Multiomics profiling of buffy coat and plasma unveils etiology-specific signatures in hepatocellular carcinoma

Background/Aims@#Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Despite identification of several biomarkers for HCC diagnosis, challenges such as low sensitivity and intratumoral heterogeneity have impeded early detection, highlighting the need for etiology-specific blood biomarkers. @*Methods@#We generated whole-transcriptome sequencing (WTS) and targeted proteome data from buffy coat and plasma samples from HCC patients. By integrating etiological information on viral infection, we investigated the etiology-specific gene expression landscape at the blood level. Validation of differentially expressed genes (DEGs) was performed using publicly available RNA-seq datasets and qRT‒PCR with AUC analyses. @*Results@#Differential expression analyses with multiomics data revealed distinct gene expression profiles between HBV-associated HCC and nonviral HCC, indicating the presence of etiology-specific blood biomarkers. The identified DEGs were validated across multiple independent datasets, underscoring their utility as biomarkers. Additionally, single-cell RNA-seq analysis of HCC confirmed differences in DEG expression across distinct immune cell types. @*Conclusions@#Our buffy coat WTS data and plasma proteome data may serve as reliable sources for identifying etiology-specific blood biomarkers of HCC and might contribute to discovery of therapeutic targets for HCC across different etiologies.

A Case of Descending Thoracic Aortic Pseudoaneurysm Associated with Thoracolumbar Pedicle Screw Removal

Vascular injuries after spine surgery may result in acute life-threatening hemorrhage, chronic arteriovenous fistula, or pseudoaneurysm formation. The interval between injury and rupture may range from seconds to years, and accordingly, a high index of suspicion is needed to make the diagnosis. Although acute and delayed vascular injury caused by placement of posterior pedicle screw fixation has been reported, the potential for large vessel disruption during posterior pedicle screw removal has been rarely reported. This case report concerns a 50-year-old man who developed an descending thoracic aortic pseudoaneurysm after posterior pedicle screw removal, diagnosed by chest computed tomography(CT) scan and transesophageal echocardiography(TEE).

Arotic Atherosclerotic Plaques as a Potential Embolic Sources in Patients with Cryptogenic Stoke

BACKGROUND: The atherosclerotic plaque in the thoracic aorta has been considered as a potential source of cerebral or peripheral embolization. Especially, complex type of atherosclerotic plaques in the thoracic aorta have strongly been associated with cerebral embolism in ischemic stroke and transesophageal echocardiography(TEE) is a useful diagnostic tool for evaluation of thoracic aorta atherosclerosis. The aim of this study was to evaluate the prevalence and significance of complex type of thoracic atherosclerotic plaques in the patients with cryptogenic stroke who have neither cardiac source nor significant carotid atherosclerosis. METHOD: From 1993 to 1998, TEE and carotid Doppler sonography were performed in 58 consecutive patients with ischemic stroke and in 30 control patients without ischemic stroke. We divided the former into two groups. One is known-cause stroke(n=37) group and the other is Cryptogenic stroke group(n=21). We evaluated cardiogenic source of embolism, thoracic aorta atherosclerotic plaques as well as carotid atherosclerosis by carotid Doppler sonography and TEE. Aortic atherosclerosis was classified as grade 1: normal-appearing aortic intima, grade 2: extensive intimal thickening, grade 3: sessile atheroma protruding 5mm, and grade 5: mobile atheroma. Carotid atherosclerosis was categorized as significant if luminal stenosis of either common carotid artery or internal carotid artery is greater than 50%. RESULTS: 1) There was no statistically significant difference among the three groups in age, gender, diabetes mellitus, hyperlipidemia and smoking. 2) Hypertension was more common in the cryptogenic stroke group(p<0.05). Atrial fibrillation was more common in the known-cause and control group than in the cryptogenic group(p<0.005). 3) The carotid atherosclerosis was found in 7(12%) out of 58 consecutive patients with ischemic stroke. 4) The thoracic aortic atherosclerotic plaque was located primarily on descending aorta. The complex type of plaque was found in 8(38%) out of 21 patients with cryptogenic stroke. The complex type of plaque was found in 10(27%) out of 37 patients with known-cause stroke. The complex type of plaque was found in 3(10%) out of 30 patients with known-cause stroke. CONCLUSION: These results suggest that complex type of thoracic atherosclerotic plaques in cryptogenic stoke can be considered as potential source of ischemic stroke and we suggest that a patient with cerebral embolism without a source identified by the routine transthoracic echocardiograpy or carotid sonography shoud undergo transesophageal echocardiography to evaluate the thoracic aorta atheroma.

A Case of Torsade de Pointes after Treatment with Terfenadine and Ketoconazole

Torsade de pointes (TdP) is a form of polymorphic ventricular tachycardia that is associated with prolongation of the QT interval. Although it occurs in many clinical settings, torsade de pointes is most commonly caused by drugs. The second generation antihistamines, including terfenadine and astemizole, have little sedation or other adverse effects on the CNS. They have been used widely to treat various allergic diseases, but it has been reported that overdoses or combinations with antifungal agents or macrolide antibiotics may lead to TdP. We report a case of TdP that occured during com-bination therapy of terfenadine and ketoconazole.

Patterns of Exercise-induced Coronary Spasm in Patients with Variant Angina: Results, Correlation with Clinical Features

BACKGROUND: Exercise-induced coronary spasm is occasionally recognized in patients with variant angina, but the patterns of exercise-induced coronary spasm and its relation to clinical features are still not clear. METHODS: Eight consecutive patients with variant angina without significant stenosis of the coronary artery performed serial treadmill exercise tests during early morning, late morning, and in the afternoon. The subjects repeated the tests after administration of atropine and doxazosin or phentolamine. RESULTS: (Upon drug administration), anginal episodes with ST-segment changes (elevation 5, depression 1) Occurred repeatedly in 6 of the 8 patients during early morning; the episodes occurred in only 2 patients during the afternoon exercise test. Four patients showed exercise-induced angina and ST-segment changes during early morning but not in the afternoon, and 2 of them showed mild episodes of exercise-induced angina and ST-segment changes during late morning. Three of the four patients had the characteristic clinical history of angina in early morning during usual activities but not during daytime activities despite the activities being more strenuous. Another 2 patients showed both exercise-induced ST-segment elevation and angina in early morning and afternoon, and they had the characteristic history of more episodes at night and in early morning but only occasionally in the daytime with or without relation to activity. One of the two patients showed intermittent ST-segment elevation during the exercise test. The other two patients had exercise-induced episodes neither in the early morning nor in the afternoon; they had a characteristic history of episodes only at night during sleep but never in the early morning nor in the daytime. Atropine did not suppress the exercise-induced angina in 4 of 5 patients studied. Doxazosin or phentolamine suppressed the exercise-induced episodes in 3 of 5 patients studied but aggravated spontaneous episodes in 3 patients. CONCLUSION: These data suggest that there's possibility of presence of different patterns of exercise-induced coronary spasm, which may be induced by different mechanisms from those in spontaneous episodes in patients with variant angina.

A Case of Malignant Mesenchymoma of the Heart

Malignant mesenchymomas by definition are composed of two or more cellular types that would ordinarily derive from primitive mesenchyme. They grow rapidly, recur frequently, metastasize, and can be found in a wide variety of locations. Malignant mesenchymomas as primary cardiac tumor are extremely rare with poor prognosis. Only 15 cases of cardiac malignant mesenchymoma were reported in worldwide literature in 1961-1992. We report a case of primary cardiac malignant mesenchymoma in 58 year-old female patient admitted due to hemoptysis and mild exertional dyspnea.

Two Cases of Asymptomatic Ruptured Aneurysm of the Sinus of Valsalva Confirmed by Transesophageal Echocardiography

Ruptured aneurysm of sinus of Valsalva is an uncommon congenital lesion, which was first reported in 1840 by Thurman. Its incidence is representing up to 3.5% of patients undergoing congenital heart disease surgery. Predominant symptoms are dyspnea, palpitation, and chest pain, present above the half. An early diagnosis is helpful because of the favorable surgical prognosis. Echocardiography remains useful in detecting abnormalities, and provides important information prior to cardiac catheterization and surgery. Cardiac catheterization and angiography are necessary for diagnosis of receiving chamber and associated lesions such as ventricular septal defect, aortic regurgitation, and other congenital abnormalities. The effective treatment is surgery. Without operation, cause of death are heart failure or bacterial endocarditis. We report two cases of asymptomatic ruptured aneurysm of sinus of Valsalva, confirmed by transesophageal echocardiography, and cardiac catheterization. The corrective surgery was performed without complication.

Usefulness of Dobutamine Stress Echocardiography for Identification of Viable Myocardium in Acute Myocardial Infarction

BACKGROUND: In patients with acute myocardial infarction(MI), dysfunctional myocardium at rest after successful reperfusion may represent either necrotic or viable myocardium. And the latter can be recovered contractility after revascularization or medication. OBJECTIVE: To evaluate the efFectiveness of the dobutamine stress echocardiography(DSE) for identifying viable but dysfunctional myocardium in acute MI before revascularization. METHOD: Twelve patients with acute MI after thrombolytic therapy underwent Tc-99m-tetrofosmin dipyridamole myocardial SPECT(Single Photon Emission Computed Tomography) and DSE before coronary angiography in 7~12 hospital days, and they were followed up for recovery of contractile reserve by two-dimensional echocardiography after revascularization procedure or medication. Regional wall motion abnorrnality was scored from l(normal) to 4(dyskinesia). Dobutamine responsiveness was defined as irnprovement or aggravation of regional wall motion in dyssynergic segment during any stage of dobutamine infusion. Reversible ischemia by SPECT was defined as increased perfusion defect after dipyridamole and interpreted by radiologist. Dobutamine responsiveness on DSE and reversible ischemia on myocardial SPECT were matched and compared each other. RESULTS: Of 69 dyssynergic segments, 38(55%) recovered contractility during follow up echocardiography after revascularization or medication. In 30(79%, sensitivity) of these latter segments, regional wall motion had changed during dobutamine. However, 31(45%) did not recovered contractility and 25(81%, specificity) of thern had not changed during dobutamine. Of 36 dobutamine responsive dyssynergic segments, 30(83%, positive predictive accuracy) had recorved contractility. In 25(76%, negative predictive accuracy) of 33 dobutamine non-responsive segments had not recovered contractility. Reversible ischemia on myocardial SPECT showed less sensitive(67%) and specific(56%) for detection of potentially recoverable myocardium than DSE. And positive(68%) and negative predictive accuracy(56%) also showed significantly lower than DSE. CONCLUSION: DSE can identify dyssynergic but recoverable myocardial segement for risk stratification before intervention in acute MI. Dobutamine responsiveness of dyssynergic segment is superior to reversible ischemia on myocardial SPECT for prediction of wall motion improvement after MI irrespective of intervention or medical therapy.

A Case of Takayasu's Arteritis Associated with Stenosis of Both Subelavian Arteries and Both Renal Arteries

Takayasu's arteritis(TA) is a nonspecific areritis of unknown etiology affecting segmentally the aorta and its main branches, which result in stenosis, occlusion or aneurysm of involved arteries. The clinical manifestations present with a variety of symptoms such as headache, dyspnea on exertion, pain and weakness of extremities, pulse deficit, and hypertension according to involves arteries. Usually it can be managed by medical or surgical treatment, and recently by percutaneous transluminal balloon angioplasty. The type III classified by Lupi-Herrena and associates is the most frequent variety of TA. However the case of type III involving both subclavin arteries and both renal arteries has rarely been reported. We experienced a case of TA involving both subcalvian arteries, and both renal arteries presented with paroxysmal hypertension and right flank pain, in which the stenosis of both subclavian arteries were managed by percutaneous transluminal balloon angioplasty and the stenosis and occlusion of both renal arteries were successfully managed by aorto-renal bypass surgery with autogenous right iliac artery and synthetic vessel(Gortex). The patient was discharged uneventfully.

A Case of Cerebral Mycotic Aneurysm Complicated with Subarachnoid Hemorrhage due to Infective Endocarditis

The relationship between infective endocarditis and mycotic aneurysm formation appers clear : In about two to ten percent of patients with infective endocarditis harbor septic intracranial aneurysms. But the pathogenesis, natural course and management of these lesions remains controversial. Aggressive medical treatment of the underlying infected cardiac valve or surgical replacement therapy have significantly reduced the morbidity and mortality rates associated with infective endocarditis. Clinical predictors of mycotic aneurysm, especially neurologic prodromes prior to rupture have been ill-defined since most series contain few patients or include patients with infective aneurysms who have no infective endoarditis. Similarly there has been no consensus regarding the indications and timing of cerebral angiography in patients with infective endocarditis. We have experienced a case of cerebral mycotic aneurysm complicated with subarachnoid hemorrhage due to infective endocarditis in a 29 year-old female patient, who admitted to our hospital because of the pain and paralysis of sudden onset in right forearm, which was diagnosed by echocardiography, brain computed tomography and 4-vessel cerebral angiography. The patient died of sudden rupture of mycotic aneurysm in the 7th hospital day despite intensive medical treatment. We report one case of cerebral mycotic aneurysm with a brief of literature.