RESUMO
The Practical Guideline for the Management of Allergic Rhinitis, the fist guideline for allergic rhinitis in Japan, was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 9th edition was published in 2020 and is widely used today. The most recent collection of evidence from the literature was supplemented to the revised guideline to incorporate evidence-based medicine. The revised guideline includes updated epidemiology of allergic rhinitis in Japan, a figure representing the mechanisms of allergic rhinitis in both the onset and sensitization phases with the introduction of regulatory T cells and type 2 innate lymphoid cells, practical assessment for diagnosis, new pharmacotherapy agents such as anti-IgE mAb and a new drug delivery system for antihistamines, sublingual immunotherapy for children, dual sublingual immunotherapy for house dust mites and Japanese cedar pollen extract, new classification for surgery for allergic rhinitis, and treatment and prescriptions for older adults. An evidence-based step-by-step strategy for treatment is also described.
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Imunidade Inata , Rinite Alérgica , Criança , Animais , Humanos , Idoso , Linfócitos , Rinite Alérgica/diagnóstico , Rinite Alérgica/epidemiologia , Rinite Alérgica/terapia , Alérgenos , PyroglyphidaeRESUMO
BACKGROUND: Sublingual immunotherapy (SLIT) often has low adherence rates. OBJECTIVE: To provide effective support for SLIT continuation, we investigated potential predictors of SLIT adherence through a prospective analysis of patient characteristics. We excluded evaluation of treatment effect and symptoms during treatment, aiming instead to identify predictors of later dropout or insufficient adherence due to indolence or forgetfulness using only information obtained at initial examination. METHODS: We provided patients with a questionnaire and monitored self-reported adherence once every 6 months. Cases of dropout for clear reasons were excluded, but cases of dropout or insufficient adherence to SLIT for indolence or forgetfulness were included. RESULTS: Fifty-three patients receiving SLIT were assessed. Nine patients dropped out after providing a clear reason. Thirty-four patients maintained good adherence. Seven patients continued SLIT but with insufficient adherence, while three patients discontinued SLIT for unclear reasons (indolence or forgetfulness) and these ten individuals were classified as the poor-adherence group. Univariate analysis and multivariate logistic regression analysis of the good-adherence and poor-adherence groups showed age to be a significant predictor of SLIT adherence. Based on analysis of a receiver operating characteristic curve, age < 40.5 years was selected as the optimal cutoff value for predicting poor adherence to SLIT. CONCLUSIONS: To prevent treatment SLIT discontinuation on account of indolence or forgetfulness, the necessity of longterm treatment continuity should be communicated clearly prior to commencing treatment, especially for patients under 40 years of age.
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Cryptomeria , Rinite Alérgica Sazonal , Imunoterapia Sublingual , Adulto , Alérgenos , Humanos , Projetos de Pesquisa , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/terapia , AutorrelatoRESUMO
Direct-acting antiviral (DAA) treatment can achieve a high sustained virological response (SVR) rate in patients with hepatitis C virus (HCV) infection regardless of a history of hepatocellular carcinoma (HCC [+]). We examined 838 patients (370 men, median age: 69 years) who were treated with DAAs for comparisons of clinical findings between 79 HCC (+) (9.4%) and 759 HCC (-) (90.6%) patients and associations with treatment outcome. Male frequency was significantly higher in the HCC (+) group (60.8% vs 42.4%, P = 0.006). There were significant differences between the HCC (+) and HCC (-) groups for platelet count (115 vs 152 ×109 /L, P < 0.001), baseline alpha fetoprotein (AFP) (9.9 vs 4.5 ng/mL, P < 0.001) and the established fibrosis markers of FIB-4 index (4.7 vs 3.0, P < 0.001), AST-to-platelet ratio index (APRI) (1.1 vs 0.7, P = 0.009), M2BPGi (3.80 vs 1.78 COI, P < 0.001) and autotaxin (1.91 vs 1.50 mg/L, P < 0.001). The overall SVR rate was 94.7% and significantly lower in the HCC (+) group (87.3 vs 95.5%, P = 0.001). Multivariate analysis revealed that a history of HCC was independently associated with DAA treatment failure (odds ratio: 3.56, 95% confidence interval: 1.32-9.57, P = 0.01). In conclusion, patients with chronic HCV infection and prior HCC tended to exhibit more advanced disease progression at DAA commencement. HCC (+) status at the initiation of DAAs was significantly associated with adverse therapeutic outcomes. DAA treatment for HCV should therefore be started as early as possible, especially before complicating HCC.
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Antivirais/uso terapêutico , Carcinoma Hepatocelular/diagnóstico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Química do Sangue , Carcinoma Hepatocelular/patologia , Feminino , Hepatite C Crônica/patologia , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento , Adulto JovemRESUMO
Japanese cedar pollen (JCP) and house dust mite (HDM) are two major allergens that cause allergic rhinitis (AR) in Japan and the prevalence of AR is increasing. Pharmacothearpy is a commonly used treatment, but the level of patient satisfaction is very low. Allergen immunotherapy (AIT) is the only therapeutic modality that provides not only symptom relief but also quality of life improvement that leads to a high rate of satisfaction. In particular, sublingual immunotherapy (SLIT) is a safe and effective treatment for AR. Here we introduce a large-scale double-blind, placebo-controlled trial of SLIT in Japanese patients using JCP droplets or HDM tablets conducted in Japan. The immediate future of SLIT in Japan is also discussed.
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Alérgenos/administração & dosagem , Hipersensibilidade/terapia , Imunoterapia Sublingual/métodos , Humanos , JapãoRESUMO
BACKGROUND: We considered the factors of poor adherence to and dropout from sublingual immunotherapy (SLIT) by verifying patient backgrounds 1 year after start of treatment. METHODS: We recruited 38 patients who began SLIT between November 2014 and September 2015. We analyzed their attributes and level of understanding of the treatment, and conducted a self-reported survey on factors behind dropout cases and poor adherence cases. RESULTS: Four patients dropped out 1 year after start of treatment. Three left for reasons related to anxiety about side effects. There were five cases of poor adherence. There was no significant difference between good adherence, poor adherence, and dropout regarding level of understanding of the treatment (p=0.59). In the comparison between good and poor adherence groups, except four dropout patients, the adherence tended to be poor in patients with short duration of disease, smoking patients, and young patients. Continuous rate of SLIT achieved about 90%, suggesting relatively high level of adherence. CONCLUSION: It appears possible that anxiety related to side effects could be a factor affecting dropout from SLIT. There was no significant difference regarding level of understanding of the treatment. The adherence tended to be poor in patients with short duration of disease, smoking patients, and young patients.
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Cryptomeria/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/terapia , Imunoterapia Sublingual , Administração Sublingual , Adulto , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Rinite Alérgica Sazonal/imunologia , Imunoterapia Sublingual/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
Nasal obstruction is a known risk factor associated with obstructive sleep apnea (OSA). Multiple methods of measuring nasal abnormalities including anterior and posterior rhinomanometry and acoustic rhinometry (AR) have been used to better quantify the relationship. These measurements are usually used in the sitting and awakening situation, which differ from the situations in the supine position and while asleep. The goal of this study was to evaluate the nasal patency in patients under general anesthesia approximating sleep as assessed with AR. The nasal minimal cross-sectional area (MCSA) and nasal volume in 50 patients who underwent general anesthesia were compared with subjects in the sitting, supine, and supine position under general anesthesia using AR to measure the nasal dimensions and patency. MCSA and nasal volume decreased more significantly in the supine than in the sitting subjects and these decrements were shown more in the supine position under general anesthesia than in the supine position without anesthesia. Furthermore, regarding nasal volume, the difference between in the sitting and in the supine was larger than the difference between in the supine position with and without general anesthesia. These results suggested that the decrements regarding nasal volume under positional change were greater than those under conditional change. The positional variation can affect the airway patency hydrodynamically and these alterations indicate the relationship of the pathophysiology in patients with OSA.
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Obstrução Nasal/fisiopatologia , Postura , Sono , Adulto , Idoso , Anestesia Geral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rinometria Acústica , Adulto JovemRESUMO
BACKGROUND: Chronic rhinosinusitis (CRS), which is clinically classified into CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP), shows considerable geographic differences and heterogeneity. Eosinophilic (E) CRS with nasal polyps (ECRSwNP) has a higher degree of disease severity and higher frequency of comorbid asthma. Epidemiologic studies in different ethnic populations have improved understanding of the pathophysiology of the disease. Here we report the clinical characteristics of Japanese patients with medically refractory CRS undergoing endoscopic sinus surgery (ESS). METHODS: We recruited a total of 210 CRS patients and assessed them by nasal endoscopy, the Lund-Mackay score using computed tomography (CT), peripheral eosinophilia and smoking status. We also examined the comorbidity of asthma, effects of age and lung functions in the patients. RESULTS: In this study, 13% of CRSwNP patients and 20% of CRSwNP patients with peripheral blood eosinophilia exhibited obstructive lung dysfunction (FEV1/FVC <70%) despite the absence of an asthma diagnosis. Among elderly nonsmoker patients (≥ 60 years) who had never been diagnosed with asthma, 50% of CRSwNP patients with peripheral blood eosinophilia showed decreased FEV1/FVC <70%. CONCLUSIONS: Our findings suggest that asthma is under-diagnosed in CRS patients who undergo ESS, especially the elderly. Although the association between CRS and asthma has been recognized, increased attention to the comorbidity of obstructive airway diseases such as asthma is still needed for management of medically refractory CRS.
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Endoscopia , Testes de Função Respiratória , Rinite/diagnóstico , Rinite/cirurgia , Sinusite/diagnóstico , Sinusite/cirurgia , Adulto , Doença Crônica , Comorbidade , Endoscopia/métodos , Eosinófilos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Pólipos Nasais/patologia , Pólipos Nasais/cirurgia , Seios Paranasais/patologia , Rinite/patologia , Fatores de Risco , Sinusite/patologia , Tomografia Computadorizada por Raios XRESUMO
We report herein two cases of allergic fungal rhinosinusitis accompanied by bone destruction of the adjacent nasal sinuses. The first case involved a 21-year-old man who presented with left exophthalmos. Computed tomography (CT) showed soft tissue lesions in the left paranasal sinuses and destruction of the left lamina papyraceae, as well as infiltration of the lesion into the orbit. In the second case, a 39-year-old man, CT showed bone destruction of the skull base and medial wall of the left orbit. In both cases, total serum immunoglobulin (Ig)E level was >1000 IU/mL and fungus-specific IgEs were increased. Fungal hyphae were identified within the mucus on histopathological examination in both cases; however, no fungal invasion of the mucosa was apparent. Final diagnosis was allergic fungal rhinosinusitis (AFRS) in both cases. AFRS is a relatively new disease concept that was proposed in the early 1980s, with disease characteristics very similar to eosinophilic rhinosinusitis. Occasionally, AFRS must be differentiated from malignant disease or invasive fungal rhinosinusitis, so an understanding of the clinical features is important.
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Micoses , Seios Paranasais/microbiologia , Seios Paranasais/patologia , Rinite Alérgica Perene/microbiologia , Rinite Alérgica Perene/patologia , Sinusite/microbiologia , Sinusite/patologia , Adulto , Biomarcadores/sangue , Diagnóstico Diferencial , Humanos , Imunoglobulina E/sangue , Imageamento por Ressonância Magnética , Masculino , Órbita/microbiologia , Órbita/patologia , Seios Paranasais/diagnóstico por imagem , Rinite Alérgica , Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Perene/terapia , Sinusite/diagnóstico , Sinusite/terapia , Base do Crânio/microbiologia , Base do Crânio/patologia , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
OBJECTIVE: Primary ciliary dyskinesia (PCD) is a relatively rare genetic disorder that affects approximately 1 in 20,000 people. Approximately 50 genes are currently known to cause PCD. In light of differences in causative genes and the medical system in Japan compared with other countries, a practical guide was needed for the diagnosis and management of Japanese PCD patients. METHODS: An ad hoc academic committee was organized under the Japanese Rhinologic Society to produce a practical guide, with participation by committee members from several academic societies in Japan. The practical guide including diagnostic criteria for PCD was approved by the Japanese Rhinologic Society, Japanese Society of Otolaryngology-Head and Neck Surgery, Japanese Respiratory Society, and Japanese Society of Pediatric Pulmonology. RESULTS: The diagnostic criteria for PCD consist of six clinical features, six laboratory findings, differential diagnosis, and genetic testing. The diagnosis of PCD is categorized as definite, probable, or possible PCD based on a combination of the four items above. Diagnosis of definite PCD requires exclusion of cystic fibrosis and primary immunodeficiency, at least one of the six clinical features, and a positive result for at least one of the following: (1) Class 1 defect on electron microscopy of cilia, (2) pathogenic or likely pathogenic variants in a PCD-related gene, or (3) impairment of ciliary motility that can be repaired by correcting the causative gene variants in iPS cells established from the patient's peripheral blood cells. CONCLUSION: This practical guide provides clinicians with useful information for the diagnosis and management of PCD in Japan.
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Testes Genéticos , Síndrome de Kartagener , Humanos , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/terapia , Síndrome de Kartagener/genética , Diagnóstico Diferencial , Cílios/ultraestrutura , Cílios/patologia , Japão , Dineínas do Axonema/genética , ProteínasRESUMO
INTRODUCTION: Until recently, Vidian neurectomy had been applied mainly in intractable vasomotor rhinitis and severe perennial allergic rhinitis. Although the results were excellent, the operation has not been applied recently because of the adverse events such as xerophthalmia and trigeminal neuralgia. To resolve these problems, a new surgical technique, posterior nasal neurectomy, was developed. In this report, we examined the effectiveness of posterior nasal neurectomy combined with the inferior turbinate surgery for severe perennial allergic rhinitis and intrinsic rhinitis by questionnaire. PATIENTS AND METHODS: Twenty patients who had undergone posterior nasal neurectomy combined with the inferior turbinate surgery between April in 2005 and March in 2009 were enrolled. Numeric Rating Scale was used to evaluate clinical symptoms and quality of life (QOL) of pre- and postsurgery. Frequency of medication (oral administration and nasal spray) was also evaluated. RESULTS: Questionnaires were collected from 17 patients. As for all patients but one, the surgery significantly reduced rhinorrhea, nasal obstruction, and sneezing. Furthermore, QOL for many symptoms such as sleep disorder and malaise/feebleness was also significantly improved after the surgery. Eighty-one percent of patients were satisfied with the surgery. CONCLUSION: Posterior nasal neurectomy combined with the inferior turbinate surgery is effective in alleviating clinical symptoms and improving QOL in the patients with severe perennial allergic rhinitis and intrinsic rhinitis, although a longer follow-up is needed.
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Procedimentos Cirúrgicos Nasais/métodos , Nariz/inervação , Rinite Alérgica Perene/cirurgia , Rinite Vasomotora/cirurgia , Conchas Nasais/cirurgia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Resultado do TratamentoRESUMO
INTRODUCTION: Allergic rhinitis and asthma are often comorbid, and allergic rhinitis has been shown to be a risk factor for asthma in adults and children. Recently, the prevalence of allergic rhinitis among bronchial asthma (BA) patients was reported to be 67.3% in Japan. However, seasonal variation in the prevalence of rhinitis in Japan remains unclear. OBJECTIVES AND METHODS: To investigate the seasonal differences in comorbid allergic rhinitis among asthmatic patients, a survey of BA outpatients aged six years and older was conducted at the Allergy Center, Saitama Medical University. In total, 150 patients (mean age, 43.8±21.8 years old) in summer 2012 and 181 patients (mean age, 48.7±18.3 years old) in spring 2013 completed the Self Assessment of Allergic Rhinitis and Asthma (SACRA) questionnaire. RESULTS: The prevalence of allergic rhinitis in BA patients was 50% in the summer of 2012 and 85.6% in the spring of 2013, indicating a significant seasonal variation. Control of asthma was significantly poorer in both seasons in patients with rhinitis compared to those without rhinitis. Furthermore, in patients with moderate/severe-persistent rhinitis, control of asthma was significantly worse than in patients with mild-intermittent rhinitis in spring 2013, but not in summer 2012. CONCLUSION: Although the comorbidity rate of rhinitis among BA patients was greater in the spring than in the summer, rhinitis is thought to be closely related with asthma control regardless of the season.
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Asma/epidemiologia , Rinite Alérgica Sazonal/epidemiologia , Estações do Ano , Adolescente , Adulto , Fatores Etários , Idoso , Asma/etiologia , Criança , Comorbidade , Progressão da Doença , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Rinite Alérgica Sazonal/complicações , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto JovemRESUMO
INTRODUCTION: Up to 30% of the Japanese population suffers from Japanese cedar pollinosis, and some of these patients also have severe perennial allergies or other pollen allergies. Posterior nasal neurectomy has recently been reported as effective treatment for severe perennial allergic and intrinsic rhinitis. However, the efficacy of this surgery for seasonal allergic rhinitis has not been shown. In this study, the effectiveness of posterior nasal neurectomy combined with inferior turbinate surgery for patients with Japanese cedar pollinosis with concomitant intractable perennial allergies was evaluated with a questionnaire. SUBJECTS AND METHODS: Nine patients with Japanese cedar pollinosis, who also had perennial allergies, and undergone posterior nasal neurectomy combined with inferior turbinate surgery from April in 2005 to July in 2008, were enrolled. A numeric rating scale (NMR) was used to evaluate clinical symptoms in the pre- and post-surgery periods. The frequency of medication (oral administration and nasal spray) during the cedar pollinosis season was also evaluated. RESULTS: The NMR scores for all nasal and eye symptoms during cedar pollinosis season were significantly reduced after the surgery. The frequency of medication during the season was dramatically decreased after surgery. CONCLUSION: The present study demonstrates that posterior nasal neurectomy combined with inferior turbinate surgery is a highly effective treatment for Japanese cedar pollinosis. Since the Japanese cedar pollinosis season is limited to 2 to 3 months, such surgery is indicated for patients who suffer from severe perennial allergies and are also sensitized to some allergens such as Japanese cedar and ragweed pollen.
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Cryptomeria , Procedimentos Cirúrgicos Nasais/métodos , Rinite Alérgica Sazonal/cirurgia , Conchas Nasais/cirurgia , Adolescente , Adulto , Feminino , Humanos , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: The primary objective of this study was to evaluate long-term (24-week) safety of eszopiclone in elderly and nonelderly Japanese patients with chronic insomnia. The secondary objectives were to evaluate short-term (4-week) efficacy and to assess for rebound insomnia or dependence after long-term treatment. METHODS: Patients (n = 164 elderly; n = 161 nonelderly), with or without psychiatric comorbidities, were randomized to receive low-dose (1 mg, elderly; 2 mg, nonelderly) or high-dose (2 mg, elderly; 3 mg, nonelderly) eszopiclone. The safety evaluation included adverse events, vital signs, clinical laboratory parameters, and electrocardiogram. Efficacy was assessed using patient reports of sleep latency (SL), total sleep time (TST), wake time after sleep onset (WASO), number of awakenings (NA), quality of sleep, depth of sleep, daytime sleepiness, daytime ability to function, and the 36-item Short Form (SF-36) Health Survey. RESULTS: The rate of adverse events was 81.5% in the 1-mg elderly group, 79.5% in the 2-mg elderly group, 82.1% in the 2-mg nonelderly group, and 87.0% in the 3-mg nonelderly group. Dysgeusia was the most common adverse event and was dose-related. Of 12 serious adverse events, none were considered by the investigator to be related to study medication. No rebound insomnia was observed. Eszopiclone significantly improved SL, TST, WASO, NA, and daytime sleepiness and function from baseline to Week 4, irrespective of age and psychiatric comorbidity. Improvements were also observed in SF-36 Mental Health Component scores in elderly and nonelderly patients with psychiatric comorbidities. CONCLUSIONS: Irrespective of age, eszopiclone appeared safe as administered in this study for 24 weeks. Eszopiclone improved sleep variables in insomnia patients with and without psychiatric disorders and health-related quality of life in those with psychiatric disorders. TRIAL REGISTRATION: ClinicalTrials.gov #NCT00770692; http://clinicaltrials.gov/ct2/show/NCT00770692.
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BACKGROUND: We sought to clarify the associations among serum cytokines, amino acid substitutions in the interferon sensitivity-determining region (ISDR) and core region, and treatment outcome of pegylated interferon and ribavirin therapy in genotype 1 hepatitis C virus (HCV)-infected patients. METHODS: We quantified a total of 8 serum cytokines before, during, and after treatment in 79 genotype 1 chronic HCV patients. Viral ISDR and core region variants were determined by direct sequencing. RESULTS: High levels of interleukin (IL)-12 and IL-18 and more than 2 mutations in the ISDR were associated with a sustained virological response (SVR). Conversely, high baseline IL-10 levels and glutamine at amino acid 70 of the HCV core protein (Gln70) were significantly associated with a nonresponse to treatment, and patients with Gln70 had significantly higher IL-10 levels. In multivariate analysis, low IL-10, high IL-12, and high IL-18 levels were independently associated with an SVR. These 3 cytokine levels were decreased from baseline levels 4 weeks into treatment and remained low in patients with an SVR. CONCLUSION: Serum IL-10, IL-12, and IL-18 levels are predictive of the response to HCV treatment with pegylated interferon and ribavirin and are associated with amino acid substitutions in the ISDR and core region.
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Antivirais/uso terapêutico , Citocinas/sangue , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Substituição de Aminoácidos , Antivirais/administração & dosagem , Biomarcadores , Antígenos da Hepatite C/sangue , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Proteínas Recombinantes , Ribavirina/administração & dosagem , Sensibilidade e Especificidade , Proteínas do Core Viral/sangueRESUMO
BACKGROUND: Because few studies have epidemiologically evaluated pollen-food allergy syndrome (PFAS), relevant information about this disease is limited in children. OBJECTIVE: We wanted to clarify the epidemiological details of PFAS by creating a questionnaire which enables to distinguish class 2 food allergy from that of class 1. METHODS: We conducted a questionnaire survey for schoolchildren attending to public elementary and junior high schools. In this questionnaire, we asked about both the allergy to fruits and/or vegetables and allergic rhinitis (AR). PFAS was, then, defined as allergy for fruits and/or vegetable which occurred after the symptoms of AR appeared. RESULTS: A total of 2,346 children (median age, 10.6±2.5 years; 1,157 boys) were evaluated. The prevalence of PFAS was 6.9% among subjects. The mean ages in the onset of AR and PFAS were 4.59±2.76 and 7.38±3.17 years old, respectively. Various kinds of foods were shown to be causative, among which kiwifruits were the commonest. As high as approximately 30% of children with PFAS experienced systemic symptoms including cutaneous (21.8%) and respiratory symptoms (9.6%). Anaphylaxis was diagnosed in 5.8% children. CONCLUSION: Our results indicated that the prevalence of PFAS was getting higher and the mean age of onset was getting lower. These may be attributed to the increasing number of patients with AR and also to the lower age of onset of AR. We have to be careful to not only local but also systemic symptoms when examining children with PFAS.
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Granulocyte-colony stimulating factor (G-CSF) is a naturally occurring glycoprotein that stimulates the proliferation and maturation of precursor cells in the bone marrow into fully differentiated neutrophils. Several reports of G-CSF-producing malignant tumors have been published, but scarcely any in the hepatobiliary system, such as in hepatocellular carcinoma (HCC). Here, we encountered a 69-yr-old man with a hepatic tumor who had received right hepatic resection. He showed leukocytosis of 25,450/microL along with elevated serum G-CSF. Histological examination of surgical samples demonstrated immunohistochemical staining for G-CSF, but not for G-CSF receptor. The patient survived without recurrence for four years, but ultimately passed away with multiple bone metastases. In light of the above, clinicians may consider G-CSF-producing HCC when encountering patients with leukocytosis and a hepatic tumor. More cases are needed to clarify the clinical picture of G-CSF-producing HCC.
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Carcinoma Hepatocelular/metabolismo , Fator Estimulador de Colônias de Granulócitos/metabolismo , Neoplasias Hepáticas/metabolismo , Idoso , Neoplasias Ósseas/secundário , Carcinoma Hepatocelular/patologia , Evolução Fatal , Humanos , Neoplasias Hepáticas/patologia , Masculino , Receptores de Fator Estimulador de Colônias de Granulócitos/metabolismoRESUMO
Glecaprevir/pibrentasvir (G/P) are direct-acting antivirals (DAAs) that achieve a high sustained virological response (SVR) rate for hepatitis C virus (HCV) infection. We investigated G/P effectiveness for HCV patients based on real-world experience and the clinical features of retreatment cases. HCV patients (n = 182) were compared for clinical features and outcomes between first treatment (n = 159) and retreatment (n = 23) G/P groups. Overall, 77 patients (42.3%) were male, the median age was 68 years, and 86/66/1/4 cases had genotype 1/2/1+2/3, respectively. An SVR was achieved in 97.8% (178/182) of cases by intention-to-treat analysis and 99.4% (178/179) of cases by per-protocol analysis. There were no remarkable differences between the first treatment and retreatment groups for male (42.8% vs. 39.1%, p = 0.70), median age (68 vs. 68 years, p = 0.36), prior hepatocellular carcinoma (5.8% vs. 8.7%, p = 0.59), or the fibrosis markers AST-to-platelet ratio index (APRI) (0.5 vs. 0.5, p = 0.80) and fibrosis-4 (FIB-4) index (2.2 vs. 2.6, p = 0.59). The retreatment group had a significantly more frequent history of interferon treatment (12.3% vs. 52.2%, p < 0.01) and the Y93H mutation (25.0% vs. 64.7%, p = 0.02). The number of retreatment patients who had experienced 3, 2, and 1 DAA treatment failures was 1, 3, and 19, respectively, all of whom ultimately achieved an SVR by G/P treatment. In conclusion, G/P was effective and safe for both HCV first treatment and retreatment cases despite the retreatment group having specific resistance mutations for other prior DAAs. As G/P treatment failure has been reported for P32 deletions, clinicians should consider resistance mutations during DAA selection.
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We here report the first case of cholangiolocellular carcinoma (CoCC) visualized with contrast-enhanced ultrasonography (CEUS) using a second-generation contrast agent, Sonazoid. A 76-year-old man was admitted to our hospital for evaluation of a hepatic tumor. The tumor was described as having hyper-enhancement in the early phase and persistent enhancement in the late phase by contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), as well as hypervascularity by angiography. CEUS assessment of the nodule showed diffuse and homogeneous enhancement in the pure arterial phase, which became progressively hypoechoic relative to the adjacent liver parenchyma during the portal vein and late phases (mixed vascular phase), and showed a contrast defect with an unclear border in the Kupffer phase. Histologically we diagnosed this hepatic tumor as CoCC. In light of the above findings and the rarity of CoCC, it is helpful to incorporate the results of several imagings, such as CT, MRI, angiography and CEUS with a second-generation contrast agent when clinically diagnosing CoCC.
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Elevated production of cysteinyl leukotrienes (cysLTs) from sinus tissues and abundant sinus eosinophils are characteristic features of chronic hyperplastic eosinophilic sinusitis (CHS). CysLTs exert their action through G-protein-coupled receptors named cysLTs receptor type I (cysLT1R) and type II (cysLT2R). These expressions of cysLT receptors in the sinus mucosa have yet to be clarified and the relationship between eosinophilia and the expression of these receptors remains obscure. We compared the expressions of cysLT1R and cysLT2R in the sinus mucosa in patients with CHS, non-eosinophilic chronic sinusitis (NECS), and control sinus tissues; and analyzed the correlation between the expression of CysLTRs and the presence of sinus eosinophils by immunohistochemistry and real-time PCR. A significantly higher percentage of eosinophils expressing cysLT2R protein was observed in patients with CHS compared with NECS and controls. In addition, cysLT2R mRNA expression in CHS was significantly higher than in NECS and controls. Furthermore, a positive correlation was observed between cysLT2R mRNA expression and the number of infiltrated eosinophils. In contrast, the cysLT1R mRNA expression did not differ significantly among these groups. The effect of cysLTs on sinus eosinophils may be mediated through the cysLT2R in patients with CHS. These results may suggest the therapeutic benefit of cysLT2R antagonists in CHS.
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Adherence to antipsychotic treatment is particularly important in the long-term management of schizophrenia and other related psychotic disorders since poor adherence to medication is associated with poor health outcomes. Although the patients' subjective satisfaction with the medication is crucial for adherence to medication, few studies have examined the relationship between subjective satisfaction with antipsychotics and adherence. In this study, we investigated subjective satisfaction with antipsychotics in patients with schizophrenia by using the Treatment Satisfaction Questionnaire for Medication (TSQM), a self-reporting instrument to assess the major dimensions of patients' satisfaction with their medication. The subjects included 121 clinically stabilized outpatients who met the following criteria: 1) patients between 20 and 65 years of age, diagnosed with schizophrenia or other psychotic disorders as defined by DSM-IV, 2) patients undergoing oral antipsychotic monotherapy or taking only an antiparkinsonian agent as an adjuvant remedy, and 3) patients who had received a stable dose of an antipsychotic for more than four weeks. Patients were asked to answer the TSQM questions, and their clinical symptoms were also evaluated by the Brief Psychiatric Rating Scale (BPRS). Satisfaction with regard to side-effects (p=0.015) and global satisfaction (p=0.035) were significantly higher in patients taking second-generation antipsychotics (SGAs, n=111) than those taking first-generation antipsychotics (FGAs, n=10), whereas no significant difference was found between the two groups in clinical symptoms according to BPRS (p=0.637) or the Drug-induced Extrapyramidal Symptoms Scale (DIEPSS, p=0.209). In addition, correlations were not significant between the subjective satisfactions and clinician-rated objective measures of the symptoms. These findings suggest that SGAs have more favorable subjective satisfaction profiles than FGAs in the treatment of schizophrenia. Since it is often difficult to detect the difference by a traditional objective assessment of the patients, it is desirable that physicians pay attention to the patients' subjective satisfaction in conjunction with their own objective clinical assessment.