Introduction: The beneficial effects of insulin in the maintenance of normoglycaemia in non-diabetic myocardial infarct and intensive care patients have recently been reported. Hyperglycaemia and neutrophilia have been shown to be independent prognostic indicators of poor outcome in the traumatised patient. The role of insulin and the maintenance of normoglycaemia in the trauma patient have as yet not been explored. We hypothesised that through the already described anti-inflammatory effects of insulin and the maintenance of normoglycaemia, that the systemic inflammatory response would be attenuated, in the injured patient. This might result in less adult respiratory distress syndrome (ARDS) and multi-organ dysfunction and therefore less morbidity and mortality in trauma patients. Materials and Methods: We used a previously validated rodent trauma model. There were 3 groups, two groups underwent bilateral femur fracture and 15% blood loss via cannulation and aspiration of the external jugular vein. The third group were anaesthetised only. The treatment group immediately receive subcutaneous insulin according to a recently identified sliding scale, and thereafter subcutaneous boluses, dependent on ½ hourly blood sugar estimations. The control groups received the same volume of normal saline ½ hourly, subcutaneously. The animals were maintained under anaesthetic for 4 hours from injury via inhaled isoflurane and oxygen. Core temperature and O2 saturations were recorded throughout. At 4 hours, each animal underwent midline laparotomy and cannulation of the IVC for blood sampling for full blood counts and lactate levels. Serum was also taken for flow cytometric analysis of neutrophil activation via respiratoy burst and CD11b levels. Broncho-alveolar lavage (BAL) was performed for neutrophil content and total protein estimation. The left lower lobe was harvested for wet-dry lung weight ratios. Results: While O2 saturations were equal throughout in both groups, respiratory rates were persistently elevated in the controls. Wet:Dry lung weight ratios (p< 0.05) and lactate levels were reduced in the insulin treated animals compared to controls. There were similiarly fewer neutrophils in the BAL specimens of the insuliln treated animals compared to injured controls (p< 0.05). Conclusions: Insulin reduces leukocyte lung sequestration in the injured animal model. This work confirms that insulin may have a role in reducing ARDS in the trauma patient, be that as an anti-inflammatory agent or anti-hyperglycaemic agent, or both, indicating that outcomes might be improved by treating hyperglycaemic trauma patients with insulin. Further work needs to done to elucidate its exact mechanism of action and role in the injured patient

Hypothesis: In severely the injured, there has been a move away from early total care to staged physiological and anatomic reconstruction, damage control orthopaedics (DCO). This seeks to limit the magnitude of the second hit insult resulting from operative treatment after trauma, deferring complex reconstructive work until a later stage. For femoral shaft fracture, this entails initial external fixation, to provide early skeletal stabilisation, and subsequent conversion to an intramedullary nail (IMN). Materials and Methods: Patients with femoral shaft fracture, who underwent primary IMN or DCO between 1996 and 2002 were identified from our database. Those with New Injury Severity Score (NISS) < 20 were excluded. The systemic inflammatory response (SIRS) and Marshall multi-organ failure scores (MMOFS) were calculated every 12h for 4 days. These systems have been previously correlated with outcome and complications in critical care. Results: 174 patients were included. The mean SIRS score was higher at each time period post operatively in the IMN group (p < 0.01). The MMOFS was slightly higher at each point in the DCO group, (only sig. at 48h). There was a higher incidence of pneumonia and mortality (significant p < 0.02), ARDS and MOF (both n.s.) in the DCO group, this being attributable to the higher incidence of head and thoracic injury (AIS severity 2 or more). The mean peak post-operative SIRS score was significantly higher in the IMN group than in the DCO group, both at primary procedure and conversion, as was the time with SIRS score above 1. The pre-op and peak post-op SIRS score correlated with the peak post op MMOFS score (p 0.0002). The conversion pre-op SIRS score correlated with post-operative peak SIRS score and MMOFS score (p 0.0001). On average, a significant rise in the MMOFS score did not occur following the conversion procedure. Conclusion: It would appear that despite having significantly more severe injuries, patients in the DCO group had a smaller, shorter postoperative systemic inflammatory response and suffered only slightly more pronounced organ failure than the IMN group. They did suffer more complications, but this was only significant for pneumonia. DCO patients undergoing conversion whilst their SIRS score was raised suffered the most pronounced subsequent inflammatory response and rise in organ failure score

Purpose: Severe compartment syndrome is associated with renal failure, end organ damage, and systemic inflammatory response syndrome (SIRS). Intravital videomicroscopy (IVVM) is a useful tool to study capillary perfusion and inflammation in end organs such as the liver and lungs. In this study, the systemic effect of hindlimb compartment syndrome was studied using hepatic IVVM. The purpose was to measure the effect of increased hindlimb intracompartmental pressure on hepatocyte viability, inflammation, and blood flow in a rodent model. Method: Ten Wistar rats were randomised into control (C) and Compartment Syndrome (CS) groups. Animals were anaesthetized with 5 % isoflurane. Mean arterial pressure was monitored using a carotid artery catheter. Elevated intracompartmental pressure (EICP) was induced by saline infusion into the anterior compartment of the hind limb and maintained for 2 hours between 30–40mmHg in the CS group. Two hours following fasciotomy, the liver was analyzed using IVVM to quantify capillary perfusion as a measure of microvascular dysfunction. The numbers of adherent and rolling leukocytes in venules and sinusoids were quantified to measure the inflammatory response. Irreversible hepatocyte injury was measured using a fluorescent vital dye which labels the nuclei of severely injured cells. Results: Hepatocellular injury was significantly higher in the CS group (325±103 PI labeled cells/10-1 mm2) compared to controls (30±12 PI labeled cells/10-1 mm2)(p=0.0087). The number of adherent venular white blood cells (WBC) was significantly higher for the CS group (5±2/hpf) than controls (0.2±0.2)(p=0.0099). Volumetric blood flow was not significantly different between CS and controls. Conclusion: After only 2 hours of compartment syndrome in this animal model, the number of activated white blood cells increased 25-fold and liver cellular injury increased 10-fold compared to controls. Marked systemic inflammation and hepatocellular damage was detected in response to isolated limb compartment syndrome. Compartment syndrome is a low-flow ischemia/reperfusion injury with a profound inflammatory response. Further research into the severe end-organ damage associated with compartment syndrome is required

Aims. Periprosthetic joint infection (PJI) demonstrates the most feared complication after total joint replacement (TJR). The current work analyzes the demographic, comorbidity, and complication profiles of all patients who had in-hospital treatment due to PJI. Furthermore, it aims to evaluate the in-hospital mortality of patients with PJI and analyze possible risk factors in terms of secondary diagnosis, diagnostic procedures, and complications. Methods. In a retrospective, cross-sectional study design, we gathered all patients with PJI (International Classification of Diseases (ICD)-10 code: T84.5) and resulting in-hospital treatment in Germany between 1 January 2019 and 31 December 2022. Data were provided by the Institute for the Hospital Remuneration System in Germany. Demographic data, in-hospital deaths, need for intensive care therapy, secondary diagnosis, complications, and use of diagnostic instruments were assessed. Odds ratios (ORs) with 95% confidence intervals (CIs) for in-hospital mortality were calculated. Results. A total of 52,286 patients were included, of whom 1,804 (3.5%) died. Hypertension, diabetes mellitus, and obesity, the most frequent comorbidities, were not associated with higher in-hospital mortality. Cardiac diseases as atrial fibrillation, cardiac pacemaker, or three-vessel coronary heart disease showed the highest risk for in-hospital mortality. Postoperative anaemia occurred in two-thirds of patients and showed an increased in-hospital mortality (OR 1.72; p < 0.001). Severe complications, such as organ failure, systemic inflammatory response syndrome (SIRS), or septic shock syndrome showed by far the highest association with in-hospital mortality (OR 39.20; 95% CI 33.07 to 46.46; p < 0.001). Conclusion. These findings highlight the menace coming from PJI. It can culminate in multi-organ failure, SIRS, or septic shock syndrome, along with very high rates of in-hospital mortality, thereby highlighting the vulnerability of these patients. Particular attention should be paid to patients with cardiac comorbidities such as atrial fibrillation or three-vessel coronary heart disease. Risk factors should be optimized preoperatively, anticoagulant therapy stopped and restarted on time, and sufficient patient blood management should be emphasized. Cite this article: Bone Jt Open 2024;5(4):367–373

Introduction: The water soluble vitamins B1, B2 and B6 are essential precursors for a wide variety of coenzymes involved in intermediary metabolism. Recent evidence suggests that the systemic inflammatory response associated with disease, injury and infection may lower micronutrient concentrations in plasma independent of tissue stores. Elective knee arthroplasty surgery has been shown to induce a significant and reproducible systemic inflammatory response and therefore provides an ideal model with which to examine the relationship between plasma and erythrocyte (intracellular) concentrations of B-vitamins and the evolution of the systemic inflammatory response. Methods: The study was approved by the local ethics committee. All subjects were informed of the purpose and procedure of the study and all gave consent. Venous blood samples (EDTA) were withdrawn pre-operatively from 12 primary knee arthroplasty patients and at 12, 24, 48, 72 and 168 hours after the start of surgery. Analysis of plasma and red cell vitamins B1, B2, B6, C-reactive protein and albumin. Data presented as median and range. Data from different time periods were tested for statistical significance using the Freidman test and where appropriate comparisons of data from different time periods were carried out using the Wilcoxon signed rank test. Results: All patients were over the age of 60 years and had circulating concentrations of B vitamins in the normal range (B1 275–675ng TDP/g Hb; B2 220–410nmol/l; B6 17–135nmol/l). On analysis of serial postoperative values over the study period 0–168hrs there were significant increases in C-reactive protein and significant decreases in albumin concentrations peaking/troughing at 48hrs returning towards normal concentrations at 7 days (p< 0.001). In contrast, during this period plasma albumin (p< 0.001), B2 (p< 0.001) and B6 (p< 0.001) concentrations fell transiently by as much as 50% returning towards normal in parallel with the fall in C-reactive protein concentrations. In contrast, neither red cell B2 nor B6 concentrations fell during the study period. Conclusions: In this study red blood cell B2 and B6 remained stable over the period of study. In contrast, plasma concentrations of B2 and B6 fell and were outwith the normal range, the trough coinciding with the peak of C-reactive protein before returning to baseline values. These results are consistent with the concept that plasma concentrations of vitamins are unlikely to be a reliable measure of status in patients with evidence of a systemic inflammatory response. Red cell B1, B2 and B6 concentrations more accurately reflect status in patients with evidence of a systemic inflammatory response

A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing. Cite this article: Bone Joint Res 2020;9(7):368–385

Background: Polytrauma patients with bilateral femur shaft fractures are known to have a higher rate of complications when compared with those who have sustained unilateral fractures. The current study tests the hypothesis that the high incidence of posttraumatic complications in patients who have no severe head or chest injury is caused by accompanying injuries rather than by the additional femur fracture. Methods: Prospective cohort study. Inclusion criteria: Injury severity score > 16 points; No AIS score value of the head or chest > 3 points. Two study groups: a unilateral (group USF) (n=146) and a bilateral femur shaft fracture (group BSF) (n=29). A further differentiation was made according to the patient’s status. All patients underwent early (< 24 hours after injury) fixation of their extremity fractures. Endpoints monitored were: Pneumonia, Acute lung injury (ALI), Systemic inflammatory response syndrome (SIRS), Sepsis. Statistics: Pearson chi-square test for binary indicators of injury severity, regression analyses regarding clinical complications. Results: Patients with bilateral femur fractures exhibited a longer ICU stay (p< 0.01), a higher incidence of pneumonia (p< 0.02) and SIRS (p=0.04) than those with unilateral fractures. Following corrective analyses for injury severity, no differences in blood transfusion rates, length of ICU stay, or complications was observed. Patients in borderline condition spend significantly more time in the ICU in comparison to those in stable condition. For analyses predicting presence of systemic inflammatory response syndrome, only the variable indicating receipt of a blood transfusion upon admission to the hospital emerged as a significant predictor. Bilateral fracture patients who were in uncertain condition preoperatively, developed significantly more complications postoperatively(p=0.02). Conclusions: Polytrauma patients with bilateral femur shaft fractures have a similar clinical course as those with unilateral fractures when no significant head or chest injury is present. An increased incidence of systemic inflammatory response syndrome was associated with three variables: presence of borderline condition, hemothorax and requirement of blood transfusion. This may have important treatment implications, including the management of major fractures

After a hip fracture, infections are common, but signs of infection resemble those of systemic inflammatory response to trauma and surgery, and conventional infection markers lack specificity. Plasma-calprotectin, a novel marker of neutrophil activation, has shown potential as an infection marker in ER and ICU settings. To investigate if plasma-calprotectin is superior compared to conventional infection biomarkers after hip fracture. Prospective cohort study of hip fracture patients admitted to our department. Calprotectin, procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) count were measured in blood plasma upon admission and on day 3 post-surgery. Patients with infection (pneumonia, UTI, sepsis, SSI, other soft tissue infections) pre- or post-surgery were compared to a control group without infection within 30 days. Statistics: Wilcoxon rank-sum test, medians with interquartile range, and area under the curve (AUC) with 95% confidence intervals. Pilot study comprises calprotectin obtained at least once for 60 patients at admission and 48 on day 3. Mean age 84 years (SD 8.4), 65% women. 9/60 patients (23%) were admitted with infections. They had higher levels of CRP (median 111 [73-149]) and PCT (0.35 [0.18–0.86]) compared to the control group (29 [16-64], p=0.037; 0.10 [0.07–0.17], p=0.007). Calprotectin (2.67 vs 2.51) and WBC (12.2 vs 9.3) did not differ significantly. AUC was highest for PCT (0.79 [CI 0.60–0.97]), followed by CRP (0.71 [0.46–0.96]), WBC (0.60 [0.35–0.84]), and calprotectin (0.58, [0.33–0.83]). Day 3, 6/48 (13%) had infections, without significant differences between groups in any marker. The median levels were: calprotectin 3.5 vs 3.1, CRP 172 vs 104, WBC 12 vs 9, PCT 0.16 vs 0.17. Calprotectin had highest AUC 0.68 (0.41–0.93, n.s.). AUC for WBC was 0.67 (0.31–1.00), CRP 0.66 (0.38–0.94), PCT 0.56 (0.29–0.82). Preliminary data show no significant associations with postoperative infection for any of the studied biomarkers. However, plasma-calprotectin might perform slightly better compared to conventional markers

Aim. Periprosthetic joint infection (PJI) is a devastating complication that develops after total joint arthroplasty (TJA) whose incidence is expected to increase over the years. Traditionally, surgical treatment of PJI has been based on algorithms, where early infections are preferably treated with debridement, antibiotics, and implant retention (DAIR), while late infections with two-stage revision surgery. Two-stage revision is considered the “gold standard” for treatment of chronic PJI. In this observational retrospective study, we investigated the potential role of inflammatory blood markers (neutrophil-to- lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory index (SII)], systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI)) as prognostic factors in two-stage exchange arthroplasty for PJI. Method. A single-center retrospective analysis was conducted, collecting clinical data and laboratory parameters from patients submitted to prosthetic explantation for chronic PJI. Laboratory parameters (PCR, NLR, MLR, PLR, SIRI, SII and AISI) were evaluated at the explantation time, at 4, 6, 8 weeks after surgery and at reimplantation time. Correlation between laboratory parameters and surgery success was evaluated, defined as infection absence/resolution at the last follow up. Results. 57 patients with PJI were evaluated (62% males; average age 70 years, SD 12.14). Fifty-three patients with chronic PJI were included. Nineteen patients completed the two-stage revision process. Among them, none showed signs of re-infection or persistence of infection at the last available follow up. The other twenty-three patients did not replant due to persistent infection: among them, some (the most) underwent spacer retention; others were submitted to Girdlestone technique or chronic suppressive antibiotic therapy. Of the patients who concluded the two-stage revision, the ones with high SIRI values (mean 3.08 SD 1.7, p-value 0.04) and MLR values (mean 0.4 SD 0.2, p-value 0.02) at the explantation time were associated with a higher probability of infection resolution. Moreover, higher variation of SIRI and PCR, also defined respectively delta-SIRI (mean −2.3 SD 1.8, p-value 0.03) and delta-PCR (mean −46 SD 35.7, p-value 0.03), were associated with favorable outcomes. Conclusions. The results of our study suggest that, in patients with PJI undergoing two-stage, SIRI and MLR values and delta-SIRI and delta-PCR values could be predictive of favorable outcome. The evaluation of these laboratory indices, especially their determination at 4 weeks after removal, could therefore help to determine which patients could be successfully replanted and to identify the best time to replant

Abstract. Introduction. The postoperative inflammatory response may be implicated in the aetiology of patient dissatisfaction following Total Knee Arthroplasty. Robotic-arm assisted TKA has been associated with reduced bone and soft tissue trauma. The objective of this Randomised Controlled Trial was to compare the inflammatory response in conventional Jig-based versus robotic arm-assisted TKA and examine the relationship with patient reported outcome measures and functional outcomes. Methodology. 30 patients with knee osteoarthritis were randomised to either conventional or robotic-arm assisted TKA. Blood samples were collected for up to 28 days post-operatively and intraarticular drain samples at 6 and 24 hours, to ascertain the systemic and local inflammatory responses. The Spearman's correlation was utilised to evaluate the relationship with PROMs and functional outcomes. Results. Reduced IL-6 drain fluid levels were noted at 6 hours [798.54 vs. 5699.2, p=0.026] and 24 hours and IL-8 at 6 hours. Patients in the robotic group had lower pain scores on post-operative day 1, 2 and 7. PROM scores were comparable at 2 years. Statistically significant correlations were evident between all serum markers except IL-1b on the 7th postoperative day and self-reported pain; between drain IL-8 levels and self-reported pain; between drain IL-6, IL-8 and TNF-a levels (6-hours) and knee flexion and extension. Conclusion. Robotic-arm assisted TKA was associated with a reduced postoperative local and systemic inflammatory responses. A moderate correlation with self-reported pain, knee flexion and extension was also demonstrated. Longer-term data and further validation on a larger scale, will be key to developing the optimal TKA procedure

Patients with bilateral femur fractures are known to be at a high risk for the Systemic Inflammatory Response Syndrome; however the impact of fracture-associated soft tissue injury in the induction of systemic inflammation following bilateral femur fracture is poorly understood. To address this, the systemic inflammatory response and remote organ dysfunction following bilateral femur fracture with various degrees of soft tissue injuries were investigated in this study. 6–8 weeks old male C57/BL6 mice (n = 4–8 animals per group) were grouped as follows: Control-group (no anaesthesia, no femoral catheterisation); Sham-group (6 hour anaesthesia, femoral catheterisation); Fx-group (6 hour anaesthesia, femoral catheterisation, bilateral femur fracture with minor soft tissue injury); Fx+STI-group (6 hour anaesthesia, femoral catheterisation, bilateral femur fracture with severe soft tissue injury). Six hours after bilateral femur fracture serum levels of IL-2, IL-4, IL-6, IL-10, IL-12, TNF-α, KC and MCP-1 were measured. Furthermore, IL-6 levels of homogenized liver tissue were assessed. Neutrophil accumulation in liver and lung was determined with a myeloperoxidase (MPO) assay. Changes in liver permeability were assessed by measuring the wet-dry-ratio. The Fx+STI-group showed significantly increased serum cytokine levels as compared to the Fx- or Sham-group. The homogenized liver tissue of the Fx+STI-group showed significantly increased IL-6 levels as compared to the Sham-group. The MPO activity in lung and liver in the Fx+STI-group was significantly increased in comparison to the Fx- or Sham-group and in the Fx-group in comparison to the Sham-group. The wet-dry-ratio of the liver was significantly increased in the Fx+STI-group as compared to the Sham-group. The degree of fracture-associated soft tissue injury appears to modify systemic inflammation following bilateral femur fracture and is able to induce remote organ dysfunction. These results may have implications that have been underestimated, thus warranting clinical follow-up studies

Tourniquet induced ischemia-reperfusion syndrome (IRS) may trigger systemic inflammatory response following a total knee arthroplasty. The IRS will be studied in a prospective randomized controlled study in humans undergoing total knee arthroplasty, by measuring blood inflammatory mediators and blood gases. Materials and Methods: Forty four (n=44) patients (female/male: 35/9 male) with a mean age of 72 years, undergoing primary total knee arthroplasty for osteoarthritis, were prospectively randomized in two groups. 22 patients operated with tourniquet [tourniquet group (TG)] and 22 patients operated without a tourniquet [non-tourniquet group (NTG)]. The mean overall ischemia time was 90 minutes. Arterial and venous blood samples were collected preoperatively, and at 1, 2, 3, 6, 24, 48 hours postoperatively. The pro-inflammatory (IL-1b, IL-6) and anti-inflammatory cytokines (IL-10) as well as the adhesion molecules (ICAM, VCAM), the CRP and blood counts were measured and correlated with the blood gases. Results: Patients in TG had higher cytokine and inflammatory mediators values, compared to the NTG group especially during the sixth postoperative hour and the first postoperative day. The most abrupt changes were evident in the patients with the highest preoperative levels of cytokines and inflammatory mediators especially when the ischemia time was more than 90 minutes. Male patients demonstrated the most significant changes. Discussion: The use of the tourniquet triggers the systemic inflammatory response. The most remarkable changes in inflammatory mediators are evident during the sixth postoperative hour and the first posoperative day. Tourniquet may be used for Total knee Replacement but care should be taken to decrease the ischemia time to the absolutely necessary specifically in males

Acute respiratory distress syndrome is a long established complication and continuing cause of significant morbidity and mortality in the multiply injured patient. Systemic inflammatory response syndrome (SIRS) is classically associated with acute pulmonary dysfunction. A variety of insults including trauma, sepsis, hypoxia, ischaemia reperfusion, can trigger systemic inflammatory response and acute lung injury. In models of sepsis, endotoxaemia and ischaemia-reperfusion, acute lung injury is characterised by widespread endothelial-neutrophil interaction and neutrophil activation. Another associated finding in these models of injury, is evidence of induced diaphragm muscle dysfunction, by electrophysiological testing of muscle strips post injury. An established model of incremental increasing skeletal trauma was employed. Adult male sprague dawley rats (mean weight 476grams, 370–520g) were randomised to control, single hindlimb fracture, bilateral hindlimb fracture and bilateral hind limb fracture + 20% haemorrhage. Indices of acute lung injury studied 2 hours post injury were bronchalveolar lavage, cell counts, and protein assays. Pulmonary tissue myeloperoxidase activity was assayed as an indicator of neutrophil activation and pulmonary wet/dry weights were measured as a marker of pulmonary oedema. Diaphragmatic electrophysiological testing was also performed 2 hours post injury. Freshly harvested diaphragmatic muscle strips had peak evoked muscle twitches measured, the maximal tetanic twitch and muscle strip fatigue times were also assessed. Statistical analysis was performed by means of analysis of variance (ANOVA). Results: The cohort of animals with the greatest injury severity manifested evidence of acute lung injury when compared with controls, this was associated with evidence of interstitial leucosequestration. This data suggests that neutrophils are involved in mediating an acute lung injury following musculoskeletal trauma

Purpose: Recent studies have examined the systemic inflammation that occurs following spinal cord injury (SCI) (Gris et al. 2008). It is believed that this systemic inflammation plays a role in the respiratory, renal and hepatic morbidity of SCI patients, ultimately contributing to mortality post-injury. Evidence of this inflammatory response has been shown as early as two hours post SCI (Gris et al. 2008) Intravital microscopy is a powerful tool for assessing inflammation acutely and in ‘real-time’ (Brock et al. 1999). This tool would be useful for demonstrating the acuteness of a systemic inflammatory response post-SCI, and for assessing the degree of inflammation to different severities of SCI. The liver has been shown to play a particularly important role in the initiation and progression of the early systemic inflammatory response to spinal cord injury (SCI), therefore the purpose was to evaluate hepatic inflammation immediately after SCI. We hypothesized that SCI would cause immediate leukocyte recruitment and that the magnitude of inflammation would increase with increasing severity of cord injury. Method: Male Wistar rats (200–225g) were randomly assigned to one of the following groups: uninjured, trauma-injured (laminectomy and no cord injury), cord compressed or cord transected. Spinal cord-injured rats were anesthetized by isoflurane, a dorsal laminectomy was performed, and the 4th thoracic spinal segment was injured by a moderately severe clip-compression injury or by a severe complete cord transection injury. Uninjured rats and trauma-injured rats served as controls. At 0.5 and 1.5 h after SCI rats had the left lobe of their livers externalized and visualized using intravital video microscopy. Results: At 0.5 hours the total number of leukocytes per post-sinusoidal venule was significantly increased after cord compression and cord transection compared to that in uninjured and trauma-injured rats (P< 0.05). Of these leukocytes significantly more were either adherent or rolling along venule walls compared to uninjured and trauma-injured rats (P< 0.05). Of the rolling leukocytes 2–fold more were observed after cord transection compared to cord compression. At 1.5 h the total number of leukocytes per post-sinusoidal venule and the number of adherent leukocytes was significantly increased only after cord transection. Conclusion: Injury to the spinal cord but not trauma alone causes immediate leukocyte recruitment to the liver within 0.5 h after injury. Also, leukocyte recruitment increases with increasing severity of injury. This is the first study to use intravital microscopy to visualize systemic inflammation in the liver following SCI

Introduction. The objectives of this study were to compare the systemic inflammatory reaction, localised thermal response and macroscopic soft tissue injury outcomes in conventional jig-based total knee arthroplasty (conventional TKA) versus robotic total knee arthroplasty (robotic TKA). Methods. This prospective randomised controlled trial included 30 patients with symptomatic knee osteoarthritis undergoing conventional TKA versus robotic TKA. Predefined serum markers of inflammation and localised knee temperature were collected preoperatively and postoperatively at 6 hours, day 1, day 2, day 7, and day 28 following TKA. Blinded observers used the Macroscopic Soft Tissue Injury (MASTI) classification system to grade intraoperative periarticular soft tissue injury and bone trauma. Plain radiographs were used to assess the accuracy of achieving the planned limb alignment and implant positioning in both treatment groups. Results. Conventional TKA and robotic TKA had comparable changes in the postoperative systemic inflammatory reaction and localised thermal response at 6 hours, day 1, day 2 and day 28 after surgery. Robotic TKA had reduced levels of interleukin-6 (p<0.001), tumour necrosis factor-α (p=0.021), erythrocyte sedimentation rate (p=0.001), C-reactive protein (p=0.004), and creatine kinase (p=0.004) at day 7 after surgery compared to conventional TKA. Robotic TKA was associated with improved intraoperative preservation of the periarticular soft tissue envelope (p<0.001) and reduced bone trauma (p=0.015) compared to conventional TKA. Robotic TKA improved accuracy of achieving the planned limb alignment (p<0.001), femoral component positioning (<0.001), and tibial component positioning (<0.001) compared to conventional TKA. Conclusion. Robotic TKA was associated with a transient reduction in the early (day 7) postoperative inflammatory response but there was no difference in the immediate (<48 hours) or late (day 28) postoperative systemic inflammatory responses compared to conventional TKA. Robotic TKA was associated with decreased iatrogenic periarticular soft tissue injury, reduced bone trauma and improved accuracy of implant positioning compared to conventional TKA

Introduction: Surgical injury induces a systemic inflammatory response proportional to the severity of the insult. An appropriate response maintains homeostasis and allows wound healing while an excessive response may trigger an inflammatory cascade resulting in the systemic inflammatory response syndrome (SIRS). Tissue injury results in cytokine release, which in turn stimulates the production of acute phase proteins such as C-reactive protein (CRP), fibrinogen, complement C3 and haptoglobin. Serum CRP levels rise following total hip arthroplasty (THA), peaking on the second to third post-operative day. Local effects of the inflammatory response manifest as the cardinal signs of inflammation, which include swelling. One of the potential benefits cited for minimally invasive THA is reduced soft tissue trauma resulting in less post-operative pain, less swelling and earlier mobilisation. Objective evidence, from well designed prospective studies, for these benefits remains lacking. The aim of this study was to investigate whether a minimally invasive technique in THA results in a reduced acute phase response and reduced post-operative swelling compared to THA performed through a standard incision of 16cm. Materials and Methods: 219 patients were randomised to either a minimally invasive (less than or equal to 10cm) or standard (16cm) incision group. Patients were blinded to their incision length. Anaesthetic and postoperative analgesic protocols were standardised. A single surgeon performed all operations using an uncemented cup and a cemented stem. Baseline CRP levels were measured pre-operatively and re-measured on the second post-operative day to determine whether there was any difference in the magnitude of the inflammatory response between the two patient groups. Pre-operative measurements were also made of the mid-thigh circumference on the affected side. The mid-thigh circumference was re-measured at 48 hours to assess postoperative swelling. Results: There was no statistically significant difference in the mean serum CRP levels at 48 hours, which were 135.7mg/L (SD 51.2) for the mini-incision group and 125.6mg/L (SD 59.4) for the standard group (p=0.20). With respect to post-operative swelling, the mean increase in mid-thigh circumference at 48 hours was 4.3cm for the mini-incision group and 3.7cm for the standard group. The difference between the two groups was not statistically significant (p=0.30). Conclusion: THA performed through a single incision minimally invasive approach does not result in reduced post-operative swelling or a reduced acute phase response, as measured from post-operative CRP rise, compared to THA performed through a standard incision of 16cm

Aim. Hospital systems have recently instituted early systemic sepsis recognition systems, where vital signs and laboratory findings are monitored and automatically alert providers to potential sepsis. Although there are very few reports evaluating the use of sepsis alert systems outside of the emergency room or intensive care unit, many hospital systems have made the decision to apply the sepsis alarm protocols to all inpatients. The purpose of this study was to evaluate if an alarm system using systemic inflammatory response syndrome (SIRS) criteria is a valuable tool to predict systemic sepsis in the immediate postoperative period (POD#0–4) after total joint arthroplasty (TJA). Method. 10,791 primary and revision TJA patients at one institution, from 2010–2014, were retrospectively reviewed for positive SIRS criteria on each hospital day from the date of surgery to postoperative day four (POD#4). SIRS criteria included temperature > 38°C or < 36°C, heart rate > 90 beats per minute, respiratory rate > 20 breaths per minute, and white blood cell (WBC) > 12,000/mm3 or < 4,000/mm3. Additionally, hospital coding data was cross-referenced to identify patients who were diagnosed with systemic sepsis within 10 days after having a TJA. Results. Of the 10,791 patients undergoing a primary or revision TJA, only 1 patient was diagnosed with sepsis within 10 days of TJA, yielding a prevalence of 0.00009. During POD#0–4, 1798 patients would have triggered at least a 2 criteria SIRS alarm, yielding a false positive rate of 16.7% and a positive predictive value for systemic sepsis of 0.06% (95%CI: 0 to 0.31%). 416 patients would have triggered at least 3 criteria SIRS alarm, yielding a false positive rate of 3.9% and positive predictive value of 0.24% (95%CI:0.01 to 1.33%). The SIRS criteria in the one septic patient in this study did become positive, but did so only after the clinical team had already initiated sepsis care. Conclusions. A SIRS based alarm system for sepsis does not appear to have any utility in the postoperative period after TJA. We are concerned that the high false positive rate of these alarms may result in unnecessary sepsis work-ups, extended hospital stays, and potentially degrade the perceived importance of the sepsis alarms in other cohorts of hospital patients. Further research is necessary to determine if TJA patients with a length of stay greater than normal may benefit from an automatic sepsis alarm system

The mechanism by which cells die is important in an immune response and its resolution. The role of apoptosis in sepsis and trauma, and its regulation by cytokines is unclear. During the systemic inflammatory response, rates of human neutrophil apoptosis are decreased. Peritoneal macrophage apoptosis has been induced by nitric oxide and Lipopolysaccharide (LPS) in vitro but this has not as yet been demonstrated in vivo. We examined the induction and effects of macrophage apoptosis in a model of trauma and sepsis. One hundred female CD-I mice were randomised into four groups: Control, Septic model, challenged with intraperitoneal LPS (1.Img/200ul/mouse), Traumatic model, received hind limb amputation (HLA) and a Combined trauma/septic model. After 24 hrs mice were sacrificed and peritoneal macrophages were assessed for apoptosis by morphology and DNA fragmentation by flow cytometry and DNA gel electrophoresis. Peritoneal lavage from septic models had a decreased percentage of macrophages in comparison to control and trauma groups. The septic model also had a significantly increased incidence of apoptosis in comparison to control and trauma levels. There was no significant difference between control and traumatic groups. These findings demonstrate that in a murine model of sepsis, lipopolysaccharide induces macrophages apoptosis. Modulation of this immune response may have important roles in the management of trauma patients

Background and Objectives: Damage control orthopaedics (DCO) seeks to minimize surgical impact while treating all long bone and pelvic fractures in an emergency basis. Temporary external fixation is the preferred method for DCO in polytrauma care and mass casualty events.. External fixation allows stabilisation of long bone fractures without prolonged surgical procedures; reduce blood loss and systemic inflammatory response, although it is not clear which is the effect on complications and mortality. Materials and Methods: Case series. Retrospective analysis of data trauma registry data. We studied the clinical outcome of a consecutive group of by DCO concepts for long bone and pelvic fractures, including a mass casualty event with multiple victims from a bomb attack. We analyzed the clinical outcomes in terms of systemic complications and mortality measured by TRISS methodology. Inclusion criteria: Age > 15, ISS> 16, external fixation in first 6 hours for long bone or pelvic fractures. Results: Between 2003 and 2008 45 patients met the inclusion criteria. Average age was 33 yrs, means ISS 35, and most patients suffered road traffic accidents. We performed 65 temporary external fixators in forty five patients. Most frequent procedures were femur external fixation in 30 cases followed by tibia external fixation in 25 patients. Systemic complication rate was high. Six patients died. We found a reduction in mortality between probability of survival by TRISS and real mortality of 0.18 (0, 67 Ps versus 0, 85 real survival). Conclusions: External fixation for early fixation of long bone fractures in polytrauma patient is a safe and successful treatment. DCO seems to reduce mortality in severe polytrauma patients with multiple fractures

The timing of definitive fracture fixation after Damage Control Surgery (DCS) remains a problem. Our unit employs a pragmatic approach, timing definitive surgery when the patient's clinical condition is judged satisfactory. Previous data implies fixation may result in a significant ‘second hit’ if executed <5 days after admission and DCS. The response to definitive fracture fixation in adult major trauma patients requiring DCS (MT ISS>25, n= 11) with fractures of the femoral shaft, pelvis or acetabulum were studied in comparison to patients with those fractures in isolation (IF n=21) and uninjured comparable surgical controls (SC n=12). Interleukin-8 (IL-8), IL-6 and sIL-6R levels, and neutrophil CD11b & monocyte HLA-DR expression were studied at admission, preoperatively and on days 2 & 5 post-operatively. Patients were divided into those undergoing definitive surgery within the first 5 days of admission (MT1st5 & IF1st5) or later (MTL & IFL). IL-8 levels were elevated in MT patients throughout, suggesting a proinflammatory state, whereas IL-6 levels were elevated but then declined steadily. This was independant of timing of surgery. The only post-operative rise observed was in IL-6 in SC patients. sIL-6R levels were increased in MT compared to IF patients post surgery. This elevated state, following increased IL-6 levels may be associated with resolution of the inflammatory response. CD11b expression in the MT group was unaffected. HLA-DR expression was reduced in the MT1st5 group, and post surgery in SC and IF1st5 groups. No post op cases of ARDS/MODS were diagnosed. These data suggest there is no associated detrimental effect upon the systemic inflammatory response even when undertaken less than 5 days from admission & DCS, and thus support a pragmatic approach in timing definitive fracture surgery based upon the patient's clinical improvement