IL-2Rα is a potential biomarker for heart failure diagnosis of patients with end-stage renal disease and haemodialysis.

AIMS: Heart failure (HF) is a leading cause of mortality in patients with end-stage renal disease (ESRD) undergoing haemodialysis. Identifying novel predictors of HF is essential for improving diagnostic precision and enhancing patient outcomes. METHODS: This study included 68 participants from the Haemodialysis Centre at the Second Hospital of Tianjin Medical University. Clinical characteristics and echocardiographic data were collected and analysed. We measured the plasma of 44 cytokines to investigate their correlation with cardiac function and their potential as HF biomarkers. RESULTS: In the HF with reduced ejection fraction (HFrEF) group, the levels of several cytokines, including stem cell growth factor-ß (SCGF-ß), C-X-C motif chemokine 10 (CXCL10), interleukin-1α (IL-1α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-16 (IL-16), interleukin-1 receptor antagonist protein (IL-1Ra), interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), leukaemia inhibitory factor (LIF), C-C motif chemokine 3 (CCL3), interleukin-10 (IL-10), interleukin-2 receptor subunit alpha (IL-2Rα), tumour necrosis factor ligand superfamily member 10 (TNFSF10), macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF), were significantly increased, while C-C motif chemokine 11 (CCL11)/eotaxin levels were decreased compared with those in the control group (P < 0.05). Receiver operating characteristic (ROC) curve analysis highlighted TNF-α [area under the ROC curve (AUC) = 0.85, odds ratio (OR) = 1.080, 95% confidence interval (CI): 1.033-1.128, P = 0.001], IFN-γ (AUC = 0.84, OR = 1.836, 95% CI: 1.289-2.615, P = 0.003) and IL-2Rα (AUC = 0.82, OR = 1.022, 95% CI: 1.009-1.035, P = 0.001) as excellent predictors for HFrEF in haemodialysis patients with ESRD, and they outperformed soluble suppression of tumourigenicity-2 (sST2) but slightly underperformed N-terminal pro-brain natriuretic peptide (NT-proBNP). IL-2Rα (AUC = 0.77, OR = 1.018, 95% CI: 1.007-1.030, P = 0.001) demonstrated superior diagnostic capabilities when distinguishing patients with HF with left ventricular ejection fraction (LVEF) <50% from controls. IL-2Rα emerged as a robust biomarker for left ventricular HF, while TNF-α (AUC = 0.89, OR = 1.140, 95% CI: 1.039-1.250, P = 0.005) showed promise in assessing HF severity in patients with ESRD. IL-2Rα (AUC = 0.80, OR = 1.017, 95% CI: 1.007-1.027, P = 0.001) also significantly predicted right ventricular systolic dysfunction. During a median follow-up of 14 months, 10 patients (14.7%) experienced all-cause mortality. Multivariate Cox regression analysis confirmed that plasma IL-2Rα was an independent predictor of all-cause death [hazard ratio (HR): 1.010, 95% CI: 1.001-1.020, P = 0.039] after adjusting for other variables. CONCLUSIONS: This study underscores the potential of IL-2Rα as a valuable biomarker for HF diagnosis and management in haemodialysis patients with ESRD and contributes to our understanding of this high-risk population.

Clinical and electrocardiographic characteristics of immune checkpoint inhibitor-related myocarditis.

BACKGROUND: Immune checkpoint inhibitor (ICI) has become a major breakthrough in the field of tumor therapy, leading to improved survival. This study evaluated the clinical and electrocardiographic characteristics of patients with ICI-related myocarditis. METHODS: Patients with ICI-related myocarditis were enrolled from 4 centers in China until September 2023. Demographic data (age, sex, comorbidity), types of ICI, clinical manifestations, electrocardiogram (ECG) and treatment were analyzed retrospectively. Arrhythmia and characteristics of ECG were compared according to prognosis and grading. RESULTS: A total of 29 participants (13 females with a median age of 63.25 years) with ICI-related myocarditis were enrolled. Lung cancer was the most, with a proportion of 31.03 % (9/29). The median time from the first administration of ICI to the diagnosis of myocarditis was 50 days. Camrelizumab was the main type of ICI (9/29). Most patients had non-specific symptoms, dyspnea (n = 16) and palpitation (n = 9) were common. The overall mortality rate was 37.93 % (11/29) with a median follow-up of 9(4,11) days. Compared with the survivors, P-wave abnormality was more common in participants who were dead (24.14 %vs6.90 %, p = 0.010). A total of 19 patients with severe ICI-related myocarditis were included in this study. The proportions of sinus tachycardia (34.48 %vs0.00 %, p = 0.005), premature ventricular complex (27.59 %vs0.00 %, p = 0.027) and atrioventricular block (34.48 %vs3.45 %, p = 0.044) were higher in severe ICI-related myocarditis. CONCLUSIONS: Clinical manifestations of ICI-related myocarditis usually lacked specificity. ECGs can be manifested as new-onset arrhythmias, ST-T segment changes, fragmented QRS complex, abnormal P wave, prolonged QTc interval and multi­lead low voltage.

Carboxylated mesoporous silica nanoparticle-nucleic acid chimera conjugate-assisted delivery of siRNA and doxorubicin effectively treat drug-resistant bladder cancer.

Chemotherapy is the main treatment for bladder cancer, but drug resistance and side effects limit its application and therapeutic effect. Herein, we constructed doxorubicin (DOX)/COOH-mesoporous silica nanoparticle/polyethylenimine (PEI)/nucleic acid chimeras (DOX/MSN/Chimeras) to reduce the toxicity of chemotherapy drugs and the resistance of bladder cancer cells. Transmission electron microscopy showed that PEI was coated on the DOX/MSN/BSA nanoparticles with a diameter of about 150 nm. DOX/MSN/PEI could control DOX release for over 48 h, and the sudden release rate was significantly lower than DOX/MSN. Immunohistochemical results showed that DOX/MSN/Chimera specifically bound to bladder cancer cells, and markedly inhibited PI3K expression and proliferation of DOX-resistant bladder cancer cells. DOX/MSN/Chimera promoted the apoptosis of drug-resistant bladder cancer cells, which was superior to DOX/MSN/Aptamer or DOX/MSN. We further carried out animal experiments and found that DOX/MSN/Chimera could reduce the volume of transplanted tumors in vivo. Compared with DOX/MSN/Aptamer group, the proliferation rate was significantly decreased and the proportion of apoptotic cells was highly increased. Through the histological observation of kidneys and lungs, we believed that DOX/MSN/Chimera can effectively reduce the damage of chemotherapy drugs to normal tissues. In conclusion, we constructed a COOH-MSN/nucleic acid chimera conjugate for the targeted delivery of siRNA and anti-cancer drugs. Our study provides a new method for personalized and targeted treatment of drug-resistant bladder cancer.

Prognostic value of cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis: A systematic review and meta-analysis.

Background: Immune checkpoint inhibitors (ICI) are increasingly used in the first-line treatment of malignant tumors. There is increasing recognition of their cardiotoxicity and, in particular, their potential to lead to myocarditis. Cardiovascular magnetic resonance (CMR) can quantify pathological changes, such as myocardial edema and fibrosis. The purpose of this systematic review and meta-analysis was to examine the evidence for the roles of CMR in predicting prognosis in ICI-associated myocarditis. Methods: PubMed, Cochrane Library, and Web of Science databases were searched until October 2023 for published works investigating the relationship between CMR parameters and adverse events in patients with ICI-associated myocarditis. The analysis included studies reporting the incidence of late gadolinium enhancement (LGE), T1 values, T2 values, and CMR-derived left ventricular ejection fraction (LVEF). Odds ratios (OR) and weighted mean differences (WMD) were combined for binary and continuous data, respectively. Newcastle-Ottawa Scale was used to assess the methodological quality of the included studies. Results: Five cohort studies were included (average age 65-68 years; 25.4% female). Of these, four studies were included in the meta-analysis of LGE-related findings. Patients with major adverse cardiovascular events (MACE) had a higher incidence of LGE compared with patients without MACE (OR = 4.18, 95% CI: 1.72-10.19, p = 0.002). A meta-analysis, incorporating data from two studies, showed that patients who developed MACE exhibited significantly higher T1 value (WMD = 36.16 ms, 95% CI: 21.43-50.89, p < 0.001) and lower LVEF (WMD = - 8.00%, 95% CI: -13.60 to -2.40, p = 0.005). Notably, T2 value (WMD = -0.23 ms, 95% CI: -1.86 to -1.39, p = 0.779) was not associated with MACE in patients with ICI-related myocarditis. Conclusions: LGE, T1 value, and LVEF measured by CMR imaging have potential prognostic value for long-term adverse events in patients with ICI-related myocarditis.

Microcirculatory dysfunction in hypertrophic cardiomyopathy with chest pain assessed by angiography-derived microcirculatory resistance.

Chest pain, a common initial symptom in hypertrophic cardiomyopathy (HCM) patients, is closely linked to myocardial ischemia, despite the absence of significant coronary artery stenosis. This study explored microvascular dysfunction in HCM patients by employing angiography-derived microcirculatory resistance (AMR) as a novel tool for comprehensive assessment. This retrospective analysis included HCM patients with chest pain as the primary symptom and control patients without cardiac hypertrophy during the same period. The AMR was computed through angiography, providing a wire-free and adenosine-free index for evaluating microcirculatory function. Propensity score matching ensured balanced demographics between groups. This study also investigated the correlation between the AMR and clinical outcomes by utilizing echocardiography and follow-up data. After matching, 76 HCM patients and 152 controls were analyzed. While there was no significant difference in the incidence of epicardial coronary stenosis, the AMR of three epicardial coronary arteries was markedly greater in HCM patients. The criterion of an AMR ≥ 250 mmHg*s/m was that 65.7% of HCM patients experienced coronary microvascular dysfunction (CMD). Independent risk factors for CMD included increased left ventricular (LV) wall thickness (OR = 1.209, 95% CI 1.013-1.443, p = 0.036). Furthermore, an AMR_LAD ≥ 250 mmHg*s/m had an increased cumulative risk of the endpoint (log-rank p = 0.023) and was an independent risk factor for the endpoint (HR = 11.64, 95% CI 1.13-120.03, p = 0.039), providing valuable prognostic insights.

Postoperative QRS duration to left ventricular end-diastolic diameter ratio as a predictor for the risk of postoperative atrial fibrillation in cardiac surgery: A single-center prospective study.

Background and aims: Postoperative atrial fibrillation (POAF) is a frequent complication following cardiac surgery and is associated with adverse clinical outcomes. Our study aimed at determining the clinical and echocardiographic predictors of POAF in patients with cardiac surgery and management of this group of patients may improve their outcome. Methods: We prospectively enrolled patients from the department of cardiovascular surgery in the Second Hospital of Tianjin Medical University from October 23, 2020 to October 30, 2022, without a history of atrial fibrillation. Cox regression was used to identify significant predictors of POAF. Results: A total of 217 patients (79 [36.41 %] were female, 63.96 ± 12.32 years) were included. 88 (40.55 %) patients met the criteria for POAF. Cox regression showed that preoperative left atrial diameter (LAD) (HR: 1.040, 95 % CI 1.008-1.073, p = 0.013) and postoperative QRS/LVEDD (HR: 0.398, 95 % CI 0.193-0.824, p = 0.013) and E/e' (HR: 1.029, 95 % CI 1.002-1.057，p = 0.033) were predictors of POAF. Conclusion: Preoperative LAD and postoperative QRS/LVEDD and E/e' were predictors of POAF in patients undergoing cardiac surgery. Trial registration site: http://www.chictr.org.cn. Registration number: ChiCTR2200063344.

Cardiovascular adverse events associated with immune checkpoint inhibitors: A retrospective multicenter cohort study.

BACKGROUND: Over the past decade, immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, ICIs inevitably may cause a spectrum of immune-related adverse events, among which cardiovascular toxicity, particularly myocarditis, while infrequent, has garnered increasing attention due to its high fatality rate. METHODS: We conducted a multicenter retrospective study to characterize ICI-associated cardiovascular adverse events. Logistic regression was performed to explore the risk factors for the development of myocarditis and severe myocarditis. Receiver operating characteristic curves were conducted to assess the diagnostic abilities of cardiac biomarkers to distinguish different cardiovascular toxicities, and the performance and calibration were evaluated using Hosmer-Lemeshow test. RESULTS: Forty-four patients were identified, including thirty-five myocarditis, five heart failure, three arrhythmias, and one myocardial infarction. Compared with other patients, myocarditis patients had higher cardiac troponin-I (cTnI) levels (p < 0.001), higher creatine kinase levels (p = 0.003), higher creatine kinase isoenzyme-MB (CK-MB) levels (p = 0.013), and shorter time to the incidence of adverse cardiovascular events (p = 0.022) after ICI treatment. Twenty-one patients (60%) were classified as severe myocarditis, and they presented higher cardiac troponin I (cTnI) levels (p = 0.013), higher N-terminal pro-B-type natriuretic peptide levels (p = 0.031), higher creatine kinase levels (p = 0.018), higher CK-MB levels (p = 0.026), and higher neutrophil to lymphocyte ratio (NLR) levels (p = 0.016) compared to non-severe myocarditis patients after ICI treatment. Multivariate logistic regression showed that CK-MB (adjusted odds ratio [OR]: 1.775, 95% confidence interval [CI]: 1.055-2.984, p = 0.031) was the independent risk factor of the development of ICI-associated myocarditis, and cTnI (adjusted OR: 1.021, 95% CI: 1.002-1.039, p = 0.03) and NLR (adjusted OR: 1.890, 95% CI: 1.026-3.483, p = 0.041) were the independent risk factors of ICI-associated severe myocarditis. The receiver operating characteristic curve showed an area under curve of 0.785 (95% CI: 0.642 to 0.928, p = 0.013) for CK-MB, 0.765 (95% CI: 0.601 to 0.929, p = 0.013) for cTnI, and 0.773 for NLR (95% CI: 0.597 to 0.948, p = 0.016). CONCLUSIONS: Elevated CK-MB after ICI treatment is the independent risk factor for the incidence of ICI-associated myocarditis, and elevated cTnI and NLR after ICI treatment are the independent risk factors for the development of ICI-associated severe myocarditis. CK-MB, cTnI, and NLR demonstrated a promising predictive utility for the identification of ICI-associated myocarditis and severe myocarditis.

CNP Ameliorates Macrophage Inflammatory Response and Atherosclerosis.

BACKGROUND: CNP (C-type natriuretic peptide), an endogenous short peptide in the natriuretic peptide family, has emerged as an important regulator to govern vascular homeostasis. However, its role in the development of atherosclerosis remains unclear. This study aimed to investigate the impact of CNP on the progression of atherosclerotic plaques and elucidate its underlying mechanisms. METHODS: Plasma CNP levels were measured in patients with acute coronary syndrome. The potential atheroprotective role of CNP was evaluated in apolipoprotein E-deficient (ApoE-/-) mice through CNP supplementation via osmotic pumps, genetic overexpression, or LCZ696 administration. Various functional experiments involving CNP treatment were performed on primary macrophages derived from wild-type and CD36 (cluster of differentiation 36) knockout mice. Proteomics and multiple biochemical analyses were conducted to unravel the underlying mechanism. RESULTS: We observed a negative correlation between plasma CNP concentration and the burden of coronary atherosclerosis in patients. In early atherosclerotic plaques, CNP predominantly accumulated in macrophages but significantly decreased in advanced plaques. Supplementing CNP via osmotic pumps or genetic overexpression ameliorated atherosclerotic plaque formation and enhanced plaque stability in ApoE-/- mice. CNP promoted an anti-inflammatory macrophage phenotype and efferocytosis and reduced foam cell formation and necroptosis. Mechanistically, we found that CNP could accelerate HIF-1α (hypoxia-inducible factor 1-alpha) degradation in macrophages by enhancing the interaction between PHD (prolyl hydroxylase domain-containing protein) 2 and HIF-1α. Furthermore, we observed that CD36 bound to CNP and mediated its endocytosis in macrophages. Moreover, we demonstrated that the administration of LCZ696, an orally bioavailable drug recently approved for treating chronic heart failure with reduced ejection fraction, could amplify the bioactivity of CNP and ameliorate atherosclerotic plaque formation. CONCLUSIONS: Our study reveals that CNP enhanced plaque stability and alleviated macrophage inflammatory responses by promoting HIF-1α degradation, suggesting a novel atheroprotective role of CNP. Enhancing CNP bioactivity may offer a novel pharmacological strategy for treating related diseases.

Complexities of Coexisting Cardiac Amyloidosis and Coronary Artery Disease: A Contemporary Review of Diagnostic and Treatment Approaches.

Cardiac amyloidosis (CA) represents an emerging challenge in cardiovascular medicine, with notable clinical overlaps and diagnostic complexities when coexisting with coronary artery disease (CAD). This integrative review navigates the intricate terrain of CA and CAD, elucidating epidemiology, clinical presentations, and diagnostic considerations. Examining both immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis, we underscore their shared demographic associations, diagnostic intricacies, and potential diagnostic confounders with CAD. Notably, we emphasize the impact of CA on epicardial coronary arteries and the consequential implications for coronary microcirculation. Further exploration reveals the connection between CA and acute myocardial infarction, emphasizing early recognition as pivotal. In terms of differential diagnosis, we underscore the significance of clinical symptoms, electrocardiography, echocardiography, cardiac magnetic resonance, and bone scintigraphy. Additionally, we scrutinize the intricate realm of treatment, encompassing medication selection, antithrombotic strategies, and revascularization modalities. Our review addresses the distinctive challenges posed by CA patients' limited tolerance for conventional therapies. This comprehensive synthesis serves as an invaluable resource for clinicians confronting the intricate intersection of CA and CAD. By offering insights into diagnostic refinement and innovative therapeutic avenues, we aim to enhance patient outcomes and quality of life within this complex clinical landscape.

Piezo-enhanced near infrared photocatalytic nanoheterojunction integrated injectable biopolymer hydrogel for anti-osteosarcoma and osteogenesis combination therapy.

Preventing local tumor recurrence while promoting bone tissue regeneration is an urgent need for osteosarcoma treatment. However, the therapeutic efficacy of traditional photosensitizers is limited, and they lack the ability to regenerate bone. Here, a piezo-photo nanoheterostructure is developed based on ultrasmall bismuth/strontium titanate nanocubes (denoted as Bi/SrTiO3), which achieve piezoelectric field-driven fast charge separation coupling with surface plasmon resonance to efficiently generate reactive oxygen species. These hybrid nanotherapeutics are integrated into injectable biopolymer hydrogels, which exhibit outstanding anticancer effects under the combined irradiation of NIR and ultrasound. In vivo studies using patient-derived xenograft models and tibial osteosarcoma models demonstrate that the hydrogels achieve tumor suppression with efficacy rates of 98.6 % and 67.6 % in the respective models. Furthermore, the hydrogel had good filling and retention capabilities in the bone defect region, which exerted bone repair therapeutic efficacy by polarizing and conveying electrical stimuli to the cells under mild ultrasound radiation. This study provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration of osteosarcoma.

Long-term efficacy and safety of cryoballoon ablation of atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis evaluated long-term efficacy and safety of cryoballoon ablation (CB) of atrial fibrillation (AF). METHODS: PubMed, Cochrane Library, and Web of Science were searched until July 31, 2023, for published works investigating efficacy and safety of CB of AF in which mean/median follow-up time was not less than 36 months. Safety was assessed by adverse events. Efficacy was assessed by AF recurrence, defined as any atrial arrhythmias lasting more than 30 s. RESULTS: A total of 19 clinical studies were included. After an average of 58.1 months of follow-up, the overall AF recurrence rate was about 37%. The predictors of recurrence were duration of AF (HR 1.00; 95% CI [1.00 ∼ 1.01]), early recurrence of atrial fibrillation (HR 3.96; 95%CI [1.12 ∼ 14.02]), left atrial diameter (HR 1.04; 95%CI [1.02 ∼ 1.06]), and persistent AF (HR1.47; 95% CI [1.19 ∼ 1.82]). In terms of safety, the incidence of transient phrenic paralysis (PNP) was the highest, about 3%; followed by vascular complications (about 2%); pseudoaneurysm, permanent PNP, and all-cause death was (about 1%); and pericardial effusion and stroke / TIA was very low. CONCLUSION: CB is associated with low rates of severe complications and reasonable success rates.

Carboxypeptidase E is a prognostic biomarker co-expressed with osteoblastic genes in osteosarcoma.

Osteosarcoma (OS) is a rare primary malignant bone tumor in adolescents and children with a poor prognosis. The identification of prognostic genes lags far behind advancements in treatment. In this study, we identified differential genes using mRNA microarray analysis of five paired OS tissues. Hub genes, gene set enrichment analysis, and pathway analysis were performed to gain insight into the pathway alterations of OS. Prognostic genes were screened using the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, then overlapped with the differential gene dataset. The carboxypeptidase E (CPE) gene, found to be an independent risk factor, was further validated using RT-PCR and Gene Expression Omnibus (GEO) datasets. Additionally, we explored the specific expression of CPE in OS tissues by reanalyzing single-cell genomics. Interestingly, CPE was found to be co-expressed with osteoblast lineage cell clusters that expressed RUNX2, SP7, SPP1, and IBSP marker genes in OS. These results suggest that CPE could serve as a prognostic factor in osteoblastic OS and should be further investigated as a potential therapeutic target.

Dysglycemia and arrhythmias.

Disorders in glucose metabolism can be divided into three separate but interrelated domains, namely hyperglycemia, hypoglycemia, and glycemic variability. Intensive glycemic control in patients with diabetes might increase the risk of hypoglycemic incidents and glucose fluctuations. These three dysglycemic states occur not only amongst patients with diabetes, but are frequently present in other clinical settings, such as during critically ill. A growing body of evidence has focused on the relationships between these dysglycemic domains with cardiac arrhythmias, including supraventricular arrhythmias (primarily atrial fibrillation), ventricular arrhythmias (malignant ventricular arrhythmias and QT interval prolongation), and bradyarrhythmias (bradycardia and heart block). Different mechanisms by which these dysglycemic states might provoke cardiac arr-hythmias have been identified in experimental studies. A customized glycemic control strategy to minimize the risk of hyperglycemia, hypoglycemia and glucose variability is of the utmost importance in order to mitigate the risk of cardiac arrhythmias.

Associations between modifiable risk factors and frailty: a Mendelian randomisation study.

BACKGROUND: Early identification of modifiable risk factors is essential for the prevention of frailty. This study aimed to explore the causal relationships between a spectrum of genetically predicted risk factors and frailty. METHODS: Univariable and multivariable Mendelian randomisation (MR) analyses were performed to explore the relationships between 22 potential risk factors and frailty, using summary genome-wide association statistics. Frailty was accessed by the frailty index. RESULTS: Genetic liability to coronary artery disease (CAD), type 2 diabetes mellitus (T2DM), ischaemic stroke, atrial fibrillation and regular smoking history, as well as genetically predicted 1-SD increase in body mass index, systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol, triglycerides, alcohol intake frequency and sleeplessness were significantly associated with increased risk of frailty (all p<0.001). In addition, there was a significant inverse association between genetically predicted college or university degree with risk of frailty (beta -0.474; 95% CI (-0.561 to -0.388); p<0.001), and a suggestive inverse association between high-density lipoprotein cholesterol level with risk of frailty (beta -0.032; 95% CI (-0.055 to -0.010); p=0.004). However, no significant causal associations were observed between coffee consumption, tea consumption, serum level of total testosterone, oestradiol, 25-hydroxyvitamin D, C reactive protein or moderate to vigorous physical activity level with frailty (all p>0.05). Results of the reverse directional MR suggested bidirectional causal associations between T2DM and CAD with frailty. CONCLUSIONS: This study provided genetic evidence for the causal associations between several modifiable risk factors with lifetime frailty risk. A multidimensional approach targeting these factors may hold a promising prospect for prevention frailty.

Case report: reuse of tirofiban leads to very severe thrombocytopenia.

Background: Telofiban is a class of small molecule non-peptide tyrosine derivatives containing RGD sequences. It is the only platelet surface glycoprotein (GP) IIb/IIIa receptor antagonist (GPI) currently marketed in China. In patients with ST-segment elevation myocardial infarction(STEMI) who receive percutaneous coronary intervention (PCI) with a heavy thrombotic load, postoperative intravenous tirofiban can prevent complications of myocardial ischemia due to sudden coronary artery occlusion. With the increase in the clinical use of tirofiban, the number of adverse reactions related to thrombocytopenia induced by tirofiban has gradually increased. Still, most of them have thrombocytopenia after the first use. We report one case of very severe thrombocytopenia following the reuse of tirofiban. Case summary: A 65-year-old man of Han nationality, 170 cm in height, 85 kg in weight, and 29.4 BMI, suffered from cerebral infarction 13 years ago and left with right limb movement disorder. Five days before this hospitalization, the patient underwent PCI, and three stents were implanted. After the operation, anti-platelet tirofiban and nadroparin calcium were given, and no thrombocytopenia was found. The patient still retains 80% stenosis due to anterior descending branches and plans to undergo PCI again half a month later. The patient with a history of hypertension, type 2 diabetes, diabetic nephropathy, and cerebral infarction usually took 100 mg of aspirin and 75 mg of clopidogrel, antiplatelet therapy, and had no history of food and drug allergy. One day after discharge, the patient suddenly felt chest tightness and wheezing. The laboratory showed hypersensitivity troponin 2.85 ng/ml (normal 0-0.0268 ng/ml), and the admission ECG showed ST-T changes in leads I, aVL, V5-V6. On the 6th day of hospitalization, PCI was performed, a stent was implanted in the proximal section of the anterior descending branch opening, and tirofiban(10 ug/kg, 3 min bolus, then 0.1 ug/kg/min) antiplatelet therapy was given after surgery. About 10 min after the tirofiban infusion, the patient suddenly shivered, accompanied by convulsions, accompanied by elevated body temperature (up to 39.4°C), accompanied by epistaxis and microscopic hematuria. An urgent blood test showed that the platelets dropped to 1 × 109/L, tirofiban and aspirin stopped immediately, and the antiplatelet therapy of clopidogrel was retained. After infusion of methylprednisolone sodium succinate and gamma globulin, the patient's platelets gradually recovered, and the patient was successfully discharged seven days later in stable condition. Conclusion: This case is typical of severe thrombocytopenia caused by reusing tirofiban. This case may provide new insights into: 1. Patients who did not have thrombocytopenia after the first use of tirofiban may still have extremely severe thrombocytopenia after re-exposure to tirofiban. Routine platelet count monitoring and early identification of thrombocytopenia are the essential links. 2. Thrombocytopenia caused by re-exposure to tirofiban may have a faster onset, deeper degree, and slower recovery due to antibodies retained after the first exposure to tirofiban; 3. Platelet transfusions may not be necessary for patients with severe thrombocytopenia; 4. Immunosuppressants help suppress the body's immune response, promote platelet recovery, and can be reduced or discontinued when platelets rise and may be safe; 5. After tirofiban for PCI, continuing the maintenance dose of clopidogrel may be safe if the patient has no significant bleeding events.

Long-Term Atherosclerotic Cardiovascular Disease Risk in Patients With Cancer: A Population-Based Study.

The long-term risk of incident atherosclerotic cardiovascular diseases (ASCVD) among cancer patients remains incompletely defined. This study aimed to evaluate the long-term ASCVD risk in cancer patients compared with the noncancer population. This was a prospective population-based study using data from the Kailuan cohort, 6204 individuals with newly diagnosed cancer, free of ASCVD, were matched in a 1:1 ratio to noncancer controls for age (±1) and sex, from June 2006 to December 2020. Multivariable competing risk analyses were performed to evaluate the association between cancer diagnosis and risk of incident ASCVD events (including myocardial infarction, ischemic stroke, heart failure, and revascularization with coronary artery bypass graft surgery or percutaneous coronary intervention). During a median follow-up of 5.3 (1.7, 9.7) years, 1019 incident ASCVD events were observed. Compared to participants without cancer, there was a similar risk for incident ASCVD events among cancer patients within the first few years after cancer diagnosis, and the risk declined over time. Overall, cancer patients showed lower risks of incident ASCVD compared to the noncancer patients over the long term, with a hazard ratio (95% confidence interval) of 0.52 (0.45-0.60) for composite ASCVD events, 0.43 (0.35-0.53) for ischemic stroke, 0.63 (0.42-0.95) for myocardial infarction, 0.63 (0.48-0.83) for heart failure, and 0.82 (0.60-1.11) for coronary revascularization. Baseline level of low-density lipoprotein cholesterol, fasting blood glucose, blood pressure, and high-sensitivity C-reactive protein could independently predict the incident ASCVD among the study population. Subgroup analyses according to cancer types revealed a significantly lower risk of ASCVD events among patients with digestive cancer or respiratory cancer compared with noncancer controls, but not for urologic or genital cancer. Multiple sensitivity analyses yielded similar results to the primary analysis. Long-term ASCVD risk among cancer survivors is not increased compared with the noncancer individuals, probably driven by a favorable profile of baseline risk factor in cancer population.

Radiotherapy-induced malfunctions of cardiac implantable electronic devices: A meta-analysis.

BACKGROUND: Radiation therapy (RT) may pose acute and long-term risks for patients with cardiac implantable electronic devices (CIEDs), including pacemakers (PMs) and implantable cardioverter-defibrillators (ICDs). OBJECTIVE: We conducted a systematic review and meta-analysis to examine the association between RT and PM/ICD malfunctions in patients with cancer. METHODS: We searched the literature using the PubMed, the Cochrane Library the Web of Science, and Embase for relative publications until April 2022. Of the 550 initially identified studies, 17 retrospective observational studies including 2454 patients were finally analyzed. RESULTS: The meta-analysis showed that RT was associated with an increased risk of ICD malfunctions (odds ratio [OR] 2.75; 95% confidence interval [CI] 1.74-4.33). Five studies were included in the subgroup analysis regarding photon beam energy, showing that radiation-induced CIED failure was more likely to occur in ICDs when beam energy was ≥10 MV (OR 5.28; 95% CI 2.14-13.03). Neutron-generating RT significantly increased the risk of CIED malfunctions (OR 3.97; 95% CI 1.70-9.26), especially the risk of reset (OR 5.79; 95% CI 2.37-14.12; P = .0001). We did not find significant differences in the risk of CIED failure between chest RT and other RT sites (OR 1.09; 95% CI 0.63-1.88). CONCLUSION: Our meta-analysis suggests that ICDs are more likely to be affected by RT than PMs. These adverse events, especially reset, in patients with cancer were associated with neutron-generating RT and beam energy ≥10 MV. Given the increasing requirement for RT in several patients with cancer as well as the increasing implantation rates of CIEDs, a better risk stratification is needed in this setting.

Electrocardiographic Features of Immune Checkpoint Inhibitor-Associated Myocarditis.

Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events including myocarditis, whilst improving cancer-related outcomes. There is thus a clinical need to identify electrocardiographic manifestations of ICI-related myocarditis to guide clinical management. PubMed was searched for clinical studies and case reports describing electrocardiographic changes in patients with ICI-related myocarditis. A total of 6 clinical studies and 79 case reports were included. This revealed a range of presentations for patients on ICIs, including supraventricular arrhythmias, ventricular arrhythmias and heart block, and new changes of ST-T segment unrelated to coronary artery disease, ST-segment elevation or depression and T-wave abnormalities. Several patients showed low voltages in multiple leads and new onset Q-wave development. Patients with ICI-related myocarditis may develop new arrhythmia and ST-T changes, and infrequently low voltages in multiple leads.

"Ghost imaging" in pericardial cavity: Disappeared "tumor-like" masses in tuberculous pericarditis.

A 66-year-old woman was admitted to our hospital due to chest distress and shortness of breath during 1 week. Transthoracic echocardiography (TTE) revealed massive pericardial effusion and multiple, irregular and high-density echo "tumor-like" masses on the heart, with the largest one on the apex. However, there were no masses found by computed tomography (CT) scan, except for increased lipids around the coronary artery. We performed emergency pericardiocentesis and drainage to relieve symptoms. The positron emission tomography/CT (PET/CT) also showed several ununiformly high accumulations in pericardial cavity. However, the high-density echo "tumor-like" masses cannot be seen by TTE after pericardiocentesis, and also cannot be detected when surgery. Pericardiotomy was performed due to severe pericardial adhesion. The diagnosis of tuberculosis (TB) was confirmed by pericardiotomy and pericardial biopsy.