Impaired AKT signaling and lung tumorigenesis by PIERCE1 ablation in KRAS-mutant non-small cell lung cancer.

KRAS-mutant non-small cell lung cancer (NSCLC) is a major lung cancer subtype that leads to many cancer-related deaths worldwide. Although numerous studies on KRAS-mutant type NSCLC have been conducted, new oncogenic or tumor suppressive genes need to be detected because a large proportion of NSCLC patients does not respond to currently used therapeutics. Here, we show the tumor-promoting function of a cell cycle-related protein, PIERCE1, in KRAS-mutant NSCLC. Mechanistically, PIERCE1 depletion inhibits cell growth and AKT phosphorylation (pAKT) at S473, which is particularly observed in KRAS-mutant lung cancers. Analyses of AKT-related genes using microarray, immunoblotting, and real-time quantitative PCR indicated that PIERCE1 negatively regulates the gene expression of the AKT suppressor, TRIB3, through the CHOP pathway, which is a key regulatory pathway for TRIB3 expression. Similarly, in vivo analyses of PIERCE1 depletion in the KRAS mutation-related lung cancer mouse models revealed the suppressive effect of PIERCE1 knockout in urethane- and KRASG12D-induced lung tumorigenesis with decreased pAKT levels observed in the tumors. Tissue microarrays of human lung cancers indicated the expression of PIERCE1 in 83% of lung cancers and its correlation with pAKT expression. Thus, we illustrate how PIERCE1 depletion may serve as a therapeutic strategy against KRAS-mutant NSCLC and propose the clinical benefit of PIERCE1.

Congenital partial defect of the left pericardium presenting as chest pain.

Congenital pericardial defect is a rare cardiac defect with variable clinical presentations. It is usually an unexpected finding during cardiac surgery or autopsy. The clinical detection of congenital absence of pericardium is important because of its life-threatening complications such as fatal myocardial strangulation, myocardial ischaemia and sudden death. We present a patient with the incidental finding of left-sided partial defect of the pericardium during evaluation of chest pain.

Multiple papillary fibroelastomas and thrombus in the left heart.

Cardiac papillary fibroelastomas (CPF) are benign cardiac tumors and usually discovered incidentally during echocardiography. This report describes the case of a 68-year-old man, referred to cardiology for multiple masses of the left ventricle and left atrium. The transthoracic echocardiography revealed multiple oscillating masses in the left ventricle and aortic valve, non-mobile mass in the left atrium with severe mitral stenosis and moderate aortic regurgitation. The patient underwent surgical resection of the masses with valve replacements. Histopathologic examination confirmed the diagnosis of CPF in the left ventricle and aortic valve, thrombus in the left atrium.

Comparison of the axillary venous approach and subclavian venous approach for efficacy of permanent pacemaker implantation. 8-Year follow-up results.

BACKGROUND: Long-term data on lead complication rates are limited for both the axillary and subclavian venous approaches for permanent pacemaker implantation. METHODS AND RESULTS: We conducted a single-center, retrospective, nonrandomized comparison. We reviewed the patients who had consented to receiving a permanent pacemaker implant. A superficial landmark or radiographic contrast guiding was used for the axillary venous approach, whereas conventional landmarks were used for the subclavian venous approach. From January 1992 to December 2005, we analyzed 1,161 permanent pacemaker leads in 655 patients [subclavian venous approach (group I: 338 patients, 542 leads) and axillary venous approach (group II: 317 patients, 619 leads)]. Baseline characteristics of the patients did not differ. However, DDD-pacemakers and atrial leads were used more often in group II than in group I (94% vs. 62% and 49% vs. 40%, P<0.01). During the 8-year follow-up, lead complication rates were lower in group II (17 leads, 3%) than in group I (31 leads, 6%) (P=0.03), and group II had a better complication-free survival curve than group I with a 49% relative risk reduction in lead complication rates (hazard ratio =0.51; 95% confidence interval, 0.27-0.94; P=0.03). CONCLUSIONS: The axillary venous approach for permanent pacemaker implantation has better long-term efficacy and lower lead complication rates than the subclavian venous approach.

The effect of CYP2C19 genotype on the time course of platelet aggregation inhibition after clopidogrel administration.

We evaluated the effect of CYP2C19 genotype over time on the antiplatelet response of clopidogrel in healthy subjects. Seventy subjects enrolled for a pharmacodynamic study and 22 subjects for a pharmacokinetic and pharmacodynamic study took 300 mg clopidogrel on the first day and 75 mg once daily for six consecutive days. The subjects with CYP2C19 poor metabolizers (PM, N = 22) and intermediate metabolizers (IM, N = 37) had significantly delayed time to inhibition of platelet aggregation (IPA) compared with CYP2C19 extensive metabolizers (EM, N = 33) (12 vs. 9 vs. 2 hours as median Tmax , P < .05) after a 300 mg of clopidogrel. During maintenance doses of clopidogrel, IPA values of only CYP2C19 PM subjects were gradually decreased from 30.0 ± 21.9% on day 2 to 23.7 ± 16.6% on day 8 (P > .05 for time effect; P < .05 for time and genotype interaction effect). CYP2C19 PM had decreased Cmax and AUC of thiol metabolite compared with CYP2C19 EM (0.42- and 0.37-fold on day 1, P < .01; 0.39- and 0.34-fold on day 7, P < .01, respectively). Delayed time to reach maximal IPA as well as decreased IPA may influence the increased risk of the acute cardiac events in CYP2C19 PM and IM.

Fatal subacute stent thrombosis induced by guidewire fracture with retained filaments in the coronary artery.

During percutaneous coronary intervention, guidewire fractures are very exceptionally encountered in medical practice, but can cause fatal complications such as intracoronary thrombus formation, embolization and perforation. Removal of the remnant segments of guidewire is important for the prognosis. There are several methods being recommended for the treatment of fractured guidewire remnants. However, the best treatment of remnant guidewire filament is still unclear. Herein, we present a case where we did not completely remove remnant guidewire filaments that caused fatal coronary thrombosis.

Low pressure pulmonary artery aneurysm with atrial septal defect.

Pulmonary artery (PA) aneurysm is a rare finding in the thoracic cavity, accompanied by pulmonary hypertension. Clinical presentation of PA aneurysms is usually asymptomatic. The guideline for PA aneurysm treatment is unclear. We report an unusual case of low pressure PA aneurysm associated with atrial septal defect in a 69-year-old man.

Multiple feeding vessels from left circumflex artery and right coronary artery to myxoma in left atrium.

A 62-year-old woman with six months history of dizziness was admitted to our hospital. A large mass in the left atrium was detected by transthoracic echocardiography. Coronary angiography showed two feeding arteries from the right coronary artery and left circumflex artery to the left atrium. Chest computed tomography, coronary computed tomographic angiography and contrast echocardiography were performed. Those showed multiple intratumoral neovascularities from surface of the mass. After those examinations, the mass was completely resected. Histopathologic examination confirmed the diagnosis of cardiac myxoma. There was no abnormal remnant mass, based on a follow-up transthoracic echocardiography.

Fatal acute right heart failure in gastric cancer patients.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare condition causing pulmonary artery hypertension and acute right heart failure in patients with cancer. However, chest computer tomography shows negative finding of pulmonary thromboembolism. Serum D-dimer level may be elevated. Echocardiography reveals a dilated right ventricle and feature of pulmonary artery hypertension. Establishing this diagnosis can be very difficult, and most cases are diagnosed during autopsy, although a history of cancer may be a predictor. PTTM should be considered in all patients with apparent pulmonary artery hypertension and elevated D-dimer level, particularly when the patient is known to have an underlying malignancy, especially adenocarcinoma and most of all, the clinical manifestation is very rapidly progressive.

An unusual case of left ventricular free wall rupture caused by a silent myocardial infarction.

Left ventricular free wall rupture (LVFWR) is a serious complication of myocardial infarction. It presents with a very high mortality rate and can be rescued by accurate diagnosis and emergency surgery. LVFWR can occur with sudden overt clinical symptoms or present insidiously. This report highlights the case of a man with no prior history of coronary artery disease, who presented with LVFWR and pericardial effusion that evolved to severe bacterial pericarditis.

Complete Atrioventricular Block Presenting With Syncope Caused by Severe Hypothyroidism.

A 75-year-old man was admitted to our hospital with syncope. Electrocardiogram showed complete atrioventricular block and bradycardia with the minimum heart rate of 22 beats/ min. There was a possible indication for temporary cardiac pacemaker implantation. Laboratory data on admission revealed high TSH level with low free T4 level. To rule out functional atrioventricular block, we treated several days with thyroxine. A follow-up electrocardiogram showed improved heart rate without any atrioventricular block. We found that severe hypothyroidism caused a complete atrioventricular block with syncope, and thyroxine replacement completely improved these conditions.

A Case of Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe complication of incomplete resolution of large pulmonary embolism (PE).Transthoracic echocardiography (TTE) and chest computed tomography (CT) are useful for the diagnosis and follow-up of CTEPH. We report a case of 40-year-old male who wasadmitted with gradually aggravated dyspnea in recent 2 years and had history of acute PE 10 years ago, was detected CTEPH by TTE and confirmed with chest CT.

Incidental diagnosis of the unicuspid aortic valve with ascending aortic aneurysm in an asymptomatic adult.

The unicuspid aortic valve is an extremely rare congenital anomaly. It usually presents with aortic stenosis and/or aortic regurgitation. Other cardiovascular complications, such as aortic dilatation and left ventricular hypertrophy can accompany it. Herein, we present a case report of a 50-year-old asymptomatic male patient with unicuspid aortic valve, complicated by ascending aortic aneurysm.