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PURPOSE: Commercial double J stents (DJS) have a uniform shape regardless of the specific nature of various ureteral diseases. We tested renovated DJS and compared them with conventional DJS using ureter models. METHODS: One straight ureter model included stenosis at the distal ureter near the ureterovesical junction and the other did not. We used conventional DJS and renovated 5- and 6-Fr soft DJS for ureter stones and 6-, 7-, and 8.5-Fr hard DJS for tumors. The DJS comprised holes in the upper, middle, or lower one-third of the shaft (length, 24 cm; 2-cm-diameter coils at both ends). More holes were created along the shaft based on the ureteral disease location. Conventional DJS had holes spaced 1 cm apart along the shaft. Renovated DJS had holes spaced 1 cm apart along the shaft with 0.5-cm intervals on the upper, middle, or lower one-third of the shaft. Urine flow was evaluated. RESULTS: As the DJS diameter increased, the flow rate decreased. The flow rates of DJS with holes in the lower shaft were relatively lower than those of conventional DJS and DJS with holes in the upper and middle shafts. In the ureter model without stenosis, 6-, 7-, and 8.5-Fr renovated stents exhibited significantly higher flow rates than conventional stents. In the ureter model with stenosis, 5-, 6-, 7-, and 8.5-Fr renovated stents did not exhibit significantly higher flow rates than conventional stents. CONCLUSION: Renovated stents and conventional stents did not exhibit significant differences in urine flow with stenosis.
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Uréter , Ureterolitiasis , Humanos , Uréter/cirugía , Constricción Patológica , StentsRESUMEN
BACKGROUND: Iatrogenic femoral artery pseudoaneurysm (IFP) incidence is increasing with increase in diagnostic and therapeutic angiography, and so, the less invasive percutaneous thrombin injection (PTI) is the most widely used treatment. Moreover, studies that minimize PTI complications and highlight therapeutic effects are lacking. OBJECTIVES: This study performed in vitro thrombosis modeling of pseudoaneurysms and analyzed thrombosis within and thromboembolism outside the sac during thrombin injection. METHODS: We evaluated PTI in terms of thrombin injection location (at the junction of the IFP sac and neck, the center, and the dome, located farthest from the neck of the sac), thrombin injection time (5 and 8 seconds), and blood flow rate (ranging from 210 mL/min to 300 mL/min). Porcine blood was used as the working fluid in this study. RESULTS: Thrombin injection at the junction of the IFP sac and the pseudoaneurysm neck led to less thrombosis within the sac but substantial thrombi consistently outside the sac, whereas thrombin injected at the sac center mostly led to complete thrombosis within the sac, preventing further blood flow into the sac and reducing likelihood of thrombi outside the sac. A longer thrombin injection time enhanced the therapeutic effect and decreased the possibility of thromboembolism. Thromboembolism occurred more frequently at flow rates of >240 mL/min. CONCLUSION: The thrombin injection site in a pseudoaneurysm significantly influences thrombogenesis within and thromboembolism outside the sac. Thus, slow and deliberate injection of thrombin into the center of the sac could potentially reduce complications and enhance treatment efficacy.
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Aneurisma Falso , Arteria Femoral , Trombina , Trombosis , Trombina/administración & dosificación , Aneurisma Falso/tratamiento farmacológico , Animales , Trombosis/tratamiento farmacológico , Trombosis/etiología , Porcinos , Inyecciones Intraarteriales , Factores de Tiempo , Humanos , Tromboembolia/tratamiento farmacológico , Tromboembolia/prevención & control , Tromboembolia/etiología , Enfermedad IatrogénicaRESUMEN
Nexavant was reported as an alternative to the TLR3 agonist of Poly(I:C) and its derivatives. The physicochemical properties, signaling pathways, anti-cancer effects, and mechanisms of Nexavant were investigated. The distinctive characteristics of Nexavant compared to that of Poly(I:C) were demonstrated by precise quantification, enhanced thermostability, and increased resistance to RNase A. Unlike Poly(I:C), which activates TLR3, RIG-I, and MDA5, Nexavant stimulates signaling through TLR3 and RIG-I but not through MDA5. Compared to Poly(I:C), an intratumoral Nexavant treatment led to a unique immune response, immune cell infiltration, and suppression of tumor growth in various animal cancer models. Nexavant therapy outperformed anti-PD-1 antibody treatment in all the tested models and showed a synergistic effect in combinational therapy, especially in well-defined cold tumor models. The effect was similar to that of nivolumab in a humanized mouse model. Intranasal instillation of Nexavant led to the recruitment of immune cells (NK, CD4+ T, and CD8+ T) to the lungs, suppressing lung metastasis and improving animal survival. Our study highlighted Nexavant's defined nature for clinical use and unique signaling pathways and its potential as a standalone anti-cancer agent or in combination with anti-PD-1 antibodies.
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The conserved MYST proteins form the largest family of histone acetyltransferases (HATs) that acetylate lysines within the N-terminal tails of histone, enabling active gene transcription. Here, we have investigated the biological and regulatory functions of the MYST family HAT SasC in the opportunistic human pathogenic fungus Aspergillus fumigatus using a series of genetic, biochemical, pathogenic, and transcriptomic analyses. The deletion (Δ) of sasC results in a drastically reduced colony growth, asexual development, spore germination, response to stresses, and the fungal virulence. Genome-wide expression analyses have revealed that the ΔsasC mutant showed 2402 significant differentially expressed genes: 1147 upregulated and 1255 downregulated. The representative upregulated gene resulting from ΔsasC is hacA, predicted to encode a bZIP transcription factor, whereas the UV-endonuclease UVE-1 was significantly downregulated by ΔsasC. Furthermore, our Western blot analyses suggest that SasC likely catalyzes the acetylation of H3K9, K3K14, and H3K29 in A. fumigatus. In conclusion, SasC is associated with diverse biological processes and can be a potential target for controlling pathogenic fungi.
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Aspergillus fumigatus , Histona Acetiltransferasas , Humanos , Aspergillus fumigatus/genética , Histona Acetiltransferasas/genética , Histona Acetiltransferasas/metabolismo , Virulencia , Histonas/metabolismo , GenomaRESUMEN
The effect of side holes morphology changes in double J stent (DJS) on encrustation was analyzed using computational fluid dynamics (CFD). We analyzed DJS side holes with inner diameter of 1 mm and outer diameters of 1 (type A), 1.2 (type B) and 1.4 (type C) mm, respectively. Concentric stenosis with three intraureteral degree (0%, 12%, and 88%) was analyzed. The flow rate, shear stress and wall shear stress (WSS) distribution were investigated. Urine flow through SH1 before the ureteropelvic junction (UPJ) differed based on the ureteral stenosis degree. The sum of flow rates through the SHs increased with diameter. In the stented ureter with 12% stenosis, the flow rate through SH1 approximately doubled than that without ureteral stenosis, and the flow rate through SH1 was maximal for the type 'C' stent in both 12% and 88% ureteral stenosis. The mean shear stress in the SHs increased with the degree of stenosis. The WSS around the SHs was higher for type 'C' than types A and B. From the flow rates and shear stresses in and around the SHs, the larger SH diameter of the DJS from the UPJ to mid-ureter is expected to induce encrustation reduction, especially in patients with urinary lithiasis.
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PURPOSE: To evaluate the formation of encrustation on double J stents (DJSs) using artificial urine. MATERIALS AND METHODS: In this study, a static urinary system containing artificial urine was created, and a total of 45 DJSs were used to evaluate the formation of encrustation. Three groups of 15 DJSs were tested for 4, 8, or 14 weeks. The formation of encrustation on the DJSs over the weeks was analyzed using methods including X-ray powder diffraction (XRD), inductively coupled plasma spectrophotometer (ICP), and scanning electron microscope (SEM). Statistical analysis and the uncertainty test were used for data analysis using R language. RESULTS: The ICP analyzed the weight of the calcium and magnesium, which are the major components of urinary stones and encrustation, and showed that it was the heaviest at 14 weeks. Measurement of the area of encrustation on the outer surface of the DJSs revealed that the encrustation area at the bottom of the stent was greater than that at the top of the stent, regardless of the experimental period (proximal part: ≤ 41,099 µm2, distal part: ≤ 183,259 µm2). Encrustation occurred around the side holes of DJSs and became bigger over time to fill up the side holes. CONCLUSION: Encrustation spots included the bottom zone of the DJS and around the side holes. These results indicate that the performance of DJSs would be improved by modifying the shape of DJSs located near the bladder and side holes.
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Uréter , Urolitiasis , Humanos , Stents , Calcio , Magnesio , OrinaRESUMEN
Post-translational modifications of chromatin structure by histone acetyltransferase (HATs) play a pivotal role in the regulation of gene expression and diverse biological processes. However, the function of GNAT family HATs, especially Elp3, in the opportunistic human pathogenic fungus Aspergillus fumigatus is largely unknown. To investigate the roles of the GNAT family HATs Elp3 and GcnE in the A. fumigatus, we have generated and characterized individual null Δelp3 and ΔgcnE mutants. The radial growth of fungal colonies was significantly decreased by the loss of elp3 or gcnE, and the number of asexual spores (conidia) in the ΔgcnE mutant was significantly reduced. Moreover, the mRNA levels of the key asexual development regulators were also significantly low in the ΔgcnE mutant compared to wild type (WT). Whereas both the Δelp3 and ΔgcnE mutants were markedly impaired in the formation of adherent biofilms, the ΔgcnE mutant showed a complete loss of surface structure and of intercellular matrix. The ΔgcnE mutant responded differently to oxidative stressors and showed significant susceptibility to triazole antifungal agents. Furthermore, Elp3 and GcnE function oppositely in the production of secondary metabolites, and the ΔgcnE mutant showed attenuated virulence. In conclusion, Elp3 and GcnE are associated with diverse biological processes and can be potential targets for controlling the pathogenic fungus.
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Aspergillus fumigatus , Proteínas Fúngicas , Humanos , Aspergillus fumigatus/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Histona Acetiltransferasas/genética , Histona Acetiltransferasas/metabolismo , Virulencia/genética , Esporas Fúngicas , Regulación Fúngica de la Expresión GénicaRESUMEN
CONTEXT: Information on factors associated with developmental competence of equine in vitro -produced (IVP) blastocysts is lacking. AIMS: To determine the relationships of stage, grade, day of development, and specific morphological parameters of equine IVP blastocysts, to pregnancy and foaling rates. METHODS: Photomicrographs of 316 IVP embryos with known pregnancy outcomes were scrutinised individually by four observers. Inter-observer variation was assessed, and pregnancy outcome evaluated in relation to day of blastocyst development and assigned grade and stage. Individual component analysis was performed to determine the association of specific morphological parameters with foaling rate. KEY RESULTS: Overall pregnancy rate was 76.9% and foaling rate was 56.3%. The day of embryo development did not affect pregnancy rate but significantly affected foaling rate. Embryo stage did not affect foaling rate. Embryo grade affected foaling rate only for Day-9 embryos. Some morphological features in the bovine grading system did not predict outcome in equine IVP embryos. Significant individual parameters differed between Stage 5 and Stage 6 equine blastocysts. CONCLUSIONS: Day of blastocyst development is the major factor related to foaling rate for equine IVP embryos. Notably, there was no effect of embryo stage on foaling rate and no evidence that prolonging culture until embryos advance in stage increases foaling rate. The standard bovine grading system is not directly applicable to equine IVP embryos; equine-specific staging and grading systems are proposed. IMPLICATIONS: This information will allow laboratories to identify embryos with the highest developmental competence. Use of the proposed systems will increase consistency in embryo assessment among laboratories.
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Blastocisto , Transferencia de Embrión , Femenino , Embarazo , Animales , Caballos , Bovinos , Transferencia de Embrión/veterinaria , Embrión de Mamíferos , Resultado del Embarazo , Desarrollo Embrionario , Fertilización In Vitro/veterinariaRESUMEN
Background: The objective of this study was to develop and validate machine learning models for data entry error detection in a national out-of-hospital cardiac arrest (OHCA) prehospital patient care report database.Methods: Adult OHCAs of presumed cardiac etiology were included. Data entry errors were defined as discrepancies between the coded data and the free-text note documenting the intervention or event; for example, information that was recorded as "absent" in the coded data but "present" in the free-text note. Machine learning models using the extreme gradient boosting, logistic regression, extreme gradient boosting outlier detection, and K-nearest neighbor outlier detection algorithms for error detection within nine core variables were developed and then validated for each variable.Results: Among 12,100 OHCAs, the proportion of cases with at least one error type was 16.2%. The area under the receiver operating characteristic curve (AUC) of the best-performing model (model with the highest AUC for each outcome variable) was 0.71-0.95. Machine learning models detected errors most efficiently for outcome place and initial rhythm errors; 82.6% of place errors and 93.8% of initial rhythm errors could be detected while checking 11 and 35% of data, respectively, compared to the strategy of checking all data.Conclusion: Machine learning models can detect data entry errors in care reports of emergency medical services (EMS) clinicians with acceptable performance and likely can improve the efficiency of the process of data quality control. EMS organizations that provide more prehospital interventions for OHCA patients could have higher error rates and may benefit from the adoption of error-detection models.
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OBJECTIVES: Area-level socioeconomic status (SES) is associated with the incidence of out-of-hospital cardiac arrest (OHCA); however, the effects of individual-level SES on OHCA occurrence are unknown. This study investigated whether individual-level SES is associated with the occurrence of OHCA. METHODS: This case-control study used data from the nationwide OHCA registry and the National Health Information Database (NHID) in Korea. All adult patients with OHCA of a medical etiology from 2013 to 2018 were included. Four controls were matched to each OHCA patient based on age and sex. The exposure was individual-level SES measured by insurance type and premium, which is based on income in Korea. National Health Insurance (NHI) beneficiaries were divided into four groups (Q1-Q4), and medical aid beneficiaries were separately classified as the lowest SES group. The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the outcomes were calculated. Stratified analyses were conducted according to age and sex. RESULTS: A total of 105,443 cases were matched with 421,772 controls. OHCA occurred more frequently in the lower SES groups. Compared with the highest SES group (Q1), the aORs for OHCA occurrence increased as the SES decreased (aORs [95% CI] were 1.21 [1.19-1.24] for Q2, 1.33 [1.31-1.36] for Q3, 1.32 [1.30-1.35] for Q4, and 2.08 [2.02-2.13] for medical aid). Disparity by individual-level SES appeared to be greater in males than in females and greater in the young and middle-aged adults than in older adults. CONCLUSIONS: Low individual-level SES was associated with a higher probability of OHCA occurrence. Efforts are needed to reduce SES disparities in the occurrence of OHCA.
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Reanimación Cardiopulmonar , Servicios Médicos de Urgencia , Paro Cardíaco Extrahospitalario , Persona de Mediana Edad , Masculino , Femenino , Humanos , Anciano , Paro Cardíaco Extrahospitalario/epidemiología , Paro Cardíaco Extrahospitalario/terapia , Estudios de Casos y Controles , Clase Social , Oportunidad Relativa , Sistema de RegistrosRESUMEN
INTRODUCTION: The aim of this study was to estimate the annual incidence of various severe injuries, case fatality rates, and case disability rates for patients in Korea. MATERIALS AND METHODS: This community-based observational study involved all residents in Korea between Jan. 1, 2018, and Dec. 31, 2018. Nationwide data were retrieved from the patient care report of the National Fire Agency and hospital medical records review of the Korea Disease Control and Prevention Agency. Severe injury was defined as any injury that resulted in emergency medical service (EMS) use and any field-based physiologic abnormality: systolic blood pressure ≤90 mm Hg, respiratory rate <10 or >29 per min, or AVPU scale nonalert. Crude and adjusted incidence rates were calculated without any exclusion. Outcomes including the Glasgow Outcome Scale (GOS) at hospital discharge were assessed according to a medical review. Case-fatality and case-disability rates were calculated after excluding patients with unknown vital status. RESULTS: During the one-year period, 36,363 severe injuries occurred, yielding a crude annual incidence rate of 70.9 per 100,000 population; 57.8% were traumatic injuries, and 42.2% were nontraumatic injuries. The adjusted annual incidence rates were 61.7/100,000 for all severe injuries, 35.3/100,000 for traumatic injuries, and 26.4/100,000 for nontraumatic injuries. The case-fatality rate was 24.3% for all severe injuries, 27.0% for traumatic injuries, and 21.0% for nontraumatic injuries. The case-disability rate of GOS 3,4 was 6.0%, and the case-disability rate of GOS 2-4 was 16.4% for all severe injury patients. CONCLUSIONS: This nationwide community-based study revealed incidence rates and outcomes of severe injury patients in Korea.
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Servicios Médicos de Urgencia , Servicios Médicos de Urgencia/métodos , Escala de Consecuencias de Glasgow , Humanos , Incidencia , Alta del Paciente , República de Corea/epidemiologíaRESUMEN
OBJECTIVE: This study investigates the effects of vesicoureteral reflux (VUR) in the upper and lower urinary tracts with and without ureteral stenosis and with a double J stent (DJS). METHODS: The entire length of the urinary tract with an implanted DJS was modeled. To assess the possibility of VUR, the measured values were used as boundary conditions for the baseline, the maximum cystometric bladder capacity (MCBC) during the filling phase, and maximum vesical pressure during the voiding phase were computed. The flow rates, flow patterns, wall shear stress (WSS) distribution, impact force induced by reflux urination, and helicity of the bladder were investigated for the urinary system. RESULTS: The flow from the bladder to the renal pelvis was detected at maximum vesical pressure (75 cmH2O) during the voiding phase, and a small amount (1.09 mL/s) of VUR was noted at the MCBC during the filling phase. The WSS increased when the reflux was large. Helicity within the bladder varied with the stenosis as well as opening and closing of the urethra. The reflux within the stent was reduced by 40% by inserting a ball into the stent. CONCLUSION: The main VUR factor was the opening and closing of the vesicoureteric junction by the detrusor muscle. The largest urine reflux (11.7 mL/s) to the kidney occurred when the detrusor muscle was relaxed. SIGNIFICANCE: Ureteral stenosis affected the VUR and reduced urine reflux. Ball insertion in the stent reduced urine reflux through the stent lumen.
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Reflujo Vesicoureteral , Constricción Patológica , Humanos , Stents , Vejiga Urinaria , Micción/fisiologíaRESUMEN
BACKGROUND: Indocyanine green (ICG) fluorescence imaging has been used to detect many types of tumors during surgery; however, there are few studies on thymic masses and the dose and time of ICG injection have not been optimized. OBJECTIVE: We aimed to evaluate the optimal ICG injection dose and timing for detecting thymic masses during surgery. METHOD: Forty-nine consecutive patients diagnosed with thymic masses on preoperative computed tomography (CT) and scheduled to undergo thymic cystectomy or thymectomy were included. Patients were administered 1, 2, or 5 mg/kg of ICG at different times. Thymic masses were observed during and after surgery using a near-infrared fluorescence imaging system, and the fluorescence signal tumor-to-normal ratio (TNR) was analyzed. RESULTS: Among the 49 patients, 14 patients with thymic cysts showed negative fluorescence signals, 33 patients with thymoma or thymic carcinoma showed positive fluorescence signals, and 2 patients showed insufficient fluorescence signals. The diagnosis of thymic masses based on CT was correct in 32 (65%) of 49 cases; however, the differential diagnosis of thymic masses based on NIR signals was correct in 47 of 49 cases (96%), including 14 cases of thymic cysts (100%) and 33 cases of thymomas or thymic carcinomas (94%). In addition, TNR was not affected by the time or dose of ICG injection, histological type, stage, or tumor size. CONCLUSIONS: Low-dose intravenous injection of ICG at flexible time can detect thymic tumors. In addition, thymic cysts can be distinguished from thymomas or thymic carcinomas during surgery by the absence of ICG fluorescence signals.
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OBJECTIVE: To analyze the computational fluid dynamics (CFD) of femoral artery pseudoaneurysm (FAP), identify a suitable location and timing for percutaneous thrombin injection (PTI) based on this analysis, and report our clinical experience with the procedure. MATERIALS AND METHODS: CFD can be used to analyze the hemodynamics of the human body. An analysis using CFD recommended that the suitable location of the needle tip for PTI is at the center of the aneurysm sac and the optimal timing for starting PTI is during the early inflow phase of blood into the sac. Since 2011, seven patients (three male and four female; median age, 60 years [range, 43-75 years]) with FAP were treated with PTI based on the devised suitable location and time. Prior to the procedure, color Doppler ultrasonography was performed to determine the location and timing of the thrombin injection. RESULTS: The technical success rate of the PTI was 100%. The amount of thrombin used for the procedure ranged from 200 IU to 1000 IU (median, 500 IU). None of the patients experienced any symptoms or signs of embolic complications during the procedure. Follow-up CT images did not reveal any embolism in the lower extremities and showed complete thrombosis of the pseudoaneurysm. CONCLUSION: Based on our study of CFD, PTI administered centrally in the FAP during early inflow, as seen on color Doppler, can be an effective technique.
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Aneurisma Falso , Trombina , Adulto , Anciano , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/tratamiento farmacológico , Femenino , Arteria Femoral/diagnóstico por imagen , Humanos , Hidrodinámica , Masculino , Persona de Mediana Edad , Trombina/administración & dosificación , Ultrasonografía IntervencionalRESUMEN
The duration of percutaneous transhepatic biliary drainage (PTBD) is a critical factor that determines the duration of treatment. This study aimed to evaluate factors affecting the PTBD duration in patients who underwent percutaneous treatment of common bile duct (CBD) stones. This study analyzed data of 169 patients who underwent percutaneous treatment of CBD stones from June 2009 to June 2019. Demographic data, characteristics of stone, procedure-related factors, and laboratory findings before the insertion of PTBD tubes were retrospectively evaluated. To assess the effect of confounding factors on the PTBD duration, multivariate linear regression analysis was applied, incorporating significant predictive factors identified in the univariate regression analysis. In the univariate regression analysis, the predictive factor that showed high correlation with the PTBD duration was the initial total bilirubin level (coefficient = 0.68, P < .001) followed by the short diameter of the largest stone (coefficient = 0.19, P = .056), and previous endoscopic sphincterotomy (coefficient = -2.50, P = .086). The multivariate linear regression analysis showed that the initial total bilirubin level (coefficient = 0.50, P < .001) and short diameter of the largest stone (coefficient = 0.16, P = .025) were significantly related to the PTBD duration. The total bilirubin level before PTBD tube insertion and the short diameter of the largest CBD stone were predictive factors for the PTBD duration in patients who underwent percutaneous CBD stone removal. Careful assessment of these factors might help in predicting the treatment period, thereby improving the quality of patient care.
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Conducto Colédoco/cirugía , Cálculos Biliares/cirugía , Anciano , Anciano de 80 o más Años , Drenaje , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: We aimed to assess the possibility of detecting esophageal cancer after intravenous injection of indocyanine green (ICG) in preclinical and clinical models. METHODS: Forty-five rabbits were surgically implanted with VX2 tumors into the esophageal muscular layer 2 weeks before esophagectomy. The rabbits received intravenous injection of ICG at doses of 1, 2, or 5 mg/kg at 3, 6, 12, 24, or 48 h before surgical removal of esophagus. Twelve patients scheduled to undergo esophagectomy were also enrolled, and all received 2 mg/kg of ICG intravenously at 3, 6, 12, or 24 h before surgical removal of esophagus. The fluorescence intensity was measured in all resected specimens from the rabbits and patients using a near-infrared (NIR) fluorescence imaging system after surgery. RESULTS: Esophageal tumors were successfully established in all rabbits, and fluorescent signals were detected in all animal and patient specimens. Tumor-to-normal ratio (TNR) analysis showed that higher doses resulted in a greater TNR. Injection of at least 2 mg/kg of ICG was required for clear visualization of the tumor, and the TNR was highest at 12 h after injection. The TNR in patients was also highest at 12 h (P=0.0004), with 2 mg/kg of ICG. None of the patients had major complications following ICG injection. CONCLUSIONS: NIR fluorescence imaging can be used to visualize esophageal cancer after systemic injection of ICG. ICG at 2 mg/kg at 12 h is optimal for tumor detection. However, since the clinical trials were conducted in a small number of patients, further studies are needed in larger populations.
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OBJECTIVE: This study was conducted to develop a fluorescent iodized emulsion comprising indocyanine green (ICG) solution and lipiodol (ethiodized oil) and evaluate its feasibility for use in a clinical setting. BACKGROUND: ICG use for the preoperative localization of pulmonary nodules is limited in terms of penetration depth and diffusion. METHODS: First, fluorescent microscopy was used to investigate the distribution of ICG-lipiodol emulsions prepared using different methods. The emulsions were injected in 15 lung lobes of 3 rabbits under computed tomography fluoroscopy guidance; evaluation with imaging and radiography was conducted after thoracotomy. Subsequently, the emulsions were used to preoperatively localize 29 pulmonary nodules in 24 human subjects, and wedge resections were performed using fluorescent imaging and C-arm fluoroscopy. RESULTS: The optimal emulsion of 10% ICG and 90% lipiodol mixed through 90 passages had even distribution and the highest signal intensity under fluorescent microscopy; it also had the best consistency in the rabbit lungs, which persisted for 24âhours at the injection site. In human subjects, the mean diameter of pulmonary nodules was 0.9â±â0.4âcm, and depth from the pleura was 1.2 ± 0.8âcm. All emulsion types injected were well localized around the target nodules without any side effects or procedure-related complications. Wedge resection with minimally invasive approach was successful in all pulmonary nodules with a free resection margin. CONCLUSIONS: A fluorescent iodized emulsion prepared by mixing ICG with lipiodol enabled accurate localization and resection of pulmonary nodules.
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Medios de Contraste/farmacología , Colorantes Fluorescentes/farmacología , Radioisótopos de Yodo/farmacología , Nódulos Pulmonares Múltiples/diagnóstico , Cirugía Torácica Asistida por Video , Tomografía Computarizada por Rayos X/métodos , Animales , Emulsiones , Humanos , Neoplasias Pulmonares/cirugía , Nódulos Pulmonares Múltiples/cirugía , Neoplasias Experimentales , Periodo Preoperatorio , ConejosRESUMEN
Pyrimidine is a privileged scaffold in many synthetic compounds exhibiting diverse pharmacological activities, and is used for therapeutic applications in a broad spectrum of human diseases. In this study, we prepared a small set of pyrimidine libraries based on the structure of two hit compounds that were identified through the screening of an in-house library in order to identify an inhibitor of anoctamin 1 (ANO1). ANO1 is amplified in various types of human malignant tumors, such as head and neck, parathyroid, and gastrointestinal stromal tumors, as well as in breast, lung, and prostate cancers. After initial screening and further structure optimization, we identified Aa3 as a dose-dependent ANO1 blocker. This compound exhibited more potent anti-cancer activity in the NCI-H460 cell line, expressing high levels of ANO1 compared with that in A549 cells that express low levels of ANO1. Our results open a new direction for the development of small-molecule ANO1 blockers composed of a pyrimidine scaffold and a nitrogen-containing heterocyclic moiety, with drug-like properties.
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Anoctamina-1/antagonistas & inhibidores , Antineoplásicos/química , Antineoplásicos/farmacología , Proteínas de Neoplasias/antagonistas & inhibidores , Pirimidinas/química , Animales , Anoctamina-1/metabolismo , Antineoplásicos/síntesis química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Proteínas de Neoplasias/metabolismo , Pirimidinas/farmacología , RatasRESUMEN
BACKGROUND: The extracellular vesicle (EV) concentration is known to be higher in cancer patients than in healthy individuals. Herein, we report that EV levels differ in the tumor-draining pulmonary vein blood and the peripheral blood of animal models and human subjects at different pathological stages of lung cancer. METHODS: Ten rabbits and 40 humans formed the study cohorts. Blood was collected from the peripheral vein of members of all groups. Pulmonary blood was collected intraoperatively from all groups except for the healthy human controls. Quantitative analysis of EV levels was performed using a nanoparticle tracking assay, a CD63 enzyme-linked immunosorbent assay, and western blotting. RESULTS: The EV levels in the peripheral blood of animals and patients with lung cancer were higher than those in the peripheral blood of healthy controls (p < 0.01 and p < 0.001, respectively). Moreover, for both animals and patients with lung cancer, the EV levels in the pulmonary blood were significantly higher than those in the preoperative peripheral blood (p < 0.01 and p < 0.0001, respectively). In patients, the pathological stages of lung cancer showed a higher correlation with the pulmonary EV levels than the peripheral EV levels. CONCLUSIONS: EV levels increased with increasing lung cancer grade, and this trend was more prominent in the pulmonary blood than in the peripheral blood.