Planned dose reduction of ocrelizumab in relapsing-remitting multiple sclerosis: a single-centre observational study.

Background: Ocrelizumab, a humanised anti-CD20 monoclonal, is a highly effective treatment for relapsing-remitting multiple sclerosis (RRMS). The long-term safety of B-cell depletion in RRMS, however, is uncertain and there are no data on dose reduction of ocrelizumab as a risk mitigation strategy. This study aimed to evaluate the effectiveness and safety of reducing ocrelizumab dose from 600 to 300 mg in patients with RRMS. Method: Data were collected through the Townsville neurology service. Following the standard randomised controlled trial regimen of 600 mg every 6 months for 2 years, sequential patients consented to dose reduction to 300 mg every 6 months. Patients were included if they were diagnosed with RRMS and received at least one reduced dose of ocrelizumab. Relapse, disability progression, new MRI lesions, CD19+ cell counts and immunoglobulin concentrations were analysed. Results: A total of 35 patients, treated with 177 full and 107 reduced doses, were included. The mean follow-up on reduced dose was 17 (1-31) months. We observed no relapses or new MRI activity in the cohort receiving the reduced dose, accompanied by persistent CD19+B cell depletion (≤0.05×109/L). Mean IgG, IgA and IgM levels remained stable throughout the study. No new safety concerns arose. Conclusions: In this single-centre observational study, dose reduction of ocrelizumab from 600 to 300 mg every 6 months after 2 years appeared to maintain efficacy in terms of new inflammatory disease activity. A randomised trial may be warranted to confirm this and explore the impact of dose reduction on long-term safety.

PET-CT for staging pT4b melanomas prior to sentinel lymph node biopsy: a 5-year review.

In this centre, patients with pT4b cutaneous melanoma are staged using 18F-FDG PET-computed tomography (PET-CT) prior to considering sentinel lymph node biopsy (SLNB). The objective was to assess the utility of PET-CT in terms of rates of detection of metastases leading to changes in planned treatment and if performing PET-CT was associated with a delay in surgical management. In this single-centre retrospective cohort study, 88 consecutive patients with pT4b melanoma were identified from February 2014 to May 2019. Data were collected from clinical records. Of the 88 patients, 76 patients underwent PET-CT and 16/76 (21%) of these demonstrated metastatic/potentially metastatic disease. In total 16/76 (21%) patients had positive findings on PET-CT, and of these 14 (18%) had alterations to their clinical care. Performing PET-CT did not significantly delay time to wide local excision (PET-CT median 74 days (range 16-220) vs. no PET-CT median 55 days (range 36-143) P = 0.56) or SLNB (PET-CT median 67 days (range 16-206) vs. no PET-CT median 124 days (range 45-203) P = 0.66). Of the 29 patients undergoing SLNB who had negative PET-CT findings, 12/29 (41%) demonstrated microscopic metastatic disease. At the median follow-up of 1.75 years, 28 patients (34%) had died. Median survival was not reached. Performing staging PET-CT prior to SLNB in patients with pT4b melanoma can reveal metastases in over a fifth of patients, leading to alteration in management without treatment delay. Due to the low sensitivity of PET-CT for small metastases, SLNB remains important for definitive staging.

Constructing 3D Macroporous Microfibrous Scaffolds with a Featured Surface by Heat Welding and Embossing.

Three-dimensional (3D) microfibrous scaffolds hold great promise for biomedical applications due to their good mechanical properties and biomimetic structure similar to that of the fibrous natural extracellular matrix. However, the large diameter and smooth surface of microfibers provide limited cues for regulating cell activity and behaviors. In this work, we report a facile heat-welding-and-embossing strategy to develop 3D macroporous microfibrous scaffolds with a featured surface topography. Here, solid monosodium glutamate (MSG) particles with crystalline ridge-like surface features play a key role as templates in both the formation of scaffold pores and the surface embossing of scaffold fibers when short thermoplastic polypropylene microfibers were heat-welded. The embossing process can be programmed by adjusting heating temperatures and MSG/fiber ratios. Compared to traditional 3D microfibrous scaffolds, the as-welded 3D scaffolds show higher compressive strength and modulus. Taking mouse C2C12 myoblasts as a model cell line, the scaffolds with embossed surface features significantly promoted the growth of cells, interactions of cells and scaffolds, and formation of myotubes. The findings indicate that the as-prepared 3D scaffolds are a good platform for cell culture study. The facile strategy can be applied to fabricate different fibrous scaffolds by changing the combination of templates and thermoplastic polymer fibers with a melting temperature lower than that of the template. The obtained insights in this work could provide a guide and inspiration for the design and fabrication of functional 3D fibrous scaffolds.

Discovery of the First Vitamin K Analogue as a Potential Treatment of Pharmacoresistant Seizures.

Despite the availability of more than 25 antiseizure drugs on the market, approximately 30% of patients with epilepsy still suffer from seizures. Thus, the epilepsy therapy market has a great need for a breakthrough drug that will aid pharmacoresistant patients. In our previous study, we discovered a vitamin K analogue, 2h, which displayed modest antiseizure activity in zebrafish and mouse seizure models. However, there are limitations to this compound due to its pharmacokinetic profile. In this study, we develop a new series of vitamin K analogues by modifying the structure of 2h. Among these, compound 3d shows full protection in a rodent pharmacoresistant seizure model with limited rotarod motor toxicity and favorable pharmacokinetic properties. Furthermore, the brain/plasma concentration ratio of 3d indicates its excellent permeability into the brain. The resulting data shows that 3d can be further developed as a potential antiseizure drug in the clinic.

Evaluation of subchronic administration of antiseizure drugs in spontaneously seizing rats.

OBJECTIVE: Approximately 30% of patients with epilepsy do not experience full seizure control on their antiseizure drug (ASD) regimen. Historically, screening for novel ASDs has relied on evaluating efficacy following a single administration of a test compound in either acute electrical or chemical seizure induction. However, the use of animal models of spontaneous seizures and repeated administration of test compounds may better differentiate novel compounds. Therefore, this approach has been instituted as part of the National Institute of Neurological Disorders and Stroke Epilepsy Therapy Screening Program screening paradigm for pharmacoresistant epilepsy. METHODS: Rats were treated with intraperitoneal kainic acid to induce status epilepticus and subsequent spontaneous recurrent seizures. After 12 weeks, rats were enrolled in drug screening studies. Using a 2-week crossover design, selected ASDs were evaluated for their ability to protect against spontaneous seizures, using a video-electroencephalographic monitoring system and automated seizure detection. Sixteen clinically available compounds were administered at maximally tolerated doses in this model. Dose intervals (1-3 treatments/d) were selected based on known half-lives for each compound. RESULTS: Carbamazepine (90 mg/kg/d), phenobarbital (30 mg/kg/d), and ezogabine (15 mg/kg/d) significantly reduced seizure burden at the doses evaluated. In addition, a dose-response study of topiramate (20-600 mg/kg/d) demonstrated that this compound reduced seizure burden at both therapeutic and supratherapeutic doses. However, none of the 16 ASDs conferred complete seizure freedom during the testing period at the doses tested. SIGNIFICANCE: Despite reductions in seizure burden, the lack of full seizure freedom for any ASD tested suggests that this screening paradigm may be useful for testing novel compounds with potential utility in pharmacoresistant epilepsy.

Evaluation of antiseizure drug efficacy and tolerability in the rat lamotrigine-resistant amygdala kindling model.

OBJECTIVE: The lamotrigine-resistant amygdala kindling model uses repeated administration of a low dose of lamotrigine during the kindling process to produce resistance to lamotrigine, which also extends to some other antiseizure drugs (ASDs). This model of pharmacoresistant epilepsy has been incorporated into the testing scheme utilized by the Epilepsy Therapy Screening Program (ETSP). Although some ASDs have been evaluated in this model, a comprehensive evaluation of ASD prototypes has not been reported. METHODS: Following depth electrode implantation and recovery, rats were exposed to lamotrigine (5 mg/kg, i.p.) prior to each stimulation during the kindling development process (~3 weeks). A test dose of lamotrigine was used to confirm that fully kindled rats were lamotrigine-resistant. Efficacy (unambiguous protection against electrically elicited convulsive seizures) was defined as a Racine score < 3 in the absence of overt compound-induced side effects. Various ASDs, comprising several mechanistic classes, were administered to fully kindled, lamotrigine-resistant rats. Where possible, multiple doses of each drug were administered in order to obtain median effective dose (ED50) values. RESULTS: Five sodium channel blockers tested (eslicarbazepine, lacosamide, lamotrigine, phenytoin, and rufinamide) were either not efficacious or effective only at doses that were not well-tolerated in this model. In contrast, compounds targeting either GABA receptors (clobazam, clonazepam, phenobarbital) or GABA-uptake proteins (tiagabine) produced dose-dependent efficacy against convulsive seizures. Compounds acting to modulate Ca2+ channels show differential activity: Ethosuximide was not effective, whereas gabapentin was moderately efficacious. Ezogabine and valproate were also highly effective, whereas topiramate and levetiracetam were not effective at the doses tested. SIGNIFICANCE: These results strengthen the conclusion that the lamotrigine-resistant amygdala kindling model demonstrates pharmacoresistance to certain ASDs, including, but not limited to, sodium channel blockers, and supports the utility of the model for helping to identify compounds with potential efficacy against pharmacoresistant seizures.

EMSY expression affects multiple components of the skin barrier with relevance to atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common, complex, and highly heritable inflammatory skin disease. Genome-wide association studies offer opportunities to identify molecular targets for drug development. A risk locus on chromosome 11q13.5 lies between 2 candidate genes, EMSY and LRRC32 (leucine-rich repeat-containing 32) but the functional mechanisms affecting risk of AD remain unclear. OBJECTIVES: We sought to apply a combination of genomic and molecular analytic techniques to investigate which genes are responsible for genetic risk at this locus and to define mechanisms contributing to atopic skin disease. METHODS: We used interrogation of available genomic and chromosome conformation data in keratinocytes, small interfering RNA (siRNA)-mediated knockdown in skin organotypic culture and functional assessment of barrier parameters, mass spectrometric global proteomic analysis and quantitative lipid analysis, electron microscopy of organotypic skin, and immunohistochemistry of human skin samples. RESULTS: Genomic data indicate active promoters in the genome-wide association study locus and upstream of EMSY; EMSY, LRRC32, and intergenic variants all appear to be within a single topologically associating domain. siRNA-knockdown of EMSY in organotypic culture leads to enhanced development of barrier function, reflecting increased expression of structural and functional proteins, including filaggrin and filaggrin-2, as well as long-chain ceramides. Conversely, overexpression of EMSY in keratinocytes leads to a reduction in markers of barrier formation. Skin biopsy samples from patients with AD show greater EMSY staining in the nucleus, which is consistent with an increased functional effect of this transcriptional control protein. CONCLUSION: Our findings demonstrate an important role for EMSY in transcriptional regulation and skin barrier formation, supporting EMSY inhibition as a therapeutic approach.

Replication of It's Your Game Keep It Real! in Southeast Texas.

Despite the recent efforts of the Office of Adolescent Health to replicate programs with demonstrated efficacy, there are still few evidence-based HIV, sexually transmitted infection (STI), and teen pregnancy prevention programs that have been replicated in "real-world" settings. To test the effectiveness of It's Your Game…Keep It Real! (IYG), an evidence-based STI and pregnancy prevention program for middle schools, the curriculum was implemented by teachers in urban and suburban middle schools in Southeast Texas from 2012 to 2015. IYG was evaluated using a group-randomized wait-list controlled effectiveness trial design in which 20 middle schools in nine urban and suburban school districts in Southeast Texas were randomized equally, using a multi-attribute randomization protocol, to either the intervention condition (received IYG) (n = 10 schools comprising 1936 eligible seventh graders) or the comparison condition (received usual care) (n = 10 schools comprising 1825 eligible seventh graders). All students were blinded to condition prior to administering the baseline survey. The analytic sample comprised 1543 students (n = 804, intervention; n = 739, comparison) who were followed from baseline (seventh grade) to the 24-month follow-up (ninth grade). Multilevel regression analyses were conducted to assess behavioral and psychosocial outcomes at follow-up. There were no significant differences in initiation of vaginal or oral sex between study conditions at follow-up. However, at 12-month follow-up, compared with students in the comparison condition, students in the intervention condition reported increased knowledge, self-efficacy, and perceived favorable norms related to HIV/STIs, condoms, and/or abstinence; decreased intentions to have sex; and increased intentions to use birth control. Knowledge outcomes were statistically significant at 24-month follow-up. This IYG effectiveness trial did not replicate the behavioral effects of the original IYG efficacy trials. However, it adds to the growing literature on the replication of evidence-based programs, and underscores the need to better understand how variations in implementation, setting, and measurement affect the behavioral impact of such programs.Clinical trial registration clinicaltrials.gov (NCT03533192).

Too Many Hats? Conflicts of Interest in Learning Community Faculty Roles.

PURPOSE: Many US medical schools have adopted learning communities to provide a framework for advising and teaching functions. Faculty who participate in learning communities often have additional educator roles. Defining potential conflicts of interest (COIs) among these roles is an important consideration for schools with existing learning communities and those looking to develop them, both for transparency with students and also to comply with regulatory requirements. METHODS: A survey was sent to the institutional contact for each of the 42 Learning Communities Institute (LCI) member medical schools to assess faculty opinions about what roles potentially conflict. The survey asked the role of learning community faculty in summative and formative assessment of students and whether schools had existing policies around COIs in medical education. RESULTS: In all, 35 (85%) LCI representatives responded; 30 (86%) respondents agreed or strongly agreed that learning community faculty should be permitted to evaluate their students for formative purposes, while 19 (54%) strongly agreed or agreed that learning community faculty should be permitted to evaluate their students in a way that contributes to a grade; 31 (89%) reported awareness of the accreditation standard ensuring "that medical students can obtain academic counseling from individuals who have no role in making assessment or promotion decisions about them," but only 10 (29%) had a school policy about COIs in education. There was a wide range of responses about what roles potentially conflict with being a learning community faculty. CONCLUSION: The potential for COIs between learning community faculty and other educator roles concerns faculty at schools with learning communities, but most schools have not formally addressed these concerns.

Student-led simulation: preparing students for leadership.

It is vital to prepare nurses to become informed leaders with the required knowledge and skills to support effective patient care and outcomes. This article describes an innovative teaching method that enables students to create simulation scenarios based on their clinical experiences, to lead simulations and to take part in self-reflection and peer review activities. The article shows how the method can help prepare nursing students to become future leaders by allowing them to practise 'real-life', real-time leadership skills, and apply theory to practice in the safety of a simulated scenario.

Results of cross-faculty 'capstone' assessments involving nursing and performing arts students.

This article describes how 'capstone' assessments were created to provide two different student groups, nursing and performing arts students, with a lived experience of learning together about their own fields of practice. Capstone assessments combine 'live' human simulation with self-reflection and peer review. A capstone assessment is the integration of a body of relatively fragmented knowledge and learning to form a unified whole and can be used as a transitional assessment and a bridging experience to connect knowledge between modules or courses. The capstone assessments involved two faculties and four modules, three nursing and one performing arts. Case studies were designed to represent real-life situations that students were likely to encounter during their careers, either playing a patient as an actor or performing a caring role as a nurse. Assessments for the capstone simulation were formative, and involved the students engaging in self-reflection and peer review. Videos were available to enhance the self-reflection and peer-review process. Evaluation was undertaken through verbal feedback during debrief, written feedback, video footage and nursing student and acting student peer review. The experience of capstone assessments for two diverse student groups provided valuable learning from their own and from a different group outside their subject area.

Simulation using 'live' adult service users and moulage in a variety of settings.

This article shows how simulation can be modified and adapted to benefit higher education institutions (HEIs) in a variety of situations. These situations can involve the engagement of service users (SUs) and moulage, or application of make-up to simulate clinical presentations, to ensure skill enhancement, ultimately to support and empower students so they can achieve their potential. This article describes a unique collaboration between staff at an HEI and SUs, who have worked together in simulation activities. The development of simulation using SUs is at the heart of developing nursing student education and recruitment. It has created communities of practice working across traditional departmental boundaries to provide innovative learning opportunities for students. This collaboration links to the political imperative to improve education in the health and social care sector, highlights the integration of skills development into theory, focuses on person-centred care and demonstrates how the HEI produces a compassionate and caring workforce.

A review of TiO2 NTs on Ti metal: Electrochemical synthesis, functionalization and potential use as bone implants.

Degenerative diseases of bone such as osteoarthritis and osteoporosis can lead to bone fractures and immobility, compromising quality of life. Titanium (Ti)-based implants have been intensively investigated for bone repair, with these implants, demonstrating improved outcomes compared to stainless steel and cobalt-chrome alloys, owing to superior mechanical properties and biocompatibility. However, osseointegration between the Ti-based implants and the surrounding bone tissue needs to be improved. Surface modification of Ti-based implants provides a solution for addressing this, with electrochemical anodization becoming a realistic approach for the fabrication of hierarchical structured for example nanotubes (NTs), implant surfaces. Using this technique, biocompatibility and osteogenesis of the implant may be improved, by providing an appropriate site for bone cell attachment. In this review, we discuss the anodization of Ti-based implants as an approach for creating titanium dioxide nanotubes (TiO2 NTs) on the implant surface. We further discuss the various ways of functionalizing the NT surface, to reduce post-operative infection and improve implant biocompatibility and osseointegration.

Ovine multiparity is associated with diminished vaginal muscularis, increased elastic fibres and vaginal wall weakness: implication for pelvic organ prolapse.

Pelvic Organ Prolapse (POP) is a major clinical burden affecting 25% of women, with vaginal delivery a major contributing factor. We hypothesised that increasing parity weakens the vagina by altering the extracellular matrix proteins and smooth muscle thereby leading to POP vulnerability. We used a modified POP-quantification (POP-Q) system and a novel pressure sensor to measure vaginal wall weakness in nulliparous, primiparous and multiparous ewes. These measurements were correlated with histological, biochemical and biomechanical properties of the ovine vagina. Primiparous and multiparous ewes had greater displacement of vaginal tissue compared to nulliparous at points Aa, Ap and Ba and lower pressure sensor measurements at points equivalent to Ap and Ba. Vaginal wall muscularis of multiparous ewes was thinner than nulliparous and had greater elastic fibre content. Collagen content was lower in primiparous than nulliparous ewes, but collagen organisation did not differ. Biomechanically, multiparous vaginal tissue was weaker and less stiff than nulliparous. Parity had a significant impact on the structure and function of the ovine vaginal wall, as the multiparous vaginal wall was weaker and had a thinner muscularis than nulliparous ewes. This correlated with "POP-Q" and pressure sensor measurements showing greater tissue laxity in multiparous compared to nulliparous ewes.

Development and pharmacologic characterization of the rat 6 Hz model of partial seizures.

OBJECTIVE: The mouse 6 Hz model of psychomotor seizures is a well-established and commonly used preclinical model for antiseizure drug (ASD) discovery. Despite its widespread use both in the identification and differentiation of novel ASDs in mice, a corresponding assay in rats has not been developed. We established a method for 6 Hz seizure induction in rats, with seizure behaviors similar to those observed in mice including head nod, jaw clonus, and forelimb clonus. METHODS: A convulsive current that elicits these seizure behaviors in 97% of rats (CC97 ) was determined using a Probit analysis. Numerous prototype ASDs were evaluated in this model using stimulus intensities of 1.5× and 2× the CC97 , which is comparable to the approach used in the mouse 6 Hz seizure model (e.g., 32 and 44 mA stimulus intensities). The ASDs evaluated include carbamazepine, clobazam, clonazepam, eslicarbazepine, ethosuximide, ezogabine, gabapentin, lacosamide, lamotrigine, levetiracetam, phenobarbital, phenytoin, rufinamide, tiagabine, topiramate, and sodium valproate. Median effective dose (ED50 ) and median toxic (motor impairment) dose (TD50 ) values were obtained for each compound. RESULTS: Compounds that were effective at the 1.5 × CC97 stimulus intensity at protective index (PI) values >1 included clobazam, ethosuximide, ezogabine, levetiracetam, phenobarbital, and sodium valproate. Compounds that were effective at the 2 × CC97 stimulus intensity at PI values >1 included ezogabine, phenobarbital, and sodium valproate. SIGNIFICANCE: In a manner similar to the use of the mouse 6 Hz model, development of a rat 6 Hz test will aid in the differentiation of ASDs, as well as in study design and dose selection for chronic rat models of pharmacoresistant epilepsy. The limited number of established ASDs with demonstrable efficacy at the higher stimulus intensity suggests that, like the mouse 6 Hz 44 mA model, the rat 6 Hz seizure model may be a useful screening tool for pharmacoresistant seizures.

What nursing students reveal about and learn from mentors when using stories of clinical practice.

Aim This article considers findings from a narrative research analysis that illustrate what nursing students can reveal about being mentored through their stories of clinical practice experience. The aim is to advocate the use of stories as tools to assist mentors in their roles, and to express to them students' concerns, sensitivities and priorities about clinical placement experiences. The findings are extracted from the author's unpublished doctoral thesis Learning from Practice: The Value of Story in Nurse Education ( Edwards 2013 ). Method The data are drawn from nursing students' stories about clinical practice experiences when engaged in the care of patients, and their perceived learning from them. Results Findings suggest stories can help develop understanding of nursing students' concerns, sensitivities and priorities, and can support mentors' important roles in students' learning. Conclusion The article illustrates the value of stories as learning tools in the workplace and, by looking at nursing students' stories about clinical practice, shows that paying attention to their concerns, sensitivities and priorities can improve the already significant role played by mentors in student learning.

Neutrophil Gelatinase-Associated Lipocalin Biomarker and Urinary Tract Infections: A Diagnostic Case-Control Study (NUTI Study).

OBJECTIVES: Acute uncomplicated urinary tract infection (UTI) in women is often treated based on symptoms alone. Urinary tract infection symptoms are highly sensitive but lack specificity and result in overuse of antibiotics. We sought to determine if urine neutrophil gelatinase-associated lipocalin (uNGAL) levels in urine can accurately discriminate between UTI and healthy women. METHODS: We recruited adult women aged 18 to 85 years presenting in the ambulatory setting from November 2014 to January 2016. Cases were defined as women with Centers for Disease Control and Prevention-defined UTI symptoms and a positive urine culture of more than 10 organisms/mL on a midstream clean-catch specimen. Women without UTI symptoms were matched by age and menopausal status as control subjects. Exclusion criteria were no UTIs within 8 weeks, urinary tract anomalies, renal disease, pregnancy, or diabetes. Clean-catch urine samples were obtained for measuring uNGAL, prior to antibiotic treatment of cases. We used Mann-Whitney U test to compare the 2 groups. Receiver operating characteristic curves were plotted to compare the performance of uNGAL to established urinary markers. RESULTS: We enrolled 50 UTI cases and 50 control subjects. Urine NGAL levels were higher in the UTI group than in the control subjects (P < 0.0001). Using a cutoff of 23.9 ng/mL, NGAL achieved 98% sensitivity and 100% specificity. The receiver operating characteristic curve had an area under the curve of 0.97 (95% confidence interval, 0.93-1.00), which was significantly high and showed that uNGAL can identify UTI. CONCLUSIONS: Urine NGAL has the potential as a biomarker for diagnosing UTIs in adult women.

Latency to vaginal mesh exposure with mesh placed abdominally versus vaginally in pelvic floor surgery: A retrospective comparative study.

The primary aim was to compare the difference in time to mesh exposure between mesh placed abdominally versus vaginally. This is a retrospective comparative study of patients presented with vaginal mesh exposure between January 2001 and July 2012. This study compares patients who had undergone vaginally placed mesh procedures to those who had had abdominally placed mesh. Kaplan-Meier survival analysis was used to measure the time to mesh exposure. There were 68 patients with mesh exposure in our cohort. Thirty eight patients had undergone vaginal placement of mesh and 30 patients had abdominal mesh. There was a statistically significant difference in time to mesh exposure between abdominal and vaginal meshes (p≤.0001). Mean time to vaginal mesh exposure with abdominal mesh was 59.8 months (95%CI 46.2-73.3) compared to 23 months (95%CI 15.9-30.2) for vaginal mesh. When controlling for age, BMI and surgeon at index surgery, the Hazard Ratio for mesh exposure in our Cox Regression model was 0.53 (95%CI 0.39-0.71) (p ≤.0001). The mean time to vaginal mesh exposure after abdominal mesh was longer compared to the time to exposure with vaginally placed mesh (60 versus 23 months, p ≤.0001). These results support the evolving evidence that mesh exposures can occur many years distant from the procedure and warrant some level of surveillance or provision of warning signs by the providers who perform procedures with mesh.

Advances in military resuscitation.

Trauma is a leading cause of death and disability worldwide, in civilian environments and on the battlefield. Trauma-induced haemorrhage is the principal cause of potentially preventable death, which is generally attributable to a combination of vascular injury and coagulopathy. Survival rates following severe traumatic injury have increased due to advanced trauma management initiatives and treatment protocols, influenced by lessons learned from recent conflicts in Iraq and Afghanistan. The use of tourniquets and intraosseous needles, early blood and blood product transfusion, administration of tranexamic acid in pre-hospital settings, and consultant-led damage control resuscitation incorporating damage control surgery have all played their part. All are quantified by trauma governance processes, including a robust trauma registry. Some of the lessons learned in combat are equally applicable to civilian environments, and this article describes several of the most important of these. It also gives an overview of advancements in UK military trauma management of severely injured combat casualties, honed over a decade of conflict.