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BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact, with millions of confirmed cases and deaths worldwide. While most cases are mild, a subset progresses to severe respiratory complications and death, with factors such as thromboembolism, age, and underlying health conditions increasing the risk. Vascular endothelial damage has been implicated in severe outcomes, but specific biomarkers remain elusive. This study investigated syndecan-1 (SDC-1), a marker of endothelial damage, as a potential prognostic factor for COVID-19, focusing on the Japanese population, which is known for its aging demographics and high prevalence of comorbidities. METHODS: A multicenter retrospective study of COVID-19 patients in Fukushima Prefecture in Japan who were admitted between February 2020 and August 2021 was conducted. SDC-1 levels were measured along with other clinical and laboratory parameters. Outcomes including thrombosis, 28-day survival, and disease severity were assessed, and disease severity was categorized according to established guidelines. RESULTS: SDC-1 levels were correlated with disease severity. Patients who died from COVID-19 had greater SDC-1 levels than survivors, and the area under the receiver operating characteristic curve (AUC) analysis suggested the potential of the SDC-1 level as a predictor of mortality (AUC 0.714). KâM analysis also revealed a significant difference in survival based on an SDC-1 cutoff of 10.65 ng/mL. DISCUSSION: This study suggested that SDC-1 may serve as a valuable biomarker for assessing COVID-19 severity and predicting mortality within 28 days of hospitalization, particularly in the Japanese population. However, further investigations are required to assess longitudinal changes in SDC-1 levels, validate its predictive value for long-term survival, and consider its applicability to new viral variants. CONCLUSIONS: SDC-1 is emerging as a potential biomarker for assessing the severity and life expectancy of COVID-19 in the Japanese population, offering promise for improved risk stratification and patient management in the ongoing fight against the virus.
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BACKGROUND: Although respiratory tract infection is a significant factor that triggers exacerbation of chronic obstructive pulmonary disease (COPD), the benefit of antibiotics for patients with COPD exacerbation remains controversial. It is necessary to evaluate the efficacy and safety of antibiotics versus placebo in such patients. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials of antibiotics versus placebo for the treatment of COPD exacerbation, and compared the frequencies of treatment failure, mortality, and adverse events between patients treated with antibiotics and those treated with placebo. RESULTS: A total of six studies were included in this meta-analysis. The frequency of treatment failure was significantly lower in the antibiotic-treated patients compared to the placebo-treated patients (odds ratios [OR] 0.50, 95% confidence intervals [CI] 0.35-0.71, p = 0.0001). There was no significant difference between the two groups in mortality (OR 0.44, 95% CI 0.05-3.76, p = 0.45) or frequency of adverse events (OR 1.05, 95% CI 0.75-1.48, p = 0.78). CONCLUSION: In the current systematic review and meta-analysis, we found that antibiotics were superior to placebo in patients with exacerbated COPD, as shown by the lower treatment failure rate.
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Antibacterianos , Progressão da Doença , Doença Pulmonar Obstrutiva Crônica , Humanos , Antibacterianos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Respiratórias/tratamento farmacológico , Falha de TratamentoRESUMO
Purpose: The prevalence of airflow obstruction in Japan is 3.8%-16.9%. This epidemiological study based on a large database aimed to reassess the prevalence of airflow obstruction in Japan and the diagnosis rate of chronic obstructive pulmonary disease (COPD). Patients and Methods: We used data regarding claims from the health insurance union and health checkups provided by JMDC. The present study included a subgroup of individuals aged ≥40 years who underwent health checkups involving spirometry between January and December 2019. The study endpoints were the prevalence of airflow obstruction, COPD diagnosis rate, disease stage, and respiratory function test results. Results: Among 102,190 participants, 4113 (4.0%) had airflow obstruction. The prevalence of airflow obstruction was 5.3% in men and 2.1% in women. Among the study population, 6.8% were current smokers, while 3.4% were never or former smokers. Additionally, the prevalence of COPD increased with age. Approximately 8.4% of participants with airflow obstruction were diagnosed with COPD. Regarding the COPD diagnosis status, participants with airflow obstruction who were diagnosed with COPD were at a more advanced stage than those not diagnosed. Finally, patients diagnosed with COPD had significantly lower FEV1/FVC and FEV1 (p < 0.0001; Wilcoxon rank sum test). Conclusion: The epidemiological study based on a large database determined the COPD diagnosis rate related to airflow obstruction. The COPD diagnosis rate was extremely low among individuals who underwent health checkups, indicating the need for increased awareness about this medical condition. Moreover, primary care physicians should identify patients with suspected COPD and collaborate with pulmonologists to facilitate the early detection of COPD and enhance the COPD diagnosis rate.
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Doença Pulmonar Obstrutiva Crônica , Espirometria , Humanos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Masculino , Feminino , Japão/epidemiologia , Pessoa de Meia-Idade , Prevalência , Idoso , Adulto , Volume Expiratório Forçado , Bases de Dados Factuais , Pulmão/fisiopatologia , Capacidade Vital , Fumar/epidemiologia , Fumar/efeitos adversos , Valor Preditivo dos Testes , Índice de Gravidade de DoençaRESUMO
DOATS score and DOAT score, COVID-19 progression prediction tools we have developed, utilize clinical information such as presence of diabetes/obesity (DO), age (A), body temperature (T), and oxygen saturation (S). They showed good predictive power, but their scoring calculation was slightly complex, leading us to develop simplified versions. This report discusses the ability of the simplified versions to assess deterioration risk in unvaccinated, mild/moderate COVID-19 patients aged <65 years. Logistic regression analysis identified independent risk factors for deterioration, to which points were assigned in order to derive overall prediction scores. The simplified versions showed high discriminating power, with the areas under the receiver operating characteristic curve for DOATS and DOAT being 0.79 and 0.77, respectively, indicating their clinical utility. Although the original versions have a slightly higher predictive power, the new versions are easier to use in emergency situations; thus, importantly, selecting the appropriate version depends on the situation.
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COVID-19 , Progressão da Doença , Humanos , COVID-19/diagnóstico , Pessoa de Meia-Idade , Masculino , Fatores Etários , Feminino , Índice de Gravidade de Doença , Fatores de Risco , Adulto , Obesidade/complicações , Modelos Logísticos , Temperatura Corporal , Curva ROC , Valor Preditivo dos Testes , Medição de Risco/métodos , Diabetes Mellitus/epidemiologiaRESUMO
Background: A previous longitudinal study of chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) score changes suggested patients fall into 3 patterns: stable, improving, and worsening. This study assessed the evolution of CAT scores over time and its relationship to exacerbations. Methods: In total, 84 participants used a telemedicine platform to complete CAT weekly for 52 weeks. Completion rates, annualized change in CAT scores, and learning effects were measured, as well as CAT changes of >4 units during look-back periods of 4 and 8 weeks. In a subgroup of participants with at least a 25% completion rate (adherent group, n=68 [81%]), the relationship between change in CAT score and exacerbations at any time during the study was examined post hoc. Results: Linear regression showed that 50%, 22%, and 28% of the adherent subgroup had CAT scores indicating worsening, stable, and improving health status, respectively. In the adherent subgroup, 70% (n=7/10) of participants who had an exacerbation during the study had worsening CAT scores, versus 47% (n=27/58) without an exacerbation. The hazard ratio association between CAT score increase and moderate exacerbation was 1.13 (95% confidence interval: 1.03-1.24). Most participants experienced at least one CAT score change of >4 units, and 7% showed an initial learning effect with a median of 2 weeks. Conclusion: Measuring trends in CAT scores may allow future studies to group patients into 3 defined categories of change over time and quantify CAT change trajectories to assess treatment response and potentially predict medium-term outcomes within individual patients.
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Forced vital capacity has been utilized as a parameter of disease progression in idiopathic pulmonary fibrosis (IPF); however, its measurement is difficult when patients do not understand or cooperate. Dynamic digital radiography (DDR) enables sequential chest X-ray imaging during breathing, with lower radiation doses compared to conventional fluoroscopy or computed tomography. There is accumulating evidence showing that parameters obtained from DDR, particularly those related to diaphragmatic dynamics, are correlated with pulmonary function parameters, and are useful for pathophysiological evaluation. We herein present two cases that suggest parameters obtained from DDR during supine normal tidal breathing may predict disease progression of IPF.
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Objective Pulmonary function tests are essential for diagnosing respiratory diseases, such as chronic obstructive pulmonary disease (COPD), but are typically not performed in Japan during annual health checkups, which hinders the early diagnosis of respiratory diseases. Methods Individuals who agreed to participate in the Yamagata-Takahata study during medical checkups in Takahata (Yamagata Prefecture, Japan) in 2011 were examined. We interviewed 669 participants (49.0% men; mean age, 67.7 years old) regarding their respiratory symptoms and smoking habits and performed pulmonary function tests during the study. Results Based on pulmonary function test results, 141 participants had pulmonary dysfunction, and 115 had obstructive pulmonary dysfunction. The risk of respiratory dysfunction, particularly obstructive respiratory dysfunction, was examined by referring to a questionnaire tool for an early COPD diagnosis. The associations between age, the smoking history, respiratory symptoms, and obstructive respiratory dysfunction were evaluated. Obstructive respiratory dysfunction was found in 17.6% of participants ≥50 years old and 19.5% ≥60 years old, 30.3% had a smoking history, and 32.8% had respiratory symptoms. Furthermore, the participants with multiple factors had a higher probability of obstructive respiratory dysfunction. Conclusion Subjects with obstructive pulmonary dysfunction are expected to be efficiently identified by extracting individuals by age and smoking habit and through a respiratory symptom questionnaire, although pulmonary function tests cannot be performed for all individuals during health checkups.
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Doença Pulmonar Obstrutiva Crônica , Fumar , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Japão/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Testes de Função Respiratória/métodos , Fumar/efeitos adversos , Fumar/epidemiologia , População do Leste AsiáticoRESUMO
Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction on spirometry and symptoms such as dyspnea on exertion and chronic cough with sputum production, thus making it a significant healthcare issue worldwide. Japanese patients with COPD have unique characteristics compared to patients in Western countries, including older age and lower exacerbation frequency. The Japanese Respiratory Society (JRS) published the 6th edition of the COPD guideline in June 2022. This article introduces the management goals of COPD and describes its management during the stable phase, as outlined in the guideline. Management goals include improving the current status, such as the symptoms, quality of life (QOL), exercise tolerance, and physical activity, and reducing future risks through prevention of exacerbation and suppression of disease progression to prevent shortening of healthy life expectancy. Management plans should include avoidance of causative substances, assessment of disease severity, and personalized treatment plans. Pharmacotherapy using inhalation bronchodilators is a key component of the treatment of stable COPD. Bronchodilators, including short- and long-acting dilators, are commonly used to relieve symptoms and improve QOL. Inhaled corticosteroids (ICSs) are used in combination with long-acting bronchodilators, especially in patients with asthma and COPD overlap, or those experiencing frequent exacerbation of eosinophilia. Combination therapy with a long-acting muscarinic antagonist (LAMA), a long-acting beta 2 agonist (LABA), and ICS is expected to improve QOL and respiratory function and reduce mortality and exacerbation compared to the LAMA + LABA combination. Non-pharmacological therapies, including smoking cessation and pulmonary rehabilitation, should also be considered.
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Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Humanos , Administração por Inalação , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2 , Broncodilatadores/uso terapêutico , Quimioterapia Combinada , População do Leste Asiático , Objetivos , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapiaRESUMO
Background: Neurturin (NRTN) is a neurotrophic factor that was originally identified in the development and maintenance of neural cells. Recent studies involving NRTN knockout mice have reported its anti-inflammatory effects in allergic airway conditions. However, the role of NRTN in human asthma has not yet been identified. Objective: The purposes of the present study were to confirm the presence of NRTN in the airways and to investigate the clinical and pathogenetic roles of NRTN in asthma. Methods: The NRTN levels in the induced sputum were measured by enzyme-linked immunosorbent assay (ELISA). Relationships between NRTN and clinical characteristics, asthma control status, and airway inflammation were assessed. Results: Sixty-four asthmatic subjects were enrolled in the study. All asthmatic subjects had detectable sputum NRTN levels, with a mean (SD) level of 2.03 (1.29) ng/mL. The sputum NRTN levels had significant positive correlations with sputum eosinophil and exhaled nitric oxide levels and were significantly higher in the atopic subjects than in the non-atopic subjects. No significant difference in sputum NRTN levels were observed for asthma control status and asthma exacerbation. In sputum inflammatory analyses, sputum NRTN level was positively correlated with interleukin (IL)-5 and IL-13 levels, and negatively correlated with matrix metalloproteinase (MMP)-9 level. Conclusion: It is plausible that sputum NRTN could serve as a new marker for Type 2 airway inflammation, implicating its role in the process of airway remodeling in asthma. Future studies should investigate the clinical relevance of sputum NRTN level in prospective analyses.
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Organelles are shaped by curvature-generating proteins, which include the reticulons and REEPs that are involved in forming the endoplasmic reticulum (ER). A conserved REEP subfamily differs from the ER-shaping REEPs in abundance and membrane topology and has unidentified functions. Here, we show that Rop1, the single member of this family in the fission yeast Schizosacharomyces pombe, is crucial for the macroautophagy of organelles and cytosolic proteins. Rop1 is needed for the formation of phagophores, cup-like structures consisting of two closely apposed membrane sheets that encapsulate cargo. It is recruited at early stages to phagophores and is required for their maturation into autophagosomes. Rop1 function relies on its ability to generate high membrane curvature and on its colocalization with the autophagy component Atg2 that is thought to reside at the phagophore rim. We propose that Rop1 facilitates the formation and growth of the double-membrane structure of the autophagosome.
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Proteínas de Membrana , Schizosaccharomyces , Proteínas de Membrana/metabolismo , Autofagossomos/metabolismo , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Macroautofagia , Autofagia , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismoRESUMO
BACKGROUND: During the fifth wave of the coronavirus disease 2019 (COVID-19) pandemic in Japan, which took place between June and September 2021, a significant number of COVID-19 cases with deterioration occurred in unvaccinated individuals < 65 years old. However, the risk factors for COVID-19 deterioration in this specific population have not yet been determined. This study developed a prediction method to identify COVID-19 patients < 65 years old who are at a high risk of deterioration. METHODS: This retrospective study analyzed data from 1,675 patients < 65 years old who were admitted to acute care institutions in Fukushima with mild-to-moderate-1 COVID-19 based on the Japanese disease severity criteria prior to the fifth wave. For validation, 324 similar patients were enrolled from 3 hospitals in Yamagata. Logistic regression analyses using cluster-robust variance estimation were used to determine predictors of disease deterioration, followed by creation of risk prediction scores. Disease deterioration was defined as the initiation of medication for COVID-19, oxygen inhalation, or mechanical ventilation starting one day or later after admission. RESULTS: The patients whose condition deteriorated (8.6%) tended to be older, male, have histories of smoking, and have high body temperatures, low oxygen saturation values, and comorbidities, such as diabetes/obesity and hypertension. Stepwise variable selection using logistic regression to predict COVID-19 deterioration retained comorbidities of diabetes/obesity (DO), age (A), body temperature (T), and oxygen saturation (S). Two predictive scores were created based on the optimism-corrected regression coefficients: the DOATS score, including all of the above risk factors, and the DOAT score, which was the DOATS score without oxygen saturation. In the original cohort, the areas under the receiver operating characteristic curve (AUROCs) of the DOATS and DOAT scores were 0.81 (95% confidence interval [CI] 0.77-0.85) and 0.80 (95% CI 0.76-0.84), respectively. In the validation cohort, the AUROCs for each score were both 0.76 (95% CI 0.69-0.83), and the calibration slopes were both 0.80. A decision curve analysis confirmed the clinical practicability of both scores in the validation cohort. CONCLUSIONS: We established two prediction scores that can quickly evaluate the risk of COVID-19 deterioration in mild/moderate patients < 65 years old.
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COVID-19 , Diabetes Mellitus , Humanos , Masculino , Idoso , COVID-19/epidemiologia , Estudos Retrospectivos , Progressão da Doença , Diabetes Mellitus/epidemiologia , Obesidade/epidemiologiaAssuntos
Febre Familiar do Mediterrâneo , Serosite , Humanos , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre Familiar do Mediterrâneo/diagnóstico , Colchicina/uso terapêutico , Serosite/tratamento farmacológico , Diagnóstico DiferencialRESUMO
Secretoglobin (SCGB) 3A2 is a bioactive molecule exhibiting various functions such as improving allergic airway inflammation and pulmonary fibrosis and promoting bronchial branching and proliferation during lung development. To determine if and how SCGB3A2 is involved in chronic obstructive pulmonary disease (COPD), a multifactorial disease with both airway and emphysematous lesions, a COPD mouse model was created by exposing Scgb3a2-deficient (KO), Scgb3a2-lung-specific overexpressing (TG), and wild type (WT) mice to cigarette smoke (CS) for 6 months. The KO mice showed loss of lung structure under control condition, and CS exposure resulted in more expansion of airspace and destruction of alveolar wall than WT mouse lungs. In contrast, TG mouse lungs showed no significant changes after CS exposure. SCGB3A2 increased the expression and phosphorylation of signal transducers and activators of transcription (STAT)1 and STAT3, and the expression of α1-antitrypsin (A1AT) in mouse lung fibroblast-derived MLg cells and mouse lung epithelial-derived MLE-15 cells. In MLg cells, A1AT expression was decreased in Stat3-knockdown cells, and increased upon Stat3 overexpression. STAT3 formed a homodimer when cells were stimulated with SCGB3A2. Chromatin immunoprecipitation and reporter assays demonstrated that STAT3 binds to specific binding sites on the Serpina1a gene encoding A1AT and upregulates its transcription in lung tissues of mice. Furthermore, nuclear localization of phosphorylated STAT3 upon SCGB3A2 stimulation was detected by immunocytochemistry. These findings demonstrate that SCGB3A2 protects the lungs from the development of CS-induced emphysema by regulating A1AT expression through STAT3 signaling.
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Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Fibrose Pulmonar , Camundongos , Animais , Secretoglobinas/genética , Secretoglobinas/metabolismo , Enfisema Pulmonar/genética , Enfisema Pulmonar/prevenção & controle , Fumar Cigarros/efeitos adversos , Pulmão/patologia , Fibrose Pulmonar/metabolismo , Inflamação/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismoRESUMO
It is unclear whether molnupiravir has a beneficial effect on vaccinated patients infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We here evaluated the efficacy of molnupiravir in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron variant surge in Fukushima Prefecture, Japan. We enrolled patients with mild-to-moderate COVID-19 who were admitted to hospitals between January and April, 2022. Clinical deterioration after admission was compared between molnupiravir users (n = 230) and non-users (n = 690) after 1:3 propensity score matching. Additionally, we performed forward stepwise multivariate logistic regression analysis to evaluate the association between clinical deterioration after admission and molnupiravir treatment in the 1:3 propensity score-matched subjects. The characteristics of participants in both groups were balanced as indicated by covariates with a standardized mean difference of < 0.1. Regarding comorbidities, there was no imbalance between the two groups, except for the presence of hypertension, dyslipidemia, diabetes mellitus, and cardiac disease. The clinical deterioration rate was significantly lower in the molnupiravir users compared to the non-users (3.90% vs 8.40%; P = 0.034). Multivariate logistic regression analysis demonstrated that receiving molnupiravir was a factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.206-0.973; P = 0.042), independent of other covariates. This real-world study demonstrates that molnupiravir contributes to the prevention of deterioration in COVID-19 patients after hospitalization during the Omicron variant phase.
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COVID-19 , Deterioração Clínica , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias , Resultado do TratamentoRESUMO
BACKGROUND: This study aimed to clarify the frequency and clinical features of monogenic cerebral small vessel disease (mgCSVD) among patients with adult-onset severe CSVD in Japan. METHODS: This study included patients with adult-onset severe CSVD with an age of onset ≤55 years (group 1) or >55 years and with a positive family history (group 2). After conducting conventional genetic tests for NOTCH3 and HTRA1, whole-exome sequencing was performed on undiagnosed patients. Patients were divided into two groups according to the results of the genetic tests: monogenic and undetermined. The clinical and imaging features were compared between the two groups. RESULTS: Group 1 and group 2 included 75 and 31 patients, respectively. In total, 30 patients had NOTCH3 mutations, 11 patients had HTRA1 mutations, 6 patients had ABCC6 mutations, 1 patient had a TREX1 mutation, 1 patient had a COL4A1 mutation and 1 patient had a COL4A2 mutation. The total frequency of mutations in NOTCH3, HTRA1 and ABCC6 was 94.0% in patients with mgCSVD. In group 1, the frequency of a family history of first relatives, hypertension and multiple lacunar infarctions (LIs) differed significantly between the two groups (monogenic vs undetermined; family history of first relatives, 61.0% vs 25.0%, p=0.0015; hypertension, 34.1% vs 63.9%, p=0.0092; multiple LIs, 87.8% vs 63.9%, p=0.0134). CONCLUSIONS: More than 90% of mgCSVDs were diagnosed by screening for NOTCH3, HTRA1 and ABCC6. The target sequences for these three genes may efficiently diagnose mgCSVD in Japanese patients.
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Doenças de Pequenos Vasos Cerebrais , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Adulto , Humanos , Pessoa de Meia-Idade , Doenças de Pequenos Vasos Cerebrais/genética , População do Leste Asiático , Serina Peptidase 1 de Requerimento de Alta Temperatura A/genética , Hipertensão , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Mutação , Acidente Vascular Cerebral LacunarRESUMO
Acquired von Willebrand syndrome (aVWS) develops with various underlying diseases. We herein report an individual with aVWS associated with mucosa-associated lymphoid tissue lymphoma in the lungs complicated by hyperviscosity syndrome, Sjögren's syndrome, and hypothyroidism. This patient developed life-threatening hemorrhaging during a lung biopsy despite transfusion of concentrate of plasma-derived VWF/factor VIII. The use of rituximab caused remission of the lymphoma and hyperviscosity syndrome in parallel with the resolution of aVWS. Thus, lymphoma and hyperviscosity might result in aVWS. Invasive procedures with a risk of bleeding should be avoided in individuals with aVWS.
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Linfoma de Zona Marginal Tipo Células B , Paraproteinemias , Doenças de von Willebrand , Humanos , Linfoma de Zona Marginal Tipo Células B/complicações , Doenças de von Willebrand/complicações , Hemorragia/complicações , Paraproteinemias/complicações , Imunoglobulina A , Fator de von WillebrandRESUMO
Background: Telemedicine may help the detection of symptom worsening in patients with chronic obstructive pulmonary disease (COPD), potentially resulting in improved outcomes. This study aimed to determine the feasibility and acceptability of telemedicine among patients with COPD and physicians and facility staff in Japan. Methods: This was a 52-week multicenter, prospective, single-arm, feasibility and acceptability cohort study of Japanese patients ≥40 years of age with COPD or asthma-COPD overlap. Participants underwent training to use YaDoc, a telemedicine smartphone App, which included seven daily symptom questions and weekly COPD Assessment Test (CAT) questions. The primary endpoint was participant compliance for required question completion. The secondary endpoint was participant and physician/facility staff acceptability of YaDoc based on questionnaires completed at Week 52. The impact of the Japanese COVID-19 pandemic state of emergency on results was also assessed. Results: Of the 84 participants enrolled (mean age: 68.7 years, 88% male), 72 participants completed the study. Completion was high in the first six months but fell after that. Median (interquartile range [IQR]) compliance for daily questionnaire entry was 66.6% (31.0-91.8) and 81.0% (45.3-94.3) for weekly CAT entry. Positive participant responses to the exit questionnaire were highest regarding YaDoc ease of use (83.8%), positive impact on managing health (58.8%), and overall satisfaction (53.8%). Of the 26 physicians and facility staff enrolled, 24 completed the study. Of these, the majority (66.7%) responded positively regarding app facilitation of communication between physicians and participants to manage disease. Compliance was similar before and after the first COVID-19 state of emergency in Japan. Conclusion: Daily telemedicine monitoring is potentially feasible and acceptable to both patients and physicians in the management of COPD. These results may inform potential use of telemedicine in clinical practice and design of future studies. Clinical Trial Registration: JapicCTI-194916.
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COVID-19 , Doença Pulmonar Obstrutiva Crônica , Telemedicina , Humanos , Masculino , Feminino , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia , Estudos de Coortes , Estudos de Viabilidade , Estudos Prospectivos , Pandemias , COVID-19/diagnóstico , COVID-19/epidemiologia , Telemedicina/métodosRESUMO
INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first broke out in Wuhan in December 2019, and has since caused a global pandemic. The efficacy of several drugs has been evaluated, and it is now evident that tocilizumab has a beneficial effect, especially combined with corticosteroids, in patients with Coronavirus Disease 2019 (COVID-19). However, the optimal timing of tocilizumab administration has not yet been established. The goal of the present study was to determine the optimal timing of tocilizumab administration after starting corticosteroid therapy in patients with COVID-19. METHODS: We retrospectively analyzed the clinical characteristics of patients who were hospitalized for COVID-19 and treated with tocilizumab and corticosteroids in our hospital. The patients were divided into concurrent and sequential groups. The concurrent group received tocilizumab ≤24 h after corticosteroids, and the sequential group received tocilizumab >24 h after corticosteroid administration. RESULTS: The baseline clinical characteristics of tocilizumab administration were similar between the two groups. White blood cell counts were significantly lower and C-reactive protein levels were significantly higher in the concurrent group than the sequential group. In the concurrent group, tocilizumab administration led to a significant decrease in maximum body temperature. In addition, there were significantly more oxygen-free days in the concurrent group than in the sequential group. However, survival rate was not significantly different between the concurrent and the sequential groups. CONCLUSIONS: In the combination therapy with tocilizumab and corticosteroids, early administration of tocilizumab after starting corticosteroid treatment is effective when treating COVID-19.
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Tratamento Farmacológico da COVID-19 , Anticorpos Monoclonais Humanizados , Proteína C-Reativa , Humanos , Estudos Retrospectivos , SARS-CoV-2 , Resultado do TratamentoRESUMO
Hyperhomocysteinemia was reported to enhance endoplasmic reticulum (ER) stress and subsequent apoptosis in several cells. However, the precise mechanisms of smoking susceptibility associated with hyperhomocysteinemia has not been fully elucidated. This study included 7- to 9-week-old C57BL6 male mice induced with hyperhomocysteinemia and were exposed to cigarette smoke (CS). A549 cells (human alveolar epithelial cell line) were cultured with homocysteine and were exposed to cigarette smoke extract (CSE) to observe cell viability and expression of proteins related to the ER stress. After 6 months of CS exposure, pulmonary emphysema was more severely induced in the group under the condition of hyperhomocysteinemia compared to that in the control group. The apoptotic A549 cells increased as homocysteine concentration increased and that was enhanced by CSE. Protein expression levels of ER stress markers were significantly increased after simultaneous stimulation. Notably, vitamin B12 and folate supplementation improved ER stress after simultaneous stimulation of A549 cells. In this study, we showed that hyperhomocysteinemia exacerbates CS exposure-induced emphysema in mice, suggesting that hyperhomocysteinemia and CS stimulation enhance ER stress and subsequent induced apoptosis in alveolar epithelial cells. It was suggested that there is a synergistic effect between homocysteine and CS.