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Importance: The effectiveness of different combinations of inhaled corticosteroid (ICS) therapies in reducing severe exacerbations of adult asthma remains unclear. Objective: This network meta-analysis (NMA) extensively evaluated the treatment effects of single ICS; dual ICS i.e., ICS/long-acting ß2-adrenergic agonists (LABA); ICS/LABA as single maintenance and reliever therapy (SMART); and triple ICS, i.e., ICS/LABA/long-acting muscarinic antagonists (LAMA) in preventing severe asthma exacerbations. Data sources: A systematic search of English databases, including PubMed and Web of Science, was conducted until December 31, 2022, using PRISMA-NMA. Study selection: Using the PICOS criteria, the questions for this study were carefully selected so that the correct keywords could be identified. Data extraction and synthesis: A pairwise meta-analysis was used to select trials based on the criteria for minimizing heterogeneity (I2). Subsequently, the "BUGSnet" package of R software was used to perform a Bayesian network meta-analysis. Main outcome measures: The main outcome measures were risk rate and annualized rate ratio of severe asthma exacerbations. Results: This review included 56 randomized control trials (RCTs; n = 78,171 patients). As the pairwise meta-analysis demonstrated that the annualized rate ratio of severe asthma exacerbation had moderate heterogeneity, we analyzed the risk rate of severe asthma exacerbation using a network meta-analysis. In terms of direct/indirect comparisons with non-ICS, single ICS, dual ICS, SMART, and triple ICS reduced severe asthma exacerbations by 34 %, 47 %, 58 %, and 57 %, respectively. SMART and triple ICS showed high effectiveness in reducing severe exacerbations. Conclusion: AND RELEVANCE: SMART and triple ICS were ranked higher in effectiveness in reducing severe asthma exacerbations in comparison with other therapies, indicating that these are the most effective treatments for reducing the future risk of severe asthma exacerbations.
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It has been postulated from a combination of evidence that a sudden increase in COVID-19 cases among pediatric patients after onset of the Omicron wave was attributed to a reduced requirement for TMPRSS2-mediated entry in pediatric airways with lower expression levels of TMPRSS2. Epidemic strains were isolated from the indigenous population in an area, and the levels of TMPRSS2 required for Delta and Omicron variants were assessed. As a result, Delta variants proliferated fully in cultures of TMPRSS2-positive Vero cells but not in TMPRSS2-negative Vero cell culture (350-fold, Delta vs 9.6-fold, Omicron). There was no obvious age-dependent selection of Omicron strains affected by the TMPRSS2 (9.6-fold, Adults vs. 12-fold, Children). A phylogenetic tree was generated and Blast searches (up to 100 references) for the spread of strains in the study area showed that each strain had almost identical homology (>99.5%) with foreign isolates, although indigenous strains had obvious differences from each other. This suggested that the differences had been present abroad for a long period. Therefore, the lower requirement for TMPRSS2 by Omicron strains might be applicable to epidemic strains globally. In conclusion, the property of TMPRSS2-independent cleavage makes Omicron proliferate with ease and allows epidemics among children with fewer TMPRSS2 on epithelial surfaces of the respiratory organs.
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COVID-19 , SARS-CoV-2 , Serina Endopeptidasas , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Humanos , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Chlorocebus aethiops , COVID-19/virología , COVID-19/metabolismo , COVID-19/epidemiología , Células Vero , Niño , Animales , Preescolar , Filogenia , Adulto , Lactante , Masculino , FemeninoRESUMEN
An evidence-based diagnostic algorithm for adult asthma is necessary for effective treatment and management. We present a diagnostic algorithm that utilizes a random forest (RF) and an optimized eXtreme Gradient Boosting (XGBoost) classifier to diagnose adult asthma as an auxiliary tool. Data were gathered from the medical records of 566 adult outpatients who visited Kindai University Hospital with complaints of nonspecific respiratory symptoms. Specialists made a thorough diagnosis of asthma based on symptoms, physical indicators, and objective testing, including airway hyperresponsiveness. We used two decision-tree classifiers to identify the diagnostic algorithms: RF and XGBoost. Bayesian optimization was used to optimize the hyperparameters of RF and XGBoost. Accuracy and area under the curve (AUC) were used as evaluation metrics. The XGBoost classifier outperformed the RF classifier with an accuracy of 81% and an AUC of 85%. A combination of symptom-physical signs and lung function tests was successfully used to construct a diagnostic algorithm on importance features for diagnosing adult asthma. These results indicate that the proposed model can be reliably used to construct diagnostic algorithms with selected features from objective tests in different settings.
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Heart failure and pneumonia are highly prevalent in elderly patients. We conducted a study to evaluate the differences in the patterns of symptoms, laboratory findings, and computed tomography (CT) results in elderly patients with acute cardiogenic pulmonary edema (ACPE) and community-acquired pneumonia (CAP). From January 1, 2015 to December 31, 2017, we studied 140 patients aged >75 years who were diagnosed with ACPE and CAP. Symptoms, laboratory findings, mean ostial pulmonary vein (PV) diameter and patterns on CT images were assessed. The primary measures of diagnostic accuracy were assessed using the positive likelihood ratio (LR+). The cutoff value of ostial PVs for differentiating patients with ACPE from CAP was evaluated using the receiver operating characteristic (ROC) analysis. Ninety-three patients with ACPE, 36 with CAP, and 11 with complicated ACPE/CAP were included. In patients with ACPE, edema (LR+ 5.4) was a moderate factor for rule-in, and a high brain natriuretic peptide level (LR+ 4.2) was weak. In patients with CAP, cough (LR+ 5.7) and leukocytosis (LR+ 5.2) were moderate factors for rule-in, while fever (LR+ 3.8) and a high C-reactive protein level (LR+ 4.8) were weak factors. The mean diameter of ostial PVs in patients with ACPE was significantly larger than that of patients with CAP (15.8±â1.8 mm vs 9.6±1.5 mm, p<â0.01). ROC analysis revealed that an ostial PV diameter cutoff of 12.5 mm was strong evidence for distinguishing ACPE from CAP with an area under the ROC curve of 0.99 and LR+ 36.0. In conclusion, as ACPE and CAP have similar symptoms and laboratory findings, dilated ostial PVs were useful in characterizing CT images to distinguish ACPE from CAP.
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Uric acid (UA) forms monosodium urate (MSU) crystals to exert proinflammatory actions, thus causing gout arthritis, urolithiasis, kidney disease, and cardiovascular disease. UA is also one of the most potent antioxidants that suppresses oxidative stress. Hyper andhypouricemia are caused by genetic mutations or polymorphism. Hyperuricemia increases urinary UA concentration and is frequently associated with urolithiasis, which is augmented by low urinary pH. Renal hypouricemia (RHU) is associated with renal stones by increased level of urinary UA, which correlates with the impaired tubular reabsorption of UA. Hyperuricemia causes gout nephropathy, characterized by renal interstitium and tubular damage because MSU precipitates in the tubules. RHU is also frequently associated with tubular damage with elevated urinary beta2-microglobulin due to increased urinary UA concentration, which is related to impaired tubular UA reabsorption through URAT1. Hyperuricemia could induce renal arteriopathy and reduce renal blood flow, while increasing urinary albumin excretion, which is correlated with plasma xanthine oxidoreductase (XOR) activity. RHU is associated with exercise-induced kidney injury, since low levels of SUA could induce the vasoconstriction of the kidney and the enhanced urinary UA excretion could form intratubular precipitation. A U-shaped association of SUA with organ damage is observed in patients with kidney diseases related to impaired endothelial function. Under hyperuricemia, intracellular UA, MSU crystals, and XOR could reduce NO and activate several proinflammatory signals, impairing endothelial functions. Under hypouricemia, the genetic and pharmacological depletion of UA could impair the NO-dependent and independent endothelial functions, suggesting that RHU and secondary hypouricemia might be a risk factor for the loss of kidney functions. In order to protect kidney functions in hyperuricemic patients, the use of urate lowering agents could be recommended to target SUA below 6 mg/dL. In order to protect the kidney functions in RHU patients, hydration and urinary alkalization may be recommended, and in some cases an XOR inhibitor might be recommended in order to reduce oxidative stress.
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Objective Both renal hypouricemia (RHU) and gout are associated with renal dysfunction and urolithiasis. The difference in renal complications associated with RHU and gout, however, has not been studied. We characterized the urate metabolism and complications of patients with RHU and compared them with patients with gout. Methods Eighteen patients with RHU who had a serum uric acid (SUA) level <2 mg/dL (10 men and 8 women), 44 patients with gout (44 men) and 16 normouricemic patients (4 men and 12 women) were included. The blood and urinary biochemical data were evaluated. A genetic analysis of uric acid transporter 1 (URAT1) was also conducted in 15 cases with RHU. Results The SUA level of RHU was 0.9±0.5/mg/dL, and the Uur/Ucr and Cur/Ccr were 0.56±0.14% and 45.7±18.0%, respectively. A genetic analysis of URAT1 in 15 RHU patients showed that 13 harbored a URAT1 gene mutation, whereas 2 harbored the wild-type gene. The SUA level was significantly lower in RHU patients (n=11) than in either gout patients (n=44) or normouricemic patients (n=16). This reduction was accompanied by the elevation of Cua/Ccr. Urinary beta 2-microglobulin levels were higher in RHU patients than in gout or normouricemia patients. Cua/Ccr correlated with normalized urinary beta 2-microglobulin levels. The prevalence of urolithiasis was 18.2% in RHU cases and 6.8% in gout cases. A homozygous URAT1 mutation was associated with urolithiasis. Conclusion Besides urolithiasis, RHU can be associated with tubular dysfunction, such as elevated urinary beta 2-microglobulin levels.
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Gota , Cálculos Urinarios , Masculino , Humanos , Femenino , Ácido Úrico , Microglobulina beta-2 , Gota/complicaciones , Gota/genética , Cálculos Urinarios/complicaciones , Cálculos Urinarios/genéticaRESUMEN
Primary Sjögren's syndrome (pSS) has multi-dimensional manifestations, including neutropenia and polyneuropathy. We herein report a 76-year-old woman with pSS initially presenting as severe granulocyte-colony-stimulating factor (G-CSF)-refractory neutropenia and axonal sensorimotor polyneuropathies (SMP). Systemic glucocorticoid administration had reduced neutrophil-associated immunoglobulin G (NAIgG) on the neutrophil surface as detected using flow cytometry, resulting in the development of neutropenia. A patient with pSS concomitant with axonal SMP might show severe neutropenia as aggressive autoimmune disease. Neutropenia can be treated with systemic glucocorticoids based on the assessment of NAIgG on the neutrophil surface.
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Neutropenia , Polineuropatías , Síndrome de Sjögren , Femenino , Humanos , Anciano , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/tratamiento farmacológico , Neutropenia/etiología , Neutropenia/complicaciones , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Polineuropatías/etiología , Polineuropatías/complicaciones , Neutrófilos , GlucocorticoidesRESUMEN
BACKGROUND: The BNT162b mRNA vaccine for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mimics the immune response to natural infection. Few studies have predicted the adverse effects (AEs) after the second-dose vaccination. We present a predictive model for AEs and immune response after the second-dose of the BNT162b mRNA vaccine. METHODS: To predict AEs, 282 healthcare workers (HCWs) were enrolled in this prospective observational study. The classification and regression tree (CART) model was established, and its predictive efficacy was assessed. To predict immune response, 282 HCWs were included in the analysis. Moreover, the factors affected by anti-SARS-CoV-2 spike protein RBD antibody (s-IgG) were evaluated using serum samples collected 2 months after the second-dose vaccination. The s-IgG level was assessed using Lumipulse G1200. Multiple regression analyses were conducted to evaluate variables associated with anti-s-IgG titer levels. RESULTS: The most common AEs after the second-dose vaccination were pain (87.6%), redness (17.0%) at the injection site, fatigue (68.8%), headache (53.5%), and fever (37.5%). Based on the CART model, headache after the first-dose vaccination and age < 30 years were identified as the first and second discriminators for predicting the headache after the second-dose vaccination, respectively. In the multiple linear regression model, anti-s-IgG titer levels were associated with age, female sex, and AEs including headache and induration at the injection site after the second-dose vaccination. CONCLUSION: Headache after the first-dose vaccination can be a predictor of headache after the second-dose vaccination, and AEs are indicators of immune response.
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BACKGROUND: Many patients visit primary care clinics with a complaint of cough. General practitioners (GPs) developed a list of the causative diseases of cough that can produce a patient's symptoms and signs. Then, the patients' medical histories were evaluated to determine whether the diagnosis of cough variant asthma (CVA) or post-infectious cough (PIC) could have been predicted. METHODS: We retrospectively investigated 195 outpatients with a complaint of cough. Medical histories of "recurrent episodes of prolonged cough" and "upper respiratory infection" were obtained during the initial visit. The accuracy of medical histories in predicting CVA and PIC was calculated on the area under the curve (AUC). RESULTS: Among eligible patients with cough, PIC was diagnosed in 99 patients (50.8%), CVA in 40 patients (20.5%), upper airway cough syndrome in 28 patients (14.4%), and chronic obstructive pulmonary disease in 11 patients (5.6%). Among the patients with CVA and those with PIC, 93% and 12%, respectively, had a history of recurrent episodes of prolonged cough. For the diagnosis of CVA, having a history of recurrent episodes of prolonged cough showed a moderately accurate AUC (0.76, 95% CI: 0.71-0.82). On the other hand, for the diagnosis of PIC, having no history of recurrent episodes of prolonged cough also showed a moderately accurate AUC (0.87, 95% CI: 0.82-0.92). CONCLUSION: The medical history of recurrent episodes of prolonged cough is useful for the prediction of CVA as well as PIC.
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BACKGROUND: BNT162b2, an mRNA COVID-19 vaccine, was launched in many countries as an intramuscular vaccination for COVID-19 infection. Few studies have assessed the physical indications of pain at the immunization site. This study aimed to characterize pain at the injection site and investigate morphological attributes using ultrasound. METHODS: Forty-three of 211 healthcare workers who received a second dose of BNT162b2 between February 2021 and March 2021 were enrolled in the study. The mean age of the subjects was 40 years. We evaluated patients' pain at the injection site using the Numerical Rating Pain Scale (NRPS). We also assessed the thickness of the deltoid muscle fascia at the injection site by ultrasound. Bayesian robust correlation was employed to explore the relationship between the pain intensity scores and ultrasound measurements. RESULTS: All eligible subjects complained of pain at the injection site. A median pain onset of 8 hours post-vaccination and a median peak intensity score of 4 were reported. Onset of relief occurred after 2 days. Ultrasound images demonstrated a 2.5-fold increase in fascia thickness at the injection site without intramuscular echogenicity change in all subjects. A correlation was established between the NRPS score and the non-injection-to-injection-side ratio of fascia thickness at the injection site (rho = 0.66). CONCLUSION: A sore arm was the most prevalent side effect of BNT162b2 vaccination and could be attributed to temporal fasciitis.
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INTRODUCTION: Post-nasal drip (PND)-induced cough is a common cause of chronic cough. However, there is little known about the characteristic physical findings of this condition. OBJECTIVES: We investigated views of the pharyngeal wall in patients with PND-induced cough using a handy endoscopic images. METHODS: The subjects were 135 consecutive patients referred to our hospital with a sensation of something "dripping down the throat" as one of their symptoms. Physical findings for the oropharynx were examined using Wi-Fi endoscope camera. The difference in probability of symptoms in patients with acute cough and those with subacute/chronic cough was assessed using a Bayesian Fisher exact test on a 2 × 2 table. RESULTS: Among the patients, 105 (78%) complained of cough, 78 (58%) of acute cough, 20 (15%) of subacute cough, and 7 (5%) of chronic cough; and 71 (53%) had coexisting asthma. Using Bayesian inference, a sore or scratchy throat and fever were more common in patients with acute cough than in those with subacute/chronic cough. In endoscopic images of the oropharynx, a reddish curtain sign on the posterior pharyngeal wall behind the palatopharyngeal arch was found in 121 patients (90%). CONCLUSION: Patients with acute PND-induced cough have a component of acute upper respiratory infection, because of high probability of a sore or scratchy throat and fever as symptom. A reddish curtain sign may be a useful finding for identifying PND-induced cough in these cases.
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Tos , Orofaringe/fisiología , Rinitis , Teorema de Bayes , Enfermedad Crónica , HumanosRESUMEN
Thrombotic thrombocytopenic purpura (TTP) is rare complication resulting from adult-onset Still's disease (AOSD). We report the case of a 69-year-old Japanese man who initially presented with fever and joint pain and was diagnosed as having concurrent AOSD with TTP 1 month later. He had extremely high ferritin levels (32 696 ng/mL). He initially responded to plasma exchange but subsequently died of septic shock. AOSD accompanied by extremely high ferritin levels might be considered a sign of concurrent TTP.
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Púrpura Trombocitopénica Trombótica/complicaciones , Choque Séptico , Enfermedad de Still del Adulto/diagnóstico , Anciano , Resultado Fatal , Humanos , Masculino , Intercambio Plasmático , Enfermedad de Still del Adulto/complicacionesRESUMEN
BACKGROUND: We explored whether the use of deep learning to model combinations of symptom-physical signs and objective tests, such as lung function tests and the bronchial challenge test, would improve model performance in predicting the initial diagnosis of adult asthma when compared to the conventional machine learning diagnostic method. METHODS: The data were obtained from the clinical records on prospective study of 566 adult out-patients who visited Kindai University Hospital for the first time with complaints of non-specific respiratory symptoms. Asthma was comprehensively diagnosed by specialists based on symptom-physical signs and objective tests. Model performance metrics were compared to logistic analysis, support vector machine (SVM) learning, and the deep neural network (DNN) model. RESULTS: For the diagnosis of adult asthma based on symptom-physical signs alone, the accuracy of the DNN model was 0.68, whereas that for the SVM was 0.60 and for the logistic analysis was 0.65. When adult asthma was diagnosed based on symptom-physical signs, biochemical findings, lung function tests, and the bronchial challenge test, the accuracy of the DNN model increased to 0.98 and was significantly higher than the 0.82 accuracy of the SVM and the 0.94 accuracy of the logistic analysis. CONCLUSIONS: DNN is able to better facilitate diagnosing adult asthma, compared with classical machine learnings, such as logistic analysis and SVM. The deep learning models based on symptom-physical signs and objective tests appear to improve the performance for diagnosing adult asthma.
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Asma/diagnóstico , Aprendizaje Profundo , Modelos Teóricos , Algoritmos , Inteligencia Artificial , Femenino , Humanos , Modelos Logísticos , Masculino , Redes Neurales de la Computación , Curva ROC , Máquina de Vectores de SoporteRESUMEN
OBJECTIVE: In elderly patients, age-related, disease-related, and drug-related factors are associated with chronic kidney disease (CKD). Little is known about which factors are the best predictors for CKD in elderly patients. MATERIALS AND METHODS: The study was based on 784 patients aged 75 years or older for whom the clinical and serum creatinine on admission to our hospital were available. Impaired renal function, including CKD and transient renal insufficiency, was defined as a non-indexed glomerular filtration rate (GFR) below 60 mL/min. A logistic regression model was developed for predictors of CKD and was internally validated using bootstrapping. RESULTS: Approximately 61% of the patients, who had CKD (46%) and transient renal insufficiency (15%), had a non-indexed GFR < 60 mL/min. Synergistic use of 3 drugs potentially impairing renal function, diuretics, ACE-I/ARB, and NSAIDs (odds ratio (OR), 4.66; 95% confidence interval (CI), 1.48 - 17.7, p = 0.012) was a significantly associated factor for CKD in a multivariate logistic regression analysis. Age (OR 1.56, 95% CI 1.04 - 2.33, p = 0.03), female gender (OR 1.58, 95% CI 1.04 - 2.39, p = 0.03), any prescription ACE-I/ARB either alone or in combinations with diuretics or NSAIDs (OR 2.74, 95% CI 1.83 - 4.13, p = 0.0001), and proteinuria (OR 1.98, 95% CI 1.27 - 3.10, p = 0.003), were included as the best model for CKD. The area under the curve (AUC) of the best model and the bootstrapping validation were 0.68 and 0.71, respectively. CONCLUSION: Given the widespread use of ACE-I/ARB for elderly patients, our findings suggest that caution is needed when they are prescribed because of the possibility of the patient developing CKD.
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Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antiinflamatorios no Esteroideos/efectos adversos , Diuréticos/efectos adversos , Prescripción Inadecuada/estadística & datos numéricos , Insuficiencia Renal Crónica/inducido químicamente , Anciano , Creatinina/sangre , Estudios Transversales , Femenino , Tasa de Filtración Glomerular , Humanos , Pacientes Internos , MasculinoRESUMEN
BACKGROUND: We obtain summary estimates of the accuracy of additional objective tests for the diagnosis of adult asthma using systematic review and meta-analysis of diagnostic test accuracy studies. METHODS: Medline, Embase, and other relevant electronic databases were searched for papers published between January 1989 and December 2016. Studies were included if they evaluated the diagnostic accuracy of objective tests, including airway reversibility (AR), airway hyperresponsiveness (AHR), and fractionated exhaled nitric oxide (FeNO) for the diagnosis of adult asthma in patients with symptoms suggestive of asthma. If papers were assessed appropriate using the adapted QUADAS-2 tool, meta-analysis was conducted using the hierarchical bivariate model. This hierarchical model accounts for both within and between study variability. RESULTS: Sixteen studies reported the performance of the evaluated objective tests at presentation. For diagnosis of adult asthma, overall sensitivity and specificity for AR were 0.39 (95% confidence interval [CI] 0.18 to 0.66) and 0.95 (95% CI 0.86 to 1.00); for AHR, 0.86 (95% CI 0.61 to 1.00) and 0.95 (95% CI 0.77 to 1.00); for FeNO, 0.65 (95% CI 0.53 to 0.77) and 0.83 (95% CI 0.75 to 0.90). Comprehensive comparison of three diagnostic tools for adult asthma using the back-calculated likelihood rate (LR) showed that AR and AHR corresponded to a higher LR+, and AHR gave a lower LR-. CONCLUSIONS: In the current situation of no gold standard for diagnosis of adult asthma, AR and AHR are appropriate for ruling-in the true diagnosis, and AHR is superior for ruling-out a diagnosis. Since each objective test had a specific characteristic, it should be chosen depending on the situation, such as the capacity of the institution and the conditions of patients.
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Asma/diagnóstico , Técnicas de Diagnóstico del Sistema Respiratorio , Adulto , Teorema de Bayes , Humanos , Reproducibilidad de los ResultadosRESUMEN
Few studies have examined variations in both the physical signs and clinical findings in the final days and hours before the death of elderly patients. We determined the physical signs and clinical findings in patients who were at least 75 years old or were diagnosed with cancer with impending death and examined the association of these parameters with the profile and timing of their endocardiography (ECG) and oxygen saturation (SpO2) changes prior to death. In this prospective, observational study, between April 2014 and June 2017, we enrolled elderly patients who were admitted to the Respiratory Medicine Ward in our hospital and were near death, which was determined based on certain symptoms such as a loss of oral intake. We recorded their physical signs (oral intake, consciousness level, and respiration with mandibular movement) 4 times a day from admission to death. We evaluated their changes in ECG and in SpO2 levels for up to 24 hours preceding death. For the 70 patients who died in our ward, we found a loss of oral intake at 6 days, consciousness impairment at 1.3 days, and then respiration with mandibular movement at 12 hours before death were the most consistent findings before death. When we analyzed the ECG and SpO2 changes during impending death, 83% of the patients showed undetectable SpO2 levels followed by a loss of heart rate. The loss of P wave in the ECG was characterized as process on impending death. Respiration with mandibular movement was one of the specific signs of impending death in ill elderly patients. The monitoring of ECG and SpO2 levels may be a useful tool to predict the impending time of death.
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Muerte , Neoplasias/fisiopatología , Oxígeno/sangre , Signos Vitales , Anciano , Anciano de 80 o más Años , Electroencefalografía , Femenino , Indicadores de Salud , Hemodinámica/fisiología , Humanos , Masculino , Estudios ProspectivosRESUMEN
IgG4-related lung disease (IgG4-RLD) is a rare and chronic progressive autoimmune disease. We report a case of IgG4-related inflammatory pseudo-tumor of the lung that was seropositive for proteinase 3 anti-neutrophil cytoplasmic antibody (PR3-ANCA). A 61-year-old male had a mass lesion in the right lower lung field in chest X-ray. Transbronchial lung biopsy resulted in a pathological diagnosis of IgG4-RLD. The condition was improved by hormonal therapy.
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BACKGROUND: Sensitization to Staphylococcus aureus enterotoxin (SE) is a known risk factor for asthma susceptibility and severity. However, how SE sensitization is involved in asthma, particularly nonatopic asthma and/or late-onset asthma, remains uncertain. OBJECTIVE: To clarify the involvement of SE sensitization in nonatopic and/or late-onset asthma and its association with a polymorphism of the cysteinyl leukotriene receptor 1 gene (CysLTR1), which was examined because CysLT signaling is closely associated with late-onset eosinophilic asthma. METHODS: We assessed associations between sensitization to SE (A and/or B) and clinical indexes in 224 patients with asthma (mean age, 62.3 years; 171 women) from a cohort of the Kinki Hokuriku Airway Disease Conference, particularly those with nonatopic asthma (not sensitized to common aeroallergens) and/or late-onset asthma. Associations between SE sensitization and CysLTR1 polymorphism (rs2806489), a potential regulatory variant for atopic predisposition in women, were also assessed in a sex-stratified manner. RESULTS: A total of 105 patients (47%) with asthma were sensitized to SE. Among patients with nonatopic asthma (n = 67) or with late-onset asthma (n = 124), those sensitized to SE had significantly higher serum total IgE and periostin levels than those not sensitized. In nonatopic patients, a rapid decrease in forced expiratory volume in 1 second was associated with SE sensitization. In women with asthma, rs2806489 was associated with sensitization to SEB and age at asthma onset. CONCLUSION: SE sensitization contributes to TH2 inflammation in nonatopic and/or late-onset asthma. In women with asthma, the CysLTR1 variant might be associated with sensitization to SEB and age at asthma onset.
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Asma/diagnóstico , Asma/etiología , Enterotoxinas/inmunología , Variación Genética , Fenotipo , Receptores de Leucotrienos/genética , Staphylococcus aureus/inmunología , Anciano , Alelos , Asma/metabolismo , Biomarcadores , Estudios de Casos y Controles , Susceptibilidad a Enfermedades , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Humanos , Inmunización , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Receptores de Leucotrienos/metabolismo , Pruebas de Función Respiratoria , Factores de RiesgoRESUMEN
BACKGROUND: Asthma guidelines suggest stepping-down of inhaled corticosteroids (ICSs) when asthma is stable. OBJECTIVE: To determine outcomes of stepping-down and prediction of outcome after stepping-down of ICSs in controlled adult asthma. METHODS: We performed a retrospective study on 21-81 year-old hospital-based outpatients with asthma in Japan. Protocol for stepping-down of ICSs was performed according to the GINA guideline. Failure/success of stepping-down is judged as occurring exacerbation or not for stepping-down of ICSs. Multiple logistic regression analysis was used to develop a prediction model for failed stepping-down, and then was validated by the leave-one-out cross-validation method. Our model of prediction score was calculated using receiver-operating characteristic area under the curve (AUC) analysis. The Nelson-Aalen curve demonstrated time to failure of stepping-down of ICSs. RESULTS: A total of 126 patients with asthma attempted the stepping-down of ICSs according to the guideline. Of patients with follow-up, 97 (77.0%) of stepping-down attempts were successful. Using multivariate logistic regression analysis, comorbidity with rhinitis/rhinosinusitis and phlegm grade were independent predictors of failed stepping-down of ICSs, with odds ratios of 3.8 (95% confidence interval, 1.04-13.3; P=0.04) and 1.3 (95% confidence interval, 1.01-11.5; P=0.04), respectively. These variables were then used to build a prediction score in terms of the prediction of failed stepping-down events. When the two variables were added to form the prediction score, the discriminative power of scores calculated by the prediction model using the AUC was 0.75 (range: 0.62-0.88) for naïve prediction and 0.72 (range: 0.60-0.86) after cross-validation. In the time-to-failure models, cumulative hazard ratio of failed stepping-down have fixed 1 year after stepping-down. CONCLUSION: Our results suggest that comorbidity with rhinitis/rhinosinusitis and phlegm grade are imperative to predict failed stepping-down of ICSs in controlled patients with adult asthma.