The suppression of the differentiation of adipocytes with Mallotus furetianus is regulated through the posttranslational modifications of C/EBPß.

Obesity is a major risk factor for various chronic diseases, especially lifestyle-related diseases. Therefore, finding a protective substance against obesity and elucidating its molecular mechanism is one of the most important problems for improving human health. In this study, we investigated the antiobesity effect of Mallotus furetianus extract (MFE). The aim of the study was to examine the in vivo and in vitro effects of MFE on lipid synthesis. We examined the effect using an in vivo experimental system with obesity model mice and an in vitro experimental system with 3T3-L1 preadipocytes. We found that the treatment of MFE significantly suppressed the increase in body weight and adipose tissue weight and morphological changes in the liver and adipose tissue of the obesity model mice. In the in vitro experimental system, we revealed that MFE treatment suppressed the expression of transcription factors such as C/EBPα, C/EBPß, and PPARγ, which are involved in the early differentiation of 3T3-L1 preadipocytes. As a result, the ability to synthesize triacylglycerol was suppressed. An interesting finding in this study was the clarification that MFE decreases the expression of C/EBPß through post-translation modifications (PTMs), followed by the transcriptional suppression of PPAR𝛾 and C/EBP𝛼.

Comparison of Percutaneous Coronary Intervention Procedures and Outcomes for Recent and Acute ST-Elevation Myocardial Infarction.

Although the primary percutaneous coronary intervention (PCI) is an established treatment for acute ST-elevation myocardial infarction (STEMI), relevant guidelines do not recommend it for recent-STEMI cases with a totally occluded infarcted related artery (IRA). However, PCI is allowed in Japan for recent-STEMI cases, but little is known regarding its outcomes. We aimed to examine the details and outcomes of PCI procedures in recent-STEMI cases with a totally occluded IRA and compared the findings with those in acute-STEMI cases.Among the 903 consecutive patients admitted with acute coronary syndrome, 250 were treated with PCI for type I STEMI with a totally occluded IRA. According to the time between symptom onset and diagnosis, patients were divided into the recent-STEMI (n = 32) and acute-STEMI (n = 218) groups. The background, procedure details, and short-term outcomes were analyzed. No significant differences between the groups were noted regarding patient demographics, acute myocardial infarction severity, or IRA distribution. Although the stent number and type were similar, significant differences were observed among PCI procedures, including the number of guidewires used, rate of microcatheter or double-lumen catheter use, and application rate of thrombus aspiration. The thrombolysis rate in the myocardial infarction flow 3-grade post-PCI did not differ significantly between the groups. Both groups had a low frequency of procedure-related complications. The in-hospital mortality rates were 0% and 4.6% in the recent-STEMI and acute-STEMI groups, respectively (P > 0.05).Although recent-STEMI cases required complicated PCI techniques, their safety, success rate, and in-hospital mortality were comparable to those of acute-STEMI cases.

Clinical Characteristics and Prognosis of Life-Threatening Acute Myocardial Infarction in Patients Transferred to an Emergency Medical Care Center.

Patients with acute myocardial infarction (AMI) triaged as life-threatening are transferred to our emergency medical care center (EMCC). However, data on these patients remain limited. We aimed to compare the characteristics and AMI prognosis of patients transferred to our EMCC with those transferred to our cardiovascular intensive care unit (CICU) using whole and propensity-matched cohorts.We analyzed the data of 256 consecutive AMI patients transferred from the scene to our hospital by ambulance between 2014 and 2017. The EMCC and CICU groups comprised 77 and 179 patients, respectively. There were no significant between-group age or sex differences. Patients in the EMCC group had more disease severity score and had the left main trunk identified as the culprit more frequently (12% versus 0.6%, P < 0.001) than those in the CICU group; however, the number of patients with multiple culprit vessels did not differ. The EMCC group had a longer door-to-reperfusion time (75 [60, 109] minutes versus 60 [40, 86] minutes, P< 0.001) and a higher in-hospital mortality (19% versus 4.5%, P < 0.001), especially from non-cardiac causes (10% versus 0.6%, P < 0.001), than the CICU group. However, peak myocardial creatine phosphokinase did not significantly differ between the groups. The EMCC group had a significantly higher 1-year post-discharge mortality than the CICU group (log-rank, P = 0.032); this trend was maintained after propensity score matching, although the difference was not statistically significant (log-rank, P = 0.094).AMI patients transferred to the EMCC exhibited more severe disease and worse overall in-hospital and non-cardiac mortality than those transferred to the CICU.

Substantial Reduction of Acute Ischemic Mitral Regurgitation Using Impella in AMI Complicated with Cardiogenic Shock.

A 77-year-old female presented with loss of consciousness, blood pressure of 90/60 mmHg, and heart rate of 47 bpm. At admission, highly sensitive Trop-T and lactate were elevated, and an electrocardiogram revealed an infero-posterior ST elevation myocardial infarction. Echocardiography revealed a depressed left ventricular ejection fraction with abnormal wall motion in the infero-posterior region and hyperkinetic apical movement along with severe mitral regurgitation (MR). Coronary angiography showed a hypoplastic right coronary artery, 100% thrombotic occlusion of the dominant left circumflex (LCx) artery, and 75% stenosis in the left anterior descending (LAD) artery. Substantial hemodynamic improvement with the reduction of acute ischemic MR was achieved by the initiation of an Impella 2.5, which is a transvalvular axial flow pump, and successful percutaneous coronary intervention (PCI) was conducted with stents to the LCx. The patient was weaned off the Impella 2.5 in 5 days, received staged PCI to LAD, and was later discharged after completion of the staged PCI to LAD.

Adjunctive Catheter-Directed Thrombolysis during Primary PCI for ST-Segment Elevation Myocardial Infarction with High Thrombus Burden.

BACKGROUND: High coronary thrombus burden has been associated with unfavorable outcomes in patients with ST-segment elevation myocardial infarction (STEMI), the optimal management of which has not yet been established. METHODS: We assessed the adjunctive catheter-directed thrombolysis (CDT) during primary percutaneous coronary intervention (PCI) in patients with STEMI and high thrombus burden. CDT was defined as intracoronary infusion of tissue plasminogen activator (t-PA; monteplase). RESULTS: Among the 1849 consecutive patients with STEMI, 263 had high thrombus burden. Moreover, 41 patients received t-PA (CDT group), whereas 222 did not receive it (non-CDT group). No significant differences in bleeding complications and in-hospital and long-term mortalities were observed (9.8% vs. 7.2%, p = 0.53; 7.3% vs. 2.3%, p = 0.11; and 12.6% vs. 17.5%, p = 0.84, CDT vs. non-CDT). In patients who underwent antecedent aspiration thrombectomy during PCI (75.6% CDT group and 87.4% non-CDT group), thrombolysis in myocardial infarction grade 2 or 3 flow rate after thrombectomy was significantly lower in the CDT group than in the non-CDT group (32.2% vs. 61.0%, p < 0.01). However, the final rates improved without significant difference (90.3% vs. 97.4%, p = 0.14). CONCLUSIONS: Adjunctive CDT appears to be tolerated and feasible for high thrombus burden. Particularly, it may be an option in cases with failed aspiration thrombectomy.

Combined use of venoarterial extracorporeal membrane oxygenation and intra-aortic balloon pump after cardiac arrest.

OBJECTIVES: We investigated whether intra-aortic balloon pump (IABP) combined with venoarterial extracorporeal membrane oxygenation (VA-ECMO) was associated with favourable neurological outcomes for patients after the return of spontaneous circulation (ROSC). Moreover, we evaluated the aetiology of cardiac arrest on the effectiveness of this therapy in a sub-study. BACKGROUND: There is insufficient research on the optimal combination of machines for patients after ROSC is not established. METHODS: This is a large-scale, multicentre, 30-day cohort study. Among 80,716 patients who delivered to the emergency room, 935 patients treated with VA-ECMO after ROSC were included using the data from the Tokyo Cardiovascular Care Unit Network Registry between 2010 and 2017. The study patients were stratified according to the use of IABP [the ECMO + IABP group (n = 762) vs. the ECMO-alone group (n = 173)]. We also evaluated the cause of cardiac arrest [acute coronary syndrome (ACS) and non-ACS] in the sub-study. To adjust the patients' backgrounds, we used the propensity score matching for additional analyses. The endpoint was 30-day favourable neurological outcome. RESULTS: The ECMO + IABP group showed significantly better neurological outcomes than the ECMO-alone group (crude; 35% vs. 25%; log-lank P < 0.001). In the ACS subgroup, the ECMO + IABP group showed significantly better neurological outcome (crude; 34% vs. 18%; log-lank P < 0.001), but not in the non-ACS subgroup (crude; 38% vs. 32%; log-lank P = 0.11). These results are similar after adjustments to their backgrounds using propensity matching. CONCLUSIONS: Compared to VA-ECMO alone, the combined use of VA-ECMO and IABP is associated with better neurological outcomes after ROSC, especially in complicated ACS.

Non-cardiovascular disorders in a contemporary cardiovascular intensive care unit in Japan.

BACKGROUND: In the modern US cardiovascular intensive care unit (CICU), the incidence of non-cardiovascular disorders has increased and non-cardiovascular disorders are associated with an increase in morbidity and mortality. In Japan, however, data regarding the association between non-cardiovascular disorders and outcomes in the CICU are limited. METHODS: This study examined 490 consecutive admissions to a closed CICU at the Nippon Medical School Hospital from January to December 2017. Characteristics, diagnoses, treatments, and outcomes of admitted patients were identified. RESULTS: The most common primary diagnosis was acute coronary syndrome (50.4%), followed by acute heart failure (20.0%), arrhythmia (6.7%), and non-cardiovascular diseases (3.7%). The mortality rate and median length of stay (LOS) in the CICU were 4.7% and 4 (interquartile range, 2-8) days, respectively. Of all patients, 42.2% (n = 207) developed non-cardiovascular complications such as acute respiratory failure, acute kidney injury, or sepsis during CICU stay. Multivariate logistic regression analysis revealed that acute respiratory failure and sepsis were significantly associated with mortality in the CICU (odds ratio, 11.014 and 25.678, respectively; both p<0.05). The multiple linear regression analysis showed that acute kidney injury was significantly associated with LOS in the CICU (ß=0.144, p = 0.002). CONCLUSIONS: Approximately half of patients admitted to the CICU had non-cardiovascular disorders including non-cardiovascular disease and non-cardiovascular complications, which were significantly associated with mortality and LOS in the CICU.

Clinical Characteristics, Achievement of Secondary Prevention Goals, and Outcomes of Patients with Recurrent Acute Coronary Syndrome.

BACKGROUND: Because development of acute coronary syndrome (ACS) worsens the prognosis of patients with coronary artery disease, preventing recurrent ACS is crucial. However, the degree to which secondary prevention treatment goals are achieved in patients with recurrent ACS is unknown. METHODS: 214 consecutive ACS patients were classified as having First ACS (n=182) or Recurrent ACS (n=32), and the clinical characteristics of these groups were compared. Fifteen patients died or developed cardiovascular (CV) events during hospitalization, and the remaining 199 patients were followed from the date of hospital discharge to evaluate subsequent CV events. RESULTS: Patients in the Recurrent ACS group were older than those in the First ACS group (76.8±10.8 years vs 68.8±13.4 years, p=0.002) and had a higher rate of diabetes mellitus (DM) (65.6% vs 36.8%, p=0.003). The rate of achieving a low-density lipoprotein cholesterol (LDL-C) level of <70 mg/dL in the Recurrent ACS group was only 28.1%, even though 68.8% of these patients were taking statins. An HbA1c level of <7.0% was achieved in 66.7% of patients with recurrent ACS who had been diagnosed with DM. Overall, 12.5% of patients with recurrent ACS had received optimal treatment for secondary prevention. CV events after hospital discharge were noted in 37.9% of the Recurrent ACS group and 21.2% of the First ACS group (log-rank test: p=0.004). However, recurrent ACS was not an independent risk factor for CV events (adjusted hazard ratio: 2.09, 95% confidence interval: 0.95 to 4.63, p=0.068). CONCLUSION: Optimal treatment for secondary prevention was not achieved in some patients with recurrent ACS, and achievement of the guideline-recommended LDL-C goal for secondary prevention was especially low in this population.

Characteristics of Inter-Arm Difference in Blood Pressure in Acute Aortic Dissection.

BACKGROUND: An inter-arm difference in blood pressure (IADBP) is characteristic of acute aortic dissection (AAD), but the importance of which arm exhibits lower blood pressure (BP) and the mechanism underlying IADBP are not well understood. METHODS: We identified consecutive patients with chest and/or back pain and suspected acute cardiovascular disease whose BP had been measured in both arms. We retrospectively compared the characteristics of such patients with AAD (n=93) to those without AAD (non-AAD group, n=122). Additionally, we separately compared patients with type A AAD (TAAD group, n=58) or type B AAD (TBAD group, n=35) to the non-AAD group. The characteristics analyzed were patient background and IADBP-related factors, including systolic BP (SBP) in the right arm (R) and left arm (L), and R-L or L-R as IADBP. Computed tomography (CT) findings of AD extending to the brachiocephalic artery (BCA) and/or left subclavian artery (LSCA) were examined in patients with an IADBP. RESULTS: In a comparison of the TAAD group and non-AAD group, the prevalences of R <130 mm Hg (38% vs. 19%, p=0.009), L-R >15 mm Hg (19% vs. 8%, p=0.047), L-R >20 mm Hg (14% vs. 4%, p=0.029) were higher in the TAAD group. Multivariate analysis showed that L-R >15 mm Hg with R <130 mm Hg was independently associated with TAAD (OR 25.97, 95% CI 2.45-275.67, p=0.007). However, IADBP-related factors were not associated with TBAD. AAD patients with L-R >20 mm Hg all had TAAD, and all aortic dissection extended to the BCA just before the right common carotid artery on CT. CONCLUSIONS: IADBP was characterized by R

Gastrointestinal bleeding increases the risk of subsequent cardiovascular events in patients with acute cardiovascular diseases requiring intensive care.

Gastrointestinal (GI) bleeding worsens the outcomes of critically ill patients in the intensive care unit (ICU). Owing to a lack of corresponding data, we aimed to investigate whether GI bleeding during cardiovascular-ICU (C-ICU) admission in acute cardiovascular (CV) disease patients is a risk factor for subsequent CV events. Totally, 492 consecutive C-ICU patients (40.9% acute coronary syndrome, 22.8% heart failure) were grouped into GI bleeding (n = 27; 12 upper GI and 15 lower GI) and non-GI bleeding (n = 465) groups. Thirty-nine patients died or developed CV events during hospitalization, and 453 were followed up from the date of C-ICU discharge to evaluate subsequent major adverse CV events. The GI bleeding group had a higher Acute Physiology and Chronic Health Evaluation II score (20.2 ± 8.2 vs. 15.1 ± 6.8, p < 0.001), higher frequency of mechanical ventilator use (29.6% vs. 13.1%, p = 0.039), and longer C-ICU admission duration (8 [5-16] days vs. 5 [3-8] days, p < 0.001) than the non-GI bleeding group. The in-hospital mortality rate did not differ between the groups. Of those who were followed-up, CV events after C-ICU discharge were identified in 34.6% and 14.3% of patients in the GI and non-GI bleeding groups, respectively, during a median follow-up period of 228 days (log rank, p < 0.001). GI bleeding was an independent risk factor for subsequent CV events (adjusted hazard ratio: 2.23, 95% confidence interval: 1.06-4.71; p = 0.035). GI bleeding during C-ICU admission was independently associated with subsequent CV events in such settings.

Three-Channeled Aortic Dissection in a Patient without Marfan Syndrome.

A 64-year-old man was admitted for evaluation of back pain. He did not have a Marfan syndrome (MFS)-like appearance, and had a history of a type B aortic dissection and total arch replacement. A connective tissue disorder had been suspected because of the histologic findings of the resected aortic wall. On admission, a computed tomography (CT) scan demonstrated a three-channeled aortic dissection (3ch-AD) measuring 63 mm in diameter. We planned to perform elective surgery during his hospitalization. On the fourth hospital day, he complained of severe back pain, and enhanced CT scan revealed an aortic rupture. The patients with 3ch-AD often have MFS. However, even if they do not have an MFS-like appearance, clinicians should consider fragility of the aortic wall in patients with 3ch-AD. If the aortic diameter is enlarged, early surgery is recommended. In particular, if a connective tissue disorder is obvious or suspected, emergent surgery is warranted.

A Case of Primary Bacterial Pericarditis with Recurrent Cardiac Tamponade.

Cardiac tamponade is an important and potentially lethal complication of acute pericarditis. However, recurrence of cardiac tamponade is rare when it is treated appropriately. We present a 49-year-old man with bacterial pericarditis and recurrent cardiac tamponade, which was caused by the rupture of an upper part of the left atrium (LA). According to the autopsy findings, bacteremia from Staphylococcus aureus developed on a substrate of poorly controlled diabetes mellitus and spread to the pericardium via the blood. Subsequently, tissue necrosis developed from the pulmonary trunk and aorta to the LA, leading to recurrence of cardiac rupture and cardiac tamponade.

Time course of the antiplatelet effect after switching to clopidogrel from initial prasugrel therapy in patients with acute coronary syndrome.

Prasugrel is often replaced with clopidogrel after a certain period of time following coronary stenting. However, the time course of platelet aggregation during this replacement is unknown. We performed a prospective, single-arm study to monitor platelet reactivity before and after the replacement. Forty-five patients (mean age 62.6 ± 13 years, 40 male) who received coronary stenting for acute coronary syndrome were initially treated with the loading dose (20 mg) of prasugrel followed by the maintenance dose (3.75 mg/day) for 7 days, then switched to 75 mg/day of clopidogrel. The P2Y12 reaction unit (PRU) level was measured at baseline and selected time points. Prasugrel effectively suppressed PRU from 248 ± 59 at baseline to 145 ± 65 on day 1 (P < 0.001). The PRU value on the final day of prasugrel treatment (day 7) was 156 ± 68 (P < 0.001 vs. baseline). After switching to clopidogrel, PRU was consistently suppressed [146 ± 60, 139 ± 54, and 135 ± 60 on days 9, 11, and 13, respectively (P < 0.001, each point vs. baseline)]. Switching from the initial prasugrel therapy to clopidogrel using the maintenance dose does not cause a drug efficacy gap and stays effective for preventing stent thrombosis.

A Fever in Acute Aortic Dissection is Caused by Endogenous Mediators that Influence the Extrinsic Coagulation Pathway and Do Not Elevate Procalcitonin.

Objective A fever is observed in approximately one-third of cases of acute aortic dissection (AAD); however, the causes remain unclear. We investigated the mechanism of a fever in AAD by measuring the serum concentrations of inflammatory markers, mediators of coagulation and fibrinolysis, and procalcitonin, a marker of bacterial infection. Methods We retrospectively studied 43 patients with medically treated AAD without apparent infection. Patients were divided into those with (Group A; n=19) and without (Group B; n=24) a maximum body temperature >38°C. We established which patients fulfilled the criteria for systemic inflammatory response syndrome (SIRS), and its relationship with a fever was examined. Mediators of inflammation, coagulation and fibrinolysis were compared by a univariate analysis. Factors independently associated with a fever were established by a multivariate analysis. Results The criteria for SIRS were fulfilled in a greater proportion of patients in Group A (79%) than in Group B (42%, p=0.001). There was no difference in the procalcitonin concentration between Groups A and B (0.15±0.17 ng/mL vs. 0.11±0.12 ng/mL, respectively; p=0.572). Serum procalcitonin concentrations lay within the normal range in all patients in whom it was measured, which showed that the fever was caused by endogenous mediators. On the multivariate analysis, there was a borderline significant relationship between a fever and the prothrombin time-International Normalized Ratio (p=0.065), likely reflecting the extrinsic pathway activity initiated by tissue factor. Conclusion Our findings suggest that a fever in AAD could be caused by SIRS, provoked by endogenous mediators that influence the extrinsic coagulation pathway without elevating the serum procalcitonin concentration.

Usefulness of N-terminal pro-brain natriuretic peptide levels to predict success of weaning from intra-aortic balloon pumping.

There is currently no reliable method of predicting the success of weaning from intra-aortic balloon pumping (IABP). The aim of this study was to investigate the ability of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level to predict the success of weaning from IABP. Consecutive patients scheduled for weaning from IABP were prospectively enrolled. NT-proBNP levels were measured at baseline (before the start of weaning) and cessation (just before cessation of IABP). Changes in NT-proBNP level between baseline and cessation were analyzed in 2 groups of patients: those who were successfully weaned and those who were not successfully weaned for any reason, including a decision to discontinue weaning, worsening of pulmonary edema after cessation of IABP, or unstable hemodynamics after cessation of IABP. A total of 30 patients were enrolled (mean age 66 ± 12 years, 16 men, 16 with acute myocardial infarctions, and 14 with acute exacerbation of chronic heart failure). Median (interquartile range) baseline NT-proBNP levels were not significantly different between the successful and unsuccessful weaning groups (4,200 [1,400 to 8,752] pg/ml vs (5,620 [2,035 to 13,950] pg/ml, p = 0.30). In the unsuccessful weaning group, the median NT-proBNP level was significantly higher at cessation (9,995 [2,920 to 15,100] pg/ml) than at baseline (p = 0.008). All patients with decreases in NT-proBNP level between baseline and cessation were successfully weaned from IABP. In conclusion, these results show that NT-proBNP levels were useful for predicting the success of weaning from IABP. If the NT-proBNP level increases during weaning from IABP, more intense management should be considered.

Miliary tuberculosis with indeterminate interferon gamma release assay results.

Recently, interferon gamma release assays (IGRAs) have become an important clinical tool for detecting latent tuberculosis. However, IGRA results may impede making a diagnosis. We herein present an interesting case of miliary tuberculosis with a nonspecific IGRA reaction due to hemophagocytosis.

Acute renal failure as the presenting sign of disseminated intravascular coagulation in a patient with metastatic prostate cancer.

Disseminated intravascular coagulation (DIC) is the most frequent coagulation disorder in patients with prostate cancer. However, renal involvement in DIC associated with prostate cancer has rarely been documented. Herein, we present a case of metastatic prostate cancer presenting with acute renal failure (RF) triggered by DIC. An 80 year old man with metastatic prostate cancer was treated with antihormone therapy at an outpatient clinic. He was admitted to our hospital because of severe dyspnea and progressive RF. A hemorrhagic tendency was not clinically evident. Laboratory tests exhibited a significant coagulation disorder, suggestive of DIC. Despite treatment, his RF and dyspnea worsened, and he eventually passed away. An autopsy study revealed hypertensive nephrosclerosis superimposed by fibrin rich thrombi formation involving glomerular capillaries and arterioles characteristic of DIC. Additionally, focal segmental glomerulosclerosis was identified, which was presumably secondary to the glomerular endothelial and/or podocyte injury augmented by DIC. Those findings showed that glomerular injury, which was induced and subsequently exacerbated by DIC associated with prostate cancer, highly contributed to the progression of RF in our case. A differential diagnosis of DIC should be considered when a patient with prostate cancer presents with renal dysfunction.