Feasibility validation of automatic diagnosis of mitral valve prolapse from multi-view echocardiographic sequences based on deep neural network.

Aims: To address the limitations of traditional diagnostic methods for mitral valve prolapse (MVP), specifically fibroelastic deficiency (FED) and Barlow's disease (BD), by introducing an automated diagnostic approach utilizing multi-view echocardiographic sequences and deep learning. Methods and results: An echocardiographic data set, collected from Zhongshan Hospital, Fudan University, containing apical 2 chambers (A2C), apical 3 chambers (A3C), and apical 4 chambers (A4C) views, was employed to train the deep learning models. We separately trained view-specific and view-agnostic deep neural network models, which were denoted as MVP-VS and MVP view-agonistic (VA), for MVP diagnosis. Diagnostic accuracy, precision, sensitivity, F1-score, and specificity were evaluated for both BD and FED phenotypes. MVP-VS demonstrated an overall diagnostic accuracy of 0.94 for MVP. In the context of BD diagnosis, precision, sensitivity, F1-score, and specificity were 0.83, 1.00, 0.90, and 0.92, respectively. For FED diagnosis, the metrics were 1.00, 0.83, 0.91, and 1.00. MVP-VA exhibited an overall accuracy of 0.95, with BD-specific metrics of 0.85, 1.00, 0.92, and 0.94 and FED-specific metrics of 1.00, 0.83, 0.91, and 1.00. In particular, the MVP-VA model using mixed views for training demonstrated efficient diagnostic performance, eliminating the need for repeated development of MVP-VS models and improving the efficiency of the clinical pipeline by using arbitrary views in the deep learning model. Conclusion: This study pioneers the integration of artificial intelligence into MVP diagnosis and demonstrates the effectiveness of deep neural networks in overcoming the challenges of traditional diagnostic methods. The efficiency and accuracy of the proposed automated approach suggest its potential for clinical applications in the diagnosis of valvular heart disease.

Development and validation of a relatively accurate gastric cancer high-risk group screening scoring system in urban residents.

PURPOSE: Our study aimed to develop a relatively accurate gastric cancer (GC) screening score system for urban residents and to validate the screening efficacy. METHODS: The present study included a derivation cohort (n = 3406) and a validation cohort (n = 868) of urban residents. Applying the full-stack engineering intelligent system platform of Hualian Health Big Data of Shandong University, the clinical physical examination data of subjects were collected. Univariate and multivariate analyses were used to identify risk factors for GC, and subsequently, an optimal prediction rule was established to create three distinct scoring systems. RESULTS: In the GC-risk scoring system I, age, plateletocrit (PCT), carcinoembryonic antigen (CEA), glucose, albumin, creatinine were independent risk factors of GC, with scores ranging from 0 to 28 and optimal cut-off was 15.5. The second scoring system consisted of age, PCT, RDW-CV, CEA, glucose, albumin, and creatinine, with scores ranging from 0 to 31. The optimal cut-off point was determined to be 15.5. The scoring system III comprise of age, sex, PCT, RDW CV, CEA, glucose, with scores ranging from 0 to 21 and optimal cut-off was 10.5. All three scoring systems demonstrated excellent discrimination for GC, achieving an AUC of 0.884, 0.89, and 0.876, respectively. In external validation, the AUC values were 0.654, 0.658, and 0.714. Notably, the GC-risk scoring system III exhibited the highest screening efficiency. CONCLUSIONS: Urban residents benefited from the effective and verified GC-risk scoring systems, which demonstrated excellent performance in identifying individuals with an elevated risk of GC.

First-in-human cases and preclinical experience of a novel ICE catheter.

Introduction: The primary objective of our study was to evaluate the first use of a novel intracardiac echocardiography (ICE) catheter in human subjects. This study aimed to assess its practicality, image clarity, and guidance role during electrophysiology procedures. Methods: Two patients underwent procedures using the novel ICE catheter. Post-procedure evaluations were conducted by four operators, who assessed the imaging quality and overall performance of the catheter. Anatomical and blood test results were also analyzed to determine the safety and impact on internal cardiac structures. Results: Both patients were discharged one day after the procedure without any complications. The novel ICE catheter provided comparable imaging quality to existing commercial catheters. The catheter's advanced design allowed for detailed imaging at short distances, essential for accurate diagnosis and treatment planning. Moreover, it successfully navigated complex anatomical structures like the atrial septum and left atrial appendage. Discussion: These preliminary studies indicate that the novel ICE catheter achieves a level of safety and effectiveness comparable to previously available commercial catheters. The findings highlight its potential to meet current clinical needs, particularly in sophisticated anatomic interventions. Despite the prolonged thrombin time after anticoagulant administration, both types of ICE catheters were non-damaging to cardiac structures during routine operations. The study underscores the importance of using trans-septal large inner diameter sheaths to minimize complications when advancing the catheter into the left atrium.

Circ_0084653 promotes the tumor progression and immune escape in triple-negative breast cancer via the deubiquitination of MYC and upregulation of SOX5.

The role of circular RNAs (circRNAs) in cancers is gaining more and more attention, yet related reporters are limited. In triple-negative breast cancer (TNBC), circRNA circ_0084653 originated from COP9 signalosome subunit 5 (COPS5), and COPS5 has been validated to be upregulated in breast cancer before. In our research, COPS5 was also upregulated in TNBC cells, and knockdown of it repressed cell proliferation, invasion, EMT, stemness and PDL-1 protein expression but increased T-cell percentage. Further, circ_0084653 was an aberrantly upregulated circRNA in TNBC cells, and similarly, circ_0084653 silence inhibited TNBC development. Besides, circ_0084653 expression was distributed in both cytoplasm and nucleus. COPS5 overexpression partially rescued the suppressing effects of circ_0084653 depletion in TNBC. Subsequently, circ_0084653 triggered deubiquitination of MYC, the upstream transcription factor of COPS5, via recruiting ubiquitin specific peptidase 36 (USP36). Moreover, circ_0084653 served as the sponge of miR-1323 to release the expression the target gene SRY-box transcription factor 5 (SOX5). SOX5 upregulation completely remedied the inhibiting influence of circ_0084653 downregulation in TNBC. Meanwhile, transcription factor SOX5 activated transcriptionally circ_0084653. To sum up, SOX5-induced circ_0084653 promotes TNBC via the deubiquitination of USP36, which may provide some fresh ideas for TNBC-related molecular mechanisms.

Evaluation of prognostic risk factors of triple-negative breast cancer with 18F-FDG PET/CT parameters, clinical pathological features and biochemical indicators.

Introduction: Breast cancer is a heterogeneous disease comprising various molecular subtypes, including Luminal A, Luminal B, human epidermal growth factor receptor-2 (HER2) positive, and triple negative types, each with distinct biological characteristics and behaviors. Triple negative breast cancer (TNBC) remains a particularly challenging subtype worldwide. Our study aims to evaluate whether Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) parameters, clinical pathological features, and biochemical indicators serve as prognostic risk factors for TNBC. Additionally, we explore correlations between biochemical indicators and 18F-FDG PET/CT parameters. Methods: We conducted a retrospective analysis of 95 TNBC patients who underwent preoperative 18F-FDG PET/CT examinations at Tianjin Medical University Cancer Institute and Hospital from 2013 to 2018. Collected data included 18F-FDG PET/CT parameters, clinical and pathological features, and biochemical indicators. We used Kaplan-Meier survival analysis and multivariate Cox regression analysis to evaluate associations between 18F-FDG PET/CT parameters/biochemical indicators and disease free survival (DFS)/overall survival (OS). The log-rank test determined significant differences in survival curves, and the Spearman correlation coefficient analyzed correlations between quantitative variables. Visualization and analysis were performed using R packages. Results: Among 95 TNBC patients, mean standardized uptake value (SUVmean) was significantly correlated with DFS. Fasting blood glucose (FBG), α- L-fucosylase (AFU) and Creatine kinase (CK) were independent predictors of DFS, while Precursor albumin (PALB) and CK were independent predictors of OS. FBG showed correlations with SUVpeak and SUVmean, and CK was correlated with peak standardized uptake value (SUVpeak). Our results indicated that 18F-FDG PET/CT parameters and biochemical indicators may constitute a new prognostic model for TNBC patients post-surgery. Discussion: We found that SUVmean, FBG, AFU and CK are predictive factors for DFS in TNBC patients post-surgery, while PALB and CK are predictive factors for OS, which prompts us to pay more attention to these indicators in clinical practice. Also 18F-FDG PET/CT parameters and biochemical indicators have potential utility in constituting a new prognostic model for TNBC patients post-surgery.

2-year results and myocardial impact of transapical mitral valve repair in patients with primary mitral regurgitation: an echocardiographic study.

BACKGROUND: There is limited data on the 2-year outcomes of transapical transcatheter edge-to-edge repair (TA-TEER) using the ValveClamp in patients with severe primary mitral regurgitation (MR) and its impact on myocardial deformation. METHODS: From July 2018 to March 2021, 53 patients with symptomatic severe primary MR underwent TA-TEER were enrolled. The endpoint was the composite of all-cause mortality, recurrent 3 + or 4 + MR, or need for mitral surgery. RESULTS: Among the 53 patients who had successfully ValveClamp implantation, 8(15.1%) reached the composite endpoint. Significant improvement in left ventricular (LV) end-diastolic volume, pulmonary artery systolic pressure, NYHA functional class, and MR severity were observed (P < 0.05 for all). Univariate Cox's regression analysis revealed that LV end-diastolic volume index, LV end-systolic volume index, left atrial volume index, and pulmonary artery systolic pressure were associated with adverse events (P < 0.05 for all). On multivariate Cox regression analysis, left atrial volume index was independently associated with the endpoint (hazard ratio, 1.049; 95% CI, 1.009-1.091; P < 0.001) after adjustment for above echocardiographic parameters. LV global longitudinal strain and apical longitudinal strain in global and regional segments decreased at 30 days, but showed a recovery at 2 years with no significant difference compared to the baseline. CONCLUSION: TA-TEER using the ValveClamp presented favorable safety and efficacy at 2-year. Myocardial deformation impairment was observed at 30 days post-procedure, but did not persist at 2 years.

Continuous 3D Myocardial Motion Tracking via Echocardiography.

Myocardial motion tracking stands as an essential clinical tool in the prevention and detection of cardiovascular diseases (CVDs), the foremost cause of death globally. However, current techniques suffer from incomplete and inaccurate motion estimation of the myocardium in both spatial and temporal dimensions, hindering the early identification of myocardial dysfunction. To address these challenges, this paper introduces the Neural Cardiac Motion Field (NeuralCMF). NeuralCMF leverages implicit neural representation (INR) to model the 3D structure and the comprehensive 6D forward/backward motion of the heart. This method surpasses pixel-wise limitations by offering the capability to continuously query the precise shape and motion of the myocardium at any specific point throughout the cardiac cycle, enhancing the detailed analysis of cardiac dynamics beyond traditional speckle tracking. Notably, NeuralCMF operates without the need for paired datasets, and its optimization is self-supervised through the physics knowledge priors in both space and time dimensions, ensuring compatibility with both 2D and 3D echocardiogram video inputs. Experimental validations across three representative datasets support the robustness and innovative nature of the NeuralCMF, marking significant advantages over existing state-of-the-art methods in cardiac imaging and motion tracking. Code is available at: https://njuvision.github.io/NeuralCMF.

Serum HER2 Level Predicts Therapeutic Efficacy and Prognosis in Advanced Breast Cancer Patients.

Background: The purpose of this study was to investigate the therapeutic efficacy and prognosis of serum HER2 (sHER2) in patients with advanced breast cancer. Methods: We analyzed the sHER2 levels of 200 patients with advanced breast cancer receiving first or second line treatment, the tissue HER2 (tHER2) level was also analyzed. Indicators of therapeutic efficacy and prognosis were objective response rate (ORR), disease control rate (DCR), and time to progression (TTP). Results: The baseline sHER2 level was high in 132 patients and low in 68 patients. The high level of sHER2 is correlated with molecular subtype (p=0.016), visceral metastasis (p<0.001), liver metastasis (p<0.001), tissue HER-2 (tHER2) (p=0.001), and, among tHER2-low tumors (59 patients), the baseline sHER2 high level was associated with a higher proportion of brain metastasis. The ORR of patients with baseline sHER2 high level is higher than those with baseline sHER2 low level (p=0.026). The TTP of patients with baseline sHER2 low level is longer than the patients with baseline sHER2 high level (p=0.024). For patients with baseline sHER2 high level, a significant decrease in sHER2 after two cycles of treatment indicates higher ORR, DCR, and an extension of TTP. After multiple cycles of treatment, for patients with tHER-2 positive and baseline sHER2 high level, the DCR in the sHER2 decrease in the negative group was higher than that in the continuous positive group (p=0.037). Patients with a rapid decline type of sHER2 dynamic change curve had higher ORR and prolonged TTP compared with patients with other types of sHER2 dynamic change curve. There is no correlation between OS and sHER2 levels. Conclusion: Our study showed that patients with advanced breast cancer had a high level of sHER2 at recurrence, regardless of whether they are tHER2 positive or negative. Dynamic detection of sHER2 can help predict therapeutic efficacy and prognosis, regardless of whether tHER-2 is positive or negative.

HDAC inhibitors target IRS4 to enhance anti­AR therapy in AR­positive triple­negative breast cancer.

Triple­negative breast cancer (TNBC) is the most malignant subtype of breast cancer. Androgen receptor (AR) has been identified as a potential therapeutic target for AR­positive TNBC; however, clinical trials have not yet produced an effective treatment. The present study aimed to identify a novel treatment regimen to improve the prognosis of AR­positive TNBC. First, a combination of an AR inhibitor (enzalutamide, Enz) and a selective histone deacetylase inhibitor (chidamide, Chid) was used to treat AR­positive TNBC cell lines, and a synergistic effect of these drugs was observed. The combination treatment inhibited cell proliferation and migration by arresting the cell cycle at the G2/M phase. Subsequently, next­generation sequencing was performed to detect changes in gene regulation. The results showed that the PI3K/Akt signalling pathway was significantly inhibited by the combination treatment of Enz and Chid. Gene Set Enrichment Analysis revealed that the combination group was significantly enriched in KRAS signalling. Analysis of the associated genes revealed that insulin receptor substrate 4 (IRS4) may have a critical role in blocking the activation of KRAS signalling. In a mouse xenograft model, combination treatment also inhibited the PI3K/Akt signalling pathway by upregulating the expression of IRS4 and thereby suppressing tumour growth. In conclusion, the results of the present study revealed that combination treatment with Enz and Chid can upregulate IRS4, which results in the blocking of KRAS signalling and suppression of tumour growth. It may be hypothesised that the expression levels of IRS4 could be used as a biomarker for screening patients with AR­positive TNBC using Enz and Chid combination therapy.

Three-dimensional echocardiography reveals early mitral valve alterations in hypertrophic cardiomyopathy genetic mutation carriers.

BACKGROUND: The mitral valve undergoes structural modifications in response to cardiac functional changes, often predating cardiac decompensation and overt clinical signs. Our study assessed the potential of mitral valve morphological changes as early indicators for detecting carriers of hypertrophic cardiomyopathy (HCM)-associated gene mutations. METHODS: We studied 505 participants: 189 without the pathogenic gene mutations and left ventricular hypertrophy (G-/LVH-), 149 carriers without LV hypertrophy (G+/LVH-), and 167 manifest HCM patients (G+/LVH+). We juxtaposed the mitral valve morphology and associated metrics across these groups, emphasizing those carrying MYH7 and MYBPC3 mutations. RESULTS: We discerned pronounced disparities in the mitral annulus and leaflet structures across the groups. The mitral valve apparatus in mutation carriers exhibited a tendency towards a flattened profile. Detailed analysis spotlighted MYBPC3 mutation carriers, whose mitral valves were notably flatter (with notably lower AHCWR values than non-carriers); this contrast was not evident in MYH7 mutation carriers. This mitral valve flattening, manifest in the mutation carriers, suggests it might be an adaptive response to incipient cardiac dysfunction in HCM's nascent stages. CONCLUSIONS: Three-dimensional echocardiography illuminates the initial mitral valve structural changes in HCM patients bearing pathogenic gene mutations. These morphological signatures hold promise as sensitive imaging markers, especially for asymptomatic carriers of the MYBPC3 mutation.

Gene-echocardiography: refining genotype-phenotype correlations in hypertrophic cardiomyopathy.

AIMS: This study aims to clarify the association between hypertrophic patterns and genetic variants in hypertrophic cardiomyopathy (HCM) patients, contributing to the advancement of personalized management strategies for HCM. METHODS AND RESULTS: A comprehensive evaluation of genetic mutations was conducted in 392 HCM-affected families using Whole Exome Sequencing. Concurrently, relevant echocardiographic data from these individuals were collected. Our study revealed an increased susceptibility to enhanced septal and interventricular septal thickness in HCM patients harbouring gene mutations compared with those without. Mid-septal hypertrophy was found to be associated predominantly with myosin binding protein C3 (MYBPC3) variants, while a higher septum-to-posterior wall ratio correlated with myosin heavy chain 7 (MYH7) variants. Mutations in MYH7, MYBPC3, and other sarcomeric or myofilament genes (troponin I3 [TNNI3], tropomyosin 1 [TPM1], and troponin T2 [TNNT2]) showed a relationship with increased hypertrophy in the anterior wall, interventricular septum, and lateral wall of the left ventricle. In contrast, alpha kinase 3 (ALPK3)-associated hypertrophy chiefly presented in the apical region, while hypertrophy related to titin (TTN) and obscurin (OBSCN) mutations exhibited a uniform distribution across the myocardium. Hypertrophic patterns varied with the type and category of gene mutations, offering valuable diagnostic insights. CONCLUSION: Our findings underscore a strong link between hypertrophic patterns and genetic variants in HCM, providing a foundation for more accurate genetic testing and personalized management of HCM patients. The novel concept of 'gene-echocardiography' may enhance the precision and efficiency of genetic counselling and testing in HCM.

The mixed subtype has a worse prognosis than other histological subtypes: a retrospective analysis of 217 patients with metaplastic breast cancer.

OBJECTIVE: Metaplastic breast cancer (MpBC) is an aggressive subtype of all breast cancer. We aimed to investigate the clinicopathological features, treatments and prognoses of MpBC patients. METHODS: We collected the data from MpBC patients diagnosed at Tianjin Medical University Cancer Hospital from 2010 to 2017. Kaplan Meier curves and Cox regression model were used to evaluating clinical outcomes and prognostic factors. After removing baseline differences by propensity score matching (PSM), we analyzed the prognosis between MpBC patients and invasive ductal carcinomas of no special type (IDC-NST) patients. RESULTS: A total of 217 MpBC patients were subsumed. Of all histological subtypes, 45.1% were mixed subtypes, followed by with mesenchymal differentiation (27.2%), pure squamous (15.2%) and pure spindle (12.4%) subtypes. 69.6% of MpBC were triple-negative, 25.3% and 6.5% were HR-positive and HER2-positive. MpBC patients had worse survival compared to IDC-NST patients, with 5-year RFS of 73.8 and 83.6% (HR = 1.177 95%CI (1.171-2.676) P = 0.0068), and 5-year BCSS of 79.0% and 89.7% (HR = 2.187 95%CI (1.357-3.523) P = 0.0013). In the multivariate COX model, AJCC stage, mixed subtype and chemotherapy were independent prognostic factors. Mixed MpBC is more aggressive than pure and with heterologous mesenchymal differentiation subtypes. And whether squamous or spindle MpBC, mixed forms have shorter outcomes than pure forms. CONCLUSIONS: MpBCs are associated with poorer prognoses than IDC-NSTs. They are heterogeneous with different clinicopathological features and clinical outcomes between histological subtypes. Pure and with heterologous mesenchymal differentiation subtypes have more survival benefits than the mixed subtype.

Development of a nomogram based on serum cytokine-related riskscore in breast cancer.

Background: Cytokines are involved in many inflammatory diseases and thus play an important role in tumor immune regulation. In recent years, researchers have found that breast cancer is not only related to genetic and environmental factors, but also to the chronic inflammation and immunity. However, the correlation between serum cytokines and blood tests indicators remain unclear. Methods: A total of 84 serum samples and clinicopathological data of breast cancer patients from Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin, P. R. China were collected. The expression levels of the 12 cytokines were detected by immunofluorescence method. Blood tests results were obtained from medical records. By stepwise Cox regression analysis, a cytokine-related gene signature was generated. Univariate and multivariate Cox regression were used to analyze the influence on the prognosis of patients. A nomogram was constructed to illustrate the cytokine-related riskscore predicting 5-year OS, which was further evaluated and validated by C-index and ROC curve. The correlation between the expression of cytokines in serum and other blood indicators was studied by using Spearman's test. Results: The riskscore was calculated as IL-4×0.99069 + TNF-α×0.03683. Patients were divided into high and low risk groups according to the median riskscore, with the high-risk group has a shorter survival time by log-rank test (training set, P=0.017; validation set, P=0.013). Combined with the clinical characteristics, the riskscore was found to be an independent factor for predicting the OS of breast cancer patients in both training cohort (HR=1.2, P<0.01) and validation cohort (HR=1.6, P=0.023). The 5-year C-index and AUC of the nomogram were 0.78 and 0.68, respectively. IL-4 was further found to be negatively correlated with ALB. Conclusion: In summary, we have developed a nomogram based on two cytokines including IL-4 and TNF-α to predict OS of breast cancer and investigated their correlation with blood test indicators.

Clinicopathological Features and Prognosis of Gastrointestinal Metastases From Breast Carcinoma: A Clinicopathological Study of 22 Patients.

Background. Breast carcinoma is the most common malignancy in women. Gastrointestinal metastasis is rarely found or diagnosed in patients with breast cancer. Methods. Clinicopathological features, treatment options, and prognosis were evaluated retrospectively for 22 patients with gastrointestinal metastases of breast carcinoma in Chinese women. Results. Presenting symptoms were non-specific: anorexia (21/22), epigastric pain (10/22), and vomiting (8/22), and 2 patients (2/22) presented with nonfatal hemorrhage. The first sites of metastases were skeleton (9/22), stomach (7/22), colorectal (7/22), lung (3/22), peritoneal (3/22), and liver (1/22). ER, PR, GATA binding protein 3 (GATA3), gross cystic disease fluid protein-15 (GCDFP-15), and keratin 7 can effectively confirm the diagnosis, especially in the case of keratin 20 negativity. Histology showed mainly ductal breast carcinoma (n = 11) was the predominant source of gastrointestinal metastases in this study, and lobular breast cancer (n = 9) accounted for a considerable proportion. The disease control rate to systemic therapy was 81% (17 of 21 treated patients), and the objective response rate was 10% (2 of 21 treated patients). Median overall survival was 71.5 months (range, 22-226 months), median survival for distant metastases was 23.5 months (range, 2-119 months) and the median survival for the time of gastrointestinal metastases diagnosis was 6 months (range, 2-73 months). Conclusions. Performing the endoscopy with biopsy was crucial for patients with any subtle gastrointestinal symptoms and a history of breast cancer. It is important to distinguish primary gastrointestinal carcinoma from breast metastatic carcinoma in order to select the optimal initial treatment and avoid unnecessary surgery.

Coupled Co-Doped MoS2 and CoS2 as the Dual-Active Site Catalyst for Chemoselective Hydrogenation.

Catalytic hydrogenation plays an important role in the industrial production of fine chemicals. Herein, we report a Co-doped MoS2 and CoS2 composite with a coupling interface and successfully apply it for the chemoselective hydrogenation of p-chloronitrobenzene to p-chloroaniline. The target catalyst 0.5CoMoS has ∼100% conversion and ∼100% selectivity. Experiments and theoretical calculations reveal that CoS2 is more favorable for adsorbing and activating H2 and provides active hydrogen (Ha) to Co-doped MoS2 by the coupling interface. By matching the production and consumption rates of Ha, the maximization of the reaction yield was achieved. This work may promote the study of MoS2-based catalysts for chemoselective hydrogenation.

Case report: Camrelizumab associated with central retinal vein occlusion.

Immunotherapy has revolutionized cancer treatment and become one of the five pillars of cancer therapy. The clinical applications of immunotherapy have been adapted to range from the management of melanoma to most tumor types. As the clinical applications of cancer immunotherapies expand, understanding the treatment-related adverse events of these drugs becomes critical in clinical practice. We report a rare case of ocular immune-related side effects associated with camrelizumab that resulted in vision loss. A 56-year-old male patient was diagnosed with small cell lung cancer. The tumor involved the porta pulmonis and mediastinum upon initial diagnosis; therefore, surgery was not possible. Upon receiving the 10th immunotherapy session with camrelizumab 200 mg, the patient's visual acuity began to decrease in his right eye and a central retinal vein occlusion. Optical coherence tomography revealed significant cystoid exudation in the macular area and vitreous hemorrhage. The patient underwent vitrectomy, phacoemulsification and intraocular lens implantation after symptom onset. Following surgery, the patient's vision was limitedly restored. This is the first clinical report in China of central retinal vein occlusion and vitreous hemorrhage associated with anti-PD-1 therapy, ultimately leading to blindness. Although rare, clinical practitioners should be concerned about ocular adverse events associated with anti-PD-1 immunotherapy and develop a high index of suspicion for this possibility since ophthalmic manifestations that are rapidly detected, closely monitored, and appropriately managed are treatable.

Drug-induced liver injury in COVID-19 treatment: Incidence, mechanisms and clinical management.

The COVID-19 outbreak triggered a serious and potentially lethal pandemic, resulting in massive health and economic losses worldwide. The most common clinical manifestations of COVID-19 patients are pneumonia and acute respiratory distress syndrome, with a variety of complications. Multiple organ failure and damage, ultimately leading to patient death, are possible as a result of medication combinations, and this is exemplified by DILI. We hope to summarize DILI caused by the antiviral drugs favipiravir, remdesivir, lopinavir/ritonavir, and hydroxychloroquine in COVID-19 patients in this review. The incidence of liver injury in the treatment of COVID-19 patients was searched on PubMed to investigate DILI cases. The cumulative prevalence of acute liver injury was 23.7% (16.1%-33.1%). We discuss the frequency of these events, potential mechanisms, and new insights into surveillance strategies. Furthermore, we also describe medication recommendations aimed at preserving DILI caused by treatment in COVID-19 patients.

Whole-genome bisulfite sequencing analysis of circulating tumour DNA for the detection and molecular classification of cancer.

BACKGROUND: Cancer cell-specific variation and circulating tumour DNA (ctDNA) methylation are promising biomarkers for non-invasive cancer detection and molecular classification. Nevertheless, the applications of ctDNA to the early detection and screening of cancer remain highly challenging due to the scarcity of cancer cell-specific ctDNA, the low signal-to-noise ratio of DNA variation, and the lack of non-locus-specific DNA methylation technologies. METHODS: We enrolled three cohorts of breast cancer (BC) patients from two hospitals in China (BC: n = 123; healthy controls: n = 40). We developed a ctDNA whole-genome bisulfite sequencing technology employing robust trace ctDNA capture from up to 200 µL plasma, mini-input (1 ng) library preparation, unbiased genome-wide coverage and comprehensive computational methods. RESULTS: A diagnostic signature comprising 15 ctDNA methylation markers exhibited high accuracy in the early (area under the curve [AUC] of 0.967) and advanced (AUC of 0.971) BC stages in multicentre patient cohorts. Furthermore, we revealed a ctDNA methylation signature that discriminates estrogen receptor status (Training set: AUC of 0.984 and Test set: AUC of 0.780). Different cancer types, including hepatocellular carcinoma and lung cancer, could also be well distinguished. CONCLUSIONS: Our study provides a toolset to generate unbiased whole-genome ctDNA methylomes with a minimal amount of plasma to develop highly specific and sensitive biomarkers for the early diagnosis and molecular subtyping of cancer.

Cardiac safety analysis of anti-HER2-targeted therapy in early breast cancer.

To evaluate the cardiac safety of anti-HER2-targeted therapy for early breast cancer; to investigate whether trastuzumab combined with pertuzumab increases cardiac toxicity compared with trastuzumab; to evaluate the predictive value of high-sensitivity Troponin (hs-TnI) and QTc for the cardiotoxicity associated with anti-HER2 targeted therapy in early breast cancer. A total of 420 patients with early-stage HER2-positive breast cancer who received trastuzumab or trastuzumab combined with pertuzumab for more than half a year in Tianjin Medical University Cancer Hospital from January 2018 to February 2021 were included. Left ventricle ejection fraction (LVEF), hs-TnI values, and QTc were measured at baseline and 3, 6, 9, 12 months. Cardiotoxicity was defined as a decrease in LVEF of at least 10 percentage points from baseline on follow-up echocardiography. Cardiotoxicity developed in 67 of the 420 patients (15.9%) and all patients had LVEF above 50% before and after treatment. The incidence of cardiotoxicity in trastuzumab and trastuzumab combined with pertuzumab was 14.3% and 17.9%, respectively (P > 0.05). Logistic regression analysis showed that age, coronary heart disease, left chest wall radiotherapy, and anthracyclines sequential therapy were independent risk factors for cardiotoxicity (P < 0.05). The value of hs-TnI and QTc at the end of treatment (12th month) were selected for ROC curve prediction analysis and the area under the ROC curve was 0.724 and 0.713, respectively, which was significantly different from the area of 0.5 (P < 0.05). The decrease of LVEF in the study was mostly asymptomatic, from the heart safety point of view, the anti-HER2 targeted therapy for early breast cancer was well tolerated. Trastuzumab combined with pertuzumab did not significantly increase cardiotoxicity. However, subgroup analysis suggests that in the presence of coronary artery disease (CAD) and sequential treatment with anthracene, trastuzumab and pertuzumab may increase the cardiac burden compared with trastuzumab. Hs-TnI and QTc may be useful in monitoring and predicting cardiotoxicity associated with anti-HER2 targeted therapy for early breast cancer.

Ado-trastuzumab emtansine in the treatment of lung adenocarcinoma with ERBB2 mutation: a case report and literature review.

The erb-b2 receptor tyrosine kinase 2 (ERBB2), also known as HER2, has long been recognized as an oncogenic driver in some breast and gastroesophageal cancers, and ERBB2-targeted therapies are standard for ERBB2-positive breast and gastric cancer. However, there are currently no standard therapies targeting the ERBB2 pathway in non-small cell lung cancer. Recently, somatic mutations in ERBB2 have been reported in 2-3% of patients with advanced lung adenocarcinoma, these mutations are trans-forming in lung cancer models and result in kinase activation, conferring some in-vitro sensitivity to trastuzumab. The ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate composed of trastuzumab joined via a stable linker to DM1. In this report, a 67-year-old male patient was diagnosed with advanced lung adenocarcinoma with multiple lymph node metastases, and multi-chemotherapy and immunotherapy were not effective. The results of genetic testing indicated a non-frameshift insertion mutation in exon 20 of the ERBB2 gene. The patients received T-DM1 at a dose of 3.6 mg/kg by intravenous infusion every 21 days until for 12 cycles. Partial response appeared in the tumor lesions after treatment for four cycles, and PET-computer tomography showed the tumor lesions were effectively controlled, and the efficacy evaluation was complete response after treatment for six cycles. Although the patient experienced second degree of thrombocytopenia during the treatment, the corresponding symptomatic treatment was taken, and the platelets could return to normal before the next cycle of T-DM1. Follow-up review showed the patient is in good health and the tumor has not recurred.