ASGBI trauma committee position statement: a national audit of trauma laparotomy in the UK - an unmet need.

Patients who undergo laparotomy for major trauma are amongst the most critically unwell patients, and they have high morbidity and mortality rates. Despite 20 yr of improvements in resuscitation practices, those who present with hypotension continue to have mortality rates of up to 50%. Currently there is no mechanism for capturing national audit data on these patients, leading to their exclusion from potential quality improvement initiatives. We argue that there is an unmet need for quality assurance in this patient cohort and outline possible mechanisms to address this.

Safety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. The TOP-ART randomized clinical trial.

PURPOSE: This study aimed at determining whether intravenous artesunate is safe and effective in reducing multiple organ dysfunction syndrome in trauma patients with major hemorrhage. METHODS: TOP-ART, a randomized, blinded, placebo-controlled, phase IIa trial, was conducted at a London major trauma center in adult trauma patients who activated the major hemorrhage protocol. Participants received artesunate or placebo (2:1 randomization ratio) as an intravenous bolus dose (2.4 mg/kg or 4.8 mg/kg) within 4 h of injury. The safety outcome was the 28-day serious adverse event (SAE) rate. The primary efficacy outcome was the 48 h sequential organ failure assessment (SOFA) score. The per-protocol recruitment target was 105 patients. RESULTS: The trial was terminated after enrolment of 90 patients because of safety concerns. Eighty-three participants received artesunate (n = 54) or placebo (n = 29) and formed the safety population and 75 met per-protocol criteria (48 artesunate, 27 placebo). Admission characteristics were similar between groups (overall 88% male, median age 29 years, median injury severity score 22), except participants who received artesunate were more shocked (median base deficit 9 vs. 4.7, p = 0.042). SAEs occurred in 17 artesunate participants (31%) vs. 5 who received placebo (17%). Venous thromboembolic events (VTE) occurred in 9 artesunate participants (17%) vs. 1 who received placebo (3%). Superiority of artesunate was not supported by the 48 h SOFA score (median 5.5 artesunate vs. 4 placebo, p = 0.303) or any of the trial's secondary endpoints. CONCLUSION: Among critically ill trauma patients, artesunate is unlikely to improve organ dysfunction and might be associated with a higher VTE rate.

Getting hit by the bus around the world - a global perspective on goal directed treatment of massive hemorrhage in trauma.

PURPOSE OF REVIEW: Major trauma remains one of the leading causes of death worldwide with traumatic brain injury and uncontrolled traumatic bleeding as the main determinants of fatal outcome. Interestingly, the therapeutic approach to trauma-associated bleeding and coagulopathy shows differences between geographic regions, that are reflected in different guidelines and protocols. RECENT FINDINGS: This article summarizes main principles in coagulation diagnostics and compares different strategies for treatment of massive hemorrhage after trauma in different regions of the world. How would a bleeding trauma patient be managed if they got hit by the bus in the United States, United Kingdom, Germany, Switzerland, Austria, Denmark, Australia, or in Japan? SUMMARY: There are multiple coexistent treatment standards for trauma-induced coagulopathy in different countries and different trauma centers. Most of them initially follow a protocol-based approach and subsequently focus on predefined clinical and laboratory targets.

Correction: Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma: A prospective cohort study.

[This corrects the article DOI: 10.1371/journal.pmed.1002352.].

Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma: A prospective cohort study.

BACKGROUND: Severe trauma induces a widespread response of the immune system. This "genomic storm" can lead to poor outcomes, including Multiple Organ Dysfunction Syndrome (MODS). MODS carries a high mortality and morbidity rate and adversely affects long-term health outcomes. Contemporary management of MODS is entirely supportive, and no specific therapeutics have been shown to be effective in reducing incidence or severity. The pathogenesis of MODS remains unclear, and several models are proposed, such as excessive inflammation, a second-hit insult, or an imbalance between pro- and anti-inflammatory pathways. We postulated that the hyperacute window after trauma may hold the key to understanding how the genomic storm is initiated and may lead to a new understanding of the pathogenesis of MODS. METHODS AND FINDINGS: We performed whole blood transcriptome and flow cytometry analyses on a total of 70 critically injured patients (Injury Severity Score [ISS] ≥ 25) at The Royal London Hospital in the hyperacute time period within 2 hours of injury. We compared transcriptome findings in 36 critically injured patients with those of 6 patients with minor injuries (ISS ≤ 4). We then performed flow cytometry analyses in 34 critically injured patients and compared findings with those of 9 healthy volunteers. Immediately after injury, only 1,239 gene transcripts (4%) were differentially expressed in critically injured patients. By 24 hours after injury, 6,294 transcripts (21%) were differentially expressed compared to the hyperacute window. Only 202 (16%) genes differentially expressed in the hyperacute window were still expressed in the same direction at 24 hours postinjury. Pathway analysis showed principally up-regulation of pattern recognition and innate inflammatory pathways, with down-regulation of adaptive responses. Immune deconvolution, flow cytometry, and modular analysis suggested a central role for neutrophils and Natural Killer (NK) cells, with underexpression of T- and B cell responses. In the transcriptome cohort, 20 critically injured patients later developed MODS. Compared with the 16 patients who did not develop MODS (NoMODS), maximal differential expression was seen within the hyperacute window. In MODS versus NoMODS, 363 genes were differentially expressed on admission, compared to only 33 at 24 hours postinjury. MODS transcripts differentially expressed in the hyperacute window showed enrichment among diseases and biological functions associated with cell survival and organismal death rather than inflammatory pathways. There was differential up-regulation of NK cell signalling pathways and markers in patients who would later develop MODS, with down-regulation of neutrophil deconvolution markers. This study is limited by its sample size, precluding more detailed analyses of drivers of the hyperacute response and different MODS phenotypes, and requires validation in other critically injured cohorts. CONCLUSIONS: In this study, we showed how the hyperacute postinjury time window contained a focused, specific signature of the response to critical injury that led to widespread genomic activation. A transcriptomic signature for later development of MODS was present in this hyperacute window; it showed a strong signal for cell death and survival pathways and implicated NK cells and neutrophil populations in this differential response.

Contemporary Patterns of Multiple Organ Dysfunction in Trauma.

BACKGROUND: Multiple organ dysfunction syndrome (MODS) is associated with poor outcomes for trauma patients. Different forms of MODS may exist and have different consequences. The ability to distinguish them clinically may have implications for prognosis and treatment. We wished to study whether prolonged MODS (PRMODS) could be observed as a distinct clinical entity to early resolving MODS (ERMODS) in critically injured patients. METHODS: Adult major trauma patients recruited to a prospective observational study at a single major trauma center were eligible for inclusion. MODS was defined as Sequential Organ Failure Assessment (SOFA) score >5; and PRMODS as lasting >7 days. Time to recovery (TTR) was calculated as the number of days before the SOFA fell below the MODS threshold (≤5). RESULTS: Five hundred ninety-five patients were enrolled of whom 285 developed ERMODS (48%) and 184 (31%) PRMODS. Organ dysfunction was more severe and protracted in PRMODS, especially in patients without brain injury (mean SOFA 11 vs. 6, Day 2, P < 0.001; TTR 17 vs. 3 days, P < 0.001). PRMODS exhibited higher rates of hepatic and renal dysfunction (84% vs. 56%; and 78% vs. 47%, P≤0.001). Patterns of recovery were distinct in hepatic, renal, and neurological systems (TTR 15 vs. 4; 20 vs. 3; and 28 vs. 7 days, P < 0.01). PRMODS was associated with higher infection and mortality rates (91% vs. 41%; and 22% vs. 7%, P < 0.001). CONCLUSION: PRMODS appears common, a distinct clinical entity, and associated with worse patient outcomes. PRMODS may represent an important endpoint for studies evaluating outcomes following trauma.

Ergonomics in Laparoscopic Surgery--A Survey of Symptoms and Contributing Factors.

PURPOSE: We aimed to investigate physical/cognitive symptoms experienced by clinicians undertaking laparoscopic surgery (LS) in relation to demographics, operating factors, and instruments. METHODS: Fifty trainees/consultants practicing LS in Southeast England completed a 17-question survey. Results were analyzed using nonparametric tests of metric, ordinal, and binomial data. RESULTS: Forty-five percent of respondents reported moderate/severe symptoms during long cases (>2 h). Worse neck/shoulder (N=45, P=0.01), back (N=44, P=0.002), and fatigue/irritability (N=42, P=0.02) symptoms were reported for long (vs. short) cases. Assistants reported worse back symptoms than principle operators (N=43, P=0.02, long cases). Females (vs. males), glove size ≤6.5 (vs. ≥7.0), and experience ≤5years (vs. 5 to 10, >10 y) reported worse symptoms relating to handle dimensions (N=45, P=0.004, 0.001, 0.01, respectively). Ninety-six percent believe ergonomics should be incorporated into LS courses. CONCLUSIONS: Principle and assistant surgeons experience adverse symptoms during LS; ergonomics training and handles dimensions, accommodating female surgeons, and smaller glove sizes may reduce this.

Biologic Drugs, Biosimilars, and Barriers to Entry.

Biologic drugs represent an important new category of drugs in the effort to improve health outcomes in this country. Yet, these cutting-edge drugs are often cost prohibitive, preventing access for many Americans. Recognizing the need for more affordable, generic substitutes for biologic drugs­or biosimilars­Congress recently created a biosimilars approval pathway that would enable these cheaper biologic drugs to obtain FDA approval and reach patients more quickly. Unfortunately, original biologics manufacturers have sought to extend their current monopoly profits by erecting various legal and regulatory barriers to entry. Their legal maneuvers take many forms, from delaying approval of safe biosimilars to abrogating previous commitments to international drug-naming protocols, and even circumventing Congressional intent for biosimilar substitution. Regrettably, these policies reduce competition in the market for biologic drugs, impede drug innovation, increase drug costs, and limit patient access to these important medications. This article explores the conflict between biologics and biosimilars, and the consequences that barriers to biosimilar entry in this market will create.