In our electronic medical record system, we retrospectively identified 438 fracture patients (with 304 of clavicle fracture and 134 of femoral fracture) who received ORIF in the Department of Orthopaedic Trauma, Shandong Provincial Hospital affiliated to Shandong University from January 2010 to May 2019. We excluded patients with pathological fractures and osteogenesis imperfecta, younger than 18 years old, with infection or leukemia, and without hematological examination (Figure 1). The final single-center retrospective cohort included 338 patients, including 251 with clavicle fractures and 87 with femoral fractures. Of these patients, 315 were completely healed and 23 showed nonunion. All patients were followed up for at least one year. This study was approved by the Ethics Committee of Shandong Provincial Hospital affiliated to Shandong University with the informed consent obtained from all patients in this study.
Demographic, injury, and surgical data of the patients were obtained from the electronic medical record system of Shandong Provincial Hospital, including age, gender, smoking and drinking habits, systolic blood pressure (SBP), the diastolic blood pressure (DBP), the time from injury to surgery (TIS), the American Society of Anesthesiologists (ASA) Classification, the mechanism of injury, malformation, mobility, and bony crepitus. As for the injury mechanism, the most common injuries were caused by fall, high fall, and traffic accident, while the other types of rare injuries were classified as other injuries. Hematological examinations included blood coagulation test and whole blood routine examination, and the data of related variables were obtained from the LIS system of the Clinical Medical Laboratory Department of Shandong Provincial Hospital. Coagulation tests included the plasma fibrinogen concentration (FIB), the plasma prothrombin time (PT), the plasma activated partial thromboplastin time (APTT), and the plasma D-dimer concentration (D-dimer). The routine examination of whole blood included the white blood cell count (WBC), the red blood cell count (RBC), the hemoglobin concentration (HGB), the platelets count (PLT), the absolute value of lymphocyte (LYMPH), the absolute value of monocytes (MONO), the absolute value of neutrophils (MEUT), standard deviation of red blood cell distribution width (RDW-SD), and coefficient of variation of red blood cell distribution width (RDW-CV). The blood coagulation test was performed on the STA-R Evolution Experts series automatic blood coagulation analyzer (Stago, France) and the full blood routine examination on the XN-9000 automatic blood humoral analyzer (Sysmex, Japan). Hematological examinations of all patients in this study were performed prior to the surgeries on the fractures.
All patients were treated with ORIF. We used clinical and radiological standards to define the fracture healing and nonunion. Specifically, a complete fracture healing was defined as, through follow-up, that no operation was required 12 months after fracture treatment with blurred fracture line shown on the X-ray image (Figure 2). According to FDA criteria, nonunion has been defined as that for at least 9 months after injury and fracture showed no further healing tendency for 3 consecutive months (Figure 3).
In this study, we used numbers or percentages to represent classification variables, with the significant difference evaluated by chi-square test or Fisher exact test, while continuous data were described as average ± standard deviation or median (inter quartile range, IQR) with significant differences detected by Student t test and Kruskal Wallis rank sum test. Univariate logistic regression analysis was performed on each variable to determine the association between the healing and the nonunion groups with the 95% confidence interval (CI) and odds ratio (OR) calculated. Variables showing significant difference identified by the univariate logistic repression analysis with P ≤ 0.05 were further analyzed to determine the variables playing an independent role in the occurrence of nonunion.
Data analyses were performed using statistical software R (http://www.r-project.org, The R Foundation), EmpowerStats (http://www.empower-stats.com, X&Y Solutions, Inc., Boston, MA), and GraphPad Prism (GraphPad Software; GraphPad, Bethesda, MD, USA). The significant difference was set at the two tailed P value less than 0.05.