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OBJECTIVE: Segmenting the aorta into zones based on anatomical landmarks is a current trend to better understand interventions for aortic dissection or aneurysm. However, comprehensive reference values for aortic zones are lacking. The aim of this study was to establish reference values for aortic size using a fully automated deep learning based segmentation method. METHODS: This retrospective study included 704 healthy adults (mean age 50.6 ± 7.5 years; 407 [57.8%] males) who underwent contrast enhanced chest computed tomography (CT) for health screening. A convolutional neural network (CNN) was trained and applied on 3D CT images for automatic segmentation of the aorta based on the Society for Vascular Surgery/Society of Thoracic Surgeons classification. The CNN generated masks were reviewed and corrected by expert cardiac radiologists. RESULTS: Aortic size was significantly larger in males than in females across all zones (zones 0 - 8, all p < .001). The aortic size in each zone increased with age, by approximately 1 mm per 10 years of age, e.g., 25.4, 26.7, 27.5, 28.8, and 29.8 mm at zone 2 in men in the age ranges of 30 - < 40, 40 - < 50, 50 - < 60, 60 - < 70, and ≥ 70 years, respectively (all p < .001). CONCLUSION: The deep learning algorithm provided reliable values for aortic size in each zone, with automatic masks comparable with manually corrected ones. Aortic size was larger in males and increased with age. These findings have clinical implications for the detection of aortic aneurysms or other aortic diseases.
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OBJECTIVE: While evoked potentials elicited by single pulse electrical stimulation (SPES) may assist seizure onset zone (SOZ) localization during intracranial EEG (iEEG) monitoring, induced high frequency activity has also shown promising utility. We aimed to predict SOZ sites using induced cortico-cortical spectral responses (CCSRs) as an index of excitability within epileptogenic networks. METHODS: SPES was conducted in 27 epilepsy patients undergoing iEEG monitoring and CCSRs were quantified by significant early (10-200 ms) increases in power from 10 to 250 Hz. Using response power as CCSR network connection strengths, graph centrality measures (metrics quantifying each site's influence within the network) were used to predict whether sites were within the SOZ. RESULTS: Across patients with successful surgical outcomes, greater CCSR centrality predicted SOZ sites and SOZ sites targeted for surgical treatment with median AUCs of 0.85 and 0.91, respectively. We found that the alignment between predicted and targeted SOZ sites predicted surgical outcome with an AUC of 0.79. CONCLUSIONS: These findings indicate that network analysis of CCSRs can be used to identify increased excitability of SOZ sites and discriminate important surgical targets within the SOZ. SIGNIFICANCE: CCSRs may supplement traditional passive iEEG monitoring in seizure localization, potentially reducing the need for recording numerous seizures.
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Research on cardiovascular diseases using CT-derived strain is gaining momentum, yet there is a paucity of information regarding reference standard values beyond echocardiography, particularly in cardiac chambers other than the left ventricle (LV). We aimed to compile CT-derived strain values from the four cardiac chambers in healthy adults and assess the impact of age and sex on myocardial strains. This study included 101 (mean age: 55.2 ± 9.0 years, 55.4% men) consecutive healthy individuals who underwent multiphase cardiac CT. CT-derived cardiac strains, including LV global and segmental longitudinal, circumferential, and transverse strains, left atrial (LA), right atrial (RA), and right ventricle (RV) strains were measured by the commercially available software. Strain values were classified and compared by their age and sex. The normal range of CT-derived LV global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were -20.2 ± 2.7%, -27.9 ± 4.1%, and 49.4 ± 12.1%, respectively. For LA, reservoir strain, pump strain, and conduit strain were 28.6 ± 8.5%, 13.2 ± 6.4%, and 15.5 ± 8.6%, respectively. The GLS of RA and RV were 27.9 ± 10.9% and -22.0 ± 5.7%, respectively. The absolute values of GLS of RA and RV of women were higher than that in men (32.4 ± 11.4 vs. 24.3 ± 9.1 and -25.2 ± 4.7 vs. -19.4 ± 5.0, respectively; p<0.001, both). Measurement of CT-derived strain in four cardiac chambers is feasible. The reference ranges of CT strains in four cardiac chambers can be used for future studies of various cardiac diseases using the cardiac strains.
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Ventrículos Cardíacos , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Persona de Mediana Edad , Valores de Referencia , Tomografía Computarizada por Rayos X/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Anciano , Adulto , Atrios Cardíacos/diagnóstico por imagenRESUMEN
In recent years, the utility of polygenic risk scores (PRS) in forecasting disease susceptibility from genome-wide association studies (GWAS) results has been widely recognised. Yet, these models face limitations due to overfitting and the potential overestimation of effect sizes in correlated variants. To surmount these obstacles, we devised the Stacked Neural Network Polygenic Risk Score (SNPRS). This novel approach synthesises outputs from multiple neural network models, each calibrated using genetic variants chosen based on diverse p-value thresholds. By doing so, SNPRS captures a broader array of genetic variants, enabling a more nuanced interpretation of the combined effects of these variants. We assessed the efficacy of SNPRS using the UK Biobank data, focusing on the genetic risks associated with breast and prostate cancers, as well as quantitative traits like height and BMI. We also extended our analysis to the Korea Genome and Epidemiology Study (KoGES) dataset. Impressively, our results indicate that SNPRS surpasses traditional PRS models and an isolated deep neural network in terms of accuracy, highlighting its promise in refining the efficacy and relevance of PRS in genetic studies.
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Puntuación de Riesgo Genético , Estudio de Asociación del Genoma Completo , Redes Neurales de la Computación , Polimorfismo de Nucleótido Simple , Humanos , Neoplasias de la Mama/genética , Estudio de Asociación del Genoma Completo/métodos , Neoplasias de la Próstata/genéticaRESUMEN
OBJECTIVE: Residual aortic dissection (AD) following DeBakey type I AD repair is associated with a high rate of adverse events that need additional intervention or surgery. This study aimed to identify clinical and early post-operative computed tomography (CT) imaging factors associated with adverse events in patients with type I AD after ascending aorta replacement. METHODS: This single centre, retrospective cohort study included consecutive patients with type I AD who underwent ascending aorta replacement from January 2011 to December 2017 and post-operative CT within three months. The primary outcome was AD related adverse events, defined as AD related death and re-operation due to aortic aneurysm or impending rupture. The location and size of the primary intimal tears, aortic diameter, and false lumen status were evaluated. Regression analyses were performed to identify factors associated with AD related adverse events. A decision tree model was used to classify patients as high or low risk. RESULTS: Of 103 participants (55.43 ± 13.94 years; 49.5% male), 24 (23.3%) experienced AD related adverse events. In multivariable Cox regression analysis, connective tissue disease (hazard ratio [HR] 15.33; p < .001), maximum aortic diameter ≥ 40 mm (HR 4.90; p < .001), and multiple (three or more) intimal tears (HR 7.12; p < .001) were associated with AD related adverse events. The three year cumulative survival free from AD related events was lower in the high risk group with aortic diameter ≥ 40 mm and multiple intimal tears (41.7% vs. 90.9%; p < .001). CONCLUSION: Early post-operative CT findings indicating a maximum aortic diameter ≥ 40 mm and multiple intimal tears may predict a higher risk of adverse events. These findings suggest the need for careful monitoring and more vigilant management approaches in these cases.
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This study analyzed how the behavioral patterns of esports and authentic sports viewers differ, adopting user and gratification theory and media transportation theory. In particular, it was investigated whether there was a difference in behavioral patterns according to the experience of playing the sport even among authentic sports viewers. As a result of analyzing the relationship between viewers' motivation and media transportation outcomes through structural equation modeling and multigroup structural equation modeling, it was observed that cognitive motivation was more important for esports viewers than for authentic sports viewers. A second analysis of comparisons among fans of authentic sports showed that viewers with sports experience had greater cognitive needs. This result shows that there is a difference between the viewer behaviors of esports and traditional sports, but it is concluded that the presence or absence of sports participation experience rather than content is the factor that separates the difference.
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UPDATE: This article was updated on May 15, 2024 because of previous errors, which were discovered after the preliminary version of the article was posted online. On page 898, in the section entitled "Materials and Methods," the sentence that had read "The WBL ratio of the knee joint was defined as the point where the GA or MA passed through the width of the tibia and intersected a line from the center of the femoral head to the center of the calcaneus (for the GA) or talus (for the MA), with the medial edge defined as 0% and the lateral edge as 100%." now reads "The WBL ratio of the knee joint was defined as the point where the GA or MA passed through the width of the tibia and intersected a line from the center of the femoral head to the lowest point of the calcaneus (for the GA) or the center of the talus (for the MA), with the medial edge defined as 0% and the lateral edge as 100%." Likewise, in the legend for Figure 3 on page 899, the sentence that had read "Depiction of the ground mechanical axis (GA), defined as the line (represented by the solid red line) from the center of the femoral head to the ground reaction point at the center of the calcaneus, passing lateral to the traditional mechanical axis (MA; represented by the dashed red line)." now reads "Depiction of the ground mechanical axis (GA), defined as the line (represented by the solid red line) from the center of the femoral head to the ground reaction point at the lowest point of the calcaneus, passing lateral to the traditional mechanical axis (MA; represented by the dashed red line)." Finally, on page 903, "HKA" was changed to "HKA angle" in Table III. BACKGROUND: The hip-to-calcaneus axis, previously known as the ground mechanical axis (GA), ideally passes through the center of the knee joint in the native knee. The aim of this study was to elucidate, with use of hip-to-calcaneus radiographs, changes in knee and hindfoot alignment and changes in outcomes following high tibial osteotomy (HTO). METHODS: We reviewed the records for 128 patients who underwent HTO between 2018 and 2020. Patients were stratified into 2 groups, a hindfoot valgus group (n = 94) and a hindfoot varus group (n = 34), on the basis of their preoperative hindfoot alignment. The hindfoot alignment was evaluated with use of the hindfoot alignment angle (HAA). To evaluate lower-limb alignment, full-length standing posteroanterior hip-to-calcaneus radiographs were utilized to measure 4 radiographic parameters preoperatively and 2 years postoperatively: the hip-knee-ankle (HKA) angle, hip-knee-calcaneus (HKC) angle, and the weight-bearing line (WBL) ratios of the mechanical axis (MA) and GA. RESULTS: The mean HAA improved significantly from 5.1° valgus preoperatively to 1.9° valgus postoperatively in the hindfoot valgus group (p < 0.001). In contrast, in the hindfoot varus group, the HAA showed no meaningful improvement in the coronal alignment of the hindfoot following HTO (p = 0.236). The postoperative mean HKC angle in the hindfoot varus group was 2° more varus than that in the hindfoot valgus group (1.0° versus 3.0°; p = 0.001), and the GA in the hindfoot varus group passed across the knee 8.0% more medially than that in the hindfoot valgus group (55% versus 63% from the most medial to the most lateral part of the tibial plateau). The hindfoot varus group had worse postoperative clinical outcomes than the hindfoot valgus group in terms of the mean Knee injury and Osteoarthritis Outcome Score for pain and American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Score. CONCLUSIONS: Although our findings did not provide sufficient evidence to establish clinically relevant differences between the groups, they indicated that the group with a preoperative fixed hindfoot varus deformity had a higher rate of undercorrection and worse clinical outcomes, especially pain, following HTO. Therefore, modification of the procedure to shift the GA more laterally may be required for these patients. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.
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Osteoartritis de la Rodilla , Osteotomía , Tibia , Humanos , Osteotomía/métodos , Tibia/cirugía , Tibia/diagnóstico por imagen , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , AncianoRESUMEN
This brief review summarizes presentations at the Temporal Lobe Club Special Interest Group session held in December 2022 at the American Epilepsy Society meeting. The session addressed newer methods to treat temporal epilepsy, including methods currently in clinical use and techniques under investigation. Brief summaries are provided for each of 4 lectures. Dr Chengyuan Wu discussed ablative techniques such as laser interstitial thermal ablation, radiofrequency ablation, focused ultrasound; Dr Joon Kang reviewed neuromodulation techniques including electrical stimulation and focused ultrasound; Dr Julia Makhalova discussed network effects of the aforementioned techniques; and Dr Derek Southwell reviewed inhibitory interneuron transplantation. These summaries are intended to provide a brief overview and references are provided for the reader to learn more about each topic.
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Interventricular membranous septal aneurysms are rare. Since these aneurysms can lead to complications such as obstruction of right ventricular outflow and thromboembolism, the detection of this aneurysm has clinical significance. Herein, we report a case of an interventricular membranous septal aneurysm with an internal thrombus thought to be the cause of a cerebral infarction.
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BACKGROUND: The risks of leaflet thrombosis and the associated cerebral thromboembolism are unknown according to different anticoagulation dosing after transcatheter aortic valve replacement (TAVR). The aim was to evaluate the incidence of leaflet thrombosis and cerebral thromboembolism between low-dose (30 mg) or standard-dose (60 mg) edoxaban and dual antiplatelet therapy (DAPT) after TAVR. METHODS: In this prespecified subgroup analysis of the ADAPT-TAVR trial, the primary endpoint was the incidence of leaflet thrombosis on 4-dimensional computed tomography at 6-months. Key secondary endpoints were new cerebral lesions on brain magnetic resonance imaging and neurological and neurocognitive dysfunction. RESULTS: Of 229 patients enrolled in this study, 118 patients were DAPT group and 111 were edoxaban group (43 [39.1%] 60 mg vs 68 [61.3%] 30 mg). There was a significantly lower incidence of leaflet thrombosis in the standard-dose edoxaban group than in the DAPT group (2.4% vs 18.3%; odds ratio [OR] 0.11; 95% confidence interval [CI], 0.01-0.55; P = .03). However, no significant difference was observed between low-dose edoxaban and DAPT (15.0% vs 18.3%; OR 0.79; 95% CI, 0.32-1.81; P = .58). Irrespective of different antithrombotic regiments, the percentages of patients with new cerebral lesions on brain MRI and worsening neurological or neurocognitive function were not significantly different. CONCLUSIONS: In patients without an indication for anticoagulation after TAVR, the incidence of leaflet thrombosis was significantly lower with standard-dose edoxaban but not with low-dose edoxaban, as compared with DAPT. However, this differential effect of edoxaban on leaflet thrombosis was not associated with a reduction of new cerebral thromboembolism and neurological dysfunction.
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Estenosis de la Válvula Aórtica , Piridinas , Tiazoles , Tromboembolia , Trombosis , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Inhibidores de Agregación Plaquetaria , Válvula Aórtica/cirugía , Resultado del Tratamiento , Tromboembolia/epidemiología , Tromboembolia/etiología , Tromboembolia/prevención & control , Trombosis/epidemiología , Trombosis/etiología , Trombosis/prevención & control , Anticoagulantes/uso terapéutico , Estenosis de la Válvula Aórtica/complicacionesRESUMEN
Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disease characterized by abnormal thickening of the myocardium caused by myocardial disarray and interstitial fibrosis. HCM is associated with sudden cardiac-related events, such as ventricular fibrillation, tachycardia, and syncope. Moreover, left ventricular or midcavity obstruction due to the thickened myocardium can result in severe heart failure and mortality in patients with HCM. Surgical myectomy is a standard treatment option for patients with symptomatic obstructive HCM; however, it is a complex procedure that requires careful planning and execution to avoid complications, such as residual flow obstruction, persistent obliteration of the left ventricular cavity in systole, or iatrogenic ventricular septal defects. Therefore, a thorough understanding of the mechanics of HCM and precise evaluation of the location and extent of the hypertrophic myocardium to be removed are crucial for preoperative planning. Multiphase cardiac CT postprocessing is important for preoperative evaluation and planning of surgical myectomy in patients with HCM. In this review, the authors highlight use of multiphase cardiac CT with step-by-step postprocessing methods to simulate successful surgical myectomy. The transaortic surgeon's view on end-diastolic phase images accurately represents the surgical field. Moreover, myocardial segmentation can be used to generate volume-rendered images and three-dimensional printing. CT evaluation can also assist in identifying concurrent abnormalities, such as mitral valve or papillary muscle abnormalities. In addition to CT, other imaging modalities for preoperative evaluation of HCM and postmyectomy evaluation methods are presented. ©RSNA, 2023 Test Your Knowledge questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.
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Procedimientos Quirúrgicos Cardíacos , Cardiomiopatía Hipertrófica , Humanos , Procedimientos Quirúrgicos Cardíacos/métodos , Tabiques Cardíacos/cirugía , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Cardiomiopatía Hipertrófica/cirugía , Cardiomiopatía Hipertrófica/complicaciones , Miocardio , Tórax , Resultado del TratamientoRESUMEN
Overexpression of transglutaminase 2 (TGase 2; TG2) has been implicated in the progression of renal cell carcinoma (RCC) through the inactivation of p53 by forming a protein complex. Because most p53 in RCC has no mutations, apoptosis can be increased by inhibiting the binding between TG2 and p53 to increase the stability of p53. In the present study, a novel TG2 inhibitor was discovered by investigating the structure of 1H-benzo[d]imidazole-4,7-dione as a simpler chemotype based on the amino-1,4-benzoquinone moiety of streptonigrin, a previously reported inhibitor. Through structure-activity relationship (SAR) studies, compound 8j (MD102) was discovered as a potent TG2 inhibitor with an IC50 value of 0.35 µM, p53 stabilization effect and anticancer effects in the ACHN and Caki-1 RCC cell lines with sulforhodamine B (SRB) GI50 values of 2.15 µM and 1.98 µM, respectively. The binding property of compound 8j (MD102) with TG2 was confirmed to be reversible in a competitive enzyme assay, and the binding interaction was expected to be formed at the ß-sandwich domain, a p53 binding site, in the SPR binding assay with mutant proteins. The mode of binding of compound 8j (MD102) to the ß-sandwich domain of TG2 was analyzed by molecular docking using the crystal structure of the active conformation of human TG2. Compound 8j (MD102) induced a decrease in the downstream signaling of p-AKT and p-mTOR through the stabilization of p53 by TG2 inhibition, resulting in tumor cell apoptosis. In a xenograft animal model using ACHN cancer cells, oral administration and intraperitoneal injection of compound 8j (MD102) showed an inhibitory effect on tumor growth, confirming increased levels of p53 and decreased levels of Ki-67 in tumor tissues through immunohistochemical (IHC) tissue staining. These results indicated that the inhibition of TG2 by compound 8j (MD102) could enhance p53 stabilization, thereby ultimately showing anticancer effects in RCC. Compound 8j (MD102), a novel TG2 inhibitor, can be further applied for the development of an anticancer candidate drug targeting RCC.
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Antineoplásicos , Carcinoma de Células Renales , Neoplasias Renales , Proteína Glutamina Gamma Glutamiltransferasa 2 , Animales , Humanos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Imidazoles/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Simulación del Acoplamiento Molecular , Proteína Glutamina Gamma Glutamiltransferasa 2/antagonistas & inhibidores , Transglutaminasas/antagonistas & inhibidores , Transglutaminasas/metabolismo , Proteína p53 Supresora de Tumor/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Polygenic risk scores (PRSs) have been studied for predicting human diseases, and various methods for PRS calculation have been developed. Most PRS studies to date have focused on European ancestry, and the performance of PRS has not been sufficiently assessed in East Asia. Herein, we evaluated the predictive performance of PRSs for East Asian populations under various conditions. Simulation studies using data from the Korean cohort, Health Examinees (HEXA), demonstrated that SBayesRC and PRS-CS outperformed other PRS methods (lassosum, LDpred-funct, and PRSice) in high fixed heritability (0.3 and 0.7). In addition, we generated PRSs using real-world data from HEXA for ten diseases: asthma, breast cancer, cataract, coronary artery disease, gastric cancer, glaucoma, hyperthyroidism, hypothyroidism, osteoporosis, and type 2 diabetes (T2D). We utilized the five previous PRS methods and genome-wide association study (GWAS) data from two biobank-scale datasets [European (UK Biobank) and East Asian (BioBank Japan) ancestry]. Additionally, we employed PRS-CSx, a PRS method that combines GWAS data from both ancestries, to generate a total of 110 PRS for ten diseases. Similar to the simulation results, SBayesRC showed better predictive performance for disease risk than the other methods. Furthermore, the East Asian GWAS data outperformed those from European ancestry for breast cancer, cataract, gastric cancer, and T2D, but neither of the two GWAS ancestries showed a significant advantage on PRS performance for the remaining six diseases. Based on simulation data and real data studies, it is expected that SBayesRC will offer superior performance for East Asian populations, and PRS generated using GWAS from non-East Asian may also yield good results.
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Neoplasias de la Mama , Catarata , Diabetes Mellitus Tipo 2 , Neoplasias Gástricas , Humanos , Femenino , Estudio de Asociación del Genoma Completo , Pueblos del Este de Asia , Predisposición Genética a la Enfermedad , Factores de Riesgo , Herencia Multifactorial , Neoplasias de la Mama/epidemiologíaRESUMEN
As cryogenic electron microscopy (cryoEM) gains traction in the structural biology community as a method of choice for determining atomic structures of biological complexes, it has been increasingly recognized that many complexes that behave well under conventional negative-stain electron microscopy tend to have preferential orientation, aggregate or simply mysteriously "disappear" on cryoEM grids, but the reasons for such misbehavior are not well understood, limiting systematic approaches to solving the problem. Here, we have developed a theoretical formulation that explains these observations. Our formulation predicts that all particles migrate to the air-water interface (AWI) to lower the total potential surface energy - rationalizing the use of surfactant, which is a direct solution to reducing the surface tension of the aqueous solution. By conducting cryogenic electron tomography (cryoET) with the widely-tested sample, GroEL, we demonstrate that, in a standard buffer solution, nearly all particles migrate to the AWI. Gradual reduction of the surface tension by introducing surfactants decreased the percentage of particles exposed to the surface. By conducting single-particle cryoEM, we confirm that applicable surfactants do not damage the biological complex, thus suggesting that they might offer a practical, simple, and general solution to the problem for high-resolution cryoEM. Application of this solution to a real-world AWI adsorption problem with a more challenging membrane protein, namely, the ClC-1 channel, has led to its first near-atomic structure using cryoEM.
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Postoperative chylous leak after esophagectomy is a rare but potentially life-threatening complication that results in hypovolemia, electrolyte imbalance, malnutrition, and immunologic deficiency. However, the management of postoperative chylous leak remains controversial. Following a diagnosis of esophageal cancer, a 64-year-old man was treated by video-assisted thoracoscopic esophagectomy, laparoscopic gastric tube formation, prophylactically thoracic duct ligation, and reconstruction with esophagogastrostomy at the neck level. Massive postoperative drainage from the thorax and abdomen did not initially meet the diagnostic criteria for chylothorax, which was ultimately diagnosed 3 weeks after the operation. Despite various treatments including total parenteral nutrition, octreotide and midodrine, reoperation (thoracic duct ligation and mechanical pleurodesis), and thoracic duct embolization, the chylous leak persisted. Finally, low-dose radiation therapy was administered with a daily dose of 2 Gy and completed at a total dose of 14 Gy. After this, the amount of pleural effusion gradually decreased over 2 weeks, and the last drainage tube was removed. The patient was alive and well at 60 months postoperatively. Herein, we describe a patient with intractable chylous leak after esophagectomy, which persisted despite conservative treatment, thoracic duct ligation, and embolization, but was finally successfully treated with radiotherapy.
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Quilotórax , Neoplasias Esofágicas , Masculino , Humanos , Persona de Mediana Edad , Esofagectomía/efectos adversos , Esofagectomía/métodos , Complicaciones Posoperatorias/prevención & control , Conducto Torácico/cirugía , Ligadura/efectos adversos , Ligadura/métodos , Quilotórax/etiología , Quilotórax/terapia , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/complicacionesRESUMEN
Pulmonary hamartoma is the most commonly resected benign neoplasm of lung. The mesenchymal cystic subtype is a rare and often bilaterally occurring variant composed of multiple cysts and nodules. Herein, we present an asymptomatic 70-year-old woman with a large and mostly cystic growth of right hilar region. Computed tomography of the chest and fluorodeoxyglucose positron emission tomography/computed tomography imaging traced its origins to right middle lobe. Overall features suggested primary lung cancer or perhaps other cystic lung disease.Because transbronchial lung biopsy failed to establish a histologic diagnosis, right middle lobectomy was undertaken by video-assisted thoracoscopic surgery. The gross surgical specimen harbored a single and sizeable (8.0 × 4.0 cm) cystic lesion containing multiple yellow-white nodules. A diagnosis of mesenchymal cystic and chondroid hamartoma was ultimately rendered. This particular case is noteworthy, given the initial clinical resemblance to primary lung cancer.
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Quistes , Hamartoma , Enfermedades Pulmonares , Neoplasias Pulmonares , Femenino , Humanos , Anciano , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Pulmón/patología , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/cirugía , Tomografía Computarizada por Rayos X , Hamartoma/diagnóstico por imagen , Hamartoma/cirugía , Quistes/cirugíaRESUMEN
In previous work, we showed that cancer cells do not depend on glycolysis for ATP production, but they do on fatty acid oxidation. However, we found some cancer cells induced cell death after glucose deprivation along with a decrease of ATP production. We investigated the different response of glucose deprivation with two types of cancer cells including glucose insensitive cancer cells (GIC) which do not change ATP levels, and glucose sensitive cancer cells (GSC) which decrease ATP production in 24 h. Glucose deprivation-induced cell death in GSC by more than twofold after 12 h and by up to tenfold after 24 h accompanied by decreased ATP production to compare to the control (cultured in glucose). Glucose deprivation decreased the levels of metabolic intermediates of the pentose phosphate pathway (PPP) and the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) in both GSC and GIC. However, glucose deprivation increased reactive oxygen species (ROS) only in GSC, suggesting that GIC have a higher tolerance for decreased NADPH than GSC. The twofold higher ratio of reduced/oxidized glutathione (GSH/GSSG) in GIS than in GSC correlates closely with the twofold lower ROS levels under glucose starvation conditions. Treatment with N-acetylcysteine (NAC) as a precursor to the biologic antioxidant glutathione restored ATP production by 70% and reversed cell death caused by glucose deprivation in GSC. The present findings suggest that glucose deprivation-induced cancer cell death is not caused by decreased ATP levels, but rather triggered by a failure of ROS regulation by the antioxidant system. Conclusion is clear that glucose deprivation-induced cell death is independent from ATP depletion-induced cell death.
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Adenosina Trifosfato , Glucosa , Neoplasias , Especies Reactivas de Oxígeno , Glucosa/deficiencia , Adenosina Trifosfato/metabolismo , Vía de Pentosa Fosfato , Especies Reactivas de Oxígeno/metabolismo , NADP/metabolismo , Glutatión/metabolismo , Acetilcisteína/metabolismo , Acetilcisteína/farmacología , Células PC-3 , Humanos , Neoplasias/metabolismo , Neoplasias/patología , Muerte CelularRESUMEN
Retrograde catheter-induced coronary artery dissection during percutaneous coronary intervention is an exceedingly rare occurrence, and the likelihood of it extending into the aorta is even more uncommon. Typically, surgical treatment involves aortic root replacement combined with coronary artery bypass grafting. However, in this particular case, a meticulous approach was employed. By carefully guiding wires into the true lumens and placing stents in the proximal left main and left anterior descending arteries, the immediate complications were averted by obstructing the retrograde flow in the false lumen. Subsequently, an off-pump coronary artery bypass was performed using the left internal mammary artery to the left anterior descending artery, without the need to manipulate the aorta. This approach resulted in a short operation time and the absence of any other complications.
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Annually, millions of new cancer cases are reported, leading to millions of deaths worldwide. Among the newly reported cases, breast and colon cancers prevail as the most frequently detected variations. To effectively counteract this rapid increase, the development of innovative therapies is crucial. Small molecules possessing pyridine and urea moieties have been reported in many of the currently available anticancer agents, especially VEGFR2 inhibitors. With this in mind, a rational design approach was employed to create hybrid small molecules combining urea and pyridine. These synthesized compounds underwent in vitro testing against breast and colon cancer cell lines, revealing potent submicromolar anticancer activity. Compound 8a, specifically, exhibited an impressive GI50 value of 0.06 µM against the MCF7 cancer cell line, while compound 8h displayed the highest cytotoxic activity against the HCT116 cell line, with a GI50 of 0.33 ± 0.042 µM. Notably, compounds 8a, 8h, and 8i demonstrated excellent safety profiles when tested on normal cells. Molecular docking, dynamic studies, and free energy calculations were employed to validate the affinity of these compounds as VEGFR2 inhibitors.
Asunto(s)
Antineoplásicos , Neoplasias del Colon , Humanos , Urea/farmacología , Relación Estructura-Actividad , Línea Celular Tumoral , Simulación del Acoplamiento Molecular , Antineoplásicos/farmacología , Piridinas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular , Estructura MolecularRESUMEN
BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major obstacle limiting long-term graft survival. Effective noninvasive surveillance modalities reflecting both coronary artery and microvascular components of CAV are needed. OBJECTIVES: The authors evaluated the diagnostic performance of dynamic computed tomography-myocardial perfusion imaging (CT-MPI) and coronary computed tomography angiography (CCTA) for CAV. METHODS: A total of 63 heart transplantation patients underwent combined CT-MPI and CCTA plus invasive coronary angiography (ICA) with intravascular ultrasonography (IVUS) between December 2018 and October 2021. The median interval between CT-MPI and heart transplantation was 4.3 years. Peak myocardial blood flow (MBF) of the whole myocardium (MBFglobal) and minimum MBF (MBFmin) among the 16 segments according to the American Heart Association model, except the left ventricular apex, were calculated from CT-MPI. CCTA was assessed qualitatively, and the degree of coronary artery stenosis was recorded. CAV was diagnosed based on both ICA (ISHLT criteria) and IVUS. Patients were followed up for a median time of 2.3 years after CT-MPI and a median time of 5.7 years after transplantation. RESULTS: Among the 63 recipients, 35 (55.6%) had diagnoses of CAV. The median MBFglobal and MBFmin were significantly lower in patients with CAV (128.7 vs 150.4 mL/100 mL/min; P = 0.014; and 96.9 vs 122.8 mL/100 mL/min; P < 0.001, respectively). The combined use of coronary artery stenosis on CCTA and MBFmin showed the highest diagnostic performance with an area under the curve of 0.886 (sensitivity: 74.3%, specificity: 96.4%, positive predictive value: 96.3%, and negative predictive value: 75.0%). CONCLUSIONS: The combination of CT-MPI and CCTA demonstrated excellent diagnostic performance for the detection of CAV. One-stop evaluation of the coronary artery and microvascular components involved in CAV using combined CCTA and CT-MPI may be a potent noninvasive screening method for early detection of CAV.