Nanosecond pulsed electric field ablation-induced modulation of sphingolipid metabolism is associated with Ly6c2+ mononuclear phagocyte differentiation in liver cancer.

Preclinical studies have proven that nanosecond pulsed electric field (nsPEF) ablation can be a safe and effective treatment for humans with unresectable liver cancer that are ineligible for thermal ablation. The concomitant activation of antitumor immunity by nsPEF can also potentially prevent tumor recurrence. However, whether nsPEF exhibits similar efficacy in a clinical setting remains to be investigated. A prospective clinical trial (clinicaltrials.gov identifier: NCT04039747) was conducted to evaluate the safety and efficacy of ultrasound (US)-guided nsPEF ablation in 15 patients with unresectable liver cancer that were ineligible for thermal ablation. We found that nsPEF ablation was safe and produced a 12-month recurrence-free survival (RFS) and local RFS of 60% (9/15) and 86.7% (13/15), respectively, in the enrolled patients. Integrative proteomic and metabolomic analysis showed that sphingolipid metabolism was the most significantly enriched pathway in patient sera after nsPEF without recurrence within 8 months. A similar upregulation of sphingolipid metabolism was observed in the intratumoral mononuclear phagocytes (MNPs), rather than other immune and nonimmune cells, of an nsPEF-treated mouse model. We then demonstrated that lymphocyte antigen 6 complex, locus C2-positive (Ly6c2+ ) monocytes first differentiated into Ly6c2+ monocyte-derived macrophages with an increase in sphingolipid metabolic activity, and subsequently into Ly6c2+ dendritic cells (DCs). Ly6c2+ DCs communicated with CD8+ T cells and increased the proportions of IFN-γ+ CD8+ memory T cells after nsPEF, and this finding was subsequently confirmed by depletion of liver Ly6c2+ MNPs. In conclusion, nsPEF was a safe and effective treatment for liver cancer. The alteration of sphingolipid metabolism induced by nsPEF was associated with the differentiation of Ly6c2+ MNPs, and subsequently induced the formation of memory CD8+ T cells with potent antitumor effect.

Major complications after ultrasound-guided liver biopsy: An annual audit of a Chinese tertiary-care teaching hospital.

BACKGROUND: As ultrasound-guided percutaneous liver biopsy (PLB) has become a standard and important method in the management of liver disease in our country, a periodical audit of the major complications is needed. AIM: To determine the annual incidence of major complications following ultrasound-guided PLB and to identify variables that are significantly associated with an increased risk of major complications. METHODS: A total of 1857 consecutive cases of PLB were included in our hospital from January 2021 to December 2021. The major complication rate and all-cause 30-d mortality rate were determined. Multivariate analyses were performed by logistic regression to investigate the risk factors associated with major complications and all-cause 30-d mortality following ultrasound-guided PLB. RESULTS: In this audit of 1857 liver biopsies, 10 cases (0.53%) of major complications occurred following ultrasound-guided PLB. The overall all-cause mortality rate at 30 d after PLB was 0.27% (5 cases). Two cases (0.11%) were attributed to major hemorrhage within 7 d after liver biopsy. Fibrinogen less than 2 g/L [odds ratio (OR): 17.226; 95% confidence interval (CI): 2.647-112.102; P = 0.003], post-biopsy hemoglobin level (OR: 0.963; 95%CI: 0.942-0.985; P = 0.001), obstructive jaundice (OR: 6.698; 95%CI: 1.133-39.596; P = 0.036), application of anticoagulants/antiplatelet medications (OR: 24.078; 95%CI: 1.678-345.495; P = 0.019) and age (OR: 1.096; 95%CI: 1.012-1.187; P = 0.025) were statistically associated with the incidence of major complications after PLB. CONCLUSION: In conclusion, the results of this annual audit confirmed that ultrasound-guided PLB can be performed safely, with a major complication rate within the accepted range. Strict patient selection and peri-biopsy laboratory assessment are more important than procedural factors for optimizing the safety outcomes of this procedure.

Clinical characteristics and outcome correlates of Chinese patients with takotsubo syndrome: Results from the first Chinese takotsubo syndrome registry.

OBJECTIVE: To investigate clinical features and outcomes of Chinese patients with Takotsubo syndrome (TTS). METHODS: We established the first Chinese Registry of Takotsubo Syndrome (ChiTTS Registry) and analyzed demographic, clinical, therapeutical, and outcome data to characterize clinical and outcome features of Chinese TTS patients. RESULTS: In 112 enrolled patients in the ChiTTS registry from 02/01/2016 to 12/28/2021, the mean age was 59.4 ± 18.7 years old, and 27.7% were men. A total of 41.1% patients experienced respiratory and circulatory complications during hospitalization, and 17.3% patients developed cardiogenic shock. Physical triggers, dyspnea, tachycardia, and younger age (< 70 years old) predicted in-hospital complications. The MACCE rate during follow up was 13.9% per patient per year and the rate of all-cause death was 12.8% per patient per year. TTS patients with in-hospital complications developed more long-term MACCE (24.6% vs. 6.6% per patient-year, P < 0.001) and higher all-cause mortality (21.9% vs. 6.6% per patient-year, P = 0.001) than those without. The Kaplan-Meier survival analysis showed that more MACCE occurred in TTS patients with tachycardia during 3-year follow-up (HR 4.18; 95% CI 1.80-9.74; log-rank test P < 0.001). Among all medications at discharge, only beta-blocker was associated with reduced long-term MACCE (HR: 0.35; 95% CI: 0.12-0.996; P = 0.049). CONCLUSION: We investigated clinical and outcome features of patients in the first Chinese TTS Registry. Tachycardiac TTS patients developed more inpatient and long-term adverse cardiovascular events.

Mechanical interventricular dependency supports hemodynamics in tako-tsubo cardiomyopathy.

BACKGROUND: Although morphological abnormalities of the heart appear to be remarkable, most patients with tako-tsubo cardiomyopathy (TTC) remain clinically stable. We investigate real time changes in the left ventricular (LV) and right ventricular (RV) mechanics and function to explore the mechanism to preserve hemodynamics. METHODS: With deformation and Doppler echocardiography, we evaluated myocardial mechanics and ventricular function/hemodynamics simultaneously in 103 consecutive TTC patients admitted from 01/01/2008 through 12/31/2015. The coronary angiography and left ventriculography were performed to rule out culprit coronary artery stenosis (CAS). We included 66 patients in a control group with matched age, sex, and risk factors for coronary artery disease (CAD), and 41 patients in a group of myocardial infarction induced cardiogenic shock, who required circulatory supporting devices to maintain hemodynamic stability. RESULTS: Although systolic myocardial strain in most of the LV segments was significantly impaired, 4 basal LV segments remained functionally active during acute stage of TTC. The impairment in the myocardial strain of the RV apex could extend to the middle segments, but basal RV systolic strain was also preserved. Despites comparable apical to basal strain gradients, LV and RV displayed discrepant functional/hemodynamic status. In contrast to LV, RV functional/hemodynamic parameters appeared to be hyper-dynamic. This unique RV strain pattern remained unchanged in patients with atypical (mid-LV cavity) TTC. In 41 patients with myocardial infarction induced cardiogenic shock, RV exhibited comparable mechanic and functional features with those in TTC patients. CONCLUSIONS: The identified LV and RV mechanic changes appear to support interventricular hemodynamic dependence during TTC, which may represent a universal rescue mechanism in a jeopardized or injured heart.

"Reverse McConnell's Sign": Interpreting Interventricular Hemodynamic Dependency and Guiding the Management of Acute Heart Failure during Takotsubo Cardiomyopathy.

Although most patients with Takotsubo cardiomyopathy (TTC) have benign clinical course and prognosis, TTC can induce acute heart failure and hemodynamic instability. TTC mimics the clinical features of acute anterior wall myocardial infarction (AMI). Bedside clinicians often have a diagnostic dilemma when cardiac catheterization and angiography are either contraindicated or can cause potential adverse consequences. Misdiagnosing TTC as AMI will lead to initiation of harmful pharmacological or device-based treatment, which worsens hemodynamic compromise. Therefore, understanding and interpreting the unique pathophysiological and hemodynamic features of TTC in a better manner becomes crucial to guide effective clinical management of acute heart failure/cardiogenic shock during TTC. We review recent advances in echocardiographic diagnosis of TTC and its role in guiding bedside management of acute heart failure and cardiogenic shock, with specific focus on the interpretation of discrepant, but reciprocally dependent, left and right ventricular hemodynamics during acute stages of TTC.