Thromboprophylaxis in lower limb immobilisation after injury (TiLLI).

Venous thromboembolic disease is a major global cause of morbidity and mortality. An estimated 10 million episodes are diagnosed yearly; over half of these episodes are provoked by hospital admission/procedures and result in significant loss of disability adjusted life years. Temporary lower limb immobilisation after injury is a significant contributor to the overall burden of venous thromboembolism (VTE). Existing evidence suggests that pharmacological prophylaxis could reduce overall VTE event rates in these patients, but the proportional reduction of symptomatic events remains unclear. Recent studies have used different pharmacological agents, dosing regimens and outcome measures. Consequently, there is wide variation in thromboprophylaxis strategies, and international guidelines continue to offer conflicting advice for clinicians. In this review, we provide a summary of recent evidence assessing both the clinical and cost effectiveness of thromboprophylaxis in patients with temporary immobilisation after injury. We also examine the evidence supporting stratified thromboprophylaxis and the validity of widely used risk assessment methods.

Isolated closed minor-muscle injury of the lower leg did not cause an obvious systemic immune response.

OBJECTIVE: A common consequence in patients with blunt trauma is a deterioration of the immune system. The specific impacts of a frequently occurring isolated soft tissue trauma on the immune response are described. However, the dimension of trauma needed to cause systemic effects has not been definitely elucidated. METHODS: Mice were traumatized on the lower leg. The extent of soft tissue trauma was quantified by determination of the wet/dry ratio, magnetic resonance imaging (MRI), and serum content of muscle proteins. Five minutes, 3, 24, 36, 48, and 72 h after trauma (a.t.) the ex vivo cytokine-expression of immune-competent cells were measured. RESULTS: Trauma resulted in an early edema that could be quantified by MRI and wet/dry ration. Release of muscle-specific proteins was detected 5 min a.t. The trauma did not cause significant changes of TNF-alpha response of isolated cells to endotoxin. IL6-response of splenocytes to endotoxin was slightly increased 72 h a.t., while IL6-response of peritoneal macrophages to endotoxin was decreased 36 h a.t. CONCLUSION: We describe a standardized trauma model for minor soft tissue injury in mice. Systemic effects on the immune system by traumatized lower leg were not found on the level of circulating cytokines or cellular responses to endotoxin.

Effect of changes in serum levels of endogenous hydrogen sulfide on fracture healing: Study protocol clinical trial (SPIRIT compliant).

BACKGROUND: Fracture is a common disease; many factors affect fracture healing. Recent studies have confirmed that hydrogen sulfide (H2S) plays an essential role in bone formation, but most of these studies are drawing conclusions based on animal experiment; whether H2S could promote fracture healing in patients is still unclear. We aim to investigate the change of serum H2S in fracture patients, and analyze its effort on fracture healing. METHODS: This is a single-center, prospective cohort study. Patients with spinal or limb fracture will be recruited. Patient's serum and urine will be collected at baseline for examination (serum H2S, ß-CTX, OC, PINP, 25-OH-VitD3, S-CTX, urinary calcium, and urinary creatinine). All patients will be followed-up for 24 months in outpatients settings, the image of X-ray or CT will be reviewed and fracture healing will be judged by 2 experienced orthopedic physicians. The difference in serum parameters especially H2S will be compared between patients with fracture healed within 9 months and those with fracture unhealed at 9 months. DISCUSSION: Results of the trial could provide insight into influence of H2S on fracture healing. ETHICS AND DISSEMINATION: The study was approved by the ethics committee of School of Medicine UESTC & Sichuan Provincial People's Hospital Ethics Committee. All the participants will be asked to provide written informed consent before data collection. The findings of the study will be published in peer-reviewed journals and will be presented at national or international conferences.

A rat model of orthopedic injury-induced hypercoagulability and fibrinolytic shutdown.

BACKGROUND: Postinjury hypercoagulability occurs in >25% of injured patients, increasing risk of thromboembolic complications despite chemoprophylaxis. However, few clinically relevant animal models of posttraumatic hypercoagulability exist. We aimed to evaluate a rodent model of bilateral hindlimb injury as a preclinical model of postinjury hypercoagulability. METHODS: Forty Wistar rats were anesthetized with isoflurane: 20 underwent bilateral hindlimb fibula fracture, soft tissue and muscular crush injury, and bone homogenate injection intended to mimic the physiological severity of bilateral femur fracture. Twenty sham rats underwent anesthesia only. Terminal citrated blood samples were drawn at 0, 6, 12, and 24 hours (n = 5 per timed group) for analysis by native thromboelastography in the presence and absence of taurocholic acid to augment fibrinolysis. Plasminogen activator inhibitor 1 and α-2 antiplasmin levels in plasma were assessed via enzyme-linked immunosorbent assay. RESULTS: Injured rats became hypercoagulable relative to baseline by 6 hours based on thromboelastography maximal amplitude (MA) and G (p < 0.005); sham rats became hypercoagulable to a lesser degree by 24 hours (p < 0.005). Compared with sham animals, injured rats were hypercoagulable by MA and G within 6 hours of injury, remained hypercoagulable by MA and G through at least 24 hours (all p < 0.01), and showed impaired fibrinolysis by taurocholic acid LY30 at 12 hours (p = 0.019) and native LY30 at 24 hours (p = 0.045). In terms of antifibrinolytic mediators, α-2 antiplasmin was elevated in trauma animals at 24 hours (p = 0.009), and plasminogen activator inhibitor 1 was elevated in trauma animals at 6 hours (p = 0.004) and 12 hours (p < 0.001) when compared with sham. CONCLUSIONS: Orthopedic injury in rodents induced platelet and overall hypercoagulability within 6 hours and fibrinolytic impairment by 12 to 24 hours, mimicking postinjury hypercoagulability in injured patients. This rodent model of orthopedic injury may serve as a preclinical testing ground for potential therapies to mitigate hypercoagulability, maintain normal fibrinolysis, and prevent thromboembolic complications.

Inflammatory biomarkers in combat wound healing.

BACKGROUND: Modern war ballistics and blast injuries inflict devastating extremity injuries, violating soft tissue, bone, and neurovascular structures. Despite advances in complex wound management, appropriate timing of war wound closure remains subjective. In addition, the pathophysiology of acute wound failure is poorly defined. METHODS: Patients with penetrating extremity wounds sustained during combat were prospectively studied and followed for 30 days after definitive wound closure. The primary outcome was wound healing. Wound dehiscence was defined as spontaneous partial or complete wound disruption after closure. Serum, wound effluent, and wound bed tissue biopsy were collected at each surgical wound debridement. Serum and wound effluent were analyzed with a multiplex array of 22 cytokines and chemokines, and wound tissue for corresponding gene transcript expression. RESULTS: Fifty-two penetrating extremity war wounds in 33 male patients were investigated. Nine (17%) wounds dehisced. Concomitant vascular injury, increased wound size, and higher injury severity score correlated with wound dehiscence. Both serum and wound effluent cytokine and chemokine protein profiles were statistically associated with healing outcome at various time points. Wound biopsy gene transcript expression demonstrated increased tissue inflammation associated with wound failure. Multiple protein and gene transcript biomarkers predictive of wound healing were identified. CONCLUSIONS: The cytokine and chemokine protein and gene transcript expression patterns demonstrate a condition of inflammatory dysregulation associated with war wound failure. A molecular biomarker panel may predict combat wound healing outcome and warrants prospective validation.

Effect of Ultrasound Debridement on Serum Inflammatory Factors and bFGF, EGF Expression in Wound Tissues.

OBJECTIVE: To determine the effect of ultrasonic debridement on serum inflammatory factors of procalcitonin (PCT), highsensitivity C-reactive protein (hs-CRP), red blood cell deposition rate (ESR) content, and expression levels of wound tissue basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Department of Emergency, Dongguan People's Hospital, China, from February 2016 to February 2018. METHODOLOGY: A total of 80 patients with limb flap repair were randomly divided into a control group and an observation group, with 40 cases in each group. Control group was treated with conventional surgical debridement, and the observation group was treated with ultrasound debridement technique. The effect was compared between two groups. RESULTS: On the 1st, 3rd, and 7th days after flap repair, Numeric Rating Scale (NRS) scores in observation group were lower than those in control group (all p <0.001). On the 7th day after the flap repair, serum levels of PCT, hs-CRP, and ESR were lower in observation group than those in control group (all p <0.001). On the 7th and 12th day after flap repair, expression levels of bFGF and EGF protein in the wound tissue of observation group were higher than those in control group (all p <0.001). Infection with sinus tract formed after the flap repair in observation group was lower than that in control group (p=0.048). CONCLUSION: Compared with conventional surgical debridement, ultrasound debridement technique can more effectively reduce postoperative inflammatory reactions, reduce postoperative wound infection, relieve pain in patients, promote the bFGF and EGF expression in the wound tissue.

Markers of blood coagulation and fibrinolysis in patients with early and delayed microsurgical reconstructions in the lower extremities.

BACKGROUND: In this study, markers of coagulation and fibrinolysis were assessed during early and delayed microsurgical reconstruction in patients with traumatic defects of their lower legs to analyse whether an imbalance of the hemostasis after trauma might predispose the development of vascular complications. METHODS: The prospective study included 70 patients. In 35 patients, surgery was performed within 72 hours after injury. In 35 other patients, delayed free flap transfer was performed between 14-21 days after trauma. In each group, reconstruction was performed with a fasciocutaneous anterior-lateral thigh flap (ALT, n = 18) or a myocutaneous flap (latissimus dorsi flap; n = 17). Blood samples were collected preoperatively, intraoperatively, and 3, 6, 12, 24, 36, 48, 72, 96 and 120 hours after the operation. Analysed parameters included markers of coagulation such as prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III-complex (TAT), and antithrombin, as well as fibrinolysis markers such as plasminogenactivator inhibitor-I (PAI-1), tissue-plasminogenactivator (t-PA), and plasminogen. RESULTS: Preoperatively, levels of F1 + 2, TAT, and PAI-1 were significantly higher in patients with delayed reconstruction (p < .05). Patients with later vascular complications in this group (n = 5) presented a significant higher concentration of TAT, F1 + 2, and PAI-1 (p < .05). Twelve and 24 hours after free flap surgery, patients with vascular complications presented significant elevated levels of these markers (p < .05). CONCLUSIONS: Patients with delayed free flap surgery after lower leg trauma present a hypercoagulable state in their blood due to activation of the coagulation system and hypofibrinolysis. Early reconstruction might minimise the risk of flap failure caused by hypercoagulability.

Canine model of crush syndrome established by a digital crush injury device platform.

OBJECTIVE: To establish a canine model of crush syndrome (CS). METHODS: A total of 16 healthy adult female Beagle dogs were randomly divided into the control group (n=8) and the experimental group (n=8). The crush injury was created in the left hind leg of each dog in the experimental group. RESULTS: The biochemical indexes in the experimental group changed significantly compared to the values before extrusion. And they were also significantly different from the values of the control group. The glomerular capillary dilation, renal tubular epithelial cell degeneration, and renal interstitial lymphocytic infiltration were found in the kidneys. CONCLUSION: The canine CS model established by the digital crush injury device platform was successful according with the diagnosis of CS. It is good for the investigation of the CS mechanism and treatment using this model.

Rhabdomyolysis following total hip arthroplasty.

We report six cases of contralateral limb involvement during total hip arthroplasty including swelling of the gluteal muscle compartments, rhabdomyolysis, myoglobinuria, and sciatic nerve palsy. The risk factors for such complications include obesity, prolonged operative time, and positioning in the lateral decubitus position. The laboratory and clinical findings are consistent with a gluteal muscle crush-injury with consequent compartment syndrome. The patients should be treated conservatively as symptoms can be expected to resolve.

Seronegative spondyloarthropathy initiated by physical trauma.

We undertook this study to demonstrate the pattern of onset and the course of arthritis on the traumatised joint in spondyloarthropathy (SpA) initiated by physical trauma. Among 288 patients with SpA, 12 (4.2%) whose arthropathies were associated with trauma were reviewed retrospectively. There were seven patients with ankylosing spondylitis (AS), three with juvenile onset AS and two undifferentiated SpA. The type of trauma was direct injury to the joint and injuries at other sites, except in spinal surgery, for example. In eight cases the initial evidence of disease was peripheral arthritis. The disease first occurred in traumatised joints in five cases. Only three cases showed recurrent inflammatory episodes in the traumatised joints throughout the disease course. SpA initiated by trauma initially manifested as peripheral arthritis at the traumatised joints in about half of the cases. Inflammatory episodes preferentially involved other joints apart from the traumatised joints throughout the whole course of the disease.

Alcohol related falls: an interesting pattern of injuries.

OBJECTIVE: To discover if there is a significant difference in the pattern and severity of injury sustained during falls in patients who have consumed alcohol and those who have not. To determine how pattern and severity of injury correlates with blood alcohol concentration. METHOD: A prospective quasi-randomised controlled study between November 2001 and July 2002. All healthy adults between 16 and 60 years who had fallen from standing height were included. A systematic history and examination permitted calculation of injury severity scores as per abbreviated injury scale update 1998. Blood alcohol concentrations were obtained from intoxicated patients with consent. RESULTS: 351 healthy adult patients were included in the study, there were 238 in the no alcohol group, 113 had consumed alcohol and blood alcohol intake were obtained for 47. The alcohol group had a higher incidence of head injuries (46 (48%) versus 22 (9%)) with a lower incidence of limb injuries (39 (39%) versus 183 (76%)) than the no alcohol group. There was a significant difference in the pattern of injury between the alcohol and no alcohol groups (chi(2), p<0.001) and there was a significant difference in the injury severity scores (p<0.001, Z = -2.5). In the alcohol group severity and pattern correlated with alcohol concentration at the time of injury. Patients with an alcohol concentration<2 g/l had mostly soft tissue limb injuries (58%), 2-2.5 mostly significant limb fractures (55%), and >2.5 mostly significant head injuries (90%). CONCLUSIONS: Alcohol related falls are more often associated with severe craniofacial injury. The severity of both limb and head injury is greater and correlates directly with blood alcohol concentration.

Pulse oximetry in closed limb fractures.

Recent sporadic reports have described the role pulse oximetry might play in monitoring trauma victims, and specifically in the assessment of patients with limb fractures where doubt exists concerning the adequacy of limb blood flow distal to the fracture after manipulation. The results of a prospective study to determine the changes in arterial oxygen saturation as shown by pulse oximetry before and after manipulation are presented. The results suggest that the pulse oximeter may be of use in confirming the presence or absence of adequate blood flow distal to a fracture, but that this information should be considered in the light of the clinical findings. The role of pulse oximetry in the early detection of a compartment syndrome complicating a closed limb fracture has yet to be determined.

[Effects of combined therapy of traditional Chinese and Western medicine on C-reactive protein in post-debridement patients].

Closely monitoring whether the secondary infection in the patients of post-debridement occurred or not and appropriately treating these patients were the important ways to reduce the incidence of infection. Through estimating the level of the serum C-reactive protein (CRP) as the monitoring index of infection, dynamically observed the effect of the combined traditional Chinese and Western medicine therapy (TCM-WM) on CRP after debridement, as was compared with the effect of the Western medicine therapy (WM) group in which only the WM was administrated. The result showed that the levels of CRP decreased in both TCM-WM and WM group on 4th day after the operation, but the level of CRP in former group was lower than that in latter one, the difference was very significant (P < 0.001). So that, it was assumed that TCM-WM significantly excelled the WM on affecting the level of CRP and reducing the incidence of infection. It was suggested that CRP could be used as an effective and objective index to determine whether the secondary infection has happened and to assess the efficacy of some drugs.

[The characteristics of the blood lipid transport system in the disabled with lost lower extremities]. / Osobennosti lipidnoi transportnoi sistemy krovi u invalidov s utrachennymi nizhnimi konechnostiami.

A comparative analysis of major blood lipoprotein values in 108 males aged 16-65 years with lower limbs amputations has shown a higher level of triglycerides (TG) and a reduced level of high density lipoprotein cholesterol (HDL C) in them than in control males with normal limbs. In the subgroup of patients who had undergone the amputation as a result of obliterative arterial disease, the TG level was the highest while HDL C the lowest; moreover, these values appeared to be the same as in the age-matched subgroup of patients with manifestations of atherosclerosis. In the subgroup of older men with posttraumatic lower limb amputations (aged 40-59 years) the TG and HDL C levels did not differ from the corresponding parameters in age-matched subgroup of healthy subjects, whereas young amputees (17-39 years) had the increased blood TG concentration and reduced level of HDL C and apolipoprotein AI. The conclusion is made: disability following limb amputation accompanied by restricted mobility, inadequate physical static efforts as well as by chronic psychological stress seem especially dangerous for young invalids because of associated lipoprotein profile changes which can be regarded as highly atherogenic.

[The dynamic of biochemical stress reaction inductors in various tactics for surgical treatment of patients with a combined trauma of cranium and lower limbs ]. / Dinamika biokhimicheskikh induktorov stress-reaktsii pri razlichnoi taktike khirurgicheskogo lecheniia bol'nykh s sochetannoi travmoi cherapa i nizhnikh konechnostei.

In 31 patients after a craniocerebral trauma combined with a trauma of locomotor system (CCCT), and in 28 patients with only a limb fractures a time course (1, 3, 7, and 14 days) of biochemical stress reaction inductors (cortisol, serotonin, histamine, lipid peroxidation products) in various tactics of surgical treatment was studied. It was established that CCCT in a significantly stronger degree increases cortisol and lipid peroxidation products' levels than an isolated locomotor system trauma. An early postponed surgical intervention in lower extremities in CCCT results in the same increase in the biochemical stress reaction inductors as a late postpone surgical intervention in the lower extremities. In an early postponed osteosynthesis in CCCT patients, a mean term of hospital stay was 67 days, and in a late postponed one 117 days. The disability period was correspondingly 200 vs 315 days.

[Hemostatic changes after local exposure to low temperatures (frostbite)]. / Izmeneniia gemostaza pri mestnom deistvii nizkikh temperatur (otmorozheniia).

Hemostatic blood potential was studied in experiments on 400 rats, 25 dogs and in 120 patients, during changes of CNS reactivity after intraventricular injection of reserpine, adrenaline, and irritation of the thalamus ventromedial nucleus (VMN) or its destruction. CNS reactivity in dogs changed after intraarterial injections of acetylcholine, reserpine, heparin and fibrinolysin solutions. It was shown that activation of adrenergic structures of the hypothalamus by intraventricular adrenaline injections, or the hypothalamus VMN irritation, stimulated coagulation and depressed anticoagulation mechanisms of the blood, and increased hemostatic blood potential, that led to rejection of frostbitten tissues. Activation of the hypothalamus cholinergic structures by intraventricular injections of reserpine, destruction of the hypothalamus VMN, and intraarterial injections of acetylcholine, reserpine, heparin, fibrilysin and contrycal mixtures stimulated the blood anticoagulation mechanisms, decreased the hemostatic potential, led to retention of cryodestructed tissues.

[Importance of determining the blood sulfhydryl groups in fractures of the long tubular bones complicated by infection]. / Znachenie opredeleniia sul'fgidril'nykh grupp krovi bol'nykh s perelomami dlinnykh trubchatykh kostei, oslozhnennymi infektsiei.

The work presents results of the investigation of the content of sulfhydryl groups in the blood of patients with fractures of long tubular bones. The content of sulfhydryl groups of blood was studied in 168 patients with open fractures. The author comes to a conclusion that the investigation of sulfhydryl groups of blood allows not only facilitating the evaluation of severity of patients in the pre- and postoperative period and detecting complications at early terms but also enables a timely correction of the disorders to be fulfilled.

[Experience with physiotherapy in a posttraumatic neurodystrophic syndrome of the extremities]. / Opyt fizioterapii pri posttravmaticheskom neirodistroficheskom sindrome konechnostei.

Combined pathogenetic treatment including physiotherapy, drugs, massage, exercise was tested in 98 patients with posttraumatic neurodystrophic syndrome in phase II and III. The responses achieved made it possible to recommend the above regimen for wide application in rehabilitation centers and clinics.

D-dimer as an applicable test for detection of posttraumatic deep vein thrombosis in lower limb fracture.

Measuring the plasma levels of D-dimer is an accurate and easy modality to detect deep vein thrombosis (DVT) in nontraumatic settings. However, the diagnostic reliability of D-dimer assays in detecting posttraumatic DVT among patients with lower limb fracture undergoing orthopedic surgery is not validated. In this study, 141 patients with lower limb fracture admitted through the emergency department and undergoing orthopedic surgery were enrolled. Postoperative venous blood samples for D-dimer assay were taken on the 1st, 7th, and 28th postoperative days. Color Doppler sonography examination of both lower limbs was performed at the same time as a standard test. Eight out of the 141 patients (6%) had acute DVT based on Color Doppler sonography. Mean D-dimer was 2160 ng/mL in DVT positive patients and 864 in DVT negative patients. D-dimer levels greater than 1000 ng/mL were 100% sensitive and 71% specific for detecting postoperative DVT. D-dimer assay is a useful and sensitive test for detecting posttraumatic DVT.

Proteomic profiling of oxidative stress in human victims of traffic-related injuries after lower limb revascularization and indication for secondary amputation.

Microsurgical replantation and revascularization are frequently performed to salvage devascularized severe lower-extremity fractures in the human victims of road traffic-related injuries. However, some patients require secondary amputation within 1 week of successful revascularization due to tissue necrosis and sepsis. Enhanced efforts to understand the underlying molecular mechanism of such events are needed and should characterized in depth. Thus, functional proteomics were applied in this study to evaluate the role of oxidative stress in acute injury following microsurgery in a set of human subjects surviving serious road traffic accidents. Changes in the levels of protein volume and the accompanying content in protein carbonylation were visualized using two-dimensional electrophoresis (2-DE) and immunoblot analysis. Since oxidation of some acute-phase proteins not only causes them to lose their function as antioxidants but also initiates the intracellular stress signaling pathway that regulates cytokine and chemokine responses, how cytokine expression correlated with oxidative stress was also evaluated via protein array assays. It was observed that the growth-regulated oncogene protein family (GRO), the range of IL-6, IL-8, IL-10 and monocyte chemotactic protein-1 (MCP-1), which are responsible for neutrophil and monocyte aggregation with subsequent cytotoxic effects, were significantly elevated in the plasma of amputees subjects, whilst the level of chemokine recruiting leucocytes into inflammatory sites (RANTES) was diminished in the salvaged group of patients. Our results suggest that severely oxidative injury during revascularization perturbs the normal redox balance and induces carbonylation of specific proteins, thereby activating pro-inflammatory factors leading to severe tissue damage. The dissimilar 2-DE protein and cytokine profiles revealed here might reflect distinct etiologies resulting in oxidative damage to tissues and may serve as pivotal indicators of local necrosis and the subsequent need for secondary amputation of limbs. We believe that the combination of proteomic and cytokine profile results presented in this work offers more reliable information and defines more sophisticated criteria in clinical practice than currently used C-reactive protein levels (CRP) or white blood cells counts (WBC) for predicting secondary amputation requirements in patients requiring limb salvage surgery.