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ObjectiveTo appraise the currency, completeness and quality of evidence from systematic reviews (SRs) of acute management of moderate to severe traumatic brain injury (TBI).MethodsWe conducted comprehensive searches to March 2016 for published, English-language SRs and RCTs of acute management of moderate to severe TBI. Systematic reviews and RCTs were grouped under 12 broad intervention categories. For each review, we mapped the included and non-included RCTs, noting the reasons why RCTs were omitted. An SR was judged as 'current' when it included the most recently published RCT we found on their topic, and 'complete' when it included every RCT we found that met its inclusion criteria, taking account of when the review was conducted. Quality was assessed using the AMSTAR checklist (trichotomised into low, moderate and high quality).FindingsWe included 85 SRs and 213 RCTs examining the effectiveness of treatments for acute management of moderate to severe TBI. The most frequently reviewed interventions were hypothermia (n = 17, 14.2%), hypertonic saline and/or mannitol (n = 9, 7.5%) and surgery (n = 8, 6.7%). Of the 80 single-intervention SRs, approximately half (n = 44, 55%) were judged as current and two-thirds (n = 52, 65.0%) as complete. When considering only the most recently published review on each intervention (n = 25), currency increased to 72.0% (n = 18). Less than half of the 85 SRs were judged as high quality (n = 38, 44.7%), and nearly 20% were low quality (n = 16, 18.8%). Only 16 (20.0%) of the single-intervention reviews (and none of the five multi-intervention reviews) were judged as current, complete and high-quality. These included reviews of red blood cell transfusion, hypothermia, management guided by intracranial pressure, pharmacological agents (various) and prehospital intubation. Over three-quarters (n = 167, 78.4%) of the 213 RCTs were included in one or more SR. Of the remainder, 17 (8.0%) RCTs post-dated or were out of scope of existing SRs, and 29 (13.6%) were on interventions that have not been assessed in SRs.ConclusionA substantial number of SRs in acute management of moderate to severe TBI lack currency, completeness and quality. We have identified both potential evidence gaps and also substantial research waste. Novel review methods, such as Living Systematic Reviews, may ameliorate these shortcomings and enhance utility and reliability of the evidence underpinning clinical care.

To explore the protective mechanism of acupuncture plus mild hypothermia for cerebral ischemia-reperfusion injury (CIRI) by observing the effects of acupuncture plus mild hypothermia on miRNA-204 and its target gene expressions in CIRI rat brain tissues. Sixty Sprague-Dawley rats were divided into a blank control group, a sham operation group, a model group, an acupuncture group, a mild hypothermia group and an acupuncture plus mild hypothermia group according to the random number table method (n=10). Except for the blank control group and the sham operation group, rats in the other 4 groups received CIRI modeling. After the model was successfully established, rats in the blank control group were bred routinely for 72 h without any interventions; rats in the sham operation group and the model group were bred routinely for 72 h, and only received binding without other interventions after surgery; rats in the acupuncture group were bred routinely for 72 h, and received acupuncture at Dazhui (GV 14), Baihui (GV 20) and Shuigou (GV 26) after binding; rats in the mild hypothermia group were bred routinely for 72 h, and received mild hypothermia intervention for 72 h after binding; rats in the acupuncture plus mild hypothermia group were bred routinely for 72 h, followed by receiving acupuncture as in the acupuncture group and mild hypothermia therapy as in the mild hypothermia group after binding. The neurological impairment score, cerebral infarction area ratio, the expressions of miRNA-204 and its target genes including Map3k8, Ntrk2 and Ppp3r1 in the ischemic hippocampus of each group were observed after 72 h of intervention. Before intervention, compared with the blank control group and the sham operation group, the neurological impairment scores and the infarction area ratios of the modelled rats were statistically significantly increased (all P

This working group of the International Society of Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) was commissioned to summarize and update current efforts in the development and characterization of animal models of hepatic encephalopathy (HE). As defined in humans, HE in animal models is based on the underlying degree and severity of liver pathology. Although hyperammonemia remains the key focus in the pathogenesis of HE, other factors associated with HE have been identified, together with recommended animal models, to help explore the pathogenesis and pathophysiological mechanisms of HE. While numerous methods to induce liver failure and disease exist, less have been characterized with neurological and neurobehavioural impairments. Moreover, there still remains a paucity of adequate animal models of Type C HE induced by alcohol, viruses and non-alcoholic fatty liver disease; the most common etiologies of chronic liver disease.

Background The aim of the study was to assess the indications, surgical strategies, and outcomes after reoperative aortic arch surgery performed generally under mild hypothermia. Methods Ninety consecutive patients (60 males, mean age, 55 ± 16 years) underwent open reoperative aortic arch surgery after previous cardiac aortic surgery. The indications included chronic-progressive arch aneurysm (55.5%), chronic aortic dissection (17.8%), contained arch rupture (16.7%), and graft infection (10%). The reoperation was performed through a repeat sternotomy (96%) or clamshell thoracotomy (4%) using antegrade cerebral perfusion under mild systemic hypothermia (28.9 ± 2.5°C) in all except three patients. Results The surgery comprised hemiarch or total arch replacement in 41 (46%) and 49 (54%) patients, respectively. The distal extension included classic or frozen elephant trunk technique, each in 12 patients, and total descending aorta replacement in 4 patients. Operative mortality was 6 (6.7%) among all patients, with age identified as the only independent predictor of operative mortality (p = 0.05). Permanent and transient neurologic deficits occurred in 1% and 9% of the patients, respectively. Estimated survival at 8 years was 59 ± 8% with advanced heart failure predictive for late mortality (p = 0.014). Freedom from second reoperation or intervention on the aorta was 78 ± 6% at 8 years, with most of these events occurring downstream in patients with chronic degenerative aneurysms. Conclusion Aortic arch reoperations performed using antegrade cerebral perfusion under mild systemic hypothermia offer favorable operative outcomes with an exceptionally low rate of neurologic morbidity without any difference between hemiarch and complex arch procedures.

Primary percutaneous coronary intervention (PPCI) is the preferred treatment for acute ST segment elevation myocardial infarction (STEMI). The goal is reperfusion within 90 minutes of first medical contact (FMC) or 120 minutes if transfer is needed. Otherwise, fibrinolytic therapy is recommended. Mild therapeutic hypothermia (MTH) (≤35°C) before coronary reperfusion decreases myocardial infarct size. If applied before reperfusion, hypothermia could potentially lengthen the FMC-reperfusion time without increasing infarct size. Thirty-six swine had their mid left anterior descending coronary artery acutely occluded. All animals had an initial 30 minutes of occlusion to simulate typical delay before seeking medical attention. Eighteen animals were studied under normothermic conditions with reperfusion after an additional 40 minutes (the porcine equivalent of a 120-minute clinical FMC to reperfusion time) and 18 were treated with hypothermia but not reperfused until another 80 minutes (clinical equivalent of 240 minutes). Primary outcome was myocardial infarct size (infarct/area at risk [AAR]) at 24 hours. The two groups differed in systemic temperature at the time of reperfusion (39.1°C ± 1.0°C vs. 35.5°C ± 0.7°C

V roce 2010 byly v casopise Minerva Anestesiologica publikovany výsledky narodniho dotaznikoveho průzkumu o použivani terapeuticke mirne hypotermie u pacientů uspěsně resuscitovaných pro nahlou zastavu oběhu na jednotkach intenzivni pece v Ceske republice. Tento clanek reflektuje výsledky prace v kontextu znalosti v době publikace a z pohledu soucasneho poznani.

The aim of the current study was to investigate dynamic changes in brain Nogo-A protein in rats, and the effects of mild hypothermia therapy on its expression after Cardio-Pulmonary Resuscitation (CPR). Western-blotting and neurological scoring of 45 rats subjected to cardiac arrest and CPR were performed to investigate the expression of Nogo-A protein in the hippocampus and cortex 6 h, 12 h, 24 h, 48 h, and 72 h after restoration of spontaneous circulation (ROSC). Nogo-A expression levels gradually increased from 6 h after CPR in the brain. In the hippocampus and cortex, Nogo-A exhibited a unimodal waveform-first it increased, but then it decreased. It peaked at 24 h in the hippocampus, and at 48 h in the cortex. The expression of Nogo-A in the mild hypothermia group was significantly lower at 12 h (p

Mild hypothermia (MH) and edaravone (EDA) exert neuroprotective effects against cerebral ischemia/reperfusion (I/R) injury through activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. However, whether MH and EDA exert synergistic effects against cerebral I/R injury remains unknown. The aim of the present study was to investigate the effects and mechanism of action of MH in combination with EDA in cerebral I/R injury. A rat cerebral I/R injury model was constructed by middle cerebral artery occlusion (MCAO) followed by reperfusion, and the mice were treated by MH, EDA or the inhibitor of the Nrf2 signaling pathway brusatol (Bru). It was observed that mice treated by MCAO had higher neurological deficit scores and oxidative stress levels, and low spatial learning and memory capacity; moreover, the CA1 region of the hippocampi of the mice exhibited reduced neuronal density and viability, and reduced mitochondrial dysfunction. However, MH in combination with EDA reversed the effects of MCAO, which were blocked by Bru injection. The levels of glutathione (GSH), GSH peroxidase, catalase and superoxide dismutase in rat ischemic hemisphere tissues were reduced by Bru. Western blotting demonstrated that the combined treatment with MH and EDA promoted the nuclear localization of Nrf2, and increased the levels of NAD(P)H quinone oxidoreductase and heme oxygenase (HO)-1. In conclusion, MH combined with EDA exerted synergistic neuroprotective effects against cerebral I/R injury involving changes in the Nrf2/HO-1 pathway.

Background and Aim Stroke is a sudden neurological disorder caused by disturbances in the brain blood flow and loss of normal brain function. Stroke is also the second leading cause of death worldwide. In the last two decades, among the various treatment options for stroke, hypothermia has shown the promise of improving the final outcome. This study aimed to investigate the effect of noninvasive hypothermia on the final outcome of patients with an acute stroke in Iran.Methods In a randomized clinical trial, 60 Iranian patients diagnosed with acute stroke were enrolled in 2018. Patients were selected by convenience sampling method and then randomized in two groups as experimental (n = 30) and control (n = 30). Mild hypothermia was applied using a cooling device for 72 hours on the patients’ heads and intervention results were compared with the control group. Data were collected by using Acute Physiology and Chronic Health Evaluation III (APACHE III), Full Outline of Un-Responsiveness (FOUR), and National Institutes of Health Stroke Scale (NIHSS), and later analyzed by Statistical Package for the Social Sciences (SPSS) software version 22.Results No significant difference was found in the mean scores of all three scales before and after the intervention in control group (p > 0.05) but statistically significant difference was found in the mean scores of all three scales for the intervention group (p < 0.05). The intervention group had an increased mean score in FOUR, while APACHE and NIHSS values dropped. Researchers found statistically significant difference between the mean scores after the intervention in the experimental group compared with the control group in all three scales (p < 0.05).Conclusion The findings of this study indicate that hypothermia has a significant statistical and clinical effect on the acute stroke outcome and it can be argued that hypothermia therapy can increase the level of consciousness and reduce the risk of death in stroke patients.

Mild hypothermia (MH) and retroperfusion are 2 techniques proposed to reduce infarct size due to myocardial infarction. The authors evaluated the effects of focal MH combined with selective coronary venous autoretroperfusion (SARP) as an acute cardioprotective modality before percutaneous coronary intervention (PCI) in a swine model of left ventricular myocardial infarction. Significant reduction in infarct size with preservation of cardiac function and cardiomyocyte viability were achieved. The authors propose that SARP alone or in combination with MH may provide a clinically relevant percutaneous short-term option of cardiac support to high-risk patients undergoing PCI.

Diaphragm dysfunction often occurs in patients with prolonged mechanical ventilation (MV) after resuscitation. Mild hypothermia (MHT) is a classical treatment to improve the outcomes of cardiac arrest (CA); however, the effect of MHT on diaphragm function remains unclear. In the present study, we aim to investigate the effect of MHT on diaphragmatic microcirculation and function using a murine cardiopulmonary resuscitation model.Thirty-two rats were randomly assigned into a resuscitation normothermia group (RNT), an intraresuscitation hypothermia group (IRH), a postresuscitation hypothermia group (PRH), or a sham control group. CA was induced by airway occlusion, and resuscitation was implemented by precordial compression and MV. The diaphragmatic microvascular blood flow velocity, diaphragmatic microcirculation flow index (MFI), and perfused vascular density (PVD) were measured. The diaphragm was then removed for in vitro contractile property examination and cross-sectional area measurement. The lipid peroxidation and superoxide dismutase (SOD) levels in the diaphragm were also assayed.Either early or delayed MHT intervention did not improve the diaphragmatic microvascular blood flow velocity, MFI, and PVD, which were significantly decreased during prolonged MV after resuscitation. Compared with the RNT group, treatment with MHT increased the diaphragm contractility, fiber dimensions, and SOD levels and decreased diaphragm lipid peroxidation. A more significant change in these indices was observed in the IRH group compared with that in the PRH group.MHT preserves the diaphragm contractility and fiber dimensions and decreases oxidative stress but does not improve the microcirculatory blood supply during prolonged MV after resuscitation. Early MHT intervention is more efficient in preventing diaphragm dysfunction than delayed intervention after CA.

AIM: To perform a systematic review and meta-analysis on targeted temperature management in adult cardiac arrest patients.METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched on June 17, 2021 for clinical trials. The population included adult patients with cardiac arrest. The review included all aspects of targeted temperature management including timing, temperature, duration, method of induction and maintenance, and rewarming. Two investigators reviewed trials for relevance, extracted data, and assessed risk of bias. Data were pooled using random-effects models. Certainty of evidence was evaluated using GRADE.RESULTS: The systematic search identified 32 trials. Risk of bias was assessed as intermediate for most of the outcomes. For targeted temperature management with a target of 32-34°C vs. normothermia (which often required active cooling), 9 trials were identified, with six trials included in meta-analyses. Targeted temperature management with a target of 32-34°C did not result in an improvement in survival (risk ratio: 1.08 [95%CI: 0.89, 1.30]) or favorable neurologic outcome (risk ratio: 1.21 [95%CI: 0.91, 1.61]) at 90 to 180 days after the cardiac arrest (low certainty of evidence). Three trials assessed different hypothermic temperature targets and found no difference in outcomes (low certainty of evidence). Ten trials were identified comparing prehospital cooling vs. no prehospital cooling with no improvement in survival (risk ratio: 1.01 [95%CI: 0.92, 1.11]) or favorable neurologic outcome (risk ratio: 1.00 [95%CI: 0.90, 1.11]) at hospital discharge (moderate certainty of evidence).CONCLUSIONS: Among adult patients with cardiac arrest, the use of targeted temperature management at 32-34°C, when compared to normothermia, did not result in improved outcomes in this meta-analysis. There was no effect of initiating targeted temperature management prior to hospital arrival. These findings warrant an update of international cardiac arrest guidelines.

Cold-water immersion (CWI) is the gold standard therapy for exertional heat illness (EHS), and it is critical to perform CWI expeditiously when the core temperature exceeds 40°C; however, the treatment comes with risks, most notably hypothermia. Following a major marathon, three runners presented to our emergency department (ED) with symptomatic mild hypothermia requiring re-warming. Prior to developing hypothermia, all three were treated at the racecourse with CWI for EHS. During CWI, there are monitoring methods to determine appropriate cessation: continuous temperature measurement, regular temperature checks, using an equation to predict immersion time, and symptom observation. There is no consensus on the best system, but a monitoring method should be used to prevent over-cooling. This case series illustrates the importance of proper CWI execution in order to avoid harm.

We examined the interactive effects of mild hypothermia and hypoxia on finger vasoreactivity to local cold stress. Eight male lowlanders performed, in a counterbalanced order, a normoxic and a hypoxic (partial pressure of oxygen: similar to 12 kPa) hand cold provocation (consisting of a 30-min immersion in 8 degrees C water), while immersed to the chest either in 21 degrees C [cold trials; 0.5 degrees C fall in rectal temperature (T-rec) from individual preimmersion values], or in 35.5 degrees C water, or while exposed to 27 degrees C air. The duration of the trials was kept constant in each breathing condition. Physiological (T-rec, skin temperature, cutaneous vascular conductance, oxygen uptake) and perceptual (thermal sensation and comfort, local pain, affective valence) reactions were monitored continually. Hypoxia accelerated the drop in T-rec by similar to 14 min (P = 0.06, d = 0.67). In the air-exposure trials, hypoxia did not alter finger perfusion during the local cooling. whereas it impaired the finger rewarming response following the cooling (P < 0.01). During the 35.5 degrees C immersion, the finger vasomotor tone was enhanced, especially in hypoxia (P = 0.01). Mild hypothermia aggravated finger vasoconstriction instigated by local cooling (P < 0.01), but the response did not differ between the two breathing conditions (P > 0.05). Hypoxia tended to attenuate the sensation of coldness (P = 0.10, r = 0.40) and thermal discomfort (P = 0.09, r = 0.46) in the immersed hand. Both in normoxia and hypoxia, the whole body thermal state dictates the cutaneous vasomotor reactivity to localized cold stimulus. QC 20191007

Targeted temperature management (TTM) is a well-accepted neuro-protective intervention in the management of comatose survivors of cardiac arrest (CA). However, the impact of TTM on cardiac performance has not been adequately evaluated.We reviewed data on consecutive CA survivors undergoing TTM at a quaternary cardiac intensive care unit between January 2015 and June 2017. Enrollment was restricted to cases with invasive hemodynamics (iHDs) at TTM initiation, every 8 h at target temperature (32-34 °C) and at completion of rewarming (36 °C), unless precluded by mortality. Cardiac index and cardiac index-derived variables were adjusted for a decreased oxygen consumption during hypothermia. We assessed the serial impact of cooling on iHDs and cardiac performance utilizing longitudinal data analysis accounting for the effects of time as surrogate for the expected change from the post arrest syndrome and instituted treatments. A Frank-Starling construct was used to evaluate changes in cardiac contractility.We evaluated the effects of cooling on iHDs and cardiac performance in 46 CA survivors. Heart rate decreased with cooling (p 0.001), to return to baseline after rewarming (p = 0.6). Mean arterial pressure and pulmonary wedge pressure decreased by cooling (p 0.001 for both), with sustained improvement after rewarming (p 0.001 for both). Systemic vascular resistance was unaffected by hypothermia (p 0.05). Left stroke work index increased with cooling (p 0.001), with return to baseline after rewarming (p = 0.6). Cooling was associated with a left-upward shift in the Frank-Starling curve indicative of increased contractility.Mild hypothermia in CA survivors appears associated to positive changes in iHDs and cardiac performance, including a potential increase in cardiac contractility. Larger studies are needed to conclusively confirm these findings.

Cold-shock proteins are thought to participate in the cold-tolerant nature of hibernating animals. We previously demonstrated that an alternative splicing may allow rapid induction of functional cold-inducible RNA-binding protein (CIRBP) in the hamster heart. The purpose of the present study was to determine the major cause of the alternative splicing in Syrian hamsters. RT-PCR analysis revealed that CIRBP mRNA is constitutively expressed in the heart, brain, lung, liver, and kidney of nonhibernating euthermic hamsters with several alternative splicing variants. In contrast, the short variant containing an open-reading frame for functional CIRBP was dominantly found in the hibernating animals. Keeping the animals in a cold and dark environment did not cause a shift in the alternative splicing. Induction of hypothermia by central administration of an adenosine A1-receptor agonist reproduced the shift in the splicing pattern. However, the agonist failed to shift the pattern when body temperature was kept at 37°C, suggesting that central adenosine A1receptors are not directly linked to the shift of the alternative splicing. Rapid reduction of body temperature to 10°C by isoflurane anesthesia combined with cooling did not alter the splicing pattern, but maintenance of mild hypothermia (~28°C) for 2 h elicited the shift in the pattern. The results suggest that animals need to be maintained at mild hypothermia for an adequate duration to induce the shift in the alternative splicing. This is applicable to natural hibernation because hamsters entering hibernation show a gradual decrease in body temperature, being maintained at mild hypothermia for several hours.

Background: Minimal invasive extracorporeal circulation (MiECC) circuits are an established alternative to conventional extracorporeal circulation (CECC). Based on the positive effects and improved perioperative outcomes of MiECC in adult cardiac surgery, this perfusion concept appears particularly attractive to pediatric cardiac surgery. So far, there are no reports on the clinical application of a MiECC system for corrective surgery in neonates and children. We report our initial experiences by using a MiECC system in pediatric cardiac surgery. Methods: A total of 38 pediatric patients underwent surgical interventions for a variety of congenital heart disease from March 2017 until August 2018 with a MiECC. Following the classification of MiECC circuits by the Minimal invasive Extra-Corporeal Technologies International Society (MiECTIS), type I and type III perfusion circuits were assembled depending on the planned intervention: type I for closed heart interventions and type III for open heart procedures. Primary outcome was conversion to CECC, secondary endpoints included major adverse cardiac or cerebrovascular events (MACCE). Results: MiECC perfusion was successfully performed in all patients (100%). Median patient age was 9.5 months (range, 0.2–176 months) with a median weight of 8.1 kg (range, 2.3–49 kg). For both MiECC types no system related technical complications were encountered. Beating heart procedures were performed in 23 cases (60%) at normothermia, while in 15 (40%) interventions cardioplegic cardiac arrest was induced at mild hypothermia. All patients had an uneventful perioperative course with no in-hospital mortality. MACCE did not occur during the hospitalization period. Conclusions: MiECC can be performed by using standard techniques for closed and open cardiac procedures for the correction of a variety of malformations in neonates and children with good results and uneventful postoperative course.

OBJECTIVES The presence of collateral network circulation to the spinal cord, which is reflected in the repair of a descending thoracic aortic aneurysm (dAo) and a thoraco-abdominal aortic aneurysm (TAAo), has been demonstrated in clinical and animal experimental data. The latissimus dorsi muscle (LDM) including the thoracodorsal artery might be one of the major sources of this collateral network. The objective of this study was to evaluate the impact on spinal cord safety of a left anteroaxillary thoracotomy with minimal muscle division including preservation of the LDM in surgery for dAo and TAAo. METHODS Sixty-nine patients [64 (23–85) years old; 56 men] who underwent surgical repair for dAo and TAAo were divided into 2 groups: 29 [65 (23–84) years old] with an anteroaxillary thoracotomy with LDM preservation (PL group) and 40 [61 (28–85) years old] with a lateral thoracotomy without LDM preservation (NL group). RESULTS Aortic repairs were performed at the dAo in 30 patients including 14 in the PL group vs 16 in the NL group and at the TAAo in 39 patients including 15 in the PL group vs 24 in the NL group. There were 2 (2.9%) 30-day deaths; 2 (7.9%) in the PL group vs none in the NL group (P = 0.173). No strokes occurred. In patients with a femoro-femoral partial cardiopulmonary bypass with mild hypothermia, the incidence of loss of signal of motor-evoked potentials (>50%) was significantly lower in the PL group; 5.6% vs 31.8% (P = 0.039). The frequency of signal reduction of the remaining motor-evoked potential after surgery was also significantly lower in the PL group: 3.7% vs 25% (P = 0.040). Subsequently, the rate of spinal cord complications were lower in the PL group: 3.4% vs 12.5% (P = 0.188). CONCLUSIONS The left anteroaxillary thoracotomy with minimal incision of the muscles including the LDM might have potential advantages for spinal cord protection via preserved intramuscular collateral circulations to the spinal cord in dAo/TAAo open repairs.

Background: Experimental trials suggest improved outcome by mild therapeutic hypothermia for cardiogenic shock after acute myocardial infarction. The objective of this study was to investigate the hemodynamic effects of mild therapeutic hypothermia in patients with cardiogenic shock complicating acute myocardial infarction. Methods: Patients (n=40) with cardiogenic shock undergoing primary percutaneous coronary intervention without classic indications for mild therapeutic hypothermia underwent randomization in a 1:1 fashion to mild therapeutic hypothermia for 24 hours or control. The primary end point was cardiac power index at 24 hours; secondary end points included other hemodynamic parameters and serial measurements of arterial lactate. Results: No relevant differences were observed for the primary end point of cardiac power index at 24 hours (mild therapeutic hypothermia versus control: 0.41 [interquartile range, 0.31–0.52] versus 0.36 [interquartile range, 0.31–0.48] W/m 2 ; P =0.50; median difference, −0.025 W/m 2 ; 95% CI, −0.12 to 0.06). Similarly, all other hemodynamic measurements were not statistically different. Arterial lactate levels at 6, 8, and 10 hours were significantly higher in patients in the mild therapeutic hypothermia group with a slower decline ( P for interaction=0.03). There were no differences in 30-day mortality (60% versus 50%; hazard ratio, 1.27; 95% CI, 0.55–2.94; P =0.55). Conclusions: In this randomized trial, mild therapeutic hypothermia failed to show a substantial beneficial effect on cardiac power index at 24 hours in patients with cardiogenic shock after acute myocardial infarction. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01890317.

This study examined cutaneous vasoconstriction to whole-body hypothermia, specifically contributions of neural and endothelial vasomotor responses in glabrous and non-glabrous skin. Eleven participants were semi-recumbent at an ambient temperature of 22 °C for 30 min, after which ambient temperature was decreased to 0 °C until rectal temperature (Tre) had decreased by 0.5 °C. Laser-Doppler fluxmetry was measured at the forehead and thigh for measures of glabrous and non-glabrous skin, respectively; wavelet analysis was performed on the laser-Doppler signal to determine endothelial and neural activities. Hypothermia took on average 97 ± 7 min and caused marked decreases at glabrous (42 ± 5%baseline, p

Introduction. The aim of the experiment was to find the relationship between the extent of myocardial infarction and the internal body temperature of the rats. Our second goal was to investigate if mild hypothermia applied during myocardial ischemia and reperfusion brings cardioprotective effects. Materials and methods. The study was performed in vivo on rat hearts. Myocardial infarction was induced by 30 minutes of the left anterior descending artery occlusion followed by 60 min reperfusion. Thirteen rats were assigned to a group depending on the internal body temperature (t) ≤ 35.5°C (n = 5), 35.6 ≥ t ≥ 37.5°C (n = 4) and t ≥ 37.6°C (n = 4). The desired temperature was achieved during pre-ischemic procedures. The presence of the infarction scar and its size were assessed in planimetry. Infraction size was calculated as the infarct area relative to the area at risk (IA/RA). Results. The incidence of infarction scar in the groups of rats with body temperature ≥ 35.6°C was significantly higher (p < 0.01) compared to the group with the temperature ≤ 35.5°C. There was statistically significant positive correlation (r = 0.787, p < 0.01) between IA/RA and the internal body temperature of the rats. Conclusions. Any reduction in the body temperature during myocardial ischemia and reperfusion seems to be beneficial for the rat’s myocardium. Moreover, hypothermia ≤ 35.5oC applied during ischemia and reperfusion fully prevents from myocardial infarction. We believe that there is a great need to intensify research on therapeutic hypothermia in humans, so that this method of treatment could be finally used in the course of myocardial infarction.

Ambient temperature has a profound influence on cellular electrophysiology through direct control over the gating mechanisms of different ion channels. In the heart, low temperature is known to favor prolongation of the action potential. However, not much is known about the influence of temperature on other important characterization parameters such as the resting membrane potential (RMP), excitability, morphology and characteristics of the action potential (AP), restitution properties, conduction velocity (CV) of signal propagation, etc. Here we present the first, detailed, systematic in silico study of the electrophysiological characterization of cardiomyocytes from different regions of the normal human atria, based on the effects of ambient temperature (5−50°C). We observe that RMP decreases with increasing temperature. At ~ 48°C, the cells lose their excitability. Our studies show that different parts of the atria react differently to the same changes in temperature. In tissue simulations a drop in temperature correlated positively with a decrease in CV, but the decrease was region-dependent, as expected. In this article we show how this heterogeneous response can provide an explanation for the development of a proarrhythmic substrate during mild hypothermia. We use the above concept to propose a treatment strategy for atrial fibrillation that involves severe hypothermia in specific regions of the heart for a duration of only ~ 200 ms. © Copyright © 2021 Majumder, Mohamed Nazer, Panfilov, Bodenschatz and Wang. This work was supported by the Max Planck Society and the German Center for Cardiovascular Research. Research at Sechenov University was financed by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers Digital biodesign and personalized healthcare No. 075-15-2020-926.

With the development of Cardiopulmonary Resuscitation (CPR) technology and the popularity of public CPR...

Objective To investigate the efficacy of different treatment times of mild cerebral hypothermia for treating moderate/severe hypoxic–ischemic encephalopathy (HIE) in neonatal patients and its effects on oxidative factors. Methods This prospective, randomized, controlled study included 92 neonatal patients with moderate/severe HIE and 30 controls. The patients with HIE received routine treatment, 48 hours of hypothermia, or 72 hours of hypothermia. Results Superoxide dismutase (SOD) values were significantly lower and malondialdehyde (MDA) and neuron-specific enolase (NSE) values were higher in patients with HIE than in controls before the study. After 24, 48, and 72 hours of treatment, SOD values in all patients with HIE gradually increased and MDA and NSE values gradually decreased. At 3, 7, and 10 days, the Neonatal Behavioral Neurological Assessment scores were highest in the mild hypothermia for 72 hours group than in the other groups. The Mental and Psychomotor Development Indices scores of the Bayley Scales were significantly higher in the mild hypothermia for 72 hours group than in the other groups. Conclusion Hypothermia treatment of 72 hours is better than 48 hours for improving oxidative conditions, reducing NSE values, and improving neurological behavior and development for neonates with moderate/severe HIE.

Objective Temperature during cardiopulmonary bypass (CPB) for cardiac surgery has been controversial. The aim of the current study is to compare the outcomes for patients with mild hypothermia versus normothermic CPB temperatures. Methods All patients who underwent cardiac surgery with CPB and temperatures ≥32°C from 2011 to 2018 were included, which consisted of mild hypothermia (32°C-35°C) and normothermia (>35°C) cohorts. Propensity matching (1:1) was performed for risk adjustment. Primary outcomes included operative and long-term survival. Secondary outcomes included postoperative complications. Results A total of 6525 patients comprised 2 cohorts: mild hypothermia (32°C-35°C; n = 3148) versus normothermia (>35°C; n = 3377). Following adjustment for surgeon preference, there were 1601 propensity-matched patients who had similar baseline characteristics (standard mean difference, ≤0.10), including CPB time, crossclamp time, and intra-aortic balloon pump placement. Kaplan-Meier analysis showed no difference in long-term survival (82.6% vs 81.6%; P = .81). Over a median follow-up of 4.4 years, there were no differences in overall mortality (18.1% vs 18.1%; P = 1.1) or readmission (50.3% vs 48.3%; P = .2). Acute renal failure (3.7% vs 2.4%; P = .03) and intensive care unit hours (46.5 vs 45.1; P = .04) were significantly higher with hypothermia. There was no difference between cohorts for postoperative stroke (2.0% vs 2.0%; P = 1.0), reoperation (5.9% vs 6.0%; P = .9), or operative intra-aortic balloon pump placement (1.7% vs 1.8%; P = .9). Conclusions Patients with mild hypothermia during CPB had increased postoperative renal failure and length of intensive care unit stay. Although there was no difference in long-term survival, mild hypothermia does not appear to offer patients appreciable benefits, compared with normothermia.

Acute kidney injury (AKI), or worsening kidney function, is a common complication after liver transplantation (20-90% in published studies). Patients who experience AKI after liver transplantation have higher mortality, increased graft loss, longer hospital and intensive care unit stays, and more progression to chronic kidney disease compared with those who do not. In this study, half of the participants will have their body temperature cooled to slightly lower than normal (mild hypothermia) for a portion of the liver transplant operation, while the other half will have their body temperature maintained at normal. The study will evaluate if mild hypothermia protects from AKI during liver transplantation. This study is a single-blinded, randomized controlled trial of mild hypothermia during liver transplantation to provide protection from AKI. Participants will be randomized to normothermia (36.5-37.5 °C) versus mild hypothermia (34-35 °C) during a portion of the liver transplant operation. The protocol is based on preliminary data from rodent models showing that hypothermia protects the kidneys from ischemia-reperfusion injury, as well as studies in deceased organ donors showing that cooling improves post-transplant organ function. Temperature will be maintained with standard techniques plus a minimally-invasive esophageal cooling device that is approved by the U.S. Food and Drug Administration. The investigators hypothesize that mild hypothermia will reduce the incidence and severity of AKI after LTx. Standard surrogates (e.g., change in serum creatinine, need for initiation of dialysis) and biomarkers will be used to assess the severity of kidney injury.

To explore the combined influences of temperature-sensitive bone mesenchymal stem cells (tsBMSCs) and mild hypothermia (MH) on neurological function and glucose metabolism in rats with severe traumatic brain injury (TBI).SD rats were randomly divided into sham, TBI, TBI + MH, TBI + BMSCs and TBI + MH +tsBMSCs groups. Then, the brain water content, serum-specific proteins (S100β, NSE, LDH, and CK), and blood glucose at different time points were measured. Furthermore, GLUT-3 expression was detected by Western blotting, and apoptotic rate was determined by TUNEL staining.After TBI rat establishment, the brain injury resulted in significant increases in mNSS scores and brain water content, and upregulations in serum levels of S100β, NSE, LDH and CK, and blood glucose, with the elevated cell apoptotic rate in the injured cortex. However, these changes were reversed by MH alone, BMSCs alone, or combination treatment of MH and tsBMSCs in varying degrees, and the combination treatment was superior to the treatment with BMSCs or MH alone.Combination therapy of tsBMSCs and MH can reduce the neuronal apoptosis in severe TBI rats, with the suppression of serum biomarkers and hyperglycemia, contributing to the recovery of neurological functions.tsBMSCs: temperature-sensitive bone mesenchymal stem cells; MH: mild hypothermia; TBI: traumatic brain injury; mNSS: modified Neurological Severity Score.

Objective This study aimed to compare the changes in sublingual and conjunctival microcirculation occurring with cerebral cortex microcirculation changes during mild hypothermia in a rat model of cardiac arrest. Methods Twenty-four rats were randomized into mild hypothermia (M) or normothermia (C) groups. Ventricular fibrillation was electrically induced and left untreated for 8 minutes, followed by 8 minutes of cardiopulmonary resuscitation. The core temperature in group M reduced to 33 ± 0.5°C at 13 minutes after restoration of spontaneous circulation and was maintained for 8 hours. In group C, the core temperature was maintained at 37 ± 0.2°C. The hemodynamics and microcirculation in the sublingual region, bulbar conjunctiva, and cerebral cortex were measured at baseline and 1, 2, 3, 4, 6, and 8 hours after restoration of spontaneous circulation. Results The M group showed significantly worse sublingual microcirculation at 6 hours post-resuscitation. However, microcirculation in the conjunctiva and cerebral cortex at 3 hours post-resuscitation were better in the M group. In the M group, microcirculation in the cerebral cortex was significantly correlated with that in the conjunctiva but not the sublingual microcirculation. Conclusions Changes in conjunctival microcirculation are closely related to cerebral cortex microcirculation during mild hypothermia, indicating that cerebral cortex microcirculation could be monitored by measuring conjunctival microcirculation.

Introduction: Less than 30% of Middle Cerebral Artery (MCA) aneurysms are amenable for endovascular coiling. Microvascular surgery still carries a large number of complications, since many perforators arteries arise near to the neck of the aneurysm and, in many cases, one or more branches of bifurcation or trifurcation of the MCA originate in the aneurysm wall. Temporary clipping of the proximal MCA avoids the aneurysmal rupture, facilitates the aneurysm dissection and clip placement but long term temporary clipping carries a great risk of ischemic complications. Objective: We developed a protocol of brain protection based on the neuroprotective properties of mild hypothermia which would intend to permit a more extended time of temporary clipping. Methods: Sixty-eight cases of MCA incidental aneurysms or after the 12nd day of hemorrhage were operated on. Brain temperature was dropped at levels that varied from 29.5ºC at 15mm parenchymal depth to 32.5ºC at ventricular level. There was no change in the patient’s body temperature. Temporary MCA clipping varied from 8 to 28 minutes. Results: There was no intraoperative aneurysm rupture. All 68 patients were alive and neurologically unchanged at the 90th and 180th follow-up days. Conclusion: Loco-regional mild hypothermia may be effective in protecting cerebral parenchyma in cases of temporary clipping over 8 minutes up to 28 minutes in MCA aneurysms surgery.

The aim of this paper is to present a novel device for heating the infusion fluids during vitrectomy surgery, to be used to avoid deep hypothermal conditions inside human eyes. The key aspect of the proposed device concerns its ability to control the temperature of infusion fluids and keep it within the mild hypothermia range, in order to reduce the post-operative complications due to low temperature. The operation of the heater has been analysed by means of a transient numerical model developed by the authors, taking into account the presence of the pipes inside which the fluids flow. Two main case studies have been considered in the present work, regarding the possible ways to operate the device that are based on preheating and no-preheating the pipes before the surgery. The numerical analysis carried out in the present study shows that the proposed device may be effectively used to obtain a favourable increase in the temperature of the infusion fluids and to avoid deep hypothermal conditions.

Hypothermia is a neuroprotective mechanism that has been validated for use in alleviating neonatal hypoxic-ischemic (HI) brain injury. Nevertheless, it is unclear whether poly (ADP-ribose) (PAR) signaling is involved in hypothermia-induced neuroprotection. In this study, we investigated whether mild hypothermia rescues oxygen glucose deprivation (OGD)-induced cell death by modifying PAR-relative protein expression, such as AIF, PARP-1, and PAR polymer, in primary-cultured hippocampal neurons.We analyzed neuronal morphology and related protein expression of PAR signaling after OGD followed by mild hypothermia in primary-cultured newborn hippocampal neurons.Hypothermic treatment resulted in improved neuronal viability and alleviated DNA damage. Results from the protein assay showed that hypothermia attenuated nuclear translocation of apoptosis-inducing factor (AIF), inhibited overactivation of poly(ADP-ribose) polymerase-1 (PARP-1), and decreased production of PAR polymer induced by PARP-1 activation after OGD.These results showed that mild hypothermia partially protects immature hippocampal neurons against OGD injury in part by interfering with the PAR signaling pathway.

Mild hypothermia (MH) renders the hearts resistant to ischemia/reperfusion (IR) injury in animal experiments. Unexpectedly, this effect was not observed in recent clinical trials. The aged hearts in mice have been demonstrated to be more susceptible to IR injury. This study aimed to examine whether the cardioprotection of MH was abolished in aged mice. Young (Y, 3 months old) and aged (A, 20 months old) male C57BL/6 mice were randomized into six groups. Sham (Y-SHAM and A-SHAM) and control (Y-CON+IR and A-CON+IR) animals maintained core body temperature at 37°C ± 0.5°C; MH groups (Y-MH+IR and A-MH+IR) received surface cooling and kept core body temperature at 32-35°C before ischemia until reperfusion. The IR mice underwent 40 minutes of ischemia followed by 24 hours of reperfusion. Finally, the cardiac function and infarct size (IS) were evaluated. The A-CON+IR group exhibited more severe cardiac dysfunction compared with the Y-CON+IR group showing as decreased ejection fraction (EF) (34.8% ± 8.5% vs. 44.2% ± 5.9%) and fraction shortening (FS) (15.2% ± 4.1% vs. 21.8% ± 3.7%). MH restored EF to 55.3% ± 6.1% and FS to 28.5% ± 3.6% in the Y-MH+IR group but not in the A-MH+IR group. Similarly, IS was significantly increased in the A-CON+IR group compared with the Y-CON+IR group (54.5% ± 10.6% vs. 42.0% ± 6.4%). MH lessened the IS to 21.3% ± 7.6% in the Y-MH+IR group but not in the A-MH+IR group. Thus, the cardioprotection rendered by MH is abolished in aged mice.

A major challenge in downstream purification of monoclonal antibodies (mAb) is the removal of host cell proteins (HCPs). Previous studies have shown that cell culture decisions significantly impact the HCP content at harvest. However, it is currently unclear how process conditions affect physiological changes in the host cell population, and how these changes, in turn, cascade down to change the HCP profile. We examined how temperature downshift (TDS) to mild hypothermia affects key upstream performance indicators, i.e. antibody titre, HCP concentration and HCP species, across the cell culture decline phase and at harvest through the lens of changes in cellular behaviour. Mild hypothermic conditions introduced on day 5 of fed-batch Chinese hamster ovary (CHO) cell bioreactors resulted in a lower cell proliferation rate but larger percentages of healthier cells across the cell culture decline phase compared to bioreactors maintained at standard physiological temperature. Moreover, the onset of apoptosis was less evident in mild hypothermic cultures. Consequently, mild hypothermic cultures took an extra five days to reach an integral viable cell concentration (IVCC) and antibody yield similar to that of the control at standard physiological temperature. When cell viability dropped below 80%, mild hypothermic cell cultures had a reduced variety of HCP species by 36%, including approximately 44% and 27% lower proteases and chaperones, respectively, despite having similar HCP concentration. This study suggests that TDS may be a good strategy to provide cleaner downstream feedstocks by reducing the variety of HCPs and to maintain product integrity by reducing the number of proteases and chaperones.

Some studies conclude that mild hypothermia causes platelet dysfunction leading to an increased bleeding risk, whereas others state that platelet aggregation is enhanced during mild hypothermia. Therefore, the aim of this study was to clarify whether standard or prolonged duration of targeted temperature management affected platelet aggregation. We randomised 82 comatose patients resuscitated after out-of-hospital cardiac arrest to either 24 hours (standard group) or 48 hours (prolonged group) of targeted temperature management at 33±1°C. Blood samples were collected 22 hours, 46 hours and 70 hours after reaching target temperature. Platelet aggregation was assessed by impedance aggregometry employing a Multiplate®Analyser, using the COLtest®, TRAPtest®, ADPtest® and ASPItest® as agonists, and with the results reported as area under the curve (AUC, AU*min). The platelet aggregation was below the normal range in all blood samples. No differences were observed between the standard group and the prolonged group in either of the blood samples (all p ≥ 0.11), except for a 24% decreased aggregation (95% confidence interval (CI) (10%;37%), p = 0.002) when using the COLtest® in the 46-hour sample. Comparing the 22-hour sample with the 46-hour sample in the prolonged group separately, we found no differences when employing the COLtest®, the ASPItest® or the ADPtest® in patients without the use of adenosine diphosphate receptor inhibitors (all p values ≥0.21), but aggregation induced by the TRAPtest® decreased by 14% (95% CI -8%;-20%), p < 0.001). We concluded that the platelet aggregation post cardiac arrest was below the normal range independent of the core temperature. Moreover, no substantial difference was found in platelet aggregation between standard and prolonged targeted temperature management. Some studies conclude that mild hypothermia causes platelet dysfunction leading to an increased bleeding risk, whereas others state that platelet aggregation is enhanced during mild hypothermia. Therefore, the aim of this study was to clarify whether standard or prolonged duration of targeted temperature management affected platelet aggregation. We randomised 82 comatose patients resuscitated after out-of-hospital cardiac arrest to either 24 hours (standard group) or 48 hours (prolonged group) of targeted temperature management at 33±1°C. Blood samples were collected 22 hours, 46 hours and 70 hours after reaching target temperature. Platelet aggregation was assessed by impedance aggregometry employing a Multiplate®Analyser, using the COLtest®, TRAPtest®, ADPtest® and ASPItest® as agonists, and with the results reported as area under the curve (AUC, AU*min). The platelet aggregation was below the normal range in all blood samples. No differences were observed between the standard group and the prolonged group in either of the blood samples (all p ≥ 0.11), except for a 24% decreased aggregation (95% confidence interval (CI) (10%;37%), p = 0.002) when using the COLtest® in the 46-hour sample. Comparing the 22-hour sample with the 46-hour sample in the prolonged group separately, we found no differences when employing the COLtest®, the ASPItest® or the ADPtest® in patients without the use of adenosine diphosphate receptor inhibitors (all p values ≥0.21), but aggregation induced by the TRAPtest® decreased by 14% (95% CI -8%;-20%), p < 0.001). We concluded that the platelet aggregation post cardiac arrest was below the normal range independent of the core temperature. Moreover, no substantial difference was found in platelet aggregation between standard and prolonged targeted temperature management.

Therapeutic hypothermia has been shown to reduce brain damage due to postcardiac arrest syndrome. Actually, there is no agreement on which is the best device to perform therapeutic hypothermia. The 'ideal' device should not only 'cool' patient until 33-34°C as fast as possible, but also maintain the target temperature and reverse the therapeutic hypothermia. For out-of-hospital cardiac arrest, there are devices that allow starting of therapeutic hypothermia on the field (prehospital hypothermia). On hospital arrival, these prehospital devices can be quickly and easily replaced with other devices more suitable for the management of therapeutic hypothermia in ICUs (in-hospital hypothermia). Some studies have compared surface and endovascular devices and found no substantial differences in neurologic outcome or survival at hospital discharge. On a clinical ground, the knowledge of the technical aspects of therapeutic hypothermia (such as characteristics of devices) is mandatory for clinicians who have to perform therapeutic hypothermia in cardiac arrest patients because the timing of therapeutic hypothermia, the choice of the device for the single patients, and avoidance of temperature fluctuation have shown to affect outcome in these patients (also in terms of reducing the incidence of complications).

Ultrafast body cooling of mammals can be achieved by ventilating the lung with a breathable liquid during total liquid ventilation. The instilled liquid into the lung allows to cool the arterial blood temperature, and consequently the organs. While total liquid ventilation can rapidly cool animals, the speed of cooling in humans remains unknown. The problem is to predict the efficiency and safety of the method for humans. The method is based on a previously published mathematical thermal model of mammals in total liquid ventilation. The thermal model is projected to humans. A direct optimal control under constraints is computed to predict the hypothermia induction speed and the sensitivity to parametric uncertainties. The simulated results in human adults illustrate that a worst case optimal control can be used to compute a robust solution in regards to uncertainties of cardiac output and thermal dead volume. In certain patients, brain temperature would reach mild hypothermia in maximum 10 min, with the majority of patients reaching it within 6 min. Hence, the direct optimal control is a potential candidate for the ultrafast therapeutic hypothermia induction for cardio- and neuroprotection of post-cardiac arrest patients.

To investigate the effect of acupuncture plus mild hypothermia on neurological function impairment score, cerebral infarct size and apoptosis-related factors in cerebral ischemia reperfusion injury (CIRI) rats. Sixty healthy male Sprague-Dawley (SD) rats were routinely reared for 1 week. Ten rats were randomly selected as the sham operation group and 10 rats as the blank control group, while the remaining 40 rats were subjected to preparing the middle cerebral artery occlusion (MCAO) model by modified filament occlusion method. The 40 MCAO rats were further randomly divided into a model group, an acupuncture group, a mild hypothermia group and an acupuncture plus mild hypothermia group, with 10 rats in each group. Rats in the sham operation group, the blank control group and the model group did not accept treatment except binding; rats in the acupuncture group received acupuncture treatment; rats in the mild hypothermia group received mild hypothermia treatment; rats in the acupuncture plus mild hypothermia group received acupuncture and mild hypothermia treatment. 72 h after the treatment, neurological function impairment score was performed; the infarct area ratio was determined by 2,3,5-tripheyl tetrazolium chloride (TTC) staining; apoptosis of brain cells was observed by TUNEL method; the expressions of Bcl-2, Bax and Caspase-3 were detected by immunohistochemistry. Compared with the blank control group and the sham operation group, the neurological function impairment score, cerebral infarct area ratio, apoptosis, and the expressions of Bax and Caspase-3 in the model group were significantly increased, while the expression of Bcl-2 was significantly decreased, and there were significant between-group differences (all P

The effect of mild hypothermia (MH) on microcirculation after resuscitation from cardiac arrest is controversial. The aim of this study was to determine whether MH improves or aggravates the disturbance of cerebral microcirculation. Twenty domestic male pigs were randomized into the MH group (n = 8), non-hypothermia (NH) group (n = 8) or sham operation group (n = 4). In the MH group, the animals were initiated rapid intravascular cooling at 1 h after return of spontaneous circulation (ROSC) from 8 min ventricular fibrillation, and the core temperature was reduced to 33 °C for 12 h and then rewarmed to 37 °C. In the NH group, animals did not receive hypothermia treatment after ROSC. In the sham operation group, the same surgical procedure was performed, but without inducing ventricular fibrillation and hypothermia treatment. The cerebral microvascular flow index (MFI) of large microvessel (diameter > 20 μm) and small microvessel (diameter

The aim of this study was to investigate the effect of mild hypothermia therapy (34–36°C) and the alterations of matrix metalloproteinase-9 (MMP-9) in 20 patients with high-risk traumatic brain injury (TBI). The neurologic status and outcome were assessed using Full Outline of UnResponsiveness (FOUR) score and Glasgow Coma Scale (GCS). A prospective randomized control study involved patients with high-risk TBI (FOUR score ≤ 7). Patients were randomized into two groups, with and without mild hypothermia therapy which were investigated within 24 and 72 h. The MMP-9 level, MMP-9 mRNA expression and -1562 C/T polymorphism were estimated using enzyme-linked immune sorbent assay (ELISA), reversing transcription polymerase chain reaction (RT-PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Different levels of these variables were compared in the two groups. In the hypothermia group, the expression of MMP-9 mRNA and the level of serum MMP-9 were significantly decreased (P < 0.05) within 72 h. There was a highly significant correlation between the expression of MMP-9 mRNA and the level of MMP-9 protein (R2 = 0.741, r = 0.861, P < 0.05). The study did not find in -1562 C/T polymorphism. The patients’ outcome was improved significantly after mild hypothermia therapy (P < 0.05). The data obtained from this study show that mild hypothermia therapy down regulated the expression of MMP-9 mRNA, the MMP-9 protein level and increased the FOUR score and GCS in high-risk TBI patients within 72 h.

Purpose: To investigate hypothermia and its potential association with core and outdoor temperatures in adolescents suffering from acute alcohol intoxication. Methods: Data were derived from the Dutch Pediatric Surveillance System, which monitors alcohol intoxication among all Dutch adolescents. Adolescents < 18 years of age with a positive blood alcohol concentration (BAC > 0 g/l) were included. This resulted in an analysis of data from the years 2011 to 2015 that were obtained through a total of 967 questionnaires. Results: This study revealed small but significantly lower core temperatures in winter time (35.59°C [96.06°F]) versus summer time (35.83°C [96.49°F]). These differences could not be attributed to the genders and ages of the patients. In winter time, 26.6% of the adolescents experienced mild hypothermia, with body temperatures of 32.00–34.99°C (89.60–94.98°F), compared to 18.0% during the summer. Although not significant, amounts of time spent in reduced consciousness, hospitalized and receiving intensive care were prolonged in adolescents with lower core temperatures. Conclusions: This article is the first to describe this trend of hypothermia among alcohol-intoxicated Dutch adolescents admitted during winter time. These findings are important for awareness of this issue and can be used for prevention strategies in the future.

Therapeutic hypothermia (TH) is an attractive target for mild traumatic brain injury (mTBI) treatment, yet significant gaps in our mechanistic understanding of TH, especially at the cellular level, remain and need to be addressed for significant forward progress to be made. Using a recently-established 3D in-vitro neural hydrogel model for mTBI we investigated the efficacy of TH after compressive impact injury and established critical treatment parameters including target cooling temperature, and time windows for application and maintenance of TH. Across four temperatures evaluated (31.5, 33, 35, and 37°C), 33°C was found to be most neuroprotective after 24 and 48 hours post-injury. Assessment of TH administration onset time and duration showed that TH should be administered within 4 hours post-injury and be maintained for at least 6 hours for achieving maximum viability. Cellular imaging showed TH reduced the percentage of cells positive for caspases 3/7 and increased the expression of calpastatin, an endogenous neuroprotectant. These findings provide significant new insight into the biological parameter space that renders TH effective in mitigating the deleterious effects of cellular mTBI and provides a quantitative foundation for the future development of animal and preclinical treatment protocols.

Experimental evidence and clinical experience demonstrate that there are multiple mechanisms involved in cellular damage following neurological insult. Laboratory experiments since the 1950s demonstrated that there are benefits of mild hypothermia. Since that time hypothermia has been proposed as a valid clinical modality for several neurologic conditions.