Drug exposure is one of the potential mechanisms implicated in the onset or exacerbation of psoriasis. To date, several cardiovascular agents have been implicated. Sacubitril/valsartan (SV) has been widely used in the treatment of hypertension and heart failure (HF). Its common adverse reactions include angioedema, hypotension, renal impairment, and hyperkalemia. However, SV may cause psoriasis, which needs clinical attention. This report describes a case of a middle-aged male patient who developed psoriasis following SV therapy. The rashes presented as well-demarcated red or violaceous plaques with noticeable scaling. After being diagnosed with psoriasis, he was started on topical clobetasol propionate ointment, and SV was discontinued and replaced with ramipril for blood pressure control. During follow-up, the skin lesions showed marked improvement. However, the patient developed similar cutaneous manifestations again when SV was re-administered. He had previously developed psoriasis while using nifedipine, but transitioned to olmesartan and subsequently improved significantly with topical medication. Sacubitril enhances the effect of natriuretic peptides, which may be accompanied by a compensatory increase in angiotensin Ⅱ (Ang Ⅱ) levels, possibly contributing to the psoriasis. To the best of our knowledge, this is the first reported case worldwide of psoriasis potentially associated with SV, and the underlying mechanism appears likely to be related to sacubitril. It serves as a caution for clinicians prescribing SV, particularly in patients with a history of psoriasis or positivity for the HLA-Cw*0602 allele. Further studies are warranted to confirm the mechanism by which sacubitril induces psoriasis.

Objective(s): This study aimed to assess the dose-dependent effect of DADLE and to explore its relationship with the TRAF6/NF-κB/NLRP3 pathway.Materials and Methods: After 45 min of ischemia, reperfusion was sustained for 24 hr in mice to establish the myocardial infarction model. DADLE was administered at doses of 0.25, 0.5, or 1 mg/kg to this model. TTC-Evans Blue double staining, HE staining, and Masson staining were conducted to evaluate myocardial injury. TUNEL staining was used to detect apoptosis. Western blotting and immunofluorescence staining were applied to measure levels of TRAF6, NF-κB p65, NLRP3, caspase-1, pro-caspase-1, and ASC. ELISA assays were used to assess TNF-α and IL-1β levels. Results: DADLE at all three doses lessened the infarcted area compared with the PBS control. DADLE at 0.5 mg/kg was more efficacious than 0.25 and 1 mg/kg in reducing the infarcted size, pathological scores, and fibrosis. DADLE effectively reduced the number of apoptotic cells as shown by the TUNEL assay. Levels of TRAF6, NF-κB p65, ASC, NLRP3, caspase-1, and pro-caspase-1 proteins were increased after ischemia-reperfusion (I/R) but were reversed by DADLE. Immunofluorescence staining results for NF-κB and NLRP3 demonstrated similar changes. ELISA assays showed that TNF-α and IL-1β concentrations were increased in the model and reversed by DADLE. Conclusion: DADLE can significantly ameliorate myocardia ischemia-reperfusion injury (MIRI), with the dosage of 0.5 mg/kg presenting the greatest benefit. DADLE may exert its protective effects by activating the TRAF6/NF-κB/NLRP3 signaling pathway.

Background Current guidelines stratify typical atrial flutter (AFL) as carrying a lower thromboembolic risk than atrial fibrillation (AF), yet surface ECG differentiation between AFL and AF is frequently ambiguous[1]. We present a case in which isolated cavotricuspid isthmus (CTI)-dependent AFL—without inducible AF—led to a massive left atrial appendage (LAA) thrombus, highlighting the limitations of ECG-based risk stratification and the role of multimodality imaging. Case presentation A 66-year-old previously healthy man presented with exertional dyspnea and peripheral edema. Initial ECG was interpreted as AF with rapid ventricular response; contrast-enhanced CTA revealed a large lobulated LAA thrombus. After 3 months of anticoagulation with complete thrombus resolution on transesophageal echocardiography (TEE), electrophysiology study demonstrated isolated counterclockwise CTI-dependent typical AFL with no inducible AF. Althrough, combined CTI ablation, prophylactic pulmonary vein isolation and LAA closure with a 31-mm WATCHMAN FLX device were performed. At 3-month follow-up, CTA showed optimal device position and complete endothelialization, permitting discontinuation of anticoagulation. Conclusions Isolated typical AFL can independently drive massive LAA thrombogenesis, warranting anticoagulation and thromboembolic risk assessment analogous to AF. Surface ECG alone is unreliable for rhythm-stratified decision-making; multimodality imaging (CTA/TEE) is essential regardless of presumed rhythm.

OBJECTIVES:Previous studies have not sufficiently examined alcoholic cardiomyopathy (ACM). Therefore, this research aimed to evaluate the prognostic value of left ventricular strain parameters determined using CMR-feature tracking (CMR-FT) in patients with ACM. METHODS:Patients with ACM who underwent CMR from September 2015 to October 2023 were enrolled in this single-center retrospective study. Major adverse cardiovascular events (MACE) included death, heart transplantation, implantable cardioverter-defibrillator (ICD), cardiac resynchronization therapy (CRT), and rehospitalization for worsening heart failure. Multiple linear regression was used to analyze the relationship of the degree of left ventricular strain impairment with daily alcohol intake and drinking duration. The risk factors for MACE were identified using multivariable Cox analysis. RESULTS:A total of 64 patients with ACM were enrolled. During a median follow-up time of 30 months(IQR: 10.0-55.4), 24 (37.5 %) patients developed MACE, including heart transplantation (2 patients), ICD (4 patients), CRT (3 patients), and rehospitalization owing to heart failure (15 patients). Left ventricular ejection fraction, global circumferential strain, global radial strain and global longitudinal strain (GLS) were significantly worse in patients with MACE than those without MACE (p < 0.05). Regression analysis indicated that daily alcohol intake and drinking duration influence left ventricular strain. Multivariate Cox regression analysis revealed a significant association between GLS and MACE. Kaplan-Meier analysis suggested that patients with GLS <6.5 % showed more favorable clinical outcomes than those with GLS ≥6.5 % (p < 0.05). CONCLUSION:GLS exhibits better independent prognostic value than conventional CMR features in patients with ACM.

This case report presents a 43-year-old male patient with severe symptoms who was admitted due to dyspnea following physical activity, cough accompanied by fever, lower limb edema, and hemoptysis. The patient had a 20-year history of hypertension. Examinations revealed bilateral lower pulmonary artery thrombosis, a left ventricular thrombus, pulmonary infarction, and reduced left ventricular systolic function, with a lowest left ventricular ejection fraction (LVEF) of 26.5%. Genetic testing indicated the presence of methylenetetrahydrofolate reductase (MTHFR) (C677T) CT type and plasminogen activator inhibitor-1 (PAI-1) (4G/5G) 4G/5G type, while pleural fluid sequencing confirmed Epstein-Barr virus (EBV)/cytomegalovirus (CMV) infection, leading to a diagnosis of viral myocarditis. Treatment included low molecular weight heparin for anticoagulation, glucocorticoids, and measures to improve cardiac function. During treatment, the patient developed a cerebral infarction. Anticoagulation was maintained post-evaluation due to the PAI-1 mutation and was later adjusted to rivaroxaban. Following treatment, inflammatory markers and coagulation function improved, cardiac function recovered (LVEF increased to 53%), and the thrombus resolved. The combination of EBV/CMV infection with MTHFR and PAI-1 mutations synergistically induced thrombosis through the "virus-inflammation-gene" pathway. This case underscores the importance of early pathogen and genetic screening, as well as personalized anticoagulation strategies, such as substituting warfarin with rivaroxaban. The potential synergistic effect of infection and hereditary thrombophilia in multi-organ embolism warrants careful consideration.

Background: Skeletal class III malocclusion is among the most common dental and maxillofacial malformations. Three-dimensional (3D) printing technology has become widely applied in orthopaedics. The data source for 3D printing of maxillofacial bones is computed tomography (CT). The issue of the CT radiation dose caused by maxillofacial bone 3D printing has attracted increasing attention. This study aimed to explore the feasibility of low-dose CT technology in maxillofacial bone 3D printing and the clinical value of low-dose maxillofacial bone 3D printing. Methods: Ninety patients with class III malocclusion who planned to undergo maxillofacial bone 3D printing and 3D-CT were prospectively enrolled and randomly divided into the conventional CT dose 3D printing group (Group A, n=28), low-CT dose 3D printing group (Group B, n=32) and 3D-CT control group (Group C, n=30). The quality of maxillofacial bone 3D printing was subjectively evaluated, and a Likert-scale questionnaire was used to assess the clinical value of maxillofacial bone 3D printing. Results: No significant differences in the general demographic characteristics were detected among Groups A, B, and C. Compared with that in Group A (0.8 +/- 0.1 mSv), the radiation effective dose (ED) in Group B (0.3 +/- 0.1 mSv) was reduced by approximately 63%. There were no significant differences between Groups A and B in 3D printing quality indices (including clarity, integrity, accuracy or artefacts) (all P>0.05). There were significantly higher subjective scores for the clinical value of maxillofacial bone 3D printing (Group A=4.1 +/- 0.5, 4.0 +/- 0.5, 4.0 +/- 0.4 and 4.1 +/- 0.5; Group B=4.0 +/- 0.5, 4.0 +/- 0.4, 4.0 +/- 0.5 and 4.0 +/- 0.5) than for 3D-CT (Group C=3.1 +/- 0.5, 3.1 +/- 0.4, 2.9 +/- 0.4 and 3.0 +/- 0.4) in diagnosing and classifying, formulating the surgical plan, simulating the surgical process, and predicting postoperative recovery (all P<0.05). Conclusions: Low-dose CT technology can be effectively applied for maxillofacial bone 3D printing, reducing the radiation dose without affecting the 3D printing quality. Maxillofacial bone 3D printing technology is superior to 3D-CT in class III malformations.

Background Acute myocardial infarction is one of the leading causes of death worldwide. Myocardial ischemia reperfusion (MI/R) injury occurs immediately after the coronary reperfusion and aggravates myocardial ischemia. Whether the Wnt/β-Catenin pathway is involved in the protection against MI/R injury by DADLE has not been evaluated. Therefore, the present study aimed to investigate the protective effect of DADLE against MI/R injury in a mouse model and to further explore the association between DADLE and the Wnt/β-Catenin pathway. Methods Forty-four mice were randomly allocated to four groups: Group Control (PBS Control), Group D 0.25 (DADLE 0.25 mg/kg), Group D 0.5 (DADLE 0.5 mg/kg), and Group Sham. In the control and DADLE groups, myocardial ischemia injury was induced by occluding the left anterior descending coronary artery (LAD) for 45 min. PBS and DADLE were administrated, respectively, 5 min before reperfusion. The sham group did not go through LAD occlusion. 24 h after reperfusion, functions of the left ventricle were assessed through echocardiography. Myocardial injury was evaluated using TTC double-staining and HE staining. Levels of myocardial enzymes, including CK-MB and LDH, in the serum were determined using ELISA kits. Expression of caspase-3, TCF4, Wnt3a, and β-Catenin was evaluated using the Western blot assay. Results The infarct area was significantly smaller in the DADLE groups than in the control group ( P < 0.01). The histopathology score and serum levels of myocardial enzymes were significantly lower in the DADLE groups than in the control group ( P < 0.01). DADLE significantly improved functions of the left ventricle ( P < 0.01), decreased expression of caspase-3 ( P < 0.01), TCF4 ( P < 0.01), Wnt3a ( P < 0.05), and β-Catenin ( P < 0.01) compared with PBS. Conclusions The present study showed that DADLE protected the myocardium from MI/R through suppressing the expression of caspase-3, TCF4, Wnt3a, and β-Catenin and consequently improving functions of the left ventricle in I/R model mice. The TCF4/Wnt/β-Catenin signaling pathway might become a therapeutic target for MI/R treatment.

Review question / Objective: What is the incidence rate of thrombosis and bleeding events among patients undergoing Extracorporeal Membrane Oxygenation (ECMO) therapy?Additionally, what are the mortality rates associated with this treatment?P: patients receiving ECMO therapy.I: ECMO therapy.C: not applicable.O: primary: thrombosis and

Dear editor,Acute massive pulmonary embolism（PE） is a common life-threatening disease with high mortality of up to 30%–50%. [1,2] Potential heterogeneous reasons for PE remain controversial, and its treatment strategies mainly include antithrombotics, fibrinolytics, and embolectomy.

经皮左心耳封堵术已成为非瓣膜性心房颤动患者卒中预防的重要非药物干预措施.经皮左心耳封堵旨在在不增加出血风险的情况下降低血栓栓塞风险,这是出血高风险患者的关键治疗策略.在过去的几十年中,经皮左心耳封堵的安全性和有效性不断得到验证,越来越多的患者正在接受这项治疗.本文对经皮左心耳封堵的现状做一述评.

BackgroundAlthough the implant success rate of left atrial appendage closure (LAAC) has increased and complications have decreased over time, there are still anatomically and technically complicated cases where novel LAA occluders may simplify the procedure and thus might potentially improve the clinical outcome.ObjectivesThis study aimed to assess the safety and efficacy of the newly designed device with isogenous barbs in LAAC.MethodsEight centers in China participated in this prospective study from July 2016 to April 2018. Peri- and post-procedural safety and efficacy were evaluated through scheduled follow-ups and transesophageal echocardiography (TEE).ResultsA total of 175 patients with a mean age of 68.4 ± 9.2 years old, a mean CHA2DS2-VASc score of 4.7 ± 1.8, and a mean HAS-BLED score of 3.2 ± 1.3, were included. The device was successfully implanted in 173 patients (98.9%). The device size ranged from 18 to 34 mm. Clinically relevant pericardial effusion (PEF) in the perioperative period, occurred in 3 patients (1.7%). TEE follow-up was available in 167 (96.5%) patients at 12-month. During follow-up, 9 patients suffered serious adverse event: 4 death (2.3%), 1 ischemic stroke (0.6%), and 2 gastro-intestinal bleeding (1.2%) and 2 device-related thrombus (DRT) (1.2%). Estimated annual thromboembolism rate reduced by 90% and estimated annual major bleeding rate reduced by 81% after LAAC with the newly designed device.ConclusionThe newly designed device with isogenous barbs for LAAC could be performed effectively with a low incidence of adverse events and a high incidence of anatomic closure.

1. Division of Cardiology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong SAR, China; 2. Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China; 3. Department of Cardiology, Ningbo First Hospital, Ningbo, China; 4. Hong Kong Asia Heart Center, Canossa Hospital, Hong Kong SAR, China

Background Leukoaraiosis (LA) is a phenomenon of the brain that is often observed in elderly people. However, little is known about the role of LA in cognitive impairment in neurodegeneration and disease. This cross-sectional, retrospective Leukoaraiosis And Disability (LADIS) study aimed to characterize the relationship between brain white matter connectivity properties with LA ratings in patients with Alzheimer's disease (AD) as compared with age-matched cognitively normal controls. Methods Patients with AD (n=76) and elderly individuals with normal cognitive (NC) function (n=82) were classified into 3 groups, LA1, LA2, and LA3, according to the rating of their white matter changes (WMCs). Diffusion tensor imaging (DTI) data were analyzed by quantifying and comparing the white matter connectivity properties and gray matter (GM) volume of brain regions of interest (ROIs). Results The rich-club network properties in the AD LA1 and LA2 groups showed significant patterns of disrupted peripheral regions and reduced connectivity compared to those in the NC LA1 and LA2 groups, respectively. However, the rich-club network properties in the AD LA3 group showed similar patterns of disrupted peripheral regions and reduced connectivity compared to those in the NC LA3 group, despite there being significant hippocampal and amygdala atrophic differences between AD patients and NC elders. Compared to the NC LA1 group, the characteristic path length of white matter fiber connectivity in the NC LA3 group was significantly increased, and the brain's global efficiency, clustering coefficient, and network connectivity strength were significantly reduced (P<0.05, respectively). However, no significant differences (P>0.05) were observed in characteristic path length, reduced global efficiency, or the clustering coefficient between the NC LA3 and AD LA1 groups, or between the NC LA3 and AD LA2 groups. Conclusions Our findings offer some insights into a potential role of LA in cognitive impairment that may predict the development of disability in older adults. The occurrence of LA, an intermediate degenerative change, during neurodegeneration and disease may potentially lead to the remodeling of the brain network through brain plasticity. LA, therefore, representing a possible compensatory mechanism to buffer cognitive decline.

Background: Percutaneous left atrial appendage (LAA) closure has been demonstrated to be an alternative to oral anticoagulation for the prevention of ischemic stroke in nonvalvar atrial fibrillation (NVAF) patients. However, there were some designed limitations of current widely-used devices. This study was designed to evaluate the efficacy and safety of a novel double-disc LAA closure (LAAC) device, the LEFTEAR, in patients with NVAF who had contraindications of long-term oral anticoagulation or still high risks of stroke with anticoagulation treatment. Subjects and Methods: A total of 200 NVAF patients who underwent LAAC were prospectively recruited in nine participating centers in China between April 2014 and March 2019 in this prospective, multi-center, single-arm study. The study was approved by the institutional review board of each clinical center. The enrolled cases had ages ranged from 38 to 89 years (mean 68.3 ± 8.7) years. There were 112 males (56%). CHA2DS2-VASc scores were 3.5 ± 1.44, and HAS-BLED scores 2.5 ± 1.18. LAAC was conducted with the LEFTEAR occluder. Successful closure of LAA was defined as there was no or a small amount of peri-device leak (PDL ≤3 mm) of residual shunt, evaluated by transesophageal echocardiography. The composite end-point events (hemorrhagic/ischemic stroke, systemic embolism, and cardiogenic/unexplained death) within 12 months after the procedure were the main efficacy indicators. Severe adverse events (SAEs) within 12 months were safety indicators. Results: Totally 196 were implanted with an occluder, and the remaining 4 were not (1 case found with an large LAA which the ostium was great than 35 mm, the upper limit of the clinical program, 1 case gave up after failed attempt of LAAC procedure, 2 cases showed “pericardial tamponade” after AF ablation and no attempts were made to continue LAAC). Among them, the “Hybrid procedures” (LAAC combined with AF ablation) reached up to 133 cases (66.5%). Up to December 31, 2019, the mean follow-up was 6 months. There were none major composite endpoint events occurred during the perioperative and follow-up periods (0%). SAEs were recorded in 10 cases, of which 7 were “pericardial tamponades” and 3 of “occluder detachment or displacements.” All SAEs occurred in “Hybrid procedures” cases, of which 9 occurred in the perioperative period (90%). Six cases of “pericardial tamponade” were recorded in the perioperative period, but only two required emergency surgeries. The successful rate of immediate LAAC was 100%, among which 178 cases (90.8%, 178/196) had no residual shunt (PDL = 0 mm). A total of 153 cases (79.7%, 153/192) had completed at least one follow-up transoesophageal echocardiography examination, and the success of mid-term LAAC was 98.7% (151/153), with no events of device-related thrombosis. Conclusions: LAAC with a novel disc-like occlude, named LEFTEAR was generally effective and safe. The “Hybrid procedures” increased the incidence of adverse events to some extent. This study was the first-in-human trial of LEFTEAR, thus further larger sample studies are still needed to verify.