Pan-cancer evaluation of clinical value of mitotic network activity index (MNAI) and its predictive value for immunotherapy.

Increased mitotic activity is associated with the genesis and aggressiveness of many cancers. To assess the clinical value of mitotic activity as prognostic biomarker, we performed a pan-cancer study on the mitotic network activity index (MNAI) constructed based on 54-gene mitotic apparatus network. Our pan-cancer assessment on TCGA (33 tumor types, 10,061 patients) and validation on other publicly available cohorts (23 tumor types, 9,209 patients) confirmed the significant association of MNAI with overall survival, progression-free survival, and other prognostic endpoints in multiple cancer types, including lower-grade gliomas (LGG), breast invasive carcinoma (BRCA), as well as many others. We also showed significant association between MNAI and genetic instability, which provides a biological explanation of its prognostic impact at pan-cancer landscape. Our association analysis revealed that patients with high MNAI benefitted more from anti-PD-1 and Anti-CTLA-4 treatment. In addition, we demonstrated that multimodal integration of MNAI and the AI-empowered Cellular Morphometric Subtypes (CMS) significantly improved the predictive power of prognosis compared to using MNAI and CMS alone. Our results suggest that MNAI can be used as a potential prognostic biomarker for different tumor types toward different clinical endpoints, and multimodal integration of MNAI and CMS exceeds individual biomarker for precision prognosis.

Treatment outcomes of posterior pilon fractures using a simple single lateral approach via stretching fibular fracture line.

Purpose: The aim of this study was to explore the treatment outcomes of a novel single lateral approach via fibular fracture line for patients with posterior pilon fractures. Patients and methods: From January 2020 to December 2021, a total of 41 patients with posterior pilon fractures who received surgical treatment in our hospital were retrospectively reviewed. Twenty patients (Group A) were treated with open reduction and internal fixation (ORIF) via posterolateral approach. Twenty-one patients (Group B) were treated with ORIF using a simple single lateral approach via stretching fibular fracture line. Clinical assessments, including operation time, intraoperative blood loss, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, visual analogue scale (VAS), and the active range of motion (ROM) of the ankle at the final follow-up visit after surgery, were performed in all patients. Radiographic outcome was evaluated by using the criteria proposed by Burwell and Charnley. Results: The mean follow-up time was 21 months (range 12-35). The average operation time and intraoperative blood loss in the Group B were significantly less than those in the Group A. Moreover, the AOFAS score and ankle ROM in the Group B were significantly higher than those in the Group A at the final follow-up visit. Eighteen cases (90%) in Group A and 19 cases (90.5%) in Group B achieved anatomical reduction of the fracture. Conclusion: The single lateral approach via stretching fibular fracture line is a simple and effective technique for reduction and fixation of posterior pilon fractures.

Repair of deep deltoid ligament ruptures near the medial malleolar attachment or midsubstance rupture by using suture anchors into the talus combined with the transosseous suture in the medial malleolar.

Purpose: For deep deltoid ligament ruptures near the medial malleolar attachment, anchors were usually placed at the posterior colliculus and intercollicular groove. However, this procedure usually requires a prolonged surgical incision to fully expose the deep deltoid ligament, causing more trauma. In order to reduce surgical trauma, we explored the treatment outcomes of suture anchor into the talus combined with transosseous suture in the medial malleolar for the treatment of deep deltoid ligament ruptures near the medial malleolar attachment or midsubstance rupture. Patients and methods: This is a retrospective study of patients who received suture anchor into the talus combined with transosseous suture in the medial malleolar for repairing deltoid ligament ruptures near the medial malleolar attachment or midsubstance rupture. The outcome measures include the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, visual analogue scale (VAS), and the active range of motion (ROM) of the ankle at the final follow-up visit after surgery. Medial malleolus gap was evaluated by radiographic examination. Results: This study included 64 patients. The mean follow-up time was 36.3 ± 15.2 months. There were 43 patients with injuries on the medial malleolar side, and 21 cases on the midsubstance. The average AOFAS and VAS were 87.5 ± 4.9 and 0.7 ± 0.5, respectively. No significance in medial malleolus gap between the contralateral side and affected side was observed. Conclusion: For deltoid ligament ruptures near the medial malleolar attachment or midsubstance rupture, suture anchor into the talus combined with transosseous suture in the medial malleolar yields good clinical effect and outcome, is an optimal management of ankle syndesmosis injuries.

Development and validation of chest CT-based imaging biomarkers for early stage COVID-19 screening.

Coronavirus Disease 2019 (COVID-19) is currently a global pandemic, and early screening is one of the key factors for COVID-19 control and treatment. Here, we developed and validated chest CT-based imaging biomarkers for COVID-19 patient screening from two independent hospitals with 419 patients. We identified the vasculature-like signals from CT images and found that, compared to healthy and community acquired pneumonia (CAP) patients, COVID-19 patients display a significantly higher abundance of these signals. Furthermore, unsupervised feature learning led to the discovery of clinical-relevant imaging biomarkers from the vasculature-like signals for accurate and sensitive COVID-19 screening that have been double-blindly validated in an independent hospital (sensitivity: 0.941, specificity: 0.920, AUC: 0.971, accuracy 0.931, F1 score: 0.929). Our findings could open a new avenue to assist screening of COVID-19 patients.

iCEMIGE: Integration of CEll-morphometrics, MIcrobiome, and GEne biomarker signatures for risk stratification in breast cancers.

BACKGROUND: The development of precision medicine is essential for personalized treatment and improved clinical outcome, whereas biomarkers are critical for the success of precision therapies. AIM: To investigate whether iCEMIGE (integration of CEll-morphometrics, MIcro biome, and GEne biomarker signatures) improves risk stratification of breast cancer (BC) patients. METHODS: We used our recently developed machine learning technique to identify cellular morphometric biomarkers (CMBs) from the whole histological slide images in The Cancer Genome Atlas (TCGA) breast cancer (TCGA-BRCA) cohort. Multivariate Cox regression was used to assess whether cell-morphometrics prognosis score (CMPS) and our previously reported 12-gene expression prognosis score (GEPS) and 15-microbe abundance prognosis score (MAPS) were independent prognostic factors. iCEMIGE was built upon the sparse representation learning technique. The iCEMIGE scoring model performance was measured by the area under the receiver operating characteristic curve compared to CMPS, GEPS, or MAPS alone. Nomogram models were created to predict overall survival (OS) and progress-free survival (PFS) rates at 5- and 10-year in the TCGA-BRCA cohort. RESULTS: We identified 39 CMBs that were used to create a CMPS system in BCs. CMPS, GEPS, and MAPS were found to be significantly independently associated with OS. We then established an iCEMIGE scoring system for risk stratification of BC patients. The iGEMIGE score has a significant prognostic value for OS and PFS independent of clinical factors (age, stage, and estrogen and progesterone receptor status) and PAM50-based molecular subtype. Importantly, the iCEMIGE score significantly increased the power to predict OS and PFS compared to CMPS, GEPS, or MAPS alone. CONCLUSION: Our study demonstrates a novel and generic artificial intelligence framework for multimodal data integration toward improving prognosis risk stratification of BC patients, which can be extended to other types of cancer.

Distinct Clinical Impact and Biological Function of Angiopoietin and Angiopoietin-like Proteins in Human Breast Cancer.

Secreted angiopoietin/angiopoietin-like (ANGPT/ANGPTL) proteins are involved in many biological processes. However, the role of these proteins in human breast cancers (BCs) remains largely unclear. Here, we conducted integrated omics analyses to evaluate the clinical impact of ANGPT/ANGPTL proteins and to elucidate their biological functions. In BCs, we identified rare mutations in ANGPT/ANGPTL genes, frequent gains of ANGPT1, ANGPT4, and ANGPTL1, and frequent losses of ANGPT2, ANGPTL5, and ANGPTL7, but observed that ANGPTL1, 2, and 4 were robustly downregulated in multiple datasets. The expression levels of ANGPTL1, 5, and 8 were positively correlated with overall survival (OS), while the expression levels of ANGPTL4 were negatively correlated with OS. Additionally, the expression levels of ANGPTL1 and 7 were positively correlated with distant metastasis-free survival (DMFS), while the expression levels of ANGPT2 and ANGPTL4 were negatively correlated with DMFS. The prognostic impacts of ANGPT/ANGPTL genes depended on the molecular subtypes and on clinical factors. We discovered that various ANGPT/ANGPTL genes were co-expressed with various genes involved in different pathways. Finally, with the exception of ANGPTL3, the remaining genes showed significant correlations with cancer-associated fibroblasts, endothelial cells, and microenvironment score, whereas only ANGPTL6 was significantly correlated with immune score. Our findings provide strong evidence for the distinct clinical impact and biological function of ANGPT/ANGPTL proteins, but the question of whether some of them could be potential therapeutic targets still needs further investigation in BCs.