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1.
Cancer Sci ; 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39351646

RESUMEN

Accurate estimation of tumor mutational burden (TMB) as a predictor of responsiveness to immune checkpoint inhibitors in gene panel assays requires an adequate panel size. The current calculations of TMB only consider coding regions, while most of gene panel assays interrogate non-coding regions. Leveraging the non-coding regions is a potential solution to address this panel size limitation. However, the impact of including non-coding regions on the accuracy of TMB estimates remains unclear. This study investigated the validity of leveraging non-coding regions to supplement panel size using the OncoGuide NCC Oncopanel System (NOP). The aim of this study was to evaluate test performance against orthogonal assays and the association with responsiveness to immune checkpoint inhibitors was not included in the evaluation. We compared TMB status and values between TMB calculated only from coding regions (NOP-coding) and from both coding and non-coding regions (NOP-overall) using whole exome sequencing (WES) and FoundationOne®CDx (F1CDx) assay. Our findings revealed that NOP-overall significantly improved the overall percent agreement (OPA) with TMB status compared with NOP-coding for both WES (OPA: 96.7% vs. 73.3%, n = 30) and F1CDx (OPA: 90.0% vs. 73.3%). Additionally, the mean difference in TMB values compared with WES was lower for NOP-overall (3.55 [95% CI: 0.98-6.13]) than for NOP-coding (6.22 [95% CI: 3.73-8.70]). These results exemplify the utility of incorporating non-coding regions to maintain accurate TMB estimates in small-sized panels.

2.
EuroIntervention ; 20(17): e1086-e1097, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39219363

RESUMEN

BACKGROUND: The clinical benefits of optical frequency domain imaging (OFDI)-guided percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain unclear. AIMS: We sought to compare intravascular ultrasound (IVUS)- and OFDI-guided PCI in patients with ACS. METHODS: OPINION ACS is a multicentre, prospective, randomised, non-inferiority trial that compared OFDI-guided PCI with IVUS-guided PCI using current-generation drug-eluting stents in ACS patients (n=158). The primary endpoint was in-stent minimum lumen area (MLA), assessed using 8-month follow-up OFDI. RESULTS: Patients presented with ST-segment elevation myocardial infarction (55%), non-ST-segment elevation myocardial infarction (29%), or unstable angina pectoris (16%). PCI procedural success was achieved in all patients, with comparably low periprocedural complications rates in both groups. Immediately after PCI, the minimum stent area (p=0.096) tended to be smaller for OFDI versus IVUS guidance. Proximal stent edge dissection (p=0.012) and irregular protrusion (p=0.03) were significantly less frequent in OFDI-guided procedures than in IVUS-guided procedures. Post-PCI coronary flow, assessed using corrected Thrombolysis in Myocardial Infarction frame counts, was significantly better in the OFDI-guided group than in the IVUS-guided group (p<0.001). The least squares mean (95% confidence interval [CI]) in-stent MLA at 8 months was 4.91 (95% CI: 4.53-5.30) mm2 and 4.76 (95% CI: 4.35-5.17) mm2 in the OFDI- and IVUS-guided groups, respectively, demonstrating the non-inferiority of OFDI guidance (pnon-inferiority<0.001). The average neointima area tended to be smaller in the OFDI-guided group. The frequency of major adverse cardiac events was similar. CONCLUSIONS: Among ACS patients, OFDI-guided PCI and IVUS-guided PCI were equally safe and feasible, with comparable in-stent MLA at 8 months. OFDI guidance may be a potential option in ACS patients. This study was registered in the Japan Registry of Clinical Trials (jrct.niph.go.jp: jRCTs052190093).


Asunto(s)
Síndrome Coronario Agudo , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Ultrasonografía Intervencional , Humanos , Ultrasonografía Intervencional/métodos , Intervención Coronaria Percutánea/métodos , Masculino , Síndrome Coronario Agudo/terapia , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/cirugía , Femenino , Persona de Mediana Edad , Anciano , Resultado del Tratamiento , Estudios Prospectivos , Tomografía de Coherencia Óptica/métodos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/cirugía , Angina Inestable/terapia , Angina Inestable/diagnóstico por imagen , Angina Inestable/cirugía
3.
J Atheroscler Thromb ; 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39245565

RESUMEN

AIMS: Healed plaque (HP) is associated with rapid plaque growth and luminal narrowing. Thin-cap fibroatheroma (TCFA) is recognized as a precursor lesion to plaque rupture. The aim of the present study was to compare the lipid size among optical coherence tomography (OCT)-derived HP, TCFA, and thick-cap fibroatheroma (ThCFA) using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). METHODS: The present study included 173 patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention. Non-culprit lesions with angiographically intermediate stenosis were assessed by both OCT and NIRS-IVUS. RESULTS: The frequency of TCFA, HP, and ThCFA was 35 (20%), 53 (30%), and 85 (49%), respectively. Minimum lumen area was not significantly different between TCFA and HP, but was smaller in TCFA and HP than in ThCFA (4.6 [interquartile range {IQR}: 3.5-6.4] mm2 vs. 4.3 [3.4-5.3] mm2 vs. 6.5 [4.8-8.6] mm2, P<0.001). Plaque burden was not significantly different between TCFA and HP, but was larger in TCFA and HP than in ThCFA (72 [IQR: 66-80] % vs. 75 [67-80] % vs. 62 [54-69] %, P<0.001). Maximum lipid core burden index in 4mm (maxLCBI4mm) was largest in TCFA, followed by HP and ThCFA (493 [IQR: 443-606] vs. 446 [347-520] vs. 231 [161-302], P<0.001). The frequency of lipid rich plaque with maxLCBI4mm >400 was highest in TCFA, followed by HP and ThCFA (89% vs. 60% vs. 7%, P<0.001). CONCLUSIONS: Based on NIRS-IVUS findings, non-culprit coronary HP in AMI was associated with vulnerable plaque characteristics, but not as much as TCFA.

4.
Beilstein J Org Chem ; 20: 2254-2260, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39286790

RESUMEN

The di(9-anthryl)methyl (DAntM) radical was synthesized and investigated to elucidate its optical, electrical properties, and reactivity. The generation of the DAntM radical was confirmed by its ESR spectrum, which showed two broad signals. The unpaired electron is primarily localized on the central sp2 carbon and slightly delocalized over the two anthryl moieties. Although the DAntM radical undergoes dimerization in solution, the radical still remains even at 190 K due to the bulky nature of the two anthryl groups. Interestingly, upon exposure to air, the purple color of the radical solution quickly fades to orange, resulting in decomposition to give 9-anthryl aldehyde and anthroxyl radical derivatives.

5.
Int J Cardiovasc Imaging ; 40(9): 1903-1910, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39042233

RESUMEN

Global longitudinal strain (GLS) is an echocardiographic measure to detect chemotherapy-related cardiovascular dysfunction. However, its limited availability and the needed expertise may restrict its generalization. Artificial intelligence (AI)-based GLS might overcome these challenges. Our aims are to explore the agreements between AI-based GLS and conventional GLS, and to assess whether the agreements were influenced by expertise levels, cardiac remodeling and cardiovascular diseases/risks. Echocardiographic images in the apical four-chamber view of left ventricle were retrospectively analyzed based on AI-based GLS in patients treated with chemotherapy, and correlation between AI-based GLS (Caas Qardia, Pie Medical Imaging) and conventional GLS (Vivid E9/VividE95, GE Healthcare) were assessed. The agreement between unexperienced physicians ("GLS beginner") and experienced echocardiographer were also assessed. Among 94 patients (mean age 69 ± 12 years, 73% female), mean left ventricular ejection fraction was 64 ± 6%, 14% of patients had left ventricular hypertrophy, and 21% had left atrial enlargement. Mean GLS was - 15.9 ± 3.4% and - 19.0 ± 3.7% for the AI and conventional method, respectively. There was a moderate correlation between these methods (rho = 0.74; p < 0.01), and bias was - 3.1% (95% limits of agreement: -8.1 to 2.0). The reproducibility between GLS beginner and an experienced echocardiographer was numerically better in the AI method than the conventional method (inter-observer agreement = 0.82 vs. 0.68). The agreements were consistent across abnormal cardiac structure and function categories (p-for-interaction > 0.10). In patients treated with chemotherapy. AI-based GLS was moderately correlated with conventional GLS and provided a numerically better reproducibility compared with conventional GLS, regardless of different levels of expertise.


Asunto(s)
Antineoplásicos , Inteligencia Artificial , Cardiotoxicidad , Ecocardiografía , Valor Predictivo de las Pruebas , Función Ventricular Izquierda , Humanos , Femenino , Masculino , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Función Ventricular Izquierda/efectos de los fármacos , Reproducibilidad de los Resultados , Antineoplásicos/efectos adversos , Anciano de 80 o más Años , Interpretación de Imagen Asistida por Computador , Variaciones Dependientes del Observador , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatología , Remodelación Ventricular/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Volumen Sistólico/efectos de los fármacos
6.
JACC Cardiovasc Imaging ; 17(9): 1062-1076, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38752951

RESUMEN

BACKGROUND: A lesion-level risk prediction for acute coronary syndrome (ACS) needs better characterization. OBJECTIVES: This study sought to investigate the additive value of artificial intelligence-enabled quantitative coronary plaque and hemodynamic analysis (AI-QCPHA). METHODS: Among ACS patients who underwent coronary computed tomography angiography (CTA) from 1 month to 3 years before the ACS event, culprit and nonculprit lesions on coronary CTA were adjudicated based on invasive coronary angiography. The primary endpoint was the predictability of the risk models for ACS culprit lesions. The reference model included the Coronary Artery Disease Reporting and Data System, a standardized classification for stenosis severity, and high-risk plaque, defined as lesions with ≥2 adverse plaque characteristics. The new prediction model was the reference model plus AI-QCPHA features, selected by hierarchical clustering and information gain in the derivation cohort. The model performance was assessed in the validation cohort. RESULTS: Among 351 patients (age: 65.9 ± 11.7 years) with 2,088 nonculprit and 363 culprit lesions, the median interval from coronary CTA to ACS event was 375 days (Q1-Q3: 95-645 days), and 223 patients (63.5%) presented with myocardial infarction. In the derivation cohort (n = 243), the best AI-QCPHA features were fractional flow reserve across the lesion, plaque burden, total plaque volume, low-attenuation plaque volume, and averaged percent total myocardial blood flow. The addition of AI-QCPHA features showed higher predictability than the reference model in the validation cohort (n = 108) (AUC: 0.84 vs 0.78; P < 0.001). The additive value of AI-QCPHA features was consistent across different timepoints from coronary CTA. CONCLUSIONS: AI-enabled plaque and hemodynamic quantification enhanced the predictability for ACS culprit lesions over the conventional coronary CTA analysis. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary Computed Tomography Angiography and Computational Fluid Dynamics II [EMERALD-II]; NCT03591328).


Asunto(s)
Síndrome Coronario Agudo , Inteligencia Artificial , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome Coronario Agudo/fisiopatología , Síndrome Coronario Agudo/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Circulación Coronaria , Vasos Coronarios/fisiopatología , Vasos Coronarios/diagnóstico por imagen , Hemodinámica , Tomografía Computarizada Multidetector , Valor Predictivo de las Pruebas , Pronóstico , Interpretación de Imagen Radiográfica Asistida por Computador , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Rotura Espontánea , Índice de Severidad de la Enfermedad , Factores de Tiempo
7.
Chem Rev ; 124(8): 4541-4542, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38654681
8.
Cancer Sci ; 115(6): 2023-2035, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38538548

RESUMEN

Established treatment options for rare cancers are limited by the small number of patients. The current comprehensive genomic profiling (CGP) testing might not fully exploit opportunities for precision oncology in patients with rare cancers. Therefore, we aimed to explore the factors associated with CGP testing utility in rare cancers and identify barriers to implementing precision oncology. Patients who underwent CGP testing at our institution between September 2019 and June 2021 were enrolled in this retrospective study. Based on their results, the patients received molecularly targeted drugs or immune checkpoint inhibitors. Univariate and multivariate analyses evaluated the association between patient characteristics and the proportion of patients receiving molecularly targeted drugs. Overall, 790 patients underwent CGP testing. Among them, 333 patients with rare cancers were identified, of whom 278 (83.5%) had actionable genomic alterations, 127 (38.1%) had druggable genomic alterations, and 25 (7.5%) received genomically matched therapy. The proportion of patients receiving molecularly targeted drugs was significantly higher among those with treatment options with evidence levels A-D (8.7%) than those without treatment options with evidence levels A-D (2.9%). A potential barrier to CGP testing utility in rare cancers is the limited number of molecularly targeted drugs with clinical evidence. We propose that CGP testing be performed in patients with rare cancers who have treatment options with evidence levels A-D to maximize CGP testing utility in real-world practice.


Asunto(s)
Terapia Molecular Dirigida , Neoplasias , Medicina de Precisión , Enfermedades Raras , Humanos , Medicina de Precisión/métodos , Femenino , Masculino , Neoplasias/genética , Neoplasias/tratamiento farmacológico , Estudios Retrospectivos , Persona de Mediana Edad , Terapia Molecular Dirigida/métodos , Anciano , Adulto , Enfermedades Raras/genética , Enfermedades Raras/tratamiento farmacológico , Anciano de 80 o más Años , Genómica/métodos , Adulto Joven , Oncología Médica/métodos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico
9.
Cardiovasc Interv Ther ; 39(2): 164-172, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38329574

RESUMEN

Fluid dynamics studies have proposed that coronary flow reserve can be calculated from coronary artery pressure instead of coronary blood flow. We sought to investigate the diagnostic performance of pressure-bounded coronary flow reserve (pb-CFR) compared with CFR measured by conventional thermodilution method (CFRthermo) in the clinical setting. Pressure guidewire was used to measure CFRthermo and fractional flow reserve (FFR) in left anterior descending coronary artery in 62 patients with stable coronary artery disease. Pb-CFR was calculated only with resting distal coronary artery pressure (Pd), resting aortic pressure (Pa) and FFR. Pb-CFR was moderately correlated with CFRthermo (r = 0.54, P < 0.001). Pb-CFR showed a poor agreement with CFRthermo, presenting large values of mean difference and root mean square deviation (1.5 ± 1.4). Pb-CFR < 2.0 predicted CFRthermo < 2.0 with an accuracy of 79%, sensitivity of 83%, specificity of 78%, positive predictive value of 48%, negative predictive value of 95%. The discordance presenting CFRthermo < 2.0 and pb-CFR ≥ 2.0 was associated with diffuse disease (P < 0.001). The discordance presenting CFRthermo ≥ 2 and pb-CFR < 2 was associated with a high FFR (P = 0.002). Pb-CFR showed moderate correlation and poor agreement with CFRthermo. Pb-CFR might be reliable in excluding epicardial coronary artery disease and microcirculatory disorders.


Asunto(s)
Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Reserva del Flujo Fraccional Miocárdico , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico , Reserva del Flujo Fraccional Miocárdico/fisiología , Microcirculación , Plomo , Vasos Coronarios/diagnóstico por imagen , Valor Predictivo de las Pruebas , Estenosis Coronaria/diagnóstico , Angiografía Coronaria
10.
Angew Chem Int Ed Engl ; 63(18): e202401027, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38415373

RESUMEN

The incorporation of Si atoms into organic compounds significantly increases a variety of functionality, facilitating further applications. Recently, on-surface synthesis was introduced into organosilicon chemistry as 1,4-disilabenzene bridged nanostructures were obtained via coupling between silicon atoms and brominated phenyl groups at the ortho position on Au(111). Here, we demonstrate a high generality of this strategy via syntheses of silole derivatives and nanoribbon structures with eight-membered sila-cyclic rings from dibrominated molecules at the bay and peri positions on Au(111), respectively. Their structures and electronic properties were investigated by a combination of scanning tunneling microscopy/spectroscopy and density functional theory calculations. This work demonstrates a great potential to deal with heavy group 14 elements in on-surface silicon chemistry.

11.
JACC Cardiovasc Interv ; 17(1): 46-56, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38199753

RESUMEN

BACKGROUND: Coronary angiography-derived radial wall strain (RWS) is a newly developed index that can be readily accessed and describes the biomechanical features of a lesion. OBJECTIVES: The authors sought to investigate the association of RWS with fractional flow reserve (FFR) and high-risk plaque (HRP), and their relative prognostic implications. METHODS: We included 484 vessels (351 patients) deferred after FFR measurement with available RWS data and coronary computed tomography angiography. On coronary computed tomography angiography, HRP was defined as a lesion with both minimum lumen area <4 mm2 and plaque burden ≥70%. The primary outcome was target vessel failure (TVF), a composite of target vessel revascularization, target vessel myocardial infarction, or cardiac death. RESULTS: The mean FFR and RWSmax were 0.89 ± 0.07 and 11.2% ± 2.5%, respectively, whereas 27.7% of lesions had HRP, 15.1% had FFR ≤0.80. An increase in RWSmax was associated with a higher risk of FFR ≤0.80 and HRP, which was consistent after adjustment for clinical or angiographic characteristics (all P < 0.05). An increment of RWSmax was related to a higher risk of TVF (HR: 1.23 [95% CI: 1.03-1.47]; P = 0.022) with an optimal cutoff of 14.25%. RWSmax >14% was a predictor of TVF after adjustment for FFR or HRP components (all P < 0.05) and showed a direct prognostic effect on TVF, not mediated by FFR ≤0.80 or HRP in the mediation analysis. When high RWSmax was added to FFR ≤0.80 or HRP, there were increasing outcome trends (all P for trend <0.001). CONCLUSIONS: RWS was associated with coronary physiology and plaque morphology but showed independent prognostic significance.


Asunto(s)
Reserva del Flujo Fraccional Miocárdico , Humanos , Angiografía Coronaria , Resultado del Tratamiento , Corazón , Angiografía por Tomografía Computarizada
12.
Virchows Arch ; 484(1): 71-81, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37704823

RESUMEN

Myxoid liposarcoma (MLS) is a common type of liposarcoma. It is characterized by variably lipogenic uniform cells in myxoid stroma with arborizing capillaries and DDIT3 fusion. Nuclear uniformity is the rule, which is maintained even in high-grade round cell examples. In this study, we conducted an in-depth investigation of four MLS tumors that demonstrated nuclear pleomorphism in three patients. These cases accounted for 2.1% of 142 patients with MLS. All patients were male aged 26, 33, and 49 years. Nuclear pleomorphism was observed in both primary and metastatic tumors in one patient, a primary tumor in one patient, and a metastatic tumor in another patient. Pleomorphism was severe in three tumors and moderate in one. Histology resembled that of dedifferentiated liposarcoma with myxoid features, pleomorphic liposarcoma with myxoid features, or myxoid pleomorphic liposarcoma in two tumors, pleomorphic sarcoma with focal cartilaginous and rhabdomyoblastic differentiation in one tumor, and epithelioid pleomorphic liposarcoma in one tumor. All tumors harbored FUS::DDIT3 fusions and immunohistochemically expressed DDIT3. All tumors had TP53 mutations, whereas previous specimens with uniform cytology from the same patients lacked TP53 mutations. One tumor showed RB1 deletion and complete loss of Rb expression, which was unclassifiable using DNA methylation-based methods. The rare occurrence of nuclear pleomorphism is underrecognized in MLS and increases the complexity to the diagnosis of liposarcoma. DDIT3 evaluation can be liberally considered in liposarcoma assessment even in the presence of nuclear pleomorphism.


Asunto(s)
Liposarcoma Mixoide , Liposarcoma , Neoplasias de los Tejidos Blandos , Adulto , Humanos , Masculino , Femenino , Liposarcoma Mixoide/genética , Liposarcoma/genética , Mutación , Diferenciación Celular
13.
Mod Pathol ; 37(1): 100359, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37871654

RESUMEN

Inflammatory rhabdomyoblastic tumors (IRMTs) are newly recognized skeletal muscle tumors with uncertain malignant potential. We investigated 13 IRMTs using clinicopathologic, genetic, and epigenetic methods. The cohort included 7 men and 6 women, aged 23 to 80 years (median, 50 years), of whom 2 had neurofibromatosis type 1. Most tumors occurred in the deep soft tissues of the lower limbs, head/neck, trunk wall, and retroperitoneum/pelvis. Two tumors involved the hypopharyngeal submucosa as polypoid masses. Eight tumors showed conventional histology of predominantly spindled cells with nuclear atypia, low mitotic activity, and massive inflammatory infiltrates. Three tumors showed atypical histology, including uniform epithelioid or plump cells and mitotically active histiocytes. The remaining 2 tumors demonstrated malignant progression to rhabdomyosarcoma; one had additional IRMT histology and the other was a pure sarcoma. All 11 IRMTs without malignant progression exhibited indolent behavior at a median follow-up of 43 months. One of the 2 patients with IRMTs with malignant progression died of lung metastases. All IRMTs were positive for desmin and PAX7, whereas myogenin and MyoD1 were expressed in a subset of cases. Targeted next-generation sequencing identified pathogenic mutations in NF1 (5/8) and TP53 (4/8). All TP53 mutations co-occurred with NF1 mutations. TP53 variant allele frequency was much lower than that of NF1 in 2 cases. These tumors showed geographic (subclonal) strong p53 immunoreactivity, suggesting the secondary emergence of a TP53-mutant clone. DNA methylation-based copy number analysis conducted in 11 tumors revealed characteristic flat patterns with relative gains, including chromosomes 5, 18, 20, 21, and/or 22 in most cases. Widespread loss of heterozygosity with retained biparental copies of these chromosomes was confirmed in 4 tumors analyzed via allele-specific profiling. Based on unsupervised DNA methylation analysis, none of the 11 tumors tested clustered with existing reference entities but formed a coherent group, although its specificity warrants further study.


Asunto(s)
Neoplasias de los Músculos , Neurofibromatosis 1 , Rabdomiosarcoma , Sarcoma , Neoplasias de los Tejidos Blandos , Masculino , Humanos , Femenino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Rabdomiosarcoma/genética , Rabdomiosarcoma/patología , Sarcoma/patología , Neoplasias de los Tejidos Blandos/genética
14.
JACC Asia ; 3(5): 689-706, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38095005

RESUMEN

Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of evidence that has led to major recommendations in clinical practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region based on updated information in the field that including both wire- and image-based physiologic assessment. This is Part 1 of the whole consensus document, which describes the general concept of coronary physiology, as well as practical information on the clinical application of physiologic indices and novel image-based physiologic assessment.

15.
JACC Asia ; 3(6): 825-842, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38155788

RESUMEN

Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of clinical data that has led to major recommendations in all practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region, based on updated information in the field that includes both wire- and image-based physiologic assessment. This is Part 2 of the whole consensus document, which provides theoretical and practical information on physiologic indexes for specific clinical conditions and patient statuses.

16.
Nat Commun ; 14(1): 7741, 2023 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-38007486

RESUMEN

Synthesis of one-dimensional molecular arrays with tailored stereoisomers is challenging yet has great potential for application in molecular opto-, electronic- and magnetic-devices, where the local array structure plays a decisive role in the functional properties. Here, we demonstrate the construction and characterization of dehydroazulene isomer and diradical units in three-dimensional organometallic compounds on Ag(111) with a combination of low-temperature scanning tunneling microscopy and density functional theory calculations. Tip-induced voltage pulses firstly result in the formation of a diradical species via successive homolytic fission of two C-Br bonds in the naphthyl groups, which are subsequently transformed into chiral dehydroazulene moieties. The delicate balance of the reaction rates among the diradical and two stereoisomers, arising from an in-line configuration of tip and molecular unit, allows directional azulene-to-azulene and azulene-to-diradical local probe structural isomerization in a controlled manner. Furthermore, our theoretical calculations suggest that the diradical moiety hosts an open-shell singlet with antiferromagnetic coupling between the unpaired electrons, which can undergo an inelastic spin transition of 91 meV to the ferromagnetically coupled triplet state.

17.
A A Pract ; 17(11): e01727, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37948548

RESUMEN

Ropivacaine is an amide local anesthetic with rare reports of anaphylaxis. To our knowledge, this is the first report of delayed nonimmune anaphylaxis induced by ropivacaine. A 70-year-old man underwent general anesthesia with a nerve block for a total knee arthroplasty. The patient developed symptoms of anaphylaxis 3.5 hours after receiving ropivacaine for femoral and tibial nerve blocks. A basophil activation test (BAT) revealed ropivacaine as the causative agent. Notably, anaphylaxis can be caused by medications even hours after their administration, and all administered drugs should be suspected of potentially causing anaphylaxis.


Asunto(s)
Anafilaxia , Bloqueo Nervioso , Masculino , Humanos , Anciano , Ropivacaína/efectos adversos , Anestésicos Locales/efectos adversos , Anafilaxia/inducido químicamente , Amidas/efectos adversos , Bloqueo Nervioso/efectos adversos
19.
JCO Precis Oncol ; 7: e2200266, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37410973

RESUMEN

PURPOSE: This single-center, prospective molecular profiling study characterizes genomic alterations and identifies therapeutic targets in advanced pediatric solid tumors. METHODS: As part of the TOP-GEAR (Trial of Onco-Panel for Gene profiling to Estimate both Adverse events and Response by cancer treatment) project at the National Cancer Center (NCC), Japan, we enrolled pediatric patients with a refractory or recurrent disease during August 2016-December 2021 and performed genomic analysis of matched tumors and blood using originally developed cancer gene panels, NCC Oncopanel (ver. 4.0) and NCC Oncopanel Ped (ver. 1.0). RESULTS: Of 142 patients (age, 1-28 years) enrolled, 128 (90%) were evaluable for genomic analysis; 76 (59%) patients harbored at least one reportable somatic or germline alteration. The tumor samples were collected during the initial diagnosis in 65 (51%) patients, after treatment initiation in 11 (9%) patients, and upon either disease progression or relapse in 52 (41%) patients. The leading altered gene was TP53, followed by MYCN, MYC, CDKN2A, and CDK4. The commonly affected molecular processes were transcription, cell-cycle regulation, epigenetic modifiers, and RAS/mitogen-activated protein kinase signaling. Twelve (9%) patients carried pathogenic germline variants in cancer-predisposing genes. Potentially actionable findings were identified in 40 (31%) patients; to date, 13 (10%) patients have received the recommended therapy on the basis of their genomic profiles. Although four patients had access to targeted therapy through clinical trials, the agents were used in nine patients in an off-label setting. CONCLUSION: The implementation of genomic medicine has furthered our understanding of tumor biology and provided new therapeutic strategies. However, the paucity of proposed agents limits the full potential of actionability, emphasizing the significance of facilitating access to targeted cancer therapies.


Asunto(s)
Neoplasias , Medicina de Precisión , Humanos , Niño , Lactante , Preescolar , Adolescente , Adulto Joven , Adulto , Japón , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Genómica , Mutación de Línea Germinal
20.
Sci Rep ; 13(1): 11544, 2023 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-37460602

RESUMEN

Acute myocardial infarction (AMI) can rarely arise from non-lipid-rich coronary plaques. This study sought to compare the clinical outcomes after percutaneous coronary intervention (PCI) between AMI showing maximum lipid-core burden index in 4 mm (maxLCBI4mm) < 400 and ≥ 400 in the infarct-related lesions assessed by near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). We investigated 426 AMI patients who underwent NIRS-IVUS in the infarct-related lesions before PCI. Major adverse cardiovascular events (MACE) were defined as the composite of cardiac death, non-fatal MI, clinically driven target lesion revascularization (TLR), clinically driven non-TLR, and congestive heart failure requiring hospitalization. 107 (25%) patients had infarct-related lesions of maxLCBI4mm < 400, and 319 (75%) patients had those of maxLCBI4mm ≥ 400. The maxLCBI4mm < 400 group had a younger median age at onset (68 years [IQR: 57-78 years] vs. 73 years [IQR: 64-80 years], P = 0.007), less frequent multivessel disease (39% vs. 51%, P = 0.029), less frequent TIMI flow grade 0 or 1 before PCI (62% vs. 75%, P = 0.007), and less frequent no-reflow immediately after PCI (5% vs. 11%, P = 0.039). During a median follow-up period of 31 months [IQR: 19-48 months], the frequency of MACE was significantly lower in the maxLCBI4mm < 400 group compared with the maxLCBI4mm ≥ 400 group (4.7% vs. 17.2%, P = 0.001). MaxLCBI4mm < 400 was an independent predictor of MACE-free survival at multivariable analysis (hazard ratio: 0.36 [confidence interval: 0.13-0.98], P = 0.046). MaxLCBI4mm < 400 measured by NIRS in the infract-related lesions before PCI was associated with better long-term clinical outcomes in AMI patients.


Asunto(s)
Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Intervención Coronaria Percutánea , Placa Aterosclerótica , Humanos , Persona de Mediana Edad , Anciano , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/complicaciones , Intervención Coronaria Percutánea/efectos adversos , Espectroscopía Infrarroja Corta , Ultrasonografía Intervencional , Infarto del Miocardio/complicaciones , Placa Aterosclerótica/etiología , Resultado del Tratamiento , Angiografía Coronaria , Vasos Coronarios/diagnóstico por imagen
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