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BackgroundExposure to extremely or moderate low temperatures is associated with increased morbidity and mortality risk. Peripheral vascular disease (PVD) is a slow and progressive circulation disorder. Given that cold temperature causes constriction of the small arteries and veins in the skin, patients who suffer from peripheral circulation problems, like PVD, may be vulnerable to cold injuries. This study aimed to investigate the association between PVD and cold-induced injuries in the winter among Korean adults. We further analyzed the association stratified by body mass index (BMI) classification.MethodsWe used the 2002–2015 National Health Insurance Service-National Sample Cohort data and included a total of 535,186 adults as the study population. Patients with underlying PVD were identified by ICD-10 code I73. Cold-related illnesses were defined by ICD-10 codes (T690, T691, T698, T699, T330 ~ T339, T340 ~ T349, and T350 ~ T357). Body mass index (BMI) was categorized into underweight, normal weight, overweight, and obese.ResultsA total of 23.21% (n = 124,224) were PVD patients, and 0.59% (n = 3154) had cold-induced injuries. PVD patients were more likely to be diagnosed with cold injuries, but it was valid only in the underweight or normal weight groups. After adjusting for age, sex, income, cigarette smoking, alcohol consumption, regular exercise, high blood pressure, and hyperglycemia, PVD patients had a significantly increased odds ratio (OR) for cold injuries [adjusted OR = 1.11; 95% confidence intervals (95% CI): 1.01–1.21]. Increased OR for cold injuries in PVD patients was also observed in adults (adjusted OR = 1.14; 95% CI: 1.03–1.25 in Model 2), but not in the elderly. When we classified study subjects into the four BMI groups, the adjusted OR of cold injuries in PVD patients was significant in the underweight group (OR = 1.83; 95% CI, 1.26–2.66) and normal weight group (OR = 1.15; 95% CI, 1.03–1.27), not in those with overweight and obese. In adults, a consistent result was found in adults in the underweight group (OR = 1.63; 95% CI, 1.08–2.47 in Model 2) and normal weight group (OR = 1.19; 95% CI, 1.07–1.33 in Model 2). In the elderly, the adjusted OR for cold injuries was only significant in the underweight group (OR = 3.37; 95% CI, 1.08–10.53 in Model 2).ConclusionsWe found a significant association between PVD and cold-induced injuries in the general population. BMI modified the association. Thus, the association observed appears to be clinically applicable to PVD patients being low to normal BMI.

Cold injury refers to local or systemic injury caused by a rapid, massive loss of body heat in a cold environment. The incidence of cold injury is high. However, the current situation regarding the diagnosis and treatment of cold injury in our country is not ideal. To standardize and improve the level of clinical diagnosis and treatment of cold injury in China, it is necessary to make a consensus that is practical and adapted to the conditions in China. We used the latest population-level epidemiological and clinical research data, combined with relevant literature from China and foreign countries. The consensus was developed by a joint committee of multidisciplinary experts. This expert consensus addresses the epidemiology, diagnosis, on-site emergency procedures, in-hospital treatment, and prevention of cold injury.

Frostbite is the most common type of traumatic injuries in the cold climate of the Arctic. Post-traumatic recovery of the patients takes a long time and often leads to the loss of the damaged limb. A promising approach for frostbite therapy could be treatment with mesenchymal stem/stromal cells (MSCs), which are widely used in regenerative medicine for different applications. Here, we aimed to discuss the possibility of frostbite treatment with MSCs. The success of MSC use for therapy of different injures depends on multiple factors including the source and functional state of MSCs. These aspects along with strategies for improvement of therapeutic effect of MSC treatment are also discussed in detail.

In spite of the fact that extremity frostbites are a widespread type of injuries in many countries, specialized equipment for frostbite treatment is lacking. Treatment is carried out by conservative methods. The best results are obtained by using thermal isolation of injured tissues and activation of internal warming. It is proposed to initiate deep warming of frostbitten extremities on exposure to low-power microwave radiation. A microwave chamber has been developed to implement this technique. The efficiency of the approach was earlier demonstrated on animals. An example is given of successful treatment of a cold injury of patient hands and feet that allowed amputation to be avoided.

From the French Invasion of Russia in 1812, to Glastonbury festival in 2007, trench foot has been reported, yet the exact nature of the condition remains unclear. This review explores the pathogenesis and treatment of trench foot. Trench foot is considered to be a nonfreezing cold injury often complicated by infection, in which exposure to cold temperatures just above freezing, combined with moisture, results in a peripheral vasoneuropathy. The presence of physical trauma, bacterial or fungal infections, malnutrition, venous hypertension and lymphoedema mean that some individuals are at greater risk of trench foot. Trench foot may be prevented by warming the feet, changing socks, staying active, rubbing the skin with oil and regularly inspecting the feet. Avoiding risk factors may help prevent the condition. The management of trench foot is less clear. Vasodilators such as iloprost and nicotinyl tartrate or sympathectomy may help. Trench foot may lead to necrosis, cellulitis, sepsis and amputation. It remains a poorly understood condition.

Purpose Corneal endothelial cell regeneration varies by species, with nonhuman primates (NHPs) and rabbits displaying low and high proliferative capacities, respectively. Recent studies report that topical application of rho-associated kinase (ROCK) inhibitors accelerates corneal endothelial wound healing in animal models and human patients with endothelial dysfunction. This study determines the regenerative capacity of canine corneal endothelial cells in vivo and their response to a topical ROCK inhibitor, Y27632, after transcorneal freezing. Methods Right eyes of 6 beagles underwent transcorneal freezing; 10 mM ROCK inhibitor Y27632 or vehicle control was applied topically to both eyes at least 4 times daily for 56 days. Endothelial cell density was evaluated by in vivo confocal microscopy, and corneal thickness was measured by Fourier-domain optical coherence tomography (FD-OCT) and ultrasound pachymetry. Results Transcorneal freezing induced severe central corneal edema in dogs, with restoration of transparency occurring within 4 weeks. Y27632 significantly decreased corneal thickness by FD-OCT and ultrasound pachymetry in the acute phase and significantly increased endothelial cell density at days 28 and 42 post-cryoinjury, suggesting faster restoration of endothelial cell recovery. Conclusions Canine corneal endothelial function recovers at a similar rate as NHPs but more slowly than rabbits after cryoinjury. Faster corneal endothelial wound healing was observed by in vivo confocal microscopy and FD-OCT in dogs treated with Y27632 versus vehicle controls. Thus, a canine cryoinjury model may be a useful alternative to NHPs in detecting a response to therapies directed at endothelial regeneration.

Background The lack of improvement in prognosis of accidental hypothermia and neonatal cold injury suggests that a major cause of mortality has not been appreciated. Aim of the article To show that thrombocytopenia that deepens on rewarming under certain conditions is that missing factor. Scientific basis Below 34 °C the first stage of aggregation is accentuated, the platelets are more sensitive to ADP and aggregation studies show an increased response “first stage hyper aggregation”. We have confirmed that the irreversible second stage of platelet aggregation does not occur below 34 °C. On rewarming, the first stage of aggregation is followed by disaggregation. When platelets are warmed to 34 °C the potential exists for the platelets to undergo an irreversible second stage of aggregation “second stage platelet hyper aggregation” that can cause a further drop in platelet count and a bleeding diathesis. This only occurs if the platelets have been sufficiently primed when cold and may not be appreciated if platelet counts are not followed. Significance of this data and correlation with the literature This thesis explains many other open questions. Why has the overall prognosis remained without improvement over the last half century? Why hypothermic cardiac surgery is free of this problem? Why the depth of hypothermia is alone not prognostic? Has following platelet counts been associated with improved prognosis? Why cardiac arrest does not affect prognosis? Why some patients die suddenly after recovering from hypothermia? Why are so many different rewarming techniques used? Why is the prognosis better in hypothermic suicide attempts? What is the pathophysiological explanation for reversible sequestration of platelets to the liver and spleen in hypothermia? Is DIC (diffuse intravascular coagulation) a problem in hypothermia? And how this new approach could improve prognosis? Conclusion Prognosis can be improved by following platelet counts during rewarming. In patients with prolonged hypothermia, this will show a life-threatening drop in such counts easily treated by platelet infusion.

A cold injury can result in devastating outcomes, leading to significant morbidity and loss of distal extremities. Amputations are common after severe frostbite injuries with delayed presentation, often mediated by post-injury arterial thrombosis. Ischemic injuries are managed according to the ischemia time. The most controversial aspect of treating a salvage injury is the time of surgical intervention, which used to be based on the previous management dogma freeze in January, amputate in July. Recently, the paradigm has shifted to early surgical management if the level of viability of the deep structure can be ascertained using 99mTc pertechnetate scintigraphy (99mTc bone scans). We present a case of a finger amputation resulting from a cold injury secondary to a crush injury.

The association between ultraviolet radiation exposure and skin cancer is well established. Limited studies have reported an association between frostbite and the development of non-melanoma skin cancer but evidence for a proven link is insufficient and possible carcinogenic mechanisms have not been fully explored. In this report, 3 cases of non-melanoma skin cancer (1 case of basal cell carcinoma and 2 cases of squamous cell carcinoma of the skin) which developed at a site of previous frostbite caused by exposure to extremely cold temperatures in Astana, the capital city of Kazakhstan, are described.

Peripheral cold injuries have disabled entire armies in the past and, as recently as the Falklands conflict of 1982, jeopardised the success of an entire military operation. They can be divided into those that involve freezing of the peripheral tissue and those that do not, termed Freezing Cold Injury (FCI) and Non-Freezing Cold Injury (NFCI) respectively.This article focuses on the recognition and management of cold injuries in the field. It draws from the current literature, briefly outlining the pathophysiological basis of the two injuries, then focuses on the challenges of field recognition of cold injuries, especially NFCI, which is characterised by a lack of overt physical signs. A framework for field management of these injuries is then outlined, with an emphasis on the contrasting re-warming strategies for FCI and NFCI, and the pharmacological therapies used in each condition.The article is pertinent to those who may train or deploy to an area with temperatures lower than 20° Celsius, the generally accepted temperature below which peripheral cold injuries may occur. It is hoped that improved awareness of the risks coupled with better field recognition and management may reduce the incidence of cold injury, especially in light of recent observations that re-exposure to cold in those with NFCI can cause more significant morbidity, highlighting the importance of getting the diagnosis and management right in the field.

Background Rapid cooling at procurement after cross-clamping has been the cornerstone of organ preservation. NanoICE is a new form of ice that has emerged in the food industry and is providing more efficient cooling and preservation than regular ice. We hypothesize that the use of NanoICE will accelerate the cooling process of the allograft and will be able to maintain a steady low temperature without causing any significant histologic damage. Methods In this randomized pilot study, 14 pigs were used to study the liver core/surface cooling in a non-survival organ procurement operation. Animals were randomly assigned to 1 of 2 groups, each arm involving 7 pigs: (1) crushed-iced normal saline cooling method (control group) and (2) NanoICE cooling method (study group). Surface and core temperatures were measured with temperature probes, and liver biopsies were obtained before cross-clamping and 15 hours after preservation to assess for any evidence and degree of freezing injury. Results NanoICE was able to reduce and sustain lower core temperatures at 30 minutes, 60 minutes, and 15 hours, compared with crushed ice. The degree of histologic damage (reflecting cold injury) at 15 hours after flushing was not significantly different between the 2 methods. Conclusions NanoICE cools the deeper liver parenchyma more quickly and sustains a cooler temperature than regular crushed ice without causing significantly histologic damage. Future research should focus on whether the effect of NanoICE has any impact on graft function and survival.

Background : Myths, misconceptions and a general lack of information surround the use of gloves and mittens in extreme cold environments. Objective . This study assessed how well an assortment of gloves and mittens performed in a very cold environment. Methods . A convenience sample of gloves and mittens were tested in Antarctica during the winter of 2016 using a calibrated thermometer (range: −148°F to +158°F/−100°C to +70°C) three times over a 0.5-mile distance (~20 minutes). A small sensor on a 10-foot-long cable was taped to the radial surface of the distal small finger on the non-dominant hand. The tested clothing was donned over the probe, the maximum temperature inside the glove/mitten was established near a building exit (ambient temperature approximately 54°F/12°C), and the building was exited, initiating the test. The hand was kept immobile during the test. Some non-heated gloves were tested with chemical heat warmers placed over the volar or dorsal wrist. Results . The highest starting (96°F/36°C) and ending (82°F/28°C) temperatures were with electrically heated gloves. The lowest starting temperature was with electrically heated gloves with the power off (63°F/17°C). Non-heated gloves with an inserted chemical hand warmer had the lowest minimum temperature (33°F/1°C). Maximum temperatures for gloves/mittens did not correlate well with their minimum temperature. Conclusions . Coverings that maintained finger temperatures within a comfortable and safe range (at or above 59°F/15°C) included the heated gloves and mittens (including some with the power off) and mittens with liners. Mittens without liners (shell) generally performed better than unheated gloves. Better results generally paralleled the item’s cost. Inserting chemical heat warmers at the wrist increased heat loss, possibly through the exposed area around the warmer. Keywords: clothing; hand warmth; Antarctica; hand protection; hand comfort; cold injury prevention; protective gear Background : Myths, misconceptions and a general lack of information surround the use of gloves and mittens in extreme cold environments. Objective . This study assessed how well an assortment of gloves and mittens performed in a very cold environment. Methods . A convenience sample of gloves and mittens were tested in Antarctica during the winter of 2016 using a calibrated thermometer (range: −148°F to +158°F/−100°C to +70°C) three times over a 0.5-mile distance (~20 minutes). A small sensor on a 10-foot-long cable was taped to the radial surface of the distal small finger on the non-dominant hand. The tested clothing was donned over the probe, the maximum temperature inside the glove/mitten was established near a building exit (ambient temperature approximately 54°F/12°C), and the building was exited, initiating the test. The hand was kept immobile during the test. Some non-heated gloves were tested with chemical heat warmers placed over the volar or dorsal wrist. Results . The highest starting (96°F/36°C) and ending (82°F/28°C) temperatures were with electrically heated gloves. The lowest starting temperature was with electrically heated gloves with the power off (63°F/17°C). Non-heated gloves with an inserted chemical hand warmer had the lowest minimum temperature (33°F/1°C). Maximum temperatures for gloves/mittens did not correlate well with their minimum temperature. Conclusions . Coverings that maintained finger temperatures within a comfortable and safe range (at or above 59°F/15°C) included the heated gloves and mittens (including some with the power off) and mittens with liners. Mittens without liners (shell) generally performed better than unheated gloves. Better results generally paralleled the item’s cost. Inserting chemical heat warmers at the wrist increased heat loss, possibly through the exposed area around the warmer. Keywords: clothing; hand warmth; Antarctica; hand protection; hand comfort; cold injury prevention; protective gear (Published: 14 November 2016) Citation: Int J Circumpolar Health 2016, 75: 33564 - http://dx.doi.org/10.3402/ijch.v75.33564

IntroductionIn April 2017, 22% of Army Full-time Trade Trained Strength was downgraded, reducing fully deployable strength to 60 546, against a target of 82 000. In June 2017, Commander 20 Armoured Infantry Brigade (20 AI Bde) initiated a study to look at the principal conditions causing medical downgrading, as a stepping stone to finding ways of reducing injury, enhancing rehabilitation and improving deployability.MethodThe Defence Medical Information Capability Programme medical records for every downgraded soldier in 20 AI Bde and supporting units were scrutinised to identify their Medical Deployment Standard and the primary condition causing downgrading.ResultsA total of 842 downgraded soldiers were identified from a held strength of 3827 personnel. Sixty-five per cent of these downgrades were due to musculoskeletal injury (MSKI). Of this 65%, the majority were due to knee (31%), spine (28%) and foot/ankle (23%). Of the remaining 35%, the majority were due to noise-induced hearing loss (NIHL) (22%), adjustment disorders (19%) and non-freezing cold injury (NFCI) (13%).Several factors that slowed an individual’s recovery pathway were identified. They mainly relate to soldiers being lost to follow-up through lack of active case management.ConclusionsMSKI is responsible for most downgraded personnel at Brigade level. The distribution of principal conditions is similar to previous studies looking at recruits and individual units.The creation of a rehabilitation troop, delivering active case management, can reduce the number of soldiers leaking out of the rehabilitation pipeline.

Localized thermal injuries in animals may be caused by exposure to fire and radiant heat, contact with hot items including hot liquids or steam, inhalation of hot air, and exposure to cold temperatures. In addition, animal fire victims may have intoxications caused by smoke gas. This article reviews the causes, pathogenetic aspects, morphological findings, additional investigations, differential diagnoses, and causes of death in various forms of thermal injuries. Since these cases do not occur frequently in diagnostic pathology, they represent a challenging task in general but also with respect to forensic or criminal aspects, such as whether a lesion represents an accidental or nonaccidental effect. Besides detailed information about the circumstances at the location, thermal injuries in animals require a thorough morphological evaluation, including additional investigations in conjunction with a profound knowledge about the possible lesion spectrum and suitable additional investigations.

Patient initials or identifier number KM ### Relevant clinical history and physical exam This case is 60 years-old woman treated for systemic lupus erythematosus with anti-phopholipid syndrome. Eight years earlier, below-knee amputation of her left lower limb was performed due to cold injury

RATIONALE The first successful ear replantation was performed by Pennigton in 1980 in Sydney. At least 84 ear replantations have been described in the literature over a period of 37 years since the first case. The authors have not found any previous case of frozen ear replantation in the literature. PATIENT CONCERNS We report the case of a 38-year-old man, who had an injury to the head while working with a machine. DIAGNOSIS The patient suffered total traumatic avulsion of the left ear. The ear was wrapped in moistened, sterile gauze and was transported on dry ice. At the time of admission to our department, the amputated ear was frozen to stiff, solid nonelastic matter. INTERVENTIONS We attempted replantation. Despite repeated arterial thrombosis during surgery, the ear was successfully replanted with arterial and venous anastomosis. OUTCOMES Venous congestion occurred within 9 h of surgery and was treated using leeches. Freezing cold injury developed during reattachment. The radix and proximal parts of the helix exhibited necrosis and so were reconstructed by contralateral conchal cartilage graft, which was wrapped with a local subauricular skin flap. On completion of treatment, a satisfactory shape was achieved, although the replanted and reconstructed left auricle slightly was smaller than the contralateral auricle. LESSONS LEARNED Our report confirms that the replantation of a frozen, amputated ear is possible, and we suggest that ear replantation should be the method of choice for the treatment of ear loss even under these conditions.

BackgroundNon-freezing cold injury (NFCI) occurs when peripheral tissue is damaged by cold exposure but not to the extent of freezing. Historically, the phenotype of NFCIs sustained was severe, whereas today the spectrum of injury represented in the UK military predominantly comprises subtler injuries. The diagnostic challenge of recognising these injuries, both in the acute and chronic settings, can lead to mismanagement and subsequent morbidity.MethodsWe characterised a recent case series of 100 UK Service Personnel referred with suspected NFCI to a Military UK NFCI clinic. We characterised the acute and chronic phenotype of those diagnosed with NFCI (n=76) and made comparison to those who received alternate diagnoses (n=24), to find discriminatory symptoms and signs.ResultsThe most common acute symptoms of NFCI were the extremities becoming cold to the point of loss of feeling for more than 30 min (sensitivity 96%, specificity 90%, pConclusionsA small collection of symptoms and signs characterise acute and chronic NFCIs and distinguish this vasoneuropathy from NFCI mimics.

Background and objectives'Frosties' are deliberate cold skin burns caused by an aerosol device. The aim of this article was to examine our own cohort, and those previously published, to identify the key features of patients presenting with frosties and inform appropriate early clinical interventions.MethodWe compared cases in our dataset that occurred between 1 January 2013 and 30 June 2017 with those reported in the literature, focusing on seven domains: sex, age at injury, days to presentation, first aid, depth of injury and outcome.ResultsThe median patient age was 13 years; 70.5% were female. Adequate first aid was not reported in any patient. Where recorded, the median time to presentation to a health service was six days. Where severity of injury was recorded, 13 of 37 cases (35.1%) were full thickness, and 10 patients received a split thickness skin graft. Two subgroups were identified: cluster injuries and psychological distress.DiscussionCluster injuries occur as the result of a mutual 'test of courage'. Solo injuries may point to underlying psychological distress. Frosties frequently result in significant burn injuries and often require skin grafting. The severity of frosties is underappreciated and, as a consequence, treatment, through first aid or presentation to a health service, is delayed or absent. General practitioners should be familiar with the appearance of frosties in order to identify them in unrelated consultations.

Проведено исследование интенсивности протекания процессов перекисного окисления липидов и состояния антиоксидантной защиты в организме больных с холодовой травмой различной степени тяжести. Установлено, что в организме больных с отморожением конечностей интенсивность свободнорадикального окисления и уровень антиоксидантной защиты зависели от степени отморожения., The authors report their study on the intensity of lipid peroxidation processes and the state of antioxidant protection in patients with cold trauma of varying severity. It was established that in the organism of patients with frostbite of extremities, the intensity of free radical oxidation and the level of antioxidant defense depended on the degree of frostbite., №2(62) (2018)

Frostbite is a cold injury mostly affecting the extremities. The objective of this study was to reveal the incidence of frostbite injuries in the Austrian Alps, to search for frostbite risk factors, and thereby optimize prevention and treatment.Out-of-hospital data in the National Registry of Alpine Accidents from January 1, 2005, to December 31, 2015, were screened for frostbite injuries. Cases in the registry were merged with clinical data from the major trauma center in western Austria, Innsbruck Medical University Hospital, and statistically analyzed.Documented in the National Registry are 114,595 injured persons in the 11-year study period. Thirty-one frostbite cases were documented nationwide, 18 (58%) of which occurred in the western states of Austria and were therefore potentially referred to the Innsbruck Medical University Hospital. Six (19.6%) patients were female. Frostbite was almost exclusively related to fingers and toes (90% of cases).Frostbite injuries in the Austrian Alps are rare. With an incidence of 0.07/100,000, three to four clinically relevant frostbite injuries occur annually. Men are at greater risk for frostbite injuries than women. Fingers and toes are at greatest risk. Proper preparation of outdoor activities and cold-protective gear can help prevent frostbite injuries.

Coffee polyphenols (CPPs) derived from coffee beans have beneficial effects on blood pressure and vascular endothelial function. In addition, CPPs suppress ultraviolet light induced erythema. However, the effects of CPPs on dry skin and cutaneous vascular function have not been clarified. We investigated the effects of CPPs on dry skin and the recovery rate (RR) of skin temperature after a cold-stress test as a measure of vascular function in subjects with visible scaliness in a double-blind, placebo-controlled, randomized study. The subjects were divided into two groups, the CPP group and the Placebo group. In the CPP group, the subjects ingested a beverage containing 297.8 mg CPPs every day for 4 wk. The degree of skin dryness was assessed quantitatively using a Visioscan to evaluate skin scaliness and smoothness. A subjective evaluation using a visual analog scale (VAS) of skin smoothness was also used. As a result, the scaliness and smoothness of cheek skin was significantly improved after 4 wk in the CPP group compared to the Placebo group. The improvements of the VAS score on 'skin smoothness' and the RR were also observed in the CPP group but the difference was not statistically significant. However, when the CPP group was divided into subgroups of high RR and low RR, the improvement of the RR was significant in the low RR subgroup. In conclusion, our results suggest that CPPs improve skin scaliness and play a role in cutaneous blood flow regulation after cold stress.

Objective To assess whether previous freezing cold injuries (FCI) would affect digit skin temperatures and rewarming rates during a follow-up cold stress test protocol. Design Nonrandomized control trial. Methods Twenty elite alpinists participated; alpinists with previous FCI requiring digit amputations (injured, INJ: n=10 total, n=8 male) were compared with ability-matched, uninjured alpinists (control, CON: n=10, all male). Digit skin temperature was measured using infrared thermography as an index of peripheral digit perfusion after a cold stress test, which consisted of 30 minutes of immersion in 8°C water. Results The INJ alpinists' injured toes were warmer (approximately 6%) than their uninjured toes immediately after cold immersion (95% CI, 0.01°C to 1.00°C; P = .05); there were no differences between the rates of rewarming of injured and uninjured toes (INJ, 0.5° ± 0.1°C/min; CON, 0.7° ± 0.3°C/min; P = .16). Although the INJ alpinists had colder injured fingers immediately after the 35°C warm bath compared with their own uninjured fingers (32.2° ± 2.0°C vs 34.5° ± 0.5°C; P = .02), there were no differences observed between the rates of rewarming of injured and uninjured fingers after cold exposure (INJ, 1.1° ± 0.2°C/min; CON, 1.3° ± 0.5°C/min; P = .22). Conclusions Even after FCI that requires digit amputation, there is no evidence of different tissue rates of rewarming between the injured and uninjured fingers or toes of elite alpinists.

BACKGROUND Non-freezing cold injury (NFCI) is a syndrome in which damage to peripheral tissues occurs without the tissues freezing following exposure to low ambient temperatures. AIMS To assess the test-retest reliability of a cold stress test (CST) used to assess cold sensitization. METHODS Volunteers with no self-reported history of NFCI undertook the CST on three occasions. Thermal images were taken of the foot and hand before, immediately after and 5min after immersion of the limb in cold water for 2min. Cold sensitization was graded by the two clinicians and the lead author. Spot temperatures from the toe and finger pads were recorded. RESULTS There were 30 white and 19 black male participants. The ratings indicated substantial agreement [a Cohen's kappa (κ) value of 0.61-0.8] to within ± one grading category for the hands and feet of the white volunteers and the hands of the black volunteers. Limits of agreement (LoA) analysis for toe and finger pad temperatures indicated high agreement (absolute 95% LoA < 5.5°C). Test-retest reliability for the feet of the black volunteers was not supported by the gradings (κ = 0.38) and toe pad temperatures (absolute 95% LoA = 9.5°C and coefficient of variation = 11%). CONCLUSIONS The test-retest reliability of the CST is considered adequate for the assessment of the cold sensitization of the hands and feet of white and the hands of black healthy non-patients. The study should be repeated with patients who have suffered a NFCI.

Brain edema is a potentially fatal pathological state that occurs after brain injuries such as stroke and head trauma. In the edematous brain, excess accumulation of extracellular fluid results in elevation of intracranial pressure, leading to impaired nerve function. Despite the seriousness of brain edema, only symptomatic treatments to remove edema fluid are currently available. Thus, the development of novel anti-edema drugs is required. The pathogenesis of brain edema is classified as vasogenic or cytotoxic edema. Vasogenic edema is defined as extracellular accumulation of fluid resulting from disruption of the blood-brain barrier (BBB) and extravasations of serum proteins, while cytotoxic edema is characterized by cell swelling caused by intracellular accumulation of fluid. Various experimental animal models are often used to investigate mechanisms underlying brain edema. Many soluble factors and functional molecules have been confirmed to induce BBB disruption or cell swelling and drugs targeted to these factors are expected to have anti-edema effects. In this review, we discuss the mechanisms and involvement of factors that induce brain edema formation, and the possibility of anti-edema drugs targeting them.

Non-freezing cold injury can be a diagnostic challenge for clinicians in the United Kingdom Armed Forces. It is associated with operations in adverse climatic conditions, and may result in significant long-term morbidity. In this article we discuss the operational importance of this condition and the current best practice in its management and prevention.

Background The prevalence of acute cold injury has increased recently. Despite new research findings, these injuries and their resulting tissue damage are still not entirely understood. Especially, little is known about alteration of skin biomechanical properties. Methods A total of 36 acute cold contact wounds with different depths were generated on the abdomen of six Gottingen minipigs. Alteration of biomechanical properties of skin was evaluated objectively after 15 and 360 min using a Cutometer device. Biopsies for histological evaluation were taken, and the depth of injury was correlated with biomechanical properties. Results Calculated elasticity (Ue), firmness of skin (R0) and overall elasticity (R8) demonstrated a continuous decrease, whereas other parameters demonstrated an initial increase with increasing depth of injury 15 min after wound generation. All parameters showed an increase compared to healthy skin, 360 min after wound generation. Furthermore, an alteration of values over time was detected. Conclusion Alteration of biomechanical properties of skin is a function of damaged tissue structures. The presented results demonstrate a decrease of main elastic parameters with increasing depth of injury and indicate progressive tissue damage over time. Skin elasticity measurements are a valuable tool in acute cold contact injury depth assessment and may act as an influencing factor in management decisions.

Notalgia paresthetica, a neurosensory syndrome that typically occurs on the upper back, has multiple clinical symptoms with variable degrees of expression in each individual afflicted with the condition. The involved site is usually hyperpigmented and is associated with burning, coldness, hypoesthesia, increased pain, pruritus and/or tingling. In the affected area, the number of nerve fibers may be increased and the cutaneous sensory nerves are altered secondary to localized impingement, central injury, or both. Although multiple therapeutic approaches for notalgia paresthetica have been described, none specifically address the essential pathogenesis of the condition—the altered cutaneous nerves. Cryolipolysis is a well-tolerated nonsurgical technique to reduce the subcutaneous fat layer. Selective apoptosis of adipocytes occurs since the lipid-rich fat cells are more susceptible to cold injury than the surrounding water-rich cells. Not only a marked decrease in pain sensitivity but also a sustained reduction in the density of myelinated and unmyelinated cutaneous nerves has been observed in cryolipolysis-treated skin. Therefore, cryolipolysis is a logical approach to the treatment of notalgia paresthetica. One or more cryolipolysis treatments may be necessary for complete or partial resolution of the individual’s notalgia paresthetica-related cutaneous symptoms. In conclusion, evaluation of cryolipolysis as a noninvasive treatment of patients with notalgia paresthetica is warranted.

Purpose To describe the self-reported ambient cold exposure in northern Sweden and to relate the level of cumulative cold exposure to the occurrence of sensory and vascular hand symptoms. We hypothesize that cold exposure is positively related to reporting such symptoms. Methods A questionnaire about cold exposure and related symptoms was sent out to 35,144 subjects aged 18–70 years and living in northern Sweden. Results A total of 12,627 out of 35,144 subjects returned the questionnaire (response rate 35.9%). Subjects living in the rural alpine areas reported more extensive cold exposure both during work and leisure time compared to the urbanized coastal regions. Frostbite in the hands was present in 11.4% of men and 7.1% of women, cold sensitivity was present in 9.7 and 14.4%, and Raynaud’s phenomenon was present in 11.0% of men and 14.0% of women. There was a positive association between cumulative cold exposure and neurovascular hand symptoms. Conclusion The present study demonstrates that the cold environment in northern Sweden might be an underestimated health risk. Our hypothesis that cold exposure is positively related to reporting of neurovascular hand symptoms was supported by our findings. In addition, such symptoms were common not only in conjunction with an overt cold injury. Our results warrant further study on pathophysiological mechanisms and suggest the need for confirmatory prevalence studies to support national public health planning. Electronic supplementary material The online version of this article (doi:10.1007/s00420-017-1221-3) contains supplementary material, which is available to authorized users.

Aesthetic medicine is growing with tremendous interest in non-surgical facial procedures, such as injectable dermal fillers and neurotoxins. As patients seek facial procedures with no downtime or anaesthesia risks, there is also a growing demand for non-surgical body contouring. Various non-surgical body sculpting technologies are available to aesthetic practitioners, and cryolipolysis is the most well established. Cryolipolysis takes advantage of the inherent susceptibility of adipocytes to cold injury, delivering controlled cooling to damage subcutaneous fat while leaving surrounding structures unharmed. Cryolipolysis can be used to treat various anatomical areas with a range of vacuum applicators to draw in fat or a surface applicator for treating non-pinchable areas, such as ‘saddlebags’ on the outer thighs. As the treatment area is numbed by the cold, patients are able to rest comfortably during the procedure and nurses can provide other treatments such as injectables. Cryolipolysis is safe and effective with high patient-satisfaction and tolerability rates.

Freezing cold injuries (frostbite) of the extremities are a common injury among alpinists participating in high altitude expeditions, particularly during inclement weather conditions. Anecdotally, a digit that has suffered frostbite may be at greater risk to future cold injuries. In this case study, we profile a 62-year-old elite alpinist who suffered multiple digit amputations on both his hands and foot after historic summit attempts on Makalu (8481 m) and Mt. Everest (8848 m) in 1974-1979. We describe the clinical treatment he received at that time, and follow up his case 40 years after the first incidence of frostbite utilizing a noninvasive evaluation of hand and foot function to a cold stress test, including rates of re-warming to both injured and non-injured digits. Finger rates of recovery to the cold stress test were not different (0.8 vs. 1.0°C·min(-1)) except one (injured, left middle finger, distal phalanx; 0.4°C·min(-1)). Toe recovery rates after cold-water immersion were identical between previously injured and non-injured toes (0.2°C·min(-1)). Thermocouple data indicate that this alpinist's previous frostbite injuries may not have significantly altered his digit rates of re-warming during passive recovery compared to his non-injured digits.

Background: Severe frostbite can result in devastating injuries leading to significant morbidity and loss of function from distal extremity amputation. The modern day management approach to frostbite injuries is evolving from a historically very conservative approach to the increasingly reported use of early interventional angiography and fibrinolysis with tPA. The aim of this study was to evaluate the results of our frostbite treatment protocol introduced 3 years ago. Methods: All frostbite patients underwent first clinical and then Doppler ultrasound examination. Angiography was conducted if certain clinical criteria indicated a severe frostbite injury and if there were no contraindications to fibrinolysis. Intra-arterial tissue plasminogen activator (tPA) was then administered at 0.5-1mg/h proximal to the antecubital fossa (brachial artery) or popliteal fossa (femoral artery) if angiography confirmed thrombosis, as well as unfractionated intravenous heparin at 500 units/h. The vasodilator iloprost was administered intravenously (0.5-2.0ng/kg/min) in selected cases. Results: 20 patients with frostbite were diagnosed between 2013-2016. Fourteen patients had a severe injury and angiography was performed in 10 cases. The total number of digits at risk was 111. Nine patients underwent fibrinolytic treatment with tPA (including one patient who received iloprost after initial non response to tPA), 3 patients were treated with iloprost alone and 2 patients received neither treatment modality (due to contraindications). The overall digital salvage rate was 74.8% and the Hennepin tissue salvage rate was 81.1%. One patient developed a catheter-site pseudoaneurysm that resolved after conservative treatment. Conclusions: Prompt referral to a facility where interventional radiology and 24/7 laboratory services are available, and the combined use of tPA and iloprost, may improve outcome after severe frostbite. (C) 2017 Elsevier Ltd and ISBI. All rights reserved.

The treatment of frostbite injuries has undergone a radical change over the past decade with a shift from supportive therapy and observation towards early and aggressive medical intervention with thrombolytics and vasodilators. Institutions that have implemented evidence-based protocols have significantly decreased their amputation rates (Bruen et al., 2007; Lindford et al., 2017a; Twomey et al., 2005). We present the case of a middle-aged male treated for frostbite of multiple fingers on both hands. Because there was no treatment protocol at our institution, there were multiple delays in the patient's care including imaging and initiation of intravenous (IV) prostanoids. This case illustrates the deleterious effects of delays in treatment and strongly suggests that all facilities located in areas of cold exposure should have protocols in place for such an occurrence.

International audience; A longstanding goal in regenerative medicine is to reconstitute functional tissues or organs after injury or disease. Attention has focused on the identification and relative contribution of tissue specific stem cells to the regeneration process. Relatively little is known about how the physiological process is regulated by other tissue constituents. Numerous injury models are used to investigate tissue regeneration, however, these models are often poorly understood. Specifically, for skeletal muscle regeneration several models are reported in the literature, yet the relative impact on muscle physiology and the distinct cells types have not been extensively characterised. We have used transgenic Tg:Pax7nGFP and Flk1GFP/+ mouse models to respectively count the number of muscle stem (satellite) cells (SC) and number/shape of vessels by confocal microscopy. We performed histological and immunostainings to assess the differences in the key regeneration steps. Infiltration of immune cells, chemokines and cytokines production was assessed in vivo by Luminex®.We compared the 4 most commonly used injury models i.e. freeze injury (FI), barium chloride (BaCl2), notexin (NTX) and cardiotoxin (CTX). The FI was the most damaging. In this model, up to 96% of the SCs are destroyed with their surrounding environment (basal lamina and vasculature) leaving a "dead zone" devoid of viable cells. The regeneration process itself is fulfilled in all 4 models with virtually no fibrosis 28 days post-injury, except in the FI model. Inflammatory cells return to basal levels in the CTX, BaCl2 but still significantly high 1-month post-injury in the FI and NTX models. Interestingly the number of SC returned to normal only in the FI, 1-month post-injury, with SCs that are still cycling up to 3-months after the induction of the injury in the other models.We compared the 4 most commonly used injury models i.e. freeze injury (FI), barium chloride (BaCl2), notexin (NTX) and cardiotoxin (CTX). The FI was the most damaging. In this model, up to 96% of the SCs are destroyed with their surrounding environment (basal lamina and vasculature) leaving a "dead zone" devoid of viable cells. The regeneration process itself is fulfilled in all 4 models with virtually no fibrosis 28 days post-injury, except in the FI model. Inflammatory cells return to basal levels in the CTX, BaCl2 but still significantly high 1-month post-injury in the FI and NTX models. Interestingly the number of SC returned to normal only in the FI, 1-month post-injury, with SCs that are still cycling up to 3-months after the induction of the injury in the other models.We compared the 4 most commonly used injury models i.e. freeze injury (FI), barium chloride (BaCl2), notexin (NTX) and cardiotoxin (CTX). The FI was the most damaging. In this model, up to 96% of the SCs are destroyed with their surrounding environment (basal lamina and vasculature) leaving a "dead zone" devoid of viable cells. The regeneration process itself is fulfilled in all 4 models with virtually no fibrosis 28 days post-injury, except in the FI model. Inflammatory cells return to basal levels in the CTX, BaCl2 but still significantly high 1-month post-injury in the FI and NTX models. Interestingly the number of SC returned to normal only in the FI, 1-month post-injury, with SCs that are still cycling up to 3-months after the induction of the injury in the other models.

Subtle blood-brain barrier (BBB) disruption is involved in numerous neurological conditions. This disruption is found diffusely in the brain and requires quantitative methods for assessment. We propose a statistical method to identify individual voxels where the BBB is disrupted using T1-weighted MRI. We used models of severe and focal vs. mild and generalized disruption of the BBB to show proof of principle with the cold injury model, hypoxia, and a model of inflammation using low- and high-dose lipopolysaccharide (LPS) treatment. Using voxel-based analysis, we found that mild hypoxia resulted in diffuse disruption of the BBB, whereas more severe hypoxia and high-dose LPS treatment resulted in prominent leakage, particularly in the periventricular area, suggestive of blood-cerebrospinal fluid (CSF) barrier disruption. Our data suggest that the periventricular area may be compromised first in conditions of inflammation and hypoxia. Voxel-based analysis could be used in future studies assessing subtle blood-CSF or BBB disruption.

Humans residing or working in cold environments exhibit a stronger cold-induced vasodilation (CIVD) reaction in the peripheral microvasculature than those living in warm regions of the world, leading to a general assumption that thermal responses to local cold exposure can be systematically improved by natural acclimatization or specific acclimation. However, it remains unclear whether this improved tolerance is actually due to systematic acclimatization, or alternately due to the genetic predisposition or self-selection for such occupations. Longitudinal studies of repeated extremity exposure to cold demonstrate only ambiguous adaptive responses. In field studies, general cold acclimation may lead to increased sympathetic activity that results in reduced finger blood flow. Laboratory studies offer more control over confounding parameters, but in most studies, no consistent changes in peripheral blood flow occur even after repeated exposure for several weeks. Most studies are performed on a limited amount of subjects only, and the variability of the CIVD response demands more subjects to obtain significant results. This review systematically surveys the trainability of CIVD, concluding that repeated local cold exposure does not alter circulatory dynamics in the peripheries, and that humans remain at risk of cold injuries even after extended stays in cold environments.

Non-freezing cold injury (NFCI) is the Cinderella of thermal injuries and is a clinical syndrome that occurs when tissues are exposed to cold temperatures close to freezing point for sustained periods. NFCI is insidious in onset, often difficult to recognize and problematic to treat, and yet the condition accounts for significant morbidity in both military and civilians who work in cold conditions. Consequently recognition of those at risk, limiting their exposure and the appropriate and timely use of suitable protective equipment are essential steps in trying to reduce the impact of the condition. This review addresses the issues surrounding NFCI.

We thank Eglin et al for their thoughtful commentary on our manuscript, in which we undertook the first detailed neurological assessment of persistent symptoms following non-freezing cold injury. Whilst we stress that sensory neuropathy is one core feature of NFCI we do not want to give the impression that vascular factors may not play a role. In fact, given the intimate relationship between peripheral neurons and blood vessels in the neurovascular unit, it would be a surprise if vascular changes were not observed.

In Central Europe, cold-induced injuries are much less common than burns. In a burn center in western Germany, the mean ratio of these two types of injury over the past 10 years was 1 to 35. Because cold-induced injuries are so rare, physicians often do not know how to deal with them.This article is based on a review of publications (up to December 2014) retrieved by a selective search in PubMed using the terms "freezing," "frostbite injury," "non-freezing cold injury," and "frostbite review," as well as on the authors' clinical experience.Freezing and cold-induced trauma are part of the treatment spectrum in burn centers. The treatment of cold-induced injuries is not standardized and is based largely on case reports and observations of use. distinction is drawn between non-freezing injuries, in which there is a slow temperature drop in tissue without freezing, and freezing injuries in which ice crystals form in tissue. In all cases of cold-induced injury, the patient should be slowly warmed to 22°-27°C to prevent reperfusion injury. Freezing injuries are treated with warming of the body's core temperature and with the bathing of the affected body parts in warm water with added antiseptic agents. Any large or open vesicles that are already apparent should be debrided. To inhibit prostaglandin-mediated thrombosis, ibuprofen is given (12 mg/kg body weight b.i.d.).The treatment of cold-induced injuries is based on their type, severity, and timing. The recommendations above are grade C recommendations. The current approach to reperfusion has yielded promising initial results and should be further investigated in prospective studies.

In persons completing exhaustive daily exercise, sleep and energy restriction have been highlighted as risk factors for hypothermia in cold environments. The present study therefore sought to determine the effect of sleep deprivation (SDEP), with and without energy restriction, on the thermal response to cold. In a random order, ten recreationally active men (mean ± SD: age 25 ± 6 years, body fat 17 ± 5 %) completed three 53 h trials: a control (CON: 436 min/night sleep), SDEP (0 min sleep), and sleep deprivation and energy restriction (SDEP + ER: 0 min sleep and 10 % daily energy requirements). Exhaustive exercise was completed after 5 and 29 h. After 53 h participants completed a semi-nude seated cold air test (CAT, 0 °C), for 4 h or until rectal core temperature (T re) reached 36 °C. Two nights of sleep and energy restriction did not impair the thermal response to cold (T re, CON 36.15 ± 0.20 °C, SDEP 36.30 ± 0.15 °C, SDEP + ER 36.25 ± 0.20 °C, P = 0.25). Rewarming was also similar as indicated by 1 h post-CAT T re (P = 0.78). In contrast, perceived thermal discomfort during the initial hour of the CAT tended to be greater after SDEP and SDEP + ER (P ≤ 0.1). Sleep and energy restriction, at least as evaluated within this experiment, should be considered minimal risk factors for hypothermia. The greater perception of cold discomfort at the same body temperature suggests that sleep and energy restriction may actually reduce cold injury risk, as people are likely to engage earlier in normal behavioral cold adaptation.

Brain edema is a potentially fatal pathological state that often occurs after brain injuries such as ischemia and trauma. However, therapeutic agents that fundamentally treat brain edema have not yet been established. We previously found that endothelin ETB receptor antagonists attenuate the formation and maintenance of vasogenic brain edema after cold injury in mice. In this study, the effects of ETB antagonists on matrixmetalloproteinase (MMP)9 and vascular endothelial growth factor (VEGF)-A expression were examined in the cold injury model. Cold injury was performed in the left brain of male ddY mice (5-6 weeks old) for the induction of vasogenic edema. Expression of MMP9 and VEGF-A mRNA in the mouse cerebrum was increased by cold injury. Immunohistochemical observations showed that the MMP9 and VEGF-A were mainly produced in reactive astrocytes in the damaged cerebrum. Intracerebroventricular administration of BQ788 (10 μg) or IRL-2500 (10 μg) (selective ETB antagonists) attenuated brain edema and disruption of the blood-brain barrier after cold injury. BQ788 and IRL-2500 reversed the cold injury-induced increases in MMP9 and VEGF-A expression. The induction of reactive astrocytes producing MMP9 and VEGF-A in the damaged cerebrum was attenuated by BQ788 and IRL-2500. These results suggest that attenuations of astrocytic MMP9 and VEGF-A expression by ETB antagonists may be involved in the amelioration of vasogenic brain edema.

The approaching 90-year anniversary of United States entry into the Great War is an apt time to examine the response to trench foot (now called nonfreezing cold injury [NFCI]) in this conflict. Trench foot appeared in the winter of 1914, characterized by pedal swelling, numbness, and pain. It was quickly recognized by military-medical authorities. There was little debate over whether it was frostbite or new condition, and it was quickly accepted as a specific disease. The major etiologies proposed were exposure, diet, and infection. The opinion emerged that it was caused by circulatory changes in the foot caused by cold, wet, and pressure. Predisposing factors included dietary inadequacy and fatigue. A number of labels were first given to the disease. However, the name "trench foot" was eventually officially sanctioned. Trench foot became a serious problem for the Allies, leading to 75 000 casualties in the British and 2000 in the American forces. Therapy for trench foot involved a number of conventional, tried-and-tested, and conservative methods. Some more innovative techniques were used. Amputation was only used as a last resort. Prevention involved general measures to improve the trench environment; modification of the footwear worn by the men; and the provision of greases to protect them from moisture. The medical reaction to this condition seems to have been relatively effective. The causation was identified, and prophylactic measures were introduced to fit this model; these seem to have been successful in reducing the prevalence of the condition by 1917-18.

The long-term preservation of organ explants and protection from cold ischaemia and subsequent rewarming reperfusion injury is essential to successful allografting and instrumental in enlarging the international donor pool. Current hypothermic preservation solutions may have reached the limit of what is possible in terms of explant longevity and viability, and research attention has been turned to novel organoprotective pharmacotherapeutics that could provide the next generation of explant/transplant nurture. Organoprotection is equally paramount during surgical procedures requiring a period of ischaemia as in coronary artery bypass grafting, angioplasty or stenting. Similarly, the phenomenon of non-freezing cold injury (NFCI), associated with microcirculatory and neuronal damage in exposed and often immersed extremities, also involves ischaemia–reperfusion injury. Whilst additions to cold storage solutions of antioxidants and modulators of cellular metabolism may extend their preservative efficacy, pharm...

Cold-induced vasodilation (CIVD) is a cyclic oscillation in blood flow that occurs in the extremities on cold exposure and that is likely associated with reduced risk of cold injury (e.g., frostbite) as well as improved manual dexterity and less pain while working in the cold. The CIVD response varies between individuals, but the within-subject reproducibility has not been adequately described. The purpose of this study was to quantify the within-subject variability in the CIVD response under standardized conditions. Twenty-one volunteers resting in a controlled environment (27°C) immersed the middle finger in warm water (42°C) for 15 min to standardize initial finger temperature and then in cold water (4°C; CWI) for 30 min, on five separate occasions. Skin temperature (Tf) and blood flow (laser-Doppler; expressed as percent change from warm-water peak) responses that describe CIVD were identified, including initial nadir reached during CWI, onset time of CIVD, initial apex during CIVD, time of that apex, and overall mean during CWI. Within-subject coefficient of variation for Tfacross the five tests for the nail bed and pad, respectively, were as follows: nadir, 9 and 21%; onset, 18 and 19%; apex, 12 and 17%; apex time, 23 and 24%; mean 10 and 15%. For blood flow, these values were as follows: nadir 52 and 64%; onset, 6 and 5%; apex, 33 and 31%; apex time 9 and 8%; and mean 43 and 34%. Greater variability was found in the temperature response of the finger pad than the nail bed, but for blood flow the variability was similar between locations. Variability in onset and apex time between sites was similar for both temperature and blood flow responses. The reproducibility of the time course of CIVD suggests this methodology may be of value for further studies examining the mechanism of the response.

Appropriate hypothermic packaging techniques are an essential part of organ procurement. We present a case in which deviation from standard packaging practice may have caused sub-zero storage temperatures during transport, resulting in a clinical picture resembling PNF. An 18-month-old male with alpha-1-antitrypsin deficiency underwent liver transplant from a size-matched pediatric donor. Upon arrival at the recipient hospital, ice crystals were noted in the UW solution. The transplant proceeded uneventfully with short ischemia times. Surprisingly, transaminases, INR, and total bilirubin were markedly elevated in the postoperative period but returned to near normal by discharge. Follow-up of over five yr has demonstrated normal liver function. Upon review, it was discovered that organ packaging during recovery included storage in the first bag with only 400 mL of UW solution, and pure ice in the second bag instead of slush. This suggests that the postoperative delayed graft function was related to sub-zero storage of the graft during transport. This is the first report of sub-zero cold injury, or frostbite, following inappropriate packaging of an otherwise healthy donor liver. The clinical picture closely resembled PNF, perhaps implicating this mechanism in other unexpected cases of graft non-function.