Machine Learning Models Reliably Predict Clinical Outcomes in Medial Patellofemoral Ligament Reconstruction.

PURPOSE: To develop the machine learning model to predict clinical outcomes following MPFLR and identify the important predictive indicators. METHODS: This study included patients who underwent MPFLR from January 2018 to December 2022. The exclusion criteria were as follows: 1) concurrent bony procedures, 2) history of other knee surgeries, and 3) follow-up period of less than 12 months. Forty-two predictive models were constructed for seven clinical outcomes (failure to achieve MCID of clinical scores, return to pre-injury sports, pivoting sports, and recurrent instability) using six machine learning algorithms (Random Forest, Logistic Regression, Support Vector Machine, Decision Tree, implemented multilayer perceptron, and K-nearest neighbor). The performance of the model was evaluated using metrics such as the area under the receiver operating characteristic curve (AUC), accuracy, specificity, and sensitivity. Additionally, Shapley Additive Explanation summary plot was employed to identify the important predictive factors of the best-performing model. RESULTS: A total of 218 patients met criteria. For the best-performing models in predicting failure to achieve the MCID for Lysholm, IKDC, Kujala, and Tegner scores, the AUCs and accuracies were 0.884 (good) and 87.3%, 0.859 (good) and 86.2%, 0.969 (excellent) and 97.0%, and 0.760 (fair) and 76.8%, respectively; 0.952 (excellent) and 95.2% for return to pre-injury sports; 0.756 (fair) and 75.4% for return to pivoting sports; and 0.943 (excellent) and 94.9% for recurrent instability. Low preoperative Tegner score, shorter time to surgery, and absence of severe trochlear dysplasia were significant predictors for return to pre-injury sports, while absence of severe trochlear dysplasia and patellar alta were significant predictors for return to pivoting sports. Older age, female sex, and low preoperative Lysholm score were highly predictive of recurrent instability. CONCLUSION: The predictive models developed using machine learning algorithms can reliably forecast the clinical outcomes of MPFLR, particularly demonstrating excellent performance in predicting recurrent instability. LEVEL OF EVIDENCE: Level III, case-control study.

Fluid shear stress-mediated Piezo1 alleviates osteocyte apoptosis by activating the PI3K/Akt pathway.

Glucocorticoid-induced osteoporosis serves as a primary cause for secondary osteoporosis and fragility fractures, representing the most prevalent adverse reaction associated with prolonged glucocorticoid use. In this study, to elucidate the impact and underlying mechanisms of fluid shear stress (FSS)-mediated Piezo1 on dexamethasone (Dex)-induced apoptosis, we respectively applied Dex treatment for 6 h, FSS at 9 dyne/cm2 for 30 min, Yoda1 treatment for 2 h, and Piezo1 siRNA transfection to intervene in MLO-Y4 osteocytes. Western blot analysis was used to assess the expression of Cleaved Caspase-3, Bax, Bcl-2, and proteins associated with the PI3K/Akt pathway. Additionally, qRT-PCR was utilized to quantify the mRNA expression levels of these molecules. Hoechst 33258 staining and flow cytometry were utilized to evaluate the apoptosis levels. The results indicate that FSS at 9 dyne/cm2 for 30 min significantly upregulates Piezo1 in osteocytes. Following Dex-induced apoptosis, the phosphorylation levels of PI3K and Akt are markedly suppressed. FSS-mediated Piezo1 exerts a protective effect against Dex-induced apoptosis by activating the PI3K/Akt pathway. Additionally, downregulating the expression of Piezo1 in osteocytes using siRNA exacerbates Dex-induced apoptosis. To further demonstrate the role of the PI3K/Akt signaling pathway, after intervention with the PI3K pathway inhibitor, the activation of the PI3K/Akt pathway by FSS-mediated Piezo1 in osteocytes was significantly inhibited, reversing the anti-apoptotic effect. This study indicates that under FSS, Piezo1 in MLO-Y4 osteocytes is significantly upregulated, providing protection against Dex-induced apoptosis through the activation of the PI3K/Akt pathway.

Single Versus Double Tunnel Fixation in Medial Patellofemoral Ligament Reconstruction: A Meta-Analysis.

The purpose of this meta-analysis was to conduct a comparative analysis of clinical scores and complication rates among patients experiencing recurrent patellar dislocation who underwent medial patellofemoral ligament (MPFL) reconstruction using both single and double tunnel techniques. A comprehensive search was conducted across electronic databases including PubMed, the Cochrane Library, Web of Science, and Google Scholar to retrieve articles relevant to MPFL reconstruction utilising the tunnel technique. Subsequently, meta-analyses were undertaken to assess complication rates and changes in clinical scores before and after surgery. Following this, sensitivity analysis and meta-regression analysis were performed to scrutinise potential confounding variables. A total of thirty-two studies were included in the analysis, comprising twenty-seven non-comparative studies and five comparative studies. The findings revealed a similarity in postoperative complication rates between the single and double tunnel fixation techniques: [9.0% (95%CI, 4.0%-15.6%) versus 8.9% (95%CI, 4.7%-14.1%, p = 0.844)]. Likewise, no statistically significant differences were observed in Lysholm scores [34.1 (95%CI, 26.7-41.5) versus 33.8 (95%CI, 27.7-40.0, p = 0.956)], Kujala scores [29.4 (95%CI, 22.3-36.4) versus 27.3 (95%CI, 22.3-32.3, p = 0.637)], and Tegner score change [1.1 (95%CI, 0.8-1.4) versus 0.7 (95%CI, -0.2-1.6, p = 0.429)] before and after MPFL reconstruction, respectively, using these two techniques. In conclusion, the authors found that the clinical functional improvement and complication rates in MPFL reconstruction using the single tunnel fixation technique are comparable to those achieved with the double tunnel fixation approach. However, to further advance the understanding in this field, additional randomised controlled studies must be conducted to provide further insights. Key Words: MPFL reconstruction, Bone tunnel, Patellar dislocation, Meta-analysis.

The development and external validation of a web-based nomogram for predicting overall survival with Ewing sarcoma in children.

Background: Ewing sarcoma remains the second most prevalent primary aggressive bone tumor in teens and young adults. The aim of our study was to develop and validate a web-based nomogram to predict the overall survival for Ewing sarcoma in children. Methods: A total of 698 patients, with 640 cases from the Surveillance, Epidemiology, and End Results (the training set) and 58 cases (the external validation set), were included in this study. Cox analyses were carried out to determine the independent prognostic indicators, which were further included to establish a web-based nomogram. The predictive abilities were tested through the concordance index, calibration curve, decision curve analysis, and area under the receiver operating characteristic curve. Results: As suggested by univariate and multivariate Cox analyses, age, primary site, tumor size, metastasis stage (M stage), and chemotherapy were included as the independent predictive variables. The area under the receiver operating characteristic curve values, calibration curves, concordance index, and decision curve analysis from training and validation groups suggested the model has great clinical applications. Conclusion: We developed a convenient and precise web-based nomogram to evaluate overall survival for Ewing sarcoma in children. The application of this nomogram would assist physicians and patients in making decisions.

METTL3-mediated m6A modification of SOX4 regulates osteoblast proliferation and differentiation via YTHDF3 recognition.

N6-methyladenosine (m6A), the most prevalent internal modification in mRNA, is related to the pathogenesis of osteoporosis (OP). Although methyltransferase Like-3 (METTL3), an m6A transferase, has been shown to mitigate OP progression, the mechanisms of METTL3-mediated m6A modification in osteoblast function remain unclear. Here, fluid shear stress (FSS) induced osteoblast proliferation and differentiation, resulting in elevated levels of METTL3 expression and m6A modification. Through Methylated RNA Immunoprecipitation Sequencing (MeRIP-seq) and Transcriptomic RNA Sequencing (RNA-seq), SRY (Sex Determining Region Y)-box 4 (SOX4) was screened as a target of METTL3, whose m6A-modified coding sequence (CDS) regions exhibited binding affinity towards METTL3. Further functional experiments demonstrated that knockdown of METTL3 and SOX4 hampered osteogenesis, and METTL3 knockdown compromised SOX4 mRNA stability. Via RNA immunoprecipitation (RIP) assays, we further confirmed the direct interaction between METTL3 and SOX4. YTH N6-Methyladenosine RNA Binding Protein 3 (YTHDF3) was identified as the m6A reader responsible for modulating SOX4 mRNA and protein levels by affecting its degradation. Furthermore, in vivo experiments demonstrated that bone loss in an ovariectomized (OVX) mouse model was reversed through the overexpression of SOX4 mediated by adeno-associated virus serotype 2 (AAV2). In conclusion, our research demonstrates that METTL3-mediated m6A modification of SOX4 plays a crucial role in regulating osteoblast proliferation and differentiation through its recognition by YTHDF3. Our research confirms METTL3-m6A-SOX4-YTHDF3 as an essential axis and potential mechanism in OP.

Artificial Intelligence Aids Detection of Rotator Cuff Pathology: A Systematic Review.

PURPOSE: To determine the model performance of artificial intelligence (AI) in detecting rotator cuff pathology using different imaging modalities and to compare capability with physicians in clinical scenarios. METHODS: The review followed the PRISMA guidelines and was registered on PROSPERO. The criteria were as follows: 1) studies on the application of AI in detecting rotator cuff pathology using medical images, and 2) studies on smart devices for assisting in diagnosis were excluded. The following data were extracted and recorded: statistical characteristics, input features, AI algorithms used, sample sizes of training and testing sets, and model performance. The data extracted from the included studies were narratively reviewed. RESULTS: A total of 14 articles, comprising 23,119 patients, met the inclusion and exclusion criteria. The pooled mean age of the patients was 56.7 years, and the female rate was 56.1%. The area under the curve (AUC) of the algorithmic model to detect rotator cuff pathology from ultrasound images, MRI images, and radiographic series ranged from 0.789 to 0.950, 0.844 to 0.943, and 0.820 to 0.830, respectively. Notably, 1 of the studies reported that AI models based on ultrasound images demonstrated a diagnostic performance similar to that of radiologists. Another comparative study demonstrated that AI models using MRI images exhibited greater accuracy and specificity compared to orthopedic surgeons in the diagnosis of rotator cuff pathology, albeit not in sensitivity. CONCLUSIONS: The detection of rotator cuff pathology has been significantly aided by the exceptional performance of AI models. In particular, these models are equally adept as musculoskeletal radiologists in using ultrasound to diagnose rotator cuff pathology. Furthermore, AI models exhibit statistically superior levels of accuracy and specificity when using MRI to diagnose rotator cuff pathology, albeit with no marked difference in sensitivity, in comparison to orthopaedic surgeons. LEVEL OF EVIDENCE: Level III, systematic review of Level III studies.

Radiographic OA, bone marrow lesions, higher body mass index and medial meniscal root tears are significantly associated with medial meniscus extrusion with OA or medial meniscal tears: a systematic review and meta-analysis.

PURPOSE: Medial meniscus extrusion (MME) refers to the protrusion of the medial meniscus beyond the tibial edge by more than 3 mm, leading to a deficiency of the hoop strain. MME commonly occurs in conjunction with osteoarthritis (OA) or medial meniscal tears (MMT). However, factors associated with concomitant MME in patients with OA or MMT have not been systematically reviewed. This study aims to perform a systematic review and meta-analysis to identify factors associated with concomitant MME in OA or MMT. METHODS: The systematic review of the literature was performed according to PRISMA. A literature search was conducted in 4 databases. All original human studies that reported the available evidence on factors associated with concomitant MME in patients with OA or MMT were included. Pooled binary variables were analyzed by odds ratios (OR) and 95% CIs, and pooled continuous variables were evaluated by mean difference (MD) and 95% CIs. RESULTS: Ten studies on OA (5993 patients) and eight studies on MMT (872 patients) met the inclusion criteria. The overall pooled incidence of MME was 43% (95% CI, 37-50%) for OA, 61% (95% CI 43-77%) for MMT, and 85% (95% CI 72-94%) for medial meniscal root tears (MMRT). For the population with OA, Factors significantly associated with MME included radiographic OA [OR 4.24; 95% CI 3.07-5.84; P < 0.0001], bone marrow lesions [OR, 3.35; 95% CI 1.61-6.99; P = 0.0013], cartilage damage [OR, 3.25; 95% CI 1.60-6.61; P = 0.0011], and higher body mass index (BMI) [MD, 1.81; 95% CI 1.15-2.48; P < 0.0001]. Factors strongly associated with increased risk of MME for MMT included medial meniscal root [OR, 8.39; 95% CI 2.84-24.82; P < 0.0001] and radial tears [OR, 2.64; 95% CI 1.18-5.92; P < 0.0001]. CONCLUSION: Radiographic OA, bone marrow lesions, cartilage damage, and higher BMI were significantly associated with concomitant MME with OA. Furthermore, medial meniscal root and radial tears were significantly associated with an increased risk of MME in patients with MMT. LEVEL OF EVIDENCE: IV.

The Association Between Bone Bruises and Concomitant Ligaments Injuries in Anterior Cruciate Ligament Injuries: A Systematic Review and Meta-analysis.

Background: Bone bruises and concomitant ligament injuries after anterior cruciate ligament (ACL) injuries have attracted attention, but their correlation and potential clinical significance remain unclear. Purpose: To assess the relationship between bone bruises and concomitant ligamentous injuries in ACL injuries. Study design: Systematic review. Methods: A comprehensive search of PubMed, Embase, Web of Science, and Cochrane Library was completed from inception to October 20, 2021. All articles that evaluated the relationship between bone bruises and related ligaments injuries were included. Methodological Index for Non-Randomized Studies (MINORS) was used for quality assessment as well as Review Manager 5.3 was used for data analysis. Results: A total of 19 studies evaluating 3292 patients were included. After meta-analysis, anterolateral ligament (ALL) injuries were associated with bone bruising on the lateral tibial plateau (LTP) (RR = 2.33; 95% CI 1.44-3.77; p = 0.0006), lateral femoral condyle (LFC) (RR = 1.97; 95% CI 1.37-2.85; p = 0.0003) and medial tibial plateau (MTP) (RR = 1.62; 95% CI 1.24-2.11; p = 0.0004); Moreover, medial collateral ligament (MCL) injuries were associated with bone bruising on the femur (RR = 1.49; 95% CI 1.17-1.90; p = 0.001), and no statistical significance was found between bone bruising on the MTP and Kaplan fiber (KF) injuries (RR = 1.58; 95% CI 1.00-2.49; p = 0.05). Nonetheless, the current evidence did not conclude that bone bruises were associated with lateral collateral ligament (LCL) injuries. Conclusion: For individuals with an ACL injury, bone bruises of the LTP, LFC, and MTP can assist in the diagnosis of ALL injuries. Furthermore, femoral bruising has potential diagnostic value for MCL injuries. Knowing these associations allows surgeons to be alert to ACL-related ligament injuries on MRI and during operations in future clinical practice.

A Scientometric Analysis of Studies on Patellar Dislocation.

Background: Patellar dislocation is attracting considerable research interest. Purpose: To assess studies on patellar dislocation using a scientometric method to better understand the current status of research and explore future study directions. Study Design: Scoping review. Methods: The Web of Science Core Collection database was selected to retrieve publications on patellar dislocation. Articles and reviews written in English with patellar dislocation as the main topic were included. Conference abstracts, notes, letters, expert opinions, and animal studies were excluded. A total of 4632 articles were identified in our initial search. In addition, Excel 2019, CiteSpace 6.1.R1, and VOSviewer 1.6.9 were used to analyze the h-index, the most highly cited publication, publication essentials, and research themes. Results: A total of 1485 articles were included in our analysis, with 36,608 citations and an h-index of 93. Overall, 1494 institutions and 195 journals were identified from these studies. The United States (n = 531) was the most productive country. The institution and journal with the largest number of articles were the Hospital for Special Surgery (n = 59) and Knee Surgery, Sports Traumatology, Arthroscopy (n = 212), respectively. The article "Scoring of Patellofemoral Disorders" by Kujala et al in 1993 was the most highly cited reference. The most commonly found terms used were patellar dislocation, patellar instability, medial patellofemoral ligament, knee, recurrent patellar dislocation, and soft tissue restraints. Four topics were identified after clustering analysis of key terms: risk factors, medial patellofemoral ligament reconstruction, patellar dislocation in skeletally immature patients, and lateral retinacular release. Conclusion: This scientometric review of articles on patellar dislocation summarized the current status of research (countries, institutions, and authors) and identified potential research directions.

Comparison of BSGI and MRI as Approaches to Evaluating Residual Tumor Status after Neoadjuvant Chemotherapy in Chinese Women with Breast Cancer.

BACKGROUND: The present retrospective study was designed to evaluate the relative diagnostic utility of breast-specific gamma imaging (BSGI) and breast magnetic resonance imaging (MRI) as means of evaluating female breast cancer patients in China. METHODS: A total of 229 malignant breast cancer patients underwent ultrasound, mammography, BSGI, and MRI between January 2015 and December 2018 for initial tumor staging. Of these patients, 73 were subsequently treated via definitive breast surgery following neoadjuvant chemotherapy (NAC), of whom 17 exhibited a complete pathologic response (pCR) to NAC. RESULTS: BSGI and MRI were associated with 76.8% (43/56) and 83.9% (47/56) sensitivity (BSGI vs. MRI, p = 0.341) values, respectively, as a means of detecting residual tumors following NAC, while both these approaches exhibited comparable specificity in this diagnostic context. The specificity of BSGI for detecting residual tumors following NAC was 70.6% (12/17), and that of MRI was 58.8% (10/17) (BSGI vs. MRI, p = 0.473). CONCLUSION: These results demonstrate that BSGI is a useful auxiliary approach to evaluating pCR to NAC treatment.

Comparison of BSGI, MRI, mammography, and ultrasound for the diagnosis of breast lesions and their correlations with specific molecular subtypes in Chinese women.

BACKGROUND: Breast cancer is a leading cause of cancer in females, and is the second leading cancer-related cause of death in this group. Early diagnosis is essential to breast cancer to be effectively treated, and ultrasound, mammography, and magnetic resonance imaging (MRI) represent three key technologies that are utilized for the diagnosis of breast lesions. Breast-specific gamma imaging (BSGI) is an approach to molecular breast imaging that allows for high-resolution radio-imaging that is not adversely impacted by breast tissue density. This study was therefore designed to assess the relative diagnostic efficacy of BSGI, MRI, mammography, and ultrasound in different molecular subtypes of breast cancer among Chinese women. METHODS: Diagnostic findings from 390 patients that had undergone diagnosis and treatment in our breast surgery department were retrospectively reviewed. Patients had been diagnosed via BSGI, mammography, ultrasound, and MRI. The diagnostic efficacy of these different imaging modalities and their associated biological characteristics were compared in the present study. RESULTS: A total of 229 of these 390 patients (58.7%) were diagnosed with malignant breast cancer, with the remaining 161 (41.3%) cases having been found to be benign. BSGI, MRI, mammography, and ultrasound yielded respective sensitivity values of 91.7, 92.5, 77.3, and 82.1%, while the respective specificity values for these imaging modalities were 80.7, 69.7, 74.5, and 70.8%. For lesions > 1 cm, BSGI offered a sensitivity of 92.5%. For mammographic breast density A, B, C, and D, BSGI offered a sensitivity of 93.3, 94.0, 91.5, and 89.3%, respectively. BSGI also yielded a significantly higher lesion-to-normal lesion ratio (LNR) for malignant lesions relative to benign lesions (2.76 ± 1.32 vs 1.46 ± 0.49). CONCLUSIONS: These findings confirm that BSGI is highly sensitive and is superior to mammography in the detection and diagnosis of ductal carcinomas in situ (DCIS). Such diagnostic efficacy can be further improved by using BSGI as an auxiliary modality to mammography and ultrasound, potentially improving the reliability of breast lesion diagnosis, thereby ensuring that patients receive rapid and effective treatment without the risk of misdiagnosis or unnecessary surgical treatment.

Breast-specific gamma imaging or ultrasonography as adjunct imaging diagnostics in women with mammographically dense breasts.

BACKGROUND: Mammography (MMG) shows decreased diagnostic accuracy in dense breast tissue, and thus, ultrasonography (US) and breast-specific gamma imaging (BSGI) have gradually been adopted for women with mammographically dense breasts. However, these two adjunct modalities have not been directly compared in previous studies. Hence, we investigated the adjunctive efficacy of US and BSGI in mammographically dense breasts. METHODS: This retrospective, comparative study recruited women with mammographically dense breasts. All enrolled women underwent US and BSGI as adjunctive imaging, and the comparative sensitivity, specificity, and diagnostic accuracy of combined MMG plus BSGI versus MMG plus US were evaluated. McNemar's test was used for paired binary data in this comparative analysis. RESULTS: From April 2013 to April 2016, 364 women with mammographically dense breasts and a final surgical or biopsy pathological diagnosis were recruited, comprising 218 cases of malignant disease (59.9%) and 146 cases of benign disease (40.1%). There was no difference between BSGI and US in enhancing the sensitivity of MMG diagnosis (Se-Difference 3.2%, p = 0.23), but the diagnostic specificity of MMG plus BSGI was superior to that of MMG plus US (Sp-Difference 10.3%, p = 0.003). The area under the ROC curve showed that MMG plus BSGI had better diagnostic accuracy than MMG plus US (0.90 vs. 0.83, p = 0.0019). CONCLUSIONS: For women with mammographically dense breasts, MMG plus BSGI or US can improve the diagnostic accuracy. In addition, BSGI has high specificity and could reduce invasive biopsies and thus may represent a viable diagnostic imaging alternative for mammographically dense breasts. KEY POINTS: • Both BSGI and US can be applied as adjunct imaging diagnostics in women with mammographically dense breasts. • The diagnostic accuracy of MMG plus BSGI was higher than that of MMG plus US. • BSGI has the potential to be used as an adjunct diagnostic modality in women with mammographically dense breasts.

Comparison of 99mTc-MIBI scintigraphy, ultrasound, and mammography for the diagnosis of BI-RADS 4 category lesions.

BACKGROUND: We sought to determine the diagnostic efficacy of Breast-specific gamma imaging (BSGI) in Chinese women with BI-RADS 4 category lesions and to compare this efficacy to that of ultrasound/mammography. METHODS: We retrospectively analyzed data from 177 women that had undergone BSGI of BI-RADS 4 category lesions originally detected via ultrasound and/or mammography. RESULTS: Of these 177 cases, 117 (66.1%) were malignant lesions and 60 (33.9%) were benign. The sensitivity, specificity, positive predictive values, and negative predictive values of BSGI were 94.9% (111/117), 78.3% (47/60), 89.5% (111/124), and 88.7% (47/53), respectively. The specificity and positive predictive values for mammography were 48.3% (29/60) and 77.5% (107/138), while for ultrasound they were 53.3% (32/60) and 79.6% (109/137), respectively. The sensitivity and specificity of BSGI for the detection of lesions ≤1 cm in size were 90.9% (10/11) and 88.0% (22/25), respectively, while for breast lesions >1 cm in size these values were 94.3% (100/106) and 71.4% (25/35), respectively. In addition, BSGI sensitivity and specificity values for dense breast tissue were 94.0% (79/84) and 78.0% (39/50), respectively, whereas for non-dense breast tissue these vales were 97.0% (32/33) and 80.0% (8/10), respectively. The sensitivity of BSGI for invasive ductal carcinomas (IDC) and ductal carcinomas in situ (DCIS) was 98.9% (95/96) and 75.0% (9/12), respectively. The tumor to normal tissue ratio of BSGI for malignant lesions was significantly higher than for benign lesions (2.18 ± 1.17 vs 1.66 ± 0.40, t = 7.56, P<0.05). CONCLUSIONS: These results indicate that BSGI is highly sensitive for the detection of such lesions, achieving good positive/negative predictive values. This suggests that for IDC in particular, BSGI is superior to ultrasound and mammography for the diagnosis of BI-RADS 4 category lesions, although this was less apparent for the diagnosis of DCIS lesions. BSGI exhibited excellent performance in dense breast tissue and for the detection of lesions ≤1 cm in size.

Retrospective and comparative analysis of (99m)Tc-Sestamibi breast specific gamma imaging versus mammography, ultrasound, and magnetic resonance imaging for the detection of breast cancer in Chinese women.

BACKGROUND: Diagnosing breast cancer during the early stage may be helpful for decreasing cancer-related mortality. In Western developed countries, mammographies have been the gold standard for breast cancer detection. However, Chinese women usually have denser and smaller-sized breasts compared to Caucasian women, which decreases the diagnostic accuracy of mammography. However, breast specific gamma imaging, a type of molecular functional breast imaging, has been used for the accurate diagnosis of breast cancer and is not influenced by breast density. Our objective was to analyze the breast specific gamma imaging (BSGI) diagnostic value for Chinese women. METHODS: During a 2-year period, 357 women were diagnosed and treated at our oncology department and received BSGI in addition to mammography (MMG), ultrasound (US) and magnetic resonance imaging (MRI) for diagnostic assessment. We investigated the sensitivity and specificity of each method of detection and compared the biological profiles of the four imaging methods. RESULTS: A total of 357 women received a final surgical pathology diagnosis, with 168 malignant diseases (58.5 %) and 119 benign diseases (41.5 %). Of these, 166 underwent the four imaging tests preoperatively. The sensitivity of BSGI was 80.35 and 82.14 % by US, 75.6 % by MMG, and 94.06 % by MRI. Furthermore, the breast cancer diagnosis specificity of BSGI was high (83.19 % vs. 77.31 % vs. 66.39 % vs. 67.69 %, respectively). The BSGI diagnostic sensitivity for mammographic breast density in women was superior to mammography and more sensitive for non-luminal A subtypes (luminal A vs. non-luminal A, 68.63 % vs. 88.30 %). CONCLUSIONS: BSGI may help improve the ability to diagnose early stage breast cancer for Chinese women, particularly for ductal carcinoma in situ (DCIS), mammographic breast density and non-luminal A breast cancer.

A Large-Scale Investigation of Hypoxia-Preconditioned Allogeneic Mesenchymal Stem Cells for Myocardial Repair in Nonhuman Primates: Paracrine Activity Without Remuscularization.

RATIONALE: The effectiveness of transplanted bone marrow mesenchymal stem cells (MSCs) for cardiac repair has been limited; thus, strategies for optimizing stem-cell-based myocardial therapy are needed. OBJECTIVE: The present study was designed to test our central hypothesis that hypoxia-preconditioned MSCs (HP-MSCs) are more effective than MSCs cultured under ambient oxygen levels for the treatment of myocardial injury in a large-scale (N=49), long-term (9 months), nonhuman primate (Cynomolgous monkeys) investigation. METHODS AND RESULTS: MSCs were engineered to express green fluorescent protein, cultured under ambient oxygen or 0.5% oxygen (HP-MSCs) for 24 hours and then tested in the infarcted hearts of Cynomolgus monkeys (1×10(7) cells per heart). Hypoxia preconditioning increased the expression of several prosurvival/proangiogenic factors in cultured MSCs, and measurements of infarct size and left-ventricular function at day 90 after myocardial infarction were significantly more improved in monkeys treated with HP-MSCs than in monkeys treated with the control vehicle; functional improvements in normal cultured bone marrow mesenchymal stem cells-treated monkeys were not significant. HP-MSCs transplantation was also associated with increases in cardiomyocyte proliferation, vascular density, myocardial glucose uptake, and engraftment of the transplanted cells and with declines in endogenous cell apoptosis, but did not increase the occurrence of arrhythmogenic complications. CONCLUSIONS: Hypoxia preconditioning improved the effectiveness of MSCs transplantation for the treatment of myocardial infarction in nonhuman primates without increasing the occurrence of arrhythmogenic complications, which suggests that future clinical trials of HP-MSCs transplantation are warranted.

Safety and efficacy of intracoronary hypoxia-preconditioned bone marrow mononuclear cell administration for acute myocardial infarction patients: The CHINA-AMI randomized controlled trial.

BACKGROUND: Pre-clinical studies have shown that hypoxia preconditioning can enhance stem cell therapeutic potential for myocardial repair. We sought to investigate the safety and feasibility of intracoronary administration of hypoxia-preconditioned bone marrow mononuclear cells (HP-BMCs) for acute ST segment elevation myocardial infarction (STEMI). METHODS: We randomized 22 patients with acute STEMI to receive intracoronary administration of normoxia bone marrow mononuclear cells (N-BMCs) (n=11) or HP-BMCs (n=11) following successful reperfusion. Another 14 patients receiving standard therapy were recruited as control (n=14). RESULTS: There were no differences in the occurrence of major adverse cardiovascular events at 30 days and 1 year among three groups. There were significant improvement in the change of left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV) in HP-BMC group both at 6 and 12 months compared with N-BMCs or control group (P<0.05). No differences were observed in the change of left ventricular ejection fraction (LVEF), or wall motion score index (WMSI) among three groups. Nevertheless, WMSI was improved in HP-BMCs and N-BMC group (P<0.05, within group), but not in control. The ratio of myocardial perfusion defect determined by SPECT was significantly decreased in HP-BMCs and N-BMC groups at 6months compared with baseline (P<0.05, within group), but no significant differences were observed among three groups. CONCLUSIONS: Our results provide the first-in-man evidence that intracoronary administration of HP-BMCs following acute MI appears to be safe and feasible. These results provide the basis for future prospective randomized clinical trials in a larger patient cohort. CLINICAL TRIAL REGISTRATION INFORMATION: NCT01234181 (http://clinicaltrials.gov/ct2/show/NCT01234181?term=NCT01234181&rank=1).

Preliminary studies of a novel cyclopentadienyl tricarbonyl technetium-99m fatty acid derivative for myocardical imaging.

This study reports the synthesis and evaluation studies of 6'-cyclopentadienyl tricarbonyl technetium-99m 6'-oxo-11-(hexanamide)undecanoic acid (1). 1 was prepared with 26.5 ± 4.3% of radiochemical yield and more than 98% of radiochemical purity. Tissue distribution in mice showed that high radioactivity accumulated in the heart with moderate clearance. However, unfortunately, similar to those of other technetium-labeled fatty acid analogs, the biodistribution studies of 1 in mice showed poor heart-to-blood ratios, which suggested that 1 cannot be used as myocardial imaging agent, and it may provide a theoretical basis or a lab experience for corresponding fatty acid tracers studies.

Imaging a pancreatic carcinoma xenograft model with 11C-acetate: a comparison study with 18F-FDG.

PURPOSE: Pancreatic carcinoma is a malignant tumor with poor prognosis and its early detection is still a clinical problem. The aim of this study was to evaluate the efficacy of carbon-11-labeled acetate (11C-acetate)-positron emission tomography (PET) for the detection of pancreatic carcinoma in a BxPC-3 human pancreatic carcinoma xenograft-bearing immunodeficiency BALB/c-nu nude mice model. METHODS: Whole-body 11C-acetate and fluorine-18-labeled fluorodeoxyglucose (F-FDG) micro-PET imaging were performed weekly on BxPC-3 human pancreatic carcinoma xenograft-bearing BALB/c-nu nude mice from the 2nd week after tumor cell inoculation. Regions of interest method and tumor-to-nontumor ratio (T/N ratio) were used for semiquantitative evaluation. Tumor proliferation was evaluated by immunohistochemistry analysis of proliferating cell nuclear antigen. RESULTS: Radiotracer accumulation in the tumor xenografts could be detected 1 week earlier in 11C-acetate-PET than that in 18F-FDG-PET. Peak T/N ratio was obtained at the 5th week in 11C-acetate-PET and at the 4th week in 18F-FDG-PET. T/N ratio in 11C-acetate-PET was lower than that in 18F-FDG-PET during the same period. By visual evaluation, tumor xenografts were more easily observed in 11C-acetate-PET than in 18F-FDG-PET in most of the mice. Linear correlation analysis indicated T/N ratios in C-acetate-PET had no significant correlation with those in 18F-FDG-PET. Tumor size, T/N ratio in 11C-acetate-PET, and T/N ratio in 18F-FDG-PET were not found to be significantly correlated with tumor proliferating cell nuclear antigen expression. CONCLUSION: 11C-acetate-PET imaging can be used for the detection of pancreatic carcinoma. In the early stage of tumor growth, 11C-acetate-PET has better detectability than that of 18F-FDG-PET.

Application of FDG-PET for detection of malignant lesions in patients with elevated blood tumor markers but without a history of malignancy.

The aim of this study was to evaluate the clinical application of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging for the detection of malignant lesions. A total of 132 patients with increased levels of blood tumor markers but without a prior history of malignancy were examined. The results of FDG-PET and conventional work-up (CWU) including computed tomography (CT), ultrasonography, radionuclide bone scintigraphy and endoscopy were compared. The final diagnosis was based on pathological evidence, other medical imaging results and a follow-up of at least 6 months. There were 61 patients with malignant lesions and 71 without (benign lesions, n=35; healthy individuals, n=36). The average number of elevated tumor markers and the average increase in these tumor markers were greater in the malignant group than in the non-malignant group. FDG-PET imaging revealed that the maximum standardized uptake value (SUVmax) of the major lesion in patients with malignant (n=61) and benign (n=35) tumors was not significantly related to increased levels of tumor markers (r=0.10, p<0.05). In patients with malignant lesions and an SUVmax ≥3.0, the diagnostic sensitivity, specificity, accuracy, positive predictive value and negative predictive value of FDG-PET were 95.1, 83.1, 88.6, 82.9 and 95.2%, respectively. CWU identified 61 (100%) true-positive patients. No statistically significant differences in sensitivity were observed between the results of FDG-PET and CWU (p>0.05). In 36 healthy subjects without abnormal CWU findings, no abnormal FDG accumulation was revealed by FDG-PET imaging. In conclusion, FDG-PET imaging is a valuable tool for the detection of malignant lesions in patients with increased levels of blood tumor markers but without a history of malignancy. It is therefore reasonable to apply FDG-PET imaging in situations in which the results of CWU are inconclusive, or when patients wish to limit the number of examinations they must undergo.