Nationwide Temporal Trends in Clinical Characteristics and Treatment of Dilated Cardiomyopathy From 2003 to 2013 in Japan　- A Report From Clinical Personal Records.

BACKGROUND: Little is known about nationwide temporal trends in the clinical characteristics and treatment of dilated cardiomyopathy (DCM) in Japan.Methods and Results: We collected data regarding demographics, echocardiography, and treatment of DCM between 2003 to 2013 from Clinical Personal Records, a national registry organized by the Japanese Ministry of Health, Labour, and Welfare. Among the 40,794 DCM patients screened, 27,702 with left ventricular ejection fraction (LVEF) <50% and age ≥18 years were enrolled in this study and divided into 3 groups according to registration year: Group 1, 2003-2005 (10,006 patients); Group 2, 2006-2010 (11,252 patients); and Group 3, 2011-2013 (6,444 patients). Over time, there were decreases in age at registration (mean [±SD] 58.6±13.0 vs. 56.8±13.8 vs. 56.2±13.8 years; P<0.001) and LVEF (33.5±10.0% vs. 31.1±9.9% vs. 29.2± 9.7%; P<0.001), and an increase in patients with New York Heart Association Class III-IV (28.2% vs. 35.2% vs. 41.0%; P<0.001). The use of ß-blockers (59.1% vs. 79.3% vs. 87.8%; P<0.001) and mineralocorticoid receptor antagonists (30.6% vs. 35.8% vs. 39.7%; P<0.001) increased over time. In multivariate analysis, male sex, systolic blood pressure, chronic kidney disease, hemoglobin, and registration year were positively associated, whereas age and LVEF were negatively associated, with ß-blocker prescription. CONCLUSIONS: Although the clinical characteristics of DCM changed, the implementation of optimal medical therapy for DCM increased from 2003 to 2013 in Japan.

Fulminant necrotizing eosinophilic myocarditis after COVID-19 vaccination survived with mechanical circulatory support.

A 69-year-old man was hospitalized for heart failure 7 days after coronavirus disease 2019 (COVID-19) mRNA vaccination. Electrocardiography showed ST-segment elevation and echocardiography demonstrated severe left ventricular dysfunction. Venoarterial extracorporeal membrane oxygenation and Impella 5.0 were instituted because of cardiogenic shock and ventricular fibrillation. Endomyocardial biopsy demonstrated necrotizing eosinophilic myocarditis (NEM). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) PCR test was negative. He had no infection or history of new drug exposure. NEM was likely related to COVID-19 vaccination. He was administered 10 mg/kg of prednisolone following methylprednisolone pulse treatment (1000 mg/day for 3 days). Left ventricular function recovered and he was weaned from mechanical circulatory support (MCS). Follow-up endomyocardial biopsy showed no inflammatory cell infiltration. This is the first report of biopsy-proven NEM after COVID-19 vaccination survived with MCS and immunosuppression therapy. It is a rare condition but early, accurate diagnosis and early aggressive intervention can rescue patients.

Biphenyl derivatives from Garcinia schomburgkiana and the cytotoxicity of the isolated compounds.

Study of the chemical constituents of the stems of Garcinia schomburgkiana Pierre (Guttiferae), collected in Thailand, led to the isolation and identification of five known compounds and two new biphenyl derivatives, schomburgbiphenyl A (1) and B (2). Six phenolic compounds isolated from this plant were screened for their cell growth inhibition activity using several human leukemia cell lines. One compound, oblongifolin C (7), showed significant cytotoxic activity towards Jurkat, NALM6, K562 and HPB-ALL cells.

High-frequency oscillation (HFO) prevents activation of NF-kappaB found with conventional mechanical ventilation (CMV) in surfactant-depleted rabbit lung.

High-frequency oscillation (HFO) has been recognized as an effective ventilatory strategy to minimize lung injury during respiratory support. Conventional mechanical ventilation (CMV) compared with HFO was shown to result in an increased number of PMNs and inflammatory cytokines in the lung lavage fluid. However how mechanical forces can be sensed by cells and converted into biochemical signals for intracellular signal transduction is still unknown. In this current study, we sought to determine whether the activation of Nuclear factor-kappa B (NF-kappaB) might be involved in the lung injury caused by CMV. Surfactant-depleted Japanese white rabbits received 1- or 4-hr CMV or 1- or 4-hr HFO. Then, activation of NF-kappaB in the lungs was assessed by conducting electrophoretic mobility shift assays (EMSA). In the experiment with whole lungs, NF-kappaB activity was much higher in the 4-hr CMV lungs than in the 4-hr HFO lungs. To clarify the origin of the cells in which NF-kappaB was activated, we did a second lung lavage at the end of ventilation and washed out the cells that had infiltrated the alveoli. The levels of NF-kappaB activity were the similar in the lungs of 4-hr HFO rabbits and in those of 4-hr CMV ones. On the other hand, NF-kappaB activity was much higher in the 4-hr CMV lungs than in the 4-hr HFO lungs in the experiment with the lung lavage fluid cells. These results show that the increase in NF-kappaB activity in the lungs of 4-hr CMV rabbits was due mainly to the cells that had infiltrated the alveoli.

Production of TNF-alpha by polymorphonuclear leukocytes during mechanical ventilation in the surfactant-depleted rabbit lung.

Previous studies showed that the production of tumor necrosis factor-alpha (TNF-alpha) and the number of recovered cells were much higher in the conventional mechanical ventilation (CMV) group than in the high-frequency oscillation (HFO) group at the end of mechanical ventilation in this model. But the type of cells that generated TNF-alpha in the lungs remained unclear. It was shown that the alveolar macrophage was the source of TNF-alpha in the early stage, but that in the later stage, the cells in the lung lavage fluid contained almost no macrophages. Thus we hypothesized that in the surfactant-depleted lung model, one of the sources of TNF-alpha after 4 hr of CMV is polymorphonuclear leukocyte (PMN), a type of cell which was numerous at that time. We performed the experiment in the same lung lavage model. The results were as follows. All PaO2 values for the HFO group were significantly greater than the corresponding values for the CMV group throughout the experiment (P < 0.05). More than 96% of the recovered cells of the lung lavage fluid at the end of ventilation were PMN. Cell counts after ventilation of HFO and CMV groups were 183.0 +/- 40.8 (mean +/- SD, n = 6)/microl and 1,106.0 +/- 310.0/microl, respectively (P < 0.05). Levels of rabbit TNF-alpha in the lavage fluid before and after 4 hr ventilation were 43.3 +/- 103.7 pg/ml and 2,406.0 +/- 1,525.1 pg/ml, respectively, in the CMV group. In the HFO group, these levels were 26.6 +/- 52.0 pg/ml and 613.3 +/- 362.2 pg/ml, respectively. The level of TNF-alpha was significantly greater in the CMV group after ventilation (P < 0.05). We performed RT-PCR analysis, in which we showed the presence of TNF-alpha mRNA in the intraalveolar cells (PMN) after 4 hr of CMV, and then demonstrated a positive immunofluorescence reaction to anti-TNF-alpha antibody in PMN separated from the lavage fluid. Our conclusion is that in this surfactant-depleted lung model, PMN is one of the sources of TNF-alpha in the lavage fluid after 4 hr of CMV.