Haematology panel biomarkers for humeral, femoral, and tibial diaphyseal fractures.

PURPOSE: The neutrophil to lymphocyte ratio (NLR) is a simple predictor used in oncology and cardiology. We aimed to analyze the NLR profile of patients with diaphyseal fractures of the humerus, femur, and tibia. METHODS: We performed a cross-sectional, consecutive-case population-based study including 148 patients (41.9% men respectively 58.1% women) with humeral (23.0%), femoral (30.4%), and tibial (46.6%) diaphyseal fractures, admitted for surgical treatment in our level 1 trauma centre over two years. RESULTS: The differences in NLR between the studied subgroups were not significant (p = 0.067), the highest value being observed in patients with femoral fracture (5.6) in contrast to patients with humeral fracture (4). In the global cohort, there was a significantly positive correlation between NLR and PLR (platelet to lymphocyte ratio; Spearman's r = 0.595; p < 0.001). The stratified subgroup analysis found significant association between NLR and duration of admission only for patients with femoral fracture (Spearman's r = - 0.308; p < 0.001). When compared with controls, all three fracture types had significantly higher neutrophil numbers and NLR and lower thrombocyte numbers. CONCLUSIONS: NLR are elevated in femur diaphyseal fractures compared with tibia and humerus, up to cut-off values with negative prediction of outcome in malignancy and cardiovascular patients. Increased NLR are predictive of longer hospital admissions for femur fractures.

Relation of thromboelastography parameters to conventional coagulation tests used to evaluate the hypercoagulable state of aged fracture patients.

Fractures are common among aged people, and rapid assessment of the coagulation status is important. The thromboelastography (TEG) test can give a series of coagulation parameters and has been widely used in clinics. In this research, we looked at fracture patients over 60 and compared their TEG results with those of healthy controls. Since there is a paucity of studies comparing TEG assessments with conventional coagulation tests, we aim to clarify the relationship between TEG values and the values given by conventional coagulation tests.Forty fracture patients (27 femur and 13 humerus) over 60 years old were included in the study. The change in their coagulation status was evaluated by TEG before surgery within 4 hours after the fracture. Changes in TEG parameters were analyzed compared with controls. Conventional coagulation test results for the patients, including activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen, and platelets, were also acquired, and correlation analysis was done with TEG parameters, measuring similar aspects of the coagulation cascade. In addition, the sensitivity and specificity of TEG parameters for detecting raised fibrinogen levels were also analyzed.The K (time to 20 mm clot amplitude) and R (reaction time) values of aged fracture patients were lower than controls. The values for angle, maximal amplitude (MA), and coagulation index (CI) were raised compared with controls, indicating a hypercoagulable state. Correlation analysis showed that there were significant positive correlations between fibrinogen and MA/angle, between platelets and MA, and between APTT and R as well. There was significant negative correlation between fibrinogen and K. In addition, K values have better sensitivity and specificity for detecting elevated fibrinogen concentration than angle and MA values.Aged fracture patients tend to be in a hypercoagulable state, and this could be effectively reflected by a TEG test. There were correlations between TEG parameters and corresponding conventional tests. K values can better predict elevated fibrinogen levels in aged fracture patients.

Quantification of TGF-ß1, PDGF and IGF-1 cytokine expression after fracture treatment vs. non-union therapy via masquelet.

INTRODUCTION: Biochemical processes during bone regeneration can be analysed via quantification of peripheral serum cytokine levels. To date, serum levels of cytokines in patients treated with masquelet technique and patients with normal bone healing have not been compared. This comparison is supposed to deliver novel insights into the process of bone regeneration. Our aim was to validate this established method in the monitoring of bone regeneration after non-union treatment in masquelet technique. MATERIALS AND METHODS: Between 04/2008 and 01/2014 three groups were recruited: G1 (10 patients) with long bone non-unions, treated successfully with masquelet therapy, G2 (6 patients) with unsuccessful masquelet therapy and G3 (10 patients) with long bone fractures and normal bone healing. Peripheral blood samples were collected over a period of six months following a standardised time pattern in combination with clinical and radiologic follow up. TGF-ß1, PDGF-AB and IGF-1 were measured using commercially available immunoassays. RESULTS: TGF-ß1 levels in G1 and G2 demonstrated a parallel and lower overall concentration over time compared to G3. G3 showed a significant TGF-ß1 peak 2 weeks after surgery compared to G1 (p=0.0054). PDGF-AB concentrations were always lower in G2 than in G1 and G3. G3 peaked at week 2 with a significant higher value than in G2 (p=0.0177). IGF-1 showed lower overall serum concentrations in G2 than in G1 and G3. G1 had a peak level during the fourth week of follow-up. Compared to G2 this peak was significant (p=0.0015). CONCLUSIONS: This study shows that successful bone regeneration via masquelet technique only partially imitates cytokine expression of physiological bone healing. High expressions of IGF-1 correspond to a successful masquelet therapy while TGF-ß seems to play a minor role. These results assume that objective analysis of an effective non-union therapy with cytokine expression analysis is possible even with a small number of patients.

VEGF serum concentrations in patients with long bone fractures: a comparison between impaired and normal fracture healing.

Vascular endothelial growth factor (VEGF) plays an important role in the bone repair process as a potent mediator of angiogenesis and it influences directly osteoblast differentiation. Inhibiting VEGF suppresses angiogenesis and callus mineralization in animals. However, no data exist so far on systemic expression of VEGF with regard to delayed or failed fracture healing in humans. One hundred fourteen patients with long bone fractures were included in the study. Serum samples were collected over a period of 6 months following a standardized time schedule. VEGF serum concentrations were measured. Patients were assigned to one of two groups according to their course of fracture healing. The first group contained 103 patients with physiological fracture healing. Eleven patients with delayed or nonunions formed the second group of the study. In addition, 33 healthy volunteers served as controls. An increase of VEGF serum concentration within the first 2 weeks after fracture in both groups with a following decrease within 6 months after trauma was observed. Serum VEGF concentrations in patients with impaired fracture healing were higher compared to the patients with physiological healing during the entire observation period. However, statistically significant differences were not observed at any time point between both groups. VEGF concentrations in both groups were significantly higher than those in controls. The present results show significantly elevated serum concentrations of VEGF in patients after fracture of long bones especially at the initial healing phase, indicating the importance of VEGF in the process of fracture healing in humans.

Changes in serum levels of receptor activator of nuclear factor-kappaB ligand, osteoprotegerin, IL-6 and TNF-alpha in patients with a concomitant head injury and fracture.

INTRODUCTION: Several reports indicated that interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF- alpha) play important regulatory roles in bone remodeling and homeostasis. In addition, receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) have been shown to be important regulators of osteoclastogenesis during bone remodeling, and their expressions were examined during fracture healing in a mouse model of tibial fracture. However, studies linking RANKL, OPG, IL-6 and TNF-alpha in patients with head injury and fracture are lacking. PATIENTS AND METHODS: Within the first few hours of admission to hospital and at 4, 8, and 12 weeks after the injury, we evaluated changes in serum levels of RANKL, OPG, IL-6 and TNF-alpha in 24 male patients with a concomitant head injury and fracture and in 26 male patients with fracture only. These levels were compared with those found in 36 healthy controls. RESULTS: The RANKL/OPG ratios were found to significantly lower in patients with a concomitant head injury and fracture than in the controls immediately after admission and at 4, 8, and 12 weeks after the injury. In addition, RANKL/OPG ratios were significantly lower in patients with a concomitant head injury and fracture than in those with fracture at 8 and 12 weeks after the injury. The serum IL-6 levels were significantly higher in patients with a concomitant head injury and fracture than in the controls upon admission, and at 4, 8, and 12 weeks after the injury. Moreover, the serum IL-6 levels were significantly higher in patients with a head injury and fracture than in those with just a fracture at 4, 8, and 12 weeks after the injury. CONCLUSIONS: Based on these changes in the profiles of RANKL, OPG, and IL-6 and the RANKL/OPG ratio, altered repair of a fracture can occur in patients with a concomitant head injury and fracture.

C-reactive protein levels for early detection of postoperative infection after fracture surgery in 787 patients.

BACKGROUND AND PURPOSE: For early detection of postoperative infections, the level of C-reactive protein (CRP) may be useful. We analyzed baseline and time-dependent reference values for the postoperative use of CRP as an indicator of infection. METHODS: We studied the kinetics of CRP levels after fracture surgery in 1,418 patients. In 787 cases the operative fracture treatment was uneventful; in 17 of the other cases a deep wound infection occurred. RESULTS: In the uneventful cases, a similar evolution in CRP concentrations was found: the peak level, which occurred on the second postoperative day, depended on the region (136 mg/L in femoral fractures and 45 mg/L in ankle fractures) and reflected the extent of surgical trauma. For deep wound infection, a cutoff level of 96 mg/L (sensitivity 92%, specificity 93%) after the fourth day of surgery was recorded. INTERPRETATION: CRP kinetics permit establishment of a time-dependent set of reference values of CRP after operative fracture treatment. Deviations of this course--especially CRP concentrations above 96 mg/L after the fourth day--may aid in early detection of surgical complications.

Elevation of IL-6 in ATL patient with a pathological fracture.

Hypercalcemia and osteolytic bone lesion are important complications in the prognosis of patients with adult T cell leukemia/lymphoma (ATL). We report a 61-year-old Japanese woman who died of ATL and had multiple osteolytic lesions and pathological fractures of her extremities. Highly increased serum levels of Interleukin-6 (IL-6) and a parathyroid hormone-related protein (PTHrP) together with a high level of serum calcium observed at the time of fractures suggested their contribution to the formation of the bone lesions.

Fracture of the humerus in ball throwers. A consequence of idiopathic juvenile osteoporosis in a female handball player?

We report a case of a spontaneous humeral shaft fracture sustained during pitching by a 22-year-old previously healthy female European team handball player. The fracture was treated by closed reposition followed by immobilization in a hanging cast. The fracture healed uneventfully, and normal function and range of motion were reached within 6 months. Between 1 and 2 years after the fracture, bone mineral measurements showed a decreased bone mass (1.43-2.56 SD below mean values of normal women) at all measuring sites; proximal tibia bilaterally (bone mineral content (right) = 2.68 g/cm, bone mineral content (left) = 2.79 g/cm), lumbar spine (bone mineral density (L2-4) = 0.814 g/cm2), and right hip (bone mineral density (neck) = 0.697 g/cm2, bone mineral density (Ward's) = 0.626 g/cm2). A thorough endocrinological examination indicated that a state of bone loss existed, but no specific endocrine disease was found. The unusual fracture presented must be considered the result of the torsional forces transmitted to a severely osteoporotic bone.

Haematological investigations in east African birds of prey.

Packed cell volume, haemoglobin and erythrocyte counts are given for 52 East African birds of prey of 21 species. Whilst the majority of the birds sampled were "normal", some were injured or diseased. The results are discussed and attention is drawn to the possible value of haematology in clinical diagnosis.