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BACKGROUND: Venoactive drugs (VADs) based on Vitis vinifera extract are widely used in Korea. However, studies on the clinical effects and head-to-head comparisons with other groups of VADs are limited. This trial aimed to evaluate whether Vitis vinifera seed extract was noninferior to the micronized purified flavonoid fraction (MPFF) in relieving venous symptoms and improving quality of life in patients with chronic venous disease. METHODS: In this double-blind prospective randomized trial, patients from 13 hospitals, who were diagnosed with venous incompetence by duplex ultrasound and classified as clinical class 1, 2, or 3 in the Clinical, Etiological, Anatomical, and Pathophysiological classifications were enrolled. The primary outcome was the change in the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) score at 8 weeks from baseline. Secondary outcomes included changes in the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score at 4 and 8 weeks from baseline. Moreover, the change in leg circumferences was measured at 8 weeks and compared to baseline. RESULTS: In total, 303 patients were enrolled and randomly assigned to receive either Vitis vinifera seed extract (n = 154) or MPFF (n = 149). The CIVIQ-20 scores at 8 weeks were significantly reduced compared to those at baseline in both groups. No significant intergroup difference in the change of CIVIQ-20 at 8 weeks from baseline was observed (-8.31 ± 14.63 vs. -10.35 ± 14.38, P = 0.29, 95% confidence interval -1.65 to 5.72). The lower limit of the 95% confidence interval was within the predefined noninferiority margin of 6.9. Furthermore, the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score scores significantly decreased at 4 and 8 weeks after randomization compared with baseline in both groups. No significant differences were observed in the reduction of each score between groups. The calf circumference measured at 8 weeks was significantly reduced compared to that at baseline in patients receiving Vitis vinifera seed extract. CONCLUSIONS: Vitis vinifera seed extract was noninferior to MPFF in relieving venous symptoms and improving the quality of life in patients with chronic venous disease.
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The N-degron pathway determines the half-life of proteins by selectively destabilizing the proteins bearing N-degrons. N-terminal glutamine amidohydrolase 1 (NTAQ1) plays an essential role in the arginine N-degron (Arg/N-degron) pathway as an initializing enzyme via the deamidation of the N-terminal (Nt) glutamine (Gln). However, the Nt-serine-bound conformation of hNTAQ1 according to the previously identified crystal structure suggests the possibility of other factors influencing the recognition of Nt residues by hNTAQ1. Hence, in the current study, we aimed to further elucidate the substrate recognition of hNTAQ1; specifically, we explored 12 different substrate-binding conformations of hNTAQ1 depending on the subsequent residue of Nt-Gln. Results revealed that hNTAQ1 primarily interacts with the protein Nt backbone, instead of the side chain, for substrate recognition. Here, we report that the Nt backbone of proteins appears to be a key component of hNTAQ1 function and is the main determinant of substrate recognition. Moreover, not all second residues from Nt-Gln, but rather distinctive and charged residues, appeared to aid in detecting substrate recognition. These new findings define the substrate-recognition process of hNTAQ1 and emphasize the importance of the subsequent Gln residue in the Nt-Gln degradation system. Our extensive structural and biochemical analyses provide insights into the substrate specificity of the N-degron pathway and shed light on the mechanism underlying hNTAQ1 substrate recognition. An improved understanding of the protein degradation machinery could aid in developing therapies to promote overall health through enhanced protein regulation, such as targeted protein therapies.
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Arginina , Humanos , Especificidad por Sustrato , Arginina/química , Arginina/metabolismo , Modelos Moleculares , Glutamina/metabolismo , Glutamina/química , Amidohidrolasas/química , Amidohidrolasas/metabolismo , Amidohidrolasas/genética , Conformación Proteica , Proteolisis , DegronesRESUMEN
Purpose: The anatomical distribution, characteristics of lesions, and treatment modalities for peripheral artery disease (PAD) are diverse. Endovascular intervention is popular for symptomatic PAD, for both intermittent claudication (IC) and chronic limb-threatening ischemia (CLTI). We aimed to investigate the endovascular devices used by comparing patients with PAD referred for endovascular revascularization with IC and CLTI. Methods: We identified 736 patients with PAD enrolled in the multicenter PAD registry in South Korea from 2019 to 2022. Of these patients, 636 received endovascular treatment at the time of this study. After excluding missing data, we analyzed 506 patients with IC or CLTI. Patients' characteristics, target lesions, and endovascular device data such as type, length, balloon diameter, and stent, were examined. Procedure outcomes of the aortoiliac, femoropopliteal, and below-the-knee lesions were analyzed. Results: Patients with CLTI were more likely to have diabetes mellitus, below-the-knee interventions, and multilevel PAD than the IC group. Patients with IC had more aortoiliac artery lesions and underwent atherectomies than the CLTI group (63.3% and 61.1% vs. 39.7% and 40.6%, respectively; P < 0.001). In patients with femoropopliteal lesions, those with CLTI were more revascularized with stents than the patients with IC, without significant differences (35.3% vs. 29.1%, P = 0.161). Compared to the IC group, the CLTI patients showed significantly worse rates of primary patency, amputation, and mortality (P = 0.029, P < 0.001, and P < 0.001, respectively). Conclusion: Among Korean patients with PAD, there is a significant difference in baseline and lesion characteristics, endovascular strategies, and short-term follow-up outcomes among those with IC and CLTI.
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OBJECTIVES: Despite advances in the maintenance of arteriovenous fistulas (AVFs), the patency rates remain suboptimal. Most AVFs fail due to outflow vein stenosis; however, the underlying mechanism of AVF stenosis remains unclear. The present study aimed to identify key factors associated with AVF outflow stenosis. METHODS: We obtained gene expression profiling data for the outflow vein of AVF from three Gene Expression Omnibus database datasets (GSE39488, GSE97377, and GSE116268) and analyzed the common differentially expressed genes (DEGs). We evaluated a common DEG in an aortocaval mouse model and the stenotic outflow veins of AVFs collected from patients. Furthermore, we isolated vascular smooth muscle cells (VSMCs) from the inferior vena cava (IVC) of wild-type (WT) and osteopontin (Opn)-knockout (KO) mice and assessed the proliferation of VSMCs following stimulation with platelet-derived growth factors (PDGFs). RESULTS: OPN was the only common upregulated DEG among all datasets. OPN was expressed in the medial layer of the outflow vein of AVF in aortocaval mouse models and co-stained with the VSMC marker (α-smooth muscle actin). OPN expression was markedly increased in the VSMCs of stenotic outflow veins of AVF collected from patients undergoing hemodialysis compared to presurgical veins acquired during AVF formation surgery. PDGF-induced VSMC proliferation was significantly increased in the VSMCs isolated from the IVC of WT mice but not in those isolated from the IVC of Opn-KO mice. CONCLUSIONS: OPN may be a key gene involved in VSMC proliferation in the AVF outflow veins and a therapeutic target to improve the AVF patency rate.
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Fístula Arteriovenosa , Derivación Arteriovenosa Quirúrgica , Ratones , Animales , Músculo Liso Vascular/metabolismo , Derivación Arteriovenosa Quirúrgica/efectos adversos , Osteopontina/genética , Osteopontina/metabolismo , Constricción Patológica/metabolismo , Factor de Crecimiento Derivado de Plaquetas , Proliferación Celular , Fístula Arteriovenosa/metabolismoRESUMEN
PURPOSE: To investigate the image quality of lower extremity computed tomography angiography (LE-CTA) using a reconstruction algorithm for monoenergetic images (MEIs) to evaluate peripheral arterial disease (PAD) at different kiloelectron volt (keV) levels. METHODS: A total of 146 consecutive patients who underwent LE-CTA on a dual-energy scanner to obtain MEIs at 40, 50, 60, 70, and 80 keV were included. The overall image quality, segmental image quality of the arteries and PAD segments, venous contamination, and metal artifacts from prostheses, which may compromise quality, were analyzed. RESULTS: The mean overall image quality of each MEI was 2.9 ± 0.7, 3.6 ± 0.6, 3.9 ± 0.3, 4.0 ± 0.2, and 4.0 ± 0.2 from 40 to 80 keV, respectively. The segmental image quality gradually increased from 40 to 70-80 keV until reaching its highest value. Among 295 PAD segments in 68 patients, 40 (13.6%) were scored at 1-2 at 40 keV and 13 (4.4%) were scored at 2 at 50 keV, indicating unsatisfactory image quality due to the indistinguishability between high-contrast areas and arterial calcifications. The segments exhibiting metal artifacts and venous contamination were reduced at 70-80 keV (2.6 ± 1.2, 2.7 ± 0.5) compared with at 40 keV (2.4 ± 1.1, 2.5 ± 0.7). CONCLUSION: The LE-CTA method using a reconstruction algorithm for MEIs at 70-80 keV can enhance the image quality for PAD evaluation and improve mitigate venous contamination and metal artifacts.
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Enfermedad Arterial Periférica , Imagen Radiográfica por Emisión de Doble Fotón , Humanos , Angiografía por Tomografía Computarizada/métodos , Artefactos , Imagen Radiográfica por Emisión de Doble Fotón/métodos , Algoritmos , Enfermedad Arterial Periférica/diagnóstico por imagen , Extremidad Inferior/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador , Relación Señal-Ruido , Estudios RetrospectivosRESUMEN
Optimal antiplatelet therapy after endovascular therapy (EVT) for peripheral artery disease is controversial. This trial aimed to evaluate whether sarpogrelate plus aspirin was non-inferior for preventing early restenosis after femoropopliteal (FP) EVT compared to clopidogrel plus aspirin. In this open-label, prospective randomized trial, 272 patients were enrolled after successful EVT for FP lesions. Patients in each group received aspirin 100 mg and clopidogrel 75 mg or sarpogrelate 300 mg orally once per day for 6 months. The primary outcome was target lesion restenosis at 6 months, tested for noninferiority. Patient characteristics and EVT patterns were similar, except for increased inflow procedures in the sarpogrelate group and increased outflow procedures in the clopidogrel group. The sarpogrelate group showed a tendency of less restenosis at 6 months than the clopidogrel group (13.0% vs. 19.1%, difference 6.1 percentage points, 95% CI for noninferiority - 0.047 to 0.169). Secondary endpoints related to safety outcomes were rare in both groups. Risks of target lesion restenosis of the two intervention arm were uniform across most major subgroups except for those with coronary artery disease. In conclusion, Sarpogrelate plus aspirin is non-inferior to clopidogrel plus aspirin in preventing early restenosis after FP EVT. Larger multi-ethnic trials are required to generalize these findings. Trial registration: National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT02959606; 09/11/2016).
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Enfermedad Arterial Periférica , Inhibidores de Agregación Plaquetaria , Humanos , Clopidogrel/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Prospectivos , Preparaciones de Acción Retardada , Aspirina/uso terapéutico , Arteria Femoral/cirugía , Enfermedad Arterial Periférica/tratamiento farmacológico , Resultado del Tratamiento , Quimioterapia CombinadaRESUMEN
OBJECTIVE: This study aimed to evaluate the current level of chronic venous disease (CVD) awareness and its relevant influencing factors. METHODS: Online and interview surveys were conducted in two distinct groups from May 14 to June 16, 2020. An online survey was conducted among 900 adults aged 20 to 64 years from the research database, whereas interviews were conducted among 124 patients who presented with CVD symptoms, which covered the awareness of such symptoms and their impact on quality of life. RESULTS: Most respondents reported low levels of CVD awareness by recognizing the disease only by an entity. In 53 respondents who visited the hospital with suspected venous symptoms, the actual diagnosis was made in only 30.2%. CVD diagnosis was associated with increased CVD awareness. Female sex, age of >29 years, higher educational level, and higher income were associated with increased CVD awareness. Approximately 60% of the patients with CVD responded that physical symptoms had a negative impact on their quality of life rather than emotion or appearance. CONCLUSIONS: The public is largely unaware of CVD but not in detail. Educational programs to improve CVD awareness should be implemented to enable appropriate CVD management.
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Calidad de Vida , Enfermedades Vasculares , Adulto , Humanos , Femenino , Factores de Riesgo , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/epidemiología , Enfermedades Vasculares/terapia , Enfermedad Crónica , República de Corea/epidemiologíaRESUMEN
Purpose: This study aimed to compare the characteristics of venous thromboembolic disease (VTE) in Korean to Caucasian population. Materials and Methods: XALIA-LEA and XALIA were phase IV non-interventional prospective studies with identical designs that investigated the effect of rivaroxaban versus standard anticoagulation for VTE. Koreans accounted for the largest proportion of the overall enrolled population of XALIA-LEA. However, in the XALIA study, most patients were Caucasian. Therefore, Korean data from XALIA-LEA and Caucasian data from XALIA were used in this study. This study compared the clinical characteristics and primary outcomes of the XALIA program, including major bleeding, recurrent VTE, and all-cause mortality. Results: The Korean population was older, was less obese, and had more active cancer at baseline than the Caucasian population. Provoked VTE was more common in the Korean population. Interestingly, Koreans showed less accompanying thrombophilia than Caucasians, and factor V Leiden mutations were not detected. Korean analyses comparing the effects of rivaroxaban and standard anticoagulation with primary outcomes showed a lower incidence of major bleeding, recurrent VTE, and all-cause mortality with rivaroxaban. Similar results were obtained in the propensity score matching analysis. Conclusion: Characteristic differences were found between Korean and Caucasian VTE patients. Despite these ethnic differences, the effectiveness and safety of rivaroxaban therapy in these patients were consistent.
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Vascular smooth muscle cell (VSMC) proliferation is a hallmark of neointimal hyperplasia (NIH) in atherosclerosis and restenosis post-balloon angioplasty and stent insertion. Although numerous cytotoxic and cytostatic therapeutics have been developed to reduce NIH, it is improbable that a multifactorial disease can be successfully treated by focusing on a preconceived hypothesis. We, therefore, aimed to identify key molecules involved in NIH via a hypothesis-free approach. We analyzed four datasets (GSE28829, GSE43292, GSE100927, and GSE120521), evaluated differentially expressed genes (DEGs) in wire-injured femoral arteries of mice, and determined their association with VSMC proliferation in vitro. Moreover, we performed RNA sequencing on platelet-derived growth factor (PDGF)-stimulated human VSMCs (hVSMCs) post-phosphoenolpyruvate carboxykinase 2 (PCK2) knockdown and investigated pathways associated with PCK2. Finally, we assessed NIH formation in Pck2 knockout (KO) mice by wire injury and identified PCK2 expression in human femoral artery atheroma. Among six DEGs, only PCK2 and RGS1 showed identical expression patterns between wire-injured femoral arteries of mice and gene expression datasets. PDGF-induced VSMC proliferation was attenuated when hVSMCs were transfected with PCK2 siRNA. RNA sequencing of PCK2 siRNA-treated hVSMCs revealed the involvement of the Akt-FoxO-PCK2 pathway in VSMC proliferation via Akt2, Akt3, FoxO1, and FoxO3. Additionally, NIH was attenuated in the wire-injured femoral artery of Pck2-KO mice and PCK2 was expressed in human femoral atheroma. PCK2 regulates VSMC proliferation in response to vascular injury via the Akt-FoxO-PCK2 pathway. Targeting PCK2, a downstream signaling mediator of VSMC proliferation, may be a novel therapeutic approach to modulate VSMC proliferation in atherosclerosis.
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Aterosclerosis , Fosfoenolpiruvato Carboxiquinasa (ATP) , Placa Aterosclerótica , Animales , Aterosclerosis/metabolismo , Movimiento Celular , Proliferación Celular/genética , Células Cultivadas , Modelos Animales de Enfermedad , Humanos , Hiperplasia/metabolismo , Hiperplasia/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Neointima/genética , Neointima/metabolismo , Fosfoenolpiruvato Carboxiquinasa (ATP)/metabolismo , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Interferente Pequeño/metabolismoRESUMEN
BACKGROUND: Surgical repair of complex abdominal aortic aneurysm is associated with a higher perioperative mortality and morbidity. The advent of endovascular aortic repair (EVAR) has reduced perioperative complications, although the utilization of such techniques is limited by lesion characteristics, such as involvement of the visceral or renal arteries (RA) and/or presence of a sealing zone. CASE SUMMARY: A 60-year-old male presented with a Crawford type IV complex thoracoabdominal aortic aneurysm (CAAA) starting directly distal to the diaphragm extending to both common iliac arteries (CIAs). The CAAA consist of a proximal and distal aneurysmal sac separated by a 1 cm-healthy zone in the infrarenal level. Due to the poor performance of the patient and the expansive disease, we planned a stepwise-combined surgery and EVAR to minimize invasiveness. A branched graft was implanted after surgical debranching of the visceral and RA. Since the patient had renal and liver injury after surgery, the second stage EVAR was performed 10 mo later. The stent graft was implanted from the distal portion of surgical branched graft to both CIAs during EVAR. The patient has been uneventful for 5-years after discharge and is being followed in the outpatient clinic. CONCLUSION: The current case demonstrates that the surgical graft can provide a landing zone for second stage EVAR to avoid aggressive surgery in patients with poor performance with a long hostile CAAA.
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The surgical workforce, like the rest of the population, is ageing. This has raised concerns about the association between the age of the surgeon and their surgical outcomes. We performed a systematic review and meta-analysis of cohort studies on postoperative mortality and major morbidity according to the surgeons' age. The search was performed on February 2021 using the Embase, Medline and CENTRAL databases. Postoperative mortality and major morbidity were evaluated as clinical outcomes. We categorized the surgeons' age into young-, middle-, and old-aged surgeons. We compared the differences in clinical outcomes for younger and older surgeons compared to middle-aged surgeons. Subgroup analyses were performed for major and minor surgery. Ten retrospective cohort studies on 29 various surgeries with 1,666,108 patients were considered. The mortality in patients undergoing surgery by old-aged surgeons was 1.14 (1.02-1.28, p = 0.02) (I2 = 80%) compared to those by middle-aged surgeon. No significant differences were observed according to the surgeon's age in the major morbidity and subgroup analyses. This meta-analysis indicated that surgeries performed by old-aged surgeons had a higher risk of postoperative mortality than those by middle-aged surgeons. Thus, it necessitates the introduction of a multidisciplinary approach to evaluate the performance of senior surgeons.
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Cirujanos , Anciano , Estudios de Cohortes , Humanos , Persona de Mediana Edad , Morbilidad , Complicaciones Posoperatorias/epidemiología , Estudios RetrospectivosRESUMEN
PURPOSE: Intensive care unit (ICU) bed availability is key to critical patient care. In many countries, older patients generally account for a significant proportion of hospitalizations and ICU admissions. Therefore, considering the rapidly increasing aging population in South Korea, it is important to establish whether the demand for critical care is currently met by available ICU beds. MATERIALS AND METHODS: We evaluated a 9-year trend in ICU bed supply and ICU length of stay in South Korea between 2011 and 2019 in a population-based cross-sectional analysis, using data from the Korean Health Insurance Review & Assessment Service and Statistics database. We described the changes in ICU bed rates in adult (≥20 years) and older adult (≥65 years) populations. ICU length of stay was categorized similarly and was used to predict future ICU bed demands. RESULTS: The ICU bed rate per 100000 adults increased from 18.5 in 2011 to 19.5 in 2019. In contrast, the ICU bed rate per 100000 older adults decreased from 127.6 in 2011 to 104.0 in 2019. ICU length of stay increased by 43.8% for adults and 55.6% for older adults. In 2019, the regional differences in the ICU bed rate nearly doubled, and the ICU length of stay increased six-fold. The ICU bed occupancy rate in South Korea is expected to rise to 102.7% in 2030. CONCLUSION: The discrepancy between the demand and supply of ICU beds in South Korea requires urgent action to anticipate future ICU demands.
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Ocupación de Camas , Unidades de Cuidados Intensivos , Anciano , Cuidados Críticos , Estudios Transversales , Humanos , Tiempo de Internación , República de CoreaRESUMEN
A recent meta-analysis addressed increased risk of death following revascularization with paclitaxel-coated devices in femopopliteal artery. We evaluated differences in all-cause mortality and amputation free survival between peripheral arterial disease (PAD) patients who were treated with paclitaxel-coated devices and non-paclitaxel-coated devices. This was retrospective population-based cohort study from the National Health Insurance Service claims in South Korea from 2015 to 2019. Multivariate Cox regression analyses after propensity score matching were applied to identify all-cause mortality and amputation-free survival. After propensity score matching, there were 6090 patients per group. The median follow-up days was 580 days (interquartile range [IQR] 240-991 days) and 433 days (IQR 175-757 days) for the non-paclitaxel-coated device group and paclitaxel-coated device group, respectively. Multivariate analysis adjusted for age, sex, diabetes, hypertension, warfarin, and new oral anticoagulants showed that the mortality rate associated with paclitaxel-coated devices was not significantly higher than non-paclitaxel-coated devices (hazard ratio [HR] 0.992; 95% CI 0.91-1.08). The rate of amputation events was higher in patients with paclitaxel-coated devices than those with non-paclitaxel-coated devices (HR 1.614; 95% CI 1.46-1.78). In this analysis, the mortality rate in patients with PAD was not associated with the use of paclitaxel-coated devices, despite a higher amputation rate.
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Angioplastia de Balón/efectos adversos , Paclitaxel/efectos adversos , Enfermedad Arterial Periférica/cirugía , Complicaciones Posoperatorias/mortalidad , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica/estadística & datos numéricos , Angioplastia de Balón/métodos , Comorbilidad , Femenino , Humanos , Pierna , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Stents/efectos adversosRESUMEN
OBJECTIVE: We compared the image quality according to the radiation dose on computed tomography (CT) venography at 80 kVp using advanced modeled iterative reconstruction for deep vein thrombus and other specific clinical conditions considering standard-, low-, and ultralow-dose CT. METHODS: In this retrospective study, 105 consecutive CT venography examinations were included using a third-generation dual-source scanner in the dual-source mode in tubes A (reference mAs, 210 mAs at 70%) and B (reference mAs, 90 mAs at 30%) at a fixed 80 kVp. Two radiologists independently reviewed each observation of standard- (100% radiation dose), low- (70%), and ultralow-dose (30%) CT. The objective quality of large veins and subjective image quality regarding lower-extremity veins and deep vein thrombus were compared between images according to the dose. In addition, the CT dose index volumes were displayed from the images. RESULTS: From the patients, 24 presented deep vein thrombus in 69 venous segments of CT examinations. Standard-dose CT provided the lowest image noise at the inferior vena cava and femoral vein compared with low- and ultralow-dose CT (p < 0.001). There were no differences regarding subjective image quality between the images of popliteal and calf veins at the three doses (e.g., 3.8 ± 0.7, right popliteal vein, p = 0.977). The image quality of the 69 deep vein thrombus segments showed equally slightly higher scores in standard- and low-dose CT (4.0 ± 0.2) than in ultralow-dose CT (3.9 ± 0.4). The CT dose index volumes were 4.4 ± 0.6, 3.1 ± 0.4, and 1.3 ± 0.2 mGy for standard-, low-, and ultralow-dose CT, respectively. CONCLUSIONS: Low- and ultralow-dose CT venography at 80 kVp using an advanced model based iterative reconstruction algorithm allows to evaluate deep vein thrombus and perform follow-up examinations while showing an acceptable image quality and reducing the radiation dose.
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Algoritmos , Flebografía , Dosis de Radiación , Intensificación de Imagen Radiográfica , Tomografía Computarizada por Rayos X , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Stents , Trombosis de la Vena/diagnóstico por imagenRESUMEN
Abdominal aortic aneurysm (AAA), when ruptured, results in high mortality. The identification of molecular pathways involved in AAA progression is required to improve AAA prognosis. The aim of the present study was to assess the key genes for the progression of AAA and their functional role. Genomic and clinical data of three independent cohorts were downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) (GSE57691, GSE7084, and GSE98278). To develop AAA diagnosis and progression-related differentially expressed genes (DEGs), we used a significance analysis of microarray (SAM). Spearman correlation test and gene set analysis were performed to identify potential enriched pathways for DEGs. Only the Frizzled-related protein (FRZB) gene and chromosome 1 open reading frame 24 (C1orf24) exhibited significant down-regulation in all analyses. With FRZB, the pathways were associated with RHO GTPase and elastin fiber formation. With C1orf24, the pathways were elastic fiber formation, extracellular matrix organization, and cell-cell communication. Since only FRZB was evolutionally conserved in the vertebrates, function of FRZB was validated using zebrafish embryos. Knockdown of frzb remarkably reduced vascular integrity in zebrafish embryos. We believe that FRZB is a key gene involved in AAA initiation and progression affecting vascular integrity.
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Aneurisma de la Aorta Abdominal/genética , Vasos Sanguíneos/patología , Péptidos y Proteínas de Señalización Intracelular/genética , Anciano , Animales , Aneurisma de la Aorta Abdominal/patología , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Sistemas de Lectura Abierta , Pez Cebra/embriologíaRESUMEN
BACKGROUND/AIM: Since pathways involving LRRC17 are related to the survival of patients with various cancers, we analyzed LRRC17 as a prognostic gene in serous ovarian cancer. MATERIALS AND METHODS: Data were collected from Gene Expression Omnibus (GSE9891, GSE13876, and GSE26712) and The Cancer Genome Atlas (TCGA). We performed survival analyses using C statistics, area under the curve, survival plot with optimal cutoff level, and cox proportional regression. Zebrafish embryos were used as an in vivo model. RESULTS: The prognosis of patients with high LRRC17 expression was poorer than that of patients with low LRRC17 expression. Multivariate regression analysis showed that LRRC17 expression, age, and stage were independently related with survival. Knockdown of lrrc17 reduced survival rate and delayed development in zebrafish embryos. We also found that lrrc17 is important for cell viability by protecting from p53-dependent apoptosis. CONCLUSION: LRRC17 could be a prognostic gene in ovarian cancer as it regulates cancer cell viability through the p53 pathway.
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Biomarcadores de Tumor/genética , Neoplasias Ováricas/genética , Proteínas/genética , Proteína p53 Supresora de Tumor/genética , Anciano , Apoptosis/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Técnicas de Silenciamiento del Gen , Humanos , Péptidos y Proteínas de Señalización Intercelular , Persona de Mediana Edad , Neoplasias Ováricas/patología , PronósticoRESUMEN
OBJECTIVE: To report the mid-term results of a single-center randomized controlled trial comparing drug-coated balloon angioplasty (DBA) and plain balloon angioplasty (PBA) for the treatment of dysfunctional radiocephalic arteriovenous fistulas (RCAVFs). MATERIALS AND METHODS: In this prospective study, 39 patients (mean age, 62.2 years; 21 males, 18 females) with RCAVFs failing due to juxta-anastomotic stenosis were randomly assigned to undergo either both DBA and PBA (n = 20, DBA group) or PBA alone (n = 19, PBA group) between June 2016 and June 2018. Primary endpoints were technical and clinical success and target lesion primary patency (TLPP); secondary outcomes were target lesion secondary patency (TLSP) and complication rates. Statistical analysis was performed using the Kaplan-Meier product limit estimator. RESULTS: Demographic data and baseline clinical characteristics were comparable between the groups. Technical and clinical success rates were 100% in both groups. There was no significant difference between the groups in the mean duration of TLPP (DBA group: 26.7 ± 3.6 months; PBA group: 27.0 ± 3.8 months; p = 0.902) and TLSP (DBA group: 37.3 ± 2.6 months; PBA group: 40.4 ± 1.5 months; p = 0.585). No procedural or post-procedural complications were identified. CONCLUSION: Paclitaxel-coated balloon use did not significantly improve TLPP or TLSP in the treatment of juxta-anastomotic stenosis of dysfunctional RCAVFs.
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Angioplastia de Balón/métodos , Fístula Arteriovenosa/terapia , Paclitaxel/administración & dosificación , Anciano , Fístula Arteriovenosa/patología , Derivación Arteriovenosa Quirúrgica , Constricción Patológica , Stents Liberadores de Fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Diálisis Renal , Método Simple Ciego , Resultado del Tratamiento , Grado de Desobstrucción VascularAsunto(s)
Colectomía/métodos , Diverticulitis del Colon/cirugía , Procedimientos Quirúrgicos Electivos/métodos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Índice de Masa Corporal , Enfermedades Cardiovasculares , Diverticulitis del Colon/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica , Factores de Riesgo , Adulto JovenRESUMEN
Purpose: The incidence of poorly differentiated thyroid carcinoma (PDTC) is extremely low among thyroid cancers and there is no standardized treatment guideline for it. In this study, we have analyzed PDTC patients and reviewed their clinicopathological features. Methods: Data of PDTC patients from our institution are collected through the electronic medical database. We analyzed them by several parameters such as basic demographics, presenting symptom, preoperative cytology results, associated pathology, surgical results, surgery type, and distant metastasis. Results: We collected 23 cases in our institution. Apart from two patients who were transferred to another hospital upon diagnosis, all 21 operated cases are analyzed. The parameters we studied were age, sex, presenting symptoms, distant metastasis and pathological features such as tumor size, associated pathology, predominant pattern and so on. We also provided descriptive analyses according to the type of presentation and treatment; patients with distant metastasis, juvenile cancer, and concurrent hyperthyroidism. Furthermore, we provided different cases in which the initial surgical plans differed. Conclusion: We present 21 cases of PDTC patients and clarify their clinicopathological features. Despite some limitations, this study may shed light for future research regarding treatment of PDTC patients.