Long-term clinical results of acute myocardial infarction at the left main trunk requiring percutaneous cardiopulmonary support.

The clinical results of patients with acute myocardial infarction (AMI) at the left main trunk (LMT) remain unclear, especially in cases requiring percutaneous cardiopulmonary support (PCPS). Twenty seven cases of AMI at the LMT requiring emergent PCPS were retrospectively investigated. These 27 patients were aged 44-83 years (65.6 ± 8.6 years) and 20 (81.5%) were men. Peak creatine kinase (CK) leakage ranged from 538 to 34,010 IU/l (13,553 ± 7656 IU/l). Eight (29.6%) patients were discharged without mechanical support. Ten (37.0%) patients underwent left ventricular assist device (LVAD) implantation, five of whom with preoperative organ failure could not survive more than 6 months after implantation. The other nine (33.3%) patients died of low output syndrome or brain damage. The overall survival rates were 53.7, 41.3, 33.0, and 28.3% at 3 months, 6 months, 1 year, and 2 years, respectively. Multivariate analysis showed that Killip class 3/4 at hospital arrival was an independent risk factor for hospital mortality (odds ratio 20.4). Patients with more than 5 days of PCPS support period (n = 6), ≥ 4 h to revascularization (n = 6) or maximum CK leakage ≥20,000 IU/dl (n = 3) were not associated with successful PCPS or IABP weaning. The long-term clinical outcomes of patients with LMT disease requiring PCPS is devastating. Rapid cardiopulmonary resuscitation and coronary revascularization and timely insertion of LVAD before the onset of complications might lead to better survival.

Impact of COVID-19 pandemic on emergency medical system and management strategies in patients with acute coronary syndrome.

The global coronavirus disease-2019 (COVID-19) pandemic is associated with reduced rate of percutaneous coronary intervention (PCI). However, there were a few data showing how emergency medical system (EMS) and management strategies for acute coronary syndrome (ACS) changed during the pandemic. We sought to clarify changes on characteristics, treatments, and in-hospital mortality of patients with ACS transported via EMS between pre- and post-pandemic. We examined consecutive 656 patients with ACS admitted to Sapporo City ACS Network Hospitals between June 2018 and November 2021. The patients were divided into pre- and post-pandemic groups. The number of ACS hospitalizations declined significantly during the pandemic (proportional reduction 66%, coefficient -0.34, 95% CI -0.50 to -0.18, p < 0.001). The median time from an EMS call to hospital was significantly longer in post-pandemic group than in pre-pandemic group (32 [26-39] vs. 29 [25-36] min, p = 0.008). There were no significant differences in the proportion of patients with ACS receiving PCI, and in-hospital mortality between the groups. The COVID-19 pandemic had a significant impact on EMS and management in patients with ACS. Although a significant decline was observed in ACS hospitalizations, the proportion of patients with ACS receiving emergency PCI remained during the pandemic.

Knockdown of macrophage migration inhibitory factor disrupts adipogenesis in 3T3-L1 cells.

Obesity is a condition in which adipose tissue mass is expanded. Increases in both adipocyte size and number contribute to enlargement of adipose tissue. The increase in cell number is thought to be caused by proliferation and differentiation of preadipocytes. Macrophage migration inhibitory factor (MIF) is expressed in adipocytes, and intracellular MIF content is increased during adipogenesis. Therefore, we hypothesized that MIF is associated with adipocyte biology during adipogenesis and focused on the influence of MIF on adipogenesis. To examine the effects of MIF on adipocytes, MIF expression in 3T3-L1 preadipocytes was inhibited by RNA interference, and cell differentiation was induced by standard procedures. The triglyceride content of MIF small interfering RNA (siRNA)-transfected 3T3-L1 cells was smaller than that of nonspecific siRNA-transfected cells. In addition, MIF knockdown apparently abrogated increases in adiponectin mRNA levels during differentiation. Gene expression of peroxisome proliferator-activated receptor (PPAR)gamma, CCAAT/enhancer binding protein (C/EBP)alpha, and C/EBPdelta decreased with MIF siRNA transfection, but C/EBPbeta expression increased. Cell number and incorporation of 5-bromo-2-deoxyuridine into cells decreased from 1-3 d and from 14-20 h, respectively, after induction of differentiation in MIF siRNA-transfected cells, thus suggesting that MIF siRNA inhibits mitotic clonal expansion. Taken together, these results indicated that MIF regulates differentiation of 3T3-L1 preadipocytes, at least partially, through inhibition of mitotic clonal expansion and/or C/EBPdelta expression.

Effects of replacing metformin with pioglitazone on glycemic control in japanese patients with poorly controlled type 2 diabetes mellitus: A 12-week, open-label, prospective study.

BACKGROUND: Insulin resistance is a critical aspect of the pathophysiology of type 2 diabetes mellitus and is also associated with other risk factors for cardiovascular disease (eg, dyslipidemia and hypertension). Accordingly, insulin resistance is a possible target for lowering plasma glucose concentration and preventing diabetic macroangiopathy. Biguanides, such as metformin, and thiazolidinediones (TZDs), such as pioglitazone, improve insulin resistance. OBJECTIVES: The aims of this study were to assess the effects of replacing a biguanide with a TZD on glycemic control in patients with poorly controlled type 2 diabetes mellitus, and also to identify the factors affecting interpatient variation in the effects of treatment change. METHODS: This was a 12-week, open-label, prospective study in which previously prescribed metformin (500 or 750 mg/d) was replaced with pioglitazone (15 or 30 mg/d) in patients with poorly controlled type 2 diabetes mellitus. Patients with a glycosylated hemoglobin (HbA1c) concentration >7% despite treatment with diet, exercise, and hypoglycemic agents other than TZDs were eligible for the study. Patients who never received TZDs were also eligible for inclusion. Vital signs, metabolic parameters, and arterial stiffness were assessed at baseline and after 12 weeks of treatment with pioglitazone. The primary end point was change in HbA1c concentration after replacing metformin with pioglitazone. Tolerability was assessed by medical history, physical examination, and laboratory tests (aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transpeptidase). RESULTS: Twenty-one Japanese patients (15 women, 6 men; mean [SD] age, 61.8 [8.4] years; body mass index, 25.5 [3.0] kg/m(2)) were included in the study. HbA1c concentration was not significantly changed from baseline after 12 weeks of pioglitazone treatment (8.0% [0.7%] vs 8.2% [0.7%]). Fasting plasma glucose (FPG) concentration also was not significantly changed after the replacement of treatment (156 [27] vs 144 [30] mg/dL). In addition, the resistin concentration did not change significantly from baseline after 12 weeks of pioglitazone treatment (6.6 [3.8] vs 6.4 [3.6] ng/mL). In contrast, significant improvement from baseline was observed in triglyceride (TG) concentrations (157 [109] vs 117 [68] mg/dL; P = 0.003), high-density lipoprotein cholesterol (HDL-C) (55 [12] vs 61 [16] mg/dL; P = 0.016), remnant-like particle cholesterol (6.6 [6.0] vs 5.3 [3.5] mg/dL; P = 0.048), and serum adiponectin (8.8 [4.3] vs 23.3 [11.7] µg/mL; P < 0.001). Pulse wave velocity was also significantly improved (1730 [361] vs 1622 [339] m/sec; P = 0.009). Changes in HbA1c were significantly correlated with serum fasting insulin concentration at baseline in the patients not receiving insulin preparations (r = -0.635, P = 0.013). The percentage change in serum adiponectin concentration was correlated with the percentage changes in HbA1c and FPG concentrations (HbA1c, r = -0.518, P = 0.019; FPG, r = -0.594, P = 0.006). Body weight was significantly increased after treatment (62.6 [11.9] vs 65.5 [12.2] kg; P < 0.001). Mild edema was reported in 5 patients. One patient discontinued treatment due to an increase in serum creatine kinase activity to ~6.6 times the upper limit of normal. CONCLUSIONS: Replacement of metformin with pioglitazone did not produce significant differences in HbA1c and FPG concentrations from baseline after 12 weeks of treatment in these patients with poorly controlled type 2 diabetes mellitus. However, the replacement was effective in a subset of patients whose serum insulin concentrations were high or whose serum adiponectin concentrations were sensitive to TZDs. In addition, the replacement was associated with significant improvements in TG, HDL-C, serum adiponectin concentration, pulse wave velocity, and body weight increase from baseline.

Small cell carcinoma of the lung exclusively localized within the left descending pulmonary artery.

We encountered a 69-year-old woman displaying a filling defect within the left descending pulmonary artery (PA) on a chest CT scan and pulmonary angiography. A subsequent 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan demonstrated focal uptake in the left hilum. A cytologic examination of transbronchial needle aspiration specimens revealed small cell carcinoma. The patient underwent concurrent radiation therapy and chemotherapy with cisplatin and etoposide, resulting in tumor shrinkage and recanalization of the involved PA. This is the first case of small cell carcinoma localized exclusively within the PA, and positive findings on FDG-PET facilitated the unexpected diagnosis.

Fatal cardiac small-vessel involvement in ANCA-associated vasculitis: an autopsy case report.

An 80-year-old Japanese man, who had fever and generalized fatigue not improved by antibiotics, was admitted to our hospital. Laboratory data indicative of renal dysfunction and antineutrophil cytoplasmic antibody (ANCA) in the serum led to the consideration of ANCA-associated vasculitis as a differential diagnosis. However, before the diagnostic confirmation, he was found dead on the bed. Autopsy revealed necrotizing crescentic glomerulonephritis in the kidneys. In addition, necrotizing granulomatous vasculitis with infiltration of multinucleated giant cells and neutrophils but not eosinophils was present in multiple organs. The direct cause of death was presumed as cardiac arrest by lethal arrhythmia because vasculitic lesions were distributed widely in the cardiac walls, acute congestion was observed in the systemic organs, and other causes of death were ruled out. This report presents the unusual manifestation of cardiac small-vessel involvement in ANCA-associated vasculitis related to sudden death.

Pilot study of short-term effects of a novel long-acting oral beraprost in patients with pulmonary arterial hypertension.

BACKGROUND: Oral prostacyclin analogs can improve the prognosis of patients with mild to moderate pulmonary arterial hypertension (PAH), but because they often provoke adverse effects, such as flushing and dizziness, administering the optimal dose can be difficult. METHODS AND RESULTS: In the present study, a novel long-acting oral beraprost (TRK-100STP: 0-360 mug/day for 12 weeks) was administered to 4 patients with mild to moderate PAH. The patients tolerated the drug well with mild adverse manifestations and negligible effects on the systemic circulation. In contrast, pulmonary vascular resistance decreased by 27+/-12% and the 6-min walk test distance increased by 11+/-11%. CONCLUSIONS: TRK-100STP is a novel option in the medical management of patients with PAH.

Oxidative stress provokes atherogenic changes in adipokine gene expression in 3T3-L1 adipocytes.

Increased oxidative stress has been associated with obesity-related disorders. In this study, we investigated how oxidative stress, in different ways of exposure, regulates gene expression of various adipokines in 3T3-L1 adipocytes. Exposure to 100-500microM H(2)O(2) for 10min, as well as exposure to 5-25mU/ml glucose oxidase for 18h, similarly decreased adiponectin, leptin, and resistin mRNAs, and increased plasminogen activator inhibitor-1 mRNA. Secretion levels of adipokines were also changed by oxidative stress in parallel with mRNA expression levels. Although a peak increase in plasminogen activator inhibitor-1 mRNA was achieved between 4 and 8h after exposure to H(2)O(2) for 10min, significant decreases in adiponectin and resistin mRNA were observed after 16h, while leptin mRNA was decreased earlier. Our results suggest that oxidative stress, even of short duration, has a significant impact on the regulation of various adipokine gene expressions favoring atherosclerosis.

Recovery of protein-losing enteropathy after living-donor lobar lung transplantation in primary pulmonary hypertension.

The patient investigated was a 43-year-old woman with primary pulmonary hypertension (PPH) and refractory protein-losing enteropathy (PLE). She underwent living-donor lobar lung transplantation (LDLLT), which led to remarkable improvement in both pulmonary hypertension and PLE. Although there have been no reports, to our knowledge, that have demonstrated PLE as a complication of PPH, the present case clearly shows how PLE could complicate PPH. In addition, and more importantly, hypo-proteinemia due to PLE should not necessarily be an exclusion criterion for lung transplantation when PPH is involved, because it could markedly improve after transplantation.

Addition of oral sildenafil to beraprost is a safe and effective therapeutic option for patients with pulmonary hypertension.

Although sildenafil, an oral phosphodiesterase type-5 inhibitor, may offer benefits in the pharmacological management of pulmonary hypertension (PH), safety and effectiveness have not been studied during coadministration with beraprost, an oral prostacyclin analogue. To address this issue, we administered oral beraprost (40 microg) on day 1 and beraprost (40 microg) plus sildenafil (25 mg) on days 2 to 6 patients with moderate to severe PH. Although sildenafil plus beraprost produced transient flushing in 2 of 6 patients, systemic hemodynamics and arterial and venous gas analyses were similar in comparisons between the 2 treatment groups. In contrast, sildenafil plus beraprost therapy resulted in a 2.2-fold greater reduction in mean pulmonary arterial pressure and a 1.6-fold greater reduction in pulmonary vascular resistance compared with beraprost alone, and reductions in these parameters persisted longer with combination therapy than with beraprost alone. Addition of oral sildenafil to beraprost appears to represent a safe and effective therapeutic option, at least in the acute phase, for patients with pulmonary hypertension.

Focal uptake on 18F-fluoro-2-deoxyglucose positron emission tomography images indicates cardiac involvement of sarcoidosis.

AIMS: To evaluate the value of (18)F-fluoro-2-deoxyglucose positron emission tomography ((18)F-FDG PET) in detecting cardiac sarcoidosis. METHODS AND RESULTS: Thirty-two patients with sarcoidosis and thirty controls were recruited. All subjects underwent cardiac (18)F-FDG PET after a 6 h fasting period, and subjects with sarcoidosis underwent blood testing, ECG, echocardiography, and (67)Ga and (99m)Tc-sestamibi (MIBI) scintigraphy. We classified (18)F-FDG PET images into four patterns ('none', 'diffuse', 'focal', and 'focal on diffuse') and found that all the control subjects exhibited either none (n=16) or diffuse (n=14) pattern. In contrast, fifteen subjects with sarcoidosis exhibited none, seven exhibited diffuse, eight exhibited focal, and two exhibited focal on diffuse patterns, with the prevalence of the focal and focal on diffuse patterns being significantly higher in the sarcoidosis group when compared with the control group (P<0.001). None of the 32 subjects with sarcoidosis exhibited abnormal findings on (67)Ga scintigraphy, and 4 exhibited abnormal findings on (99m)Tc-MIBI scintigraphy. CONCLUSION: Focal uptake of the heart on (18)F-FDG PET images is a characteristic feature of patients with sarcoidosis. Furthermore, (18)F-FDG PET has the potential to detect cardiac sarcoidosis that cannot be diagnosed by (67)Ga or (99m)Tc-MIBI scintigraphy.