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.

Wilderness Medical Society Clinical Practice Guidelines for the Prevention, Diagnosis, and Treatment of Acute Altitude Illness: 2024 Update.

To provide guidance to clinicians about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for prevention, diagnosis, and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. Recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches for managing each form of acute altitude illness that incorporate these recommendations as well as recommendations on how to approach high altitude travel following COVID-19 infection. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in Wilderness & Environmental Medicine in 2010 and the subsequently updated WMS Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness published in 2014 and 2019.

Flying to high-altitude destinations: Is the risk of acute mountain sickness greater?

BACKGROUND: Altitude sojourns increasingly attract individuals of all ages and different health statuses due to the appeal of high-altitude destinations worldwide and easy access to air travel. The risk of acute mountain sickness (AMS) when flying to high-altitude destinations remains underemphasized. Thus, this review aims to evaluate the altitude-dependent AMS incidence depending on the mode of ascending, e.g. by air vs terrestrial travel. METHODS: A literature search was performed to identify the observational studies assessing AMS incidence after acute ascent of primarily healthy adults to real high altitude. In addition, placebo arms of interventional trials evaluating the prophylactic efficacy of various drugs have been separately analysed to confirm or refute the findings from the observational studies. Linear regression analyses were used to evaluate the altitude-dependent AMS incidence. RESULTS: Findings of 12 observational studies, in which the AMS incidence in 11 021 individuals ascending to 19 different altitudes (2200-4559 m) was evaluated, revealed an impressive 4.5-fold steeper increase in the AMS incidence for air travel as compared with slower ascent modes, i.e. hiking or combined car and/or air travel and hiking. The higher AMS incidence following transportation by flight vs slower means was also confirmed in placebo-treated participants in 10 studies of drug prophylaxis against AMS. CONCLUSIONS: Due to the short time span in going from low to high altitude, reduced acclimatization likely is the main reason for a higher AMS risk when travelling to high-altitude destinations by flight. To avoid frustrating travel experiences and health risks, appropriate and timely medical advice on how to prepare for air travel to high altitude is of vital importance. Effective preparation options include the use of modern pre-acclimatization strategies and pharmacological prophylaxis by acetazolamide or dexamethasone, or even considering alternate itineraries with more gradual ascent.

Strengthening Altitude Knowledge: A Delphi Study to Define Minimum Knowledge of Altitude Illness for Laypersons Traveling to High Altitude.

Berendsen, Remco R., Peter Bärtsch, Buddha Basnyat, Marc Moritz Berger, Peter Hackett, Andrew M. Luks, Jean-Paul Richalet, Ken Zafren, Bengt Kayser, and the STAK Plenary Group. Strengthening altitude knowledge: a Delphi study to define minimum knowledge of altitude illness for laypersons traveling to high altitude. High Alt Med Biol. 23:330-337, 2022. Introduction: A lack of knowledge among laypersons about the hazards of high-altitude exposure contributes to morbidity and mortality from acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE) among high-altitude travelers. There are guidelines regarding the recognition, prevention, and treatment of acute-altitude illness for experts, but essential knowledge for laypersons traveling to high altitudes has not been defined. We sought expert consensus on the essential knowledge required for people planning to travel to high altitudes. Methods: The Delphi method was used. The panel consisted of two moderators, a core expert group and a plenary expert group. The moderators made a preliminary list of statements defining the desired minimum knowledge for laypersons traveling to high altitudes, based on the relevant literature. These preliminary statements were then reviewed, supplemented, and modified by a core expert group. A list of 33 statements was then presented to a plenary group of experts in successive rounds. Results: It took three rounds to reach a consensus. Of the 10 core experts invited, 7 completed all the rounds. Of the 76 plenary experts, 41 (54%) participated in Round 1, and of these 41 a total of 32 (78%) experts completed all three rounds. The final list contained 28 statements in 5 categories (altitude physiology, sleeping at altitude, AMS, HACE, and HAPE). This list represents an expert consensus on the desired minimum knowledge for laypersons planning high-altitude travel. Conclusion: Using the Delphi method, the STrengthening Altitude Knowledge initiative yielded a set of 28 statements representing essential learning objectives for laypersons who plan to travel to high altitudes. This list could be used to develop educational interventions.

Posttranslational regulation of mitochondrial frataxin and identification of compounds that increase frataxin levels in Friedreich's ataxia.

Friedreich's ataxia (FRDA) is a degenerative disease caused by a decrease in the mitochondrial protein frataxin (Fxn), which is involved in iron-sulfur cluster (ISC) synthesis. Diminutions in Fxn result in decreased ISC synthesis, increased mitochondrial iron accumulation, and impaired mitochondrial function. Here, we show that conditions that result in increased mitochondrial reactive oxygen species in yeast or mammalian cell culture give rise to increased turnover of Fxn but not of other ISC synthesis proteins. We demonstrate that the mitochondrial Lon protease is involved in Fxn degradation and that iron export through the mitochondrial metal transporter Mmt1 protects yeast Fxn from degradation. We also determined that when FRDA fibroblasts were grown in media containing elevated iron, mitochondrial reactive oxygen species increased and Fxn decreased compared to WT fibroblasts. Furthermore, we screened a library of FDA-approved compounds and identified 38 compounds that increased yeast Fxn levels, including the azole bifonazole, antiparasitic fipronil, antitumor compound dibenzoylmethane, antihypertensive 4-hydroxychalcone, and a nonspecific anion channel inhibitor 4,4-diisothiocyanostilbene-2,2-sulfonic acid. We show that top hits 4-hydroxychalcone and dibenzoylmethane increased mRNA levels of transcription factor nuclear factor erythroid 2-related factor 2 in FRDA patient-derived fibroblasts, as well as downstream antioxidant targets thioredoxin, glutathione reductase, and superoxide dismutase 2. Taken together, these findings reveal that FRDA progression may be in part due to oxidant-mediated decreases in Fxn and that some approved compounds may be effective in increasing mitochondrial Fxn in FRDA, delaying disease progression.

Using triallelic SNPs for determining parentage in North American yak ( Bos grunniens) and estimating cattle ( B. taurus) introgression.

Background: Genetic testing for pedigree accuracy is critical for managing genetic diversity in North American (NA) yak ( Bos grunniens), a population expanded mostly from imported zoological park specimens.  DNA testing also enhances species conservation by identifying recent B. taurus F1 hybrid ancestors (within three generations).  Biallelic single nucleotide polymorphisms (SNPs) can accomplish either task, but increases the marker count and costs necessary to achieve both.  Our aim was to identify novel, multifunctional, triallelic yak SNPs (tySNPs), with each having two alleles for yak parentage testing, and a third allele for identifying recent cattle introgression.  Methods:  Genome sequences were aligned to the cattle UMD3.1 assembly and SNPs were screened for 1) heterozygosity in a NA and a Chinese yak, 2) a third allele at high frequency in cattle, and 3) flanking sequences conserved in both species.  Subsequently, tySNPs were filtered for unique alignment to the haplotype-resolved F1 yak assembly.  Allele frequencies were estimated in a subset of 87 tySNPs by genotyping 170 NA yak. Results:  We identified 610 autosomal tySNPs, distributed in 441 clusters with 5 Mb average genome spacing.  The average NA yak minor allele frequency was high (0.296), while average introgressed cattle alleles were low (0.004).  In simulations with tySNPs, 28 were sufficient for globally-unique animal identification (P I=5.81x10 -12), 87 were able to exclude 19 random bulls from parentage at the 99% level without using the dam's genotype (P E=5.3x10 -4), and 87 were able to detect F1 hybridization events after three generations of yak backcrosses (1/16th B. taurus germplasm). Conclusions:  Identifying animals, determining parentage and detecting recent hybridization events was efficient with as few as 87 tySNPs.  A similar triallelic approach could be used with other bottlenecked Bos species that hybridize with cattle, such as NA plains bison ( B. bison).

No Relevant Analogy Between COVID-19 and Acute Mountain Sickness.

Berger, Marc Moritz, Peter H. Hackett, and Peter Bärtsch. No relevant analogy between COVID-19 and acute mountain sickness. High Alt Med Biol. 21:315-318, 2020.-Clinicians and scientists have suggested therapies for coronavirus disease-19 (COVID-19) that are known to be effective for other medical conditions. A recent publication suggests that pathophysiological mechanisms underlying acute mountain sickness (a syndrome of nonspecific neurological symptoms typically experienced by nonacclimatized individuals at altitudes >2500 m) may overlap with the mechanisms causing COVID-19. In this short review, we briefly evaluate this mistaken analogy and demonstrate that this concept is not supported by scientific evidence.

Continuous chromosome-scale haplotypes assembled from a single interspecies F1 hybrid of yak and cattle.

BACKGROUND: The development of trio binning as an approach for assembling diploid genomes has enabled the creation of fully haplotype-resolved reference genomes. Unlike other methods of assembly for diploid genomes, this approach is enhanced, rather than hindered, by the heterozygosity of the individual sequenced. To maximize heterozygosity and simultaneously assemble reference genomes for 2 species, we applied trio binning to an interspecies F1 hybrid of yak (Bos grunniens) and cattle (Bos taurus), 2 species that diverged nearly 5 million years ago. The genomes of both of these species are composed of acrocentric autosomes. RESULTS: We produced the most continuous haplotype-resolved assemblies for a diploid animal yet reported. Both the maternal (yak) and paternal (cattle) assemblies have the largest 2 chromosomes in single haplotigs, and more than one-third of the autosomes similarly lack gaps. The maximum length haplotig produced was 153 Mb without any scaffolding or gap-filling steps and represents the longest haplotig reported for any species. The assemblies are also more complete and accurate than those reported for most other vertebrates, with 97% of mammalian universal single-copy orthologs present. CONCLUSIONS: The high heterozygosity inherent to interspecies crosses maximizes the effectiveness of the trio binning method. The interspecies trio binning approach we describe is likely to provide the highest-quality assemblies for any pair of species that can interbreed to produce hybrid offspring that develop to sufficient cell numbers for DNA extraction.

Wilderness Medical Society Clinical Practice Guidelines for the Out-of-Hospital Evaluation and Treatment of Accidental Hypothermia: 2019 Update.

To provide guidance to clinicians, the Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for the out-of-hospital evaluation and treatment of victims of accidental hypothermia. The guidelines present the main diagnostic and therapeutic modalities and provide recommendations for the management of hypothermic patients. The panel graded the recommendations based on the quality of supporting evidence and a balance between benefits and risks/burdens according to the criteria published by the American College of Chest Physicians. The guidelines also provide suggested general approaches to the evaluation and treatment of accidental hypothermia that incorporate specific recommendations. This is the 2019 update of the Wilderness Medical Society Practice Guidelines for the Out-of-Hospital Evaluation and Treatment of Accidental Hypothermia: 2014 Update.

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Frostbite: 2019 Update.

The Wilderness Medical Society convened an expert panel to develop a set of evidence-based guidelines for 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 2014.

Day of Ascent Dosing of Acetazolamide for Prevention of Acute Mountain Sickness.

Background: Acetazolamide is the most common medication used for prevention of acute mountain sickness (AMS), usually administered the day or night before ascent. The objective of this study was to evaluate the efficacy of day of ascent dosing of acetazolamide for AMS prevention. Methods: Double-blind, randomized, controlled noninferiority trial of acetazolamide 125 mg twice daily beginning either the night before or the morning of ascent. Healthy low altitude adults ascended from 1240 m (4100 ft) to 3810 m (12,570 ft) during summer 2018 on White Mountain, California. Primary outcome was incidence of AMS with the two different dosing patterns, assessed by the 1993 Lake Louise Questionnaire (LLQ) of ≥3 with headache and a minimum of 1 for other symptom. Results: One hundred four participants completed the study, with 54 (52%) randomized to night before acetazolamide and 50 (48%) to day of ascent dosing, without differences in baseline characteristics. There was 9% greater incidence of AMS in the day of ascent acetazolamide group (48.0% vs. 39%, 95% confidence interval [CI] -11.8 to 30, p = 0.46, number needed to treat [NNT] = 5.6 vs. 3.7), with the CI just surpassing the predetermined 26% noninferiority margin. There was a lower incidence of severe AMS (1993 LLQ >5) in the day of ascent group (n = 5, 10%, NNT = 2.3) compared with night before dosing (n = 12, 22%, NNT = 3.1) (95% CI -28 to 3.6), and lower average symptom severity in the day of ascent group (3 vs. 3.5, 95% CI -0.5 to 1.4). Conclusions: Day of ascent acetazolamide demonstrated higher rates of AMS compared with traditional dosing by a small margin. With similar rates of severe AMS and overall symptom severity, the potential for improved convenience and compliance may support day of ascent use.

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2019 Update.

To provide guidance to clinicians about best preventive and therapeutic practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for prevention and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. Recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches to prevention and management of each form of acute altitude illness that incorporate these recommendations. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in 2010 and subsequently updated as the WMS Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness in 2014.

Altitude Sickness Prevention with Ibuprofen Relative to Acetazolamide.

BACKGROUND: Acute mountain sickness is a common occurrence for travel to high altitudes. Although previous studies of ibuprofen have shown efficacy for the prevention of acute mountain sickness, recommendations have been limited, as ibuprofen has not been compared directly with acetazolamide until this study. METHODS: Before their ascent to 3810 m on White Mountain in California, adult volunteers were randomized to ibuprofen (600 mg, 3 times daily, started 4 hours before the ascent), or to acetazolamide (125 mg, twice daily, started the night before the ascent). The main outcome measure was acute mountain sickness incidence, using the Lake Louise Questionnaire (LLQ), with a score of >3 with headache. Sleep quality and headache severity were measured with the Groningen Sleep Quality Survey (GSQS). This trial was registered at ClinicalTrials.gov: NCT03154645 RESULTS: Ninety-two participants completed the study: 45 (49%) on ibuprofen and 47 (51%) on acetazolamide. The total incidence of acute mountain sickness was 56.5%, with the incidence for the ibuprofen group being 11% greater than that for acetazolamide, surpassing the predetermined 26% noninferiority margin (62.2% vs 51.1%; 95% confidence interval [CI], -11.1 to 33.5). No difference was found in the total LLQ scores or subgroup symptoms between drugs (P = .8). The GSQS correlated with LLQ sleep (r = 0.77; 95% CI, 0.67-0.84)=%. The acetazolamide group had higher peripheral capillary oxygen saturation than the ibuprofen group (88.5% vs 85.6%; P = .001). CONCLUSION: Ibuprofen was slightly inferior to acetazolamide for acute mountain sickness prevention and should not be recommended over acetazolamide for rapid ascent. Average symptoms and severity were similar between drugs, suggesting prevention of disease.

Case Report: Severe Frostbite in Extreme Altitude Climbers-The Kathmandu Iloprost Experience.

Severe frostbite occurs frequently at extreme altitude in the Himalayas, often resulting in amputations. Recent advances in treatment of frostbite injuries with either intravenous or intra-arterial tissue plasminogen activator, or with iloprost, have improved outcomes in frostbite injuries, but only if the patient has access to these within 24 to 48 h postinjury, and ideally even sooner. Frostbitten Himalayan climbers are seldom able to reach medical care in this time frame. We wished to see if delayed iloprost use (up to 72 h) would help reduce tissue loss in grade 3 to 4 frostbite. In a series of 5 consecutive climbers with severe frostbite in whom we used iloprost, 4 of whom received treatment between 48 and 72 h from injury, 2 had excellent results with minimal tissue loss, and 2 had good results with tissue loss less than expected. The 1 patient with a poor outcome likely experienced a freeze-thaw-refreeze injury. This small series suggests that iloprost can be beneficial for severe frostbite, even after the standard 48-h window and perhaps for up to 72 h.