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

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

Exploring and validating heating dynamics in a radio-frequency electromagnetic field-based resonant chamber for mouse hyperthermia research.

Mild whole-body hyperthermia has been shown to have anti-tumor effects through an immune-modulating mechanism. Before it is widely applied in the clinic, tremendous mechanistic research in animals is necessary to adhere to evidence-based principles. The radio frequency electromagnetic field (RF-EMF) based heating facility could be a good choice for hyperthermia treatment, but the heating characteristics of a facility, including structure design, electromagnetic and thermal dosimetry, and the biologic effects of hyperthermia, need to be well elucidated. Here, we reported the heating characteristic study on a resonant chamber (RC) excited by a 1800 MHz solid source. The EMF in the RC was stirred by 24 static reflectors, which resulted in the standard deviation of electric field intensity being below 3 dB in the EM homogeneity evaluation. For the exposure scenario, six free-moving mice were loaded into separate cases and exposed simultaneously in the RC. The EMF energy absorption and distribution in exposed mice were calculated with the 12-plane-waves method of numerical simulation. Different levels of core body temperature increment in exposed mice were achieved through regulation of the source output power. Overexpression of heat shock proteins (HSPs) was detected in the liver, lung and muscle, but not in the brain of the exposed mice. The levels of representative inflammatory cytokines in the serum, TNF-α and IL-10 increased post RC exposure. Based on the heating characteristic study and validation, the applied RC would be a qualified heating system for mild whole-body hyperthermia effect research in mice.

Mild whole-body hyperthermia has potential anti-tumor effects by modulating the immune system. A radio frequency electromagnetic field (RF-EMF)-based heating facility emerges as a suitable option for hyperthermia treatment. However, a qualified heating facility for scientific research must elucidate its heating characteristics and validate the biological effects associated with hyperthermia. In this study, we report the characteristics of a rodent heating chamber using EMF energy. The special structure of the chamber not only achieved efficient EMF usage but also ensured the homogeneity in EMF spatial distribution, animal EM absorption, and EMF-caused biological effects. Our work may offer insights for designing a low-cost yet reliable heating facility for scientific research.

Post-exercise management of exertional hyperthermia in dogs participating in dog sport (canicross) events in the UK.

Exercise is a common trigger of heat-related illness (HRI) events in dogs, accounting for 74% of canine HRI cases treated under primary veterinary care in the United Kingdom. However, few empirical studies have evaluated the effectiveness of differing cooling methods for dogs with exertional hyperthermia or HRI. This study aimed to prospectively evaluate effects of ambient conditions and post-exercise management practices (cooling methods and vehicular confinement) on the post-exercise temperature change of dogs participating in UK canicross events. Canine temperature was recorded at three intervals post-exercise: as close as possible to 0- (immediately post-exercise), 5-, and 15-min post-exercise. Ambient conditions and post-exercise management were recorded for 115 cooling profiles from 52 dogs. In 28/115 (24.4%) profiles, the dog's temperature increased during the first 5-min post-exercise. Overall, 68/115 (59.1%) profiles included passive cooling (stood or walked outside), 35 (30.4%) active cooling (cold-water immersion or application of a cooling coat), and 12 (10.4%) involved no cooling and were immediately housed in vehicles. No dogs developed hypothermia during the study and no adverse effects were observed from any cooling method. In hyperthermic dogs, overall post-exercise body temperature change was significantly negatively associated (i.e. the dogs cooled more) with 0-min post-exercise body temperature (ß = -0.93, p < 0.001), and not being housed in a vehicle (ß = -0.43, p = 0.013). This study provides evidence cold-water immersion (in water at 0.1-15.0 °C) can be used to effectively and safely cool dogs with exertional hyperthermia. Progressive temperature increases in many dogs - even after exercise has terminated - supports the message to "cool first, transport second" when managing dogs with HRI. When transporting dogs post-exercise or with HRI even after active cooling, care should be taken to cool the vehicle before entry and promote air movement around the dog during transport to facilitate ongoing cooling and prevent worsening of hyperthermia during travel.

Intelligent Size-Switchable Iron Carbide-Based Nanocapsules with Cascade Delivery Capacity for Hyperthermia-Enhanced Deep Tumor Ferroptosis.

The ferroptosis pathway is recognized as an essential strategy for tumor treatment. However, killing tumor cells in deep tumor regions with ferroptosis agents is still challenging because of distinct size requirements for intratumoral accumulation and deep tumor penetration. Herein, intelligent nanocapsules with size-switchable capability that responds to acid/hyperthermia stimulation to achieve deep tumor ferroptosis are developed. These nanocapsules are constructed using poly(lactic-co-glycolic) acid and Pluronic F127 as carrier materials, with Au-Fe2 C Janus nanoparticles serving as photothermal and ferroptosis agents, and sorafenib (SRF) as the ferroptosis enhancer. The PFP@Au-Fe2 C-SRF nanocapsules, designed with an appropriate size, exhibit superior intratumoral accumulation compared to free Au-Fe2 C nanoparticles, as evidenced by photoacoustic and magnetic resonance imaging. These nanocapsules can degrade within the acidic tumor microenvironment when subjected to laser irradiation, releasing free Au-Fe2 C nanoparticles. This enables them to penetrate deep into tumor regions and disrupt intracellular redox balance. Under the guidance of imaging, these PFP@Au-Fe2 C-SRF nanocapsules effectively inhibit tumor growth when exposed to laser irradiation, capitalizing on the synergistic photothermal and ferroptosis effects. This study presents an intelligent formulation based on iron carbide for achieving deep tumor ferroptosis through size-switchable cascade delivery, thereby advancing the comprehension of ferroptosis in the context of tumor theranostics.

Influence of different heat transfer models on therapeutic temperature prediction and heat-induced damage during magnetic hyperthermia.

Magnetic hyperthermia regulates the therapeutic temperature within a specific range to damage malignant cells after exposing the magnetic nanoparticles inside tumor tissue to an alternating magnetic field. The therapeutic temperature of living tissues can be generally predicted using Pennes' bio-heat equation after ignoring both the inhomogeneity of biological structure and the microstructural responses. Although various of the bio-heat transfer models proposed in literature fix these shortages, there is still a lack of a comprehensive report on investigating the discrepancy for different models when applied in the magnetic hyperthermia context. This study compares four different bio-heat equations in terms of the therapeutic temperature distribution and the heat-induced damage situation for a proposed geometric model, which is established based on computed tomography images of a tumor bearing mouse. The therapeutic temperature is also used as an index to evaluate the effect of two key relaxation times for the phase lag behavior on bio-heat transfer. Moreover, this work evaluates the effects of two blood perfusion rates on both the treatment temperature and the cumulative equivalent heating minutes at 43 °C. Numerical analysis results reveal that relaxation times for phase-lag behavior as well as the porosity for living tissues directly affect the therapeutic temperature variation and ultimately the thermal damage for the malignant tissue during magnetic hyperthermia. The dual-phase-lag equation can be converted into Pennes' equation and simple-phase-lag equation when relaxation times meet specific conditions during the process of heat transfer. In addition, different blood perfusion rates can result in an amplitude discrepancy for treatment temperature, but this parameter does not change the characteristics of thermal propagation during therapy.

Photonic Hyperthermia Synergizes with Immune-Activators to Augment Tumor-Localized Immunotherapy.

Photothermal immunotherapy, the combination of photothermal hyperthermia and immunotherapy, is a noninvasive and desirable therapeutic strategy to address the deficiency of traditional photothermal ablation for tumor treatment. However, insufficient T-cell activation following photothermal treatment is a bottleneck to achieve satisfactory therapeutic effectiveness. In this work, a multifunctional nanoplatform is rationally designed and engineered on the basis of polypyrrole-based magnetic nanomedicine modified by T-cell activators of anti-CD3 and anti-CD28 monoclonal antibodies, which have achieved robust near infrared laser-triggered photothermal ablation and long-lasting T-cell activation, realizing diagnostic imaging-guided immunosuppressive tumor microenvironment regulation following photothermal hyperthermia by reinvigorating tumor-infiltrating lymphocytes. By virtue of high-efficient immunogenic cell death and dendritic cell maturation combined with T-cell activation, this nanosystem markedly restrains primary and abscopal tumors as well as metastatic tumors with negligible side effects in vivo, exerting the specific function for suppressing tumor recurrence and metastasis by establishing a long-term memory immune response.

Optimization of hyperthermia process applied to cancer treatment using multi-objective optimization differential evolution.

Due to the number of cancer cases diagnosed each year and the fatality rate resulting from some more severe types, the improvement of less invasive and more efficient treatment techniques is of great importance. In this context, hyperthermia is a medical procedure in which the tumor region is heated by using an applicator for a certain period, aiming to destroy pathological cells. Computational models can be used to simulate the heating effect of tumors and adjacent cells. In general, the solution to an optimization problem considering factors such as heating temperature, applicator position, and the time in which the region will be subjected to heating can provide important information about the procedure. Traditionally, this type of problem has been addressed in a single objective context, focusing on minimizing the destruction of adjacent healthy tissue considering the area of the applicator constant. Our fundamental objective is to propose a multi-objective design problem considering the minimization of the area subject to the procedure and the time required for the process of hyperthermia in a breast cancer treatment. The problem is constrained by the degree of tissue destruction and by a partial differential equation that describes the phenomenon of heat transfer in both healthy and tumor tissues. The results obtained demonstrate that a point with a good compromise between the objectives can be chosen in such a way that a particular strategy can be defined for each patient.

ACSM Expert Consensus Statement on Exertional Heat Illness: Recognition, Management, and Return to Activity.

ABSTRACT: Exertional heat stroke (EHS) is a true medical emergency with potential for organ injury and death. This consensus statement emphasizes that optimal exertional heat illness management is promoted by a synchronized chain of survival that promotes rapid recognition and management, as well as communication between care teams. Health care providers should be confident in the definitions, etiologies, and nuances of exertional heat exhaustion, exertional heat injury, and EHS. Identifying the athlete with suspected EHS early in the course, stopping activity (body heat generation), and providing rapid total body cooling are essential for survival, and like any critical life-threatening situation (cardiac arrest, brain stroke, sepsis), time is tissue. Recovery from EHS is variable, and outcomes are likely related to the duration of severe hyperthermia. Most exertional heat illnesses can be prevented with the recognition and modification of well-described risk factors ideally addressed through leadership, policy, and on-site health care.

Synergistic effect of tumor chemo-immunotherapy induced by leukocyte-hitchhiking thermal-sensitive micelles.

Some specific chemotherapeutic drugs are able to enhance tumor immunogenicity and facilitate antitumor immunity by inducing immunogenic cell death (ICD). However, tumor immunosuppression induced by the adenosine pathway hampers this effect. In this study, E-selectin-modified thermal-sensitive micelles are designed to co-deliver a chemotherapeutic drug (doxorubicin, DOX) and an A2A adenosine receptor antagonist (SCH 58261), which simultaneously exhibit chemo-immunotherapeutic effects when applied with microwave irradiation. After intravenous injection, the fabricated micelles effectively adhere to the surface of leukocytes in peripheral blood mediated by E-selectin, and thereby hitchhiking with leukocytes to achieve a higher accumulation at the tumor site. Further, local microwave irradiation is applied to induce hyperthermia and accelerates the release rate of drugs from micelles. Rapidly released DOX induces tumor ICD and elicits tumor-specific immunity, while SCH 58261 alleviates immunosuppression caused by the adenosine pathway, further enhancing DOX-induced antitumor immunity. In conclusion, this study presents a strategy to increase the tumor accumulation of drugs by hitchhiking with leukocytes, and the synergistic strategy of chemo-immunotherapy not only effectively arrested primary tumor growth, but also exhibited superior effects in terms of antimetastasis, antirecurrence and antirechallenge.

Manejo não farmacológico da febre e hipertermia da criança: revisão integrativa / Manejo no farmacológico de la fiebre e hipertermia en niños: revisión integradora / Non-pharmacological fever and hyperthermia management in children: an integrative review

Resumo Objetivo: Identificar as intervenções não farmacológicos para febre e hipertermia em crianças indicados na literatura científica. Métodos: Trata-se de uma revisão integrativa da literatura realizada nas bases de dados Lilacs, PubMed e CINAHL e as bibliotecas COCHRANE e SciELO. Foram incluídos artigos que abordassem as intervenções não farmacológicas para febre e hipertermia, publicados em português e inglês, no período de 2000 a 2019. Resultados: A amostra foi constituída por 27 artigos, que foram agrupados, conforme suas similaridades, em sete categorias. As intervenções utilizadas foram: banhos; compressas mornas; sponging ; incentivo à ingestão de líquidos; bolsas de gelo e cobertores refrigerados; e, por último, a categoria ventilação do ambiente. Observaram-se diferentes intervenções no manejo não farmacológico de febre e hipertermia. Conclusão: A prática de medidas não farmacológicas isoladamente não é recomendada para o tratamento de febre em crianças, exceto as intervenções que auxiliem nas respostas fisiológicas do corpo. Os resultados ressaltam a recomendação da realização de novas pesquisas que redundem em evidências para fundamentar o melhor cuidado do enfermeiro pediatra à criança com febre.

Resumen Objetivo: Identificar las intervenciones no farmacológicas para la fiebre e hipertermia en niños recomendadas en la literatura científica. Métodos: Se trata de una revisión integradora de la literatura realizada en las bases de datos Lilacs, PubMed y CINAHL y las bibliotecas COCHRANE y SciELO. Se incluyeron artículos que abordaran las intervenciones no farmacológicas para la fiebre e hipertermia, publicados en portugués e inglés, en el período de 2000 a 2019. Resultados: La muestra estuvo compuesta por 27 artículos, que fueron agrupados en siete categorías según sus similitudes. Las intervenciones utilizadas fueron: baños, compresas tibias, sponging , incentivo a la ingesta de líquidos, bolsas de hielo y mantas refrigeradas y, por último, la categoría ventilación del ambiente. Se observaron diferentes intervenciones en el manejo no farmacológico de la fiebre e hipertermia. Conclusión: No se recomienda la práctica de medidas no farmacológicas de forma aislada para tratar la fiebre en niños, excepto las intervenciones que ayuden a las respuestas fisiológicas del cuerpo. Los resultados resaltan la recomendación de realizar nuevos estudios que tengan como resultado evidencias para fundamentar un mejor cuidado del enfermero pediatra a niños con fiebre.

Abstract Objective: To identify non-pharmacological interventions for fever and hyperthermia in children indicated in the scientific literature. Methods: an integrative literature review carried out in the LILACS, PubMed and CINAHL databases and in the COCHRANE and SciELO libraries. Articles that addressed non-pharmacological interventions for fever and hyperthermia, published in Portuguese and English, from 2000 to 2019, have been included. Results: The sample consisted of 27 articles, which were grouped, according to their similarities, into seven categories. The interventions used were baths, warm compresses, sponging, encouraging fluid intake, ice packs, cooled blankets, and room ventilation. Different interventions were observed in non-pharmacological fever and hyperthermia management. Conclusion: Practicing non-pharmacological measures alone is not recommended for fever treatment in children, except for interventions that assist in the physiological responses of the body. The results highlight the recommendation of conducting further research that results in evidence to support the best care provided by pediatric nurses to children with fever.

2020 International Consensus on First Aid Science With Treatment Recommendations.

This is the summary publication of the International Liaison Committee on Resuscitation's 2020 International Consensus on First Aid Science With Treatment Recommendations. It addresses the most recent published evidence reviewed by the First Aid Task Force science experts. This summary addresses the topics of first aid methods of glucose administration for hypoglycemia; techniques for cooling of exertional hyperthermia and heatstroke; recognition of acute stroke; the use of supplementary oxygen in acute stroke; early or first aid use of aspirin for chest pain; control of life-threatening bleeding through the use of tourniquets, hemostatic dressings, direct pressure, or pressure devices; the use of a compression wrap for closed extremity joint injuries; and temporary storage of an avulsed tooth. Additional summaries of scoping reviews are presented for the use of a recovery position, recognition of a concussion, and 6 other first aid topics. The First Aid Task Force has assessed, discussed, and debated the certainty of evidence on the basis of Grading of Recommendations, Assessment, Development, and Evaluation criteria and present their consensus treatment recommendations with evidence-to-decision highlights and identified priority knowledge gaps for future research.

Evaluation of human brain hyperthermia using exergy balance equation.

Hyperthermia is caused by disturbance in the thermoregulatory system of the human body and requires emergency treatment to prevent disability or possible mortality. To design any therapeutic device for hyperthermia, an exhaustive effort is required to establish the extremities of such thermal traumas. In this context, the authors have incorporated the human-body exergy-balance equation to compute the hyperthermia thresholds. This is a pioneer attempt to model hyperthermia states. An induced-hyperthermia technique is used to evaluate the extremities of metabolic heat generation and other dependent parameters. Moreover, a case study is also presented to calculate the parameters of prime importance i.e. exergy consumption (EC) and entropy generation rate (δSg) to provide the body's accumulative and exhaustive thermal energy maxima, respectively. Furthermore, the thresholds have been evaluated and simulated by the varying body and/or environmental conditions. The resulting states have been analysed to setup critical ranges to provide the guidelines for rehabilitation therapy. A thermal manikin has also been developed, mimicking the blood circulation in humans, to further substantiate the use of an exergy-based approach. The results indicate that the exergy-based approach is well suited to model hyperthermia at pathophysiological boundaries, contrary to existing approaches which predominantly are limited to the physiological domain.

Deep brain stimulation as a possible treatment of hyperthermia in patients with serotonin syndrome.

Maintaining a body temperature within a narrow range is vital for the survival of all mammals, including humans. With the help of optogenetics, a better understanding of the thermoregulatory organs and pathways is achieved. Optogenetic activation of the GABAergic neurons in the ventral part of the lateral preoptic nucleus (VLPO) leads to decrease in the body temperature. On the other hand, number of drugs could alter the thermoregulatory balance, leading to a hyperthermic state, such as serotonin syndrome (SS). SS is a potentially life-threatening clinical condition that occurs as a result of a drug-induced increase in the intrasynaptic serotonin (5-hydroxytryptamine, 5-HT) levels due to overdose of a single drug or due to interaction between two or more drugs with serotonergic mechanism of action. In this hypothesis, we propose a novel method for the treatment of hyperthermia, a core clinical sign of serotonin syndrome, through deep brain stimulation (DBS). An electrode is stereotactically placed in the VLPO, which may lead to reduction of the core body temperature. If proven effective, this technique should be left as a salvage method for reduction of hyperthermia, where the drug treatment is insufficient or ineffective. This technique could be used for the treatment of other syndromes, where hyperthermia takes a central place, including malignant hyperthermia, neuroleptic malignant syndrome, etc. DBS, on the other hand, could be used alone to induce hyperthermia in patients with malignant diseases. Hyperthermia improves the immune response, improves the drug penetration and stop the repair of already damaged tumor cells after chemotherapy or radiotherapy.

Quality indicators for hyperthermia treatment: Italian survey analysis.

AIM: Nowadays, no Quality Indicators (QI) have been proposed for Hyperthermia treatments. Starting from radiotherapy experience, the aim of this work is to adapt radiotherapy indicators to Hyperthermia and to propose a new specific set of QI in Hyperthermia field. MATERIAL AND METHODS: At first, radiotherapy quality indicators published in literature have been adapted to hyperthermia setting. Moreover, new specific indicators for the treatment of hyperthermia have been defined. To obtain the standard reference values of quality indicators, a questionnaire was sent to 7 Italian hyperthermia Institutes with a list of questions on physical and clinical hyperthermia treatment in order to highlight the different therapeutic approaches. RESULTS: Three structure, five process and two outcome QI were selected. It has been possible to adapt seven indicators from radiotherapy, while three indicators have been defined as new specific indicators for hyperthermia. Average values used as standard reference values have been obtained and proposed. CONCLUSION: The survey performed on 7 Italian centres allowed to derive the standard reference value for each indicator. The proposed indicators are available to be investigated and applied by a larger number of Institutes in which hyperthermia treatment is performed in order to monitor the operational procedures and to confirm or modify the reference standard value derived for each indicator.

Do Alternative Cooling Methods Have Effective Cooling Rates for Hyperthermia Compared With Previously Established CWI Cooling Rates?

Clinical Scenario: In the last few years, there have been several studies examining alternative cooling strategies in the treatment of exertional heat stroke (EHS). Morbidity and mortality with EHS are associated with how long the patient's core body temperature remains above the critical threshold of 40.5°C. Although cold-water immersion (CWI) is the gold standard of treatment when cooling a patient with EHS, more recent alternative cooling techniques have been examined for use in settings where CWI may not be feasible (ie, remote locations). Clinical Question: Do alternative cooling methods have effective core body temperature cooling rates for hyperthermia compared with previously established CWI cooling rates? Summary of Key Findings: The authors searched for studies using alternative cooling methods to cool hyperthermic individuals. To be included, the studies needed a PEDro score ≥6 and a level of evidence ≥2. They found 9 studies related to our focused clinical question; of these, 5 studies met the inclusion criteria. The cooling rates for hand cooling, cold-water shower, and ice-sheet cooling were 0.03°C/min, 0.08°C/min, and 0.06°C/min, respectively, whereas the tarp-assisted cooling with oscillation (TACO) method was the only method that had an acceptable cooling rate (range 0.14-0.17°C/min). Clinical Bottom Line: When treating EHS, if CWI is not available, the tarp-assisted cooling method may be a reasonable alternative. Clinicians should not use cold shower, hand cooling, or ice-sheet cooling if better cooling methods are available. Clinicians should always use CWI when available. Strength of Recommendation: Five level 2 studies with PEDro scores ≥6 suggest the TACO method is the only alternative cooling method that decreases core body temperature at a similar, though slower, rate of CWI. Hand cooling, cold showering, and ice-sheet cooling do not decrease core body temperature at an appropriate rate and should not be used in EHS situations if a modality with a better cooling rate is available.