrast, in neonatal intensive care, the pathophysiology of brain damage caused by hypoxic-ischemic encephalopathy (HIE) is attributed to circulatory disturbances resulting from ischemia/reperfusion, for which neonatal brain cryotherapy is used. The International Liaison Committee on Resuscitation, 2010, recommends cerebral cryotherapy for HIE associated with severe neonatal pseudoparenchyma death. The usefulness of BHT for neuroprotection in infants and children, especially in pediatric acute encephalopathy, is expected. Theoretically, BHT could be useful in basic medical science and animal experiments. However, there are limitations in clinical planning for treating pediatric acute encephalopathy. No international collaborative study has been conducted, and no clinical evidence exists for neuroprotection using BHT. In this review, we will discuss the pathogenesis of neuronal damage in hypoxic and hypoperfused brains; the history of BHT, its effects, and mechanisms of action; the success of BHT; cooling and monitoring methods of BHT; adverse reactions to BHT; literature on BHT. We will review the latest literature on targeted temperature management, which is used for maintaining and controlling body temperature in adults in intensive care. Finally, we will discuss the development of BHT and targeted temperature management as treatments for pediatric acute encephalopathy.

The role of SUMOylation in the protective mechanisms of therapeutic hypothermia on neonatal hypoxic-ischemic encephalopathy / 中国新生儿科杂志

Objective:To study the role of SUMOylation in the process of therapeutic hypothermia on neural stem cells (NSCs) in neonatal hypoxic-ischemic encephalopathy.Methods:SUMOylation is an essential post-translational modification involving small ubiquitin-like modifiers (SUMOs). Primary-cultured NSCs from mice were assigned into four groups: control group, hypoxia group, hypothermia group and hypoxia+hypothermia group. Western Blot was used to detect the protein levels of SUMO2/3, hypoxia-inducible factor-1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator factor 1α (PGC-1α) and octamer binding transcription factor 4 (Oct4). The diameters of NSCs were compared. ELISA was used to detect lactate dehydrogenase (LDH) level. Apoptosis was examined using flow cytometry. Immunofluorescence method was used to measure the differentiation of NSCs into neuronal cells.Results:Compared with the control group, the levels of SUMO2/3, HIF-1αand PGC-1α in NSCs of the hypoxia group increased 33%, 126% and 140%, respectively ( P<0.05). Compared with the control group, the levels of SUMO2/3 and PGC-1α in NSCs of the hypothermia group increased 52% and 536%, respectively ( P<0.05). Compared with the hypoxia group, the levels of SUMO2/3, HIF-1α, PGC-1α and Oct4 in the hypoxia+hypothermia group increased 44%, 40%, 230% and 59%, respectively ( P<0.05). The diameters of NSCs in hypoxia group, hypothermia group and hypoxia+hypothermia group were smaller than control group, and hypoxia+hypothermia group smaller than hypoxia group ( P<0.05). No significant differences existed in LDH levels between hypothermia group and control group ( P>0.05). LDH level in hypoxia+hypothermia group were significantly lower than hypoxia group ( P<0.05). No significant differences existed in the cell death rates between hypothermia group and control group ( P>0.05). The cell death rate in hypoxia+hypothermia group was significantly lower than hypoxia group ( P<0.05). Compared with the control group, the expressions of Nestin in both hypoxia group and hypothermia group were increased, but neuron specific enolase (NSE) were decreased ( P<0.05). Compared with hypoxia group and hypothermia group, the level of Nestin in hypoxia+hypothermia group was further increased, while NSE was further decreased ( P<0.05). Conclusions:Therapeutic hypothermia may increase the tolerance of NSCs to hypoxia by enhancing SUMO modification of proteins, providing theoretical basis for the treatment of hypoxic-ischemic encephalopathy with therapeutic hypothermia.

Early predictors of brain injury in patients with acute carbon monoxide poisoning and the neuroprotection of mild hypothermia.

INTRODUCTION: Carbon monoxide (CO) poisoning can cause serious neurological sequelae. However, there is neither effective treatment strategy nor reliable indicators to determine the prognosis of patients with CO poisoning. The present study aimed to observe the changes of neurological function score, disease severity score, cerebral oxygen utilization (O2UCc), bispectral (BIS) index and neuron-specific enolase (NSE) concentration, and to elucidate the clinical significance of these potential indicators and the neuroprotective effect of mild hypothermia on brain injury in patients with severe acute CO poisoning. MATERIALS AND METHODS: A total of 277 patients with acute severe CO poisoning from 2013 to 2018 were enrolled in our hospital. Patients were divided into three groups according to their body temperature on the day of admission and their willingness to treat: a fever group (n = 78), a normal temperature group (NT group, n = 113), and a mild hypothermia group (MH group, n = 86). All patients were given hyperbaric oxygen therapy, while those in the MH group received additional mild hypothermia treatment. The severity of the disease, the neurobehavioral status, the incidence of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP), and other indicators including BIS, O2UCc, NSE were further evaluated in all patients at given time-points. RESULTS: Mild hypothermia therapy improved the prognosis of patients with CO poisoning, significantly decreased the value of O2UCc and NSE, and up-regulated BIS. The incidence of DEACMP at 6 months was 27% in the fever group, 23% in the NT group, and 8% in the MH group. The values of Glasgow-Pittsburgh coma scale (G-P score), BIS index and NSE were closely related to the occurrence of DEACMP, the cutoff values were 12.41, 52.17 and 35.20 ng/mL, and the sensitivity and specificity were 79.3%, 77.6%, 79.3% and 67.6%, 89.5%, 88.6% in the receiver operating characteristic curve (ROC), respectively. CONCLUSIONS: Early mild hypothermia treatment could significantly reduce the severity of brain injury after CO poisoning, and might be further popularized in clinic. G-P scores, NSE and BIS index can be regarded as the prediction indicators in the occurrence and development of DEACMP. CLINICAL TRIAL REGISTRATION: The study protocol was granted from Qingdao University Research Ethics Committee (Clinical trial registry and ethical approval number: QD81571283).

Thermal analysis of different shape nanoparticles on hyperthermia therapy on breast cancer in a porous medium: A fractional model.

Cancer is clearly a major cause of disease and fatality around the world, yet little is known about how it starts and spreads. In this study, a model in mathematical form of breast cancer guided by a system of (ODE'S) ordinary differential equations is studied in depth to examine the thermal effects of various shape nanoparticles on breast cancer hyperthermia therapy in the existence of a porous media with fractional derivative connection, when utilizing microwave radiative heating. The unsteady state is determined precisely using the Laplace transform approach to crop a more decisive examination of temperature dissemination of blood temperature inside the breast tissues. Durbin's and Zakian's techniques are used to find Laplace inversion. Mild temperature hyperthermia is used in the treatment, which promotes cell death by increasing cell nervousness to radiation therapy and flow of blood in tumor. In the graphical findings, we can witness the distinct behavior of hyperthermia therapy on tumor cells by applying various metabolic heat generation rates across various time intervals to attain the optimal therapeutic temperature point. Particularly, we used graphs to visualize the behavior of different Nanoparticles with different shaped during hypothermia therapy. In comparison to other nanoparticles and shapes, it demonstrates that gold nanoparticles with a platelet shape are the best option for improving heat transmission. Which assess of heat transfer up to 16.412%.

Analysis of risk factors for early-onset ventilator-associated pneumonia in a neurosurgical intensive care unit.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a severe infection among patients in the neurosurgery intensive care unit (NICU). METHODS: We retrospectively evaluated risk factors for early-onset ventilator-associated pneumonia (EOVAP) from January 2019 to December 2019 at a NICU. A total of 89 NICU patients who were intubated within 48 h of onset and whose mechanical ventilation time was at least 7 days were enrolled. We evaluated EOVAP that occurred within the first 7 days after the onset of mechanical ventilation. The enrolled patients had no history of chronic lung disease and no clinical manifestations of infection before intubation. Clinical data of patients were recorded, and the incidence of and risk factors for EOVAP were analyzed. Patients were also grouped by age (≥ 65 vs. < 65 years) and whether they had received hypothermia treatment or not. RESULTS: Among 89 mechanically ventilated patients (49 men and 40 women; the mean age ± SD was 60.1 ± 14.3 years), 40 patients (44.9%) developed EOVAP within 7 days and 14 patients (15.7%) had a multidrug resistant bacterial infection. Binary logistic regression analysis indicated that older age (≥ 65 years) (odds ratio [OR]:3.53, 95% confidence interval [CI]:1.27-9.79, P = 0.015) and therapeutic hypothermia (OR:3.68, CI:1.10-12.31, p = 0.034) were independent predictors of EOVAP. Levels of peripheral blood leukocytes, neutrophils and platelets were lower in the therapeutic hypothermia group than those who did not receive hypothermia treatment. CONCLUSIONS: This study found that older age (≥ 65 years) and therapeutic hypothermia were independently associated with the risk of EOVAP in NICU patients.

Effects of mild hypothermia therapy combined with minimally invasive debridement in patients with hypertensive intracranial hemorrhage: a randomized controlled study.

OBJECTIVE: To investigate the clinical effect of mild hypothermia therapy (MHT) combined with minimally invasive debridement (MID) in patients with severe hypertensive intracranial hemorrhage (HICH). METHODS: A total of 120 patients with severe HICH who received clinical intervention in our hospital were enrolled as study subjects. In this randomized, controlled, double-blind trial, they were divided into a study group (SG, n=70) and a control group (CNG, n=50). The CNG was treated with MID, and the SG was treated with MID combined with MHT. The general surgical indices, short-term postoperative outcomes, postoperative neurological and recovery in activities of daily living, and complications were compared between the two groups. Patients' Glasgow prognosis (Glasgow Outcome Scale, GOS) scores at 1 year after surgery were analyzed. RESULTS: The operative time, intraoperative blood loss and intensive care unit (ICU) admission were shorter/lower in the SG than in the CNG (P<0.05). The SG had higher hematoma clearance rate at 1 d and 3 d postoperatively, and lower residual hematoma volume at 3 d and 7 d postoperatively than the CNG (P<0.05). Patients in the SG had higher Barthel scores and lower National Institutes of Health Stroke Scale (NIHSS) scores than the CNG at 1-12 months after intervention (P<0.05). The incidence of complications in the SG was lower than that in the CNG (P<0.05). The percentage of GOS grade IV and V was significantly higher in the SG than in the CNG 1 year after surgery (P<0.05). CONCLUSION: The combination of MID and MHT in patients with severe HICH has better clinical results in the short and long term, and improves the postoperative outcomes and quality of life. It can also reduce the incidence of perioperative complications.

Giant deep vein thrombus complicating endovascular cooling therapy after cardiac arrest in a boy with hypertrophic cardiomyopathy.

Mild hypothermia therapy (33-36 °C) is useful in preventing anoxic brain injury occurring after return of spontaneous circulation among survivors of cardiac arrest. Adverse events generally include bleeding, pneumonia, bradycardia, and deep vein thrombosis (DVT). However, one rare complication is huge DVT. We recently encountered a boy with ventricular fibrillation due to hypertrophic cardiomyopathy complicated by huge DVT from bilateral common femoral veins close to the hepatic vein during endovascular cooling therapy via his femoral vein. We successfully managed this case without any complications after infusion of unfractionated heparin to maintain a relatively high activated partial thromboplastin time. .

Crocin enhances hypothermia therapy in hypoxic ischemia-induced brain injury in mice.

Hypoxic-ischemic encephalopathy (HIE) is a serious medical situation at labor which leads to severe brain damage. Hypothermia therapy is the standard treatment for infants with HIE, but the efficacy is limited. Combination treatments are considered to enhance the efficacy of hypothermia. Crocin is an extract from saffron which has anti-inflammatory, anti-oxidant, and neuroprotective properties. The present study sought to investigate whether crocin could act as a combined treatment with hypothermia in a mouse model of HIE. C57BL/6J mice at post-natal day 7 were subjected to left common carotid artery ligation, followed by treatment of crocin (10 mg/kg) and hypothermia, either alone or in combination. Brain edema and tissue infarct were measured to evaluate brain damage. Mediators involved in inflammatory response and oxidative stress were measured. Neurological severity score test was performed to evaluate the functional outcome. Results show that crocin treatment alone could reduce inflammation and brain damage after hypoxia-ischemia. Combined treatment of crocin and hypothermia exerted enhanced therapeutic effect compared with single treatment, resulting in significantly less brain damage, reduced inflammatory and oxidative responses, and improved functional outcome. Together, these data suggest that crocin plays a beneficial effect in the mouse model of HIE. It could also enhance the neuroprotective effect of hypothermia and might be considered as a combination therapeutic treatment with hypothermia in HIE.

Association of perinatal risk factors with neurological outcome in neonates with hypoxic ischemic encephalopathy.

OBJECTIVE: Neonates exposed to perinatal insults typically present with hypoxic ischemic encephalopathy (HIE). The aim of our study was to analyze the association between known risk factors for HIE and the severity of encephalopathy after birth and neurological outcome in neonates during the first 4 d of life. METHODS: Retrospective cohort study including 174 neonates registered between 2011 and 2013 in the National Asphyxia and Cooling Register of Switzerland. RESULTS: None of the studied perinatal risk factors is associated with the severity of encephalopathy after birth. Fetal distress during labor (OR, 2.06; 95% CI, 1.02-4.25, p = .049) and neonatal head circumference (HC) above 10th percentile (p10) at birth (OR, 1.33; 95% CI, 1.05-1.69, p = .02) were associated with neurological benefit in the univariate analysis. Fetal distress on maternal admission for delivery was the only risk factor for neurological harm in the univariate (OR, 0.26; 95% CI, 0.12-0.57, p < .01) and the multivariate analysis (OR, 0.15; 95% CI, 0.04-0.67, p = .013). We identified two different patient scenarios: the probability for neurological benefit during the first 4 d of life was only 20% in neonates with the combination of all the following risk factors (gestational age >41 weeks, chorioamnionitis, fetal distress on maternal admission for delivery, fetal distress during labor, sentinel events during labor, HC below 10th percentile), whereas in the absence of these risk factors the probability for neurological benefit increased to 80%. CONCLUSIONS: We identified a constellation of risk factors that influence neurological outcome in neonates with HIE during the first 4 d of life. These findings may help clinicians to counsel parents during the early neonatal period. (ClinicalTrials.gov NCT02800018).

The efficacy of systemic hypothermia therapy initiated at different times on neonatal hypoxic-ischemic encephalopathy / 中国新生儿科杂志

Objective:To study the clinical efficacy, safety and prognosis of systemic hypothermia therapy on neonatal hypoxic-ischemic encephalopathy (HIE)initiated at different times after birth.Method:From January 2013 to August 2018, term neonates (within 12 hours after birth) diagnosed with neonatal moderate to severe HIE and received systemic treatment in the neonatal intensive care unit of our hospital were retrospectively included. According to the starting time of hypothermia therapy, the neonates were assigned into three groups: within 6 h after birth (TH1 group), 6~12 h (TH2 group) and conventional treatment group (control group). Their clinical data during perinatal period, hospitalization period and follow-up at 6-month were reviewed. Their clinical and neurodevelopmental outcomes were compared using SPSS 25.0 statistical software.Result:A total of 147 neonates with moderate to severe HIE were enrolled. 111 received 72-hour hypothermia therapy, including 79 in the TH1 group, 32 in the TH2 group and 36 in the control group. The neurobehavioral test scores at 10-day of life in the TH1 group were significantly higher than the control group ( P<0.05). No significant differences existed among the TH2 group, the TH1 group and the control group ( P>0.05). The brain magnetic resonance imaging (MRI) showed injuries in the TH1 group and the TH2 group were significantly milder than the control group ( P<0.05). No significant differences of brain injuries existed between TH1 group and TH2 group ( P>0.05). 100 patients completed Bailey Infant Intelligence Development Scale at 6-month follow-up. 21 had abnormal scores. No statistically significant differences existed in the psychomotor development index (PDI) scores among the three groups ( P>0.05). TH1 and TH2 groups had significantly fewer cases with mental development index (MDI) <70 points than the control group ( P<0.05). No statistically significant differences existed of MDI scores between the TH1 group and the TH2 group ( P>0.05). No statistically significant differences existed of PDI scores among the 3 groups ( P>0.05). At 6-month, the mortality rate of the control group (32.1%, 9/28) was significantly higher than the TH1 group (6.6%, 4/61) ( P<0.05). No significant differences existed of mortality rate at 6-month among the TH2 group, the TH1 group and the control group ( P>0.05). Conclusion:Systemic hypothermia therapy for neonatal HIE is safe. Starting systemic hypothermia therapy at 6~12-hour after birth may also be effective in reducing mortality rate and improving neurodevelopmental outcome.

Effective Management with IMPELLA CP® and Hypothermia Therapy for a Case of Severe Ischemic Coronary Disease after Cardiopulmonary Arrest / 日本心臓血管外科学会雑誌

A 67-year-old man was admitted to our hospital following cardiopulmonary arrest (CPA) during work. After resuscitation, coronary angiography revealed left main coronary artery stenosis and three-vessel disease. We considered that coronary artery revascularization was required, but the neurological prognosis was unknown. Thus, an IMPELLA CP® device was inserted and systemic management, including hypothermic therapy, was initiated. Circulatory conditions were stable during hypothermia therapy. Rewarming was initiated 24 h later, and we confirmed no abnormal neurological findings. Emergency off-pump coronary artery bypass was then performed. During the procedure, hemodynamic status was maintained using the IMPELLA CP® device. After surgery, the patient was discharged without neurological complications. We report the management of a patient with severe three-vessel disease after resuscitation for CPA using an IMPELLA CP® device and hypothermic therapy.

Efficacy of hypothermia therapy in patients with acute encephalopathy with biphasic seizures and late reduced diffusion.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized by biphasic seizures and impaired consciousness. The efficacy of hypothermia/normothermia therapy in patients with AESD has rarely been reported on. METHODS: We enrolled 15 patients with AESD admitted to Yamaguchi University Hospital and Yamaguchi-ken Saiseikai Shimonoseki General Hospital between 2005 and 2019 and retrospectively evaluated the long-term efficacy of hypothermia therapy compared to that of non-hypothermia therapy. We compared the long-term sequelae of patients with AESD treated with or without hypothermia therapy. We used the Pediatric Cerebral Performance Category (PCPC) scale and intelligence tests including the Wechsler Intelligence Scale for Children, Tanaka-Binet Intelligence Scale, and Enjoji Infantile Developmental Scale to evaluate neurological sequelae and mental disability. The preventive effect of hypothermia therapy was assessed based on the development of post-encephalopathic epilepsy (PEE). RESULTS: There was no significant between-group difference in the PCPC score (p = 0.53). The subjects with severe mental disability in the hypothermia therapy group were 0 (0%), while those in the non-hypothermia group were 2 (29%); however, the difference was not significant. Notably, there were no patients with onset of PEE in the hypothermia therapy group, while there were 4 (57.1%) in the non-hypothermia group (p = 0.03). CONCLUSIONS: Our study suggests that hypothermia therapy may be effective in the long-term sequelae of AESD in terms of preventing the development of PEE. We propose that hypothermia therapy could contribute to improve the quality of life in these patients by preventing the subsequent onset of PEE.

[Hypothermia therapy for babies: an interminable wait for the parents]. / Hypothermie thérapeutique du bébé : une interminable attente pour les parents.

Hypothermia therapy is a protocol put in place to treat neonatal hypoxic ischemic encephalopathy in the first six hours after birth in order to prevent irreversible brain damage. The parents are therefore immediately separated from the newborn and endure an interminable 72-hour wait before being able to really meet their baby. Psychological support is therefore necessary to be able to think the unthinkable.

Intravenous thrombolysis in combination with mild hypothermia therapy in the treatment of acute cerebral infarction.

OBJECTIVE: To investigate the efficacy of recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis in combination with mild hypothermia therapy in the treatment of acute cerebral infarction. METHODS: One hundred and thirty-two patients with acute cerebral infarction who were admitted to our hospital were selected and grouped into a control group and an observation group, 66 each group. Patients in the control group were given conventional treatment in combination with local mild hypothermia therapy, and patients in the observation group were given rt-PA intravenous thrombolysis on the basis of conventional treatment and local mild hypothermia therapy. National institute of health stroke scale (NIHSS) score and intracranial pressure (ICP) of the two groups before and after treatment was recorded. The efficacy of the two groups was evaluated. The modified Rankin scale (MRS) score was followed up for three months. The blood samples of the patients were collected before and after thrombolysis. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels in the plasma were detected. RESULTS: The NIHSS score of the two groups decreased in the 1st, 3rd and 7th day after treatment compared to before treatment (p<0.05), but the NIHSS score of the two groups had no significant difference at different time points after treatment (p>0.05). The ICP of the two groups decreased in the 1st, 3rd and 7th day after treatment compared to before treatment (p<0.05), and the decrease of ICP of the observation group was more significant than that of the control group at the same time point (1st, 3rd and 7th day after treatment) (p<0.05). The clinical efficacy of the observation group was higher than that of the control group after treatment, and the difference was statistically significant (p<0.05). The MDA concentration of both groups decreased at different time points after treatment (p<0.05), but the SOD concentration increased (p<0.05). The MDA concentration of the observation group was lower than that of the control group at different time points after treatment (p<0.05), and the SOD concentration of the observation group was higher than that of the control group (p<0.05). CONCLUSION: rt-PA intravenous thrombolysis in combination with mild hypothermia therapy has significant efficacy in the treatment of acute cerebral infarction. It can effectively relieve neurological function. Its action mechanism may be realized by relieving oxidative stress response.

Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO): study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III).

BACKGROUND: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. METHODS: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. DISCUSSION: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. TRIAL REGISTRATION: NCT03162653, www.ClinicalTrials.gov , May 22, 2017.

Hypoxia-Ischemia and Hypothermia Independently and Interactively Affect Neuronal Pathology in Neonatal Piglets with Short-Term Recovery.

Therapeutic hypothermia is the standard of clinical care for moderate neonatal hypoxic-ischemic encephalopathy. We investigated the independent and interactive effects of hypoxia-ischemia (HI) and temperature on neuronal survival and injury in basal ganglia and cerebral cortex in neonatal piglets. Male piglets were randomized to receive HI injury or sham procedure followed by 29 h of normothermia, sustained hypothermia induced at 2 h, or hypothermia with rewarming during fentanyl-nitrous oxide anesthesia. Viable and injured neurons and apoptotic profiles were counted in the anterior putamen, posterior putamen, and motor cortex at 29 h after HI injury or sham procedure. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) identified genomic DNA fragmentation to confirm cell death. Though hypothermia after HI preserved viable neurons in the anterior and posterior putamen, hypothermia prevented neuronal injury in only the anterior putamen. Hypothermia initiated 2 h after injury did not protect against apoptotic cell death in either the putamen or motor cortex, and rewarming from hypothermia was associated with increased apoptosis in the motor cortex. In non-HI shams, sustained hypothermia during anesthesia was associated with neuronal injury and corresponding viable neuron loss in the anterior putamen and motor cortex. TUNEL confirmed increased neurodegeneration in the putamen of hypothermic shams. Anesthetized, normothermic shams did not show abnormal neuronal cytopathology in the putamen or motor cortex, thereby demonstrating minimal contribution of the anesthetic regimen to neuronal injury during normothermia. We conclude that the efficacy of hypothermic protection after HI is region specific and that hypothermia during anesthesia in the absence of HI may be associated with neuronal injury in the developing brain. Studies examining the potential interactions between hypothermia and anesthesia, as well as with longer durations of hypothermia, are needed.