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Critically ill post-surgical, post-trauma and/or septic patients are characterised by severe inflammation. This immune response consists of both a pro- and an anti-inflammatory component. The pro-inflammatory component contributes to (multiple) organ failure whereas occurrence of immune paralysis predisposes to infections. Strikingly, infectious complications arise in these patients despite the presence of a clear neutrophilia. We propose that dysfunction of neutrophils potentially increases the susceptibility to infections or can result in the inability to clear existing infections. Under homeostatic conditions these effector cells of the innate immune system circulate in a quiescent state and serve as the first line of defence against invading pathogens. In severe inflammation, however, neutrophils are rapidly activated, which affects their functional capacities, such as chemotaxis, phagocytosis, intra-cellular killing, NETosis, and their capacity to modulate adaptive immunity. This review provides an overview of the current understanding of neutrophil dysfunction in severe inflammation. We will discuss the possible mechanisms of downregulation of anti-microbial function, suppression of adaptive immunity by neutrophils and the contribution of neutrophil subsets to immune paralysis.

To compare re-rupture rate, complication rate, and functional outcome after operative versus nonoperative treatment of Achilles tendon ruptures; to compare re-rupture rate after early and late full weight bearing; to evaluate re-rupture rate after functional rehabilitation with early range of motion; and to compare effect estimates from randomised controlled trials and observational studies. Systematic review and meta-analysis. PubMed/Medline, Embase, CENTRAL, and CINAHL databases were last searched on 25 April 2018 for studies comparing operative versus nonoperative treatment of Achilles tendon ruptures. Randomised controlled trials and observational studies reporting on comparison of operative versus nonoperative treatment of acute Achilles tendon ruptures. Data extraction was performed independently in pairs, by four reviewers, with the use of a predefined data extraction file. Outcomes were pooled using random effects models and presented as risk difference, risk ratio, or mean difference, with 95% confidence interval. 29 studies were included-10 randomised controlled trials and 19 observational studies. The 10 trials included 944 (6%) patients, and the 19 observational studies included 14 918 (94%) patients. A significant reduction in re-ruptures was seen after operative treatment (2.3%) compared with nonoperative treatment (3.9%) (risk difference 1.6%; risk ratio 0.43, 95% confidence interval 0.31 to 0.60; P<0.001; I =22%). Operative treatment resulted in a significantly higher complication rate than nonoperative treatment (4.9% 1.6%; risk difference 3.3%; risk ratio 2.76, 1.84 to 4.13; P<0.001; I =45%). The main difference in complication rate was attributable to the incidence of infection (2.8%) in the operative group. A similar reduction in re-rupture rate in favour of operative treatment was seen after both early and late full weight bearing. No significant difference in re-rupture rate was seen between operative and nonoperative treatment in studies that used accelerated functional rehabilitation with early range of motion (risk ratio 0.60, 0.26 to 1.37; P=0.23; I =0%). No difference in effect estimates was seen between randomised controlled trials and observational studies. This meta-analysis shows that operative treatment of Achilles tendon ruptures reduces the risk of re-rupture compared with nonoperative treatment. However, re-rupture rates are low and differences between treatment groups are small (risk difference 1.6%). Operative treatment results in a higher risk of other complications (risk difference 3.3%). The final decision on the management of acute Achilles tendon ruptures should be based on patient specific factors and shared decision making. This review emphasises the potential benefits of adding high quality observational studies in meta-analyses for the evaluation of objective outcome measures after surgical treatment.

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.

Background Many factors of trauma care have changed in the last decades. This review investigated the effect of these changes on global all-cause and cause-specific mortality in polytrauma patients admitted to the intensive care unit (ICU). Moreover, changes in trauma mechanism over time and differences between continents were analyzed. Main body A systematic review of literature on all-cause mortality in polytrauma patients admitted to ICU was conducted. All-cause and cause-specific mortality rates were extracted as well as trauma mechanism of each patient. Poisson regression analysis was used to model time trends in all-cause and cause-specific mortality. Thirty studies, which reported mortality rates for 82,272 patients, were included and showed a decrease of 1.8% (95% CI 1.6–2.0%) in all-cause mortality per year since 1966. The relative contribution of brain injury-related death has increased over the years, whereas the relative contribution of death due to multiple organ dysfunction syndrome (MODS), acute respiratory distress syndrome, and sepsis decreased. MODS was the most common cause of death in North America, and brain-related death was the most common in Asia, South America, and Europe. Penetrating trauma was most often reported in North America and Asia. Conclusions All-cause mortality in polytrauma patients admitted to the ICU has decreased over the last decades. A shift from MODS to brain-related death was observed. Geographical differences in cause-specific mortality were present, which may provide region-specific learning possibilities resulting in improvement of global trauma care.

Severe trauma can lead to the development of infectious complications after several days, such as sepsis. Early identification of patients at risk will aid anticipating these complications. The aim of this study was to test the relation between the acute (<24 hours) inflammatory response after injury measured by neutrophil responsiveness and the late (>5 days) development of septic complications and validate this in different trauma populations. Two prospective, observational, cohort series in the Netherlands and South Africa, consisting of severely injured trauma patients. Neutrophil responsiveness by fMLF-induced active FcγRII was measured in whole blood flowcytometry, as read out for the systemic immune response within hours after trauma. Sepsis was scored daily. Ten of the 36 included Dutch patients developed septic shock. In patients with septic shock, neutrophils showed a lower expression of fMLF-induced active FcγRII immediately after trauma when compared to patients without septic shock (P = 0.001). In South Africa 11 of 73 included patients developed septic shock. Again neutrophils showed lower expression of fMLF induced active FcγRII (P = 0.001). In the combined cohort, all patients who developed septic shock demonstrated a decreased neutrophil responsiveness. Low responsiveness of neutrophils for the innate stimulus fMLF immediately after trauma preceded the development of septic shock during admission by almost a week and did not depend on a geographical/racial background, hospital protocols and health care facilities. Decreased neutrophil responsiveness appears to be a prerequisite for septic shock after trauma. This might enable anticipation of this severe complication in trauma patients.

To determine the effectiveness and safety of interventions used for rehabilitation after open reduction and internal fixation of ankle fractures. A systematic review and meta-analysis was performed using both randomized trials and cohort studies. The effect of mobilization, weight-bearing, and unprotected weight-bearing as tolerated on postoperative recovery was compared using the Olerud Molander score, return to work/daily activities, and the rate of complications. A total of 25 articles were included. Ankle exercises resulted in earlier return to work and/or daily activities compared to immobilization (mean difference (MD) -20.76 days; 95% confidence interval (CI) -40.02 to -1.50). There was no difference in the rate of complications between exercises and immobilization (risk ratio (RR) 1.22; 95% CI 0.60 to 2.45) or between early and late weight-bearing (RR 1.26; 95%CI 0.56 to 2.85). Results of this meta-analysis show that following ankle surgery, 1) active exercises accelerate return to work and daily activities compared to immobilization, 2) early weight-bearing tends to accelerate return to work and daily activities compared to late weight-bearing. Active exercises in combination with immediate weight-bearing may be a safe option.

Early incorporation of rehabilitation services for severe traumatic brain injury (TBI) patients is expected to improve outcomes and quality of life. This study aimed to compare the outcomes regarding the discharge destination and length of hospital stay of selected TBI patients before and after launching an acute intensive trauma rehabilitation (AITR) program at King Saud Medical City. It was a retrospective observational before-and-after study of TBI patients who were selected and received AITR between December 2018 and December 2019. Participants’ demographics, mechanisms of injury, baseline characteristics, and outcomes were compared with TBI patients who were selected for rehabilitation care in the pre-AITR period between August 2017 and November 2018. A total of 108 and 111 patients were managed before and after the introduction of the AITR program, respectively. In the pre-AITR period, 63 (58.3%) patients were discharged home, compared to 87 (78.4%) patients after AITR (p = 0.001, chi-squared 10.2). The pre-AITR group’s time to discharge from hospital was 52.4 (SD 30.4) days, which improved to 38.7 (SD 23.2) days in the AITR (p < 0.001; 95% CI 6.6–20.9) group. The early integration of AITR significantly reduced the percentage of patients referred to another rehabilitation or long-term facility. We also emphasize the importance of physical medicine and rehabilitation (PM&R) specialists as the coordinators of structured, comprehensive, and holistic rehabilitation programs delivered by the multi-professional team working in an interdisciplinary way. The leadership and coordination of the PM&R physicians are likely to be effective, especially for those with severe disabilities after brain injury.

Deep vein thrombosis (DVT) is common among the severely injured and may lead to pulmonary embolism (PE), which can be life threatening. Thromboprophylaxis may reduce the incidence of venous thromboembolism (VTE); it does not guarantee complete protection. This study's primary aim was to determine the incidence and nature of lower-limb DVT in polytrauma patients taking prophylaxis. The secondary objective was to assess the incidence of DVT-related complications, including the development of PE and death. This prospective observational study included patients age 18 years or older who presented with polytrauma directly from the scene and were admitted into the trauma unit between March 1, 2020 and August 31, 2020. All patients underwent lower-limb ultrasound during their hospital course to diagnose DVT. A total of 169 patients underwent extremity Doppler ultrasound to detect DVT. Of these, 69 patients (40.8%) were considered at the highest-risk for VTE development. For VTE prophylaxis, 115 patients (68%) received pharmacologic agents, and 54 patients (32%) had intermittent pneumatic compression on admission. Three patients (1.8%) developed DVT despite prophylaxis. Four patients (2.4%) developed PE during the index presentation and were diagnosed between days 3 and 13 after injury. Early DVT was not detected in any patients with diagnosed PE. Overall, nine patients (5.33%) died, but no in-hospital deaths were related to DVT and/or PE. The incidence of DVT in polytrauma patients remains low in our small series, perhaps because of the mandatory VTE risk assessment for all hospitalized patients and the early initiation of prophylaxis. Using a trauma center registry to measure DVT and PE incidence regularly is recommended to improve trauma care quality.

Traumatic brain injury (TBI) is a leading cause of death and disability. Epidemiology seems to be changing. TBIs are increasingly caused by falls amongst elderly, whilst we see less polytrauma due to road traffic accidents (RTA). Data on epidemiology is essential to target prevention strategies. A nationwide retrospective cohort study was conducted. The Dutch National Trauma Database was used to identify all patients over 17 years old who were admitted to a hospital with moderate and severe TBI (AIS ≥ 3) in the Netherlands from January 2015 until December 2017. Subgroup analyses were done for the elderly and polytrauma patients. 12,295 patients were included in this study. The incidence of moderate and severe TBI was 30/100.000 person-years, 13% of whom died. Median age was 65 years and falls were the most common trauma mechanism, followed by RTAs. Amongst elderly, RTAs consisted mostly of bicycle accidents. Mortality rates were higher for elderly (18%) and polytrauma patients (24%). In this national database more elderly patients who most often sustained the injury due to a fall or an RTA were seen. Bicycle accidents were very frequent, suggesting prevention could be an important aspect in order to decrease morbidity and mortality.

Background Early hemorrhage control is important in trauma-related death prevention. Tranexamic acid (TXA) has shown to be beneficial in patients in hemorrhagic shock, although widespread adoption might result in incorrect TXA administration leading to increased morbidity and mortality. Methods A 7-year prospective cohort study with consecutive trauma patients admitted to a Level-1 Trauma Center ICU was performed to investigate administration of both pre- and in-hospital TXA and its relation to morbidity and mortality. Indication for prehospital and in-hospital TXA administration was (suspicion of) hemorrhagic shock, and/or systolic blood pressure (SBP) ≤ 90 mmHg. Demographics, data on physiology, resuscitation and outcomes were prospectively collected. Results Four hundred and twenty-two patients (71% males, median ISS 29, 95% blunt injuries) were included. Even though TXA patients were more severely injured with more deranged physiology, no differences in outcome were noted. Overall, thrombo-embolic complication rate was 8%. In half the patients, hemorrhagic shock was the indication for prehospital TXA, whereas 79% of in-hospital TXA was given based on suspicion of hemorrhagic shock. Thirteen percent of patients with SBP ≤ 90 mmHg in ED received no TXA at all. Based on SBP alone, 22% of prehospital TXA and 25% of in-hospital TXA were justified. Conclusions Despite being more severely injured, TXA patients had similar outcome compared to patients without TXA. Thrombo-embolic complication rate was low despite liberal use of both prehospital and in-hospital TXA. Caution should be exercised in selecting patients for TXA, although this might be challenging based on SBP alone in patients who do not yet show signs of deranged physiology on arrival in ED.