Consideration of Acute Porphyria in an Emergency Department Patient: A Case Report and Discussion of Common Pitfalls.

INTRODUCTION: Porphyria refers to a group of disorders associated with defects in heme synthesis. They can be associated with severely debilitating features, including abdominal pain, psychiatric symptoms, neurological defects, and cardiovascular irregularities. Although these diseases are rare, patients with attacks often do present to the emergency department (ED) where consideration of porphyria is generally not included in the differential. CASE REPORT: Here, we examine a case of a 16-year-old male who presented to our ED for evaluation of recurring abdominal pain and auditory hallucinations in which porphyria was considered by the emergency physician. DISCUSSION: Not considering acute porphyria in patients with recurring neurovisceral symptoms in the ED can lead to missed opportunities for diagnosing such pathologies.

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Management of Tick-Borne Illness in the United States.

The Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for the prevention and management of tick-borne illness (TBI). Recommendations are graded based on quality of supporting evidence according to criteria put forth by the American College of Chest Physicians. The guidelines include a brief review of the clinical presentation, epidemiology, prevention, and management of TBI in the United States, with a primary focus on interventions that are appropriate for resource-limited settings. Strong recommendations are provided for the use of DEET, picaridin, and permethrin; tick checks; washing and drying clothing at high temperatures; mechanical tick removal within 36 h of attachment; single-dose doxycycline for high-risk Lyme disease exposures versus "watchful waiting;" evacuation from backcountry settings for symptomatic tick exposures; and TBI education programs. Weak recommendations are provided for the use of light-colored clothing; insect repellents other than DEET, picaridin, and permethrin; and showering after exposure to tick habitat. Weak recommendations are also provided against passive methods of tick removal, including the use of systemic and local treatments. There was insufficient evidence to support the use of long-sleeved clothing and the avoidance of tick habitat such as long grasses and leaf litter. Although there was sound evidence supporting Lyme disease vaccination, a grade was not offered as the vaccine is not currently available for use in the United States.

Epidemiology of Ice Climbing Injuries Among Recreational Ice Climbers at the 2019 Ouray Ice Climbing Festival.

INTRODUCTION: As a close relative to the sports of mountaineering and rock climbing, water ice climbing has been traditionally considered "high risk." There is little data to support or refute this assertion. Prior estimates of the injury rate range from 4.8 to 248 injuries per 1000 participation hours. In this study, we characterized the types of injuries and determined an injury incidence among water ice climbing participants at the 2019 Ouray Ice Festival climbing manmade ice walls. METHODS: A survey was distributed during the 2019 Ouray Ice Festival in Ouray, Colorado. Respondents were asked to include festival-related injuries and estimate their participation time at the 4-d festival. Individuals who reported an injury were asked to provide additional details with regard to injury type, location, and timing. The injury incidence rate was calculated as the total number of injuries reported divided by the total number of participation hours and is reported as injuries per 1000 participation hours. RESULTS: A total of 75 surveys were analyzed. A total of 16 injuries, all which were minor, and 912 participation hours were reported, resulting in an injury incidence of 17.6 injuries per 1000 participation hours. CONCLUSIONS: This study reports an injury incidence based on an unselected sample of water ice climbers at an ice climbing festival. Water ice climbing at festivals appears to result in injuries of minor severity with no major accidents or fatalities. This study could be repeated to confirm its validity with a larger sample size.

Sequelae of Anticoagulant Therapy in a Patient with History of Pulmonary Malignancy: A Case Report.

INTRODUCTION: In patients with known malignancy and possible intracranial metastatic disease who are receiving treatment with therapeutic anticoagulation, limited data exist regarding risk of intracranial bleeding. CASE REPORT: We present a case of a 64-year-old female with known lung malignancy, evidence of possible metastatic disease, and bilateral deep vein thrombosis, who suffered severe intracranial hemorrhage following initiation of therapeutic anticoagulation. Current guidelines, available risk- stratification tools, and treatment options with their risks are discussed. CONCLUSION: In patients with known or suspected intracranial metastatic disease, clinical decision tools can assist both the clinician and the patient in weighing risks and benefits of anticoagulation.

Psychological Care Augmented by Telemedicine after a Polar Bear Encounter at an Arctic Research Station: A Case Report.

Background: Psychologically stressful events can be particularly challenging in the wilderness or extreme environments due to a lack of immediate medical or psychological support. Telemedicine consultations may provide a means to supply medical providers in austere environments with expertise when confronted with these situations. Methods: In this study, we detail a case of psychological care imparted to residents at a remote, arctic research station after they encountered a polar bear. The health care provider at the camp was not a dedicated mental health professional but was able to deliver psychological care with assistance from a trained provider through use of telemedicine. We provide a brief overview of the evidence behind psychological first aid and incident support sessions for the treatment of stress injuries. We also review the evidence for telemedicine for psychological care in wilderness situations and describe its use in this scenario. Results: All station residents were able to resume regular arctic activities. Resident feedback was that the sessions were advantageous. Conclusions: We anticipate the need for psychological care in austere situations to increase in the future, and further training in this field and the advancement of telemedicine consultation will be of benefit to wilderness providers.

Effect of Fluctuating Extreme Temperatures on Tranexamic Acid.

INTRODUCTION: Tranexamic acid (TXA) is an antifibrinolytic agent shown to reduce morbidity and mortality in hemorrhagic shock. It has potential use in prehospital and wilderness medicine; however, in these environments, TXA is likely to be exposed to fluctuating and extreme temperatures. If TXA degrades under these conditions, this may reduce antifibrinolytic effects. PROBLEM: This study sought to determine if repetitive temperature derangement causes degradation of TXA. METHODS: Experimental samples underwent either seven days of freeze/thaw or heating cycles and then were analyzed via mass spectrometry for degradation of TXA. An internal standard was used for comparison between experimental samples and controls. These samples were compared to room temperature controls to determine if fluctuating extreme temperatures cause degradation of TXA. RESULTS: The coefficient of variability of ratios of TXA to internal standard within each group (room temperature, freeze, and heated) was less than five percent. An independent t-test was performed on freeze/thaw versus control samples (t = 2.77; P = .17) and heated versus control samples (t = 2.77; P = .722) demonstrating no difference between the groups. CONCLUSION: These results suggest that TXA remains stable despite repeated exposure to extreme temperatures and does not significantly degrade. These findings support the stability of TXA and its use in extreme environments.

Asymptomatic Hypotension in a Patient with Catheter-related Right Atrial Thrombus.

Atrial thrombi can be a complication in patients with indwelling central-line catheters, and failure to diagnose can potentially be lethal. This condition is generally associated with profound hypo-perfused states. Here we present a case of a 77-year-old female who arrived to our emergency department for evaluation of a leg laceration and was incidentally found to have a catheter-related right atrial thrombus using point-of-care ultrasound.

Enhancing osteoconductivity of fibrin gels with apatite-coated polymer microspheres.

Fibrin gels are a promising material for use in promoting bone repair and regeneration due to their ease of implant formation, tailorability, biocompatibility, and degradation by natural processes. However, these materials lack necessary osteoconductivity to nucleate calcium, integrate with surrounding bone, and promote bone formation. Polymeric substrata formed from poly(lactide-co-glycolide) (PLG) are widely used in bone tissue engineering. A carbonated apatite layer of bone-like mineral can be successfully grown on the surface of PLG microspheres after a multiday incubation process in modified simulated body fluid. Such coatings improve the osteoconductivity of the polymer, provide nucleation sites for cell-secreted calcium, and enhance the potential osseointegration with host tissue. We examined the capacity of mineralized polymeric microspheres suspended within fibrin hydrogels to enhance the osteoconductivity of fibrin gels and increase the osteogenic potential of these materials. The inclusion of microparticles, both nonmineralized and mineralized, reduced the capacity of mesenchymal stem cells (MSCs) to contract the gel. When cultured in osteogenic media, we detected a near linear increase in both calcium and phosphate incorporation in gels containing mineralized microspheres and entrapped MSCs. The osteoconductivity of acellular fibrin gels with mineralized and nonmineralized microspheres was assessed in a rodent calvarial bone defect over 12 weeks. Compared to untreated rodent calvarial bone defects, we detected significant increases in early vascularization when treated with fibrin gels, with greater vascularization, on average, occurring with gels containing microspheres. We detected a trend for increased bone mineral density in gels containing mineralized microspheres after 12 weeks. These findings demonstrate that the osteoconductivity of fibrin gels can be increased by inclusion of mineralized microspheres, but additional signals may be required to rapidly accelerate bone repair.

Neurite outgrowth in fibrin gels is regulated by substrate stiffness.

Fibrin is a promising matrix for use in promoting nerve repair given its natural occurrence in peripheral nerve injuries, and the biophysical properties of this matrix can be regulated to modulate tissue regeneration. In this study, we examined the effect of physical and mechanical properties of fibrin gels on dorsal root ganglia (DRG) neurite extension. Increases in fibrinogen concentration increased the number of fibrin strands, resulting in decreased pore size and increased stiffness. Neurite extension was reduced when DRG explants were cultured within fibrin gels of increasing fibrinogen concentrations (from 9.5 to 141 mg/mL). The addition of NaCl also increased the number of fibrin strands, reducing fiber diameter and porosity, while increasing mechanical strength, and reductions in neurite extension correlated with increases in NaCl content. We determined that neurite extension within fibrin gels is dependent on fibrinolysis and is mediated by the secretion of serine proteases and matrix metalloproteinases by entrapped DRGs, as confirmed by culturing cells in the presence of inhibitors against these enzymes and real-time-polymerase chain reaction. Taken together, the results of this study provide new insight into the effect of fibrin gel biophysical properties on neurite extension and suggest new opportunities to improve the efficacy of these materials when used as nerve guidance conduits.

Osteogenic response to BMP-2 of hMSCs grown on apatite-coated scaffolds.

Osteoconductive materials play a critical role in promoting integration with surrounding bone tissue and resultant bone repair in vivo. However, the impact of 3D osteoconductive substrates coupled with soluble signals on progenitor cell differentiation is not clear. In this study, we investigated the influence of bone morphogenetic protein-2 (BMP-2) concentration on the osteogenic differentiation of human mesenchymal stem cells (hMSCs) when seeded in carbonated apatite-coated polymer scaffolds. Mineralized scaffolds were more hydrophilic and adsorbed more BMP-2 compared to non-mineralized scaffolds. Changes in alkaline phosphatase (ALP) activity within stimulated hMSCs were dependent on the dose of BMP-2 and the scaffold composition. We detected more cell-secreted calcium on mineralized scaffolds at all time points, and higher BMP-2 concentrations resulted in increased ALP and calcium levels. RUNX2 and IBSP gene expression within hMSCs was affected by both substrate and soluble signals, SP7 by soluble factors, and SPARC by substrate-mediated cues. The present data indicate that a combination of apatite and BMP-2 do not simply enhance the osteogenic response of hMSCs, but act through multiple pathways that may be both substrate- and growth factor-mediated. Thus, multiple signaling strategies will likely be necessary to achieve optimal bone regeneration.

Designing bioactive delivery systems for tissue regeneration.

The direct infusion of macromolecules into defect sites generally does not impart adequate physiological responses. Without the protection of delivery systems, inductive molecules may likely redistribute away from their desired locale and are vulnerable to degradation. In order to achieve efficacy, large doses supplied at interval time periods are necessary, often at great expense and ensuing detrimental side effects. The selection of a delivery system plays an important role in the rate of re-growth and functionality of regenerating tissue: not only do the release kinetics of inductive molecules and their consequent bioactivities need to be considered, but also how the delivery system interacts and integrates with its surrounding host environment. In the current review, we describe the means of release of macromolecules from hydrogels, polymeric microspheres, and porous scaffolds along with the selection and utilization of bioactive delivery systems in a variety of tissue-engineering strategies.

Biomimetic scaffolds fabricated from apatite-coated polymer microspheres.

The deposition of a bonelike mineral on the surface of polymer scaffolds results in the formation of hybrid biomaterials, possessing enhanced osteoconductivity while retaining appropriate biodegradability. However, current methods of fabricating such composite scaffolds use a prolonged incubation process, which permits scaffold deformation and premature loss of incorporated macromolecules. We hypothesized that the fabrication of biomineralized polymer scaffolds could be achieved using premineralized polymer microspheres generated through incubation in a modified simulated body fluid (mSBF). We explored the material characteristics of these substrates and characterized the in vitro osteogenic differentiation of human mesenchymal stem cells (hMSCs) when cultured on these novel scaffolds. Unlike scaffolds prepared using the conventional approach, premineralized scaffolds maintained their initial conformation after fabrication, achieved improved mineral distribution throughout the substrate, and enabled significantly greater incorporation efficiency of a model protein. We did not detect differences in osteogenic differentiation as determined by alkaline phosphatase activity and osteopontin secretion. However, we did observe a significant increase in cell-secreted calcium by hMSCs seeded on scaffolds prepared from premineralized polymer. These results demonstrate that the use of premineralized polymeric materials to fabricate biodegradable polymer scaffolds is an improved method for composite scaffold formation and may have numerous advantages for use in bone tissue engineering.