Volume 103 · Issue 42 · 2023

The field of oncology has made remarkable progress over the past two decades. With the aging of the population, the number of cancer survivors is increasing. At the same time, cancer therapy-related cardiovascular toxicity (CTR-CVT) has become an important cause that seriously affects the quality of life and survival of cancer patients. In this context, cardio-oncology, an emerging interdisciplinary field, emerged. The types and treatment strategies of oncological diseases are heterogeneous, and the management of cancer patients also requires the participation of multiple disciplines. Currently, there are still insufficient clinical research and evidence-based practice in the field of cardio-oncology, resulting in a lack of standardization in its diagnosis and treatment. Additionally, the training model of physicians in cardio-oncology is still being explored. This article provides a comprehensive exploration of the opportunities and challenges faced by physicians and researchers in the field of cardio-oncology. It also delves into the prevailing landscape of clinical research in China and outlines the future training model for physicians in cardio-oncology.

Venous thromboembolism (VTE) is a formidable disease that poses a serious threat to the health and well-being of hospitalized patients. Owing to its high incidence, debilitating morbidity, and alarming mortality rates, VTE has gained increasing attention from the clinical medicine community worldwide. Unfortunately, the current state of clinical prevention and treatment of VTE is not very optimistic, necessitating the establishment of large disease-specific databases and real-world studies, which can accumulate effective evidence-based medical evidence to gradually standardize the clinical prevention and treatment and quality control of VTE. The construction and development of large medical databases depend greatly on standardized datasets, which establish the conceptual data models of VTE through data standardization routes, set the object classes according to the model, define the attributes of the classes, standardize the data types and property values, and organize the standardized data elements. This article focuses on providing an in-depth overview of the unique characteristics of various domestic and foreign VTE datasets, describing their application and research progress in VTE, as well as the role of datasets in standardizing clinical and research practices to strengthen quality control and artificial intelligence. Through this comprehensive discussion, we hope to promote the establishment of VTE datasets and enable their use in high-quality large real-world studies.

Cardiovascular disease (CVD) and cancer are two intimately interconnected conditions with leading causes of mortality worldwide. Emerging evidence suggests that CVD and cancer have common risk factors and share genetics and molecular mechanisms. With recent advancements in diagnosis and treatment, the number of long-term survivors have been continuously increasing. However, cancer patients have significantly higher cardiovascular mortality than general population, mostly resulting from cardiotoxic side effects of anticancer treatments. The prevalence and severity of cardiotoxicity and vascular abnormalities led to the emergence of a clinical branch of cardiology, known as cardio-oncology. Immune checkpoint inhibitors (ICIs) are currently widely used for treatment of various types of cancers. Recent studies suggest that ICIs lead to cardiotoxicity including myocarditis with an incidence of 0.04%-2.4% and a mortality of 25%-50%. However, the molecular and pathophysiologic mechanisms underlying the cardiovascular toxicity induced by ICIs are poorly understood. Therefore, this article combines the recent research results of the pathophysiology of cardiovascular toxicity induced by ICIs and explores novel diagnostic, monitoring, and therapeutic approaches to improve cardiac function and prevent cardiovascular injury.

Acute kidney injury (AKI), a common and severe disease, is associated with a high risk of developing chronic kidney disease (CKD) and end-stage renal disease (ESRD), which is a global health burden with high morbidity and mortality. Although many foreign clinical practice guidelines have standardized the management and treatment of AKI, there is a lack of overall guidance for AKI which is suitable for our national conditions. Thus, an expert group in related fields were organized by the National Clinical Research Center for Kidney Diseases and Chinese Nephrologist Association to collaborate to complete the Chinese Clinical Practice Guideline for Acute Kidney Injury based on the latest existing evidence-based medical evidence both domestically and internationally. The guideline systematically introduces the definition and epidemiological feature, diagnosis and monitoring of AKI, pharmacological approaches to prevent or treat AKI, and management of renal replacement therapy, management of AKI on special populations, and the outcome and prognosis of AKI, aiming to provide reasonable recommendations for all level clinicians in China.

Cardiovascular damage caused by cancer treatment has become an important cause of death for tumor survivors. With the recognition of cardiovascular diseases and cancer therapy-related cardiovascular toxicity (CTR-CVT) in tumor patients, noninvasive imaging technologies play pivotal roles in the risk stratification, early diagnosis, monitoring and follow-up for CTR-CVT. In recent years, the field of cardio-oncology has witnessed continual updates in diagnostic and therapeutic strategies, with several pertinent guidelines and expert consensus documents issued in China and abroad. However, there remains a conspicuous absence of systematic guidance documents on the application of imaging techniques in the clinical practice of cardio-oncology. Therefore, the Chinese Anti-Cancer Association Society of Integrative Cardio-oncology, the Ultrasound Branch of the Chinese Medical Association, and the Chinese Society of Echocardiography convened experts to formulate the"Chinese guideline for the clinical application of noninvasive imaging technology in accessing cancer therapy-related cardiovascular toxicity". Building upon the systematic evaluation of guidelines and the latest evidence-based medical research in the field of cardio-oncology domestically and abroad, and in conjunction with data derived from evidence-based medical research in China, this guideline proposes noninvasive imaging examination methods and monitoring strategies for CTR-CVT, aiming to further standardize and guide the clinical practice of multidisciplinary physicians specializing in cardio-oncology in China.

To investigate the role of neutrophil extracellular traps (NETs) in immune checkpoint inhibitor-associated myocarditis (ICIAM) with programmed death protein-1 (PD-1) inhibitors involvement, and to explore the therapeutic potential of targeting NETs in the treatment of ICIAM.

Thirty 6-week-old male BALB/c mice were randomly divided into control group (n=10), myocarditis group (n=10), and treatment group (n=10). Apart from the control group, each mouse was subcutaneously injected with 100 μl of complete Freund′s adjuvant containing 250 μg of mouse cardiac troponin I peptide on the 1st and 7th day. Starting on the 8th day, PD-1 inhibitor (15 μg/per mouse) was intraperitoneally injected every other day for a total of 5 times. Since 1 day before the beginning of PD-1+TnI injection, the treatment group was injected with PF-1355 (50 mg·kg^-1·d^-1) for 16 consecutive days. The mice′s general state was observed during the whole process. Real-time fluorescence quantitative PCR (RTFQ-PCR) was carried out to evaluate the transcriptional regulation of neutrophil related chemokines, NETs, pyronecrosis related factors and proinflammatory cytokines. Immunohistochemistry, immunofluorescence and western blot were applied to determine the changes of pyrosis related molecules. Echocardiography showed the differences of main cardiac indexes while cardiac pathology compared the degree of inflammatory infiltration in 3 gruops.

The immunofluorescence intensity of myocardial NETs in the myocarditis group was significantly increased compared to the control group mice (2.49±0.08 and 0.99±0.26, P<0.001). The protein expression levels of pyroptosis-related NLRP3, cleaved-Caspase 1, Caspase 1, cleaved-GSDMD, GSDMD, IL-1β and IL-18 in myocardial tissue of the model group were higher than those of the control group (all P<0.05). After treatment with PF-1355, compared to the myocarditis group, the left ventricular ejection fraction (LVEF) (73.58%±5.31% and 58.12%±3.19%, P<0.001) and left ventricular fraction shortening (LVFS) (39.78%±4.31% and 33.89%±2.19%, P<0.001) increased. H-E staining showed a reduction in inflammatory infiltration area in the treatment group compared to the myocarditis group (30.12%±3.57% and 14.92%±2.46%, P<0.001). The immunofluorescence intensity of NETs decreased in the treatment group compared to the myocarditis group (2.52±0.04 and 1.03±0.05, P<0.001). The levels of NLRP3 and other pyroptosis-related molecules were downregulated in the treatment group compared to the myocarditis group (all P<0.05).

NETs lead to myocardial cell pyroptosis by activating the NLRP3 inflammasome in PD-1 inhibitor-associated myocarditis. The specific MPO inhibitor PF-1355 shows a therapeutic potential by regulating the formation of NETs, decreasing NLRP3 level and relieving myocardial pyroptosis, thus reducing myocardial damage.

To analyze the clinical characteristics of patients with severe immune checkpoint inhibitors (ICIs) related myocarditis.

A retrospective study was conducted on the 50 patients with ICIs-related myocarditis in the multidisciplinary cardio-oncology clinic of Zhongshan Hospital affiliated to Fudan University from April 2020 to April 2022. The age of patients was (63.7±10.8) years old, including 37 males and 13 females. The patients were divided into the mild group (n=37) and the severe group (n=13) according to severity. The differences of basic characteristics, clinical manifestations, laboratory tests, auxiliary examination, combined irAEs, treatment and outcomes between the two groups of patients were analyzed.

The immunotherapy time [M(Q₁,Q₃)] of patients in the mild group and severe group were 81 (49, 134) and 24 (20, 116) days, respectively (P<0.05). In the severe group, the levels of cTnT [0.605 (0.317, 1.072) μg/L], NT-proBNP [1 126 (386, 1 744) ng/L], CK-MB [78 (48, 238) U/L], and CK-MM [240 (45, 6 543) U/L] were higher than those in the mild group [0.104 (0.045, 0.189) μg/L, 237 (39, 785) ng/L, 24 (20, 33) U/L, 108 (72, 168) U/L, respectively] (all P<0.05). The left ventricular ejection fraction of the severe group [64% (57%, 65%)] was lower than that of the mild group [66% (63%, 69%)] (P<0.05), and the incidence of conduction block (n=4, 4/13) and abnormal ventricular wall motion (n=4, 4/13), the incidence of ICIs-related myositis (n=10, 10/13), ICIs-related hepatitis (n=4, 4/13) and ICIs-related neurotoxicity (n=4, 4/13) were higher than those in the mild group (n=1, 2.7%; n=2, 5.4%; n=16, 43.2%; n=2, 5.4%; n=1, 2.7%, respectively) (all P<0.05). The proportion of patients receiving intensified immunosuppressive therapy and mortality rate in the severe group were 12/13 (n=12) and 4/13 (n=4), which were both higher than those in the mild group [10.8% (n=4) and 0] (both P<0.05).

The incidence of ICIs-related myocarditis is not high, but the severe rate and mortality are high. The differential diagnosis of severe ICIs related myocarditis should be combined with myocardial markers, electrocardiogram and echocardiogram, and early diagnosis and treatment can improve the prognosis of patients.

This study aimed to evaluate the associations between the number of cardiovascular risk factor goals achieved with all-cause mortality, atherosclerotic cardiovascular diseases (ASCVD)-related mortality, and cancer-related mortality amongst cancer patients.

From 2006 to 2020, a total of 2 079 individuals with newly diagnosed cancer, free of ASCVD, were enrolled in this study from the Kailuan cohort. Patients were classified into three groups (group 1,≤1 risk factor at goal, n=407; group 2, 2 risk factors at goal, n=865; group 3,≥3 risk factors at goal, n=807) according to the control status of blood pressure, fasting blood glucose, low-density lipoprotein cholesterol and high-sensitivity C-reactive protein, using health checkup results of the latest survey after cancer diagnosis. Multivariable Cox regression analyses were performed to examine the associations between the number of risk factors at goals with all-cause mortality, ASCVD-related mortality, and cancer-related mortality.

The mean age at diagnosis was (60.4±10.4) years, and 71.2% were male. During a median follow-up of 2.95 (1.38, 5.12) years, 600 cases of all-cause mortality, 63 cases of ASCVD-related mortality, and 314 cases of cancer-related mortality were observed. After adjusting for age, gender, education level, smoking status, alcohol consumption, salt intake, physical activity, body mass index, triglyceride, high-density lipoprotein cholesterol, family history of cardiovascular diseases, antihypertensive drugs, hypoglycemic drugs, lipid-lowering drugs, and anti-cancer medications, compared with cancer patients achieving ≤1 risk factor goal, those achieving ≥3 risk factor goals showed significantly decreased risk of all-cause mortality, ASCVD mortality, and cancer mortality, with HR (95%CI) of 0.68 (0.54-0.86), 0.35 (0.16-0.77), and 0.60 (0.43-0.82), respectively (all P values <0.05). Significant relationships between the number of risk factor goals achieved and decreased mortality of all kinds were observed (all P values for trend<0.05). Results of the subgroup analyses suggested that the associations between the number of risk factor goals achieved and lower mortality of all kinds were more prominent among individuals who were ≥60 years, male, and those with respiratory and reproductive cancers (all P values <0.05).

This study suggested a significant association between the number of cardiovascular risk factor goals achieved and survival in cancer patients, especially amongst those who were older, male, with respiratory cancers and reproductive cancers.

To evaluate the association between digestive tract cancer and anatomical severity of coronary artery disease.

This study enrolled 142 patients with digestive tract cancer who underwent coronary angiography in the Department of Cardiology of the First Medical Center of Chinese PLA General Hospital from 2009 to 2020 as the cancer group. The patients in cancer group were matched with 426 non-cancer patients who underwent coronary angiography at our hospital during the same period in a 1∶3 ratio based on gender and age. All enrolled patients had no previous history of percutaneous coronary intervention or coronary artery bypass grafting surgery. The severity of coronary artery disease was documented and assessed using the SYNTAX score based on angiogram. High SYNTAX score (SXhigh) was defined as SYNTAX score≥22 (upper quartile), while low SYNTAX score (SXlow) was SYNTAX score<22. High NLR (NLRhigh) was NLR≥2.287 (median), while low NLR (NLRlow) was NLR<2.287. The association between digestive tract cancer and severity of coronary artery disease was analyzed using logistic regression analysis.

This study included a total of 568 patients, with a mean age of (66.6±8.7) years. Among them, 430 patients (75.7%) were male. The cancer group consisted of 142 patients with digestive tract cancers, with a mean age of (66.5±8.4) years. The non-cancer group consisted of 426 patients, with a mean age of (66.7±8.8) years. The proportion of SXhigh in patients with digestive tract cancers (33.1%, 47 patients) was higher than that in non-cancer patients (23.9%, 102 patients) (P=0.032). Compared to non-cancer patients, SXhigh in patients with digestive tract cancers was higher (OR: 1.614, 95%CI: 1.051-2.481, P=0.029). Subgroup analysis stratified by NLR levels revealed that in the NLRhigh group, patients with digestive tract cancers exhibited a higher severity of coronary artery disease compared to non-cancer patients, with an OR of 1.948 (95%CI: 1.005-3.779, P=0.048). In the NLRlow group, there was no significant relationship between digestive tract cancers and the severity of coronary artery disease, with an OR of 1.277 (95%CI: 0.586-2.781, P=0.538).

Digestive tract cancer is associated with the severity of coronary artery disease, and patients with digestive tract cancers have a higher risk of severe coronary artery disease than non-cancer patients. Additionally, there is an association between digestive tract cancers and the severity of coronary artery disease under conditions of high levels of inflammation.

To evaluate the hemostatic efficacy, safety and immunogenicity of recombinant human thrombin in the treatment of liver wounds that still ooze after conventional surgical hemostasis.

A multicenter, stratified randomized, double-blind, placebo-controlled phase Ⅲ trial with a planned enrollment of 510 subjects at 33 centers, with a 2∶1 randomization to the thrombin group versus the placebo group. An interim analysis will be conducted after approximately 70% of the subjects have completed the observation period. The primary efficacy endpoint was the rate of hemostasis within 6 minutes at the point of bleeding that could be evaluated. Safety analysis was performed one month after surgery, and the positive rates of anti-drug antibody (ADA) and neutralizing antibody were evaluated.

At the interim analysis, a total of 348 subjects had been randomized and received the study drug (215 were male and 133 were female). They were aged 19-69 (52.9±10.9)years. Among them, 232 were in the thrombin group and 116 were in the placebo group, with balanced and comparable demographics and baseline characteristics between the two groups. The hemostasis rate at 6 minutes was 71.6% (95%CI:65.75%-77.36%) in the thrombin group and 44.0% (95%CI: 34.93%-53.00%) in the placebo group, respectively (P<0.001). No grade≥3 drug-related adverse events and no drug-related deaths were reported from the study.No recombinant human thrombin-induced immunologically-enhanced ADA or immunologically-induced ADA was detected after topical use in subjects.

Recombinant human thrombin has shown significant hemostatic efficacy and good safety in controlling bleeding during liver resection surgery, while also demonstrating low immunogenicity characteristics.

To explore the predictive effect of the renal tumor scoring system on the surgical outcomes of cystic renal masses (CRM).

A retrospective analysis was performed on the data of 234 patients who received robotic-assisted partial nephrectomy (RAPN) treatment in the First Affiliated Hospital of Xi′an Jiaotong University from January 2018 to June 2020. And 31 cases had CRM and 203 cases had solid renal masses (SRM). The propensity score of patients was calculated by logistic regression model, and 1∶2 matching was performed by the nearest neighbor method. The changes in perioperative indexes and long-term estimated glomerular filtration rate (eGFR) in CRM group and SRM group were compared. The CRM group and SRM group were stratified according to the complexity grading of R.E.N.A.L. score and PADUA score, respectively, to compare the difference in the achievement rate of ideal surgical outcome between the two groups, and analyze the predictive factors affected. The CRM diameter was stratified with 4 cm as the cut-off value (CRM1 group with a diameter<4 cm, CRM2 group with a diameter≥4 cm), and the surgical results were compared with the matched SRM1 group and SRM2 group.

In the matching cohort, the CRM group comprised 29 patients with a mean age of (48.7±10.8) years, of which 22 (75.9%) were males. The SRM group included 58 patients with a mean age of (50.4±10.2) years, of which 41 (70.7%) were males, with no statistically significant difference (all P>0.05). The warm ischemia time (WIT) [M (Q₁,Q₃)] in the CRM group was longer than that in the SRM group [23(18, 25) vs 19(17, 25) min, P=0.040]. The operation time (OT) [M (Q₁,Q₃)] in the CRM group was also longer than that of the SRM group [130(100, 150) vs 108(86, 120) min, P=0.006]. The change in serum creatinine before and after the operation [M (Q₁,Q₃)] was higher in the CRM group than in the SRM group [15(10, 23) vs 12(6, 17) μmol/L, P=0.030]. The ideal surgical outcomes were achieved in 7 patients (24.1%) in the CRM group and 36 patients (62.1%) in the SRM group. The number of patients achieving ideal surgical outcomes in R.E.N.A.L. intermediate complex surgery and PADUA advanced complex surgery in the SRM group were 24 (58.5%) and 15 (51.7%), respectively, which were higher than those in the CRM group 6 (27.3%) and 1 (5.9%) respectively (P<0.05). Preoperative eGFR (OR=0.758, 95%CI: 0.719-0.799) and the nature of the tumor (CRM as reference, OR=4.883, 95%CI: 1.550-15.378) were influencing factors for achieving the ideal surgical outcome. Subgroup analysis showed that eGFR changes before and after surgery and the estimated blood loss (EBL) in the CRM2 group were higher than those in the SRM2 group, and WIT and OT were longer than those in the SRM2 group (all P<0.05). The EBL and WIT of the CRM1 group were shorter than those of the CRM2 group (P<0.05).

The surgical risk of RAPN in complex CRMs with a maximum diameter of≥4 cm is higher than the risk of RAPN in SRM with equivalent R.E.N.A.L. and PADUA scores.

Two patients with heart disease complicated with SMARCA4 deletion pulmonary tumor were reported. Case 1 went to the doctor due to dizziness and was diagnosed with SMARCA4 deletion right lung tumor and brain metastasis; Previous diagnosis of dilated cardiomyopathy and atrial fibrillation; He has survived for more than 17 months after receiving cardiac treatment, tumor radiotherapy and targeted therapy. Case 2 went to the doctor for cough and expectoration, and was diagnosed as an undifferentiated tumor of right lung with SMARCA4 deletion, with RET fusion and KEAP1 mutation; Previous history of atrial fibrillation; After the patients received chemotherapy and targeted therapy successively, the tumors progressed for a short time and eventually died, with a survival period of 7 months.

Single cell sequencing, as a new generation sequencing technology for sequencing RNA and DNA at the single cell level, has been widely used in all aspects of rhinological diseases through its excellent ability in analyzing cell-level problems. This review aims to discuss the basic principles and application status of single cell sequencing technology in rhinology, analyze the clinical guidance significance of single cell sequencing technology in rhinology diseases from the single cell level, and prospect the future application direction of this technology in rhinology.

Osteosarcoma and Ewing's sarcoma are common clinical malignant bone tumors, and their onset age is frequent<30 years old, the main treatment mode was surgery combined with systemic chemotherapy, and the chemotherapy regimen included high-dose anthracyclines. Observing the occurrence of anthracycline-related heart failure in such patients is helpful for people to find out the objective law of this type of cardiotoxicity, and it is helpful to improve its prevention and treatment level.

Three factors, such as clinical characteristics of tumor patients, tumor stage, and anti-tumor therapy (especially anti-vascular endothelial growth factor antibodies such as bevacizumab and tyrosine kinase inhibitors), can cause endothelial cell dysfunction and hypercoagulability, which increases the risk of arterial thrombotic events (ATE) in tumor patients. Although the use of low molecular weight heparin for the treatment of venous thromboembolism (VTE) has been shown to be safe and effective in ambulatory tumor patients, whether anticoagulant therapy is equally beneficial for the prevention of ATE is unclear.

Anthracyclines can lead to dose-related myocardial damage and tumor treatment-related cardiac insufficiency (CTRCD) while improving survival for multiple cancers. Cardiac CARE is a multicenter, prospective, randomized, open, blinded endpoint clinical trial to observe whether carvedilol and candesartan combination therapy guided by high-sensitivity troponin can prevent left ventricular dysfunction in patients at high risk for CTRCD during anthracycline chemotherapy.

Article "Clinical Practice Guidelines for Transarterial Chemoembolization (TACE) Treatment of Hepatocellular Carcinoma in China (2023 Edition)", Vol. 103, No. 34, 2023, Chinese Journal of Medicine, Page 2679 "Recommended angiographic validation at least 5 min after the end of embolization to accurately assess the efficacy of embolization (Evidence Level 1, Recommended Strength A)", "Evidence Level 1" here should be "Evidence Level 5", and the 59th reference here should be "de Baere T, Arai Y, Lencioni R, et al. Treatment of Liver Tumors with Lipiodol TACE: Technical Recommendations from Experts Opinion [J]. Cardiovasc Intervent Radiol, 2016, 39 (3): 334-343. DOI: 10.1007/s00270-015-1208-y. "; The reviewing expert "Jin Guiyun (Hainan Provincial People's Hospital)" should be "Jin Guiyun (the First Affiliated Hospital of Hainan Medical College)"; Page 2682 "Carrelizumab" shall be "Carrelizumab". Corrections are hereby made.