Topical frankincense treatment for frostbite based on microcirculation improvements.

ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese traditional medicine frankincense, which can promote blood circulation, is often used to treat skin lesions, including frostbite. AIM OF THE STUDY: To explore the properties of frankincense oil extract (FOE) and its active ingredients and their effect on frostbite wound recovery as an approach to understand the mechanism associated with microcirculation-improvement therapy. MATERIALS AND METHODS: The microcirculation-improving effects of FOE and its active ingredients were evaluated using liquid nitrogen-induced frostbite animal models. The rewarming capacity of FOE on the skin was determined through infrared detection, and frostbite wound healing was evaluated following haematoxylin and eosin (H&E) staining and fibre analysis. Moreover, related factors were examined to determine the anti-apoptotic, anti-inflammatory, and microcirculatory properties of FOE and its active ingredients on affected tissue in the context of frostbite. RESULTS: FOE and its active ingredients rapidly rewarmed wound tissue after frostbite by increasing the temperature. Moreover, these treatments improved wound healing and restored skin structure through collagen and elastin fibre remodelling. In addition, they exerted anti-apoptotic effects by decreasing the number of apoptotic cells, reducing caspase-3 expression, and eliciting anti-inflammatory effects by decreasing COX-2 and ß-catenin expression. They also improved microcirculatory disorders by decreasing HIF-1α expression and increasing CD31 expression. CONCLUSIONS: FOE and its active components can effectively treat frostbite by enhancing microcirculation, inhibiting the infiltration of inflammatory cells, decreasing cell apoptosis, and exerting antinociceptive effects. These findings highlight FOE as a new treatment option for frostbite, providing patients with an effective therapeutic strategy.

Construction and validation of a risk prediction model for soldiers with frostbite in northeast China: a cross-sectional study.

BACKGROUND: One of the challenges of physical training in extreme condition is frostbite, especially in Northeast China. In this study, we aimed to construct a risk prediction model for frostbite among soldiers in Northeast China, and verify its effect. METHODS: 698 participants were selected via convenience sampling from Northeast China from December 2021 to January 2022 (winter). They were randomly divided into a training set (N = 479) and a testing set (N = 202) in a ratio of 7:3. All participants completed a researcher-made questionnaire on frostbite. The prediction model was constructed through the use of Logistic regression analysis, which was used to predict the independent risk factors for frostbite formation and screen significant indicators. The model's performance was assessed using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) to evaluate the prediction efficiency and goodness of fit. RESULTS: The incidence of frostbite in the training set was 19.83% (95 people), all of which were first-degree frostbite. Among them, frostbite in multiple parts was the most common (58.95%), followed by singular body parts like hands (24.21%), ears (11.58%) and feet (5.26%). Single factor logistic regression analyses showed that ambient temperature, ambient wind speed, outdoor stationary time, stationary status, and history of frostbite are independent risk factors that affect the occurrence of frostbite. Furthermore, we constructed the frostbite risk prediction model for soldiers in the northeastern region of China. The area under the receiver operating characteristic curve (AUC) for the risk of frostbite in the training set and testing set was 0.816 (95% CI, 0.770 ~ 0.862) and 0.787 (95% CI, 0.713 ~ 0.860), respectively. The Hosmer-Lemeshow test of the model showed χ2 = 11.328 and P = 0.184 (> 0.05). The DCA curve indicated that most of the clinical net benefits of the model are greater than 0, demonstrating good clinical usefulness. CONCLUSION: The constructed frostbite prediction model can effectively identify soldiers with a higher risk of frostbite. It provided theoretical support for commanders to take preventive measures to reduce the incidence of frostbite among soldiers and was of great clinical guiding significance.

Biophysical evidence that frostbite is triggered on nanocrystals of biogenic magnetite in garlic cloves (Allium sativum).

Trace levels of biologically precipitated magnetite (Fe3O4) nanocrystals are present in the tissues of many living organisms, including those of plants. Recent work has also shown that magnetite nanoparticles are powerful ice nucleation particles (INPs) that can initiate heterogeneous freezing in supercooled water just below the normal melting temperature. Hence there is a strong possibility that magnetite in plant tissues might be an agent responsible for triggering frost damage, even though the biological role of magnetite in plants is not understood. To test this hypothesis, we investigated supercooling and freezing mortality in cloves of garlic (Allium sativum), a species which is known to have moderate frost resistance. Using superconducting magnetometry, we detected large numbers of magnetite INPs within individual cloves. Oscillating magnetic fields designed to torque magnetite crystals in situ and disturb the ice nucleating process produced significant effects on the temperature distribution of supercooling, thereby confirming magnetite's role as an INP in vivo. However, weak oscillating fields increased the probability of freezing, whereas stronger fields decreased it, a result that predicts the presence of magnetite binding agents that are loosely attached to the ice nucleating sites on the magnetite crystals.

Limb Salvage Using Microsurgical Free Tissue Transfer in Severe Frostbite.

PURPOSE: Frostbite is often managed conservatively; however, in severe cases, microsurgical free tissue transfer is required for soft tissue coverage and limb salvage. Given its rarity, the techniques and outcomes of these cases are not well described. The purpose of this report is to present the largest case series, to date, of frostbite injuries requiring microsurgical reconstruction for limb salvage. METHODS: A single-center retrospective review was conducted of all patients who underwent free tissue transfer by a single surgeon from 2008 to 2022. Patients of all ages were included if they suffered a frostbite injury requiring free tissue transfer. Demographics, operative details, and surgical outcomes were recorded. RESULTS: Eight patients with frostbite injuries were included in the report. Patients had frostbite injuries either to the lower extremities (n = 4) or to both upper and lower extremities (n = 4). Sixteen free flaps were done in total including four paired chimeric and eight single free flaps. Flap recipient sites included knees (n = 5), foot/ankle (n = 3), dorsal hands (n = 2), and thumbs (n = 2). All 16 flaps survived. Five patients had complications: four with major complications requiring operative management and two with minor complications requiring conservative management. Mean follow-up time was 505.7 days (range 115-1564). All lower extremity reconstructions were able to weight-bear at an average of 125.2 days post-injury (range 87-164). CONCLUSIONS: This case series demonstrates that free tissue transfer is a robust option for soft tissue coverage and functional limb salvage in patients with severe frostbite injuries to both upper and lower extremities.

Cold-Induced Vasodilation, Rewarming, and Dexterity Impairment Following Second-Degree Frostbite.

Frostbite, a severe cold injury resulting from exposure to subfreezing temperatures, damages the skin and underlying tissues of the affected area and ranges in severity from first to fourth degree. This case report investigates the impact of second-degree frostbite suffered by a marine during winter training on cold-induced vasodilation (CIVD). Comparisons of CIVD before and after the injury revealed significant alterations in CIVD responses. CIVD, a physiological mechanism characterized by blood vessel dilation in response to cold exposure, plays a crucial role in operating in cold-weather environments and enhancing dexterity. The marine exhibited prolonged CIVD onset time, lower finger temperatures, increased pain sensations, and diminished dexterity after the frostbite injury during follow-up CIVD testing. The findings suggest that the frostbite-induced damage possibly compromised the microvascular function, contributing to the observed changes in CIVD. The marine reported persistent cold sensitivity and difficulty in maintaining hand warmth when assessed postinjury. This case underscores the potential long-term consequences of frostbite on CIVD and manual dexterity, emphasizing the importance of understanding these physiological changes for individuals engaged in cold-weather activities, particularly for military and occupational personnel.

Cold Injury.

Cold injury has been documented for centuries and remains a concern for military personnel, winter recreationalists, and urban homeless populations. Treatment advances in the last decades have included thrombolytic and prostaglandin therapies however the mainstay remains early recognition and rapid rewarming. This chapter focuses on frostbite, with a brief overview of other cold related conditions.

A Case of Frostbite on Hands Due to Liquid Nitrogen.

This study examines a rare case of frostbite on the hands caused by liquid nitrogen, focusing on the scar maturation process. Frostbite is typically less prone to abnormal scarring compared to burns, and this report contrasts the differences in scar maturation between the two. A 31-year-old male hospital employee sustained first- to second-degree frostbite on his gloved hands from a 20-s exposure to liquid nitrogen while changing a cylinder. Conservative treatment was applied, and the patient was monitored for 9 months. The deeply affected area took 50 days to epithelialize but healed without hypertrophic scarring. A mild extension contracture was noted in the distal interphalangeal joint of the right index finger, but the skin remained supple and soft. Incidents of liquid nitrogen-induced frostbite are uncommon, with only 14 cases reported in PubMed previously. In frostbite, the wound healing involves a slow replacement of damaged connective tissue, which acts as an internal splint, reducing wound contraction. This contrasts with burns, where rapid connective tissue replacement occurs, often leading to significant wound contraction due to the presence of myofibroblasts in granulation tissue. In the presented case, the slow healing process and minimal wound contraction led to mature scarring without abnormalities, underlining a distinctive healing trajectory in frostbite injuries compared to burns.

Elucidation of the Role of TRPV1, VEGF-A, TXA2, Redox Homeostasis, and Inflammatory Cascades in Protection against Cold Injuries by Herbosomal-Loaded PEG-Poloxamer Topical Formulation.

High-altitude regions, cold deserts, permafrost regions, and the polar region have some of the severest cold conditions on earth and pose immense perils of cold injuries to exposed individuals. Accidental and unintended exposures to severe cold, either unintentionally or due to occupational risks, can greatly increase the risk of serious conditions including hypothermia, trench foot, and cold injuries like frostbite. Cold-induced vasoconstriction and intracellular/intravascular ice crystal formation lead to hypoxic conditions at the cellular level. The condition is exacerbated in individuals having inadequate and proper covering and layering, particularly when large area of the body are exposed to extremely cold environments. There is a paucity of preventive and therapeutic pharmacological modalities that have been explored for managing and treating cold injuries. Given this, an efficient modality that can potentiate the healing of frostbite was investigated by studying various complex pathophysiological changes that occur during severe cold injuries. In the current research, we report the effectiveness and healing properties of a standardized formulation, i.e., a herbosomal-loaded PEG-poloxamer topical formulation (n-HPTF), on frostbite. The intricate mechanistic pathways modulated by the novel formulation have been elucidated by studying the pathophysiological sequelae that occur following severe cold exposures leading to frostbite. The results indicate that n-HPTF ameliorates the outcome of frostbite, as it activates positive sensory nerves widely distributed in the epidermis transient receptor potential vanilloid 1 (TRPV1), significantly (p < 0.05) upregulates cytokeratin-14, promotes angiogenesis (VEGF-A), prominently represses the expression of thromboxane formation (TXA2), and significantly (p < 0.05) restores levels of enzymatic (glutathione reductase, superoxide dismutase, and catalase) and nonenzymatic antioxidants (glutathione). Additionally, n-HPTF attenuates oxidative stress and the expression of inflammatory proteins PGF-2α, NFκB-p65, TNF-α, IL-6, IL-1ß, malondialdehyde (MDA), advanced oxidative protein products (AOPP), and protein carbonylation (PCO). Masson's Trichrome staining showed that n-HPTF stimulates cellular proliferation, and increases collagen fiber deposition, which significantly (p < 0.05) promotes the healing of frostbitten tissue, as compared to control. We conclude that protection against severe cold injuries by n-HPTF is mediated via modulation of pathways involving TRPV1, VEGF-A, TXA2, redox homeostasis, and inflammatory cascades. The study is likely to have widespread implications for the prophylaxis and management of moderate-to-severe frostbite conditions.

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Frostbite: 2024 Update.

The Wilderness Medical Society convened an expert panel to develop a set of evidence-based guidelines for the prevention and treatment of frostbite. We present a review of pertinent pathophysiology. We then discuss primary and secondary prevention measures and therapeutic management. Recommendations are made regarding each treatment and its role in management. These recommendations are graded on the basis of the quality of supporting evidence and balance between the benefits and risks or burdens for each modality according to methodology stipulated by the American College of Chest Physicians. This is an updated version of the guidelines published in 2019.

Proximal phalanx flexor tendon tenodesis after severe frostbite in a rock climber.

A 32 year-old climber sustained a grade IV frostbite injury to the right hand which required amputation at the neck of the proximal phalanges of all the long fingers. To increase range of motion and strength in the remaining metacarpophalangeal joints, tenodesis of the flexor digitalis superficialis and profundus tendons onto the proximal phalanges was performed. Several revisions for removal of bony spurs, dorsal skin advancement flaps and web space deepening were necessary. After 2 years, the patient achieved 10-0-100° metacarpophalangeal joint range of motion in extension-flexion and could do full body-weight pull-ups on 1 cm deep holds, lift 50 kg on a 2 cm deep hold (normal contralateral side, 40 kg), climb up to F7a routes and use a mechanical 4-finger functional prosthesis.

Update on Cold-Induced Injuries.

Cold-induced injuries are a major challenge for burn surgeons, leading to significant sequelae for the patients including amputations, long-term disability, and death. Rapid assessment and diagnosis are essential for optimal outcomes. Various therapies have emerged to improve outcomes. Topical, oral, and intravenous agents have shown to minimize the impact of cold-induced injuries. Thrombolytics have shown the greatest promise in improving tissue perfusion outcomes in cold-induced injuries. This article provides an update on the evidence-based assessment and management of cold-induced injuries, as well as reviews outcomes and future directions of this challenging pathology.

Oropharyngeal Swelling and Airway Obstruction from Environmental Cold Exposure: A Case Report.

A 19-year-old male presented with facial frostbite and severe oropharyngeal edema after prolonged riding of a snowmobile without any facial covering. The diffuse swelling eventually progressed to airway obstruction, requiring a surgical airway. No alternative explanation was found for his presentation, making this the first case found in the literature of airway obstruction secondary to environmental cold exposure.

Prolonged critical avalanche burial for nearly 23 h with severe hypothermia and severe frostbite with good recovery: a case report.

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.

Dermorphin [D-Arg2, Lys4] (1-4) Amide Alleviates Frostbite-Induced Pain by Regulating TRP Channel-Mediated Microglial Activation and Neuroinflammation.

Cold injury or frostbite is a common medical condition that causes serious clinical complications including sensory abnormalities and chronic pain ultimately affecting overall well-being. Opioids are the first-choice drug for the treatment of frostbite-induced chronic pain; however, their notable side effects, including sedation, motor incoordination, respiratory depression, and drug addiction, present substantial obstacle to their clinical utility. To address this challenge, we have exploited peripheral mu-opioid receptors as potential target for the treatment of frostbite-induced chronic pain. In this study, we investigated the effect of dermorphin [D-Arg2, Lys4] (1-4) amide (DALDA), a peripheral mu-opioid receptor agonist, on frostbite injury and hypersensitivity induced by deep freeze magnet exposure in rats. Animals with frostbite injury displayed significant hypersensitivity to mechanical, thermal, and cold stimuli which was significant ameliorated on treatment with different doses of DALDA (1, 3, and 10 mg/kg) and ibuprofen (100 mg/kg). Further, molecular biology investigations unveiled heightened oxido-nitrosative stress, coupled with a notable upregulation in the expression of TRP channels (TRPA1, TRPV1, and TRPM8), glial cell activation, and neuroinflammation (TNF-α, IL-1ß) in the sciatic nerve, dorsal root ganglion (DRG), and spinal cord of frostbite-injured rats. Treatment with DALDA leads to substantial reduction in TRP channels, microglial activation, and suppression of the inflammatory cascade in the ipsilateral L4-L5 DRG and spinal cord of rats. Overall, findings from the present study suggest that activation of peripheral mu-opioid receptors mitigates chronic pain in rats by modulating the expression of TRP channels and suppressing glial cell activation and neuroinflammation.

Frostbite in the Pediatric Population: A Comprehensive Review and a Prospective Canadian Survey.

INTRODUCTION: Frostbite in the pediatric population, where skeletal maturity has not been achieved, can have important repercussions on subsequent growth. Yet, the optimal management of frostbite injuries in children remains vague. This review aims to summarize the current evidence for frostbite management in children and understand Canadian practice trends on this topic. METHODS: A review using Medline, Scopus, Web of Science, and gray literature was performed to identify relevant literature on the clinical manifestations, diagnostic methods, and treatment options in pediatric frostbite. An online survey was sent to plastic surgeons through the Canadian Society of Plastic Surgeons (CSPS) mailing list to further identify national practices and trends for pediatric frostbite management. RESULTS: A total of 109 articles were reviewed. No article provided a specific algorithm for pediatric frostbite, with existing recommendations suggesting the use of adult guidelines for treating children. Our survey yielded 9 responses and highlighted the rarity of pediatric frostbite cases, with no responder treating more than 10 cases per year. Most (55.6%) do not use a pediatric-specific treatment algorithm, whereas 30% apply adult guidelines. A conservative approach focusing on rewarming (55.6%), limb elevation (50%), and tetanus status verification (66.7%) was predominant. Imaging and surgical interventions seem to be reserved for severe cases. CONCLUSIONS: The current literature for pediatric frostbite management lacks specificity. Canadian practices vary, with a trend toward a conservative approach. The limited evidence and rarity of experience highlight the need for further research, ideally in a collaborative multicentric manner, to create a consensus for pediatric frostbite care.

Development and validation of clinically Mimicable model of frostbite injury-induced chronic pain.

Frostbite, a debilitating condition, significantly affects the well-being of military veterans and high-altitude residents, causing severe clinical complications such as chronic pain that markedly impacts overall quality of life. There has been a notable increase in the development of pre-clinical models for studying frostbite injury, but their suitability for pain evaluation remains limited. The major hurdle in the development of novel therapeutics for the treatment of frostbite-induced chronic pain is the unavailability of well-established preclinical models. In this study, we employed deep-frozen magnets to induce frostbite injury and conducted validation for chronic pain through assessments of face, predictive, and mechanistic validity. Behavioral assays demonstrated that frostbite injury exhibited significant mechanical, thermal & cold hypersensitivity in rats. Further, molecular analysis indicated that frostbite injury triggered the activation of TRP channels (TRPA1, TRPV1 and TRPM8), microgliosis, and neuroinflammation in the dorsal root ganglion (DRG) and spinal cord of rats. Notably, NR2B protein expressions were significantly upregulated in the DRG of injured rats, while no changes were observed in spinal NR2B expressions. Furthermore, the administration of ibuprofen (25, 50, and 100 mg/kg, i.p.) resulted in a significant improvement in behavioral, biochemical, and molecular alterations in frostbite-injured rats. Overall, results suggested that established frostbite model effectively recapitulates face, pharmacological, and mechanistic validity, highlighting its potential for screening future treatment modalities and exploring the intricate mechanisms associated with frostbite-induced chronic pain.