Hypothermia Therapy Research Articles

Clinical Assessment and Management of Acute Spinal Cord Injury.

The information contained in this article is suitable for clinicians practicing in the United States desiring a general overview of the assessment and management of spinal cord injury (SCI), focusing on initial care, assessment, acute management, complications, prognostication, and future research directions. SCI presents significant challenges, affecting patients physically, emotionally, and financially, with variable recovery outcomes ranging from full functionality to lifelong dependence on caregivers. Initial care aims to minimize secondary injury through thorough neurological evaluations and imaging studies to assess the severity of the injury. Acute management prioritizes stabilizing respiratory and cardiovascular functions and maintaining proper spinal cord perfusion. Patients with unstable or progressive neurological decline benefit from timely surgical intervention to optimize neurological recovery. Subacute management focuses on addressing common complications affecting the respiratory, gastrointestinal, and genitourinary systems, emphasizing a holistic, multidisciplinary approach. Prognostication is currently based on neurological assessments and imaging findings, but emerging biomarkers offer the potential to refine outcome predictions further. Additionally, novel therapeutic interventions, such as hypothermia therapy and neuroprotective medications are being explored to mitigate secondary damage and enhance recovery. This paper serves as a high-yield refresher for clinicians for the assessment and management of acute spinal cord injury during index admission.

Mild hypothermia therapy alleviates neuronal damage and repairs cerebral ischemia-reperfusion injury through the SIRT1/AMPK pathway.

Cerebrovascular disease, one of the high-risk diseases worldwide, is high in morbidity, disability, mortality, and recurrence rates, which brings many harms to human beings such as physical and mental harm, economic losses, and impairment of social relations. Cerebral ischemia-reperfusion injury (CIRI) is one of the most common pathological manifestations, with mild hypothermia therapy being the most commonly used treatment in clinical practice. In this study, the research team established a CIRI animal model and found that the neuronal apoptosis rate was significantly increased, accompanied by significant ferroptosis, increased inflammation and oxidative stress damage in brain tissue, and obviously inhibited SIRT1/AMPK pathway. However, after mild hypothermia treatment, the pathological changes of CIRI rats were significantly reversed, and the SIRT1/AMPK pathway was reactivated. Therefore, mild hypothermia may achieve the purpose of CIRI repair by activating the SIRT1/AMPK signaling pathway, and targeted regulation of the SIRT1/AMPK signaling pathway may be a research direction for optimizing mild hypothermia therapy or developing new treatment plans for CIRI.

Efficacy of Hypothermic Compression Bandages in Cardiac Device Surgical Wounds: A Randomized Controlled Trial.

Pocket hematoma is the most prevalent complication with cardiac implantable electronic devices (CIEDs), especially in patients who are undergoing oral anticoagulation and/or antiplatelet therapy. To evaluate the efficacy of hypothermic compression bandaging versus conventional compression bandaging for the prevention of surgical wound hematoma of CIEDs in patients who are undergoing chronic anticoagulant drug use and/or antiplatelet therapy. This was a single-center randomized prospective study. The intervention group received a hypothermic compression bandage, and the control group received a conventional compression bandage. The primary endpoint was the appearance of hematoma 10 days after the intervention. A total of 310 patients participated in the study. The mean age of the participants was 73.77 ± 10.68 years, and 74.8% were men. In the intervention group, 5.88% (n = 18) of patients developed ecchymosis, and 1.3% (n = 4) developed mild hematoma. In the control group, 5.88% (n = 18) of patients developed ecchymosis, and 2.9% (n = 9) developed mild hematoma. No patient in either group had a severe hematoma. No significant differences were observed between the two types of dressing in any of the three degrees of hematoma. This study demonstrated that compression bandaging with or without hypothermic therapy effectively prevents pocket hematoma of CIEDs in patients at high risk of bleeding.

Palliative care consultation in patients hospitalized with out-of-hospital cardiac arrest: Impact on invasive procedures, do-not-resuscitate orders, and healthcare costs

BackgroundThe impact of palliative care consultation on the management and outcomes of patients hospitalized with out-of-hospital cardiac arrest (OHCA) remains poorly understood. This study examined associations between palliative care consultation and in-hospital outcomes of patients hospitalized with OHCA, stratified by survival status. MethodThis cross-sectional study used data from the National Inpatient Sample (2016–2021). Adult patients hospitalized with OHCA who received cardiopulmonary resuscitation were included. Multivariable analyses assessed associations between palliative care consultation and outcomes in non-terminal and terminal OHCA hospitalizations, adjusting for demographics, hospital characteristics, and comorbidities. ResultsAmong 488,700 OHCA hospitalizations, palliative care consultation was associated with lower odds of invasive procedures in non-terminal hospitalizations, including percutaneous coronary intervention (PCI) (aOR 0.30, 95 % CI 0.25–0.36), mechanical circulatory support (aOR 0.54, 95 % CI 0.44–0.68), permanent pacemaker (aOR 0.27, 95 % CI 0.20–0.37) and implantable cardioverter defibrillator insertion (aOR 0.22, 95 % CI 0.16–0.31), and cardioversion (aOR 0.62, 95 % CI 0.55–0.70). In terminal hospitalizations, palliative care was associated with lower odds of PCI (aOR 0.78, 95 % CI 0.70–0.87) and cardioversion (aOR 0.91, 95 % CI 0.85–0.97), but higher odds of therapeutic hypothermia (aOR 3.12, 95 % CI 2.72–3.59), gastrostomy (aOR 1.22, 95 % CI 1.05–1.41), and renal replacement therapy (aOR 1.19, 95 % CI 1.12–1.26). Palliative care was associated with higher DNR utilization in both subgroups and lower hospital costs in non-terminal hospitalizations but higher costs in terminal hospitalizations. ConclusionPalliative care consultation in OHCA is associated with differences in invasive procedures, DNR utilization, and hospital costs, varying by survival status.

Model-predicted brain temperature computational imaging by multimodal noninvasive functional neuromonitoring of cerebral oxygen metabolism and hemodynamics: MRI-derived and clinical validation.

Brain temperature, a crucial yet under-researched neurophysiological parameter, is governed by the equilibrium between cerebral oxygen metabolism and hemodynamics. Therapeutic hypothermia has been demonstrated as an effective intervention for acute brain injuries, enhancing survival rates and prognosis. The success of this treatment hinges on the precise regulation of brain temperature. However, the absence of comprehensive brain temperature monitoring methods during therapy, combined with a limited understanding of human brain heat transmission mechanisms, significantly hampers the advancement of hypothermia-based neuroprotective therapies. Leveraging the principles of bioheat transfer and MRI technology, this study conducted quantitative analyses of brain heat transfer during mild hypothermia therapy. Utilizing MRI, we reconstructed brain structures, estimated cerebral blood flow and oxygen consumption parameters, and developed a brain temperature calculation model founded on bioheat transfer theory. Employing computational cerebral hemodynamic simulation analysis, we established an intracranial arterial fluid dynamics model to predict brain temperature variations across different therapeutic hypothermia modalities. We introduce a noninvasive, spatially resolved, and optimized mathematical bio-heat model that synergizes model-predicted and MRI-derived data for brain temperature prediction and imaging. Our findings reveal that the brain temperature images generated by our model reflect distinct spatial variations across individual participants, aligning with experimentally observed temperatures.

Current status and controversies in the treatment of neonatal hypoxic-ischemic encephalopathy: A review.

Neonatal hypoxic-ischemic encephalopathy is a type of traumatic brain injury caused by insufficient cerebral perfusion and oxygen supply in the perinatal neonate, which can be accompanied by different types of long-term neurodevelopmental sequelae, such as cerebral palsy, learning disabilities, mental retardation and epilepsy It is one of the main causes of neonatal death and disability, and it has caused a great burden on families and society. Therefore, this article mainly reviews the latest developments in mild hypothermia therapy and related drugs for neonatal hypoxic-ischemic encephalopathy.

A Systematic Review of the Relationship Between Neonatal Hypoxic-Ischemic Encephalopathy and Long-Term Cognitive Outcomes: Where Do We Stand?

This study aims to systematically review the existing literature on long-term cognitive outcomes in neonates with hypoxic-ischemic encephalopathy (HIE). A thorough search of PubMed, MEDLINE, and Embase was conducted to find studies that satisfied the inclusion requirements. Rayyan (Qatar Computing Research Institute, Doha, Qatar) was utilized during the whole operation.Our results included seven studies with a total of 521 patients and 247 (47.4%) were females. All of the included participants were assessed for the incidence of cognitive functions following hypothermia therapy. Newborns with significant HIE are at high risk for neurodevelopmental complications even in the absence of magnetic resonance imagining (MRI) abnormalities, such as poor performance score and hearing-language score, functional status, delayed language skills, emotional processing, sensory movement, learning, and memory.Independent of motor deficits, participants with a history of HIE are susceptible to issues with cognition and executive function during late childhood and adolescence. It is crucial to keep an eye on their intellectual development after infancy since cognitive dysfunction and memory problems might manifest subtly or not at all in the early years of life, but they can cause problems in later childhood and adolescence. Long-term follow-up research is also required to ascertain whether the enhanced cognitive outcomes will continue throughout adolescence. Even in cases where overt neuromotor abnormalities are not evident, children with watershed injuries on brain MRIs should be closely monitored to evaluate cognitive function, particularly language development.

Differential Mitochondrial Bioenergetics in Neurons and Astrocytes Following Ischemia-Reperfusion Injury and Hypothermia.

The close interaction between neurons and astrocytes has been extensively studied. However, the specific behavior of these cells after ischemia-reperfusion injury and hypothermia remains poorly characterized. A growing body of evidence suggests that mitochondria function and putative transference between neurons and astrocytes may play a fundamental role in adaptive and homeostatic responses after systemic insults such as cardiac arrest, which highlights the importance of a better understanding of how neurons and astrocytes behave individually in these settings. Brain injury is one of the most important challenges in post-cardiac arrest syndrome, and therapeutic hypothermia remains the single, gold standard treatment for neuroprotection after cardiac arrest. In our study, we modeled ischemia-reperfusion injury by using in vitro enhanced oxygen-glucose deprivation and reperfusion (eOGD-R) and subsequent hypothermia (HPT) (31.5 °C) to cell lines of neurons (HT-22) and astrocytes (C8-D1A) with/without hypothermia. Using cell lysis (LDH; lactate dehydrogenase) as a measure of membrane integrity and cell viability, we found that neurons were more susceptible to eOGD-R when compared with astrocytes. However, they benefited significantly from HPT, while the HPT effect after eOGD-R on astrocytes was negligible. Similarly, eOGD-R caused a more significant reduction in adenosine triphosphate (ATP) in neurons than astrocytes, and the ATP-enhancing effects from HPT were more prominent in neurons than astrocytes. In both neurons and astrocytes, measurement of reactive oxygen species (ROS) revealed higher ROS output following eOGD-R, with a non-significant trend of differential reduction observed in neurons. HPT after eOGD-R effectively downregulated ROS in both cells; however, the effect was significantly more effective in neurons. Lipid peroxidation was higher after eOGD-R in neurons, while in astrocytes, the increase was not statistically significant. Interestingly, HPT had similar effects on the reduction in lipoperoxidation after eOGD-R with both types of cells. While glutathione (GSH) levels were downregulated after eOGD-R in both cells, HPT enhanced GSH in astrocytes, but worsened GSH in neurons. In conclusion, neuron and astrocyte cultures respond differently to eOGD-R and eOGD-R + HTP treatments. Neurons showed higher sensitivity to ischemia-reperfusion insults than astrocytes; however, they benefited more from HPT therapy. These data suggest that given the differential effects from HPT in neurons and astrocytes, future therapeutic developments could potentially enhance HPT outcomes by means of neuronal and astrocytic targeted therapies.

Hypoxic-Ischemic Encephalopathy: Pathogenesis and Promising Therapies.

Hypoxic-ischemic encephalopathy (HIE) is a brain lesion caused by inadequate blood supply and oxygen deprivation, often occurring in neonates. It has emerged as a grave complication of neonatal asphyxia, leading to chronic neurological damage. Nevertheless, the precise pathophysiological mechanisms underlying HIE are not entirely understood. This paper aims to comprehensively elucidate the contributions of hypoxia-ischemia, reperfusion injury, inflammation, oxidative stress, mitochondrial dysfunction, excitotoxicity, ferroptosis, endoplasmic reticulum stress, and apoptosis to the onset and progression of HIE. Currently, hypothermia therapy stands as the sole standard treatment for neonatal HIE, albeit providing only partial neuroprotection. Drug therapy and stem cell therapy have been explored in the treatment of HIE, exhibiting certain neuroprotective effects. Employing drug therapy or stem cell therapy as adjunctive treatments to hypothermia therapy holds great significance. This article presents a systematic review of the pathogenesis and treatment strategies of HIE, with the goal of enhancing the effect of treatment and improving the quality of life for HIE patients.

Whole-body hypothermia in mild neonatal encephalopathy: protocol for a multicentre phase III randomised controlled trial

BackgroundMild hypoxic ischemic encephalopathy is associated with sub optimal cognition and learning difficulties at school age. Although whole-body hypothermia reduces death and disability after moderate or severe encephalopathy in high-income countries, the safety and efficacy of hypothermia in mild encephalopathy is not known. The cooling in mild encephalopathy (COMET) trial will examine if whole-body hypothermia improves cognitive development of neonates with mild encephalopathy.MethodsThe COMET trial is a phase III multicentre open label two-arm randomised controlled trial with masked outcome assessments. A total of 426 neonates with mild encephalopathy will be recruited from 50 to 60 NHS hospitals over 2 ½ years following parental consent. The neonates will be randomised to 72 h of whole-body hypothermia (33.5 ± 0.5 C) or normothermia (37.0 ± 0.5 C) within six hours or age. Prior to the recruitment front line clinical staff will be trained and certified on expanded modified Sarnat staging for encephalopathy. The neurological assessment of all screened and recruited cases will be video recorded and centrally assessed for quality assurance. If recruitment occurs at a non-cooling centre, neonates in both arms will be transferred to a cooling centre for continued care, after randomisation. All neonates will have continuous amplitude integrated electroencephalography (aEEG) at least for the first 48 h to monitor for seizures. Predefined safety outcomes will be documented, and data collected to assess resource utilization of health care. A central team masked to trial group allocation will assess neurodevelopmental outcomes at 2 years of age. The primary outcome is mean difference in composite cognitive scores on Bayley scales of Infant and Toddler development 4th Edition.DiscussionThe COMET trial will establish the safety and efficacy of whole-body hypothermia for mild hypoxic ischaemic encephalopathy and inform national and international guidelines in high income countries. It will also provide an economic assessment of whole-body hypothermia therapy for mild encephalopathy in the NHS on cost-effectiveness grounds.Trial registration numberNCT05889507 June 5, 2023.

Cold inducible RNA binding protein-regulated mitochondria associated endoplasmic reticulum membranes-mediated Ca2+ transport play a critical role in hypothermia cerebral resuscitation

Cardiac arrest is a global health issue causing more deaths than many other diseases. Hypothermia therapy is commonly used to treat secondary brain injury resulting from cardiac arrest. Previous studies have shown that CIRP is induced in specific brain regions during hypothermia and inhibits mitochondrial apoptotic factors. However, the specific mechanisms by which hypothermia-induced CIRP exerts its anti-apoptotic effect are still unknown. This study aims to investigate the role of Cold-inducible RNA-binding protein (CIRP) in mitochondrial-associated endoplasmic reticulum membrane (MAM)-mediated Ca2+ transport during hypothermic brain resuscitation.We constructed a rat model of cardiac arrest and resuscitation and hippocampal neuron oxygen-glucose deprivation/reoxygenation model. We utilized shRNA transfection to interfere the expression of CIRP and observe the effect of CIRP on the structure and function of MAM.Hypothermia induced CIRP can reduce the apoptosis of hippocampal neurons, and improve the survival rate of rats. Hypothermia induced CIRP can reduce the expressions of calcium transporters IP3R and VDAC1 in MAM, reduce the concentration of calcium in mitochondria, decrease the expression of ROS, and stabilize the mitochondrial membrane potential. Immunofluorescence and immunocoprecipitation showed that CIRP could directly interact with IP3R-VDAC1 complex, thereby changing the structure of MAM, inhibiting calcium transportation and improving mitochondrial function in vivo and vitro.Both in vivo and in vitro experiments have confirmed that hypothermia induced CIRP can act on the calcium channel IP3R-VDAC1 in MAM, reduce the calcium overload in mitochondria, improve the energy metabolism of mitochondria, and thus play a role in neuron resuscitation. This study contributes to understanding hypothermia therapy and identifies potential targets for brain injury treatment.

Trends and hotspots of the neuroprotection of hypothermia treatment: A bibliometric and visualized analysis of research from 1992 to 2023.

Recent studies have extensively investigated hypothermia as a therapeutic approach for mitigating neural damage. Despite this, bibliometric analyses specifically focusing on this area remain scarce. Consequently, this study aims to comprehensively outline the historical framework of research and to pinpoint future research directions and trends. Articles spanning from 2003 to 2023, relevant to both "neuroprotection" and "hypothermia", were sourced from the Web of Science Core Collection. The CiteSpace software facilitated a comprehensive evaluation and analysis of these publications. This analysis included examining the annual productivity, collaboration among nations, institutions, and authors, as well as the network of co-cited references, authors and journals, and the co-occurrence of keywords, and their respective clusters and trends, all of which were visualized. This study included 2103 articles on the neuroprotection effects of hypothermia, noting a consistent increase in publications since 1992. The United States, the University of California System, and Ji Xunming emerged as the most productive nation, institution, and author, respectively. Analysis of the top 10 co-cited publications revealed that seven articles focused on the effects of hypothermia in infants with hypoxic-ischemic encephalopathy, while three studies addressed cardiac arrest. Shankaran S and the journal Stroke were the most frequently co-cited author and journal, respectively. Keyword cluster analysis identified ischemic stroke as the primary focus of hypothermia therapy historically, with cardiac arrest and neonatal hypoxic-ischemic encephalopathy emerging as current research foci. Recent studies on the neuroprotective effects of hypothermia in cardiac arrest and neonatal hypoxic-ischemic encephalopathy suggest that hypothermia may mitigate neural damage associated with these conditions. However, the application of hypothermia in the treatment of ischemic stroke remains confined to animal models and invitro studies, with a notable absence of evidence from multicenter randomized controlled trials (RCTs). Further research is required to address this gap.

Observation of the effect of hypothermia therapy combined with optimized nursing on brain protection after cardiopulmonary resuscitation: A retrospective case-control study.

This study aimed to investigate the impact of optimized emergency nursing in conjunction with mild hypothermia nursing on neurological prognosis, hemodynamics, and complications in patients with cardiac arrest. A retrospective analysis was conducted on the medical records of 124 patients who received successful cardiopulmonary resuscitation (CPR) at Fujian Provincial Hospital South Branch. The patients were divided into control and observation groups, each consisting of 62 cases. The brain function of both groups was assessed using the Glasgow Coma Scale and the National Institutes of Health Stroke Scale. Additionally, serum neuron-specific enolase level was measured in both groups. The vital signs and hemodynamics of both groups were analyzed, and the complications and satisfaction experienced by the 2 groups were compared. The experimental group exhibited significantly improved neurological function than the control group (P < .05). Furthermore, the heart rate in the experimental group was significantly lower than the control group (P < .05). However, no significant differences were observed in blood oxygen saturation, mean arterial pressure, central venous pressure, and systolic blood pressure between the 2 groups (P > 0.05). Moreover, the implementation of optimized nursing practices significantly reduced complications and improved the quality of life and satisfaction of post-CPR patients (P < .05). The integration of optimized emergency nursing practices in conjunction with CPR improves neurological outcomes in patients with cardiac arrest.

Human Placenta-Derived Mesenchymal Stem Cells Improve Neurological Function in Rats with Intrauterine Hypoxic-Ischaemic Encephalopathy by Reducing Apoptosis and Inflammatory Reactions.

Hypoxic-ischaemic encephalopathy (HIE) is a major cause of neonatal disability and mortality. Although hypothermia therapy offers some neuroprotection, the recovery of neurological function is limited. Therefore, new synergistic therapies are necessary to improve the prognosis. Mesenchymal stem cell-based therapy is emerging as a promising treatment option for HIE. In this study, we studied the therapeutic efficacy of human placenta-derived mesenchymal stem cells (PD-MSCs) in the HIE rat model and analyzed the underlying therapeutic mechanisms. Rats were divided into 6 groups (n = 9 for each) as follows: control, HIE model, HIE + normal saline, and HIE + PD-MSC transplantation at days 7, 14 and 28 postpartum. Following PD-MSC transplantation, neurological behavior was evaluated using rotarod tests, traction tests, and the Morris water maze test. The degree of brain tissue damage was assessed by histological examination and Nissl staining. Expression levels of apoptosis-related proteins and inflammatory factors were quantified by Western blotting and enzyme-linked immunosorbent assays. Immunofluorescence was used to investigate the ability of PD-MSCs to repair the morphology and function of hippocampal neurons with hypoxic-ischaemic (HI) injury. PD-MSC transplantation enhanced motor coordination and muscle strength in HIE rats. This treatment also improved spatial memory ability by repairing pathological damage and preventing the loss of neurons in the cerebral cortex. The most effective treatment was observed in the HIE + PD-MSC transplantation at day 7 group. Expression levels of microtubule-associated protein-2 (MAP-2), B-cell lymphoma-2 (BCL-2), interleukin (IL)-10, and transforming growth factor (TGF -β1) were significantly higher in the HIE + PD-MSC treatment groups compared to the HIE group, whereas the levels of BCL-2-associated X protein (BAX), BCL-2-associated agonist of cell death (BAD), IL-1β and tumour necrosis factor α (TNF-α) were significantly lower. We demonstrated that intravenous injection of PD-MSC at 7, 14 and 28 days after intrauterine HI damage in a rat model could improve learning, memory, and motor function, possibly by inhibiting apoptosis and inflammatory damage. These findings indicate that autologous PD-MSC therapy could have potential application for the treatment of HIE.

Cold-induced FOXO1 nuclear transport aids cold survival and tissue storage

Cold-induced injuries severely limit opportunities and outcomes of hypothermic therapies and organ preservation, calling for better understanding of cold adaptation. Here, by surveying cold-altered chromatin accessibility and integrated CUT&Tag/RNA-seq analyses in human stem cells, we reveal forkhead box O1 (FOXO1) as a key transcription factor for autonomous cold adaptation. Accordingly, we find a nonconventional, temperature-sensitive FOXO1 transport mechanism involving the nuclear pore complex protein RANBP2, SUMO-modification of transporter proteins Importin-7 and Exportin-1, and a SUMO-interacting motif on FOXO1. Our conclusions are supported by cold survival experiments with human cell models and zebrafish larvae. Promoting FOXO1 nuclear entry by the Exportin-1 inhibitor KPT-330 enhances cold tolerance in pre-diabetic obese mice, and greatly prolongs the shelf-life of human and mouse pancreatic tissues and islets. Transplantation of mouse islets cold-stored for 14 days reestablishes normoglycemia in diabetic mice. Our findings uncover a regulatory network and potential therapeutic targets to boost spontaneous cold adaptation.

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.

Characterizing the impact of thermoregulation in patients after cardiac arrest: a retrospective cohort study.

Core body temperature has been extensively investigated as a thereuptic target in care after cardiac arrest. Nevertheless, the integrity of thermoregulation in patients after cardiac arrest has not been well studied. We sought to evaluate whether low spontaneous body temperature after cardiac arrest is associated with increased death and a worse neurologic outcome, and whether patients with low spontaneous body temperature exhibit features suggestive of impaired thermoregulation. We conducted a single-centre retrospective cohort study. We included all adult patients who underwent temperature control with hypothermia after cardiac arrest between 1 January 2014 and 30 June 2020. The primary exposure was low spontaneous core body temperature (< 35°C) at initiation of hypothermia therapy. The primary outcome was in-hospital death and the secondary outcome was poor neurologic outcomes at discharge. Five hundred and ninety-seven adult patients, comprising both in- and out-of-hospital cardiac arrests, were included. Patients with low spontaneous body temperature also had slightly lower average temperature, and more frequent transient but controlled breakthrough fever episodes in the first 24hr. In the multivariable logistic regression analysis, low spontaneous body temperature was associated with higher odds of in-hospital death (odds ratio, 2.9; 95% confidence interval, 1.9 to 4.2; P < 0.001). In this single-centre retrospective cohort study, low spontaneous core body temperature was associated with poor outcomes in patients after cardiac arrest. Patients with low spontaneous body temperature also exhibited features suggestive of impaired thermoregulation. Further research is needed to determine whether body temperature upon presentation reflects the robustness of the patient's underlying physiology and severity of brain insult after a cardiac arrest.

A novel intracoronary hypothermia device reduces myocardial reperfusion injury in pigs.

Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury. This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed. The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH. The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Metabolite Biomarkers for Early Ischemic-Hypoxic Encephalopathy: An Experimental Study Using the NeoBase 2 MSMS Kit in a Rat Model.

Hypoxic-ischemic encephalopathy (HIE) is one of the most common causes of childhood disability. Hypothermic therapy is currently the only approved neuroprotective approach. However, early diagnosis of HIE can be challenging, especially in the first hours after birth when the decision to use hypothermic therapy is critical. Distinguishing HIE from other neonatal conditions, such as sepsis, becomes a significant problem in diagnosis. This study explored the utility of a metabolomic-based approach employing the NeoBase 2 MSMS kit to diagnose HIE using dry blood stains in a Rice-Vannucci model of HIE in rats. We evaluated the diagnostic fidelity of this approach in a range between 3 and 6 h after the onset of HIE, including in the context of systemic inflammation and concomitant hypothermic therapy. Discriminant analysis revealed several metabolite patterns associated with HIE. A logistic regression model using glycine levels achieved high diagnostic fidelity with areas under the receiver operating characteristic curve of 0.94 at 3 h and 0.96 at 6 h after the onset of HIE. In addition, orthogonal partial least squares discriminant analysis, which included five metabolites, achieved 100% sensitivity and 80% specificity within 3 h of HIE. These results highlight the significant potential of the NeoBase 2 MSMS kit for the early diagnosis of HIE and could improve patient management and outcomes in this serious illness.

Investigation of gadolinium doped manganese nano spinel ferrites via magnetic hypothermia therapy effect towards MCF-7 breast cancer

Magnetic spinel ferrite nanoparticles (MSF-NPs) are potential candidates for biomedical applications, especially in cancer diagnosis and therapy due to their excellent physiochemical and magnetic properties. In the current study, MSF-NPs were fabricated by sol-gel auto combustion method. The crystal structure and surface morphology were confirmed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The magnetic properties were studied by VSM (vibrating sample magnetometer). As increasing Gd3+ concentration, the saturation magnetization values decreased from (17.8-2.3) emu/g, while the coercivity decreased from (499-133) Oe at room temperature. Finally, the fabricated MSF-NPs were tested against anticancer activity by MTT assay. The IC50 = 21.27 μg/mL value was observed, showing the strong antiproliferative activity of these nanoparticles. These results suggested that the obtained MSF-NPs would be useful for remote-controlled hyperthermia therapy for cancer treatment and MRI application due to their excellent magnetic properties. These distinct properties make MSF-NPs most suitable for cancer treatment and bright Contrast Agents (T1-MRI).