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Preoperative left ventricular (LV) ejection fraction (LVEF) and LV end-systolic dimension (LVESD) are established predictors of LV dysfunction (LVD) after mitral valve repair (MVr) for mitral regurgitation (MR). Although elevated estimated right ventricular systolic pressure (eRVSP) indicating pulmonary hypertension is the best proposed additional predictor, we hypothesized that transthoracic echocardiography (TTE) parameters more directly reflecting left atrial pressure (LAP) would more accurately predict LVD than eRVSP. Furthermore, predictors of a significant decline in LVEF remain unknown. We retrospectively studied 622 patients, aged 20-87 years, who underwent MVr for severe chronic primary MR. As previously reported predictors of postoperative LVD, we collected seven preoperative TTE parameters, including LVESD, LVEF, eRVSP, LV end-diastolic dimension, left atrial volume index (LAVI), early transmitral annular (e') velocity, and atrial fibrillation. Furthermore, as LAP-related TTE parameters, we collected left atrial dimension, E-wave velocity, and E/e' ratio, in addition to eRVSP and LAVI. Using multivariate logistic regression and receiver operating characteristic curve analyses, we explored predictors of early postoperative LVD, defined as LVEF < 50% measured on postoperative day 7. We further explored predictors of a significant decline in LVEF, defined as an absolute decline in LVEF of > 12 percentage points, the third quintile of the data. Incidences of postoperative LVD and a significant LVEF decline were 12.9% and 23.2%, respectively. In addition to LVESD and LVEF, E-wave velocity, but not eRVSP, remained a significant predictor of postoperative LVD. E-wave velocity, LVESD, and LVEF had additive effects in risk prediction. Furthermore, E-wave velocity was the strongest predictor of a significant LVEF decline. E-wave velocities > 121.5 cm/s and > 101.5 cm/s were associated with increased risks of postoperative LVD (odds ratio [OR], 2.896; 95% confidence interval [95%CI], 1.792-4.681; p < 0.001) and a significant LVEF decline (OR, 6.345; 95%CI, 3.707-10.86; p < 0.001), respectively. After adjustment for multiple TTE parameters, E-wave velocity, but not eRVSP, remained significant predictors of postoperative LVD and a significant LVEF decline after MVr. These results were reproducible in 461 patients who underwent follow-up TTE at 1 year, suggesting an important role of E-wave velocity in risk prediction.
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AIM: Abundant data are available on the effect of the A118G (rs1799971) single-nucleotide polymorphism (SNP) of the µ-opioid receptor OPRM1 gene on morphine and fentanyl requirements for pain control. However, data on the effect of this SNP on intraoperative remifentanil requirements remain limited. We investigated the effect of this SNP on intraoperative remifentanil requirements. METHODS: We investigated 333 Japanese women, aged 21-69 years, who underwent laparoscopic gynecological surgery for benign gynecological disease under total intravenous anesthesia at Juntendo University Hospital. Average infusion rates of propofol and remifentanil during anesthesia and the average bispectral index (BIS) during surgery were recorded. Associations among genotypes of the A118G and phenotypes were examined with the Mann-Whitney U test. RESULTS: The average propofol infusion rate was not different between patients with different genotypes. The average remifentanil infusion rate was significantly higher in patients with the AG or GG genotype than the AA genotype (p = 0.028). The average intraoperative BIS was significantly higher in patients with the GG genotype than the AA or AG genotype (p = 0.039). CONCLUSIONS: The G allele of the A118G SNP was associated with higher intraoperative remifentanil requirements and higher intraoperative BIS values but was not associated with propofol requirements. Given that remifentanil and propofol act synergistically on the BIS, these results suggest that the G allele of the A118G SNP is associated with lower effects of remifentanil in achieving adequate intraoperative analgesia and in potentiating the sedative effect of propofol on the BIS.
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PURPOSE: This study aimed to investigate whether smoking is an independent risk factor for central sensitization syndrome (CSS) in individuals with pain as measured by the Central Sensitization Inventory (CSI). METHODS: In 2020, we conducted an Internet survey targeting 2000 ordinary residents of Japan (aged 20-69 years) who had pain symptoms from October to November 2020. A multiple regression analysis was performed on the association between smoking status (nonsmokers and current smokers; Brinkman index) and CSI values. Moreover, compared to nonsmokers, the relative risk (RR) of the CSI cut-off score of 40 points or higher among current smokers was calculated using a modified Poisson regression model. Covariates included age, sex, body mass index, marital status, equivalized income, exercise habits, history of hypertension, history of hyperlipidemia, history of diabetes, pain chronicity, and Pain Catastrophizing Scale score. RESULTS: This study analyzed 1,822 individuals (1,041 men and 781 women). Among those experiencing pain, current smoking was associated with the increase in CSI values (ß = 0.07). The Brinkman index was also significantly associated with the increase in CSI values (ß = 0.06). Current smoking also increased the risk of being over the CSI cut-off score, with a relative risk (RR) of 1.29 (95% confidence intervals, 1.04-1.60). Younger age, being women, experiencing chronic pain, and higher pain catastrophizing thinking were also significantly associated with increased CSS severity, independent of smoking status. CONCLUSION: Smoking is an independent risk factor for CSS. This indicates that smoking may be an important factor in the management of central pain disorders.
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Dor Crônica , Neuralgia , Masculino , Humanos , Feminino , Sensibilização do Sistema Nervoso Central , Estudos Transversais , Dor Crônica/diagnóstico , Inquéritos e Questionários , Fumar/efeitos adversos , Fumar/epidemiologiaRESUMO
The diagnosis of pulmonary lymphoma using small tissue samples is difficult and often requires surgical procedures; thus, a less invasive sampling method is desirable. Moreover, pulmonary involvement in adult T-cell lymphoma (ATL) is often difficult to diagnose, especially in cases without characteristic flower cells. Here, we present the case of a 78-year-old man, in whom pathological examination of the transbronchial lung biopsy (TBLB) specimen did not reveal malignant findings; therefore, transbronchial lung cryobiopsy (TBLC) in combination with endobronchial ultrasonography (EBUS) was used to diagnose ATL based on the pathological findings. A literature review identified 18 cases of pulmonary lymphomas diagnosed using TBLC. Among the 19 cases, including our own, 16 cases were of B-cell lymphoma (84.2%), and the present case is the first case of ATL diagnosed using TBLC. Eighty percent of the cases underwent a biopsy (more than two samples) of the middle or lower lobe and were diagnosed without major complications. EBUS was used with TBLC in three cases to identify the location of the pulmonary lesions. In the present case, EBUS was also useful for avoiding vascular biopsy. Although large-scale prospective studies are required to establish precise guidelines for diagnosing pulmonary lymphomas using TBLC, our case report and review contributes to a deeper understanding of the diagnosis of rare diseases.
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Doenças Pulmonares Intersticiais , Neoplasias Pulmonares , Linfoma de Células T , Linfoma , Masculino , Humanos , Adulto , Idoso , Doenças Pulmonares Intersticiais/diagnóstico , Broncoscopia/métodos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Biópsia/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Linfoma/patologia , Linfoma de Células T/patologiaRESUMO
Pulmonary nodular lymphoid hyperplasia (PNLH) is a very rare disease, and it is difficult to diagnose PNLH and distinguish it from mucosa-associated lymphoid tissue (MALT) lymphoma. In addition, information on bronchoalveolar lavage fluid (BALF) analyses is lacking. We herein report a 36-year-old Japanese woman diagnosed with PLNH by a surgical biopsy and analysis of BALF. The BALF showed an increase in B-cell marker-positive lymphocytes, normal patterns of B-cell clonality, mucosa-associated lymphoid tissue 1 gene, and immunoglobulin heavy chain at 14q32 translocations. We also reviewed Japanese cases of PNLH described in Japanese or English to explore the characteristics of such cases.
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Pneumopatias , Linfoma de Zona Marginal Tipo Células B , Feminino , Humanos , Adulto , Líquido da Lavagem Broncoalveolar , Hiperplasia/diagnóstico , População do Leste Asiático , Pneumopatias/diagnóstico , Pneumopatias/patologia , Linfoma de Zona Marginal Tipo Células B/patologiaRESUMO
A 36-year-old Japanese man presented with cavities and nodular shadows in the lower lobes of his lungs and osteolytic lesions in the thoracic spine. He was diagnosed with multisystem Langerhans cell histiocytosis (LCH). Three years earlier, he had been noted to have small cavities and granular lesions noted in the upper lobes of his lungs, which later improved with smoking cessation. It was likely that his single-system pulmonary LCH (PLCH) progressed to multisystem LCH despite smoking cessation. Relapse or progression may occur in cases where PLCH lesions improve after smoking cessation. Thus, close follow-up is vital.
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Histiocitose de Células de Langerhans , Abandono do Hábito de Fumar , Masculino , Humanos , Adulto , Histiocitose de Células de Langerhans/diagnóstico por imagem , Histiocitose de Células de Langerhans/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Tomografia Computadorizada por Raios X , RecidivaRESUMO
A 26-year-old Japanese woman was admitted with a 1-month history of diarrhea, a high fever for a few days, and exacerbation of dyspnea. She was treated with an antifibrotic drug and long-term oxygen therapy for Hermansky-Pudlak syndrome-related pulmonary fibrosis. New ground-glass attenuation appeared on chest computed tomography (CT), and a colon biopsy showed an inflammatory cell accumulation with a high titer of myeloperoxidase (MPO)-specific anti-neutrophil cytoplasmic antibodies (ANCA). Systemic inflammation related to MPO-ANCA titer elevation was suspected. Steroid pulse therapy and intravenous cyclophosphamide improved chest CT findings and diarrhea. Therefore, immunosuppressant treatment should be considered for systemic inflammation related to MPO-ANCA.
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Anticorpos Anticitoplasma de Neutrófilos , Síndrome de Hermanski-Pudlak , Feminino , Humanos , Adulto , Síndrome de Hermanski-Pudlak/complicações , Síndrome de Hermanski-Pudlak/diagnóstico , Peroxidase , Inflamação , DiarreiaRESUMO
Idiopathic pulmonary fibrosis is a chronic intractable lung disease, leading to respiratory failure and death. Although anti-fibrotic agents delay disease progression, they are not considered curative treatments, and alternative modalities have attracted attention. We examined the effect of human γδ T cells on collagen type I in lung fibroblasts. Collagen type I was markedly reduced in a γδ T cell number-dependent manner following treatment with γδ T cells expanded with tetrakis-pivaloxymethyl 2-(thiazole-2-ylamino) ethylidene-1,1-bisphosphonate (PTA) and interleukin-2. Collagen type I levels remained unchanged on addition of γδ T cells to the culture system through a trans-well culture membrane, suggesting that cell-cell contact is essential for reducing its levels in lung fibroblasts. Re-stimulating γδ T cells with (E)-4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP) reduced collagen type I levels without cell-cell contact, indicating the existence of HMBPP-induced soluble anti-fibrotic factors in γδ T cells. Adding anti-interferon-γ (IFN-γ)-neutralizing mAb restored collagen type I levels, demonstrating that human γδ T cell-derived IFN-γ reduces collagen type I levels. Conversely, interleukin-18 augmented γδ T cell-induced suppression of collagen type I. Therefore, human γδ T cells reduce collagen levels in lung fibroblasts via two distinct mechanisms; adoptive γδ T cell transfer is potentially a new therapeutic candidate.
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Colágeno Tipo I , Fibroblastos , Receptores de Antígenos de Linfócitos T gama-delta , Colágeno Tipo I/metabolismo , Difosfonatos/metabolismo , Difosfonatos/farmacologia , Fibroblastos/metabolismo , Humanos , Interleucina-18/metabolismo , Interleucina-2/metabolismo , Pulmão/metabolismo , Compostos Organofosforados , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , TiazóisRESUMO
A 65-year-old Japanese man with interstitial pneumonia demonstrated honeycomb lung with thickened walls on chest high-resolution computed tomography (HRCT) and predominance of neutrophils in the cell fraction of the bronchoalveolar lavage fluid. Although there were no centrilobular nodular or branching shadows on chest HRCT suggestive of diffuse panbronchiolitis, he exhibited sinusitis and had the human leukocyte antigen (HLA)-B54 antigen. With long-term macrolide therapy, the cough and sputum production markedly improved, wall thickening of the honeycomb lung on chest HRCT decreased, and the forced vital capacity increased. Confirming the presence of HLA-B54 antigen may help determine the indication for long-term macrolide therapy in interstitial pneumonia patients.
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Eritromicina , Doenças Pulmonares Intersticiais , Masculino , Humanos , Idoso , Eritromicina/farmacologia , Eritromicina/uso terapêutico , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Antígenos HLA-B , Macrolídeos , Antibacterianos/uso terapêuticoRESUMO
BACKGROUND: Anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies are myositis-specific autoantibodies that have been identified in a subset of patients with interstitial pneumonia who do not present with dermatomyositis or polymyositis. Anti-ARS antibody-positive interstitial pneumonia is commonly treated with steroids or immunosuppressive agents and is usually responsive to these therapies. Here, we present in detail a case in which respiratory failure of a patient diagnosed with anti-ARS antibody-positive interstitial pneumonia was exacerbated by treatment with steroids and immunosuppressive agents. Further examination revealed misdiagnosis of this patient and a subsequent diagnosis of autoimmune pulmonary alveolar proteinosis. CASE PRESENTATION: A 66-year-old man presented to the hospital with dyspnea on exertion, which resulted in the detection of interstitial pneumonia. Serum anti-ARS antibodies were detected; however, there were no other findings suggestive of myositis. Pulmonary alveolar proteinosis (PAP) was suspected based on the marked increase in serum KL-6 and chest computed tomography findings. The bronchoalveolar lavage revealed no milky changes in the lavage fluid. After treatment with steroids and initiation of immunosuppressive agents for anti-ARS antibody-positive interstitial pneumonia, respiratory failure and chest imaging findings showed worsening of the condition. Bronchoscopy was repeated, and milk-like alveolar lavage fluid was collected; serum anti-granulocyte macrophage colony-stimulating factor antibody was identified. Steroids and immunosuppressive agents were gradually tapered and discontinued, and the patient's condition stabilized after repeated alveolar lavage under general anesthesia. CONCLUSION: Due to similar presentation, PAP can be misdiagnosed as interstitial pneumonia. If pulmonary lesions due to interstitial pneumonia are exacerbated by immunosuppressive treatment, physicians should reconsider the diagnosis and include PAP in the differential diagnosis.
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Aminoacil-tRNA Sintetases , Doenças Autoimunes , Doenças Pulmonares Intersticiais , Proteinose Alveolar Pulmonar , Idoso , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/tratamento farmacológico , Erros de Diagnóstico , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Masculino , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/tratamento farmacológicoRESUMO
We describe a rare case of a 20-year-old Japanese man with idiopathic pulmonary hemosiderosis (IPH) recurrence in adults with childhood onset (racIPH). IPH commonly occurs in children, and data regarding racIPH are lacking. A review of the literature showed that only five cases of racIPH have been reported (including the present case) and that racIPH shows features that are intermediate between childhood- and adult-onset IPH with respect to age and a lower frequency of smoking history. We also found that the degree of anemia was usually not severe, and a favorable response to corticosteroid therapy is expected in racIPH.
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Anemia , Hemossiderose , Pneumopatias , Adulto , Criança , Hemossiderose/complicações , Hemossiderose/tratamento farmacológico , Humanos , Pneumopatias/complicações , Pneumopatias/tratamento farmacológico , Masculino , Adulto Jovem , Hemossiderose PulmonarRESUMO
PURPOSE: This trial was conducted to compare effects of continuing versus withholding single-pill combination tablets consisting of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) on perioperative hemodynamics and clinical outcomes. METHODS: Patients undergoing minor abdominal or urological surgery (n = 106) were randomly assigned to Group C, in which ARB/CCB combination tablets were continued until surgery, or Group W, in which they were withheld within 24 h of surgery. Perioperative hemodynamics and clinical outcomes were compared between the Groups. RESULTS: The incidence of hypotension during anesthesia requiring repeated treatment with vasoconstrictors was higher in Group C than Group W (p = 0.0052). Blood pressure during anesthesia was generally lower in Group C than Group W (p < 0.05) despite significantly more doses of ephedrine and phenylephrine administrated in Group C (p = 0.0246 and p = 0.0327, respectively). The incidence of postoperative hypertension did not differ between Groups (p = 0.3793). Estimated glomerular filtration rate (eGFR) on the preoperative day did not differ between Groups (p = 0.7045), while eGFR was slightly lower in Group C than Group W on the first and third postoperative days (p = 0.0400 and p = 0.0088, respectively), although clinically relevant acute kidney injury did not develop. CONCLUSIONS: Continuing ARB/CCB combination tablets preoperatively in patients undergoing minor surgery increased the incidence of hypotension during anesthesia, increased requirements of vasoconstrictors to treat hypotension, and might deteriorate postoperative renal function, albeit slightly. These results suggest that withholding ARB/CCB tablets preoperatively is preferable to continuing them. CLINICAL TRIAL REGISTRATION: This trial is registered with the Japan Registry of Clinical Trials (jRCT) at Japanese Ministry of Health, Labour, and Welfare (Trial ID: jRCT1031190027).
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Hipertensão , Hipotensão , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina , Pressão Sanguínea , Bloqueadores dos Canais de Cálcio/efeitos adversos , Quimioterapia Combinada , Humanos , Hipotensão/induzido quimicamente , Hipotensão/epidemiologia , Procedimentos Cirúrgicos Menores , Período Perioperatório , Comprimidos/farmacologia , Comprimidos/uso terapêutico , Vasoconstritores/uso terapêuticoRESUMO
Primary ciliary dyskinesia (PCD) is a genetic and congenital disease associated with an abnormal ciliary ultrastructure and function and is estimated to affect 1 in 15,000-20,000 individuals. A PCD diagnosis can be achieved by genotyping. Here, we performed whole-exome analysis for the diagnosis of PCD and described the detailed clinical characteristics of the case. A 39-year-old Japanese woman with sinusitis and bronchiectasis without situs inversus had had upper and lower respiratory symptoms since childhood and had received long-term macrolide therapy without an accurate diagnosis. A moderate deterioration of cilia function was observed by high-speed video microscopy analysis; additionally, the number of cells with moving cilia was fewer than that in patients without PCD. Electron microscopy revealed no apparent structural abnormalities. We performed whole-exome analysis and identified novel biallelic variants of SPEF2 in the homozygous state (c.1860_1861insCT). We confirmed the absence of SPEF2 protein expression in the cilia of the nasal mucosa using fluorescent immunostaining. Accordingly, she was diagnosed as having PCD with the SPEF2 variant. The present case suggests that the deterioration of cilia function is moderate, the number of respiratory cells with moving cilia might be reduced, and the respiratory condition could be severe in patients with PCD with the SPEF2 variant.
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An 88-year-old bedridden man with Alzheimer's disease developed fever and hypoxaemia. Chest radiography showed obstructive pneumonia caused by a foreign body in the airway. Examination using a flexible bronchoscope revealed a silver-crowned molar, thought to have fallen out due to root caries, at the left lower lobe branch. Removal of the foreign body was unsuccessful with grasping or basket forceps, but successful with cryoadhesion using a cryoprobe. Removal of an airway foreign body by a cryoprobe depends on the nature of the foreign body, namely its water content. Therefore, cryoprobes are not inherently suitable for removing foreign bodies of aspirated teeth, but a tooth covered with mucus for a long time after aspiration can be cryoadhered with cryoprobes. Airway foreign bodies that remain in the airway for a long time should also be considered for removal by cryoprobe, regardless of the water content of the material.
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Diagnosis of pulmonary lymphoma using small tissue samples is difficult and often requires surgical procedures; thus, a less invasive sampling method is desirable. We previously showed that pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma can be diagnosed by detecting MALT lymphoma translocation gene 1 (MALT1) translocations in bronchoalveolar lavage fluid (BALF) cells. Analysis of B-cell clonality based on immunoglobulin heavy chain (IGH) gene rearrangements was also reportedly useful for diagnosing pulmonary lymphoma. The aim of this prospective multicenter study was to evaluate the yet unknown diagnostic potential of combined detection of MALT1 translocations and clonality using BALF. We analyzed B- and T-cell clonality based on IGH and T-cell receptor (TCR) rearrangements together with MALT1 translocations using BALF of patients with clinically suspected pulmonary lymphomas. In total, 39 patients were evaluated and categorized into three groups: B-cell lymphoma, lymphoproliferative disorders, and other diseases. IGH rearrangement detection for B-cell lymphoma diagnosis exhibited sensitivity and specificity of 88.9% and 90.0%, respectively. TCR rearrangements were not observed in patients with B-cell lymphomas. The presence of IGH rearrangements together with the absence of TCR rearrangements indicated 96.0% specificity for the diagnosis of B-cell lymphoma. The sensitivity and specificity of MALT1 translocations for diagnosing MALT lymphoma were 28.6% and 100%, respectively. The combined detection of lymphocyte clonality and MALT1 translocations using BALF is suitable for screening and diagnosis of B-cell lymphomas. Analysis of specific genes such as MALT1 should improve the precision of B-cell lymphoma diagnosis.
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Líquido da Lavagem Broncoalveolar , Imunoglobulinas/química , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Linfócitos/citologia , Linfoma/diagnóstico , Linfoma/metabolismo , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Aberrações Cromossômicas , Feminino , Rearranjo Gênico , Humanos , Neoplasias Pulmonares/imunologia , Linfoma/imunologia , Linfoma de Zona Marginal Tipo Células B/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
A 60-year-old Japanese man with a history of heavy smoking came to our hospital for a detailed examination, suspecting interstitial pneumonia because of gradually increasing dyspnea on exertion over a period of one year. Chest high-resolution computed tomography revealed ground-glass shadows with emphysematous changes. Pathological analysis of samples obtained using transbronchial lung cryobiopsy revealed an accumulation of alveolar macrophages with abundant eosinophilic cytoplasm in the alveolar space. Following a multidisciplinary discussion, the patient was diagnosed with desquamative interstitial pneumonia. To our knowledge, this is the first detailed report of desquamative interstitial pneumonia diagnosed using transbronchial lung cryobiopsy.
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PURPOSE: Pneumonia is a major cause of respiratory-related hospitalization and an important prognostic factor in patients with chronic interstitial lung disease (ILD). However, the relationship between the incidence of pneumonia and human leukocyte antigen (HLA) serotype has not been fully elucidated. Therefore, this study aimed to determine if there is a relationship between HLA serotype and the incidence of pneumonia in Japanese patients with ILD. METHODS: The medical records of patients with ILD treated at any of three centers in Japan were reviewed to determine their HLA-A and HLA-B serotypes. The characteristics of patients with and without pneumonia were compared. Cox regression analysis was performed to identify risk factors for pneumonia and death in these patients. RESULTS: One hundred and forty-four patients with ILD (pneumonia group, n = 27; non-pneumonia group, n = 117) and complete HLA serology data available were included. HLA-B54 positivity was significantly more common in the pneumonia group than in the non-pneumonia group (37.0% vs. 15.4%, p = 0.010). HLA-B54 positivity was also a significant risk factor for pneumonia (hazard ratio [HR] 4.166, 95% confidence interval [CI] 1.862-9.320, p = 0.001) and death (HR 4.050, 95% CI 1.581-10.374, p = 0.004) in patients with ILD. Furthermore, HLA-B54 positivity was a significant risk factor for pneumonia (HR 3.964, 95% CI 1.392-11.090, p = 0.010) and death (HR 8.131, 95% CI 1.763-37.494, p = 0.007) in patients with idiopathic pulmonary fibrosis. CONCLUSION: HLA-B54 positivity was a significant risk factor for pneumonia and death in patients with ILD, including those with idiopathic pulmonary fibrosis.
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Antígenos HLA-B/imunologia , Doenças Pulmonares Intersticiais/complicações , Pneumonia/imunologia , Idoso , Biomarcadores/análise , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is causally related to fibrotic diseases, including idiopathic pulmonary fibrosis. The identification of Compounds that interfere with the HSP47-collagen interaction is essential for the development of relevant therapeutics. Herein, we prepared human HSP47 as a soluble fusion protein expressed in E. coli and established an assay system for HSP47 inhibitor screening. We screened a natural and synthetic Compound library established at Nagasaki University. Among 1023â Compounds, 13â exhibited inhibitory activity against human HSP47, of which three inhibited its function in a dose-dependent manner. Epigallocatechin-3-O-gallate, one of these three Compounds, is a typical polyphenol Compound derived from tea leaves. Structurally related Compounds were synthesized and examined for their activity, revealing a hydroxyl group at A-ring position 5 as important for its activity. The present findings provide valuable insight for the development of natural product-derived therapeutics for fibrotic diseases, including idiopathic pulmonary fibrosis.
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Catequina/análogos & derivados , Desenvolvimento de Medicamentos , Proteínas de Choque Térmico HSP47/antagonistas & inibidores , Fibrose Pulmonar Idiopática/tratamento farmacológico , Catequina/síntese química , Catequina/química , Catequina/farmacologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Proteínas de Choque Térmico HSP47/metabolismo , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Influenza pneumonia, which causes acute respiratory distress syndrome and multiple organ failure, has no established management protocol. Recently, corticosteroid therapy was used to treat coronavirus disease 2019 with respiratory failure; however, its effectiveness as a treatment for influenza pneumonia remains controversial. To investigate the impact of corticosteroid therapy for the early phase of severe influenza pneumonia, we compared influenza pneumonia patients with respiratory failure treated with or without corticosteroids within 7 days after hospital admission using a Japanese nationwide administrative database. The primary endpoint was the mortality rate. The secondary endpoints were duration of intensive-care unit management, invasive mechanical ventilation, and hospital stay. The inverse probability weighting method with estimated propensity scores was used to minimize the data collection bias. We included 3519 patients with influenza pneumonia with respiratory failure. Of these, 875 were treated with corticosteroids. There was no significant difference between the groups regarding 30-day and 90-day mortality, duration of intensive-care unit management, invasive mechanical ventilation, and hospital stay. However, the in-hospital mortality rate was higher in the corticosteroid group. The use of systematic corticosteroid therapy in patients with influenza pneumonia was associated with a higher in-hospital mortality rate.
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We evaluated a novel transcription-reverse transcription concerted reaction (TRC) assay that can detect influenza A and B within 15 min using nasopharyngeal swab and gargle samples obtained from patients with influenza-like illness, between January and March 2018 and between January and March 2019. Based on the combined RT-PCR and sequencing results, in the nasal swabs, the sensitivity and specificity of TRC for detecting influenza were calculated as 1.000 and 1.000, respectively. In the gargle samples, the sensitivity and specificity of TRC were 0.946 and 1.000, respectively. The TRC assay showed comparable performance to RT-PCR in the detection of influenza viruses.