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Abstract Background Treatment strategy against immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) frequently requires other immunosuppressive agents. Tofacitinib is a rapidly acting JAK-STAT inhibitor with proven efficacy in multiple autoimmune diseases. We aimed to evaluate the efficacy and safety of tofacitinib in the management of irAEs in cancer patients. Methods Cancer patients who received ICIs and were treated with tofacitinib for the management of irAEs at 6 institutions were retrospectively included in this study. Demographic and clinical characteristics were obtained from electronic medical records. Longitudinal assessment of cardiac troponin T (cTnT) with clinical assessment was utilized to evaluate the benefit of tofacitinib treatment in patients with ICI myocarditis. Overall survival (OS) was also assessed. Results Fifty-three patients were included in this study. The median time from irAE onset to tofacitinib therapy was 17 (range, 2–186) days and the median duration of tofacitinib treatment was 52.5 (range, 3–277) days. Enrolled patients were subdivided into 3 groups based on clinical severity and steroid responsiveness including 11 life-threatening cases, 30 steroid-resistant cases, and 12 cases with steroid taper failure. Clinical remission rate in each group was 54.5%, 96.7%, and 100%, respectively (P

Abstract Background Pulmonary vein perforation is an uncommon complication during cardiac intervention. We present a rare case of pulmonary vein perforation into the respiratory tract with systemic air embolism during left atrial appendage closure (LAAC). Case presentation A 77-year-old man with persistent nonvalvular atrial fibrillation was referred for percutaneous LAAC under local anaesthesia (CHA2DS2-VASc score of 4, HAS-BLED score of 3, and prior ischaemic stroke). During the procedure, after delivering a super-stiff guidewire into the left superior pulmonary vein (LSPV), the patient suddenly developed a severe cough with haemoptysis upon advancement of a delivery sheath along the guidewire. Fluoroscopy showed signs of blood entering the left main bronchus, and fast transthoracic echocardiography revealed bubbles in the left heart without pericardial effusion. The procedure was terminated because of a major complication indicated by the repeated haemoptysis and headache, and haemostatic drugs were immediately administered. Subsequent chest computed tomography angiography (CTA) revealed a filling defect in the LSPV branches and bubbles in the aorta. The patient was transferred to the critical care unit for haemostasis and antibacterial treatment. Transthoracic echocardiography later that day showed no bubbles in the heart. The headache and haemoptysis significantly abated the following day. The bubbles in the aorta disappeared on chest CTA 7 days later. Conclusions Interventional cardiologists should pay attention to anatomical variations of the pulmonary vein, which are associated with a high risk of complications of pulmonary vein perforation during LAAC. Preoperative CTA examination and intraoperative transoesophageal echocardiography might be helpful to avoid this complication.

Thrombin is an important ischemia/reperfusion injury (IRI) mediator in patients with ST-elevation myocardial infarction (STEMI). This study examines the use of bivalirudin, a direct thrombin inhibitor, in reducing IRI in STEMI patients. STEMI patients (n = 21) were treated with bivalirudin and compared to 21 patients treated with unfractionated heparin (UFH) from the EARLY Assessment of Myocardial Tissue Characteristics by CMR in STEMI (EARLY-MYO-CMR) registry (NCT03768453). Infarct size (IS) and left ventricular ejection fraction (LVEF) were comparable between the two groups at follow up. During the first cardiac magnetic resonance (CMR) scan within the first week after percutaneous coronary intervention (PCI), all patients in both the bivalirudin and UFH groups exhibited myocardial edema. However, the myocardium edema volume was significantly less in the bivalirudin group (p < 0.05). At the one-month follow-up, a smaller proportion of patients in the bivalirudin group than in the UFH group exhibited myocardial edema (4.7% vs. 33.3%, p < 0.05). At the three-month follow-up, myocardial edema had completely resolved in the bivalirudin group, while it persisted in two patients in the UFH group. The incidence and volume of microvascular obstruction (MVO) were significantly lower in the bivalirudin group during the acute phase. Additionally, the incidence of intramyocardial hemorrhage (IMH) was significantly lower in the bivalirudin group during both the acute and follow up (p < 0.05). These findings were corroborated by T2 and T1 mapping results. The study concluded that the use of bivalirudin for anticoagulation is associated with attenuated IRI in STEMI patients who receive primary PCI.

Myocardial fibrosis, a common pathophysiological consequence of various cardiovascular diseases, is characterized by fibroblast activation and excessive deposition of extracellular matrix (ECM) collagen. Accumulating evidence indicates that myocardial fibrosis contributes to ventricular stiffness, systolic and diastolic dysfunction, and ultimately leads to the development of heart failure (HF). Early detection and targeted treatment of myocardial fibrosis is critical to reverse ventricular remodeling and improve clinical outcomes in patients with cardiovascular diseases. However, despite considerable progresses made in understanding molecular mechanisms of myocardial fibrosis, non-invasive imaging to assess myocardial fibrosis and guide clinical treatment is still not widely available, limiting the development of innovative treatment strategies. This review summarizes recent progresses of imaging modalities for detecting myocardial fibrosis, with a focus on nuclear medicine, echocardiography and cardiac magnetic resonance (CMR).

Receptor tyrosine kinases (RTKs) are a class of membrane spanning cell-surface receptors that transmit extracellular signals through the membrane to trigger diverse intracellular signaling through tyrosine kinases (TKs), and play important role in cancer development. Therapeutic approaches targeting RTKs such as vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), and platelet-derived growth factor receptor (PDGFR), and TKs, such as c-Src, ABL, JAK, are widely used to treat human cancers. Despite favorable benefits in cancer treatment that prolong survival, these tyrosine kinase inhibitors (TKIs) and monoclonal antibodies targeting RTKs are also accompanied by adverse effects, including cardiovascular toxicity. Mechanisms underlying TKI-induced cardiovascular toxicity remain unclear. The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed chanzyme consisting of a membrane-based ion channel and intracellular α-kinase. TRPM7 is a cation channel that regulates transmembrane Mg2+ and Ca2+ and is involved in a variety of (patho)physiological processes in the cardiovascular system, contributing to hypertension, cardiac fibrosis, inflammation, and atrial arrhythmias. Of importance, we and others demonstrated significant cross-talk between TRPM7, RTKs, and TK signaling in different cell types including vascular smooth muscle cells (VSMCs), which might be a link between TKIs and their cardiovascular effects. In this review, we summarize the implications of RTK inhibitors (RTKIs) and TKIs in cardiovascular toxicities during anti-cancer treatment, with a focus on the potential role of TRPM7/Mg2+ as a mediator of RTKI/TKI-induced cardiovascular toxicity. We also describe the important role of TRPM7 in cancer development and cardiovascular diseases, and the interaction between TRPM7 and RTKs, providing insights for possible mechanisms underlying cardiovascular disease in cancer patients treated with RTKI/TKIs.

AimsEthanol infusion into the VOM (EIVOM) adjunctive to radiofrequency catheter ablation (RFCA) was a novel approach facilitating mitral isthmus (MIth) block for persistent atrial fibrillation (PeAF); However, there were remarkable disparities in its technical aspects. This study aimed to evaluate the impact of EIVOM technical aspects on acute MIth block.MethodsEighty consecutive patients (63 males, average age 66.4 ± 8.6 years) undergoing de novo PeAF ablation were assigned to different groups. The procedural parameters in “EIVOM first” (n = 13) or “RFCA first” (n = 13) as well as small dose ([SD], ≤4 ml, n = 26) or big dose ([BD], >4 ml, n = 54) approaches were analyzed to identify the predictors for acute MIth block.ResultsCompared with the “EIVOM first” approach, the “RFCA first” approach was associated with longer procedural and MIth ablation time (134 ± 27 min vs. 112 ± 17 min; 14.9 ± 5.5 min vs. 9.3 ± 5.1 min, both P < 0.05, respectively), but with comparable success of MIth block. The ethanol dose was 6.3 ± 1.5 ml in BD group vs. 3.1 ± 1.0 ml in SD group (P < 0.001) and was correlated significantly with the size of Δlow voltage area (r = 0.66, P < 0.001). The success of MIth block was 92.6% in BD group vs. 73.1% in SD group, P = 0.03. The ethanol dose >5.75 ml independently predicted successful MIth block (OR: 0.428, 95% CI: 0.219–0.839, P = 0.01).ConclusionsDespite the comparable effectiveness on MIth block, the “EIVOM first” approach was associated with shorter procedural and MIth ablation time than the “RFCA first” approach. The ethanol dose in EIVOM was an independent predictor for MIth block.

Background: Coronary inflammation causes significantly increased risk of cardiovascular disease (CVD) in diabetic patients. This study investigated the relationship between coronary local inflammation, detected by pericoronary fat attenuation index (FAI), and different blood glucose control levels in low-risk acute coronary syndrome (ACS) patients with or without diabetes. Methods: A total of 309 patients with low-risk ACS were classified into three groups: non-diabetes, well-regulated diabetes, and poorly regulated diabetes. Pericoronary FAI around the proximal or left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA), were evaluated by coronary computed tomography angiography (CCTA), and systemic inflammatory variables and other biochemical indicators were detected by flow cytometry. Results: Pericoronary FAI values around the proximal LAD, LCX, and RCA in poorly regulated diabetes were significantly higher than those in well-regulated diabetes and non-diabetes, whereas those in well-regulated diabetes were not statistically different from those in non-diabetes. Further, plasma glycated hemoglobin (HbA1c) level was positively correlated with the pericoronary FAI values in LAD, LCX, and RCA. However, no significantly increased systemic inflammatory mediators were found in diabetic patients with poor glycemic control. Conclusions: Diabetic patients with poor glycemic control may have higher coronary local inflammation as detected by pericoronary FAI surrounding the three major coronary arteries. Clinical Trial Registration: NCT05590858.

Magnesium (Mg2+) is an essential divalent cation in human body. Its balance is tightly controlled via a balanced interplay among intestinal absorption, storage, and renal excretion, involving multiple transporters across cell membrane that regulate Mg2+ influx and efflux. Mg2+ is involved in a variety of physiological and pathological processes such as enzymatic reactions, energy metabolism, cell proliferation, apoptosis, oxidative stress, and inflammation. In particular, Mg2+ contributes to the molecular hallmarks of aging. Emerging evidence demonstrates that altered Mg2+ status has been associated with many aging-related diseases, including cancer, cardiovascular disease, neurodegenerative disease, musculoskeletal function, metabolic syndrome, and COVID-19. In this review, we focus on Mg2+ and its association with molecular hallmarks of aging. We also summarize recent findings supporting an important role of Mg2+ in aging-related disease including the COVID-19 pandemic.

Photosynthetic bacteria (PSB) bioconversion is a new technology for wastewater treatment and resource recovery. The C/N ratio is an important factor in biological wastewater treatment. For the first time, the efficient C/N ratio range for PSB bioconversion, and the effects of the C/N ratio on wastewater treatment efficiency and cell proliferation, were studied. The results of this study showed that PSB bioconversion was efficient when the wastewater C/N ratio was within the range of 400-0.1. Chemical oxygen demand (COD) removal was higher than 60% in this C/N range. The change in the NH4 +-N concentration was fitted by the logistic model for each C/N ratio. The Vmax of nitrogen removal was similar to that of other technologies and it decreased as the C/N ratio decreased. This shows that this technology exhibits reliable pollutant removal in the C/N ratio range of 400-0.1. The nitrogen transformation study indicated that the PSB might use a specific mechanism under a low C/N ratio. PSB cell proliferation was fitted by the logistic model in the C/N ratio range of 400-2, and µmax was found to be not correlated with the C/N ratio. The protein content in the cells was 40-60% in the C/N ratio range of 400-0.1. The results showed that PSB bioconversion technology has a very high resource value and the value of the C/N ratio places little restriction on it. [ABSTRACT FROM AUTHOR]

FeNiCeOx was firstly prepared by ultrasonic impregnation method and used to remove diclofenac in a Fenton-like system. The catalytic activity was improved successfully by doping Ni into FeCeOx. The diclofenac removal efficiency reached 97.9% after 30 min reaction. The surface morphology and properties of FeNiCeOx were characterized by Brunauer--Emmett--Teller (BET), scanning electron microscopy (SEM), X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), Raman and X-ray photoelectron spectroscopy (XPS) analyses. FeNiCeOx in this paper had larger specific surface area than those prepared by other methods, which was attributed to the cavitation effect and hot-spot effect during the ultrasonic synthesis process. Low crystallinity of Fe2O3 and NiO showed by characterization could lead to high interaction of Fe and Ni ions with support of CeO2. They substituted Ce in CeO2, caused lattice contraction and formed more oxygen vacancies, which favoured the catalytic reaction. Meanwhile, Fe and Ce ions both had redox cycles of Fe3+/Fe2+ and Ce4+/Ce3+, which facilitated the electron transfer in the reaction. The synergistic effect among Fe, Ni and Ce might lead to better catalytic performance of FeNiCeOx than any binary metal oxides constituted from the above three elements. Finally, the potential mechanism of diclofenac removal in FeNiCeOx-H2O2 system is proposed. [ABSTRACT FROM AUTHOR]