Safety and Feasibility of a Sheath Cryoprobe for Bronchoscopic Transbronchial Biopsy: The FROSTBITE Trial.

BACKGROUND: Bronchoscopic lung biopsy is typically performed using transbronchial forceps. However, this method is limited by small sample size and presence of crush artifact. Cryobiopsy offers the potential to overcome these limitations with larger artifact-free samples but has not been widely adopted due to concerns over increased rates of bleeding and pneumothorax. A new, smaller 1.1-mm cryoprobe has been developed that operates in a similar fashion to forceps, though the safety profile of this cryoprobe has not yet been prospectively studied. OBJECTIVE: The aim of this study was to investigate the safety of transbronchial biopsy using a novel 1.1-mm cryoprobe. METHODS: This prospective, single-arm study enrolled patients referred for transbronchial biopsy. All procedures were performed using the 1.1-mm cryoprobe with oversheath. The primary outcome was the composite of significant complications related to the cryobiopsy procedure (bleeding Grade ≥3, pneumothorax Grade ≥2, and respiratory failure). Bleeding and pneumothorax were graded according to previously published scales. RESULTS: Fifty participants from two academic medical centers underwent transbronchial cryobiopsy. Indications for biopsy included evaluation of lung transplant allograft (50%), diffuse lung disease (44%), and pulmonary parenchymal lesion (6%). There were two pneumothoraces (4%), neither of which required aspiration or chest tube placement. There were no Grade 3 or 4 bleeding events. Mild bleeding (Grade ≤2) was observed in 25 cases (50%). No complications occurred that met the a priori primary outcome of bleeding Grade ≥3, pneumothorax Grade ≥2, and respiratory failure. CONCLUSIONS: Transbronchial cryobiopsy using a 1.1-mm cryoprobe is feasible with an acceptable safety profile.

An Institutional Protocol for the Treatment of Severe Frostbite Injury-A 6-Year Retrospective Analysis.

The treatment of severe frostbite injury has undergone rapid development in the past 30 years with many different diagnostic and treatment options now available. However, there is currently no consensus on the best method for management of this disease process. At our institution, we have designed a protocol for severe frostbite injury that includes diagnosis, medical treatment, wound cares, therapy, and surgery. This study assess the efficacy of our treatment since its implementation six years ago. During this time, all patients with severe frostbite injury were included in prospective observational trial of the protocol. We found that this protocol results in significant tissue salvage with over 80.7% of previously ischemic tissue becoming viable and not requiring amputation. We also were able to improve our center's efficiency over the course of six years and now our current average time from rapid rewarming to delivery of thrombolytics is under six hours.

Protective Effect of Extract of Ginkgo biloba 761 against Frostbite Injury in Rats.

BACKGROUND: When frostbite thaws, reperfusion injury has a crucial impact on tissue injury, and production of free radicals induces further tissue damage. This study examined whether extract of Ginkgo biloba 761 could ameliorate frostbite injury as a free radical scavenger. METHODS: Seventy-five Fisher 344 rats were divided into five groups of 15, and frostbite injury was created in each animal by sandwiching the left hind foot between a frozen magnet (-78.5°C) and a room-temperature magnet. Group I received saline; groups II, III, and IV received extract of Ginkgo biloba 761 (200, 100, and 50 mg/kg, respectively); and group V received superoxide dismutase (12 mg/kg). All drugs were injected intraperitoneally three times at 24-hour intervals. The wound surface area was measured throughout the wound healing period. Wounds were also harvested at various times to count cells stained by monoclonal antibodies for 4-hydroxy-2-nonenal and 8-hydroxy-2'-deoxyguanosine. RESULTS: Compared to group I, the wound surface area was significantly smaller in groups II and III on days 1 and 3 after wound creation. Histologic examination revealed significantly more 4-hydroxy-2-nonenal-stained cells and 8-hydroxy-2'-deoxyguanosine-stained cells in group I compared to other groups on day 1. However, there was no difference in the total healing period among the groups. A higher dose test of extract of Ginkgo biloba 761 (300 mg/kg daily) induced animal death, probably because of toxicity. CONCLUSION: Extract of Ginkgo biloba 761 demonstrated a protective effect against frostbite in the present model and probably alleviated reperfusion injury by reducing tissue peroxidation.

Pedicled Abdominal Flaps for Enhanced Digital Salvage After Severe Frostbite Injury.

Extremities are the area of the body most commonly affected by frostbite, which can also affect the face, ears, perineum, or genitals. Optimum management has moved away from early amputation and debridement toward maximizing tissue preservation and delaying surgical intervention. Increasing length of digit amputation increases morbidity, in terms of loss of hand function, experienced by patients. Reconstruction of affected digits is limited by bone necrosis, which often leads to shortened residual stumps and limited functional outcomes. This case describes the management of a severe frostbite injury affecting both hands and feet in a 39-y-old man, sustained during descent of Mount Everest. The use of a pedicled abdominal flap to provide soft-tissue cover permitted optimized digit length and function and sensate digits. The case highlights the benefits of early multidisciplinary team involvement in the management of severe frostbite to optimize functional outcome.

Reversed First Dorsal Metatarsal Artery Island Flap for First Ray Defects.

Reconstruction of the first ray is challenging because of poor skin laxity, bone and tendon exposure, and limited local flap options. Repair using full- or split-thickness skin grafts is generally not an option because of the bone and tendon exposure. Reconstructive options using local flaps from the distal foot area are restricted owing to insufficient soft tissue. Many reconstructive options have been described to overcome these difficult situations. We present 2 cases in which the great toe and first ray defect were repaired using a reversed first dorsal metatarsal artery island flap. The findings from these clinical cases and anatomic studies have shown that the reversed first dorsal metatarsal artery island flap is an alternative and suitable option for reconstruction of soft tissue defect of the distal foot, especially first and second ray defects, because it is thin and simple, has anatomic characteristics similar to those at the recipient site, and results in minimal donor site morbidity.

Analytical expressions for estimating endurance time and glove thermal resistance related to human finger in cold conditions.

Frostbite is considered the severest form of cold injury and can lead to necrosis and loss of peripheral appendages. Therefore, prediction of endurance time of limb's tissue in cold condition is not only necessary but also crucial to estimate cold injury intensity and to choose appropriate clothing. According to the previous work which applied a 3-D thermal model for human finger to analyze cold stress, in this study, an expression is presented for endurance time in cold conditions to prevent cold injury. A formula is also recommended to select a proper glove with specific thermal resistance based on the ambient situation and cold exposure time. By employing linear extrapolation and real physical conditions, the proposed formulas were drawn out from numerical simulation. Analytical results show good agreement with numerical data. The used numerical data had been also validated with experimental data existed in the literature. Furthermore, the effect of different parameters such as glove thermal resistance and ambient temperature is investigated analytically.

Successful conservative treatment of severe frostbite lesions in a Greenlandic Inuit.

Frostbite may cause lesions. The severity ranges from superficial wounds to severe cases with loss of limbs and tissue. Hence, proper treatment is of utmost importance. We present a case of an 18-year-old man from Arctic Greenland who was admitted with severe frostbite lesions involving both hands. The patient had fallen asleep outside during extreme temperatures. He was treated conservatively with proper wound care, antibiotics and intensive physical therapy. The patient made a full recovery without sequelae. The current report emphasises that non-operative treatment should be attempted for frostbite lesions, as conservative treatment often results in good outcomes.

A 3D thermal model to analyze the temperature changes of digits during cold stress and predict the danger of frostbite in human fingers.

The existing computational models of frostbite injury are limited to one and two dimensional schemes. In this study, a coupled thermo-fluid model is applied to simulate a finger exposed to cold weather. The spatial variability of finger-tip temperature is compared to experimental ones to validate the model. A semi-realistic 3D model for tissue and blood vessels is used to analyze the transient heat transfer through the finger. The effect of heat conduction, metabolic heat generation, heat transport by blood perfusion, heat exchange between tissues and large vessels are considered in energy balance equations. The current model was then tested in different temperatures and air speeds to predict the danger of frostbite in humans for different gloves. Two prevalent gloves which are commonly used in cold climate are considered for investigation. The endurance time and the fraction of necrotic tissues are two main factors suggested for obtaining the response of digit tissues to different environmental conditions.

SPECT/CT in the Evaluation of Frostbite.

Frostbite remains a challenging clinical scenario with multiple treatment algorithms and variable results. Currently, frostbite management often follows a conservative approach with rewarming followed by wound care and delayed amputation. We review seven patients where single-photon emission computed tomography (SPECT) fused with conventional computed tomography was used to evaluate tissue viability for earlier directed debridement and limb salvage. The goal of this report is to evaluate SPECT/CT as an appropriate modality for the screening of necrotic bone for earlier amputation in patients with frostbite. We retrospectively analyzed the records of seven patients (19 extremities) with frostbite who received SPECT/CT scans to evaluate deep tissue necrosis before digit amputation. All patients who presented within the first 24 hr following their injury without contraindications were initially treated with tissue plasminogen activator. Three patients met criteria and were treated with tissue plasminogen activator. Of the seven patients analyzed, none required revision amputation beyond the level predicted on SPECT/CT scan. No patients had viable tissue distal to the most distal extent of bone perfusion. In six of the patients, the SPECT/CT scan led to more distal amputation with proximal debridement of soft tissues thus maintaining extremity length. Frostbite remains a challenging clinical scenario for which there are a wide number of clinical algorithms. SPECT/CT appears to be valuable in the evaluation of frostbite to determine the need for amputation. Fusion of the nuclear images with the CT allows for more exact delineation of the level of amputation than a bone scan alone.

Effects of low-frequency pulsed electromagnetic fields on plateau frostbite healing in rats.

Plateau frostbite (PF) treatments have remained a clinical challenge because this condition injures tissues in deep layers and affected tissues exhibit unique pathological characteristics. For instance, low-frequency pulsed electromagnetic field (PEMF) can affect tissue restoration and penetrate tissues. Therefore, the effect of PEMF on PF healing should be investigated. This study aimed to evaluate the effects of low-frequency PEMF on PF healing systematically. Ninety-six Sprague-Dawley rats were randomly and equally divided into three groups: normal control, partial thickness plateau frostbite (PTPF), and PTPF with low-frequency PEMF exposure (PTPF + PEMF). PTPF wounds were induced in the dorsum of the rats. The PTPF + PEMF group was exposed to low-frequency PEMF daily. During PF healing, wound microcirculation in each group was monitored through contrast ultrasonography. Wound appearance, histological observation, and wound tensile strength were also evaluated. Results showed that the rate of the microcirculation restoration of the PTPF + PEMF group was nearly 25% faster than that of the PTPF group, and wound appearance suggested that the healing of the PTPF group was slower than that of the PTPF + PEMF group. Histological observation revealed that PEMF accelerated the growth of different deep tissues, as confirmed by tensile strength examination. Low-frequency PEMF could penetrate PF tissues, promote their restoration, and provide a beneficial effect on PF healing. Therefore, this technique may be a potential alternative to treat PF.

Application of a novel rectal cooling device in hypothermia therapy after cerebral hypoxia-ischemia in rats.

BACKGROUND: A new rectal cooling device for therapeutic hypothermia (TH) therapy is designed and is applied in TH treatment of SD rats with ischemic-hypoxic brain damage. METHODS: Healthy adult SD rats (n = 45) were randomly assigned into four groups: the healthy control group (n = 5), the ischemia and hypoxia group (n = 10), the rectal TH cooling group (n = 18), and the ice blanket TH cooling group (n = 11). The rats in the rectal cooling and ice blanket TH groups received 12 h treatment after hypoxic-ischemic brain damage had been established, while those in the ischemia and hypoxia group did not. Taking the start of TH as the zero point, rats were sacrificed after 24 h and the brain and rectum tissues were sampled for histological analysis. RESULTS: The TH induction time (37.3 ± 14.7 min) in the rectal cooling group was significantly shorter (F = 4.937, P < 0.05) than that in the ice blanket cooling group (75.6 ± 27.2 min). The HE and NISSL staining results showed that rats in the rectal TH cooling group had significantly decreased (P < 0.01) positive neurons cell count compared to those in ischemia and hypoxia group. In addition, TUNEL staining indicated that the number of apoptotic cells (3.9 ± 1.8 cells / × 400 field) and the apoptosis index (4.4 % ± 1.5) were significantly lower in rectal TH cooling group (P < 0.05) than in ischemia and hypoxia group (23.2 ± 12.1 cells / × 400 field, 26.6 % ± 12.1). Also, no rectal frostbite or inflammatory infiltration was observed in rats in the rectal TH treatment groups. CONCLUSION: Our new cooling device realized rapid TH induction in SD rats with ischemic-hypoxic brain damage, inhibited the apoptosis of cells in the hippocampal CAl region, and did not cause histological damage to the rectal tissues.

Management of Severe Frostbite in a Grey-Headed Parrot (Poicephalus fuscicollis suahelicus).

An approximately 5-year-old female grey-headed parrot (Poicephalus fuscicollis suahelicus) was evaluated after exposure to outdoor temperatures below -20°C (-4°F) for approximately 22 hours. Severe frostbite affecting multiple digits, as well as dehydration and a depressed attitude, were diagnosed. Treatment included oral antibiotics, antifungals, nonsteroidal anti-inflammatories (NSAIDs), pentoxifylline, and topical aloe vera. Surgical amputation of the affected toes was not performed. Mild to moderate pododermatitis over the intertarsal joints developed because of a shift in weight bearing after the loss of most digits. Within 5 months after initial presentation, all frost-damaged toes had self-amputated, and the bird was able to function independently with no limitations in mobility.

Nanogel for dermal application of the triterpenoids isolated from Ganoderma lucidum (GLT) for frostbite treatment.

OBJECTIVE: The purpose of this study was to formulate stable Ganoderma lucidum (GLT) nanogels suitable for topical delivery with a view to improve the therapeutic effect for frostbite. METHODS: GLT nanosuspensions were formulated using the high-pressure homogenization technique and then suitably gelled for characterized. In order to confirm the advantages of GLT nanogel for dermal application, skin permeation studies in vitro and pharmacodynamic evaluation in vivo were studied and compared with GLT-carbopol gel. RESULTS: The particle size analysis and SEM studies revealed that GLT nanosuspensions were still stably kept their particle size after suitably gelled by carbopol preparation. The drug content, pH, and spreadability of the GLT nanogel was found to be 99.23 ± 1.8%, 6.07 ± 0.1, and 26.42 (g·cm)/s, which were within acceptable limits. In vitro permeation studies through rat skin indicated that the amount of GLT permeated through skin of GLT nanogel after 24 h was higher than GLT-carbopol gel, and GLT nanogel increased the accumulative amount of GLT in epidermis five times than GLT-carbopol gel. No oedema and erythema were observed after administration of GLT nanogel on the rabbits' skin. Pharmacodynamic study showed that GLT nanogel was more effective than GLT-carbopol gel in treatment of frostbite. CONCLUSION: The GLT nanogel possess superior therapeutic effect for frostbite compared with the GLT-carbopol gel, which indicates that nanogels are eligible for the use as a suitable nanomedicine for dermal delivery of poorly soluble drugs such as GLT.

Lymphocyte-platelet interactions in patients with deep frostbites with various nutritional statuses.

The purpose of the study was to determine the relative number and degree of lymphocyte-platelet adhesion in patients with frostbites of III-IV degree of extremities with malnutrition and eutrophia. Methods: Non-randomized prospective controlled study was performed in 49 patients of both sexes, aged from 16 to 60 years, with frostbites of III-IV degree of extremities. The object of the study was the blood plasma. Test subjects were divided into two groups according to the trophic status on the scale of Luft V.M and Kostyuchenko A.L. By the original method of the Professor Vitkovsky Yu.A. (1999) number of lymphocyte-platelet coaggregations was counted in 100 cells (percentage), which is relative number of the lymphocyte-platelet adhesion (LTA). In this case lymphocyte which adhered to its surface one or more platelets was named the coaggregation. Lymphocyte-platelet index (LTI) or the degree of LTA was determined as the arithmetic mean of the number of platelets which have adhered to a single lymphocyte. Results: The relative number of LTA greater in patients with eutrophia (n = 19) vs. (p<0.001) the control group (n = 20) and vs. (p = 0.008) patients with malnutrition (n = 20). The relative number of LTA is not different in patients with malnutrition vs. (p = 0.085) the control group. LTI greater in patients with eutrophia vs. the control group (p<0.001), and vs. patients with malnutrition (p = 0.020). LTI greater in patients with malnutrition vs. the control group (p = 0.006). Conclusion: It was established that LTI increased irrespective of premorbid trophic status, and LTA percentage increased only in patients with eutrophia. In patients with malnutrition LTA degree and LTA percentage were detected less than in patients with normal nutritional status.

[Frostbite injuries causing compromised airway after inhalation of propane]. / Forfrysninger som årsag til truet luftvej efter inhalation af flaskegas.

We describe a case report of a 23-year-old man with acute pharyngeal injuries due to frostbite subsequent to inhalation of propane. He was fiber-optically intubated on admission to hospital since his airways were considered acutely compromised. He was subsequently kept intubated for 11 days due to persistent pharyngeal oedema and frostbite injuries. The latter is caused by low temperature of propane upon release from a pressurized container. Injuries caused by frostbite often gradually progress and thus caution should be exerted in regards to airway management.

[Treatment of 568 patients with frostbite in northeastern China with an analysis of rate of amputation].

OBJECTIVE: To study the key points of treatment and amputation in patients with frostbite, so as to increase the successful rate of the treatment. METHODS: Five hundred and sixty-eight patients with frostbite admitted to our department from January 2005 to December 2014. (1) For the patients admitted to our department within one week after injury, the frostbite wounds were soaked in 42 °C herbal fluid (twice per day, 30 min for each time) and irradiated with infrared or red light (three times per day, 40 min for each time) from the day of admission to the 7th day after injury. Meanwhile, treatment for improvement of microcirculation, vasodilation, and anti-infection were also given. Then they received infrared or red light irradiation to the wound sites. For the patients admitted to our department longer than one week after frostbite, the frostbite wounds were irradiated with infrared or red light, and treated with antibiotics if inflammation was found around the wound. Among all the patients, 5 cases suffered from frozen stiff, and they were given fluid resuscitation as well as above-mentioned treatments after admission. (2) All patients were given wound treatment immediately after admission. The superficial partial-thickness wounds and deep partial-thickness wounds of 264 patients were given routine dressing change. The full-thickness wounds in 79 patients were treated with exposure therapy after routine dressing change first, and then granulation tissue of these wounds were grafted with autologous thigh split-thickness skin grafts. After debridement and exposure therapy, amputation was done in 225 patients 3 to 4 weeks after injury when the underlying bone was exposed. In 4 patients with exposure of calcaneus, the wounds were covered with reverse sural nerve nutrient vessels island flap. Mean healing time of superficial partial-thickness wound and deep partial-thickness wound, survival rate of skin graft in full-thickness wound, and survival rate of flap covering wound deep to bone at the heel were all recorded. The amputation rate of patients injured in December, January, February, and other months, that of patients admitted shorter than 1 day after frostbite, 1 to 3 days after frostbite, longer than 3 days and shorter than or equal to 5 days after frostbite, and longer than 5 days after frostbite, that of patients caused by drunkenness, mental disorders, improper protection, going astray, and trauma including traffic accident etc., and that of patients treated with rewarming under room temperature, rubbing with snow, wrapping with quilt, and soaking in warm water before admission were all recorded and analyzed. Parts of the data were processed with χ(2) test. RESULTS: All patients were survived after treatment. Average wound healing time of superficial partial -thickness wound and deep partial-thickness wound was respectively 10 and 23 days. The survival rate of skin graft on full-thickness wound was about 95%. Survival rate of flap on wound deep to bone at the heel was 100%. Amputation rates of patients injured in December and January were respectively 47.46% (84/177), 42.56% (103/242), and both were significantly higher than those of patients injured in February and the other months [respectively 29.55% (26/88), 13.11% (8/61), with χ(2) values from 42.595 to 220.900, P values below 0.01]. Amputation rate of patients with admission time shorter than 1 day after frostbite was 32.06% (84/262), which was obviously lower than that of patients with admission time from 1 to 3 days after frostbite, longer than 3 days and less than or equal to 5 days after frostbite, or longer than 5 days after frostbite [respectively 40.48% (68/168), 49.02% (50/102), 52.78% (19/36), with χ(2) values from 107.284 to 165.350, P values below 0.01]. Amputation rates of patients with frostbite occurring after getting drunkenness, mental disorders, and trauma including traffic accident etc. were respectively 42.06% (106/252), 43.48% (60/138), and 53.12% (17/32), and they were all significantly higher than those of patients with frostbite caused by improper protection and going astray [respectively 27.45% (28/102), 22.73% (10/44), with χ(2) values from 187.260 to 209.738, P values below 0.01]. Amputation rates of patients undergoing treatment of rewarming under room temperature, rubbing with snow, wrapping with quilt before admission were respectively 44.29% (62/140), 48.28% (84/174), and 35.38% (46/130), and they were significantly higher than the amputation rate of patients who received the treatment of soaking in warm water [23.39% (29/124), with χ(2) values from 97.364 to 136.189, P values below 0.01]. CONCLUSIONS: Early diagnosis and treatment, properly rewarming at early stage, and correct wound treatment are the key points for reducing amputation rate of patients after frostbite. Attention should be paid to the occurrence of frostbite in December and January, and also to protection of high-risk groups (patients with mental disorders and drunker).

Frostbite of both first digits of the foot treated with delayed hyperbaric oxygen:a case report and review of literature.

BACKGROUND: Frostbite is an uncommon event that can occur from exposure to temperatures below -4 degrees C and can lead to potential serious tissue damage and necrosis. This in turn can result in debilitating amputations in otherwise healthy people. The pathophysiological mechanisms of frostbite have marked similarities to those seen in thermal burns, ischemia/reperfusion injuries and crush injuries--i.e., non-healing wounds and inflammatory processes. These injuries are commonly treated with hyperbaric oxygen therapy. OBJECTIVES: Evidence for treating frostbite with hyperbaric oxygen (HBO2) is scarce, and to date HBO2 is not a standard addition in the multidisciplinary care of freezing injuries. We aim to contribute to the available evidence with a case report and review the literature to reassess the multidisciplinary treatment of frostbite injuries. CASE REPORT AND REVIEW OF LITERATURE: We present a case report of a woman with deep frostbite of the toes treated with hyperbaric oxygen therapy, after a delay of 21 days, with good results. No surgical intervention was needed. A literature search revealed 17 human case reports on frostbite and four animal studies in which hyperbaric oxygen was applied. All case reports showed positive effects, and in none of the cases was amputation necessary. In the animal studies, two showed significant positive results regarding tissue loss and reduction of inflammatory markers, whereas two did not. CONCLUSIONS: Based on our case report as well as the literature and the mechanisms of hyperbaric oxygen, we make the recommendation that this therapy be considered as an addition to the multidisciplinary treatment of frostbite, even after significant delay of treatment.