Background: Although the phrase “time is fascia” is well acknowledged in the case of necrotizing soft tissue infections (NSTIs), solid evidence is lacking. The aim of this study is to review the current literature concerning the timing of surgery in relation to mortality and amputation in patients with NSTIs. Methods: A systematic search in PubMed/MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Controlled Register of Trials (CENTRAL) was performed. The primary outcomes were mortality and amputation. These outcomes were related to the following time-related variables: (1) time from onset symptoms to presentation; (2) time from onset symptoms to surgery; (3) time from presentation to surgery; (4) duration of the initial surgical procedure. For the meta-analysis, the effects were estimated using random-effects meta-analysis models. Result: A total of 109 studies, with combined 6051 NSTI patients, were included. Of these 6051 NSTI patients, 1277 patients died (21.1%). A total of 33 studies, with combined 2123 NSTI patients, were included for quantitative analysis. Mortality was significantly lower for patients with surgery within 6 h after presentation compared to when treatment was delayed more than 6 h (OR 0.43; 95% CI 0.26–0.70; 10 studies included). Surgical treatment within 6 h resulted in a 19% mortality rate compared to 32% when surgical treatment was delayed over 6 h. Also, surgery within 12 h reduced the mortality compared to surgery after 12 h from presentation (OR 0.41; 95% CI 0.27–0.61; 16 studies included). Patient delay (time from onset of symptoms to presentation or surgery) did not significantly affect the mortality in this study. None of the time-related variables assessed significantly reduced the amputation rate. Three studies reported on the duration of the first surgery. They reported a mean operating time of 78, 81, and 102 min with associated mortality rates of 4, 11.4, and 60%, respectively. Conclusion: Average mortality rates reported remained constant (around 20%) over the past 20 years. Early surgical debridement lowers the mortality rate for NSTI with almost 50%. Thus, a sense of urgency is essential in the treatment of NSTI.

Immune dysfunction can provoke (multiple) organ failure in severely injured patients. This dysfunction manifests in two forms, which follow a biphasic pattern. During the first phase, in addition to the injury by trauma, organ damage is caused by the immune system during a systemic inflammatory response. During the second phase the patient is more susceptible for sepsis due to host defence failure (immune paralysis). The pathophysiological model outlined in this review encompasses etiological factors and the contribution of the innate immune system in the end organ damage. The etiological factors can be divided into intrinsic (genetic predisposition and physiological status) and extrinsic components (type of injury or "traumaload" and surgery or "intervention load"). Of all the factors, the intervention load is the only one which, can be altered by the attending emergency physician. Adjustment of the therapeutic approach and choice of the most appropriate treatment strategy can minimize the damage caused by the immune response and prevent the development of immunological paralysis. This review provides a pathophysiological basis for the damage control concept, in which a staged approach of surgery and post-traumatic immunomonitoring have become important aspects of the treatment protocol. The innate immune system is the main objective of immunomonitoring as it has the most prominent role in organ failure after trauma. Polymorphonuclear phagocytes and monocytes are the main effector-cells of the innate immune system in the processes that lead to organ failure. These cells are controlled by cytokines, chemokines, complement factors and specific tissue signals. The contribution of tissue barrier integrity and its interaction with the innate immune system is further evaluated.

Although the gut is often considered the motor of sepsis, the relation between systemic inflammation and intestinal permeability in humans is not clear. We analyzed intestinal permeability during experimental endotoxemia in humans. Before and during experimental endotoxemia (Escherichia coli LPS, 2 ng/kg), using polyethylene glycol (PEG) as a permeability marker, intestinal permeability was analyzed in 14 healthy subjects. Enterocyte damage was determined by intestinal fatty acid binding protein. Endotoxemia induced an inflammatory response. Urinary PEGs 1,500 and 4,000 recovery increased from 38.8 +/- 6.3 to 63.1 +/- 12.5 and from 0.58 +/- 0.31 to 3.11 +/- 0.93 mg, respectively (P < 0.05). Intestinal fatty acid binding protein excretion was not affected by endotoxemia. The peak serum IL-10 concentrations correlated with the increase in PEG 1,500 recovery (r = 0.48, P = 0.027). Systemic inflammation results in an increased intestinal permeability. The increase in intestinal permeability is most likely caused by inflammation-induced paracellular permeability, rather than ischemia-mediated enterocyte damage.

Purpose The goal of this study was to assess if unprotected weight-bearing as tolerated is superior to protected weight-bearing and unprotected non-weight-bearing in terms of functional outcome and complications after surgical fixation of Lauge-Hansen supination external rotation stage 2–4 ankle fractures. Methods A multicentered randomized controlled trial was conducted in patients ranging from 18 to 65 years of age without severe comorbidities. Patients were randomized to unprotected non-weight-bearing, protected weight-bearing, and unprotected weight-bearing as tolerated. The primary endpoint of the study was the Olerud Molander Ankle Score (OMAS) 12 weeks after randomization. The secondary endpoints were health-related quality of life using the SF-36v2, time to return to work, time to return to sports, and the number of complications. Results The trial was terminated early as advised by the Data and Safety Monitoring Board after interim analysis. A total of 115 patients were randomized. The O’Brien–Fleming threshold for statistical significance for this interim analysis was 0.008 at 12 weeks. The OMAS was higher in the unprotected weight-bearing group after 6 weeks c(61.2 ± 19.0) compared to the protected weight-bearing (51.8 ± 20.4) and unprotected non-weight-bearing groups (45.8 ± 22.4) (p = 0.011). All other follow-up time points did not show significant differences between the groups. Unprotected weight-bearing showed a significant earlier return to work (p = 0.028) and earlier return to sports (p = 0.005). There were no differences in the quality of life scores or number of complications. Conclusions Unprotected weight-bearing and mobilization as tolerated as postoperative care regimen improved short-term functional outcomes and led to earlier return to work and sports, yet did not result in an increase of complications.

Neutrophils are important assets in defense against invading bacteria like staphylococci. However, (dysfunctioning) neutrophils can also serve as reservoir for pathogens that are able to survive inside the cellular environment. Staphylococcus aureus is a notorious facultative intracellular pathogen. Most vulnerable for neutrophil dysfunction and intracellular infection are immune-deficient patients or, as has recently been described, severely injured patients. These dysfunctional neutrophils can become hide-out spots or “Trojan horses” for S. aureus. This location offers protection to bacteria from most antibiotics and allows transportation of bacteria throughout the body inside moving neutrophils. When neutrophils die, these bacteria are released at different locations. In this review, we therefore focus on the capacity of several groups of antibiotics to enter human neutrophils, kill intracellular S. aureus and affect neutrophil function. We provide an overview of intracellular capacity of available antibiotics to aid in clinical decision making. In conclusion, quinolones, rifamycins and sulfamethoxazole-trimethoprim seem very effective against intracellular S. aureus in human neutrophils. Oxazolidinones, macrolides and lincosamides also exert intracellular antibiotic activity. Despite that the reviewed data are predominantly of in vitro origin, these findings should be taken into account when intracellular infection is suspected, as can be the case in severely injured patients.

Emergency department utilization has increased tremendously over the past years, which is accompanied by an increased necessity for emergency medicine research to support clinical practice. Important sources of evidence are systematic reviews (SRs) and meta-analyses (MAs), but these can only be informative provided their quality is sufficiently high, which can only be assessed if reporting is adequate. The purpose of this study was to assess the quality of reporting of SRs and MAs in emergency medicine using the PRISMA statement. The top five emergency medicine related journals were selected using the 5-year impact factor of the ISI Web of Knowledge of 2015. All SRs and MAs published in these journals between 2015 and 2016 were extracted and assessed independently by two reviewers on compliance with each item of the PRISMA statement. The included reviews (n = 112) reported a mean of 18 ± 4 items of the PRISMA statement adequately. Reviews mentioning PRISMA adherence did not show better reporting than review without mention of adherence (mean 18.6 (SE 0.4) vs. mean 17.8 (SE 0.5); p = 0.214). Reviews published in journals recommending or requiring adherence to a reporting guideline showed better quality of reporting than journals without such instructions (mean 19.2 (SE 0.4) vs. mean 17.2 (SE 0.5); p = 0.001). There is room for improvement of the quality of reporting of SRs and MAs within the emergency medicine literature. Therefore, authors should use a reporting guideline such as the PRISMA statement. Active journal implementation, by requiring PRISMA endorsement, enhances quality of reporting.