Early posterior column internal fixation: A staged treatment of type C3 tibial pilon fracture.

Pilon fractures represent a challenging subset of tibial fractures. The management of AO/OTA Type C3 fractures remains complex due to associated complications and lack of clear guidelines for surgical timing and methods. A prospective cohort study was conducted to evaluate two staged treatment strategies for AO/OTA Type C3 tibial pilon fractures. The study focused on assessing surgical difficulty, complications, and patient prognosis. One group of patients received early internal fixation of the fibula and tibial posterior column combined with external fixation, while the other group received external fixation alone in the first stage. Patients who received early internal fixation of the fibula and tibial posterior column combined with external fixation had better outcomes, including lower rate of allogeneic bone grafting (67.74 % versus 94.64 %), reduced incidence of wound delay and skin necrosis (3.23 % versus 21.43 %), shorter surgical time (133.06 ± 23.99 min versus 163.04 ± 26.83 min), shorter hospital stay (13.77 ± 2.53 days versus 18.25 ± 3.67 days), and higher AOFAS (83.05 ± 8.68 versus 79.36 ± 8.92). Additionally, avoiding fibular shortening was shown to be crucial in preventing prolonged surgery and improving patient function. The study demonstrated that the staged treatment approach with early internal fixation led to shorter operative times, improved ankle function, and reduced complications, including a lower risk of infection. The findings support the use of this treatment to optimize outcomes in AO/OTA Type C3 pilon fractures.

Case report: Microwave ablation is a safe and effective method for primary hyperparathyroidism in pregnancy.

Primary hyperparathyroidism (PHPT) is a rare disease in pregnancy and endangers the health of both pregnant women and fetuses. However, the treatments are very limited for PHPT and most of them are unsatisfactory because of the peculiar state in pregnancy. The only curable method is parathyroidectomy which can be safely performed in the second trimester of pregnancy. In this case, we reported a pregnant woman with primary parathyroid adenoma presenting hypercalcemia and severe vomit at the end of first trimester. Finally, she got cured by microwave ablation at the end of first trimester and gave birth to a healthy baby boy.

Identification and characterization of shark VNARs targeting the Helicobacter pylori adhesin HpaA.

Helicobacter pylori (H. pylori) is recognized as a pathogen associated with several gastrointestinal diseases. The current treatments exhibit numerous drawbacks, including antibiotic resistance. H. pylori can adhere to and colonize the gastric mucosa through H. pylori adhesin A (HpaA), and antibodies against HpaA may be an effective therapeutic approach. The variable domain of immunoglobulin new antigen receptor (VNAR) is a novel type of single-domain antibody with a small size, good stability, and easy manufacturability. This study isolated VNARs against HpaA from an immune shark VNAR phage display library. The VNARs can bind both recombinant and native HpaA proteins. The VNARs, 2A2 and 3D6, showed high binding affinities to HpaA with different epitopes. Furthermore, homodimeric bivalent VNARs, biNb-2A2 and biNb-3D6, were constructed to enhance the binding affinity. The biNb-2A2 and biNb-3D6 had excellent stability at gastrointestinal pH conditions. Finally, a sandwich ELISA assay was developed to quantify the HpaA protein using BiNb-2A2 as the capture antibody and BiNb-3D6 as the detection antibody. This study provides a potential foundation for novel alternative approaches to treatment or diagnostics applications of H. pylori infection.

Development and validation of nomograms for predicting survival outcomes in patients with T1-2N1 breast cancer to identify those who could not benefit from postmastectomy radiotherapy.

Purpose: In this study, we aimed to develop and validate nomograms for predicting the survival outcomes in patients with T1-2N1 breast cancer to identify the patients who could not benefit from postmastectomy radiotherapy (PMRT). Methods: Data from 10191 patients with T1-2N1 breast cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Of them, 6542 patients who had not received PMRT formed the training set. Concurrently, we retrospectively enrolled 419 patients from the Affiliated Hospital of North Sichuan Medical College (NSMC), and 286 patients who did not undergo PMRT formed the external validation set. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were used for selecting prognostic factors in the training set. Using the selected factors, two prognostic nomograms were constructed. The nomograms' performance was assessed using the concordance index (C-index), calibration curves, decision curve analysis (DCA), and risk subgroup classification. The stabilized inverse probability of treatment weights (IPTWs) was used to balance the baseline characteristics of the different risk groups. Finally, the survival outcomes and effectiveness of PMRT after IPTW adjustment were evaluated using adjusted Kaplan-Meier curves and Cox regression models. Results: The 8-year overall survival (OS) and breast cancer-specific survival (BCSS) rates for the SEER cohort were 84.3% and 90.1%, with a median follow-up time of 76 months, while those for the NSMC cohort were 84.1% and 86.9%, with a median follow-up time of 73 months. Moreover, significant differences were observed in the survival curves for the different risk subgroups (P < 0.001) in both SEER and NSMC cohorts. The subgroup analysis after adjustment by IPTW revealed that PMRT was significantly associated with improved OS and BCSS in the intermediate- (hazard ratio [HR] = 0.72, 95% confidence interval [CI]: 0.59-0.88, P=0.001; HR = 0.77, 95% CI: 0.62-0.95, P = 0.015) and high- (HR=0.66, 95% CI: 0.52-0.83, P<0.001; HR=0.74, 95% CI: 0.56-0.99, P=0.039) risk groups. However, PMRT had no significant effects on patients in the low-risk groups. Conclusion: According to the prognostic nomogram, we performed risk subgroup classification and found that patients in the low-risk group did not benefit from PMRT.

Early Reduction of the Posterior Column: A Surgical Technique in AO/OTA C3 Tibial Pilon Fractures.

Staged treatment for pilon fractures is widely accepted. It remains to be discussed how to reduce and fix posterior column fractures while avoiding clinical complications. We provided a staged treatment protocol with detailed surgical techniques for closed AO Foundation/Orthopaedic Trauma Association (AO/OTA) C3 tibial pilon fractures with fibular fractures. In the first stage, the internal fixation of the fibula and distal tibial posterior column is accompanied by an external fixator. After swelling, the medial and anterior columns were fixed via the posteromedial approach in the second stage. We advocate early reduction and fixation of the posterior column and lateral column. The right timing of surgery can ensure well-reduced articular surface and alignment while minimizing soft tissue complications.

A modified separate vertical fixation by wires and titanium cables for comminuted inferior patella fracture: A technique note and finite element analysis.

PURPOSE: Comminuted inferior patellar pole fractures are challenging injuries and require adequate treatment due to the extension mechanism of the knee. METHODS: A modified separate vertical fixation by wires and Titanium cables was established according to a finite element biomechanical study. Between September 2018 and May 2021, 18 patients with inferior pole fractures of the patella were retrospectively enrolled in this study. RESULTS: The results of the finite element analysis showed the concentration of stress in the intermediate vertical wire and the cerclage wire. As a partial replacement for steel wires, Titanium cables provide less concentration of stress on the vertical wire (489.4 MPa vs 441.2 Mpa) and less cutting force on the bone (75.87 Mpa vs 53.27), which reduces the possibility of internal fixation failure and improves the stability of internal fixation. In the clinic study, No patients experienced non-union of the fracture, loss of fracture repositioning, malunion of wounds, or wire breakage. At the last follow-up, the average range of motion was 134.7°±11.2°, and the Lysholm Score was 90.7 ± 3.9. CONCLUSIONS: The separate vertical fixation by wires and titanium cables is an effective fixation method for treating displaced, comminuted inferior pole fractures, which attributes to early exercise and better function.

A double-suture cerclage reduction technique with Nice knots for comminuted patella fractures (AO/OTA 34-C3).

BACKGROUND: Comminuted patella fractures place high demands on surgeons' surgical skills. We used a double-suture cerclage reduction with Nice knots as an intra-operative reduction technique to displaced comminuted patella fractures. METHODS: Patients were divided into two groups by whether or not an intra-operative suture cerclage reduction technique was used. Fragments count, surgical time, quality of the reduction, and fracture healing time were recorded. The postoperative function was assessed by Böstman score and range of motion. RESULTS: With the inclusion and exclusion criteria, 48 patients we included in the cohort between Sept. 2016 and Oct. 2021. The double-suture cerclage reduction technique with a Nice knot achieved a satisfactory reduction. When the number of fragments was over 5, this technique showed significant advantages in saving surgery time. CONCLUSIONS: In this study, the double-suture cerclage reduction technique combined with the Nice knot shows significant advantages for displaced highly comminuted patella fractures. This technique simplifies the operation and saves surgical time, which is helpful for clinical practice.

Characteristic Genes and Immune Infiltration Analysis for Acute Rejection after Kidney Transplantation.

Background: Renal transplantation can significantly improve the survival rate and quality of life of patients with end-stage renal disease, but the probability of acute rejection (AR) in adult renal transplant recipients is still approximately 12.2%. Machine learning (ML) is superior to traditional statistical methods in various clinical scenarios. However, the current AR model is constructed only through simple difference analysis or a single queue, which cannot guarantee the accuracy of prediction. Therefore, this study identified and validated new gene sets that contribute to the early prediction of AR and the prognosis prediction of patients after renal transplantation by constructing a more accurate AR gene signature through ML technology. Methods: Based on the Gene Expression Omnibus (GEO) database and multiple bioinformatic analyses, we identified differentially expressed genes (DEGs) and built a gene signature via LASSO regression and SVM analysis. Immune cell infiltration and immunocyte association analyses were also conducted. Furthermore, we investigated the relationship between AR genes and graft survival status. Results: Twenty-four DEGs were identified. A 5 gene signature (CPA6, EFNA1, HBM, THEM5, and ZNF683) were obtained by LASSO analysis and SVM analysis, which had a satisfied ability to differentiate AR and NAR in the training cohort, internal validation cohort and external validation cohort. Additionally, ZNF683 was associated with graft survival. Conclusion: A 5 gene signature, particularly ZNF683, provided insight into a precise therapeutic schedule and clinical applications for AR patients.

A prospective cohort study: platelet-rich plasma combined with carpal tunnel release treating carpal tunnel syndrome.

BACKGROUND: PRP injection was proved to promote the health condition of individuals with mild to moderate Carpal Tunnel Syndrome (CTS). However, carpal tunnel release (CTR) was still a necessary treatment for individuals with moderate and severe CTS. METHODS: To explore whether adjuvant PRP treatment would improve the prognosis while using CTR, we included 82 patients in this study. Preoperative and postoperative visual analog scale (VAS), Boston carpal tunnel syndrome questionnaire-symptom severity scale (BCTQ-SSS), Boston carpal tunnel syndrome questionnaire-functional status scale (BCTQ-FSS), and grip strength were used to examine the patient's symptoms and function. RESULTS: CTR combined with PRP treatment improved the VAS (1.9 ± 0.5 versus 1.4 ± 0.4, P < .05), BCTQ-SSS (1.8 ± 0.4versus 1.5 ± 0.3, P < .05) and BCTQ-FSS (1.8 ± 0.5 versus 1.4 ± 0.6, P < .05) in patients with moderate symptoms within one month after surgery. At the same time, it does not show any advantages in treating individuals with severe carpal tunnel syndrome. CONCLUSIONS: PRP does not affect long-term prognosis while increasing the surgery cost. To conclude, PRP as an adjuvant treatment of CTR has limited effect. Considering the additional financial burden on patients, CTR combined with PRP should be cautious in CTS treatment.

[Preparation and application of rabbit polyclonal antibody against human glutamine fructose-6-phosphate amidotransferase 1(GFPT1)].

Objective To prepare rabbit polyclonal antibody specifically against human glutamine fructose-6-phosphate amidotransferase 1(GFPT1). Methods The protein sequences of GFPT1 and its highly homologous isozyme GFPT2 were compared. Two peptides for the specific sequence of GFPT1 were designed and synthesized. New Zealand rabbits were immunized by peptide coupled with Keyhole Limpet hemocyanin (KLH) as antigen. Antiserum was obtained after 3 booster immunizations. The titer of the antiserum against GFPT1 were detected by ELISA. The E.coli expression vectors of GFPT1 and GFPT2 were constructed, and the recombinant proteins of GFPT1 and GFPT2 were obtained by induced expression. GFPT1 and GFPT2 recombinant proteins were analyzed by Western blot to verify the specificity of the antiserum. Immuno-fluorescence cytochemical staining for GFPT1 expression in 786-O cells was verified as for whether the obtained antiserum could recognize the endogenously expressed GFPT1. Results Polyclonal antibody specifically recognizing GFPT1 was obtained and the titer of polyclonal antibody reached 1:1 458 000. Conclusion The experiment successfully prepared the specific rabbit polyclonal antibody against GFPT1.

Effect of cell density on the malignant biological behavior of breast cancer by altering the subcellular localization of ANXA2 and its clinical implications.

OBJECTIVE: To investigate the subcellular localization of ANXA2 in breast cancer of different cell densities in humans and its relationship with the clinicopathological features of patients. To investigate the differences in ANXA2 subcellular localization in MDA-MB-231 cells of different cell densities. To compare the proliferation, invasion, and migration ability of MDA-MB-231 cells under different ANXA2 subcellular localization. METHODS: Immunohistochemistry was applied to detect the subcellular localization of ANXA2 in tissue sections of 60 breast cancer patients, and the association with ANXA2 subcellular localization was verified in conjunction with cell density. To investigate the relationship between cell density and clinicopathological data of breast cancer patients. To establish high- and low-density models of MDA-MB-231 breast cancer cell lines and verify the subcellular localization of ANXA2 using immunofluorescence and observation under confocal microscopy. The proliferation, migration, and invasion ability of MDA-MB-231 cells under different subcellular localization of ANXA2 were detected and compared using CCK-8 assay and Transwell assay. After changing the subcellular localization of ANXA2 in high-density MDA-MB-231 cells with PY-60, changes in biological behaviors of the compared MDA-MB-231 cells were observed. Two different 4T1 cell lines with high and low densities were implanted subcutaneously in nude mice to observe the effects of different cell densities on tumor growth in nude mice. RESULTS: The clinical data showed that breast cancer with high cell density had higher T stage and higher TNM stage, and the cell density was positively correlated with breast cancer mass size. ANXA2 was mainly localized to the cell membrane when the cell density of breast cancer cells was high and to the cytoplasm when the cell density was low. The CCK-8 assay showed that the proliferation rate of MDA-MB-231 cells increased (P < 0.05) after shifting the subcellular localization of ANXA2 from the cell membrane to the cytoplasm. Transwell invasion assay and Transwell migration assay showed that the invasion and migration ability of MDA-MB-231 cells increased significantly after the subcellular localization of ANXA2 was transferred from the cell membrane to the cytoplasm (P < 0.05). The animal experiments showed that high-density breast cancer cells could promote the growth of subcutaneous tumors in nude mice relative to low-density breast cancer cells. CONCLUSION: Cell density can regulate the subcellular localization of ANXA2, and changes in the subcellular localization of ANXA2 are accompanied by the changes in the biological behavior of breast cancer.

A nomogram for decision-making assistance on surgical treatment of chronic osteomyelitis in long bones: Establishment and validation based on a retrospective multicenter cohort.

BACKGROUND: Chronic osteomyelitis remains a major challenge for orthopedic surgeons due to its high recurrence rate. Surgeons currently have few tools to estimate the likelihood of individual recurrence. We here aimed to develop a nomogram to better estimate individual recurrence rate after surgical treatment of chronic osteomyelitis in long bones. METHODS: We first retrospectively identified patients as training cohort who had received surgical treatment of chronic osteomyelitis in long bones between January 2010 and January 2016 from four hospitals. Patient demographic, microbiological, clinical, and therapeutic variables were collected and analyzed. Univariate and multivariate analyses were performed successively to identify independently predictive factors for recurrence. To reduce overfitting, the Bayesian information criterion was used to reduce variables in the original model. Nomograms were created with the reduced model after model selection. The nomogram was then internally validated with bootstrap resampling. We then further validated the performance of the established nomogram in validation cohort (data from two distinct institutions). RESULTS: Recurrence was found in 136 of 655 (20.8%) and 52 of 201 patients (25.9%) in training and validation cohorts respectively. We included six independent prognostic factors for recurrence in our prediction model: number of previous recurrences, epiphysial involvement, preoperative serum albumin level, axial length of the infectious lesion, lesion-removal method, and application of a muscular flap. After incorporating these six factors, the nomogram achieved good discrimination, with concordance indexes of 0.82 (95% CI, 0.79-0.85) and 0.80 (95% CI, 0.78-0.83) in predicting recurrence in the training and validation cohorts, respectively. Calibration curves were well fitted for both training and validation cohorts. CONCLUSIONS: Our nomogram achieved good preoperative prediction of recurrence in chronic osteomyelitis of long bones. Using this nomogram, the recurrence risk can be confidently predicted for each patient and treatment plan. After considering and discussing the functional prognosis with patients, physicians can establish a rational therapeutic plan. LEVEL OF EVIDENCE: Prognostic, Level III.

Serum Amyloid A Correlates With the Osteonecrosis of Femoral Head by Affecting Bone Metabolism.

Osteonecrosis of femoral head (ONFH) is a progressive hip joint disease without disease-modifying treatment. Lacking understanding of the pathophysiological process of ONFH has become the humper to develop therapeutic approach. Serum amyloid A (SAA) is an acute phase lipophilic protein during inflammation and we found that SAA is increased for the first time in the serum of ONFH patients through proteomic studies and quantitatively verified by ELISA. Treating rBMSCs with SAA inhibited the osteogenic differentiation via Wnt/ß-catenin signaling pathway deactivation and enhanced the adipogenic differentiation via MAPK/PPARγ signaling pathway activation. Finally, bilateral critical-sized calvarial-defect rat model which received SAA treated rBMSCs demonstrated reduction of bone formation when compared to untreated rBMSCs implantation control. Hence, SAA is a vital protein in the physiological process of ONFH and can act as a potential therapeutic target to treat ONFH.

Correlation Analysis of Breast and Thyroid Nodules: A Cross-Sectional Study.

OBJECTIVE: Based on physical examination, to explore the relationship between breast mass (BM) and thyroid nodule (TN) prevalence, and to further explore other related factors that affect the occurrence of BM and TN. METHODS: From January 1, 2018, to January 1, 2021, 12,538 female subjects received breast and thyroid ultrasound examinations at the same time in the health examination center of the Affiliated Hospital of North Sichuan Medical College. Univariate analysis and multivariate logistic analysis were used to screen the relevant factors affecting TN and BM, and propensity score matching was used to further verify the results of the relationship between breast and thyroid. RESULTS: A total of 4975 (39.7%) of the included subjects have BM and a total of 6315 (50.4%) have TN,2557 (20.4%) had both BM and TN. The logistic regression results show that patients with TN are more likely to suffer from BM [OR = 1.185, 95% CI (1.099-1.278), p<0.0001]. In addition, age, free T4, HDL, height, BMI, systolic blood pressure, diastolic blood pressure, and albumin are independent factors affecting the occurrence of BM; patients with BM are more likely to have TN [OR = 1.180, 95% CI (1.094-1.272), p<0.0001], and age, free T3, free T4, AST, ALT, albumin, height, and BMI are independent influencing factors on the occurrence of TN. The result of propensity score matching confirmed the relationship between BM and TN. CONCLUSION: There is a bidirectional pathogenic relationship between BM and TN, women with BM are at increased risk of TN, and women with TN are more likely to have BM. Thyroid hormone is not only related to the occurrence of TN but also affects the occurrence of BM.

Erratum: Inhibition of PERK Signaling Prevents Against Glucocorticoid-induced Endotheliocyte Apoptosis and Osteonecrosis of the Femoral Head: Erratum.

[This corrects the article DOI: 10.7150/ijbs.35256.].

Inhibition of PERK Signaling Prevents Against Glucocorticoid-induced Endotheliocyte Apoptosis and Osteonecrosis of the Femoral Head.

Vascular injury is considered an important pathological process during glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). In this study, we tried to investigate whether the endoplasmic reticulum (ER) stress is triggered in the GC-induced endotheliocyte (EC) apoptosis and ONFH. The results showed that a GC upregulated the expression of ER stress-related proteins, and PERK-CHOP signaling played an important role and induced EC apoptosis. The inhibition of PERK by GSK2656157 significantly decreased the GC-induced EC apoptosis in vitro and in vivo, thus protecting a rat model from vascular injury and significantly preventing GC-induced ONFH.

Vascularized Fibular Grafting in Treatment of Femoral Neck Nonunion: A Prognostic Study Based on Long-Term Outcomes.

BACKGROUND: The purpose of this study was to evaluate the long-term efficacy and prognostic factors predicting success of revision surgery with free vascularized fibular grafting (FVFG) for treatment of femoral neck nonunion. METHODS: We prospectively enrolled patients who underwent revision surgery with FVFG between January 2001 and January 2013 in a tertiary hospital in China. A total of 98 patients with a minimum 5-year follow-up were included for analysis. The criteria for FVFG failure were conversion to hip arthroplasty, recommendation for a hip arthroplasty, or a Harris hip score of <80 points. Demographic information, the preoperative neck shortening ratio (NSR), the fixation method, and postoperative radiographic parameters including the postoperative NSR and neck-shaft angle (NSA) were recorded for prognostic analysis. RESULTS: At an average of 9.8 ± 3.5 years (range, 3 to 17 years) postoperatively, the overall success rate of this surgical procedure was 77% (75 of 98). The success and failure groups had no significant differences in age, fixation method, interval between initial fixation and revision surgery, or postoperative NSA. The success group had a significantly higher NSR than the failure group both preoperatively (77.8% versus 62.4%, p < 0.001) and postoperatively (87.6% versus 78.4%, p = 0.001). The receiver operating characteristic (ROC) curve analysis revealed an optimal cutoff for preoperative NSR of 60% to predict the outcome. Patients with a preoperative NSR of >60% had a success rate of 91% (68 of 75). CONCLUSIONS: Revision surgery with FVFG and internal fixation is an effective and important option for treating nonunion of the femoral neck in young patients without severe preoperative shortening and neck resorption (preoperative NSR of >60%). LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Clinical Characteristics Associated with the Prognosis of One-Stage Grafting for Flexor Digitorum Profundus Reconstruction in Zones I and II.

BACKGROUND: The authors aimed to identify clinical characteristics related to the prognosis after one-stage grafting for flexor digitorum profundus reconstruction in zones I and II. METHODS: A total of 401 patients who underwent one-stage flexor digitorum profundus reconstruction after injuries in zones I and II, between January 1, 2006, and June 1, 2016, were included for analysis. The authors recorded the following clinical characteristics: duration from injury to reconstruction, graft type and length, handling (preservation or removal) of flexor digitorum superficialis, tenorrhaphy technique, and duration of postoperative immobilization. RESULTS: There was no significant difference in age, sex, duration between injury and reconstruction, graft type, and handling of flexor digitorum superficialis between subjects who underwent successful reconstruction and those who did not. Univariate and multivariate analyses revealed that end-to-end tenorrhaphy, immediate controlled motion, and immobilization for less than 2 weeks all independently were related to improved final outcomes. Grafting within zones I and II contributed to increased incidence of failure. In a subgroup having an injury-reconstruction duration of less than 2 weeks, the authors observed that grafting from zone III to zones I and II tended to result in better outcomes compared with grafting from zone III to the flexor digitorum profundus insertion. This, however, was not statistically significant (p = 0.11). CONCLUSIONS: The authors recommend end-to-end tenorrhaphy, reducing immobilization to less than 2 weeks, and avoiding grafting within zones I and II. In addition, further studies are still needed to clarify the optimal length of grafting. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

A Prospective Evaluation of Patient-Reported Opioid Utilization After Nonoperative Treatment of Fractures and Dislocations.

BACKGROUND: Prescription of opioid analgesics is currently a common practice to relieve pain for musculoskeletal injuries in many regions of the world, especially in the United States and Canada. However, overprescription may underlie opioid misuse. Details on the utilization of prescribed opioids after nonoperative treatment of fractures and dislocations and whether consumption is related to injury location are unknown. METHODS: A total of 1,513 consecutive patients in China who underwent nonoperative treatment of a fracture and/or dislocation and who were prescribed opioids were studied over a 3-month period. Demographic information, alcohol consumption, smoking status, injury location, volume of prescription, and consumption patterns were recorded and were summarized. RESULTS: The mean number of opioid pills prescribed was 14.7, and the mean patient-reported number of pills consumed was 7.2. Overall, 152 patients (10.0%) reported taking no prescribed opioid analgesics, and 924 patients (61.1%) ceased their prescribed opioids prior to completing the regimen. Injury location, alcohol consumption, and type of fracture or dislocation were all significantly associated with the patient-reported number of opioid pills consumed (p < 0.05). Patients with fracture and/or dislocation of the wrist or forearm (9.4 pills for 3.8 days); ankle, tibia, or fibula (9.3 pills for 3.7 days); or elbow or humerus (9.1 pills for 3.7 days) used more opioid pills compared with patients with injuries at other locations (not exceeding 6.4 pills and 3 days). When compared with patients who had no, low, or moderate daily alcohol consumption, there was more opioid use in patients with high daily alcohol consumption (8.5 pills for 3.4 days) and those with very high daily alcohol consumption (11.3 pills for 4.7 days). Patients with a dislocation and/or displaced fracture reported consuming 8.2 pills for 3.3 days, which was more than the consumption in patients with a nondisplaced fracture (6.2 pills for 2.5 days) and patients with an avulsion fracture (6.2 pills for 2.5 days). CONCLUSIONS: Surgeons and patients should try to avoid opioids if possible after nonoperatively treated fractures and dislocations. If opioids are used, surgeons should prescribe the smallest dose for the shortest time after considering the injury location and type of fracture or dislocation. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

IL-6 Triggers the Migration and Invasion of Oestrogen Receptor-Negative Breast Cancer Cells via Regulation of Hippo Pathways.

Breast cancer is one of the major challenges for women's health. However, the role and mechanisms of interleukins (ILs) on the progression of breast cancer are not well illustrated. Our present study revealed that the expressions of IL-6 and IL-8 were significantly increased in oestrogen receptor-negative (ER-) breast cancer cells. Increased expression of IL-6 was observed in 83.9% (26/31) ER- breast cancer tissues as compared with their matched adjacent normal tissues. In vitro studies indicated that IL-6 can significantly promote the migration and invasion of ER- breast cancer cells via increasing the dephosphorylation, nuclear translocation and transcriptional activities of YAP in breast cancer cells. Knockdown of YAP can attenuate IL-6-induced migration and invasion of cancer cells, suggesting that YAP plays an essential role in IL-6-induced malignancy of breast cancer cells. Furthermore, IL-6 treatment also decreased the phosphorylation of LATS1/2. The knockdown of LATS1/2 synergistically suppressed si-IL-6-induced deactivation of YAP. Targeted inhibition of IL-6/YAP can significantly suppress the invasion of ER- breast cancer cells. Collectively, our study revealed that IL-6 can trigger the malignancy of breast cancer cells via activation of YAP signals. Targeted inhibition of IL-6/YAP might be a novel therapeutic approach for the treatment of ER- breast cancer.