The prediction of pCR and chemosensitivity for breast cancer patients using DLG3, RADL and Pathomics signatures based on machine learning and deep learning.

BACKGROUND: Limited studies have investigated the predictive value of multiomics signatures (radiomics, deep learning features, pathological features and DLG3) in breast cancer patients who underwent neoadjuvant chemotherapy (NAC). However, no study has explored the relationships among radiomic, pathomic signatures and chemosensitivity. This study aimed to predict pathological complete response (pCR) using multiomics signatures, and to evaluate the predictive utility of radiomic and pathomic signatures for guiding chemotherapy selection. METHODS: The oncogenic function of DLG3 was explored in breast cancer cells via DLG3 knockdown. Immunohistochemistry (IHC) was used to evaluate the relationship between DLG3 expression and docetaxel/epirubin sensitivity. Machine learning (ML) and deep learning (DL) algorithms were used to develop multiomics signatures. Survival analysis was conducted by K-M curves and log-rank. Multivariate logistic regression analysis was used to develop nomograms. RESULTS: A total of 311 patients with malignant breast tumours who underwent NAC were retrospectively included in this multicentre study. Multiomics (DLG3, RADL and PATHO) signatures could accurately predict pCR (AUC: training: 0.900; testing: 0.814; external validation: 0.792). Its performance is also superior to that of clinical TNM staging and the single RADL signature in different cohorts. Patients in the low DLG3 group more easily achieved pCR, and those in the high RADL Signature_pCR and PATHO_Signature_pCR (OR = 7.93, 95 % CI: 3.49-18, P < 0.001) groups more easily achieved pCR. In the TEC regimen NAC group, patients who achieved pCR had a lower DLG3 score (4.00 ± 2.33 vs. 6.43 ± 3.01, P < 0.05). Patients in the low RADL_Signature_DLG3 and PATHO_Signature_DLG3 groups had lower DLG3 IHC scores (P < 0.05). Patients in the high RADL signature, PATHO signature and DLG3 signature groups had worse DFS and OS. CONCLUSIONS: Multiomics signatures (RADL, PATHO and DLG3) demonstrated great potential in predicting the pCR of breast cancer patients who underwent NAC. The RADL and PATHO signatures are associated with DLG3 status and could help doctors or patients choose proper neoadjuvant chemotherapy regimens (TEC regimens). This simple, structured, convenient and inexpensive multiomics model could help clinicians and patients make treatment decisions.

Exploring the Anticancer Properties of Sakuranin Flavanone in Human Oropharyngeal Squamous Carcinoma Cells by Studying Its Effects on Caspase-driven Apoptosis, Mitochondrial Membrane Potential (MMP) Loss, Cell Migratory and Invasiveness and m-TOR/PI3K/AKT Signalling Pathway.

Sakuranin is a flavanone which is a class of flavonoids found abundantly in Prunus species. Flavonoids have been long known for their anticancer properties against a range of human cancers. However, there are no previous reports on the anticancer effects of sakuranin flavanone molecule. This study was designed to study the anticancer effects of sakuranin against human oropharyngeal carcinoma cells along with investigating its effects on caspase-mediated apoptosis, mitochondrial membrane potential (MMP) loss, cell migration and invasion and m-TOR/PI3K/AKT signalling pathway. MTT assay was used to study effects on cell viability. The apoptotic studies were carried out through AO/EB staining, annexin V/FITC staining, comet assay and western blotting assay. Transwell chambers assay was used to study effects on cell migration and invasion. Flow cytometry was used to study effects of Sakuranin on mitochondrial membrane potential loss (MMP). Finally, western blotting was used to investigate m-TOR/PI3K/AKT signalling pathway. Results indicated that Sakuranin led to potent cell proliferation inhibition in a dose-dependent manner. Sakuranin also induced apoptotic cell death as indicated by fluorescence microscopy and annexin V/FITC staining assays. The apoptotic induction was mediated via activation of caspase-3, caspase-9, and Bax while as it led to downregulation of Bcl-2. Sakuranin also caused inhibition of cell migration and cell invasion along with causing significant decrease in MMP. Sakuranin also caused inhibition of expressions of proteins related with m-TOR/PI3K/AKT signalling pathway. In conclusion, the current findings clearly indicate anticancer effects of Sakuranin flavanone in human oropharyngeal cancer cells and are mediated via caspase activated apoptosis, inhibition of cell migration and invasion, loss of mitochondrial membrane potential and targeting m-TOR/PI3K/AKT signalling pathway.

A single-centre, real-world study of BTK inhibitors for the initial treatment of MYD88mut /CD79Bmut diffuse large B-cell lymphoma.

BACKGROUND: MCD (MYD88L265P /CD79Bmut ) diffuse large B-cell lymphoma has a poor prognosis. There is no published clinical research conclusion regarding zanubrutinib or orelabrutinib for the initial treatment of MCD DLBCL. AIMS: This study aimed to analyse the efficacy and safety of Bruton's tyrosine kinase inhibitor (BTKi) (zanubrutinib or orelabrutinib) therapy for newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut . MATERIALS AND METHODS: Twenty-three newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut from June 2020 to June 2022 received BTKi combined with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or rituximab + lenalidomide (R2 ). A control group of 17 patients with MYD88mut and/or CD79Bmut DLBCL who received the standard R-CHOP therapy was also assessed. We retrospectively analysed clinical characteristics, safety, overall response rate (ORR), complete response (CR) rate and progression-free survival (PFS) of the two groups. RESULTS: The main clinical features were a high International Prognostic Index (IPI) score (≥3, 22/40, 55%) and a high rate of extranodal involvement (27/40,67.5%). Among the 23 DLBCL patients, 18 received BTKi + R-CHOP, and five elderly DLBCL patients were treated with BTKi + R2 . Compared with those in the control group (ORR 70.6%, CRR 52.9%, 1-year PFS rate 41.2%), improved ORR, CRR and PFS results were observed in the BTKi + R-CHOP group (100%, 94.4% and 88.9%, p = 0.019, 0.007, and 0.0001). In subgroup analyses based on genetic subtypes, cell origin, dual expression or IPI score, patients in the BTKi + R-CHOP group had better PFS than patients in the control group. In the BTKi + R-CHOP group, no significant difference was found in ORR, CRR and PFS based on subtype analysis, while BTKi-type subgroups exhibited statistically significant differences in 1-year PFS (p = 0.028). There were no significant differences in grade 3-4 haematological toxicity (p = 1) and grade 3-4 non-haematological toxicity (p = 0.49) between the BTKi + R-CHOP and R-CHOP treatment groups. In the BTKi + R2 group, the ORR was 100%, the CRR was 80%, and the 1-year PFS rate was 80%. The incidences of grade 3-4 haematologic toxicity and non-haematological toxicity were both 40%. No bleeding or cardiovascular events of grade 3 or higher occurred in any patients. DISCUSSION: The efficacy of BTKi combined with R-CHOP was similar to previous reports, which was significantly better than R-CHOP alone. It is necessary to fully consider that 14 patients in the BTKi + R-CHOP group received a BTKi as maintenance therapy when evaluating efficacy. Meanwhile, the addition of a BTKi may improve the prognosis of non-GCB, DEL or high-IPI-score DLBCL patients with MYD88mut and/or CD79Bmut . In our study, five elderly DLBCL patients with MYD88mut and/or CD79Bmut were achieved better ORR, CRR, PFS than the historical data of R-miniCHOP treatment and Ibrutinib + R2 treatment. However, the efficacy and benefit of BTKis for this type of DLBCL need to be further analysed using a larger sample size. CONCLUSION: This study suggests that newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut may benefit from BTKis according to real-world clinical data.

EBV-associated lymphoproliferative disease post-CAR-T cell therapy.

Epstein-Barr virus (EBV)-associated lymphoproliferative diseases (EBV-LPDs) are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation (HSCT). However, their occurrence and treatment post-chimeric antigen receptor-modified T (CAR-T) cell therapy has not been reported. Two patients had been diagnosed with EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of treatment. After receiving CAR-T cell therapy in tandem with autologous HSCT, the patients achieved complete remission. However, with a median time of 38.5 months after CAR-T cell therapy, B-cell-derived EBV-LPDs were diagnosed, and they were relieved through the administration of immune checkpoint inhibitor or B-cell-depleting agents. Collectively, our report suggests that EBV-LPDs may represent a long-term adverse event after CAR-T cell therapy, especially in patients who previously had EBV-positive disorders, and they can be resolved by immune normalization strategy or B-cell depleting therapy.

The chronic rhinosinusitis with nasal polyp patient journey in the United States and Europe.

In this letter to the editor, we present questionnaire-based data assessing the patient journey of adults with moderate-severe Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) in the USA and five European countries. These data highlight how long and difficult the patient journey with CRSwNP can be and how improved disease awareness among physicians could lead to more timely diagnosis and treatment, and hence improved management of patients.

The segregation of physician networks providing care to black and white patients with heart disease: Concepts, measures, and empirical evaluation.

Black-White disparities in cardiac care may be related to physician referral network segregation. We developed and tested new geographic physician network segregation measures. We used Medicare claims to identify Black and White Medicare heart disease patients and map physician networks for 169 hospital referral regions (HRRs) with over 1000 Black patients. We constructed two network segregation indexes ranging from 0 (integration) to 100 (total segregation): Dissimilarity (the unevenness of Black and White patient distribution across physicians [Dn]) and Absolute Clustering (the propensity of Black patients' physicians to have closer ties with each other than with other physicians [ACLn]). We employed conditional logit models to estimate the probability of using the best (lowest mortality) geographically available hospital for Black and White patients undergoing coronary artery bypass grafting (CABG) surgery in 126 markets with sufficient sample size at increasing levels of network segregation and for low vs. high HRR Black patient population. Physician network segregation was lower than residential segregation (Dissimilarity 21.9 vs. 48.7, and Absolute Clustering 4.8 vs. 32.4) and positively correlated with residential segregation (p < .001). Network segregation effects differed by race and HRR Black patient population. For White patients, higher network segregation was associated with a higher probability of using the best available hospitals in HRRs with few black patients but unchanged (ACLn) or lower (Dn) probability of best hospital use in HRRs with many Black patients. For Black patients, higher network segregation was not associated with a substantial change in the probability of best hospital use regardless of the HRR Black patient population size. Measuring physician network segregation is feasible and associated with nuanced effects on Black-White differences in high-quality hospital use for heart disease. Further work is needed to understand underlying mechanisms and potential uses in health equity policy.

Clinicopathological Characteristics of Breast Cancer Patients with HER-2 Low Expression Receiving Neoadjuvant Therapy.

INTRODUCTION: Human epidermal growth factor receptor-2 (HER-2) low expression breast malignant tumors have become a research hotspot in recent years, but it is still unclear whether HER-2 low expression represents a special subtype of breast cancer. However, this molecular type requires more effective treatment regimens in the neoadjuvant therapy stage. METHODS: This study enrolled breast cancer patients who were treated at Harbin Medical University Cancer Hospital with neoadjuvant treatment between October 2011 and May 2019 and was a single-center retrospective study. RESULTS: A total of 1,053 breast cancer patients who received preoperative therapy, including 279 (26%) HER-2 low expression patients, were included in this retrospective study. The HER-2 low expression group had a higher proportion of patients under 50 years old than the other two molecular subtype groups (p = 0.047, 62.0% vs. 57.2% and 52.5%), and the percentage of patients with Ki67 index above 15% was lower than that in HER-2-negative and HER-2-positive patients (p < 0.001, 50.2% vs. 63.6% and 71.5%). Most of the patients with HER-2 low expression were hormone receptor (HR) positive (p < 0.001, 85.7% vs. 60.4% and 36.0%), and their pathologic complete response (pCR) rate after neoadjuvant therapy was significantly lower than that of HER-2-negative and HER-2-positive patients (p < 0.001, 5.7% vs. 11.8% and 20.5%). The results of the subgroup analysis showed HR-positive patients with HER-2 low expression had a lower pCR rate (p < 0.001, 4.6% vs. 14.6%) and objective response rate (p = 0.001, 77.8% vs. 91.0%) than HER-2-positive patients and had no significant difference in these rates compared to HER-2-negative patients. There were no significant differences in overall survival (OS) and disease-free survival (DFS) up to 67 months (the median follow-up time) among HER-2 low, HER-2-negative, and HER-2-positive patients. The results of Cox hazard proportional showed that the Ki67 index and T stage (T3) were independent influencing factors for DFS. In terms of OS, Ki67 index, P53, T stage, and objective response were independent influencing factors for OS in HER-2 low expression patients. CONCLUSIONS: In general, further studies are needed to confirm that HER-2 low expression is a special breast cancer molecular subtype. The efficacy of neoadjuvant therapy in patients with HER-2 low expression is relatively poor, and the efficacy of neoadjuvant therapy can predict the prognosis of patients with HER-2 low expression.

Naples score: a novel prognostic biomarker for breast cancer patients undergoing neoadjuvant chemotherapy.

BACKGROUND AND PURPOSE: The Naples Score (NPS) is a novel prognostic indicator that has been used in various cancers, but its potential in breast malignant tumor patients receiving neoadjuvant chemotherapy (NAC) has not been discovered. This study aimed to investigate the relationship between NPS and overall survival (OS) and disease-free survival (DFS) in breast cancer patients. METHODS: A total of 217 breast cancer patients undergoing NAC were incorporated into this retrospectively research. K-M survival curves and log-rank tests are used to determine OS and DFS. Cox regression model was used to evaluate the relationship between NPS and OS and DFS. Nomogram was developed based on the results of multivariate Cox regression analysis. Prognostic models were internally validated using bootstrapping and the consistency index (C-index). RESULTS: Age group was correlated with NPS (p < 0.05). Low and moderate Naples risk patients had higher 5-year OS and DFS rates than high risk Naples patients (93.8% vs. 75.4% vs. 60.0%; X2 = 9.2, P = 0.01; 82.4% vs 64.5% vs 43.7%; X2 = 7.4, P = 0.024; respectively). The nomogram based on demonstrated good performance in predicting OS and DFS (AUC = 0.728, 0.630; respectively). CONCLUSIONS: In breast cancer patients who have undergone NAC, NPS is a novel prognostic indicator. NPS combined with clinicopathological features showed good predictive ability, and its performance was better than that of traditional pathological TNM staging.

Prediction of nonsentinel lymph node metastasis in breast cancer patients based on machine learning.

BACKGROUND: Develop the best machine learning (ML) model to predict nonsentinel lymph node metastases (NSLNM) in breast cancer patients. METHODS: From June 2016 to August 2022, 1005 breast cancer patients were included in this retrospective study. Univariate and multivariate analyses were performed using logistic regression. Six ML models were introduced, and their performance was compared. RESULTS: NSLNM occurred in 338 (33.6%) of 1005 patients. The best ML model was XGBoost, whose average area under the curve (AUC) based on 10-fold cross-verification was 0.722. It performed better than the nomogram, which was based on logistic regression (AUC: 0.764 vs. 0.706). CONCLUSIONS: The ML model XGBoost can well predict NSLNM in breast cancer patients.

Ultrasound Triggered Tumor Metabolism Suppressor Induces Tumor Starvation for Enhanced Sonodynamic Immunotherapy of Breast Cancer.

Introduction: Sonodynamic therapy (SDT) as an emerging tumor treatment gained wide attention. However, tumor vascular destruction and oxygen depletion in SDT process may lead to further hypoxia. This may lead to enhanced glycolysis, lactate accumulation, and immunosuppression. Methods: A glycolysis inhibitor (3PO) loaded and PEG modified black phosphorus nanosheets (BO) is constructed for potent starvation therapy and efficient immune activation. Results: Under ultrasound irradiation, the BO can produce ROS to destroy tumors and tumor blood vessels and lead to further hypoxia and nutrients block. Then, the released 3PO inhibits tumor glycolysis and prevents the hypoxia-induced glycolysis and lactate accumulation. Both SDT and 3PO can cut off the source of lactic acid, as well as achieve antitumor starvation therapy through the blockade of the adenosine triphosphate (ATP) supply. In addition, the combination of starvation treatment and SDT further facilitates dendritic cells (DC) maturation, promotes antigen presentation by DCs, and eventually propagates the antitumor immunity and inhibition of abscopal tumor growth. Conclusion: This is the first time that combines SDT with inhibition of glycolysis, achieving admirable tumor treatment and decreasing adverse events caused by SDT process and that has caused good immune activation. Our system provides a new idea for the future design of anti-tumor nanomedicines.

Gold nanoparticle doped Cuhemin nanosheets with a remodeling tumor microenvironment for multiple radiotherapy sensitization.

Effective radiosensitizers are urgently needed due to the serious negative effects that high radiation doses might have. We created an integrated nano-system (Cuhemin-Au) made of Cuhemin nanosheets and Au nanoparticles (Au NPs) for sensitizing radiotherapy to solve this issue. This system can manifest enzyme-like activities to universally suppress the resistance pathways in breast cancer cells for amplifying radiation damage. Cuhemin-Au NPs increase the energy deposition of radiation owing to the high X-ray attenuation coefficient of Au. In addition, Cuhemin-Au has peroxidase (POD)-like and glucose oxidase (Gox)-like activity, and can also consume intracellular GSH, which can reduce intracellular GSH levels to reduce tumor cells' capacity to repair DNA and deplete intracellular glucose via their characteristic Gox-like catalytic activities, which can cause an increase in the oxidative stress and further produce H2O2. Cuhemin-Au then produced ˙OH, which upsets redox equilibrium and destroys mitochondria, leading to radiation sensitivity, after reacting with enough hydrogen peroxide in tumor cells. Cuhemin-Au combined with low dose RT (4 Gy) could significantly limit tumor development with fewer adverse effects, according to in vivo and in vitro experiments. This platform generated a fresh concept for the construction of a radiotherapy sensitization system and accomplished synergistic radiotherapy sensitization.

Serum Metabolomic Profiles for Distinguishing Lung Cancer From Pulmonary Tuberculosis: Identification of Rapid and Noninvasive Biomarker.

BACKGROUND: Pulmonary tuberculosis (PTB) and lung cancer (LC) have similar clinical symptoms and atypical imaging findings, which are easily misdiagnosed. There is an urgent need for a noninvasive and accurate biomarker to distinguish LC from PTB. METHODS: A total of 694 subjects were enrolled and divided into discovery set (n = 122), identification set (n = 214), and validation set (n = 358). Metabolites were identified by multivariate and univariate analyses. Receiver operating characteristic curve were used to evaluate the diagnostic efficacy of biomarkers. RESULTS: Seven metabolites were identified and validated. Phenylalanylphenylalanine for distinguishing LC from PTB yielded an area under the curve of 0.89, sensitivity of 71%, and specificity of 92%. It also showed good diagnostic abilities in discovery set and identification set. Compared with that in healthy volunteers (median [interquartile range], 1.57 [1.01, 2.34] µg/mL), it was elevated in LC (4.76 [2.74, 7.08] µg/mL; ratio of median, [ROM] = 3.03, P < .01) and reduced in PTB (1.06 [0.51, 2.09] µg/mL; ROM = 0.68, P < .05). CONCLUSIONS: The metabolomic profile of LC and PTB was described and a key biomarker identified. We produced a rapid and noninvasive method to supplement existing clinical diagnostic examinations for distinguishing LC from PTB.

Targeting GPR133 via miR-106a-5p inhibits the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of glioma cells.

Background: Glioma is the most common malignant brain tumor. GPR133 is a key factor in the progression of glioma. However, the role of GPR133 in glioma invasion and EMT and the microRNAs (miRNAs) associated with this pathway are still poorly understood.Objective: This study aims to elucidate the biological function of miR-106a-5p and GPR133 in glioma as well as the molecular mechanism of their interaction.Methods: The mRNA expression of miR-106a-5p and GPR133 in glioma specimens and cells was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The protein level of GPR133 and the levels of invasion- and EMT-related proteins were measured by western blotting. miR-106a-5p and GPR133 function in glioma cells was determined through cell counting kit-8 (CCK-8), transwell, wound healing, colony formation assays in vitro and xenograft assays in vivo. To determine the targeting relationship between miR-106a-5p and GPR133, a dual-luciferase reporter assay was conducted.Results: A marked reduction in miR-106a-5p expression was observed in glioma cells and specimens. Patients with high expression of miR-106a-5p had a good prognosis, while patients with high expression of GPR133 had a shorter OS. Additionally, overexpression of miR-106a-5p or downregulation of GPR133 inhibited the progression of glioma cells. Furthermore, miR-106a-5p negatively regulated GPR133 expression by binding to its 3'-UTR, and restrained the invasion, migration, proliferation and EMT of glioma cells by targeting GPR133.Conclusions: miR-106a-5p is a tumor suppressor that negatively regulates GPR133. The miR-106a-5p/GPR133 axis could potentially serve as a therapeutic target for glioma.

Correlation analysis between androgen receptor and the clinicopathological features and prognosis of mammary Paget's disease.

PURPOSE: Little is known about the prognostic value of androgen receptor (AR) status in mammary Paget's disease (MPD). The purpose of this study was to explore AR status and the distribution of molecular subtypes in MPD as well as the relationship between AR expression and clinicopathological factors and to evaluate its prognostic value. METHODS: We analyzed 170 MPD patients of varying subtypes. AR expression was verified by immunohistochemical staining, and the correlations between AR expression and clinicopathological characteristics and survival status were analyzed. We further investigated 91 MPD patients with invasive ductal carcinoma (MPD-IDC). RESULTS: AR was expressed in 55.3% of overall MPD patients, and 78.2% had the human epidermal growth factor receptor 2 (HER2) overexpression subtype. AR positivity was significantly correlated with BMI (P = 0.037) and pathological N stage (P = 0.023). Multivariate analysis indicated that pathological T stage and pathological N stage were independent prognostic factors for overall survival (OS). The positive AR group was significantly associated with better OS (P = 0.014). Among 91 MPD-IDC patients, AR was expressed in 56.0%, and 80.0% had the HER2 overexpression subtype. AR positivity was significantly correlated with pathological N stage (P = 0.033). Multivariate analysis indicated that AR and pathological T stage were independent prognostic factors for OS. Furthermore, AR positivity was significantly related to better OS (P = 0.005) in MPD-IDC patients as well as in patients with the HER2 overexpression subtype (P = 0.029). CONCLUSION: Our results confirmed that AR is a potential biomarker for evaluating the prognosis of patients.

A Novel Inflammatory and Nutritional Prognostic Scoring System for Nonpathological Complete Response Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy.

Background: It has been demonstrated that inflammatory and nutritional variables are associated with poor breast cancer survival. However, some studies do not include these variables due to missing data. To investigate the predictive potential of the INPS, we constructed a novel inflammatory-nutritional prognostic scoring (INPS) system with machine learning. Methods: This retrospective analysis included 249 patients with malignant breast tumors undergoing neoadjuvant chemotherapy (NAC). After comparing seven potent machine learning models, the best model, Xgboost, was applied to construct an INPS system. K-M survival curves and the log-rank test were employed to determine OS and DFS. Univariate and multivariate analyses were carried out with the Cox regression model. Additionally, we compared the predictive power of INPS, inflammatory, and standard nutritional variables using the Z test. Results: After comparing seven machine learning models, it was determined that the XGBoost model had the best OS and DFS performance (AUC = 0.865 and 0.771, respectively). For overall survival (OS, cutoff value = 0.3917) and disease-free survival (cutoff value = 0.4896), all patients were divided into two groups by the INPS. Those with low INPS had higher 5-year OS and DFS rates (77.2% vs. 50.0%, P < 0.0001; and 59.6% vs. 32.1%, P < 0.0001, respectively) than patients with high INPS. For OS and DFS, the INPS exhibited the highest AUC compared to the other inflammatory and nutritional variables (AUC = 0.615, P = 0.0003; AUC = 0.596, P = 0.0003, respectively). Conclusion: The INPS was an independent predictor of OS and DFS and exhibited better predictive ability than BMI, PNI, and MLR. For patients undergoing NAC for nonpCR breast cancer, INPS was a crucial and comprehensive biomarker. It could also forecast individual survival in breast cancer patients with low HER-2 expression.

Prognostic value of a modified systemic inflammation score in breast cancer patients who underwent neoadjuvant chemotherapy.

BACKGROUND AND PURPOSE: The modified systemic inflammation score (mSIS) system, which is constructed based on the neutrophil to lymphocyte ratio (NLR) and albumin (Alb), has not been applied to evaluate the prognosis of malignant breast cancer patients who underwent neoadjuvant chemotherapy (NAC). The present study aimed to explore the relationship between the mSIS and overall survival (OS), disease-free survival (DFS) and pathological complete response (pCR). METHODS: A total of 305 malignant breast tumor patients who underwent NAC were incorporated into this retrospective analysis. We determined OS and DFS using K-M survival curves and the log-rank test. The relationship between the mSIS and OS and DFS was evaluated by a Cox regression model. A nomogram was constructed based on Cox regression analysis. RESULTS: Patients in the mSIS low-risk group had better 5- and 8-year OS rates than those in the mSIS high-risk group (59.8% vs. 77.0%; 50.1% vs. 67.7%; X2 = 8.5, P = 0.0035, respectively). Patients in the mSIS (1 + 2 score) + pCR subgroup had the highest 5- and 8-year OS and disease-free survival (DFS) rates (OS: 55.0% vs. 75.7% vs. 84.8, 42.8% vs. 65.7% vs. 79.8%, X2 = 16.6, P = 0.00025; DFS: 38.8% vs. 54.7% vs. 76.3%, 33.3% vs. 42.3 vs. 72.1%, X2 = 12.4, P = 0.002, respectively). Based on the mSIS, clinical T stage and pCR results, the nomogram had better predictive ability than the clinical TNM stage, NLR and Alb. CONCLUSIONS: mSIS is a promising prognostic tool for malignant breast tumor patients who underwent NAC, and the combination of mSIS and pCR is helpful in enhancing the ability to predict a pCR.

Endoscopy-assisted high anterior cervical approach in craniovertebral junction (CVJ).

Background: Surgical procedures in the craniovertebral junction (CVJ) suffer from specific challenges due to the proximity between the cranium and spine containing the critical neurovascular structures and the brainstem, respectively. Owing to the complex transitional zone, it is highly challenging for classic surgical approaches to practically acquire the additional exposure to neurovascular structures of the CVJ. Inspired by these facts, we explore the feasibility of an endoscopy-assisted high anterior cervical approach in the CVJ. Methods: To explore the feasibility of an endoscopy-assisted approach, we quantitatively assessed the surgical corridor and extent of exposure of the CVJ in 6 cadaveric specimens using 0° and 30° endoscopes. Results: The applied endoscopes provided adequate exposure to neurovascular structures and the brainstem in the CVJ. Notably, the resection of the anterior arch of C1 is avoided in minimal anterior clivectomy. Further, improved exposure of the CVJ is obtained after removing the odontoid. Conclusion: An endoscope-assisted high anterior cervical approach in the CVJ significantly preserved the cervical spine stability while minimalizing the risk of neurovascular injury within the surgical corridor.

Integrated analysis of competitive endogenous ribose nucleic acids (ceRNAs)-related regulatory networks in invasive and non-invasive non-functioning pituitary adenomas (NFPAs).

Background: This study aims to identify the differentially expressed (DE) non-coding ribose nucleic acids (ncRNAs), messenger RNA (mRNA) expression profiles, and competitive endogenous RNA (ceRNA)-related regulatory networks in invasive and non-invasive nonfunctioning pituitary adenomas (NFPAs). Methods: A full-transcriptome sequencing of invasive and non-invasive NFPAs is carried out to evaluate the expression profiles of circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNA expression profiles. Results: The screening criteria resulted in 118 DEcircRNAs (88 up-regulated and 30 down-regulated), 105 DElncRNAs (68 up-regulated and 37 down-regulated), 43 DEmiRNAs (22 up-regulated and 21 down-regulated), and 268 DEmRNAs (194 up-regulated and 74 down-regulated). Accordingly, a ceRNA regulatory network related to invasive NFPA is constructed. Further, the Gene Ontology and Kyoto Encylopedia of Genes and Genomes analyses showed that circRNAs and lncRNAs in the network are related to chromatin remodeling, participating in the Janus kinase/signal transducer and activator of transcription (JAK-STAT) and calcium signaling pathways. Hsa-miR-1248 showed exceptional connectivity in the ceRNA regulatory network, which could be closely related to the invasiveness of NFPAs. Conclusions: Together, these findings clarified the regulatory mechanisms of invasive and non-invasive NFPAs, providing innovative research avenues and therapeutic targets for invasive NFPAs.

Prediction of lymph node metastasis in patients with breast invasive micropapillary carcinoma based on machine learning and SHapley Additive exPlanations framework.

Abstract: Background and purpose: Machine learning (ML) is applied for outcome prediction and treatment support. This study aims to develop different ML models to predict risk of axillary lymph node metastasis (LNM) in breast invasive micropapillary carcinoma (IMPC) and to explore the risk factors of LNM. Methods: From the Surveillance, Epidemiology, and End Results (SEER) database and the records of our hospital, a total of 1547 patients diagnosed with breast IMPC were incorporated in this study. The ML model is built and the external validation is carried out. SHapley Additive exPlanations (SHAP) framework was applied to explain the optimal model; multivariable analysis was performed with logistic regression (LR); and nomograms were constructed according to the results of LR analysis. Results: Age and tumor size were correlated with LNM in both cohorts. The luminal subtype is the most common in patients, with the tumor size <=20mm. Compared to other models, Xgboost was the best ML model with the biggest AUC of 0.813 (95% CI: 0.7994 - 0.8262) and the smallest Brier score of 0.186 (95% CI: 0.799-0.826). SHAP plots demonstrated that tumor size was the most vital risk factor for LNM. In both training and test sets, Xgboost had better AUC (0.761 vs 0.745; 0.813 vs 0.775; respectively), and it also achieved a smaller Brier score (0.202 vs 0.204; 0.186 vs 0.191; 0.220 vs 0.221; respectively) than the nomogram model based on LR in those three different sets. After adjusting for five most influential variables (tumor size, age, ER, HER-2, and PR), prediction score based on the Xgboost model was still correlated with LNM (adjusted OR:2.73, 95% CI: 1.30-5.71, P=0.008). Conclusions: The Xgboost model outperforms the traditional LR-based nomogram model in predicting the LNM of IMPC patients. Combined with SHAP, it can more intuitively reflect the influence of different variables on the LNM. The tumor size was the most important risk factor of LNM for breast IMPC patients. The prediction score obtained by the Xgboost model could be a good indicator for LNM.

Valve implantation for successful sealing of a balloon predilatation-induced annular rupture during transcatheter aortic valve replacement.

Annular rupture is a rare and dreaded complication of transcatheter aortic valve replacement (TAVR) and even rarer when caused by predilatation balloon aortic valvuloplasty. This complication often presents as sudden cardiac tamponade with hypotension and requires urgent intervention. The traditional rescue strategy for patients with annular rupture is emergency surgical repair. However, the mortality rate is still high, considering that most patients who undergo TAVR are not candidates for conventional cardiac surgery. Therefore, there is a need for additional emergency treatment strategies to decrease mortality. This report describes a case of predilatation-induced annular rupture during TAVR that was successfully sealed at the rupture site by valve implantation. This case suggests that continuing with valve deployment may be a successful treatment for predilatation-induced annular rupture during TAVR.