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1.
Cancer Sci ; 114(2): 630-639, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36285515

RESUMEN

The role of previous thoracic radiation therapy as a risk factor of immune-related pneumonitis is unclear. Furthermore, some patients develop radiation recall pneumonitis, which is characterized by a radiation pneumonitis-like imaging pattern with consolidation progressing within a previous radiation field. In this multicenter retrospective study, we analyzed the relationship of previous thoracic radiation therapy with immune-related pneumonitis and the characteristics of radiation recall pneumonitis. The medical records of patients with non-small-cell lung cancer who had received nivolumab between December 2015 and March 2017 at five institutions were retrospectively reviewed. Incidence, imaging patterns, clinical course, and risk factors of immune-related pneumonitis and radiation recall pneumonitis were evaluated. A total of 669 patients were evaluated, and the incidences of all-grade and grade 3 or higher immune-related pneumonitis were 8.8% and 2.6%, respectively. The incidences of immune-related pneumonitis were 13.2% (34/257) and 6.1% (25/412) in patients with and those without previous thoracic radiation therapy, respectively. A history of previous thoracic radiation therapy was associated with immune-related pneumonitis (odds ratio, 2.11; 95% confidence interval, 1.21-3.69 in multivariate analysis). Among the patients with previous thoracic radiation therapy, 6.2% (16/257) showed radiation recall pattern. This study found an increased risk of nivolumab-induced immune-related pneumonitis associated with a history of thoracic radiation therapy. Radiation recall pattern was one of the major patterns of immune-related pneumonitis among the patients with previous thoracic radiation therapy. Incidence, risk factors, and clinical outcome of radiation recall pneumonitis were elucidated.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neumonía , Neumonitis por Radiación , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Nivolumab/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Estudios Retrospectivos , Neumonitis por Radiación/etiología , Neumonitis por Radiación/inducido químicamente , Neumonía/inducido químicamente , Neumonía/epidemiología
2.
Cancer Sci ; 114(5): 2087-2097, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36704833

RESUMEN

The safety of osimertinib is limited in patients with severe or moderate renal impairment, or low body weight. This study aimed to investigate the safety, pharmacokinetics (PK) and recommended dose (RD) of osimertinib in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with impaired renal function and low body weight. Thirty-one eligible patients were enrolled and allocated into four cohorts: A, normal renal function (estimated glomerular filtration rate [eGFR] ≥ 50 mL/min/1.73 m2 ) and normal body weight (≥45 kg); B, moderate renal impairment (eGFR = 30-50 mL/min/1.73 m2 ); C, low body weight (<45 kg); and D, severe renal impairment (eGFR <30 mL/min/1.73 m2 or undergoing dialysis). PK parameters and safety were evaluated with a starting dose of 80 mg osimertinib administered orally once daily in cohorts A, B, and C and 40 mg once daily in cohort D. The PK parameters in cohorts A, B, and C were found to be similar. No dose-limiting toxicity was observed, and the RD was determined to be 80 mg once daily in patients with moderate renal function and low body weight. Four serious adverse events, acneiform rash, diarrhea, QTc prolongation, and interstitial lung disease, were noted. Although the PK parameters of osimertinib were similar across all cohorts, toxicity occurred more frequently in patients with impaired renal function and low body weight. Clinicians should prescribe osimertinib with caution in NSCLC patients with impaired renal function and low body weight.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Insuficiencia Renal , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Compuestos de Anilina/efectos adversos , Riñón/fisiología , Peso Corporal , Mutación , Inhibidores de Proteínas Quinasas/efectos adversos
3.
Jpn J Clin Oncol ; 51(1): 37-44, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33147606

RESUMEN

Major issues in anaplastic lymphoma kinase-positive non-small cell lung carcinoma are acquired resistance against anaplastic lymphoma kinase inhibitors and control of central nervous system metastasis. The development of these inhibitors has changed therapeutic strategy in patients with advanced anaplastic lymphoma kinase-positive non-small cell lung carcinoma. Brigatinib and lorlatinib were designed to penetrate the blood-brain barrier and to inhibit resistant mutations against anaplastic lymphoma kinase inhibitors. We review the clinical data supporting treatment of advanced anaplastic lymphoma kinase-positive non-small cell lung carcinoma with brigatinib and lorlatinib. Brigatinib has shown promising antitumour activity, including substantial activity against central nervous system metastases, in crizotinib-treated (ALTA trial) patients and crizotinib-naïve (ALTA-1L trial) patients with anaplastic lymphoma kinase-positive non-small cell lung carcinoma. In addition, brigatinib improved progression-free survival compared with crizotinib in anaplastic lymphoma kinase inhibitor-naïve patients with anaplastic lymphoma kinase-positive non-small cell lung carcinoma. Lorlatinib has demonstrated clinical antitumour activity against both intracranial and extracranial lesions in patients with anaplastic lymphoma kinase- or c-ros oncogene 1 (ROS1)-positive non-small cell lung carcinoma. Ongoing trials and further studies of these agents' biological and clinical properties would provide insight into the optimal therapeutic strategy for administering them to achieve the best survival benefit.


Asunto(s)
Quinasa de Linfoma Anaplásico/antagonistas & inhibidores , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/secundario , Lactamas Macrocíclicas/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Mutación , Compuestos Organofosforados/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Aminopiridinas , Quinasa de Linfoma Anaplásico/análisis , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Crizotinib/uso terapéutico , Resistencia a Antineoplásicos/genética , Humanos , Lactamas , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Pirazoles
4.
Cancer Sci ; 111(7): 2488-2498, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32426898

RESUMEN

Cryoprobe is a novel transbronchial biopsy (TBB) tool that yields larger tissue samples than forceps. Pathological diagnosis and biomarker analysis, such as genetic alterations and programmed death-ligand 1 (PD-L1) expression, are paramount for precision medicine against lung cancer. We evaluated the safety and usefulness of cryoprobe TBB for lung cancer diagnosis and biomarker analysis. In this single-center, prospective single-arm study, patients suspected of having or diagnosed with primary lung cancer underwent cryoprobe TBB using flexible bronchoscopy after conventional forceps TBB from the same lesion. Cryoprobe TBB was performed in 121 patients. The incidence rate of severe bleeding and serious adverse events (4% [90% confidence interval: 2%-9%]) was significantly lower than the expected rate (20% with 30% threshold, P < 0.01). Combining both central and peripheral lesions, the diagnostic yield rate of cryoprobe samples was 76% and that of forceps samples was 84%. Compared with forceps TBB samples, cryoprobe TBB samples were larger (cryoprobe 15 mm2 vs forceps 2 mm2 ) and resulted in a larger proportion of definite histomorphological diagnosis (cryoprobe 86% vs forceps 74%, P < 0.01), larger amounts of DNA extracted from samples (median: cryoprobe, 1.60 µg vs forceps, 0.58 µg, P = 0.02) and RNA (median: cryoprobe, 0.62 µg vs forceps, 0.17 µg, P < 0.01) extracted from samples, and tended to yield greater rates of PD-L1 expression >1% (51% vs 42%). In conclusion, cryoprobe is a safe and useful tool for obtaining lung cancer tissue samples of adequate size and quality, which allow morphological diagnosis and biomarker analysis for precision medicine against lung cancer.


Asunto(s)
Broncoscopía/métodos , Biopsia Guiada por Imagen/métodos , Neoplasias Pulmonares/diagnóstico , Medicina de Precisión , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Broncoscopía/normas , Femenino , Humanos , Biopsia Guiada por Imagen/normas , Inmunohistoquímica , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Medicina de Precisión/métodos , Medicina de Precisión/normas , Carga Tumoral , Adulto Joven
5.
Pathol Int ; 69(8): 472-480, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31339210

RESUMEN

Humoral factors from cancer-associated fibroblasts (CAFs) reportedly affect epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance in cancer cells with EGFR mutations. The aim of this study was to identify the robust humoral factors secreted from CAFs that induce the primary resistance to EGFR-TKI. We evaluated the EGFR-TKI sensitivity of EGFR-mutant lung adenocarcinoma cell line (PC-9) treated with condition media (CM) from 18 cases of CAFs and matched non-cancerous-tissue-associated fibroblasts (NCAFs). We measured the expression levels of hepatocyte growth factor (HGF), interleukin-6, fibroblast growth factor-2, insulin-like growth factor-1, and vascular endothelial growth factor-A in CAFs and NCAFs. We examined whether HGF neutralizing antibody could annul the EGFR-TKI resistance induced by CM from CAFs. Compared to CM from NCAFs, CM from CAFs increased the resistance of PC-9 cells to EGFR-TKI in five out of 18 cases. Relative expression ratio of HGF messenger RNA was significantly higher in these five CAFs compared to others (P = 0.0013), whereas other cytokines were not. In four of these five cases, the addition of HGF neutralizing antibody significantly decreased the survival ratio of PC-9 cells. This study suggests that the secretion of higher amounts of HGF is the robust feature of EGFR-TKI resistance-promoting CAFs.


Asunto(s)
Fibroblastos Asociados al Cáncer/metabolismo , Resistencia a Antineoplásicos/fisiología , Factor de Crecimiento de Hepatocito/metabolismo , Fenotipo , Inhibidores de Proteínas Quinasas/metabolismo , Adenocarcinoma/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Receptores ErbB/metabolismo , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/farmacología
7.
Phys Chem Chem Phys ; 17(12): 8120-4, 2015 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-25729788

RESUMEN

The Seebeck coefficient, according to Ioffe's approximation, is inversely proportional to carrier density and decreases with doping. Herein, we find that the incorporation of multi-walled carbon nanotubes into rutile TiO2 improves the electrical conductivity and Seebeck coefficient at a low filling fraction of tubes; moreover, the former was due to the lengthening of the mean free path and doping modified carrier mobility for the latter. Tube-oxide mixing also causes significant phonon drag at the interfaces and the reduced thermal conductivity was verified by the promoted figure of merit.

8.
Eur J Neurosci ; 39(6): 934-945, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24393437

RESUMEN

In the primary visual cortex (V1), the spike synchronization seen in neuron pairs with non-overlapping receptive fields can be explained by similarities in their preferred orientation (PO). However, this is not true for pairs with overlapping receptive fields, as they can still exhibit spike synchronization even if their POs are only weakly correlated. Here, we investigated the relationship between spike synchronization and suppressive modulation derived from classical receptive-field surround (surround suppression). We found that layer 4 and layer 2/3 pairs exhibited mainly asymmetric spike synchronization that had non-zero time-lags and was dependent on both the similarity of the PO and the strength of surround suppression. In contrast, layer 2/3 and layer 2/3 pairs showed mainly symmetric spike synchronization that had zero time-lag and was dependent on the similarity of the strength of surround suppression but not on the similarity in POs. From these results, we propose that in cat V1 there exists a functional network that mainly depends on the similarity in surround suppression, and that in layer 2/3 neurons the network maintains surround suppression that is primarily inherited from layer 4 neurons.


Asunto(s)
Sincronización Cortical , Potenciales Evocados Visuales , Corteza Visual/fisiología , Animales , Gatos
9.
J Vis ; 14(13): 23, 2014 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-25413628

RESUMEN

Several physiological studies in cats and monkeys have reported that the spatial frequency (SF) tuning of visual neurons varies depending on the luminance contrast and size of stimulus. However, comparatively little is known about the effect of changing the stimulus contrast and size on SF tuning in human perception. In the present study, we investigated the effects of stimulus size and luminance contrast on human SF tuning using the subspace-reverse-correlation method. Measuring SF tunings at six different stimulus sizes and three different luminance contrast conditions (90%, 10%, and 1%), we found that human perception exhibits significant stimulus-size-dependent SF tunings. At 90% and 10% contrast, participants exhibited relative SF tuning (cycles/image) rather than absolute SF tuning (cycles/°) at response peak latency. On the other hand, at 1% contrast, the magnitude of the size-dependent-peak SF shift was too small for strictly relative SF tuning. These results show that human SF tuning is not fixed, but varies depending on the stimulus size and contrast. This dependency may contribute to size-invariant object recognition within an appropriate contrast rage.


Asunto(s)
Sensibilidad de Contraste/fisiología , Reconocimiento Visual de Modelos/fisiología , Procesamiento Espacial/fisiología , Adulto , Femenino , Humanos , Luz , Masculino , Orientación , Psicofísica , Tiempo de Reacción , Neuronas Retinianas/fisiología , Adulto Joven
10.
Lung Cancer ; 191: 107540, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38614069

RESUMEN

OBJECTIVES: Osimertinib is a standard treatment for patients with EGFR-mutant non-small cell lung cancer (NSCLC) and is highly effective for brain metastases (BMs). However, it is unclear whether local treatment (LT) for BMs prior to osimertinib administration improves survival in EGFR-mutant NSCLC. We aimed to reveal the survival benefit of upfront local treatment (LT) for BMs in patients treated with osimertinib. MATERIALS AND METHODS: This multicenter retrospective study included consecutive patients with EGFR mutation (19del or L858R)-positive NSCLC who had BMs before osimertinib initiation between August 2018 and October 2021. We compared overall survival (OS) and central nervous system progression-free survival (CNS-PFS) between patients who received upfront LT for BMs (the upfront LT group), and patients who received osimertinib only (the osimertinib-alone group). Inverse-probability treatment weighting (IPTW) analysis was performed to adjust for potential confounding factors. RESULTS: Of the 121 patients analyzed, 57 and 64 patients had 19del and L858R, respectively. Forty-five and 76 patients were included in the upfront LT group and the osimertinib-alone groups, respectively. IPTW-adjusted Kaplan-Meier curves showed that the OS of the upfront LT group was significantly longer than that of the osimertinib-alone group (median, 95 % confidence intervals [95 %CI]: Not reached [NR], NR-NR vs. 31.2, 21.7-33.2; p = 0.021). The hazard ratio (HR) for OS and CNS-PFS was 0.37 (95 %CI, 0.16-0.87) and 0.36 (95 %CI, 0.15-0.87), respectively. CONCLUSIONS: The OS and CNS-PFS of patients who received upfront LT for BMs followed by osimertinib were significantly longer than those of patients who received osimertinib alone. Upfront LT for BMs may be beneficial in patients with EGFR-mutant NSCLC treated with osimertinib.


Asunto(s)
Acrilamidas , Compuestos de Anilina , Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Indoles , Neoplasias Pulmonares , Mutación , Pirimidinas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Masculino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Femenino , Receptores ErbB/genética , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidad , Estudios Retrospectivos , Acrilamidas/uso terapéutico , Compuestos de Anilina/uso terapéutico , Persona de Mediana Edad , Anciano , Antineoplásicos/uso terapéutico , Anciano de 80 o más Años , Inhibidores de Proteínas Quinasas/uso terapéutico
11.
J Cancer Res Clin Oncol ; 149(13): 12435-12442, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37439826

RESUMEN

PURPOSE: Vascular endothelial growth factor (VEGF) inhibitors are widely used in chemotherapy for non-small lung cancer (NSCLC). The purpose of the current study was to examine the impact of background cardiovascular risk factors on VEGF inhibitor-related adverse vascular events (VEGF-related AVEs) in patients with NSCLC who also had comorbidities. METHODS: We conducted a retrospective study of 118 NSCLC patients treated with bevacizumab or ramucirumab from April 2010 to December 2022. We compared baseline cardiovascular risk factors with VEGF-related AVEs. RESULTS: VEGF-related AVEs and discontinuation due to VEGF-related AVEs were reported in 54 patients and 21 patients, respectively. VEGF-related AVEs were significantly more common with male sex, smoking history, history of hypertension, dyslipidemia, diabetes mellitus, or cardiovascular disease. Discontinuation due to VEGF-related AVEs was significantly more common in patients with history of hypertension or chronic kidney disease. VEGF-related AVEs were significantly more common in patients with ≥ 3 cardiovascular risk factors than patients with < 3. Discontinuation due to VEGF-related AVEs was significantly more common in patients with ≥ 4 cardiovascular risk factors than patients with < 4. Multivariate analysis demonstrated that male sex, hypertension, and ≥ 6 cycles of VEGF inhibitors were each associated with VEGF-related AVEs and hypertension was associated with discontinuation due to VEGF-related AVEs. CONCLUSION: Our study demonstrated that history of hypertension was independently associated with increased risk of both VEGF-related AVEs and discontinuation due to VEGF-related AVEs. In conclusion, we need to be aware of VEGF-related AVEs when using VEGF inhibitors for patients with ≥ 3 cardiovascular risk factors.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Enfermedades Cardiovasculares , Hipertensión , Neoplasias Pulmonares , Humanos , Masculino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inducido químicamente , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Inhibidores de la Angiogénesis/efectos adversos , Bevacizumab/efectos adversos , Factores de Riesgo de Enfermedad Cardiaca , Hipertensión/inducido químicamente , Hipertensión/epidemiología , Hipertensión/tratamiento farmacológico
12.
Cureus ; 15(11): e49273, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38143696

RESUMEN

Objectives This retrospective study aimed to investigate the relationships between the Keros classification, the Gera classification, the vertical height of the posterior ethmoid roof (ER), and anterior ethmoidal artery (AEA) types in Japanese patients. Methods We investigated the computed tomography (CT) slices of paranasal sinuses (120 sides) of 60 patients; measured the cribriform plate (CP) depth, lateral lamella CP angle (LLCPA), and vertical height of the lateral ER from the hard palate (LERHP) at the coronal plane of the posterior ethmoidal artery (PEA); and reviewed the AEA types, whether floating or non-floating. Results CP depth was positively correlated with LLCPA (r=0.63; p<0.01) and the height of LERHP (r=0.19; p<0.05). The height of the LERHP in females was significantly lower than that in males. With increased CP depth, floating AEAs became prevalent (p<0.001). Conclusion In females, low height of the posterior ethmoid sinus roof, where cerebrospinal fluid (CSF) leaks occurred while penetrating the basal lamella, often existed; the heights positively correlated with the Keros classification in Japanese patients. The Keros and Gera classifications, AEA type, and posterior ER height do not individually constitute a complete risk assessment but may correlate, preventing major complications, such as CSF leak and orbital hemorrhage.

13.
Diagnostics (Basel) ; 12(2)2022 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-35204545

RESUMEN

Sinonasal inverted papilloma (SNIP) can recur; however, the factors related to tumor recurrence remain unclear. This study aimed to analyze risk factors, including human papillomavirus (HPV) infection, as well as other factors associated with SNIP recurrence. Thirty-two patients who were diagnosed with SNIP and underwent surgery between 2010 and 2019 were enrolled: 24 men and 8 women, with a mean age of 59.2 years. The mean follow-up was 57.3 months. Demographics and information about history of smoking, diabetes mellitus (DM), hypertension, allergic rhinitis, alcohol consumption, tumor stage, surgical approach, and recurrence were reviewed retrospectively. Specimens were investigated using polymerase chain reaction to detect HPV DNA (high-risk subtypes: 16, 18, 31, 33, 35, 52b, and 58; low-risk subtypes: 6 and 11). Seven patients (21.9%) experienced recurrence. HPV DNA was detected in five (15.6%) patients (high-risk subtypes, n = 2; low-risk subtypes, n = 3). Patients with recurrence of SNIP had a higher proportion of young adults and displayed higher rates of HPV infection, DM, and advanced tumor stage than those without recurrence. HPV infection, young adulthood, DM, and advanced tumor stage could be associated with a high recurrence rate, which suggests that patients with these risk factors could require close follow-up after surgery.

14.
JTO Clin Res Rep ; 3(11): 100404, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36275911

RESUMEN

Introduction: Pembrolizumab is a programmed death-ligand 1 inhibitor that was initially indicated for monotherapy in patients with advanced lung cancer. The Japanese Lung Cancer Society conducted an observational study on pembrolizumab using confirmative data obtained through postmarketing all-case surveillance (PMACS), which was performed by a pharmaceutical company under the Japanese law in 2017. Methods: This multicenter observational study was conducted by the Japanese Lung Cancer Society using PMACS data with the newly created central registration system regarding patients with NSCLC who received pembrolizumab monotherapy between February 1, 2017 and June 30, 2017; a new database was created by adding the clinical information regarding prognosis for 3 years after therapy to the existing data collected by PMACS. Results: A total of 300 patients from 43 facilities were enrolled in this study. The median overall survival and progression-free survival after pembrolizumab initiation were 558 and 188 days, respectively. Moreover, the 1- and 3-year survival rates were 58.9% and 33.7%, respectively. Results of multivariate analysis revealed performance status (p < 0.0001), histology (p = 0.0118), previous chemotherapy (p = 0.0007), programmed death-ligand 1 expression status (p = 0.0195), and previous steroid use (p = 0.0460) as significant factors that affected overall survival. The toxicity profile was similar to that previously reported. Conclusions: In this first attempt to use PMACS data, we successfully collected clinical information and found the real-world efficacy and safety of pembrolizumab.

15.
Eur J Neurosci ; 33(5): 923-32, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21255126

RESUMEN

Surround suppression is a phenomenon whereby stimulation of the extraclassical receptive field suppressively modulates the visual responses of neurons in the primary visual cortex (V1) (also known as area 17). It is known that surround suppression tunes to spatial frequencies (SFs) that are much lower and broader than the frequencies to which the classical receptive field tunes. In this study, we tested the effects of varying SFs on surround suppression by using a circular sinusoidal grating patch that covered both the classical receptive field and the extraclassical receptive field. Using area-summation tuning curves, we found high-SF-tuned surround suppression in the cat V1. This high-SF-tuned surround suppression causes the SF tuning to shift to low SF for large stimuli. By simulating a model neuron lacking a suppressive surround mechanism, we confirmed that these preferred SF shifts do not occur in the absence of surround suppression. We surmise that the high-SF-tuned suppression, which shifts the preferred SF according to size, functionally contributes to the scale-invariant processing of visual images in V1.


Asunto(s)
Inhibición Neural/fisiología , Estimulación Luminosa/métodos , Corteza Visual/fisiología , Vías Visuales/fisiología , Animales , Gatos , Neuronas/citología , Neuronas/fisiología , Corteza Visual/citología , Campos Visuales , Vías Visuales/citología
16.
Vision Res ; 185: 68-76, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33945908

RESUMEN

Theoretical studies suggest that several mechanisms underlie human visual aesthetic experiences: perceptual processing, which has small variability among individuals (shared properties) and strong correlation with image statistics (e.g. color statistics); cognitive processing, which is idiosyncratic and has weak correlation with image statistics; and emotional processing, which determines the affective part of the aesthetic experience. Furthermore, several experimental studies have reported that the visual aesthetic experience can be largely explained by only a few latent factors. However, it is unclear whether the idiosyncrasy and sensitivity to the image statistics of the latent factors from empirical studies are consistent with the multi-stage processing hypothesis from theoretical studies. In the present study, using exploratory factor analysis, we derived three latent factors of visual aesthetic experiences from participants observing landscape paintings and photographs. Then we examined the difference in the idiosyncrasy of the factors and the relationship between the factors and color statistics. We found that there were significant correlations among the color statistics and Factors 1 and 3, which had a small variance of factor scores (low idiosyncrasy), and no or weak correlation among the color statistics and Factor 2, which had a large variance of factor scores (high idiosyncrasy). Our results provide experimental evidence for the perceptual and cognitive processing of visual aesthetic experiences.


Asunto(s)
Emociones , Pinturas , Cognición , Estética , Humanos
17.
Transl Lung Cancer Res ; 10(9): 3745-3758, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34733625

RESUMEN

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is generally performed for the diagnosis of hilar/mediastinal lymph node metastasis in patients with lung cancer. Recently, a 25-gauge (G) needle became available, but robust evidence of its usefulness in routine clinical practice is still lacking. METHODS: A prospective randomized crossover trial was performed, in which patients with suspected hilar/mediastinal lymph node metastasis of lung cancer underwent EBUS-TBNA. The primary endpoint was the rate of yield histology specimens containing malignant cells. RESULTS: From December 2018 to February 2020, 102 patients were randomly assigned to EBUS-TBNA using a 22G needle first, followed by a 25G needle (n=50) or EBUS-TBNA using a 25G needle first, followed by a 22G needle (n=52). There was no difference in the diagnostic yield of malignancy between the histology specimens obtained by using the 22G and 25G needles (75% vs. 75%, respectively, P=0.37). The sizes of the tissue samples (16.4 vs. 4.9 mm2, respectively) and number of malignant cells in the tissue samples (626 vs. 400, respectively) were both significantly higher when using the 22G needle than when using the 25G needle. CONCLUSIONS: No significant difference in the diagnostic yield between the 22G and 25G needles was observed for the diagnosis of lymph node metastasis of lung cancer, suggesting that needles of either gauge could be used for the biopsy. However, we would recommend use of the 22G needle, because it provided larger specimens and specimens containing larger numbers of malignant cells. TRIAL REGISTRATION: University hospital Medical Information Network Clinical Trial Registry (ID: UMIN000036680).

18.
Cereb Cortex ; 19(8): 1915-28, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19056862

RESUMEN

To study the molecular mechanism how cortical areas are specialized in adult primates, we searched for area-specific genes in macaque monkeys and found striking enrichment of serotonin (5-hydroxytryptamine, 5-HT) 1B receptor mRNA, and to a lesser extent, of 5-HT2A receptor mRNA, in the primary visual area (V1). In situ hybridization analyses revealed that both mRNA species were highly concentrated in the geniculorecipient layers IVA and IVC, where they were coexpressed in the same neurons. Monocular inactivation by tetrodotoxin injection resulted in a strong and rapid (<3 h) downregulation of these mRNAs, suggesting the retinal activity dependency of their expression. Consistent with the high expression level in V1, clear modulatory effects of 5-HT1B and 5-HT2A receptor agonists on the responses of V1 neurons were observed in in vivo electrophysiological experiments. The modulatory effect of the 5-HT1B agonist was dependent on the firing rate of the recorded neurons: The effect tended to be facilitative for neurons with a high firing rate, and suppressive for those with a low firing rate. The 5-HT2A agonist showed opposite effects. These results suggest that this serotonergic system controls the visual response in V1 for optimization of information processing toward the incoming visual inputs.


Asunto(s)
Neuronas/fisiología , Receptor de Serotonina 5-HT1B/metabolismo , Receptor de Serotonina 5-HT2A/metabolismo , Corteza Visual/metabolismo , Potenciales de Acción/efectos de los fármacos , Animales , Chlorocebus aethiops , Electrofisiología , Expresión Génica , Hibridación in Situ , Macaca , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Estimulación Luminosa , Receptor de Serotonina 5-HT1B/fisiología , Receptor de Serotonina 5-HT2A/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Agonistas de Receptores de Serotonina/metabolismo , Agonistas de Receptores de Serotonina/farmacología , Corteza Visual/efectos de los fármacos , Corteza Visual/fisiología
19.
Auris Nasus Larynx ; 47(6): 990-995, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32536502

RESUMEN

OBJECTIVE: Infected mucocele of the paranasal sinuses can induce orbital infection, including orbital subperiosteal abscess, which may lead to life-threatening intracranial complications. Effective diagnosis is important, and treatment should be aggressive. This paper presents our experiences in endoscopic surgical management of orbital complications secondary to infected paranasal sinus mucoceles. METHODS: From our retrospective review of the medical charts for 82 patients with 92 sides diagnosed with paranasal sinus mucoceles, we present 7 sides in 7 adult patients with orbital complications secondary to infected mucoceles. The collected data include the suggested etiology, side of sinus involvement, localization of abscess in the orbit, orbital wall bone defects caused by mucocele compression, ophthalmic symptoms, duration between symptom onset and initial visit, operation date, type of surgery performed, and follow-up. RESULTS: The mucocele was located in the ethmoid-frontal region in 9.8% of the sides (9/92), in the frontal sinus in 7.6% (7/92), in the ethmoidal sinus in 9.8% (9/92), in the maxillary sinus in 67.4% (62/92), in the maxillary-ethmoidal sinus in 3.3% (3/92), and in the sphenoid sinus in 2.2% (2/92). The patients with ethmoid-frontal mucoceles had a significantly higher incidence of orbital complications (6/9) as compared with the other sub-types of mucoceles (frontal, 0/7; ethmoidal, 0/9; maxillary, 1/62; maxillary-ethmoidal, 0/3; sphenoid, 0/2). Chandler's classification showed Type I in one, Type II in three, and Type III in three. Sinus involvement was observed at the ethmoid-frontal sinuses in six cases and the maxillary sinus in one case. All seven cases had a partial defect of the orbital wall bone (lamina papyracea, or inferior orbital wall bone) by mucocele compression, and the patients underwent endoscopic marsupialization. For the cases with subperiosteal abscess, the lamina papyracea was also removed partially for draining the abscess. In all cases, symptoms were resolved without any recurrence of the mucocele. CONCLUSIONS: Infected ethmoid-frontal mucoceles with a defect of the lamina papyracea tend to induce orbital infection, so prompt surgery for the infected mucoceles should be considered early even with Types I and II, before visual acuity is impaired, because surgery is the only curative treatment for the mucoceles.


Asunto(s)
Mucocele/complicaciones , Enfermedades Orbitales/etiología , Enfermedades de los Senos Paranasales/complicaciones , Absceso/diagnóstico por imagen , Absceso/etiología , Anciano , Anciano de 80 o más Años , Drenaje , Edema/diagnóstico por imagen , Edema/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mucocele/diagnóstico por imagen , Mucocele/cirugía , Celulitis Orbitaria/diagnóstico por imagen , Celulitis Orbitaria/etiología , Celulitis Orbitaria/cirugía , Enfermedades Orbitales/diagnóstico por imagen , Enfermedades Orbitales/cirugía , Enfermedades de los Senos Paranasales/diagnóstico por imagen , Enfermedades de los Senos Paranasales/cirugía , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
20.
SAGE Open Med Case Rep ; 8: 2050313X20915415, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32284867

RESUMEN

Perforation of the larynx is very rare but may result in severe airway complications that include pneumothorax, pneumonia, mediastinitis, and retropharyngeal abscess. If conservative treatment fails, aggressive treatments including reconstructive surgery with pedicle flap are considered. Negative pressure wound therapy has been used for large skin defects, necrotizing fasciitis, pharyngocutaneous fistula, stoma dehiscence, osteoradionecrosis of the mandible, chyle fistula, flap failure, and lymphangioma in the field of head and neck surgery. We report a case of false vocal cord perforation with abscess successfully treated by negative pressure wound therapy after abscess treatment. The result suggests that negative pressure wound therapy can be an alternative or adjunctive approach for larynx perforation when the perforation is difficult to close after conservative therapy.

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