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1.
J Am Heart Assoc ; 13(8): e032397, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38591334

RESUMEN

BACKGROUND: This study investigated whether initial SGLT2 (sodium-glucose cotransporter 2) inhibitor-based treatment is superior to metformin-based regimens as a primary prevention strategy among low-risk patients with diabetes. METHODS AND RESULTS: In this nationwide cohort study, a total of 38 496 patients with diabetes with low cardiovascular risk were identified (age 62.0±11.6 years, men 50%) from January 1 to December 31, 2016. Patients receiving SGLT2 inhibitors-based and metformin-based regimens were 1:2 matched by propensity score. Study outcomes included all-cause mortality, cardiovascular death, hospitalization for heart failure, stroke, and progression to end-stage renal disease. Compared with 1928 patients receiving metformin-based regimens, 964 patients receiving SGLT2 inhibitor-based regimens had similar all-cause mortality (hazard ratio [HR], 0.75 [95% CI, 0.51-1.12]), cardiovascular death (HR, 0.69 [95% CI, 0.25-1.89]), hospitalization for heart failure (HR, 1.06 [95% CI, 0.59-1.92]), stroke (HR, 0.78 [95% CI, 0.48-1.27]), and progression to end-stage renal disease (HR, 0.88 [95% CI, 0.32-2.39]). However, SGLT2 inhibitors were associated with a lower risk of all-cause mortality (HR, 0.47 [95% CI, 0.23-0.99]; P for interaction=0.008) and progression to end-stage renal disease (HR, 0.22 [95% CI, 0.06-0.82]; P for interaction=0.04) in patients under the age of 65. CONCLUSIONS: In comparison to metformin-based regimens, SGLT2 inhibitor-based regimens showed a similar risk of all-cause mortality and adverse cardiorenal events. SGLT2 inhibitors might be considered as first-line therapy in select low-risk patients, for example, younger patients with diabetes.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Fallo Renal Crónico , Metformina , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Accidente Cerebrovascular , Masculino , Humanos , Persona de Mediana Edad , Anciano , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Metformina/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Estudios de Cohortes , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/inducido químicamente , Factores de Riesgo , Resultado del Tratamiento , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/inducido químicamente , Factores de Riesgo de Enfermedad Cardiaca , Accidente Cerebrovascular/inducido químicamente , Glucosa , Hipoglucemiantes/uso terapéutico
2.
Redox Biol ; 66: 102861, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37666118

RESUMEN

Uterine fibroids, the most common benign tumors of the myometrium in women, are characterized by abnormal extracellular matrix deposition and uterine smooth muscle cell neoplasia, with high recurrence rates. Here, we investigated the potential of the marine natural product manzamine A (Manz A), which has potent anti-cancer effects, as a treatment for uterine fibroids. Manz A inhibited leiomyoma cell proliferation in vitro and in vivo by arresting cell cycle progression and inducing caspase-mediated apoptosis. We performed target prediction analysis and identified sterol o-acyltransferases (SOATs) as potential targets of Manz A. Cholesterol esterification and lipid droplet formation were reduced by Manz A, in line with reduced SOAT expression. As a downstream target of SOAT, Manz A also prevented extracellular matrix deposition by inhibiting the ß-catenin/fibronectin/metalloproteinases axis and enhanced autophagy turnover. Excessive free fatty acid accumulation by SOAT inhibition led to reactive oxygen species to impair mitochondrial oxidative phosphorylation and trigger endoplasmic reticulum stress via PERK/eIF2α/CHOP signaling. The inhibitory effect of ManzA on cell proliferation was partially restored by PERK knockdown and eliminated by tauroursodeoxycholic acid, suggesting oxidative stress plays a critical role in the mechanism of action of Manz A. These findings suggest that targeting SOATs by Manz A may be a promising therapeutic approach for uterine fibroids.


Asunto(s)
Leiomioma , Estrés Oxidativo , Femenino , Humanos , Carbazoles , Leiomioma/tratamiento farmacológico , Leiomioma/genética , Proliferación Celular
3.
J Cardiothorac Surg ; 18(1): 82, 2023 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-36882839

RESUMEN

BACKGROUND: Pump exchange surgery of left ventricular assist device (LVAD) has been demonstrated in several studies; however, information for Asian patients was limited. CASE PRESENTATION: A 63-year-old man underwent a pump upgrade from HeartMate II to HeartMate 3 for driveline damage through limited left anterior thoracotomy and lower partial sternotomy. He did not experience any hemodynamic adverse events or device malfunction during postoperative follow-ups of 12 months. We also reviewed all published cases with HeartMate II exchange to HeartMate 3. CONCLUSIONS: The case demonstrated that it was safe and feasible to perform HMII LVAD exchange to HM3 through a limited approach for Asian patients.


Asunto(s)
Corazón Auxiliar , Masculino , Humanos , Persona de Mediana Edad , Corazón Auxiliar/efectos adversos , Periodo Posoperatorio , Esternotomía
4.
Molecules ; 27(14)2022 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-35889404

RESUMEN

Melissa officinalis (MO), known as lemon balm, is a popular ingredient blended in herbal tea. In recent decades, the bioactivities of MO have been studied in sub-health and pathological status, highlighting MO possesses multiple pharmacological effects. We previously showed that hot water MO extract exhibited anticancer activity in colorectal cancer (CRC). However, the detailed mechanisms underlying MO-induced cell death remain elusive. To elucidate the anticancer regulation of MO extract in colon cancer, a data-driven analysis by proteomics approaches and bioinformatics analysis was applied. An isobaric tandem mass tags-based quantitative proteome analysis using liquid chromatography-coupled tandem mass spectrometry was performed to acquire proteome-wide expression data. The over-representation analysis and functional class scoring method were implemented to interpret the MO-induced biological regulations. In total, 3465 quantifiable proteoforms were identified from 24,348 peptides, with 67 upregulated and 54 downregulated proteins in the MO-treated group. Mechanistically, MO impeded mitochondrial respiratory electron transport by triggering a reactive oxygen species (ROS)-mediated oxidative stress response. MO hindered the mitochondrial membrane potential by reducing the protein expression in the electron transport chain, specifically the complex I and II, which could be restored by ROS scavenger. The findings comprehensively elucidate how MO hot water extract activates antitumor effects in colorectal cancer (CRC) cells.


Asunto(s)
Neoplasias del Colon , Melissa , Mitocondrias , Extractos Vegetales , Neoplasias del Colon/tratamiento farmacológico , Humanos , Melissa/química , Mitocondrias/fisiología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Proteoma , Especies Reactivas de Oxígeno/metabolismo , Agua
6.
Int J Mol Sci ; 23(10)2022 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-35628349

RESUMEN

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary disease of the heart muscle. Clinical challenges remain, however, in identifying patients with ARVC in the early or concealed stages with subtle clinical manifestations. Therefore, we wanted to identify potential targets by immunohistochemical (IHC) analysis in comparison with controls. Pathogenic mutations were identified in 11 of 37 autopsied patients with ARVC. As observed from IHC analysis of the RV, expression of αT-catenin and plakophilin-2 is significantly decreased in autopsied patients with ARVC as compared to controls, and the decreased expression is consistent in patients with and without pathogenic mutations. Furthermore, ARVC specimens demonstrated a reduced localization of αT-catenin, desmocollin-2, desmoglein-2, desmoplakin, and plakophilin-2 on intercalated discs. These findings have been validated by comparing RV specimens obtained via endomyocardial biopsy between patients with ARVC and those without. The pathogenic mutation was present in 3 of 5 clinical patients with ARVC. In HL-1 myocytes, siRNA was used to knockdown CTNNA3, and western blotting analysis demonstrated that the decline in αT-catenin expression was accompanied by a significant decline in the expression of plakophilin-2. The aforementioned effect was directed towards protein degradation rather than mRNA stability. Plakophilin-2 expression decreases concurrently with the decline in CTNNA3 expression. Therefore, the expression of αT-catenin and plakophilin-2 could be potential surrogates for the diagnosis of ARVC.


Asunto(s)
Displasia Ventricular Derecha Arritmogénica , Cateninas , Placofilinas , Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/genética , Displasia Ventricular Derecha Arritmogénica/metabolismo , Displasia Ventricular Derecha Arritmogénica/patología , Cateninas/metabolismo , Moléculas de Adhesión Celular/metabolismo , Humanos , Inmunohistoquímica , Mutación , Miocardio/metabolismo , Miocardio/patología , Placofilinas/biosíntesis , Placofilinas/genética , Placofilinas/metabolismo
7.
Biomedicines ; 9(8)2021 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-34440086

RESUMEN

5-Fluorouracil (5-FU) is one of several chemotherapeutic agents in clinical use as a standard of care to treat colorectal cancers (CRCs). As an antimetabolite, 5-FU inhibits thymidylate synthase to disrupt the synthesis and repair of DNA and RNA. However, only a small proportion of patients benefit from 5-FU treatment due to the development of drug resistance. This study applied pharmacogenomic analysis using two public resources, the Genomics of Drug Sensitivity in Cancer (GDSC) and the Connectivity Map, to predict agents overcoming 5-FU resistance in CRC cells based on their genetic background or gene expression profile. Based on the genetic status of adenomatous polyposis coli (APC), the most frequent mutated gene found in CRC, we found that combining a MEK inhibitor with 5-FU exhibited synergism effects on CRC cells with APC truncations. While considering the gene expression in 5-FU resistant cells, we demonstrated that targeting ROCK is a potential avenue to restore 5-FU response to resistant cells with wild-type APC background. Our results reveal MEK signaling plays a pivotal role in loss-of-function, APC-mediated 5-FU resistance, and ROCK activation serves as a signature in APC-independent 5-FU resistance. Through the use of these available database resources, we highlight possible approaches to predict potential drugs for combinatorial therapy for patients developing resistance to 5-FU treatment.

8.
Front Cardiovasc Med ; 8: 676897, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34336945

RESUMEN

Background: The clinical significance and outcomes of ventricular tachyarrhythmias (VTa) in patients undergoing valve replacement have rarely been reported. Objective: This study aimed to investigate the incidence and outcome of VTa after surgical valve replacement. Methods: We conducted a population-based retrospective cohort study using data obtained from the Taiwan National Health Insurance Research Database. In total, 10,212 patients were selected after 1:1 propensity-score matching based on the type of prosthetic valve used (mechanical vs. bioprosthetic). Various outcomes during long-term follow-up were analyzed. Results: After a median follow-up period of 59.6 months, the crude incidence rate of VTa after surgical valve replacement was 4.8/1,000 person-years, and the cumulative incidence of VTa persistently increased after surgery. Furthermore, the occurrences of VTa after valve replacement significantly increased the risk of cardiovascular (CV) death (P < 0.001, HR 1.67, 95% CI 1.41-1.96), stroke- (P < 0.001, HR 1.66, 95% CI 1.37-2.01), atrial fibrillation- (P < 0.001, HR 2.80, 95% CI 2.42-3.24), and congestive heart failure-related hospitalization (P < 0.001, HR 2.61, 95% CI 2.30-2.95). Among patients with VTa, all-cause mortality (P = 0.001, HR 0.49, 95% CI 0.32-0.75) and CV death (P = 0.047, HR 0.58, 95% CI 0.34-0.99) in those with implantable cardioverter-defibrillator (ICD) implantation were lower than those without. Conclusion: The crude incidence rate of VTa after surgical valve replacement was 4.8/1,000 person-years, and the cumulative incidence of VTa persistently increased during follow-up. The presence of VTa after surgical valve replacement increases hospitalization and CV death, while ICD implantation reduced the mortality rate in these patients.

9.
Molecules ; 26(9)2021 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-33923185

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a 5-year survival rate of <8%. Therefore, finding new treatment strategies against PDAC cells is an imperative issue. Betulinic acid (BA), a plant-derived natural compound, has shown great potential to combat cancer owing to its versatile physiological functions. In this study, we observed the impacts of BA on the cell viability and migratory ability of PDAC cell lines, and screened differentially expressed proteins (DEPs) by an LC-MS/MS-based proteomics analysis. Our results showed that BA significantly inhibited the viability and migratory ability of PDAC cells under a relatively low dosage without affecting normal pancreatic cells. Moreover, a functional analysis revealed that BA-induced downregulation of protein clusters that participate in mitochondrial complex 1 activity and oxidative phosphorylation, which was related to decreased expressions of RNA polymerase mitochondrial (POLRMT) and translational activator of cytochrome c oxidase (TACO1), suggesting that the influence on mitochondrial function explains the effect of BA on PDAC cell growth and migration. In addition, BA also dramatically increased Apolipoprotein A1 (APOA1) expression and decreased NLR family CARD domain-containing protein 4 (NLRC4) expression, which may be involved in the dampening of PDAC migration. Notably, altered expression patterns of APOA1 and NLRC4 indicated a favorable clinical prognosis of PDAC. Based on these findings, we identified potential proteins and pathways regulated by BA from a proteomics perspective, which provides a therapeutic window for PDAC.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Triterpenos Pentacíclicos/farmacología , Proteoma/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Fosforilación Oxidativa/efectos de los fármacos , Proteoma/efectos de los fármacos , Proteómica/métodos , Espectrometría de Masas en Tándem , Ácido Betulínico
11.
Surg Infect (Larchmt) ; 22(7): 680-683, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33337972

RESUMEN

Background: Abdominal aortic stent graft infection (AAGI) is a severe complication. The optimal management of AAGI remains unclear. This study provides updated results of bilateral axillofemoral bypasses (AFBs) for patients with AAGI. Patients and Methods: In total, 31 patients (25 men; mean age, 67.1 years) with AAGI treated using AFB between January 2006 and April 2020 were included. Overall, the mean follow-up duration was 24 months (range, 1-72). In the 23 patients who survived the post-operative period, the mean follow-up duration was 32 months (range, 12-72). Results: Thirty-day and in-hospital mortality rates was 16% and 26%, respectively. The 12-month primary and secondary patency rates for the AFB graft were both 91%. In total, seven (30%) patients received re-interventions such as thrombectomy and balloon angioplasty. No amputation was required during follow-up. Culture results were positive in 87% of pre-operative cultures and 84% of intra-operative cultures. Staphylococcus aureus was the most prevalent pathogen, with four cases of methicillin-resistant Staphylococcus aureus and one each of vancomycin-resistant enterococci, carbapenem-resistant Klebsiella pneumoniae, and carbapenem-resistant Enterobacteriaceae. In-hospital mortality rate was 57% in patients with drug-resistant pathogens. Conclusions: Reconstruction with bilateral AFB and stent graft removal in patients with AAGI is a feasible treatment modality and provided an acceptable patency rate and low amputation rate. Additional studies investigating long-term results and the optimal treatment of AAGI are required.


Asunto(s)
Aneurisma de la Aorta Abdominal , Implantación de Prótesis Vascular , Staphylococcus aureus Resistente a Meticilina , Anciano , Aneurisma de la Aorta Abdominal/cirugía , Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/efectos adversos , Remoción de Dispositivos , Humanos , Masculino , Estudios Retrospectivos , Stents/efectos adversos , Resultado del Tratamiento
12.
Interact Cardiovasc Thorac Surg ; 32(1): 97-105, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33346345

RESUMEN

OBJECTIVES: Although commercial iliac branch devices offer a new and valid endovascular approach to treating iliac aneurysm and effectively preserve antegrade flow of the internal iliac artery, their use may not be suited for all types of challenging anatomy, especially isolated common iliac artery aneurysm. Our custom-made iliac bifurcation device has a unique design and excludes both combined and isolated iliac branch aneurysm. This study validated the efficacy and safety of the custom device by comparing clinical outcomes between groups receiving commercial and custom devices. METHODS: Data of consecutive patients receiving iliac bifurcation device implantation for iliac aneurysm with or without concomitant endovascular repair for abdominal aortic aneurysm from January 2010 to May 2019 were reviewed. RESULTS: Iliac bifurcation device implantation with or without concomitant abdominal aortic aneurysm stent grafting was completed in 46 patients (commercial, n = 35; custom, n = 11). No significant differences were observed regarding postoperative complications, occlusion or endoleak. Comparisons of primary (80.8% vs 85.7%, P = 0.88) and secondary (86.5% vs 85.7%, P = 0.85) patency and freedom from reintervention (88.2% vs 100%, P = 0.33), all-cause mortality (78.6% vs 100%, P = 0.25) and aneurysm-related mortality (100% vs 100%, P = 1.00) also indicated no differences at a 5-year surveillance point. Furthermore, the iliac aneurysms of the groups displayed similar shrinkage 1 year after procedures. CONCLUSIONS: For iliac aneurysm, the novel custom-made iliac bifurcation device is an adaptable design not inferior to commercial devices with regard to postoperative complications, bridge occlusion, endoleak and short-term aneurysm remodelling. It provides an alternative for treatment, particularly when certain anatomic challenges are present. CLINICAL TRIAL REGISTRATION: 2018-07-050BC, 2017-01-023ACF.


Asunto(s)
Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/cirugía , Procedimientos Endovasculares/instrumentación , Aneurisma Ilíaco/complicaciones , Aneurisma Ilíaco/cirugía , Anciano , Anciano de 80 o más Años , Implantación de Prótesis Vascular/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Aneurisma Ilíaco/mortalidad , Arteria Ilíaca/cirugía , Estimación de Kaplan-Meier , Masculino , Complicaciones Posoperatorias/etiología , Cuidados Preoperatorios , Estudios Retrospectivos , Resultado del Tratamiento
13.
Heart Vessels ; 36(2): 235-241, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32767084

RESUMEN

OBJECTIVES: To compare the outcomes of using iliac branch devices (IBD) and the crossover chimney (COCh) technique for preserving the internal iliac artery (IIA) during endovascular aortic repair in patients with common iliac aneurysm (CIA). METHODS: From February 2010 to July 2016, we recruited 61 consecutive and elective patients. Thirty of them received the IBD, and the remaining 31 received the COCh. Their medical chart was reviewed retrospectively, and computed tomographic angiography was performed at 3, 6, and 12 months postoperatively and then yearly as a follow-up. RESULTS: The median follow-up time was 19.72 ± 5.45 months. The technical success rate reached 100% in both groups. The 12-month and 24-month primary IIA patency rates between IBD and COCh group were 90.00% versus 93.54% (p = 0.67) and 83.33% versus 93.54% (p = 0.25). The numbers of stents were 1.00 ± 0.00 and 1.93 ± 0.24 in the IBD and COCh group (p < 0.001). No significant difference was observed for the incidence of type 1a (IBD/COCh = 3.33%/6.45%, p > 0.99) and type 2 endoleak (IBD/COCh = 13.33%/12.90%, p > 0.99) between two groups. Neither type 1b or type 3 endoleak nor delayed aortic rupture appeared in our series. The postoperative complication rates did not exhibit significant differences either. Free from reintervention was also similar in both groups (IBD/COCh = 22.50 ± 4.62/23.00 ± 3.87 months, p = 0.64). CONCLUSIONS: The IBD and COCh techniques exhibited similar success rates and IIA patency rates at the 24-month follow-up. Both these techniques are feasible for the preservation of IIA in patients with CIA.


Asunto(s)
Implantación de Prótesis Vascular/métodos , Procedimientos Endovasculares/métodos , Aneurisma Ilíaco/cirugía , Arteria Ilíaca/cirugía , Anciano , Angiografía por Tomografía Computarizada , Procedimientos Quirúrgicos Electivos/métodos , Femenino , Estudios de Seguimiento , Humanos , Aneurisma Ilíaco/diagnóstico , Arteria Ilíaca/diagnóstico por imagen , Masculino , Diseño de Prótesis , Estudios Retrospectivos , Resultado del Tratamiento
14.
ACS Omega ; 5(49): 31792-31800, 2020 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-33344833

RESUMEN

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide. Lifestyle-related factors, such as diet, are associated with the development of CRC. Cumulating evidence indicates noticeable chemopreventive effects of phytochemicals on CRC, suggesting that drinking herbal tea potentially reduces the risk of distal colon cancer via its antiproliferative and anti-angiogenic activities. We examine the antitumor effects of nine components frequently found in herbal tea and uncover the underlying molecular mechanism. Among them, the hot water extract of Melissa officinalis (MO) exhibited the highest anticancer activity on CRC cells. We revealed that MO reduced cell proliferation, induced cell cycle arrest at the G2/M phase, triggered caspase-dependent apoptotic cell death, and inhibited cell migration ability by modulating the epithelial-mesenchymal transition in HCT116 CRC cells. To examine the metabolite composition in the MO hot water extract, we applied mass spectrometry-based analysis and identified 67 compounds. Among them, the phenolic compounds, including lignans, phenylpropanoids, and polyketides, are widely found in natural products and possess various bioactivities such as anti-inflammatory, antioxidation, and anticancer effects. The results indicate that herbal tea consumption benefits CRC prevention and management.

15.
AJR Am J Roentgenol ; 214(6): 1409-1416, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32286876

RESUMEN

OBJECTIVE. The purpose of this study was to compare the volume alteration and effective renal plasma flow of kidneys supplied by false lumens (FLs) with those of kidneys supplied by true lumens (TLs), to show the discrepancy in perfusion between the two lumens. We sought to corroborate malperfusion of FL-supplied kidneys with imaging characteristics observed on CT angiography. MATERIALS AND METHODS. A retrospective analysis was conducted using prospectively collected data for 87 patients with a diagnosis of residual chronic aortic dissection between 2005 and 2013 who had one kidney perfused by a TL and the other kidney perfused by a FL. RESULTS. Overall, at follow-up, FL-supplied kidneys had a mean (± SD) effective renal plasma flow (117.5 ± 42.6 vs 146.6 ± 41.0 mL/min; p = 0.004) and volume (131.1 ± 37.1 vs 146.5 ± 33.3 cm3; p = 0.004) that were lower than those of TL-supplied kidneys. Multivariate analysis revealed the presence of a proximal major inlet (odds ratio, 0.306; 95% CI, 0.103-0.910; p = 0.033) and large FL area (odds ratio, 0.104; CI, 0.012-0.880; p = 0.038) as factors protecting against malperfusion of FL-supplied kidneys. In patients with dissected renal arteries, the FL-supplied kidney had low effective renal plasma flow (mean, 88.5 ± 26.8 vs 149.6 ± 43.5 mL/min; p = 0.004) and diminished volume (mean, 120.4 ± 30.4 vs 152.3 ± 24.6 cm3; p = 0.001). CONCLUSION. In the present study, kidneys perfused by FLs showed decreased volume and reduced effective renal plasma flow during follow-up, particularly those kidneys with dissected renal arteries, a small FL area at the renal level, and lack of a proximal major inlet. Further studies are warranted to identify the clinical relevance of malperfusion in FL-supplied kidneys.


Asunto(s)
Disección Aórtica/complicaciones , Angiografía por Tomografía Computarizada/métodos , Riñón/irrigación sanguínea , Riñón/diagnóstico por imagen , Enfermedad Crónica , Medios de Contraste , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
16.
Cell Death Dis ; 10(11): 786, 2019 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-31624245

RESUMEN

MYCN-amplified (MNA) neuroblastoma is an aggressive neural crest-derived pediatric cancer. However, MYCN is indispensable for development and transcriptionally regulates extensive network of genes. Integrating anti-MYCN ChIP-seq and gene expression profiles of neuroblastoma patients revealed the metabolic enzymes, MTHFD2 and PAICS, required for one-carbon metabolism and purine biosynthesis were concomitantly upregulated, which were more susceptible to metastatic neuroblastoma. Moreover, we found that MYCN mediated the folate cycle via MTHFD2, which contributed one-carbon unit to enhance purine synthesis, and further regulated nucleotide production by PAICS in response to cancer progression. Dual knockdown of the MYCN-targeted gene pair, MTHFD2 and PAICS, in MNA neuroblastoma cells synergically reduced cell proliferation, colony formation, migration ability, and DNA synthesis. By systematically screening the compound perturbagens, the gene expression levels of MTHFD2 and PAICS were specifically suppressed by anisomycin and apicidin across cell lines, and our co-treatment results also displayed synergistic inhibition of MNA neuroblastoma cell proliferation. Collectively, targeting a combination of MYCN-targeted genes that interrupts the interconnection of metabolic pathways may overcome drug toxicity and improve the efficacy of current therapeutic agents in MNA neuroblastoma.


Asunto(s)
Aminohidrolasas/metabolismo , Carboxiliasas/metabolismo , Metilenotetrahidrofolato Deshidrogenasa (NADP)/metabolismo , Enzimas Multifuncionales/metabolismo , Purinas/biosíntesis , Aminohidrolasas/genética , Carboxiliasas/genética , Ciclo Celular/fisiología , Procesos de Crecimiento Celular , Línea Celular Tumoral , Técnicas de Silenciamiento del Gen , Humanos , Metabolómica , Metilenotetrahidrofolato Deshidrogenasa (NADP)/genética , Terapia Molecular Dirigida , Enzimas Multifuncionales/genética , Neuroblastoma/genética , Neuroblastoma/metabolismo , Neuroblastoma/patología , Neuroblastoma/terapia , Transcriptoma , Transfección , Regulación hacia Arriba
17.
J Chin Med Assoc ; 82(9): 710-713, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31335630

RESUMEN

BACKGROUND: Endovascular repair with stent-graft is a treatment option for patient with common iliac artery aneurysm (CIAA). However, the preservation of the internal iliac artery (IIA) is a concern. The commercially available iliac branched device (IBD) requires a common iliac length of at least 5 cm, which is usually too long for Asian people. Here, we report our medium-term results of using tailor-made IBD for patients with short common iliac artery (CIA) with and without abdominal aortic aneurysm (AAA). METHODS: A selected iliac limb of the AAA stent-graft was unloaded from the delivery system. A 6-mm fenestration hole was made at the length of the CIA from the proximal end. The edge of the hole was reinforced with the soft and radiopaque tip of a 0.014´´ wire. Then, the iliac limb was reloaded into the introduced sheath as the tailor-made IBD. It was inserted from the selected side of the femoral artery and deployed. The ipsilateral IIA was cannulated through the fenestration hole. Then, a balloon-expandable or self-expandable covered stent with an appropriate size was deployed as the bridging stent-graft. RESULTS: Between March 2013 and March 2017, a total of 10 patients received the tailor-made IBDs. One patient died of systemic thromboembolism 2 days after the operation. The bridging stent-grafts remained patent in all patients, except one occluded at 1 year after operation. CONCLUSION: A tailor-made IBD is an easy-to-apply, alternative option for preserving the IIA perfusion in short CIAA patients with and without AAA.


Asunto(s)
Implantación de Prótesis Vascular/instrumentación , Procedimientos Endovasculares/instrumentación , Aneurisma Ilíaco/cirugía , Stents , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
18.
J Vasc Interv Radiol ; 30(7): 979-986, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30982639

RESUMEN

PURPOSE: To evaluate the effect of renal stent-graft placement on kidney function and size alternation in chronic aortic dissection. MATERIALS AND METHODS: Twenty-five consecutive patients with chronic aortic dissection after thoracic endovascular aortic repair who underwent renal stent-graft placement between January 2015 and December 2016 were retrospectively reviewed. Forty-three patients with chronic aortic dissection who received thoracic endovascular aortic repair in the same period were reviewed as a control group for kidney volume comparison. RESULTS: Twenty-five stent-grafts were deployed over 25 renal arteries. Overall renal function was assessed by the slope of the regression line constructed from the plots of creatinine clearance versus time within 2 years after the procedure (-0.2810 vs -0.3146 mL/min-1/mo-1, P = .868), kidney volume at 12 months (129.4 ± 40.9 vs 137.0 ± 44.2 cm2, P = .193) and effective renal plasma flow at 6 months (106.3 ± 46.9 vs 124.4 ± 55.5 mL/min, P = .050) and was not significantly deteriorated. Seven treated patients (87.5%) with a renal artery supplied by a false lumen had a decrease in kidney volume, as did 14 patients (56%) in the control group (P = .206). Three patients with a dissected renal artery (75%) in the stent-graft group had an increase in kidney volume compared with 1 patient (11.1%) in the control group (P = .052). CONCLUSIONS: Occlusion of the re-entry tear by a stent-graft in the renal artery remains a safe strategy to promote false lumen thrombosis. The stent-graft poses a potential risk of reducing the kidney volume in kidneys supplied by the false lumen but may provide a positive effect in kidney volume with a concomitant dissected renal artery in chronic aortic dissection.


Asunto(s)
Aneurisma de la Aorta/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular/instrumentación , Prótesis Vascular , Procedimientos Endovasculares/instrumentación , Riñón/irrigación sanguínea , Arteria Renal/cirugía , Stents , Adulto , Anciano , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/fisiopatología , Aneurisma de la Aorta/diagnóstico por imagen , Aneurisma de la Aorta/fisiopatología , Implantación de Prótesis Vascular/efectos adversos , Enfermedad Crónica , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Arteria Renal/diagnóstico por imagen , Arteria Renal/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
19.
J Thorac Cardiovasc Surg ; 158(4): 1007-1016, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-30773384

RESUMEN

OBJECTIVES: Our objective was to examine the role of the provisional extension to induce complete attachment (PETTICOAT) aortic dissection repair technique with bare metal stents (BMSs) in abdominal remodeling of residual DeBakey type I aortic dissection. METHODS: We retrospectively reviewed the records of patients with chronic aneurysm formation and residual DeBakey type I aortic dissection (ie, original acute aortic dissection DeBakey type I after primary surgical open repair) who underwent arch reoperation with frozen elephant trunk replacement or endovascular debranching with or without an abdominal BMS between December 2006 and December 2016. We analyzed diameters and volumes in 3 dimensions for the true and false lumens of the thoracic and abdominal aorta as well as the thrombosis percentage of the false lumen between the non-BMS (non-PETTICOAT) and BMS (PETTICOAT) groups. RESULTS: Forty-seven patients who had completed at least 1 year of follow-up were included. The non-BMS (without abdominal BMS) and BMS groups had significant differences in abdominal true lumen diameter and volumetric change at the first postoperative examination and at the examination 1 year after surgery (26.8 mL, median [19.4-34.1 mL, interquartile range (IQR)]) in non-BMS vs 42.5 mL, median [31.1-57.9 mL, IQR]) in BMS (postoperative survey [F test, 33.775; P = .000]) and (30.1 mL, median [20.5-34.1 mL, IQR] in non-BMS vs 46.6 mL, median [31.3-57.4 mL, IQR]) in BMS (12-month survey [F test, 14.001; P = .001]). The abdominal false lumen thrombosis percentage was higher in the BMS group than in the non-BMS group (25.6%, median [16.4%-58.9%, IQR] in non-BMS vs 54.0%, median [36.7%-65.3%, IQR] in the BMS group (F test, 6.318; P = .016). CONCLUSIONS: Following reintervention for chronic residual DeBakey type I aortic dissection, PETTICOAT abdominal dissection BMS effectively expanded the thoracic and abdominal true lumen and augmented false lumen thrombosis percentage during the first postoperative year.


Asunto(s)
Aorta Abdominal/cirugía , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Remodelación Vascular , Anciano , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/fisiopatología , Aorta Abdominal/diagnóstico por imagen , Aorta Abdominal/fisiopatología , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/fisiopatología , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/fisiopatología , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/instrumentación , Enfermedad Crónica , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Stents , Factores de Tiempo , Resultado del Tratamiento
20.
J Vasc Surg ; 69(1): 141-147, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30104098

RESUMEN

OBJECTIVE: Common femoral artery (CFA) occlusive disease remains a debatable site for endovascular therapy, and the outcome of drug-eluting balloon (DEB) angioplasty in treating CFA occlusive disease is largely unknown. This study compared the efficacy, safety, and short-term patency rate of DEB angioplasty and femoral endarterectomy for treatment of CFA occlusive disease. METHODS: From March 2013 to June 2016, there were 100 patients with symptomatic CFA occlusive disease who were retrospectively reviewed. Forty patients were treated with DEB angioplasty and 60 were treated with femoral endarterectomy. Each patient received regular follow-up. Patency rate, ankle-brachial index, target lesion revascularization, and adverse events were assessed. RESULTS: Technical success was 100% in all patients. The DEB group had a lower 1-year primary patency rate (75.0% vs 96.7%; P = .003), but the secondary patency rate was similar between the two groups (97.5% vs 98.3%; P = 1.000). At 2-year follow-up, the primary patency was lower in the DEB group (57.1%) than in the endarterectomy group (94.1%; P = .001), whereas the secondary patency rate had no significant difference (90.5% vs 97.1%; P = 1.000). Both groups had significant improvement in ankle-brachial index. Freedom from target lesion revascularization was lower in the DEB group both at 1 year (75.0% vs 96.7%; P = .003) and at 2 years (57.1% vs 94.1%; P = .001). There was no significant difference in the incidence of complications and adverse events. CONCLUSIONS: Femoral endarterectomy has a better primary patency rate compared with DEB angioplasty in treating CFA occlusive disease without significant increase in complications. In patients not suitable for endarterectomy, DEB angioplasty provides a similar secondary patency rate and could be considered an alternative treatment.


Asunto(s)
Angioplastia de Balón/instrumentación , Fármacos Cardiovasculares/administración & dosificación , Materiales Biocompatibles Revestidos , Endarterectomía , Arteria Femoral/cirugía , Enfermedad Arterial Periférica/terapia , Dispositivos de Acceso Vascular , Anciano , Anciano de 80 o más Años , Angioplastia de Balón/efectos adversos , Índice Tobillo Braquial , Fármacos Cardiovasculares/efectos adversos , Endarterectomía/efectos adversos , Diseño de Equipo , Femenino , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/fisiopatología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción Vascular
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