Impacts of the SYNTAX score I, II and SYNTAX score II 2020 on left main revascularization.

Patients with left main coronary artery disease (LMCAD) with a high SYNTAX score (SS) were excluded from randomized studies that comparing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). We sought to compare PCI and CABG in the real-world practice and investigate the impact of SS I, SS II, and SS II 2020 on clinical outcomes. In total, 292 Patients with LMCAD (173 PCI, 119 CABG) treated between 2017 and 2021 were enrolled. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, stroke, or myocardial infarction (MI). The mean SS I was high in both groups (PCI vs. CABG: 31.64 ± 11.45 vs. 32.62 ± 11.75, p = 0.660). The primary outcome occurred in 28 patients (16.2%) in the PCI group and in 19 patients (16.0%) in the CABG group without significant difference [adjusted hazard ratio, 95% CI = 0.98 (0.51-1.90), p = 0.97] over the follow-up period (26.9 ± 17.7 months). No significant difference was observed in all-cause mortality (11.6% vs. 11.8%, p = 0.93) or stroke rates (3.5% vs. 5.0%, p = 0.51) between groups. However, PCI was associated with higher MI (4.6% vs. 0.8%, p < 0.05) and revascularization rates (26% vs. 5.9%, p < 0.001). Prognostic value of the SS I, SS II and SS II 2020 on the primary outcome was not relevant in the PCI group. Among patients with LMCAD, PCI and CABG did not significantly differ in the composite endpoint of all-cause death, stroke, and MI. These results support the potential expansion of PCI indications in LMCAD management for whom are ineligible for CABG with complex coronary artery disease.

Blockade of endothelin-1 release contributes to the anti-angiogenic effect by pro-opiomelanocortin overexpression in endothelial cells.

Pro-opiomelanocortin (POMC) is the precursor of several neuropeptides, such as corticotropin (ACTH), alpha-melanocyte-stimulating hormone (MSH), and the endogenous opioid, beta-endorphin (EP). ACTH-dependent Cushing's syndrome is characterized by ACTH overproduction and is associated with an increased risk of cardiovascular disease. Endothelial dysfunction has been recognized as an early marker of cardiovascular disease. However, the mechanism underlying endothelial dysfunction by ACTH overexpression in Cushing's patients remains elusive. Endothelial cells, the primary cells producing endothelin (ET)-1, are both the source and target of POMC-derived peptides. In the present study, we generated adenovirus vectors (Ad) encoding POMC (Ad-POMC) and green fluorescent protein (GFP; Ad-GFP) to investigate whether POMC gene transfer altered the ET-1 homeostasis and angiogenic functions in human EA.hy926 endothelial cells. Via adenovirus gene delivery, the POMC-transduced EA.hy926 cells released significantly elevated ACTH and beta-EP levels (P < 0.001). In addition, POMC gene delivery significantly decreased the ET-1 release (P < 0.001) without affecting the ET-1 messenger RNA (mRNA) level. Despite no effect on the secretion of matrix metalloproteinases (MMPs) and cell proliferation, POMC gene delivery significantly inhibited the migration (P < 0.01) and tube-forming capability (P < 0.01) of endothelial cells. Moreover, the POMC-induced inhibition of tube formation could be partially reversed by adding exogenous ET-1 (P < 0.05). In summary, the attenuated ET-1 release and angiogenic processes by POMC overexpression may contribute to endothelial dysfunction, thereby providing a link between Cushing's syndrome and cardiovascular diseases.

Gene transfer of pro-opiomelanocortin prohormone suppressed the growth and metastasis of melanoma: involvement of alpha-melanocyte-stimulating hormone-mediated inhibition of the nuclear factor kappaB/cyclooxygenase-2 pathway.

Pro-opiomelanocortin (POMC) is a prohormone of various neuropeptides, including corticotropin, alpha-melanocyte-stimulating hormone (alpha-MSH), and beta-endorphin (beta-EP). POMC neuropeptides are potent inflammation inhibitors and immunosuppressants and may exert opposite influences during tumorigenesis. However, the role of POMC expression in carcinogenesis remains elusive. We evaluated the antineoplastic potential of POMC gene delivery in a syngenic B16-F10 melanoma model. Adenovirus-mediated POMC gene delivery in B16-F10 cells increased the release of POMC neuropeptides in cultured media, which differentially regulated the secretion of pro- and anti-inflammatory cytokines in lymphocytes. POMC gene transfer significantly reduced the anchorage-independent growth of melanoma cells. Moreover, pre- or post-treatment with POMC gene delivery effectively retarded the melanoma growth in mice. Intravenous injection of POMC-transduced B16-F10 cells resulted in reduced foci formation in lung by 60 to 70% of control. The reduced metastasis of POMC-transduced B16-F10 cells could be attributed to their attenuated migratory and adhesive capabilities. POMC gene delivery reduced the cyclooxygenase-2 (COX-2) expression and prostaglandin (PG) E(2) synthesis in melanoma cells and tumor tissues. In addition, application of NS-398, a selective COX-2 inhibitor, mimicked the antineoplastic functions of POMC gene transfer in melanoma. The POMC-mediated COX-2 down-regulation was correlated with its inhibition of nuclear factor kappaB (NFkappaB) activities. Exogenous supply of alpha-MSH inhibited NFkappaB activities, whereas application of the alpha-MSH antagonist growth hormone-releasing peptide-6 (GHRP-6) abolished the POMC-induced inhibition of NFkappaB activities and melanoma growth in mice. In summary, POMC gene delivery suppresses melanoma via alpha-MSH-induced inhibition of NFkappaB/COX-2 pathway, thereby constituting a novel therapy for melanoma.

Salivary immunoreactive endothelin in patients with upper gastrointestinal diseases.

Endothelins have been implicated in gastric mucosal damage in a variety of animal models. Furthermore, clinical reports also show elevated gastric mucosal endothelin-1 levels in patients suffering from peptic ulcer diseases. We have demonstrated, first, the presence of immunoreactive endothelin (IR-ET) in human saliva. We also show that endothelins are rather stable in human saliva. The present study was undertaken to determine whether patients with endoscopically proven upper gastrointestinal diseases have a salivary excess of IR-ET, compared with patients with a normal esophagogastroduodenoscopy. Saliva was collected from fasting subjects prior to esophagogastroduodenoscopy. The levels of IR-ET were measured by the radioimmunoassay method. The salivary concentrations of IR-ET in the studied subjects were as follows: 8.9 +/- 1.0 fmol/mL (mean +/- standard error of the mean) for patients with gastric ulcers (n = 18); 7.3 +/- 1.0 fmol/mL for patients with duodenal ulcers (n = 22); and 6.8 +/- 0.6 fmol/mL for patients with gastritis (n = 28). These values are all higher than that of normal subjects (4.4 +/- 0.5 fmol/mL, n = 20; P < 0.001, P < 0.01, and P < 0.05, respectively). No significant differences in salivary IR-ET were noted between patients with a normal esophagogastroduodenoscopy and patients with esophagitis (3.8 +/- 0.7 fmol/mL, n = 4) or gastric cancer (5.3 +/- 1.4 fmol/mL, n = 4). There were no significant differences in the salivary IR-ET levels between males and females. However, the salivary IR-ET levels in the smokers (8.0 +/- 0.6 fmol/mL, n = 38) were significantly higher (P < 0.01) than those of the non-smokers (6.0 +/- 0.4 fmol/mL, n = 58). There was no correlation of IR-ET levels with age. Our findings suggest that salivary endothelin may have a contributing role in certain gastroduodenal diseases.

Immunoreactive endothelin in Taiwanese thyroid cystic fluid.

Endothelin-1 is a major vasoconstrictor peptide, first found in endothelial cells and later in many other tissues, including the thyroid gland. It is well known that endothelins can act as autocrine and/or paracrine regulators of thyroid homeostasis and growth. Previously we have demonstrated that immunoreactive endothelins (IR-ET) are present in various human body fluids, and IR-ET has also been detected in pathologic breast and thyroid cystic fluids. In this study, the IR-ET in Taiwanese thyroid cystic fluid was measured by radioimmunoassay and characterized by chromatography. Human thyroid cystic fluid was obtained by fine needle aspiration, was centrifuged, and the supernatant was stored at -20 degrees C until IR-ET assay. IR-ET has been detected in 25 of 33 samples of thyroid cystic fluid [25 cases, 4.11 +/- 0.31 fmol/mL (mean +/- standard error of the mean); other eight cases, undetectable]. Gel permeation chromatography of the extract of pooled cystic fluid showed only one major peak at the elution position of human endothelin-1 standard. No difference in cystic IR-ET levels was found in our patients with cystic nodules in relation to differences in thyroid function. It is probable that endothelin-1 is produced by the epithelial cells lining the thyroid cysts, and the increased levels of IR-ET in cystic fluid found in our patients could either be secondary to cystic nodule development or have a role in goiter formation.

Sclerotherapy of thyroid cystic nodules.

BACKGROUND AND PURPOSE: Percutaneous ethanol injection (PEI) has been established as an effective and safe treatment for thyroid cystic nodules (TCN). Certain tetracyclines have also been used successfully as sclerosing agents, and it has been proposed that a low pH might account for their efficacy in this indication. This study compared the effectiveness of ethanol and dilute hydrochloric acid (pH 1.0) in the sclerotherapy of TCN. METHODS: A total of 27 patients with TCN with a mean cystic volume of 16.6 mL (5-45 mL) were randomly assigned to receive 1 of the following 3 treatments: 1) needle aspiration only, 9 patients; 2) PEI, 10 patients; or 3) percutaneous hydrochloric acid injection (PHI), 8 patients. The procedures were performed weekly until cure was evident. Resolution was defined as the disappearance of cyst or reduction of cystic volume to below 0.5 mL. Treatment was considered a failure if the condition did not resolve after 5 sessions of intervention. The 10 original patients treated by PEI and 14 additional patients subsequently enrolled and treated by PEI were followed for 24 months in order to evaluate the long-term effects of PEI treatment. Follow-up physical examination and ultrasound scan was performed every 3 months during the first year and every 6 months during the second year. A cystic volume of greater than 1 mL was regarded as a recurrence. RESULTS: PHI did not have a better cure rate than aspiration alone (37.5% vs 44.4%, p = 0.778). PEI had a significantly higher cure rate than PHI (90% vs 37.5%, p = 0.023) and aspiration alone (90% vs 44.4%, p = 0.038). No patient who received aspiration only complained of cervical pain. Four patients who received PEI and 3 patients who received PHI complained of self-limited cervical pain soon after sclerosant injection. Completed follow-up in the 24 patients ranged from 3 to 24 months (mean, 15.5 +/- 7.7 months), and only 3 patients (12.5%) were found to have recurrence within the first 9 months. The likelihood of recurrence was not correlated with pretreatment cystic volume. CONCLUSIONS: Use of a low-pH sclerosant (PHI) was of no benefit. PEI provides a rapid, tolerable, and sustained effect and can be used as first-line treatment in patients with TCN.