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Introduction: Hypothermia increases mortality in trauma populations and frequently occurs in military casualties due to the nature of combat environments. The association between hypothermia and the time of year when injured remains unclear. We sought to determine the association between seasonal changes in temperature and hypothermia among combat casualties., Materials and Methods: This observational study was a secondary analysis of a previously described Department of Defense Trauma Registry dataset which included U.S. military and Coalition casualties who received prehospital care from January 2007 to March 2020 in Afghanistan and Iraq. We tested for associations between hypothermia (<36.2°C) and seasonal ambient temperatures by constructing multivariable logistic regression models. Summer was defined as June through August and winter as December through February. We assumed that the combat operations occurred in the area near the point of first contact with the deployed military treatment facilities. This study was determined to be exempt from Institutional Review Board oversight., Results: There were 5,821 that met inclusion for this study. Within the multivariable logistic regression model, we adjusted for injury severity score, mechanism of injury, and imputed transport time, finding that combat casualties were 2.28 (odds ratio, 95% confidence interval 1.93-2.69) times more likely to develop hypothermia in the winter versus summer. When using temperature as a continuous outcome, casualties had a lower emergency department temperature during the winter (parameter estimate -0.133°C, P < 0.001) after adjusting for confounders. In casualties experiencing hypothermia, mortality was higher (4% versus 1%, P < 0.001), and composite median injury severity score values were higher (10 versus 5, P < 0.001). Among hypothermic casualties, serious injuries were significantly more common (all P < 0.001) to the head (15% versus 7%), thorax (15% versus 7%), abdomen (9% versus 6%), extremities (35% versus 22%), and skin (4% versus 2%)., Conclusions: We found a seasonal variation in the occurrence of hypothermia in a large cohort of trauma casualties. Despite adjustment for multiple known confounders, our findings substantiate probable ambient temperature variations to trauma-induced hypothermia. Furthermore, our findings, when taken in the context of other studies on the efficacy of current hypothermia prevention and treatment strategies, support the need for better methods to mitigate hypothermia in future cold-weather operations., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Introduction: The association between hypothermia, coagulopathy, and acidosis in trauma is well described. Hypothermia mitigation starts in the prehospital setting; however, it is often a secondary focus after other life-saving interventions. The deployed environment further compounds the problem due to prolonged evacuation times in rotary wing aircraft, resource limitations, and competing priorities. This analysis evaluates hypothermia in combat casualties and the relationship to resuscitation strategy with blood products., Methods: Using the data from the Department of Defense Joint Trauma Registry from 2003 to 2021, a retrospective analysis was conducted on adult trauma patients. Inclusion criteria was arrival at the first military treatment facility (MTF) hypothermic (<95ºF). Study variables included: mortality, year, demographics, battle vs non-battle injury, mechanism, theater of operation, vitals, and labs. Subgroup analysis was performed on severely injured (15 < ISS < 75) hypothermic trauma patients resuscitated with whole blood (WB) vs only component therapy., Results: Of the 69,364 patients included, 908 (1.3%) arrived hypothermic; the vast majority of whom (N = 847, 93.3%) arrived mildly hypothermic (90-94.9°F). Overall mortality rate was 14.8%. Rates of hypothermia varied by year from 0.7% in 2003 to 3.9% in 2014 (P <0.005). On subgroup analysis, mortality rates were similar between patients resuscitated with WB vs only component therapy; though base deficit values were higher in the WB cohort (-10 vs -6, P < 0.001)., Conclusion: Despite nearly 20 years of combat operations, hypothermia continues to be a challenge in military trauma and is associated with a high mortality rate. Mortality was similar between hypothermic trauma patients resuscitated with WB vs component therapy, despite greater physiologic derangements on arrival in patients who received WB. As the military has the potential to conduct missions in environments where the risk of hypothermia is high, further research into hypothermia mitigation techniques and resuscitation strategies in the deployed setting is warranted., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

This case report highlights the effective use of intermittent hemodialysis (IHD) in warming a 71-year-old female patient with severe hypothermia who presented with a rectal temperature of 25 °C and signs of hemodynamic instability. The patient, found unconscious after prolonged exposure to cold exacerbated by alcohol consumption, initially showed some improvement in core temperature through active external rewarming methods. However, soon, her temperature plateaued at 27 °C. Patient was deemed unsuitable for extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass (CPB) due to her age, and urgent IHD was initiated. This approach resulted in a stable increase in core temperature at approximately 2.0 °C/hr, along with normalization of lactic acidosis, creatinine phosphokinase, and correction of electrolyte imbalances, culminating in her full recovery and discharge after seven days in the hospital.After reviewing this case alongside similar ones from before, this case report highlights the efficacy and safety of IHD as an efficient, readily available, and less invasive method for rewarming moderate to severe hypothermic patients who are hemodynamically unstable patients but do not have cardiac arrest or renal dysfunction. IHD is especially useful when less invasive cooling devices (Artic Sun/ CoolGard) are not available or more invasive extracorporeal life support options (ECMO/ CPB) are either not indicated or unavailable. IHD can also help improve concurrent electrolyte imbalances and/or toxin buildup. The report further emphasizes the necessity of monitoring for potential complications, such as post-dialysis hypophosphatemia and rebound hyperkalemia, following successful rewarming., (© 2024. The Author(s).)

SummaryShapiro's syndrome is a rare neurological disease. The triad of Shapiro's syndrome includes episodes of hyperhidrosis, hypothermia and complete/partial agenesis of the corpus callosum. We report a case of a young male who had episodic chills, increased sweating and fatigue. During these episodes, he was found to have bradycardia, hypotension and hypothermia. Clinical and neurological examinations were unremarkable. The MRI of the brain revealed agenesis of the corpus callosum. There was a good response to carbamazepine therapy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Diamond Blackfan Anemia (DBA) is a rare disease characterized by anemia secondary to impaired red blood cell production from bone marrow failure. We present a case of infantile hypothermia and shock caused by this clinical pathology. A seven-week-old infant was brought to the emergency department by the father with the chief complaint of abnormal breathing and low activity level throughout the day. Medical history was unremarkable for both the patient and the family. On examination, the infant was breathing 30 breaths per minutes, had a heart rate of 116, and a core temperature of 33 degrees Celsius. The infant was ashen in color, limp, with grunted breathing and minimal movement. Numerous abnormal laboratory readings were reported, with the most significant being a hemoglobin of 1.7 and a hematocrit of 7.4. Emergent blood transfusion was initiated, and the patient was eventually air-lifted to a pediatric hospital two hours away. This case highlights the imperative of a thorough history and examination and consideration of a broad differential for neonatal hypothermia and shock, especially in the setting of no obvious bleeding., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

The present study aimed to investigate the combination effects of hypothermia (HT) and intranasal insulin (INS) on structural changes of the hippocampus and cognitive impairments in the traumatic brain injury (TBI) rat model. The rats were divided randomly into the following five groups (n = 10): Sham, TBI, TBI with HT treatment for 3 h (TBI + HT), TBI with INS (ten microliters of insulin) treatment daily for 7 days (TBI + INS), and TBI with combining HT and INS (TBI + HT + INS). At the end of the 7th day, the open field and the Morris water maze tests were done for evaluation of anxiety-like behavior and memory performance. Then, after sacrificing, the brain was removed for stereological study. TBI led to an increase in the total volume of hippocampal subfields CA1 and DG and a decrease in the total number of neurons and non-neuronal cells in both sub-regions, which was associated with anxiety-like behavior and memory impairment. Although, the combination of HT and INS prevented the increased hippocampal volume and cell loss and improved behavioral performances in the TBI group. Our study suggests that the combined treatment of HT and INS could prevent increased hippocampal volume and cell loss in CA1 and DG sub-regions and consequently improve anxiety-like behaviors and memory impairment following TBI., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: There is an extensive body of research regarding neurological outcomes following neonatal hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH), with limited data on growth outcomes. We examined perinatal characteristics associated with postnatal growth in this population., Methods: Convenience cohort of 66 infants with HIE who underwent TH and participated in follow-up at 24 months of age were included. Regression modeling including perinatal anthropomorphics, markers of HIE, and systemic injury was used to evaluate growth at 24 months., Results: Birth head circumference was associated with weight (p = 0.036). MRI severity, pH at admission and birth head circumference were associated with height (p = 0.043, p = 0.015 and p = 0.043 respectively). MRI severity and length of intubation were associated with head circumference (p = 0.038 and p < 0.001 respectively)., Conclusion: There was a significant association between specific early factors and growth at 24 months among infants with HIE treated with TH., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Study Objective: To indicate predictors of witnessed hypothermic cardiac arrest., Methods: We conducted a retrospective analysis of 182 patients with severe accidental hypothermia (i.e., with core body temperature of ≤28 °C) who presented with preserved spontaneous circulation at first contact with medical services. We divided the study population into two groups: patients who suffered hypothermic cardiac arrest (HCA) at any time between encounter with medical service and restoration of normothermia, and those who did not sustain HCA. The analyzed outcome was the occurrence of cardiac arrest prior to achieving normothermia. Hemodynamic and biochemical parameters were analyzed with regard to their association with the outcome., Results: Fifty-two (29%) patients suffered HCA. In a univariable analysis, four variables were significantly associated with the outcome, namely heart rate (p < 0.001), systolic blood pressure (p = 0.03), ventricular arrhythmia (p = 0.001), and arterial oxygen partial pressure (p = 0.002). In the multivariable logistic regression the best model predicting HCA included heart rate, PaO 2 , and Base Excess (AUROC = 0.78). In prehospital settings, when blood gas analysis is not available, other multivariable model including heart rate and occurrence of ventricular arrhythmia (AUROC = 0.74) can be used. In this study population, threshold values of heart rate of 43/min, temperature-corrected PaO 2 of 72 mmHg, and uncorrected PaO 2 of 109 mmHg, presented satisfactory sensitivity and specificity for HCA prediction., Conclusions: In patients with severe accidental hypothermia, the occurrence of HCA is associated with a lower heart rate, hypoxemia, ventricular arrhythmia, lower BE, and lower blood pressure. These parameters can be helpful in the early selection of high-risk patients and their allocation to extracorporeal rewarming facilities., Competing Interests: Declaration of competing interest None declared by the authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Even nowadays, the question of whether hypothermia can genuinely be considered therapeutic care for patients with traumatic spinal cord injury (SCI) remains unanswered. Although the mechanisms of hypothermia action are yet to be fully explored, early hypothermia for patients suffering from acute SCI has already been implemented in clinical settings. This article discusses measures for inducing various forms of hypothermia and summarizes several hypotheses describing the likelihood of hypothermia mechanisms of action. We present our objective neuro-electrophysiological results and demonstrate that early hypothermia manifests neuroprotective effects mainly during the first- and second-month post-SCI, depending on the severity of the injury, time of intervening, duration, degree, and modality of inducing hypothermia. Nevertheless, eventually, its beneficial effects gradually but consistently diminish. In addition, we report potential complications and side effects for the administration of general hypothermia with a unique referment to the local hypothermia. We also provide evidence that instead of considering early hypothermia post-SCI a therapeutic approach, it is more a neuroprotective strategy in acute and sub-acute phases of SCI that mostly delay, but not entirely avoid, the natural history of the pathophysiological events. Indeed, the most crucial rationale for inducing early hypothermia is to halt these devastating inflammatory and apoptotic events as early and as much as possible. This, in turn, creates a larger time-window of opportunity for physicians to formulate and administer a well-designed personalized treatment for patients suffering from acute traumatic SCI.

BACKGROUND Intraoperative and postoperative hypothermia of patients can be caused by the use of anesthetic drugs and the complicated and time-consuming procedures of interventional surgery. This retrospective study included 184 patients to investigate the incidence and factors associated with hypothermia during intraoperative anesthesia in a single center in China between January and October 2023. MATERIAL AND METHODS A convenient sampling method was used to select 184 patients who underwent general anesthesia intervention in a tertiary hospital in Sichuan Province from January to October 2023 as the study population. The independent factors influencing the occurrence of intraoperative hypothermia were analyzed. A survey was conducted to collect 5 demographic factors, 4 preoperative-related factors, and 10 surgically related factors. According to the occurrence of intraoperative hypothermia, the independent influencing factors of unplanned hypothermia during perioperative period were further analyzed. RESULTS Among 184 patients, 64 (34.78%) experienced perioperative unplanned hypothermia, of which 5 (7.81%) cases occurred before the start of surgery, 7 (10.94%) occurred before the start of surgery after anesthesia, and 52 (81.25%) occurred during surgery. Logistic regression analysis showed that body temperature at the beginning of surgery (P<0.001), set operating room temperature (P<0.001), duration of anesthesia (P=0.006), and age (P=0.001) were independent influencing factors for unplanned hypothermia during perioperative period. CONCLUSIONS The incidence of intraoperative hypothermia is high in patients undergoing general anesthesia interventions. Age, duration of anesthesia, set operating room temperature, and body temperature at the beginning of the operation were independent influencing factors for the occurrence of unplanned hypothermia during the perioperative period.

Drowning is a common cause of childhood morbidity and mortality worldwide. Anoxia, hypothermia, and metabolic acidosis are mainly responsible for this morbidity. Drowning may lead to multiple organ damage, especially cardiac damage, in cases in which severe hypothermia and hypoxemia occur. We report a case of a 4-year-old girl who was admitted to our hospital's Emergency Department because of drowning. She had elevated troponin I concentrations and ST-segment elevation with T wave inversion. However, cardiovascular computed tomography showed no obvious abnormalities in the coronary arteries. We suggest that cardiac damage in this situation is caused by coronary artery spasms. To the best of our knowledge, this is the first case of cardiac damage with electrocardiographic changes after drowning in a preschool child., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Objectives: Shapiro's syndrome (SS) is a rare condition characterized by spontaneous periodic hypothermia. The underlying pathophysiological mechanisms and etiology of this syndrome remain controversial, and fewer than 100 cases have been reported to date. The objective of this case report is to present a unique iatrogenic case of SS and contribute additional insights into the underlying etiology of this rare disorder., Methods: We conducted an analysis of existing medical literature and described a clinical case of SS secondary to a neurosurgical procedure., Results: To our knowledge, we present the first iatrogenic case of SS in a 53-year-old woman who underwent a partial right parieto-occipital lobectomy in 2003 as a treatment for refractory epilepsy. Several years after the surgical procedure, she began experiencing recurrent episodes of hypothermia. Brain magnetic resonance imaging (MRI) revealed the absence of the splenium of the corpus callosum (CC) and pituitary hyperplasia. After ruling out other potential causes of hypothermia, a diagnosis of SS was made., Discussion: The most plausible mechanism to explain the recurrent hypothermia associated with SS in our patient is a probable disruption of the pathways involved in thermoregulation through the CC as a consequence of the surgical procedure. This case report provides further insights into the etiology of this rare disorder., (© 2023. Fondazione Società Italiana di Neurologia.)

Background: Accidental hypothermia with severe frostbite is a rare combination of injuries with a high risk for long-term sequelae. There are widely accepted recommendations for the management of avalanche victims and for frostbite treatment, but no recommendation exists for the treatment of frostbite in severe hypothermic patients, specifically for the management of hypothermic avalanche victims presenting with frostbite., Case Presentation: We present a case of a previously healthy, 53-year-old male skier who was critically buried by an avalanche at 2300 m of altitude at an ambient temperature of - 8 °C for nearly 23 h. The victim was found with the right hand out of the snow and an air connection to outside. He was somnolent with Glasgow Coma Scale 11 (Eye 4, Verbal 2, Motor 5) and spontaneously breathing, in a severely hypothermic state with an initial core temperature of 23.1 °C and signs of cold injuries in all four extremities. After rescue and active external forced air rewarming in the intensive care unit, the clinical signs of first-degree frostbite on both feet and the left hand vanished, while third- to fourth-degree frostbite injuries became apparent on all fingers of the right hand. After reaching a core body temperature of approximately 36 °C, aggressive frostbite treatment was started with peripheral arterial catheter-directed thrombolysis with alteplase, intravenous iloprost, ibuprofen, dexamethasone and regional sympathicolysis with a right-sided continuous axillary block. After ten months, the patient had no tissue loss but needed neuropathic pain treatment with pregabalin., Conclusion: The combination of severe accidental hypothermia and severe frostbite is rare and challenging, as drug metabolism is unpredictable in a hypothermic patient and no recommendations for combined treatment exist. There is general agreement to give hypothermia treatment the priority and to begin frostbite treatment as early as possible after full rewarming of the patient. More evidence is needed to identify the optimal dosage and time point to initiate treatment of frostbite in severely hypothermic patients. This should be taken into consideration by future treatment recommendations., (© 2024. The Author(s).)

Importance: Induced hypothermia, the standard treatment for hypoxic-ischemic encephalopathy (HIE) in high-income countries (HICs), is less effective in the low-income populations in South Asia, who have the highest disease burden., Objective: To investigate the differences in blood genome expression profiles of neonates with HIE from an HIC vs neonates with HIE from South Asia., Design, Setting, and Participants: This case-control study analyzed data from (1) a prospective observational study involving neonates with moderate or severe HIE who underwent whole-body hypothermia between January 2017 and June 2019 and age-matched term healthy controls in Italy and (2) a randomized clinical trial involving neonates with moderate or severe HIE in India, Sri Lanka, and Bangladesh recruited between August 2015 and February 2019. Data were analyzed between October 2020 and August 2023., Exposure: Whole-blood RNA that underwent next-generation sequencing., Main Outcome and Measures: The primary outcomes were whole-blood genome expression profile at birth associated with adverse outcome (death or disability at 18 months) after HIE in the HIC and South Asia cohorts and changes in whole-genome expression profile during the first 72 hours after birth in neonates with HIE and healthy controls from the HIC cohort. Blood samples for RNA extraction were collected before whole-body hypothermia at 4 time points (6, 24, 48, and 72 hours after birth) for the HIC cohort. Only 1 blood sample was drawn within 6 hours after birth for the South Asia cohort., Results: The HIC cohort was composed of 35 neonates (21 females [60.0%]) with a median (IQR) birth weight of 3.3 (3.0-3.6) kg and gestational age of 40.0 (39.0-40.6) weeks. The South Asia cohort consisted of 99 neonates (57 males [57.6%]) with a median (IQR) birth weight of 2.9 (2.7-3.3) kg and gestational age of 39.0 (38.0-40.0) weeks. Healthy controls included 14 neonates (9 females [64.3%]) with a median (IQR) birth weight of 3.4 (3.2-3.7) kg and gestational age of 39.2 (38.9-40.4) weeks. A total of 1793 significant genes in the HIC cohort and 99 significant genes in the South Asia cohort were associated with adverse outcome (false discovery rate <0.05). Only 11 of these genes were in common, and all had opposite direction in fold change. The most significant pathways associated with adverse outcome were downregulation of eukaryotic translation initiation factor 2 signaling in the HIC cohort (z score = -4.56; P < .001) and aldosterone signaling in epithelial cells in the South Asia cohort (z score = null; P < .001). The genome expression profile of neonates with HIE (n = 35) at birth, 24 hours, 48 hours, and 72 hours remained significantly different from that of age-matched healthy controls in the HIC cohort (n = 14)., Conclusions and Relevance: This case-control study found that disease mechanisms underlying HIE were primarily associated with acute hypoxia in the HIC cohort and nonacute hypoxia in the South Asia cohort. This finding might explain the lack of hypothermic neuroprotection.

Surgical site infections (SSIs) may pose a significant risk to patients undergoing surgery. This study aims to explore the risk factors for SSIs in patients undergoing laparoscopic radical nephrectomy for renal cell carcinoma and the impact of infection on tumour-specific survival (CSS) after nephrectomy for renal cell carcinoma. To explore the risk factors for SSIs in patients undergoing laparoscopic radical nephrectomy for renal cell carcinoma and the impact of infection on tumour-specific survival (CSS) after nephrectomy for renal cell carcinoma. A retrospective analysis was conducted on 400 patients in our hospital from June 2021 to June 2023. This study divided patients into two groups: those with SSI and those without SSI. Collect general data and information related to the operating room. Clearly defined inclusion and exclusion criteria. Select surgical time, laminar mobile operating room use, and intraoperative hypothermia as observation indicators. Perform statistical analysis using SPSS 25.0 software, including univariate, multivariate, and survival analyses of wound-infected and uninfected patients. Out of 400 patients, 328 had no SSIs, 166 died during follow-up, 72 had SSIs, and 30 died during follow-up. There was no statistically significant difference (p > 0.05) in comparing primary data between individuals without SSIs and those with SSIs. There were statistically significant differences (p < 0.05) in surgical time, nonlaminar flow operating room use, and intraoperative hypothermia. The postoperative survival time of SSI patients with a tumour diameter of 7.0-9.9 cm was significantly longer than that of SSI patients, and the difference was statistically significant (p < 0.05). The occurrence of severe infection in patients with other tumour diameters did not affect postoperative survival, and the difference was not statistically significant (p > 0.05). After multiple factor analysis, it was found that severe infection can prolong the postoperative survival of patients with tumour diameter exceeding 7 cm (HR = 0.749, p < 0.05). This study identified nonlaminar flow operating rooms, prolonged surgical time, and intraoperative hypothermia as significant risk factors for SSIs. After nephrectomy for renal cell carcinoma patients with a tumour diameter of 7-9.9 μ m, perioperative infection can prolong their survival. However, it has no significant effect on patients with other tumour diameters., (© 2024 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Abstract: Trauma-induced coagulopathy (TIC) is a global inflammatory state accompanied by coagulation derangements, acidemia, and hypothermia, which occurs after traumatic injury. It occurs in approximately 25% of severely injured patients, and its incidence is directly related to injury severity. The mechanism of TIC is multifaceted; proposed contributing factors include dysregulation of activated protein C, increased tPA, systemic endothelial activation, decreased fibrinogen, clotting factor consumption, and platelet dysfunction. Effects of TIC include systemic inflammation, coagulation derangements, acidemia, and hypothermia. Trauma-induced coagulopathy may be diagnosed by conventional coagulation tests including platelet count, Clauss assay, international normalized ratio, thrombin time, prothrombin time, and activated partial thromboplastin time; viscoelastic hemostatic assays such as thrombelastography and rotational thrombelastography; or a clinical scoring system known as the Trauma Induced Coagulopathy Clinical Score. Preventing TIC begins in the prehospital phase with early hemorrhage control, blood product resuscitation, and tranexamic acid therapy. Early administration of prothrombin complex concentrate is also being studied in the prehospital environment. The mainstays of TIC treatment include hemorrhage control, blood and component transfusions, and correction of abnormalities such as hypocalcemia, acidosis, and hypothermia., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Infection following implant-based breast reconstruction can lead to devastating complications. Risk factors for infection include smoking, diabetes, and obesity. Intraoperative hypothermia may represent another modifiable risk factor. This study analyzed the effect of hypothermia in postmastectomy immediate implant-based reconstruction on postoperative surgical-site infection (SSI)., Methods: This was a retrospective review of 122 patients with intraoperative hypothermia, defined as less than 35.5°C, and 106 normothermic patients who underwent postmastectomy implant-based reconstruction between 2015 and 2021. Demographics, comorbidities, smoking status, hypothermia (and its duration), and length of surgery were collected. The primary outcome was SSI. Secondary outcomes included reoperation and delayed wound healing., Results: A total of 185 patients (81%) underwent staged reconstruction with tissue expander placement and 43 patients (18.9%) had a direct-to-implant procedure. Over half (53%) of the patients experienced intraoperative hypothermia. In the hypothermic group, a higher proportion of patients had SSIs (34.4% versus 17% of normothermic patients; P < 0.05) and wound healing complications (27.9% versus 16%; P < 0.05). Intraoperative hypothermia predicted SSI (OR, 2.567; 95% CI, 1.367 to 4.818; P < 0.05) and delayed wound healing (OR, 2.023; 95% CI, 1.053 to 3.884; P < 0.05). Longer duration of hypothermia significantly correlated with SSI, with an average 103 minutes versus 77 minutes ( P < 0.05)., Conclusions: This study demonstrates that intraoperative hypothermia is a significant risk factor for postoperative infection in postmastectomy implant-based breast reconstruction. Maintaining strict normothermia during implant-based breast reconstruction procedures may improve patient outcomes by reducing the risk of postoperative infection and delayed wound healing., Clinical Question/level of Evidence: Risk, II., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Macrophages play critical roles in inflammation and tissue homeostasis, and their functions are regulated by various autocrine, paracrine, and endocrine factors. We have previously shown that CTRP6, a secreted protein of the C1q family, targets both adipocytes and macrophages to promote obesity-linked inflammation. However, the gene programs and signaling pathways directly regulated by CTRP6 in macrophages remain unknown. Here, we combine transcriptomic and phosphoproteomic analyses to show that CTRP6 activates inflammatory gene programs and signaling pathways in mouse bone marrow-derived macrophages (BMDMs). Treatment of BMDMs with CTRP6 upregulated proinflammatory, and suppressed the antiinflammatory, gene expression. We also showed that CTRP6 activates p44/42-MAPK, p38-MAPK, and NF-κB signaling pathways to promote inflammatory cytokine secretion from BMDMs, and that pharmacologic inhibition of these signaling pathways markedly attenuated the effects of CTRP6. Pretreatment of BMDMs with CTRP6 also sensitized and potentiated the BMDMs response to lipopolysaccharide (LPS)-induced inflammatory signaling and cytokine secretion. Consistent with the metabolic phenotype of proinflammatory macrophages, CTRP6 treatment induced a shift toward aerobic glycolysis and lactate production, reduced oxidative metabolism, and elevated mitochondrial reactive oxygen species production in BMDMs. Importantly, in accordance with our in vitro findings, BMDMs from CTRP6-deficient mice were less inflammatory at baseline and showed a marked suppression of LPS-induced inflammatory gene expression and cytokine secretion. Finally, loss of CTRP6 in mice also dampened LPS-induced inflammation and hypothermia. Collectively, our findings suggest that CTRP6 regulates and primes the macrophage response to inflammatory stimuli and thus may have a role in modulating tissue inflammatory tone in different physiological and disease contexts., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Hypothermia in older patients is a serious symptom, with high morbidity and mortality, and often an atypical presentation of an underlying problem. The most common causes are an infection and exposure to extreme cold ('accidental hypothermia'), but there are other, less common causes. These two cases show hypothermia as one of the symptoms in atypical presentations of underlying conditions. It is important to run diagnostics for infectious diseases and other underlying causes, and start antibiotics promptly. If there is no response to antibiotics and diagnostics do not reveal evidence of an infection, clinicians need to consider other causes of hypothermia.

Brachial plexus avulsion (BPA) is a combined injury involving the central and peripheral nervous systems. Patients with BPA often experience severe neuropathic pain (NP) in the affected limb. NP is insensitive to the existing treatments, which makes it a challenge to researchers and clinicians. Accumulated evidence shows that a BPA-induced pain state is often accompanied by sympathetic nervous dysfunction, which suggests that the excitation state of the sympathetic nervous system is correlated with the existence of NP. However, the mechanism of how somatosensory neural crosstalk with the sympathetic nerve at the peripheral level remains unclear. In this study, through using a novel BPA C7 root avulsion mouse model, we found that the expression of BDNF and its receptor TrκB in the DRGs of the BPA mice increased, and the markers of sympathetic nervous system activity including α1 and α2 adrenergic receptors (α1-AR and α2-AR) also increased after BPA. The phenomenon of superexcitation of the sympathetic nervous system, including hypothermia and edema of the affected extremity, was also observed in BPA mice by using CatWalk gait analysis, an infrared thermometer, and an edema evaluation. Genetic knockdown of BDNF in DRGs not only reversed the mechanical allodynia but also alleviated the hypothermia and edema of the affected extremity in BPA mice. Further, intraperitoneal injection of adrenergic receptor inhibitors decreased neuronal excitability in patch clamp recording and reversed the mechanical allodynia of BPA mice. In another branch experiment, we also found the elevated expression of BDNF, TrκB, TH, α1-AR, and α2-AR in DRG tissues from BPA patients compared with normal human DRGs through western blot and immunohistochemistry. Our results revealed that peripheral BDNF is a key molecule in the regulation of somatosensory-sympathetic coupling in BPA-induced NP. This study also opens a novel analgesic target (BDNF) in the treatment of this pain with fewer complications, which has great potential for clinical transformation., (© 2023. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

The present study aimed to investigate the association between intraoperative body temperature and prolonged length of stay (PLOS) after free flap reconstruction. A total of 753 patients who underwent head and neck surgery with free flap reconstruction were collected and randomly assigned into primary and validation cohorts. In the primary cohort, univariable and multivariable analyses were conducted to evaluate associations between intraoperative time-weighted (TW) temperature (TW average [TWA] temperature, TW hypothermia and TW hyperthermia) and PLOS. Nomograms were developed with and without intraoperative TW temperature, and validated in the validation cohort. Severe intraoperative TW hypothermia (OR = 1.004; 95% CI: 1.000, 1.007; p = 0.032) was identified as an independent risk factor for PLOS. Intraoperative TWA temperature and TW hypothermia showed linear related predictive effect for PLOS. The nomogram incorporating intraoperative TW temperature showed higher C-index (0.652, 95% CI: 0.591, 0.713) and improved net reclassification improvement for non-event (0.277, 95% CI: 0.118, 0.435; p < 0.001). Lower TWA temperature with mild TW hypothermia had a preventive effect on PLOS with a linear association, which may provide a modified range for intraoperative temperature management. The proposed nomogram incorporating intraoperative TW temperature could be used to develop personalized preventive strategies for PLOS after free flap reconstruction. IRB NUMBER: SYSEC-KY-KS-2022-037. CLINICAL TRIAL REGISTRATION NUMBER: Not applicable., (Copyright © 2023 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives: Predicting neurodevelopmental outcome for neonates with hypoxic-ischemic encephalopathy (HIE) is important for clinical decision-making, care planning, and parent communication. We examined the relationship between EEG background and neurodevelopmental outcome among children enrolled in a trial of erythropoietin or placebo for neonates with HIE treated with therapeutic hypothermia., Methods: Participants had EEG recorded throughout hypothermia. EEG background was classified as normal, discontinuous, or severely abnormal (defined as burst suppression, low voltage suppressed, or status epilepticus) at 5 1-hour epochs: onset of recording, 24, 36, 48, and 72 hours after birth. The predominant background pattern during the entire continuous video EEG monitoring recording was calculated using the arithmetic mean of the 5 EEG background ratings (normal = 0; discontinuous = 1; severely abnormal = 2) as follows: "predominantly normal" (mean = 0), "normal/discontinuous" (0 < mean<1), "predominantly discontinuous" (mean = 1), "discontinuous/severely abnormal" (1 < mean<2), or "predominantly severely abnormal" (mean = 2). Primary outcome was death or neurodevelopmental impairment (NDI) defined as cerebral palsy, Gross Motor Function Classification Score ≥1, or cognitive score <90 on Bayley Scales of Infant Toddler Development, third edition at age 2 years. Neurodevelopment was also categorized into a 5-level ordinal measure: no, mild, moderate, severe NDI, or death for secondary analysis. We used generalized linear regression models with robust standard errors to assess the relative risk of death or NDI by EEG background in both unadjusted and adjusted analyses controlling for the effects of treatment group, sex, HIE severity, and study recruitment site., Results: Among 142 neonates, the predominant background EEG pattern was predominantly normal in 35 (25%), normal/discontinuous in 68 (48%), predominantly discontinuous in 11 (7.7%), discontinuous/severely abnormal in 16 (11%), and predominantly severely abnormal in 12 (8.5%). Increasing severity of background across monitoring epochs was associated with increasingly worse clinical outcomes. Children with severe EEG background abnormality at any time point (n = 36, 25%) were significantly more likely to die or have severe NDI at 2 years (adjusted relative risk: 7.95, 95% CI 3.49-18.12)., Discussion: EEG background is strongly associated with NDI at age 2 years. These results can be used to assist health care providers to plan follow-up care and counsel families for decision-making related to goals of care., (© 2023 American Academy of Neurology.)

Aim: The aim of the study was to determine whether overcooling (temperature <33°C) during passive hypothermia when transporting neonates with perinatal asphyxia increased the risk of short-term neurological injury., Methods: A retrospective observational study was performed. Newborns transferred to the LaCardio neonatal unit between January 2021 and April 2022 with moderate and severe perinatal asphyxia and who received passive hypothermia during transport were included. A temperature of <33°C was considered overcooling. A composite outcome of neurological injury was defined by the presence of abnormalities on brain magnetic resonance imaging, video telemetry, seizure before discharge or both., Results: The study included 101 newborns. A total of 18 neonates had a temperature <33°C after transportation. Neurological injuries were present in 21.8% of the temperature <33°C group and 78.2% of the temperature ≥33°C group. Temperature <33°C at the end of transport (aOR 9.2, 95% CI 1.1-77.3) were associated with neurological injury before discharge from the unit., Conclusion: During transportation, overcooling in neonates with asphyxia increases the risk of neurological injury before discharge from the neonatal unit. It is important to qualify the transport team with adequate training and equipment for therapeutic hypothermia., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Hypothermia develops during systemic anaphylaxis in rodents. The aim of this study was to elucidate the mechanism for the hypothermia by assessing the roles of locomotor activity, tail heat dissipation, heat production in the brown adipose tissue (BAT) activity, and chemical mediators during ovalbumin-induced anaphylactic hypotension in awake rats. We measured the core body temperature (T core ) and mean blood pressure (MBP), along with the surface temperature of the interscapular region (T iScap ), an indirect measure of BAT activity, and the tail (T tail ). During anaphylaxis, MBP decreased to the nadir of 53 ± 2 mmHg at 8 min with recovery toward baseline. T core began to decrease at 7.5 min with the nadir of 36.1 ± 0.2°C at 30 min from the baseline of 38.0 ± 0.1°C. T iScap also significantly decreased, but its onset was preceded by that of T core . T tail decreased after antigen, suggesting the absence of increased heat dissipation from the tail. The physical activity, as evaluated by moved distances, did not decrease until 20 min after antigen, followed by a progressive decrease. Reduced movement using a restraint maneuver not only reduced T core in nonsensitized rats but also augmented the anaphylactic hypothermia in the early phase (1.5-18 min) in sensitized rats. Combined antagonism against platelet-activating factor (PAF) and histamine H 1 receptors abolished antigen-induced hypotension but only attenuated hypothermia. In conclusion, decreased locomotor activity, but not tail heat dissipation or decreased BAT activity, may at least in part contribute to this hypothermia. PAF and histamine are involved mainly in hypotension but only partly in hypothermia during rat anaphylaxis. NEW & NOTEWORTHY Anaphylactic shock is a life-threatening systemic hypotension. Hypothermia is observed during systemic anaphylaxis of rats. We determined the mechanism as follows: decreased locomotor activity, but not tail heat dissipation or decreased BAT activity, may at least in part contribute to this hypothermia. PAF and histamine are involved mainly in hypotension, but only partly in hypothermia during rat anaphylaxis.

Introduction: Perinatal asphyxia is one of the three most important causes of neonatal mortality and morbidity. Therapeutic hypothermia represents the standard treatment for infants with moderate-severe perinatal asphyxia, resulting in reduction in the mortality and major neurodevelopmental disability. So far, data in the literature focusing on the endocrine aspects of both asphyxia and hypothermia treatment at birth are scanty, and many aspects are still debated. Aim of this narrative review is to summarize the current knowledge regarding the short- and long-term effects of perinatal asphyxia and of hypothermia treatment on the endocrine system, thus providing suggestions for improving the management of asphyxiated children., Results: Involvement of the endocrine system (especially glucose and electrolyte disturbances, adrenal hemorrhage, non-thyroidal illness syndrome) can occur in a variable percentage of subjects with perinatal asphyxia, potentially affecting mortality as well as neurological outcome. Hypothermia may also affect endocrine homeostasis, leading to a decreased incidence of hypocalcemia and an increased risk of dilutional hyponatremia and hypercalcemia., Conclusions: Metabolic abnormalities in the context of perinatal asphyxia are important modifiable factors that may be associated with a worse outcome. Therefore, clinicians should be aware of the possible occurrence of endocrine complication, in order to establish appropriate screening protocols and allow timely treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Improda, Capalbo, Poloniato, Garbetta, Dituri, Penta, Aversa, Sessa, Vierucci, Cozzolino, Vigone, Tronconi, del Pistoia, Lucaccioni, Tuli, Munarin, Tessaris, de Sanctis and Salerno.)

Objectives: This study aimed to identify the predictors of neurologic outcomes and mortality in physically abused and unintentionally injured children admitted to intensive care units (ICUs)., Methods: All maltreated children were admitted to pediatric, neurosurgical, and trauma ICUs between 2001 and 2019. Clinical factors, including age, sex, season of admission, identifying settings, injury severity score, etiologies, length of stay in the ICU, neurologic outcomes, and mortality, were analyzed and compared between the physically abused and unintentionally injured groups. Neurologic assessments were conducted using the Pediatric Cerebral Performance Category scale. The study was approved by the Institutional Review Board of Chang Gung Memorial Hospital and the Ethics Committee waived the requirement for informed consent because of the anonymized nature of the data., Results: A total of 2481 children were investigated; of them, there were 480 (19.3%) victims admitted to the ICUs, including 156 physically abused and 324 unintentionally injured. Age, history of prematurity, clinical outcomes, head injury, neurosurgical interventions, clinical manifestations, brain computed tomography findings, and laboratory findings significantly differed between them (all p < 0.05). Traumatic brain injury was the major etiology for admission to the ICU. The incidence of abusive head trauma was 87.1% among the physically abused group. Only 46 (29.4%) and 268 (82.7%) cases achieved favorable neurologic outcomes in the physically abused and unintentionally injured groups, respectively. Shock within 24 h, spontaneous hypothermia (body temperature, < 35 °C), and post-traumatic seizure were strongly associated with poor neurologic outcomes and mortality in both groups., Conclusions: Initial presentation with shock, spontaneous hypothermia at ICU admission, and post-traumatic seizure were associated with poor neurologic outcomes and mortality in physically abused and unintentionally injured children., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Aim: To evaluate delivery room (DR) interventions to prevent hypothermia and improve outcomes in preterm newborn infants <34 weeks' gestation., Methods: Medline, Embase, CINAHL and CENTRAL were searched till 22nd July 2022. Randomized controlled trials (RCTs), non-RCTs and quality improvement studies were considered. A random effects meta-analysis was performed, and the certainty of evidence was evaluated using GRADE guidelines., Results: DR temperature of ≥23 °C compared to standard care improved temperature outcomes without an increased risk of hyperthermia (low certainty), whereas radiant warmer in servo mode compared to manual mode decreased mean body temperature (MBT) (moderate certainty). Use of a plastic bag or wrap (PBW) improved normothermia (low certainty), but with an increased risk of hyperthermia (moderate certainty). Plastic cap improved normothermia (moderate certainty) and when combined with PBW improved MBT (low certainty). Use of a cloth cap decreased moderate hypothermia (low certainty). Though thermal mattress (TM) improved MBT, it increased risk of hyperthermia (low certainty). Heated-humidified gases (HHG) for resuscitation decreased the risk of moderate hypothermia and severe intraventricular hemorrhage (very low to low certainty). None of the interventions was shown to improve survival, but sample sizes were insufficient., Conclusions: DR temperature of ≥23 °C, radiant warmer in manual mode, use of a PBW and a head covering is suggested for preterm newborn infants <34 weeks' gestation. HHG and TM could be considered in addition to PBW provided resources allow, in settings where hypothermia incidence is high. Careful monitoring to avoid hyperthermia is needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Neonatal hypoxic-ischemic encephalopathy (HIE) is the primary reason for neonatal mortality and prolonged disablement. Currently, hypothermia is the only approved clinical treatment available for HIE. However, hypothermia's limited therapeutic efficacy and adverse effects suggest an urgent need to advance our knowledge of its molecular pathogenesis and develop novel therapies. The leading cause of HIE is impaired cerebral blood flow and oxygen deprivation-initiated primary and secondary energy failure. Lactate was traditionally regarded as a marker of energy failure or a waste product of anaerobic glycolysis. Recently, the beneficial aspects of lactate as supplementary energy for neurons have been demonstrated. Under the conditions of HI, lactate supports various functions of neuronal cells, including learning and memory formation, motor coordination, and somatosensory. Furthermore, lactate contributes to the regeneration of blood vessels and has shown its beneficial effects on the immune system. This review first introduces the hypoxic or ischemic events-induced fundamental pathophysiological changes in HIE and then discusses the potential neuroprotective properties of lactate for the treatment and prevention of HIE. Finally, we discuss the possible protective mechanisms of lactate in the context of the pathological features of perinatal HIE. We conclude that exogenous and endogenous lactate exert neuroprotective effects in HIE. Lactate administration may be a potential approach to treating HIE injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The current American Heart Association 2022 guidelines recommend actively preventing fever by targeting a temperature ≤37.5°C for comatose patients after cardiac arrest. Contemporary randomized controlled trials (RCTs) show conflicting results regarding the benefit of targeted hypothermia (TH). We performed this updated meta-analysis of RCTs to evaluate the role of hypothermia in patients after a cardiac arrest. We searched Cochrane, MEDLINE, and EMBASE from inception to December 2022. Trials with patients randomly allocated for targeted temperature monitoring and reported neurologic and mortality outcomes were included. Statistical analysis was performed using Cochrane Review Manager using the random-effects model and calculated the pooled risk ratios of outcomes using the Mantel-Haenszel method. A total of 12 RCTs and 4,262 patients were included in the review. Compared with normothermia, the TH group had significantly improved neurologic outcomes (risk ratio 0.90, 95% confidence interval 0.83 to 0.98). However, no significant difference in mortality was observed (risk ratio 0.97, 95% confidence interval 0.90 to 1.06) between the groups. This meta-analysis supports the role of TH in patients after a cardiac arrest, especially secondary to improvement in neurologic outcomes., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Early closure of the meningocele, meningomyelocele, is essential to prevent complications such as hypothermia, infection in the postnatal period. But for some reasons, it is not always possible to repair early. The possibility of malign transformation should be considered in long-term due to nonhealing ulcers and cerebrospinal fluid (CSF) fistula and frequent infections in an adult patient with meningomyelocele. The possibility of conversion to malignancy in the control of an untreated meningomyelocele patient with (CSF) drainage should be especially kept in mind., Case Description: A case is described of a malignant transformation at the site of a myelomeningocele in a 22-year-old woman. The lumbosacral region was deformed by a large meningomyelocele 10 cm in diameter, with areas of scar and ulcer. For 7 years prior to this presentation, the lesion was a large fistula in the roof of the open myelomeningocele. She underwent continuous CSF draining. A biopsy was done which revealed it as squamous cell carcinoma., Conclusion: Early closure of meningocele, meningomyelocele is essential to prevent complications such as hypothermia, infection in the postnatal period. Also, especially if there is continuous CSF exposure, the possibility of malignant change should be kept in mind in neglected cases presenting in an adult.

Study Objective: The effect of perioperative body temperature derangement on postoperative delirium remains unclear. This study aimed to evaluate the association between intraoperative body temperature and postoperative delirium in patients having noncardiac surgery., Design: Single-center retrospective observational study., Setting: Tertiary university hospital., Patient: Adult patients who had major noncardiac surgery under general anesthesia for at least two hours between 2019 and 2021., Interventions: Patients were classified into three groups according to their intraoperative time-weighted average body temperature: severe hypothermia (<35.0 °C), mild hypothermia (35.0 °C-36.0 °C), and normothermia (≥36.0 °C) groups., Measurements: The primary outcome was the risk of delirium occurring within seven days after surgery, which was compared using logistic regression analysis. A multivariable procedure was performed adjusting for potential confounders including demographics, history of hypertension, diabetes, atrial fibrillation or flutter, myocardial infarction, congestive heart failure, and stroke or transient ischemic attack, preoperative use of antidepressants and statins, preoperative sodium imbalance, high-risk surgery, emergency surgery, duration of surgery, and red blood cell transfusion. Cox regression analysis was also performed using the same covariates., Main Results: Among 27,674 patients analyzed, 5.5% experienced postoperative delirium. The incidence rates of delirium were 6.2% (63/388) in the severe hypothermia group, 6.4% (756/11779) in the mild hypothermia group, and 4.6% (712/15507) in the normothermia group. Compared with the normothermia group, the risk of delirium was significantly higher in the severe hypothermia (adjusted odds ratio, 1.43; 95% confidence interval, 1.04-1.97) and mild hypothermia (1.15; 1.02-1.28) groups. The mild hypothermia group also had a significantly increased risk of cumulative development of delirium than the normothermia group (adjusted hazard ratio 1.14; 95% confidence interval, 1.03-1.26)., Conclusions: Intraoperative hypothermia (even mild hypothermia) was significantly associated with an increased risk of postoperative delirium., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Sudden unexpected death in epilepsy (SUDEP) has been linked to respiratory dysfunction, but the mechanisms underlying this association remain unclear. Here we found that both focal and generalized convulsive seizures (GCSs) in epilepsy patients caused a prolonged decrease in the hypercapnic ventilatory response (HCVR; a measure of respiratory CO 2 chemoreception). We then studied Scn1a R1407X /+ (Dravet syndrome; DS) and Scn8a N1768D /+ (D/+) mice of both sexes, two models of SUDEP, and found that convulsive seizures caused a postictal decrease in ventilation and severely depressed the HCVR in a subset of animals. Those mice with severe postictal depression of the HCVR also exhibited transient postictal hypothermia. A combination of blunted HCVR and abnormal thermoregulation is known to occur with dysfunction of the serotonin (5-hydroxytryptamine; 5-HT) system in mice. Depleting 5-HT with para -chlorophenylalanine (PCPA) mimicked seizure-induced hypoventilation, partially occluded the postictal decrease in the HCVR, exacerbated hypothermia, and increased postictal mortality in DS mice. Conversely, pretreatment with the 5-HT agonist fenfluramine reduced postictal inhibition of the HCVR and hypothermia. These results are consistent with the previous observation that seizures cause transient impairment of serotonergic neuron function, which would be expected to inhibit the many aspects of respiratory control dependent on 5-HT, including baseline ventilation and the HCVR. These results provide a scientific rationale to investigate the interictal and/or postictal HCVR as noninvasive biomarkers for those at high risk of seizure-induced death, and to prevent SUDEP by enhancing postictal 5-HT tone. SIGNIFICANCE STATEMENT There is increasing evidence that seizure-induced respiratory dysfunction contributes to the pathophysiology of sudden unexpected death in epilepsy (SUDEP). However, the cellular basis of this dysfunction has not been defined. Here, we show that seizures impair CO 2 chemoreception in some epilepsy patients. In two mouse models of SUDEP we found that generalized convulsive seizures impaired CO 2 chemoreception, and induced hypothermia, two effects reported with serotonergic neuron dysfunction. The defects in chemoreception and thermoregulation were exacerbated by chemical depletion of serotonin and reduced with fenfluramine, suggesting that seizure-induced respiratory dysfunction may be due to impairment of serotonin neuron function. These findings suggest that impaired chemoreception because of transient inhibition of serotonergic neurons may contribute to the pathophysiology of SUDEP., (Copyright © 2023 the authors.)

Objective: Hypothermia is common among trauma patients and can lead to a serious rise in morbidity and mortality. This study was performed to investigate the effect of active and passive warming measures implemented in the prehospital phase on the body temperature of trauma patients., Methods: In a multicenter, multinational prospective observational design, the effect of active and passive warming measures on the incidence of hypothermia was investigated. Adult trauma patients who were transported by helicopter emergency medical services (HEMS) or ground emergency medical services with an HEMS physician directly from the scene of injury were included. Four HEMS/ground emergency medical services programs from Canada, the United States, and the Netherlands participated., Results: A total of 80 patients (n = 20 per site) were included. Eleven percent had hypothermia on presentation, and the initial evaluation occurred predominantly within 60 minutes after injury. In-line fluid warmers and blankets were the most frequently used active and passive warming measures, respectively. Independent risk factors for a negative change in body temperature were transportation by ground ambulance (odds ratio = 3.20; 95% confidence interval, 1.06-11.49; P = .03) and being wet on initial presentation (odds ratio = 3.64; 95% confidence interval, 0.99-13.36; P = .05)., Conclusion: For adult patients transported from the scene of injury to a trauma center, active and passive warming measures, most notably the removal of wet clothing, were associated with a favorable outcome, whereas wet patients and ground ambulance transport were associated with an unfavorable outcome with respect to temperature., (Copyright © 2023 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.)

Background: Stroke is a major global public health problem, affecting 13.7 million people worldwide. Previous studies have found a neuroprotective effect of hypothermia therapy and the efficacy and safety of combined hypothermia and mechanical thrombectomy or thrombolysis in the treatment of ischemic stroke have also attracted attention., Objective: In the present research, the authors conducted a meta-analysis to comprehensively assess the safety and efficacy of hypothermia combining mechanical thrombectomy or thrombolysis in the treatment of ischemic stroke., Methods: Articles published from January 2001 to May 2022 were searched from Google Scholar, Baidu Scholar and PubMed to evaluate the clinical significance of hypothermia treatment in ischemic stroke. Complications, short-term mortality, and the modified Rankin Scale (mRS) in the full text was extracted., Results: 89 publications were selected and 9 among them were included in this study with sample size of 643. All selected studies are in accordance with the inclusion criteria. Forest plot of clinical characteristics was as follows: complications (RR = 1.132, 95% CI 0.942‒1.361, p = 0.186, I 2  = 37.2%), mortality within 3 months (RR = 1.076, 95% CI 0.694‒1.669, p = 0.744, I 2  = 0.00%), mRS ≤ 1 at 3 months (RR = 1.138, 95% CI 0.829‒1.563, p = 0.423, I 2  = 26.0%), mRS ≤ 2 at 3 months (RR = 1.672, 95% CI 1.236‒2.263, p = 0.001, I 2 =49.6%) and mRS ≤ 3 at 3 months (RR = 1.518, 95% CI 1.128‒2.043, p = 0.006, I 2  = 0.00%). The funnel plot suggested that there was no significant publication bias in the meta-analysis on complications, mortality within 3 months, mRS ≤ 1 at 3 months and mRS ≤ 2 at 3 months., Conclusion: In summary, the results showed that hypothermia treatment was correlated with mRS ≤ 2 at 3 months, but not linked with complications and mortality within 3 months., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: Studies have identified perioperative hypothermia as a risk factor for impaired wound healing, increased hospital length of stay, and surgical site infection. This study examines the effect of intraoperative hypothermia on postoperative outcomes in autologous microvascular free flap breast reconstruction., Methods: This was a retrospective review of 55 patients who experienced intraoperative hypothermia, defined as less than 35.0°C core body temperature and 99 normothermic patients who underwent autologous-based microvascular free flap breast reconstruction from 2013 to 2021. Demographics, comorbidities, smoking status, intraoperative warming devices, type of autologous reconstruction, hypothermia (and its duration), and length of surgery were collected. The outcomes assessed were infection rate, reoperation within 90 days, skin necrosis, wound healing complications, hematoma, seroma, and readmission within 90 days., Results: In the study population of 154 consecutive patients, 8.4% had type 1 or type 2 diabetes and 3.2% were current smokers. A total of 90.3% of patients (139) underwent deep inferior epigastric perforator flap reconstruction, 7.1% (11) superficial inferior epigastric artery flap reconstruction, and 4 (2.6%) another free flap type. A total of 35.7% of the patients (55) experienced intraoperative hypothermia defined as less than 35.0°C. In the hypothermic group, a higher proportion of patients had wound healing complications (52.7% vs 29.3%, P < 0.05), hematoma (16.4% vs 5.1%, P < 0.05), and readmission for postoperative complications (34.5% vs 14.1%, P < 0.05). There was also a trend toward higher incidence of seroma (7.3% vs 5.1%), surgical site infection (12.7% vs 9.1%), skin necrosis (12.7% vs 9.1%), and unplanned reoperation within 90 days (10.9% vs 7.1%). Further analysis via Firth logistic regression demonstrated intraoperative hypothermia predicted postoperative hematoma (odds ratio [OR], 3.68; 95% confidence interval [CI], 1.17-11.60; P < 0.05), readmission within 90 days (OR, 3.20; 95% CI, 1.45-7.08; P < 0.05), and wound healing complications (OR, 2.69; 95% CI, 1.36-5.33; P < 0.05)., Conclusions: This study demonstrates that intraoperative hypothermia is a significant risk factor for postoperative wound healing complications, hematoma, and readmission within 90 days in autologous breast reconstruction. Because of a finite amount of donor sites, it is important to find ways to minimize the risk of postoperative complications. Our results support that maintaining strict normothermia during autologous breast reconstruction can significantly improve patient outcomes and reduce morbidity., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The pathobiological mechanisms associated with perinatal asphyxia and hypoxic-ischemic encephalopathy are complex and poorly understood. The metabolic effects of therapeutic hypothermia have been partially explored., Methods: We conducted a single-center longitudinal study to investigate the metabolic effects of perinatal asphyxia and hypoxic-ischemic encephalopathy on the urinary metabolome of a group of 12 asphyctic infants over time compared to 22 matched healthy newborns, using untargeted metabolomics based on mass spectrometry., Findings: Over-representation pathway analysis identified the steroidogenesis pathway as being significantly disrupted, with reduced steroid levels in the first three days of life despite treatment with hypothermia. Comparison with matched healthy newborns showed that the urinary steroid content was lower in asphyctic infants before hypothermia. The lysine degradation and carnitine synthesis pathways were also significantly affected., Interpretation: Steroidogenesis is significantly disrupted in asphyctic infants compared to healthy newborns. Given how neurosteroids are involved in neuromodulation and neuroprotection, translational research is warranted on the potential role of neurosteroid-based intervention in asphyctic infants., Funding: None., Competing Interests: Declaration of interests The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Libersa, Marie, Louis Marxer, Ken Zafren, Stephane Oggier, Lorenzo Pucci, and Mathieu Pasquier. Takotsubo cardiomyopathy following complete avalanche burial: a case report. High Alt Med Biol . 24:149-151, 2023.-Takotsubo cardiomyopathy is a transient left ventricular dyskinesia triggered by a stressful physical or emotional event. We report a case of mid-ventricular Takotsubo stress cardiomyopathy in an avalanche victim. The patient was a 41-year-old woman who was completely buried under 1.2 m of snow for 30 minutes. On arrival at the hospital, she was conscious and hypothermic (core temperature 33.7°C). Her ECG showed rapid atrial fibrillation (142 beats/min) that converted to sinus rhythm after rewarming and administration of crystalloids. Echocardiography showed akinesia of the left mid-ventricle with a left ventricular ejection fraction of 41%. At 48-hour follow-up, echocardiography showed an almost complete recovery. During her hospital stay the patient was diagnosed with an acute stress disorder with symptoms of dissociation. She was discharged home after 5 days. At 2-week follow-up echocardiography was normal. Psychological follow-up was normal at 7 months. The physical and psychological stress of the avalanche, as well as hypothermia, were all possible triggers of Takotsubo cardiomyopathy.

Background: Acute brain injured (ABI) patients are at high risk of developing ventilator-associated pneumonia (VAP). However, incidence, risk factors and effects on outcome of VAP are not completely elucidated in this population. The primary aim of this study was to determine the incidence of VAP in a cohort of ABI patients. The secondary objectives included the identification of risk factors for development of VAP, and the impact of VAP on clinical outcomes. Clinical outcomes were defined as intensive care unit length of stay (ICU-LOS), duration of invasive mechanical ventilation (IMV), and ICU mortality., Methods: Pre-planned sub-analysis of the Extubation strategies in Neuro-Intensive care unit (ICU) patients and associations with Outcomes (ENIO) international multi-center prospective observational study. Patients with available data on VAP, who received at least 48 h of IMV and ICU-LOS ≥ 72 h were included., Results: Out of 1512 patients included in the ENIO study, 1285 were eligible for this analysis. The prevalence of VAP was 39.5% (33.7 cases /1000 ventilator-days), with a high heterogeneity across countries and according to the type of brain injury. VAP was significantly more frequent in male patients, in those with smoke habits and when intraparenchymal probe (IP), external ventricular drain (EVD) or hypothermia (p < 0.001) were used. Independent risk factors for VAP occurrence were male gender, the use of IP, hypothermia, and the occurrence of tracheobronchitis during ICU stay. VAP was not an independent risk factor for ICU mortality (Hazard Ratio, HR = 0.71 95%CI 0.43-1.16, p = 0.168), but was independently associated with longer ICU stay (OR = 2.55 95%CI 2.01-3.23, p < 0.001)., Conclusions: VAP is common in ABI patients. Male gender, IP and EVD insertion, tracheobronchitis, and the use of therapeutic hypothermia were significantly associated with VAP occurrence. VAP did not affect mortality but increased ICU-LOS., (© 2023. The Author(s).)

Background: Acute kidney injury (AKI) remains common among infants with hypothermia-treated hypoxic-ischaemic encephalopathy (HIE). Little is known about long-term kidney outcomes following hypothermia treatment. We recently reported that 21% of survivors of hypothermia-treated HIE had decreased estimated glomerular filtration rate (eGFR) based on plasma creatinine in early adolescence. Here, we assessed kidney functions more comprehensively in our population-based cohort of children born in Stockholm 2007-2009 with a history of hypothermia-treated HIE., Methods: At 10-12 years of age, we measured cystatin C (cyst C) to estimate GFR. Children with decreased cyst C eGFR also underwent iohexol clearance examination. We measured urine-albumin/creatinine ratio, blood pressure (BP) and kidney volume on magnetic resonance imaging. Fibroblast growth factor 23 (FGF 23) levels in plasma were assessed by enzyme-linked immunosorbent assay (ELISA). Outcomes were compared between children with and without a history of neonatal AKI., Results: Forty-seven children participated in the assessment. Two children (2/42) had decreased cyst C eGFR, for one of whom iohexol clearance confirmed mildly decreased GFR. One child (1/43) had Kidney Disease Improving Global Outcomes (KDIGO) category A2 albuminuria, and three (3/45) had elevated office BP. Subsequent ambulatory 24-h BP measurement confirmed high normal BP in one case only. No child had hypertension. Kidney volume and FGF 23 levels were normal in all children. There was no difference in any of the parameters between children with and without a history of neonatal AKI., Conclusion: Renal sequelae were rare in early adolescence following hypothermia-treated HIE regardless of presence or absence of neonatal AKI. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s).)

Background: Supraphysiologic oxygen administration causes unfavorable clinical outcomes in various diseases, including traumatic brain injury, post-cardiac arrest syndrome, and acute lung injury. Accidental hypothermia is a critical illness that reduces oxygen demands, and excessive oxygen is likely to emerge. This study aimed to determine whether hyperoxia would be associated with increased mortality in patients with accidental hypothermia., Methods: A post-hoc analysis of a nationwide multicenter prospective observational study (ICE-CRASH study) on patients with accidental hypothermia admitted in 2019-2022 was conducted. Adult patients without cardiac arrest whose core body temperature was < 32 °C and whose arterial partial pressure of oxygen (PaO 2 ) was measured at the emergency department were included. Hyperoxia was defined as a PaO 2 level of 300 mmHg or higher, and 28-day mortality was compared between patients with and without hyperoxia before rewarming. Inverse probability weighting (IPW) analyses with propensity scores were performed to adjust patient demographics, comorbidities, etiology and severity of hypothermia, hemodynamic status and laboratories on arrival, and institution characteristics. Subgroup analyses were conducted according to age, chronic cardiopulmonary diseases, hemodynamic instability, and severity of hypothermia., Results: Of the 338 patients who were eligible for the study, 65 had hyperoxia before rewarming. Patients with hyperoxia had a higher 28-day mortality rate than those without (25 (39.1%) vs. 51 (19.5%); odds ratio (OR) 2.65 (95% confidence interval 1.47-4.78); p < 0.001). IPW analyses with propensity scores revealed similar results (adjusted OR 1.65 (1.14-2.38); p = 0.008). Subgroup analyses showed that hyperoxia was harmful in the elderly and those with cardiopulmonary diseases and severe hypothermia below 28 °C, whereas hyperoxia exposure had no effect on mortality in patients with hemodynamic instability on hospital arrival., Conclusions: Hyperoxia with PaO 2 levels of 300 mmHg or higher before initiating rewarming was associated with increased 28-day mortality in patients with accidental hypothermia. The amount of oxygen to administer to patients with accidental hypothermia should be carefully determined., Trial Registration: The ICE-CRASH study was registered at the University Hospital Medical Information Network Clinical Trial Registry on April 1, 2019 (UMIN-CTR ID, UMIN000036132)., (© 2023. The Author(s).)

Background: Accelerated idioventricular rhythm (AIVR) is a slow ventricular arrhythmia, commonly due to myocardial ischemia in coronary artery disease. It is a transitory rhythm that rarely causes hemodynamic instability or necessitates any specific therapy. Besides, the common predisposing factors for ventricular arrhythmias after open-heart surgery are hemodynamic instability, electrolyte imbalances, hypoxia, hypovolemia, myocardial ischemia and infarction, acute graft closure, reperfusion injury, and administration of inotropes and antiarrhythmic drugs. Here we report a case of AIVR after cardiac surgery, mostly due to hypothermia that to our knowledge, it is the first report., Case Presentation: We describe a 76-year-old man presenting with typical chest pain. Following routine investigations, the patient underwent coronary artery bypass grafting. Postoperatively, he was transferred to the intensive care unit with good hemodynamic status. However, about 3 h later, he developed rhythm disturbances, leading to hemodynamic instability without response to volume replacement or inotropic support. His rhythm was AIVR, although, at first glance, it resembled the left bundle branch block. Given his unstable hemodynamic status, he was emergently transferred to the operating room. Cardiopulmonary bypass (CPB) was resumed for hemodynamic support. After the patient was rewarmed to about 35 ºC, AIVR returned to normal. He was weaned from CPB successfully and with an uneventful hospital course., Conclusions: Hypothermia is a potential cause of rhythm disturbance. Preventing the causes of arrhythmias, including hypothermia, is the best strategy., (© 2023. The Author(s).)

Objectives: Hypothermia is an established method of treating severe forms of perinatal hypoxia in newborns. Some of them develop neonatal encephalopathy, which is associated with high morbidity and mortality. Therefore, prophylaxis of this pathology is important as well as determining environmental factors in mothers of newborns affected by this pathology. The aim of the study was to assess of selected environmental factors in mothers of newborns qualified for hypothermia., Material and Methods: The material consisted of 102 subjects, including 51 mothers of newborns with hypoxic-ischemic encephalopathy referred for hypothermia treatment (group I) and 51 mothers of newborns without signs of hypoxia (group II). The case-control study was carried out in the third level reference centre. It is 1 of 20 centers of therapeutic hypothermia for newborn in Poland. Data was collected based on a data collection sheet. Study groups were compared in terms of demographic and environmental data. The odds ratio (OR) was determined and the logistic regression analysis of univariate and multivariate regression was used to determine the probability of the need for hypothermia in the study group., Results: The groups did not differ in terms of age, BMI and place of living. The need to use hypothermia increased in pregnant women living together with their parents (OR = 6.8, 95% CI: 2.4-19.6) also in case of exposure to factors at the workplace, i.e., noise (OR = 4.1, 95% CI: 1.1-15.5)., Conclusions: Based on the results of our case-control study we postulate to pay attention during preconception care to proper preparation for pregnancy especially in younger women exposed to nuisance in the work environment and at home. In this area postulated activities should include education programs, in close cooperation occupational medicine practitioners and obstetricians even before the conception as a part of pre-conception counseling. Int J Occup Med Environ Health. 2023;36(1):59-68., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Competing Interests: Competing interests: None declared.