Damage-control vascular surgery in Canada: supporting surgeons and teams.

SummaryIn Canada, trauma patients often present initially to non-trauma hospitals without vascular surgeons on site. Local surgeons need skills and support for damage-control vascular surgery. Canadian training programs in general surgery should equip trainees with skills in this area, including resuscitation, identification of vascular injury, hemorrhage control, and temporizing measures (e.g., shunts, ligation). Caring for trauma patients is a multidisciplinary endeavour; understanding local/regional skill sets and from whom to seek help is vital. Opportunities for skills maintenance should also be encouraged for surgeons practising at sites where acutely injured patients present.

Central Centrifugal Cicatricial Alopecia Associated With PDL1 Loss and Increased Expression of Caspase 3: A Case Series.

ABSTRACT: Central centrifugal cicatricial alopecia (CCCA) is a scarring alopecia that disproportionately affects patients with skin of color. Genetic studies have revealed that approximately 30% of CCCAs are associated with peptidyl arginine deiminase 3 misfolding mutations. Patients with CCCA usually have a poor prognosis with progressive and permanent hair loss. To further characterize CCCA, we evaluated the inflammatory milieu, PDL1, and caspase 3 expression. The data support the idea of CCCA being a CD4-predominant T-cell process. The loss of PDL1 and increase in caspase 3 expression raises the possibility of involvement of the PD1/PDL1 pathway in CCCA.

The seventh international RASopathies symposium: Pathways to a cure-expanding knowledge, enhancing research, and therapeutic discovery.

RASopathies are a group of genetic disorders that are caused by genes that affect the canonical Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Despite tremendous progress in understanding the molecular consequences of these genetic anomalies, little movement has been made in translating these findings to the clinic. This year, the seventh International RASopathies Symposium focused on expanding the research knowledge that we have gained over the years to enhance new discoveries in the field, ones that we hope can lead to effective therapeutic treatments. Indeed, for the first time, research efforts are finally being translated to the clinic, with compassionate use of Ras/MAPK pathway inhibitors for the treatment of RASopathies. This biannual meeting, organized by the RASopathies Network, brought together basic scientists, clinicians, clinician scientists, patients, advocates, and their families, as well as representatives from pharmaceutical companies and the National Institutes of Health. A history of RASopathy gene discovery, identification of new disease genes, and the latest research, both at the bench and in the clinic, were discussed.

Neurothekeoma With PI3K w552*, ALK P1469S, SMO G461S, and ERBB3 L77M Genetic Alterations.

ABSTRACT: Neurothekeoma, a lesion of possible fibrohistiocytic origin, is a rare, benign, superficial soft tissue tumor, histologically subclassified in 3 types: myxoid, cellular, or mixed. It clinically presents as a solitary, pink to brown nodule, ranging from 0.3 to 2.0 cm. Four point mutations (PI3K w552*, ALK P1469S, SMO G461S, and ERBB3 L77M) were identified by next-generation sequencing of a neurothekeoma presenting in the left inner thigh of a 53-year-old man. We highlight novel genetic alterations (SMO G461S and ERBB3 L77M) and previously known mutations (PI3KCA w552* and ALK P1469S) that play a role in other pathogenic pathways, but to the best of our knowledge, these have not yet been reported in neurothekeoma.

Preliminary Characterization of NP339, a Novel Polyarginine Peptide with Broad Antifungal Activity.

Fungi cause disease in nearly one billion individuals worldwide. Only three classes of antifungal agents are currently available in mainstream clinical use. Emerging and drug-resistant fungi, toxicity, and drug-drug interactions compromise their efficacy and applicability. Consequently, new and improved antifungal therapies are urgently needed. In response to that need, we have developed NP339, a 2-kDa polyarginine peptide that is active against pathogenic fungi from the genera Candida, Aspergillus, and Cryptococcus, as well as others. NP339 was designed based on endogenous cationic human defense peptides, which are constituents of the cornerstone of immune defense against pathogenic microbes. NP339 specifically targets the fungal cell membrane through a charge-charge-initiated membrane interaction and therefore possesses a differentiated safety and toxicity profile to existing antifungal classes. NP339 is rapidly fungicidal and does not elicit resistance in target fungi upon extensive passaging in vitro. Preliminary analyses in murine models indicate scope for therapeutic application of NP339 against a range of systemic and mucocutaneous fungal infections. Collectively, these data indicate that NP339 can be developed into a highly differentiated, first-in-class antifungal candidate for poorly served invasive and other serious fungal diseases.

Xanthomatous Dermal Changes in a Patient With Locally Advanced Basal Cell Carcinoma Treated Using Vismodegib.

ABSTRACT: Basal cell carcinoma (BCC) is the most commonly diagnosed cutaneous cancer in the United States with more than 2.5 million treated annually. Genetic studies have revealed that approximately 90% of BCCs have a mutation in the hedgehog-signaling pathway. Patients with BCC usually have an excellent prognosis with surgical modalities, however, patients with locally advanced BCC may potentially experience significant cosmetic or functional impairment, with only surgical intervention. Vismodegib is a hedgehog pathway inhibitor that has been successful in treating patients with locally advanced BCC. We report a patient with BCC with a good response to vismodegib and a novel xanthomatous change in the excision specimen.

Vascular trauma: Does experience in the United States apply to a Canadian centre?

Summary: Trauma care has evolved similarly in the United States and Canada over the last 3 decades. Like much of modern trauma care, management of vascular trauma has been influenced by combat surgery experiences in recent wars. The American Association for the Surgery of Trauma sponsored the Prospective Observational Vascular Injury Treatment (PROOVIT) registry to document changes in the treatment of vascular trauma and determine outcomes in the US. However, differences in trauma populations and trauma systems between Canada and the US need to be considered. Here we compare the vascular trauma experience at a Canadian level I trauma centre over a 5-year period to the data in the PROOVIT registry.

Treatment of human polyomavirus-7-associated rash and pruritus with topical cidofovir in a lung transplant patient: Case report and literature review.

Human polyomavirus-7-associated rash and pruritus (PVARP) is a chronic superficial viral skin infection, which primarily impacts immunocompromised individuals. We report on a case of PVARP in a lung transplant recipient. Our patient developed symptoms 13 years after being on his immunosuppressive regimen, with an insidious course of progressive gray lichenification with marked islands of sparing and quality of life-altering pruritus. Treatment for PVARP is not established; however, topical cidofovir combined with immunomodulation may offer sustained therapeutic benefit.

A novel REBOA system: prototype and proof of concept

Background: Lower torso hemorrhage is a significant cause of death from injuries in combat. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been used to rescue patients successfully in the hospital setting, but its prehospital use is controversial. We designed a device that would be easy to use, safer in injured vessels, migration-resistant and amenable to a prehospital environment. Methods: We designed a novel, balloon-led device using common commercial materials. Thin latex rubber was reassembled in cylindrical conformation aligned to the shape of the aorta and invaginated into vinyl tubing. The catheter is placed into the femoral vessel, followed by expression of the balloon with CO2 inflation in a proximal direction to navigate and treat damaged pelvic vasculature, occluding the distal aorta. The system was tested on model aortas (both intact and injured cadaveric porcine aorta) with inline fluid flow and pressure monitoring to determine the maximum pressure the balloons could occlude. The device was also tested on a perfused human cadaveric model. Results: Flow was occluded with the balloon up to an average of 561.1 ± 124.3 mm Hg. It always ruptured before causing damage to the porcine aorta and was able to occlude injured iliac vessels and proceed to occlude the distal aorta. The device was effective in occluding the distal aorta of a perfused human cadaver. Conclusion: This novel, high-volume, low-pressure device can occlude the distal aorta in a simulated human aorta model, cadaveric porcine model and perfused human cadaver. It can occlude fluid flow to supraphysiologic pressures. It is easy to use, migration-resistant, able to navigate and treat injured pelvic vessels, and amenable to prehospital care.

Contexte: L'hémorragie au bas du corps est une importante cause de décès suite aux blessures subies au combat. L'occlusion aortique endovasculaire par ballonnet a été utilisée avec succès comme mesure de réanimation chez des patients hospitalisés, mais son utilisation dans un contexte préhospitalier est controversée. Nous avons conçu un instrument qui serait facile à utiliser, plus sécuritaire en présence de vaisseaux lésés, peu sujet à migrer et adapté au contexte préhospitalier. Méthodes: Nous avons conçu un nouvel instrument guidé par ballonnet et fabriqué à l'aide de matériaux d'usage courant. Du caoutchouc de latex mince a été façonné en cylindre pour épouser la forme de l'aorte et introduit dans un tube de vinyle. Le cathéter est ensuite inséré dans la veine fémorale, après quoi il est gonflé avec du CO2 en direction proximale pour atteindre et traiter le réseau vasculaire pelvien et créer une occlusion aortique distale. Le système a été mis à l'essai sur des aortes modèles (aortes de cadavres de porcs intactes et lésées), avec surveillance interne du débit et de la pression pour déterminer la pression maximale contre laquelle le ballonnet est capable de créer l'occlusion. L'instrument a aussi été testé sur un modèle de cadavre humain perfusé. Résultats: Le ballonnet a permis l'occlusion à une pression moyenne pouvant atteindre 561,1 ± 124,3 mm Hg. Il s'est toujours rompu avant de pouvoir endommager l'aorte porcine et a permis l'occlusion des vaisseaux iliaques lésés et ensuite de l'aorte distale. L'instrument a permis l'occlusion efficace de l'aorte distale d'un cadavre humain perfusé. Conclusion: Ce nouvel instrument à fort volume et faible pression permet de créer l'occlusion de l'aorte distale dans un modèle simulé d'aorte humaine, dans un modèle de cadavre porcin et sur un cadavre humain perfusé. Il est facile à utiliser, peu susceptible de migrer; il se déploie et traite facilement les vaisseaux pelviens lésés et convient au contexte préhospitalier.

Impact of traumatic upper-extremity amputation on the outcome of injury caused by an antipersonnel improvised explosive device

Background: We have previously reported a higher than expected rate of upper-extremity amputation (UEA) in victims of an antipersonnel improvised explosive device (AP-IED) compared with a similar cohort injured by antipersonnel mines (APM). The goal of this study was to describe the rate, severity and impact of UAE caused by an AP-IED. Methods: We analyzed a prospective database of 100 consecutive dismounted AP-IED victims with pattern 1 injuries to compare the outcomes of the cohort with UEA to that without. Results: We found that UEA (8 above elbow, 19 below elbow, 1 through elbow, 3 hand, 15 digit(s)) was much more prevalent with AP-IED than with APM (40% v. 6%, p < 0.001). In addition, UEA was associated with a higher rate of multiple amputations (39 [98%] v. 32 [53%], p < 0.001), bilateral lower-extremity amputation (LEA; 33 [82.5%] v. 30 [53.3%], p = 0.003) and facial injury (8 [20%] v. 4 [6.4%], p = 0.044), but not with pelvic disruption (10 [25%]), genitoperineal mutilation (19 [48%]), eye injury (6 [15%]), or skull fracture (6 [15%]). The fatality rate was higher in patients with UEA than in those without (12 [30%] v. 7 [12%], p = 0.022). Conclusion: Upper-extremity amputation is more prevalent with AP-IED than APM. Presence of UEA is associated with more severe injury and increased risk of death in AP-IED victims. Upper-limb injury has significant consequences for rehabilitation from LEA, which universally accompanies UEA in AP-IED victims. Upper-extremity injury should be amenable to prevention by innovative personal protective equipment designed to protect the flexed elbow.

Contexte: Nous avons déjà fait état d'un taux plus élevé que prévu d'amputations des membres supérieurs (AMS) chez les victimes d'engins explosifs artisanaux (EEA) comparativement à une cohorte similaire blessée par des mines antipersonnel (MAP). L'objectif de cette étude est de décrire le taux, la gravité et l'impact des AMS causées par des EEA. Méthodes: Nous avons analysé une base de données prospective de 100 victimes consécutives d'EEA alors qu'elles se trouvaient hors de leur véhicule et présentant des blessures de type 1 afin de comparer les résultats des cohortes ayant subi ou non des AMS. Résultats: Nous avons constaté que l'AMS (8 au-dessus du coude, 19 sous le coude, 1 au niveau du coude, 3 mains et 15 doigts) était beaucoup plus prévalente avec les EEA qu'avec les MAP (40 % c. 6 %, p < 0,001). De plus, l'AMS a été associée à un taux plus élevé d'amputations multiples (39 [98 %] c. 32 [53 %], p < 0,001), d'amputations bilatérales des membres inférieurs (AMI) (33 [82,5 %] c. 30 [53,3 %], p = 0,003) et de blessures au visage (8 [20 %] c. 4 [6,4 %], p = 0,044), mais non de blessures au bassin (10 [25%]), de mutilations génitopérinéales (19 [48 %]), de blessures oculaires (6 [15 %]), ou de fractures du crâne (6 [15 %]). Le taux de létalité a été plus élevé chez les patients ayant subi une AMS que chez ceux qui n'en ont pas subi (12 [30 %] c. 7 [12 %], p = 0,022). Conclusion: L'amputation des membres supérieurs est plus prévalente avec les EEA qu'avec les MAP. L'AMS est associée à des blessures plus graves et à un risque plus grand de décès chez les victimes d'un EEA. Les blessures aux membres supérieurs ont de graves conséquences sur la réadaptation nécessaire après l'AMI, qui accompagne presque toujours l'AMS chez les victimes d'un EEA. Les blessures aux membres supérieurs devraient pouvoir être évitées grâce à de l'équipement de protection individuelle novateur conçu pour protéger le coude fléchi.

The future of resuscitative endovascular balloon occlusion in combat operations.

Damage control resuscitation and early thoracotomy have been used to increase survival after severe injury in combat. There has been a renewed interest in resuscitative endovascular balloon occlusion of the aorta (REBOA) in both civilian and military medical practices. REBOA may result in visceral and limb ischaemia that could be harmful if use of REBOA is premature or prolonged. The purpose of this paper is to align our experience of combat injuries with the known capability of REBOA to suggest an implementation strategy for the use of REBOA in combat care. It may replace the resuscitative effect of thoracotomy; can provide haemostasis of non-compressible torso injuries such as the junctional and pelvic haemorrhage caused by improvised explosive devices. However, prehospital use of REBOA must be in the context of an overall surgical plan and should be restricted to deployment in the distal aorta. Although REBOA is technically easier than a thoracotomy, it requires operator training and skill to add to the beneficial effect of damage control resuscitation and surgery.

Performance Evaluation of a Salivary Amylase Biosensor for Stress Assessment in Military Field Research.

BACKGROUND: A convenient biosensor for real-time measurement of biomarkers for in-field psychophysiological stress research and military operations is desirable. We evaluated a hand-held device for measuring salivary amylase as a stress marker in medical technicians undergoing combat casualty care training using two different modalities in operating room and field settings. METHODS: Salivary amylase activity was measured by two biosensor methods: directly sampling saliva with a test strip placed under the tongue or pipetting a fixed volume of precollected saliva onto the test strip, followed by analyzing the sample on the strip using a biosensor. The two methods were compared for their accuracy and sensitivity to detect the stress response using an enzyme assay method as a standard. RESULTS: The measurements from the under-the-tongue method were not as consistent with those from the standard assay method as the values obtained from the pipetting method. The under-the-tongue method did not detect any significant increase in the amylase activity due to stress in the operating room (P > 0.1), in contrast to the significant increases observed using the pipetting method and assay method with a significance level less than 0.05 and 0.1, respectively. Furthermore, the under-the-tongue method showed no increased amylase activity in the field testing, while both the pipetting method and assay method showed increased amylase activity in the same group (P < 0.1). CONCLUSION: The accuracy and consistency of the biosensors need to be improved when used to directly measure salivary amylase activity under the tongue for stress assessment in military medical training.

An infant with an ectopic torsed testis in the abdominal wall.

We report a unique case of an infant with testicular torsion in the anterior abdominal wall. In the work-up of acute abdominal pain in a male infant with nonpalpable testes, a careful search for the testes using ultrasound can often identify undescended or ectopic testes. Testicular torsion should remain an important consideration as a potential cause of abdominal pain in this selected group of individuals.

Management of Rib Fractures in the Combat Environment.

Rib fractures in combat casualties are an under-appreciated injury, and their treatment may become more common as more patients survive because of modern body armor and point-ofinjury care. The combat environment has challenges such as equipment availability and sterility. A simple and thoughtful rib fracture treatment algorithm may be useful to reduce the morbidity and mortality of rib fractures in the combat environment. Intravenous lidocaine infusions for patients with traumatic rib fractures may have important combat applications. We propose an algorithm for the management of combat casualties with traumatic rib fractures.

Antiplatelets versus anticoagulants in the treatment of blunt cerebrovascular injury (BCVI) - A systematic review and meta-analysis.

INTRODUCTION: Blunt cerebrovascular injury (BCVI) occurs in 1-3% of blunt traumas and is associated with stroke, disability, and mortality if unrecognized and untreated. Early detection and treatment are imperative to reduce the risk of stroke, however, there is significant variation amongst centers and trauma care providers in the specific medical management strategy used. This study compares antiplatelets vs. anticoagulants to determine BCVI-related stroke risk and bleeding complications to better understand the efficacy and safety of various treatment strategies. METHODS: A systematic review of MEDLINE, Embase, and Cochrane CENTRAL databases was conducted with the assistance of a medical librarian. The search was supplemented with manual review of the literature. Included studies reported treatment-stratified risk of stroke following BCVI. All studies were screened independently by two reviewers, and data was extracted in duplicate. Meta-analysis was conducted using pooled estimates of odds ratios (OR) with a random-effects model using Mantel-Haenszel methods. RESULTS: A total of 3315 studies screened yielded 39 studies for inclusion, evaluating 6552 patients (range 8 - 920 per study) with a total of 7643 BCVI. Stroke rates ranged from 0% to 32.8%. Amongst studies included in the meta-analysis, there were a total of 405 strokes, with 144 (35.5%) occurring on therapy, for a total stroke rate of 4.5 %. Meta-analysis showed that stroke rate after BCVI was lower for patients treated with antiplatelets vs. anticoagulants (OR 0.57; 95% CI 0.33-0.96, p = 0.04); when evaluating only the 9 studies specifically comparing ASA to heparin, the stroke rate was similar between groups (OR 0.43; 95% CI 0.15-1.20, p = 0.11). Eleven studies evaluated bleeding complications and demonstrated lower risk of bleeding with antiplatelets vs. anticoagulants (OR 0.29; 95% CI 0.13-0.63, p = 0.002); 5 studies evaluating risk of bleeding complications with ASA vs. heparin showed lower rates of bleeding complications with ASA (OR 0.16; 95% CI 0.04-0.58, p = 0.005). CONCLUSIONS: Treatment of patients with BCVI with antiplatelets is associated with lower risks of stroke and bleeding complications compared to treatment with anticoagulants. Use of ASA vs. heparin specifically was not associated with differences in stroke risk, however, patients treated with ASA had fewer bleeding complications. Based on this evidence, antiplatelets should be the preferred treatment strategy for patients with BCVI.

Preclinical Studies on Mechanisms Underlying the Protective Effects of Propranolol in Traumatic Brain Injury: A Systematic Review.

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity amongst trauma patients. Its treatment is focused on minimizing progression to secondary injury. Administration of propranolol for TBI maydecrease mortality and improve functional outcomes. However, it is our sense that its use has not been universally adopted due to low certainty evidence. The literature was reviewed to explore the mechanism of propranolol as a therapeutic intervention in TBI to guide future clinical investigations. Medline, Embase, and Scopus were searched for studies that investigated the effect of propranolol on TBI in animal models from inception until June 6, 2023. All routes of administration for propranolol were included and the following outcomes were evaluated: cognitive functions, physiological and immunological responses. Screening and data extraction were done independently and in duplicate. The risk of bias for each individual study was assessed using the SYCLE's risk of bias tool for animal studies. Three hundred twenty-three citations were identified and 14 studies met our eligibility criteria. The data suggests that propranolol may improve post-TBI cognitive and motor function by increasing cerebral perfusion, reducing neural injury, cell death, leukocyte mobilization and p-tau accumulation in animal models. Propranolol may also attenuate TBI-induced immunodeficiency and provide cardioprotective effects by mitigating damage to the myocardium caused by oxidative stress. This systematic review demonstrates that propranolol may be therapeutic in TBI by improving cognitive and motor function while regulating T lymphocyte response and levels of myocardial reactive oxygen species. Oral or intravenous injection of propranolol following TBI is associated with improved cerebral perfusion, reduced neuroinflammation, reduced immunodeficiency, and cardio-neuroprotection in preclinical studies.

Pharmacotherapy for the prevention of chronic pain after surgery in adults.

BACKGROUND: Chronic pain can often occur after surgery, substantially impairing patients' health and quality of life. It is caused by complex mechanisms that are not yet well understood. The predictable nature of most surgical procedures has allowed for the conduct of randomized controlled trials of pharmacological interventions aimed at preventing chronic postsurgical pain. OBJECTIVES: The primary objective was to evaluate the efficacy of systemic drugs for the prevention of chronic pain after surgery by examining the proportion of patients reporting pain three months or more after surgery. The secondary objective was to evaluate the safety of drugs administered for the prevention of chronic pain after surgery. SEARCH METHODS: We identified randomized controlled trials (RCTs) of various systemically administered drugs for the prevention of chronic pain after surgery from CENTRAL, MEDLINE, EMBASE and handsearches of other reviews and trial registries. The most recent search was performed on 17 July 2013.   SELECTION CRITERIA: Included studies were double-blind, placebo-controlled, randomized trials involving adults and evaluating one or more drugs administered systemically before, during or after surgery, or both, which measured pain three months or more after surgery. DATA COLLECTION AND ANALYSIS: Data collected from each study included the study drug name, dose, route, timing and duration of dosing; surgical procedure; proportion of patients reporting any pain three months or more after surgery, reporting at least 4/10 or moderate to severe pain three months or more after surgery; and proportion of participants dropping out of the study due to treatment-emergent adverse effects. MAIN RESULTS: We identified 40 RCTs of various pharmacological interventions including intravenous ketamine (14 RCTs), oral gabapentin (10 RCTs), oral pregabalin (5 RCTs), non-steroidal anti-inflammatories (3 RCTs), intravenous steroids (3 RCTs), oral N-methyl-D-aspartate (NMDA) blockers (3 RCTs), oral mexiletine (2 RCTs), intravenous fentanyl (1 RCT), intravenous lidocaine (1 RCT), oral venlafaxine (1 RCT) and inhaled nitrous oxide (1 RCT). Meta-analysis suggested a modest but statistically significant reduction in the incidence of chronic pain after surgery following treatment with ketamine but not gabapentin or pregabalin. Results with ketamine should be viewed with caution since most of the included trials were small (that is < 100 participants per treatment arm), which could lead to the overestimation of treatment effect. AUTHORS' CONCLUSIONS: Additional evidence from better, well designed, large-scale trials is needed in order to more rigorously evaluate pharmacological interventions for the prevention of chronic pain after surgery. Furthermore, available evidence does not support the efficacy of gabapentin, pregabalin, non-steroidal anti-inflammatories, intravenous steroids, oral NMDA blockers, oral mexiletine, intravenous fentanyl, intravenous lidocaine, oral venlafaxine or inhaled nitrous oxide for the prevention of chronic postoperative pain.

A Systematic Review of Prehospital Combat Airway Management.

Medical leadership must decide how prehospital airways will be managed in a combat environment, and airway skills can be complicated and difficult to learn. Evidence informed airway strategies are essential. A search was conducted in Medline and EMBASE databases for prehospital combat airway use. The primary data of interest was what type of airway was used. Other data reviewed included: who performed the intervention and the success rate of the intervention. The search strategy produced 2,624 results, of which 18 were included in the final analysis. Endotracheal intubation, cricothyroidotomy, supraglottic airways, and nasopharyngeal airways have all been used in the prehospital combat environment. This review summarizes the entirety of the available combat literature such that commanders may make an evidence-based informed decision with respect to their airway management policies.