Association between tranexamic acid administration and mortality based on the trauma phenotype: a retrospective analysis of a nationwide trauma registry in Japan.

BACKGROUND: In trauma systems, criteria for individualised and optimised administration of tranexamic acid (TXA), an antifibrinolytic, are yet to be established. This study used nationwide cohort data from Japan to evaluate the association between TXA and in-hospital mortality among all patients with blunt trauma based on clinical phenotypes (trauma phenotypes). METHODS: A retrospective analysis was conducted using data from the Japan Trauma Data Bank (JTDB) spanning 2019 to 2021. RESULTS: Of 80,463 patients with trauma registered in the JTDB, 53,703 met the inclusion criteria, and 8046 (15.0%) received TXA treatment. The patients were categorised into eight trauma phenotypes. After adjusting with inverse probability treatment weighting, in-hospital mortality of the following trauma phenotypes significantly reduced with TXA administration: trauma phenotype 1 (odds ratio [OR] 0.68 [95% confidence interval [CI] 0.57-0.81]), trauma phenotype 2 (OR 0.73 [0.66-0.81]), trauma phenotype 6 (OR 0.52 [0.39-0.70]), and trauma phenotype 8 (OR 0.67 [0.60-0.75]). Conversely, trauma phenotypes 3 (OR 2.62 [1.98-3.47]) and 4 (OR 1.39 [1.11-1.74]) exhibited a significant increase in in-hospital mortality. CONCLUSIONS: This is the first study to evaluate the association between TXA administration and survival outcomes based on clinical phenotypes. We found an association between trauma phenotypes and in-hospital mortality, indicating that treatment with TXA could potentially influence this relationship. Further studies are needed to assess the usefulness of these phenotypes.

Thrombosis prophylaxis following trauma.

PURPOSE OF REVIEW: This review explores the persistent occurrence of venous thromboembolic events (VTE) in major trauma patients despite standard thrombosis prophylaxis with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH). It investigates the inadequacies of standard pharmacologic prophylaxis and proposes alternative approaches not covered in current trauma guidelines. RECENT FINDINGS: Recent studies highlight the effectiveness of monitoring and adjusting subcutaneous LMWH doses based on anti-Xa levels for the purpose of reducing VTE in trauma patients. The need for dose adaptation arises due to factors like fluctuating organ function, varying antithrombin levels, interaction with plasma proteins, and altered bioavailability influenced by oedema or vasopressor use. Additionally, promising alternatives such as intravenous LMWH, UFH, and argatroban have shown success in intensive care settings. SUMMARY: The standard dosing of subcutaneous LMWH is often insufficient for effective thrombosis prophylaxis in trauma patients. A more personalised approach, adjusting doses based on specific effect levels like anti-Xa or choosing an alternative mode of anticoagulation, could reduce the risk of insufficient prophylaxis and subsequent VTE.

Antidote vs. unspecific hemostatic agents for the management of direct oral anticoagulant-related bleeding in trauma.

PURPOSE OF REVIEW: The advent of direct oral anticoagulants (DOACs) marks a significant milestone in anticoagulant treatment. However, DOACs can exacerbate bleeding, which is challenging for the treating clinician, especially when combined with traumatic injury. RECENT FINDINGS: In major bleeding associated with DOACs, rapid reversal of the anticoagulant effects is crucial. Recent observational and nonrandomized interventional trials have demonstrated the effectiveness of the specific antidotes andexanet alfa and idarucizumab as well as the unspecific prothrombin complex concentrates (PCCs) to counteract the anticoagulant effects of DOACs. The European Society of Anaesthesiology and Intensive Care guideline for severe perioperative bleeding and the European trauma guideline propose divergent recommendations for the use of andexanet alfa and PCC to obtain hemostasis in Factor Xa inhibitor-related bleeding. The conflicting recommendations are due to limited evidence from clinical studies and the potential increased risk of thromboembolic complications after the administration of andexanet. Regarding dabigatran-associated major bleeding, both guidelines recommend the specific reversal agent idarucizumab as first-line therapy. SUMMARY: Current guidelines recommend specific antidots and PCCs in DOAC-related major bleeding. Prospective randomized trials comparing specific vs. nonspecific hemostatic agents in the perioperative setting are needed to evaluate the effectiveness and safety of the hemostatic agents.

Direct oral anticoagulants in trauma patients.

PURPOSE OF REVIEW: Direct oral anticoagulants (DOACs) are increasingly prescribed for prevention of thromboembolic events. Thus, trauma care providers are facing a steadily raising number of injured patients on DOACs. RECENT FINDINGS: Despite a predictable pharmacokinetic profile, the resulting plasma levels of trauma patients upon admission and bleeding risks remain uncertain. Therefore, recent guidelines recommend the measurement of DOAC plasma concentrations in injured patients. Alternatively, DOAC specific visco-elastic tests assays can be applied to identify DOAC patients at bleeding risk.Bleeding complications in trauma patients on DOACs are generally higher compared to nonanticoagulated subjects, but comparable to vitamin K antagonists (VKAs). In particular, a traumatic brain injury does not carry an increased risk of intracranial bleeding due to a DOAK intake compared to VKAs. Current studies demonstrated that up to 14% of patients with a hip fracture are on DOACs prior to surgery. However, the majority can be operated safely within a 24h time window without an increased bleeding rate.Specific antagonists facilitate rapid reversal of patients on DOACs. Idarucizumab for dabigatran, and andexanet alfa for apixaban and rivaroxaban have been approved for life threatening bleeding. Alternatively, prothrombin complex concentrate can be used. Dialysis is a potential treatment option for dabigatran and haemoabsorption with special filters can be applied in patients on FXa-inhibitors. SUMMARY: Current guidelines recommend the measurement of DOAC plasma levels in trauma patients. Compared to VKAs, DOACs do not carry a higher bleeding risk. DOAC specific antagonists facilitate the individual bleeding management.

Associations with Prehospital Antibiotic Receipt among Combat Casualties with Open Wounds: A Department of Defense Trauma Registry Study.

INTRODUCTION: Current Tactical Combat Casualty Care (TCCC) guidelines recommend antibiotic administration for all open wounds to prevent infection. We identified associations between demographics, procedures, and medicines with the receipt of prehospital antibiotics among combat casualties. MATERIALS AND METHODS: We used a series of emergency department procedure codes to identify adult subjects within the Department of Defense Trauma Registry from January 2007 to August 2016 who sustained open wounds. We compared demographics, procedures, and medicines administered among casualties receiving prehospital wound prophylaxis versus casualties not receiving antibiotic prophylaxis. We controlled for confounders with multivariable logistical regression. RESULTS: We identified 18,366 encounters meeting inclusion criteria. Antibiotic recipients (n = 2384) were comparable to nonrecipients (n = 15,982) with regard to age and sex. Antibiotic recipients were more likely to sustain injuries from firearms and undergo all procedures examined related to hemorrhage control, airway management, pneumothorax treatment, and volume replacement except for intraosseous access. Antibiotic recipients were less likely to sustain injuries from explosives. Antibiotic recipients had a modestly higher survival than nonrecipients (97.4% versus 96.0%). Associations with prehospital antibiotic receipt in multivariable logistic regression included non-North Atlantic Treaty Organization military force affiliation (odds ratio (OR) 4.65, 95% CI, 1.0-20.8), tachycardia (OR 3.4, 95% CI, 1.1-10.5), intubation (OR 2.0, 95% CI, 1.1-3.8), and administration of tranexamic acid (OR 5.6, 95% CI, 1.2-26.5). CONCLUSIONS: The proportion of combat casualties with open wounds receiving prehospital antibiotics was low despite published recommendations for early antibiotics in patients with open wounds. These findings highlight the ongoing need for additional educational and quality assurance initiatives to continue improving adherence to TCCC guidelines with regard to prehospital antibiotic administration. Future studies are necessary to determine reasons for suboptimal TCCC guideline compliance.

Propriedades Químicas e Farmacológicas do Gênero Copaifera no Tratamento de Lesões/feridas: Revisão Integrativa / Chemical and Pharmacological Properties of the Genus Copaifera in the Treatment of Injuries/wounds: Integrative Review / Propiedades Químicas y Farmacológicas del Género Copaifera en el Tratamiento de Lesiones/heridas: Revisión Integradora

Objetivo:Identificar propriedades químicas e farmacológicas do gênero Copaifera no tratamento de lesões e feridas. Método: Revisão integrativa da literatura realizada nas bases de dados LILACS, MEDLINE, PubMed, Taylor & Francis e Scopus, em janeiro de 2022, por meio da estratégia de busca: "Chemical Properties" AND "Copaifera" AND "Wounds and Injuries" e "Pharmacology" AND "Copaifera" AND "Wounds and Injuries". Foram incluídos artigos originais, de texto completo, identificados de acordo nível de evidência, redigidos em português, inglês ou espanhol. Resultados: Na busca primária foram encontrados 261 artigos. Após a seleção sistematizada, 12 estudos foram selecionados para análise qualitativa. Espécies do gênero Copaifera apresentam propriedades farmacológicas favoráveis ao tratamento de feridas: controle da dor inflamatória, diminuição da reação inflamatória, reepitelização e reparo tecidual, angiogênese, retração da ferida e remodelagem de cicatrizes. Dentre as propriedades químicas associadas ao tratamento de lesões, destacam-se presença de compostos bioativos: diterpenos, 3-hidroxi-copálico, sesquiterpenos, éster kolavic-15-metílico. Entre os diterpenos testados, o caurenoico e os ácidos copálicos mostraram atividades hemolíticas significativas. Apenas o ácido copálico e o ácido hardwíckiico inibiram a produção de óxido nítrico em macrófagos ativados por lipopolissacarídeos. Conclusão: As plantas do gênero Copaifera apresentam propriedades químicas e farmacológicas favoráveis ao tratamento de lesões e feridas

Objective:To identify chemical and pharmacological properties of Copaifera in the treatment of injuries and wounds. Method: Integrative literature review conducted in the LILACS, MEDLINE, PubMed, Taylor & Francis and Scopus databases in January 2022, using the search strategy: "Chemical Properties" AND "Copaifera" AND "Wounds and Injuries" and "Pharmacology" AND "Copaifera" AND "Wounds and Injuries." Original articles, full text, identified according to level of evidence, written in Portuguese, English or Spanish, were included. Results: In the primary search 261 articles were found. After systematized selection, 12 studies were selected for qualitative analysis. Species of the genus Copaifera have pharmacological properties favorable for wound treatment: control of inflammatory pain, reduction of inflammatory reaction, tissue reepithelialization and repair, angiogenesis, wound retraction and scar remodeling. Among the chemical properties associated with the treatment of injuries, the presence of bioactive compounds stand out: diterpenes, 3-hydroxy-copalic, sesquiterpenes, kolavic-15-methyl ester. Among the tested diterpenes, kaurenoic and copalic acids showed significant hemolytic activities. Only copalic acid and hardwickiic acid inhibited nitric oxide production in lipopolysaccharide-activated macrophages. Conclusion: Plants of the genus Copaifera have chemical and pharmacological properties favorable for the treatment of injuries and wounds.

Objetivo:Identificar las propiedades químicas y farmacológicas del género Copaifera en el tratamiento de lesiones y heridas. Método: Revisión integradora de la literatura realizada en las bases de datos LILACS, MEDLINE, PubMed, Taylor & Francis y Scopus, en enero de 2022, mediante la estrategia de búsqueda: "Chemical Properties" AND "Copaifera" AND "Wounds and Injuries" e "Pharmacology" AND "Copaifera" AND "Wounds and Injuries". Se incluyeron artículos originales, a texto completo, identificados según el nivel de evidencia, escritos en portugués, inglés o español. Resultados: En la búsqueda primaria se encontraron 261 artículos. Tras una selección sistematizada, se seleccionaron 12 estudios para el análisis cualitativo. Las especies del género Copaifera presentan propiedades farmacológicas favorables para el tratamiento de las enfermedades: control del dolor inflamatorio, disminución de la reacción inflamatoria, reepitelización y reparación tecidual, angiogénesis, retracción de la piel y remodelación de las cicatrices. Entre las propiedades químicas asociadas al tratamiento de las lesiones, destaca la presencia de compuestos bioactivos: diterpenos, 3-hidroxicopálico, sesquiterpenos, éster kolavico-15-metilo. Entre los diterpenos probados, los ácidos kaurenoico y copálico mostraron actividades hemolíticas significativas. Sólo el ácido copálico y el ácido hardwickiico inhibieron la producción de óxido nítrico en macrófagos activados por lipopolisacáridos. Conclusión: Las plantas del género Copaifera presentan propiedades químicas y farmacológicas favorables para el tratamiento de lesiones y heridas.

Nationwide analysis of prehospital tranexamic acid for trauma demonstrates systematic bias in adherence to treatment guidelines: a retrospective cohort study.

BACKGROUND: Prehospital (PH) tranexamic acid (TXA) improves survival from trauma haemorrhage. Injury mechanism, physiology, and sex demographics vary with patient age. The authors hypothesised that these factors influence TXA guideline compliance and examined national trends in PH use to identify any systematic biases in bleeding management. MATERIALS AND METHODS: The UK Trauma Audit and Research Network data for TXA eligible patients admitted to major trauma centres were divided into two cohorts: 2013-2015 ( n =32 072) and 2017-2019 ( n =14 974). Patients were stratified by PH, emergency department or no TXA use. Logistic regression models explored interaction between PH variables and TXA administration. Results are presented as odds ratios with a 95% CI. RESULTS: PH TXA use increased from 8% to 27% over time ( P <0.001). Only 3% of eligible patients who fell less than 2 m received PH TXA versus 63% with penetrating injuries ( P <0.001). Older patients eligible for PH TXA were less likely to receive it compared to younger patients [≥65 years old: 590 (13%) vs. <65 years old: 3361 (33%), P <0.001]. There was a significant interaction between age and sex with fewer older women receiving PH TXA. In shocked patients, one third of females compared to a fifth of men did not receive TXA ( P <0.001). There was a decrease in PH TXA use as age increased ( P <0.001). CONCLUSIONS: Despite a threefold increase in use, treatment guidance for PH TXA is not universally applied. Older people, women, and patients with low energy injury mechanisms appear to be systematically under treated. Training and education for PH providers should address these potential treatment biases.

Xenoinjertos de piel de tilapia en quemaduras cutáneas. Una revisión exploratoria / Tilapia skin xenografts in skin burns. An exploratory review

Introducción y objetivo: El tratamiento de heridas, y en particular el de las quemaduras es complejo, son lesiones de alto costo e implican amplios periodos de hospitalización, además de incapacidades físicas, laborales y alteraciones emocionales. Existen diferentes tratamientos para su manejo, entre ellos, recientemente, los xenoinjertos de piel de tilapia, del Nilo (Oreochromis niloticus), un pez de agua dulce nativo de África que se encuentra y cultiva comúnmente en diferentes países tropicales y subtropicales. Es un tejido rico en fibras de colágeno tipo I y III, con resistencia a la humedad y estructura similar a la piel humana. Usada como xenoinjerto, posee propiedades antiinflamatorias y antibacterianas que apoyan y mejoran la cicatrización. Evaluamos la eficacia de los injertos de piel de tilapia en comparación con técnicas alternativas para el tratamiento de quemaduras. Material y método: Búsqueda bibliográfica sistemática en las bases de datos PubMed y ScienceDirect, utilizando los términos MeSH, con la ecuación de búsqueda (tilapia skin) AND (burns), incluyendo estudios de casos y controles, reportes de caso y ensayos controlados aleatorios. Resultados: Analizamos 5 trabajos para el estudio final; 4 eran de Brasil (país que actualmente tiene más experiencia en el uso de piel de tilapia en regeneración tisular) y el quinto de Indonesia. Todos en inglés. Conclusiones: De nuestra revisión podemos concluir que, en la actualidad, no existe una técnica estándar para tratar heridas, sin embargo, los injertos de piel de tilapia demostraron una mejor y más rápida cicatrización de heridas, menos cambios de apósitos, menos dolor y costos más bajos, en comparación con las técnicas convencionales.Nivel de evidencia científica 5c Terapéutico.(AU)

Background and objective: Treatment of wounds, and burns in particular, is complex, they are high-cost injuries, imply long periods of hospitalization, additionally physical and work disabilities and emotional disturbances. There are different treatments available for its management, recently including tilapia skin xenografts. Nile tilapia (Oreochromis niloticus) is a fresh water fish, native to Africa and commonly found and farmed in different tropical and subtropical countries. The skin It is a tissue rich in type I and III collagen fibers and has resistance to moisture and skin alterations similar to human skin. Used as a xenograft, it possess anti-inflammatory and antibacterial properties that support and enhance healing. In this study, we evaluate the efficacy of tilapia skin grafts in comparison with alternative techniques for the treatment of burns. Methods: A systematic bibliographic search was carried out using the PubMed and ScienceDirect data bases, MeSH terms were used with the search equation (tilapia skin) AND (burns), including case-control studies, case reports, and randomized controlled trials. Results: Five papers were included for the final study; 4 were from Brazil (the country that currently has the most experience in the use of tilapia skin in tissue regeneration) and 1 from Indonesia, all of them were written in English. Conclusions: There is currently no standard technique for treating wounds, however, fish skin grafts demonstrated faster and improved wound healing, fewer dressing changes, less pain, and lower costs, compared with conventional techniques. Level of evidence 5c Terapeutic.(AU)

Efectividad de la insulina tópica en el tratamiento de patologías de la superficie corneal / Effectiveness of topical insulin for the treatment of surface corneal pathologies

El propósito es identificar a través de una revisión sistemática de la literatura, la evidencia actual frente a la eficacia del tratamiento de la insulina tópica en patologías de la superficie ocular. Se implementó una búsqueda de literatura en bases de datos de indexación médica Medline (Pubmed), Embase y Web Of Science a través de palabras claves como «insulin» AND «córnea» OR «corneal» OR «dry eye» artículos publicados en inglés o español en los últimos once años (2011-2022). Se identificaron nueve artículos con 180 participantes provenientes de Estados Unidos, España, Irlanda, Canadá, Portugal y Malasia, con defectos epiteliales persistentes refractarios y secundarios a vitrectomía, cuya extensión de la lesión fue de 3,75 mm2 hasta 65,47 mm2. La preparación fue disuelta con lágrimas artificiales y la concentración de insulina fue desde 1 UI/ml hasta 100 UI/ml. En todos los casos la resolución del cuadro clínico fue completa con un tiempo de curación desde 2,5 días hasta 60,9 días siendo este último un caso secundario a una quemadura por cáusticos de difícil control. La insulina tópica ha sido efectiva para el tratamiento de defectos epiteliales persistentes; la de acción intermedia y en bajas concentraciones demostró menor tiempo de resolución, en úlceras neurotróficas y secundarias a vitrectomías (AU)

The purpose is to identify, through a systematic literature review, the current evidence regarding the effectiveness of topical insulin treatment in ocular surface pathologies. A literature search was implemented in Medline (Pubmed), Embase and Web Of Science medical indexing databases by using keywords such as “insulin” AND “cornea” OR “corneal” OR “dry eye” in published papers in English or Spanish within the last eleven years (2011-2022). Nine papers were identified with 180 participants from the United States, Spain, Ireland, Canada, Portugal and Malaysia, with persistent refractory epithelial defects and secondary to vitrectomy, whose extension of the lesion was from 3.75 mm2 to 65.47 mm2. The preparation was dissolved with artificial tears and the insulin concentration ranged from 1 IU/ml to 100 IU/ml. In all cases, the resolution of the clinical picture was complete with a healing time from 2.5 days to 60.9 days, the latter being a secondary case to a difficult-to-control caustic burn. Topical insulin has been effective for the treatment of persistent epithelial defects. The intermediate action and low concentrations showed a shorter resolution time in neurotrophic ulcers and induced during vitreoretinal surgery (AU)

Impact of institutional prophylaxis guidelines on rates of pediatric venous thromboembolism following trauma-A multicenter study from the pediatric trauma society research committee.

BACKGROUND: A paucity of data exists with regard to the incidence, management, and outcomes of venous thromboembolism (VTE) in injured children. We sought to determine the impact of institutional chemoprophylaxis guidelines on VTE rates in a pediatric trauma population. METHODS: A retrospective review of injured children (≤15 years) admitted between 2009 and 2018 at 10 pediatric trauma centers was performed. Data were gathered from institutional trauma registries and dedicated chart review. The institutions were surveyed as to whether they had chemoprophylaxis guidelines in place for high-risk pediatric trauma patients, and outcomes were compared based on the presence of guidelines using χ 2 analysis ( p < 0.05). RESULTS: There were 45,202 patients evaluated during the study period. Three institutions (28,359 patients, 63%) had established chemoprophylaxis policies during the study period ("Guidelines"); the other seven centers (16,843 patients, 37%) had no such guidelines ("Standard"). There were significantly lower rates of VTE in the Guidelines group, but these patients also had significantly fewer risk factors. Among critically injured children with similar clinical presentations, there was no difference in VTE rate. Specifically within the Guidelines group, 30 children developed VTE. The majority (17/30) were actually not indicated for chemoprophylaxis based on institutional guidelines. Still, despite protocols only one VTE patient in the guidelines group who was indicated for intervention ended up receiving chemoprophylaxis prior to diagnosis. No consistent ultrasound screening protocol was in place at any institution during the study. CONCLUSION: The presence of an institutional policy to guide chemoprophylaxis for injured children is associated with a decreased overall frequency of VTE, but this disappears when controlling for patient factors. However, the overall efficacy is impacted by a combination of deficits in guideline compliance and structure. Further prospective data are needed to help determine the ideal role for chemoprophylaxis and protocols in pediatric trauma. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Prehospital Tranexamic Acid Administration in Pediatric Trauma Patients: A Propensity-Matched Analysis of the Israeli Defense Forces Registry.

OBJECTIVES: Tranexamic acid (TXA) administration confers a survival benefit in bleeding trauma patients; however, data regarding its use in pediatric patients are limited. This study evaluates the prehospital treatment with TXA in pediatric trauma patients treated by the Israel Defense Forces Medical Corps (IDF-MC). DESIGN: Retrospective, cohort study using the Israel Defense Forces registry, 2011-2021. PATIENTS: Pediatric trauma patients less than 18 years old. We excluded patients pronounced dead at the scene. INTERVENTIONS: None. SETTING: All cases of pediatric trauma in the registry were assessed for treatment with TXA. Propensity score matching was used to assess the association between prehospital TXA administration and mortality. MEASUREMENTS AND MAIN RESULTS: Overall, 911 pediatric trauma patients were treated with TXA by the IDF-MC teams; the median (interquartile) age was 10 years (5-15 yr), and 72.8% were male. Seventy patients (7.6%) received TXA, with 52 of 70 (74%) receiving a 1,000 mg dose (range 200-1,000 mg). There were no prehospital adverse events associated with the use of TXA (upper limit of 95% CI for 0/70 is 4.3%). Compared with pediatric patients who did not receive TXA, patients receiving TXA were more likely to suffer from shock (40% vs 10.7%; p < 0.001), sustain more penetrating injuries (72.9% vs 31.7%; p < 0.001), be treated with plasma or crystalloids (62.9% vs 11.4%; p < 0.001), and undergo more lifesaving interventions (24.3% vs 6.2%; p < 0.001). The propensity score matching failed to identify an association between TXA and lesser odds of mortality, although a lack of effect (or even adverse effect) could not be excluded (non-TXA: 7.1% vs TXA: 4.3%, odds ratio = 0.584; 95% CI 0.084-3.143; p = 0.718). CONCLUSIONS: Although prehospital TXA administration in the pediatric population is feasible with adverse event rate under 5%, more research is needed to determine the appropriate approach to pediatric hemostatic resuscitation and the role of TXA in this population.