Background: Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. Methods:We randomised 2970 patients from 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were ≥45 years of age were eligible. Patients were randomly assigned to accelerated surgery (goal of surgery within 6 hours of diagnosis; 1487 patients) or standard care (1483 patients). The co-primary outcomes were 1.) mortality, and 2.) a composite of major complications (i.e., mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Outcome adjudicators were masked to treatment allocation, and patients were analysed according to the intention-to-treat principle; ClinicalTrials.gov, NCT02027896. Findings:The median time from hip fracture diagnosis to surgery was 6 hours (interquartile range [IQR] 4-9) in the accelerated-surgery group and 24 hours (IQR 10-42) in the standard-care group, p<0.0001. Death occurred in 140 patients (9%) assigned to accelerated surgery and 154 patients (10%) assigned to standard care; hazard ratio (HR) 0.91, 95% CI 0.72-1.14; absolute risk reduction (ARR) 1%, 95% CI -1-3%; p=0.40. The primary composite outcome occurred in 321 patients (22%) randomised to accelerated surgery and 331 patients (22%) randomised to standard care; HR 0.97, 95% CI 0.83-1.13; ARR 1%, 95% CI -2-3%; p=0.71.Interpretation: Among patients with a hip fracture, accelerated surgery did not significantly lower the risk of mortality or a composite of major complications compared to standard care.

Purpose Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic. The toughest issue traumatic orthopaedic surgeons are faced with is how to maintain a balance between adequate COVID-19 screening and timely surgery. In this study, we described our experience with pre-operative COVID-19 screening in patients with traumatic fractures. Furthermore, we analysed the clinical results of fracture patients undergoing confined or emergency surgery during the COVID-19 outbreak. Methods This was a case series study. Patients with traumatic fractures who were admitted to our hospital for surgery were enrolled in this study during the COVID-19 outbreak from March to April 2020. All patients were enrolled and managed using the standardized clinical pathway we designed for preoperative COVID-19 screening. Clinical, laboratory and outcome data were analysed. Results The average surgery waiting time from injury to surgery was 8.7 ± 3.4 days. The average waiting time from admission to surgery was 5.3 ± 2.8 days. These average waiting times were increased by 4.1 days and 2.0 days, respectively, compared with 2019 data. Cardiovascular complications, venous thromboembolism and pneumonia occurred in one, two and one patient, respectively. Three and two patients developed pre-operative and postoperative fevers, respectively. Conclusions We introduced a novel clinical pathway for pre-operatively screening of COVID-19 in traumatic orthopaedic patients. The delay in surgery caused by COVID-19 screening was minimized to a point at which reasonable and acceptable clinical outcomes were achieved. Doctors should pay more attention to perioperative complications, such as cardiovascular complications, venous thromboembolism, pneumonia and fever.

Background Gross deformity of the foot in Charcot neuroarthropathy can lead to foot collapse and subsequent ulceration, infection, amputation, or premature death. Total-contact casting (TCC) is a well-established treatment for neuropathic diabetic plantar foot ulcers. It was hypothesized that arthrodesis plus TCC may have advantages over TCC alone. This pilot study compared the effectiveness of arthrodesis plus TCC with TCC alone for the prevention, treatment, and recurrence of midfoot ulcerations associated with Charcot neuroarthropathy. Material/Methods Twenty-one subjects with plantar ulcers associated with unilateral diabetic Charcot midfoot neuroarthropathy were randomly assigned to ADS or TCC groups. The ADS group underwent an extended medial column arthrodesis procedure and TCC; ulcers were sutured directly. The TCC group underwent TCC alone with dressing changes. All patients underwent nerve conduction studies and quantitative sensory testing at baseline and during follow-up (6 and 12 months). Healing time and ulcer relapse rate were evaluated. Result Compared with the TCC group, there were fewer lesions in the ADS group after treatment (P<0.05). Temperature testing and vibration perception threshold improved significantly after ADS (P<0.05). Although the number of patients positive for pinprick and light touch sensations increased after surgery, not all patients recovered these sensations. Healing time was not significantly different between the 2 groups (24.25±3.89 vs. 25.89±2.84 days, P>0.05). There was no ulcer recurrence after 12 months in the ADS group compared with 33.3% in the TCC group. Conclusions An extended medial column arthrodesis may partly improve sensory impairments and restore protective sensation in patients with Charcot neuroarthropathy.

Sulfur dioxide (SO2) is naturally synthesized by glutamate-oxaloacetate transaminase (GOT) from L-cysteine in mammalian cells. We found that SO2 may have a protective effect on acute lung injury (ALI) induced by limb ischemia/reperfusion (I/R) in rats. The PI3K/Akt, p38MAPK, and JAK2/STAT3 pathways are crucial in cell signaling transduction. The present study aims to verify the role of SO2 on limb I/R-induced ALI, and investigate whether PI3K/Akt, p38MAPK, and JAK2/STAT3 pathways were involved, as well as the relationship among the three pathways; we used specific inhibitors (LY294002, SB03580, and Stattic) to block them, respectively. The experimental methods of Western, ELISA, TUNEL, etc., were used to test the results. In the I/R group, the parameters of lung injury (MDA, MPO, TUNEL, cytokines) increased significantly, but the administration of Na2SO3/NaHSO3 attenuated the damage in the lung. The Western results showed that the rat's lung exist expression of P-STAT3, P-AKT, and P-p38 proteins. After I/R, P-STAT3, P-Akt, and P-p38 proteins expression all increased. After using Na2SO3/NaHSO3, P-Akt, and P-p38 proteins expression increased, but P-STAT3 protein expression decreased. We also found a strange phenomenon; compared to the I/R + SO2 group, the administration of stattic, P-p38 protein expression showed no change, but P-Akt protein expression increased (p < 0.05). In conclusion, SO2 has a protective effect on rats with limb I/R-induced ALI. The JAK2/STAT3, PI3K/Akt, and p38MAPK pathways are likely all involved in the process, and the JAK2/STAT3 pathway may have an impact on the P13K/Akt pathway.

Background: Macrophage exosomes and vascular endothelial cells (VECs) are critical to bone healing. However, few studies explore the molecular regulation of them in the bone fracture microenvironment. Methods: In this study, we explored the effects of adenosine receptor A2A (ADA2AR) in macrophage exosomes and VECs during bone healing. CGS21680 (an ADA2AR agonist) and ZM241385 (an ADA2AR antagonist) were used. First, the effects of the ADA2AR on VECs during bone healing were studied in vivo in a rat tibial fracture model. Second, the effects of ADA2AR on VECs and in the regulation of VECs by macrophages were examined in the bone fracture microenvironment. Third, the effects of ADA2AR on the regulation of macrophage exosomes on VECs were analyzed. Finally, the genes and long non-coding RNAs (lncRNAs) associated with the regulation of VECs by the ADA2AR were examined by high-throughput sequencing and bioinformatics analysis. Results: CGS21680 accelerated VEC proliferation in the early stage of bone healing and that ZM241385 suppressed VEC proliferation in vivo. ZM241385 inhibited cell viability and tube formation in vitro. However, CGS21680 did not promote tube formation, cell proliferation, or cell migration in vitro. The inhibition of macrophage exosomes could suppress tube formation and VEC migration. CGS21680 had no effects on tube formation in a macrophage-VEC co-culture. The macrophage exosomes were purified and CGS21680 promoted the macrophage secretion of exosomes. In contrast, ZM241385 inhibited the macrophage secretion exosomes. Finally, the lncRNA and mRNA involved in the activation of the ADA2AR in VECs were analyzed. CGS21680 upregulated 3274 mRNAs and downregulated 2236 mRNAs, and upregulated 1696 lncRNAs and downregulated 1882 lncRNAs. The hub genes involved in angiogenesis were Flt1, Fgf2, Mapk14, Fn1, and Jun. Conclusion:The activation of ADA2AR was essential for angiogenesis and the secretion of exosomes by macrophages during bone healing; moreover, the inactivation of the ADA2AR led to poor angiogenesis and bone nonunion.

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Objective To explore the efficacy of antibiotic bone cement (ABC) combined with the modified tibial transverse transport (mTTT) on the treatment of severe diabetic foot with infection. Methods A retrospective cohort study was conducted of 243 patients with TEXAS grade 3/4 stage D diabetic foot ulcers from December 2016 to December 2019. A total of 115 patients treated with mTTT were classified as the mTTT group (78 male and 37 female, mean age: 70.4 ± 6 years) and 128 patients who were treated with ABC combined with mTTT were in the ABC + mTTT group (89 male and 39 female, mean age: 68.9 ± 8 years). Follow‐up records during treatment and 6 months after surgery were collected, including the time required for white blood cells (WBC) and C‐reactive protein (CRP) to return to normal range, wound healing time, pain visual analog scale (VAS), ankle‐brachial index (ABI), foot skin temperature, transcutaneous oxygen pressure measurement (TcPO2), complications, and other indicators. Normally distributed data were compared using the independent sample t‐test, non‐normally distributed data were analyzed by one‐way ANOVA analysis of variance. Results There were 128 cases in the ABC + mTTT group (89 male and 39 female, mean age: 68.9 ± 8 years) treated with ABC and mTTT, and 115 cases in the TTT group (78 male and 37 female, mean age: 70.4 ± 6 years) treated with mTTT alone. The time required for WBC and CRP to return to the normal range and wound healing time in the ABC + mTTT group were significantly shorter than those in the mTTT group (12.9 ± 4.6 vs. 22.6 ± 1.6 days, t = 3.979, p < 0.001; 25.3 ± 1.3 vs. 31.3 ± 2.3 days, t = 4.261, p = 0.001; 11.9 ± 3.8 vs. 15.9 ± 3.9 days, t = 4.539, p < 0.001). There were no significant intergroup differences in the foot skin temperature, VAS score, ABI, and TcPO2 (t = 0.349, 0.542, 0.765, 0.693 while all p > 0.05). Conclusion Although the application of ABC with mTTT for treatment of diabetic foot ulcers did not affect the wound healing time and ankle blood supply in the mid‐term, it could control ulcer infection faster and accelerate wound healing.

Background:Open reduction and internal fixation with plate and screws are the gold standard for the surgical treatment of humeral shaft fractures, this study was to compare the mechanical properties of anteromedial, anterolateral, and posterior plating for humeral shaft fractures.Methods:A distal third humeral shaft fracture model was constructed using fourth-generation sawbones (#3404, composite bone). A total of 24 sawbones with a distal third humeral shaft fracture was randomly divided into three Groups: A, B, and C (n = 8 in each group) for anteromedial, anterolateral, and posterior plating, respectively. All sawbones were subjected to horizontal torsional fatigue tests, horizontal torsional and axial compressive fatigue tests, four-point bending fatigue tests in anteroposterior (AP) and mediolateral (ML) directions and horizontal torsional destructive tests.Results:In the horizontal torsional fatigue tests, the mean torsional angle amplitude in Groups A, B, and C were 6.12°, 6.53°, and 6.81°. In horizontal torsional and axial compressive fatigue tests, the mean torsional angle amplitude in Groups A, B, and C were 5.66°, 5.67°, and 6.36°. The mean plate displacement amplitude was 0.05 mm, 0.08 mm, and 0.10 mm. Group A was smaller than Group C (P < 0.05). In AP four-point bending fatigue tests, the mean plate displacement amplitude was 0.16 mm, 0.13 mm, and 0.20 mm. Group B was smaller than Group C (P < 0.05). In ML four-point bending fatigue tests, the mean plate displacement amplitude were 0.16 mm, 0.19 mm, and 0.17 mm. In horizontal torsional destructive tests, the mean torsional rigidity in Groups A, B, and C was 0.82, 0.75, and 0.76 N·m/deg. The yielding torsional angle was 24.50°, 25.70°, and 23.86°. The mean yielding torque was 18.46, 18.05, and 16.83 N·m, respectively.Conclusions:Anteromedial plating was superior to anterolateral or posterior plating in all mechanical tests except in AP four-point bending fatigue tests compared to the anterolateral plating group. We can suggest that anteromedial plating is a clinically safe and effective way for humeral shaft fractures.