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1.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(4): 362-368, 2020 Apr 12.
Artigo em Chinês | MEDLINE | ID: mdl-32294819

RESUMO

Objective: To investigate the clinical features and prognosis of interstitial lung disease patients with positive anti-neutrophil cytoplasmic antibody. Methods: The patients with interstitial lung disease who visited Peking Union Medical College Hospital from March 2006 to March 2016 were divided into three groups: interstitial lung disease with ANCA-positive(ANCA-ILD), connective tissue disease associated interstitial lung disease and interstitial pneumonia with autoimmune features (CTD-ILD/IPAF) and idiopathic interstitial pneumonia (IIP). The three groups were analyzed in terms of clinical manifestations, serology, lung function, imaging, survival and recurrence. Results: Two hundred and seventy four patients were enrolled and 38 (14%) were ANCA-positive of whom 16 were male and 22 were female. The age of 38 ANCA-positive patients was (59±10) years and the follow-up time was (52±31) months. Seven among the 38 ANCA-positive patients died and the death rate is 18.42%. The ANCA-positive patients with interstitial lung disease have higher onset age (ANCA-ILD:59±10,CTD-ILD/IPAF:52±10,IIP:53±11,H=19.29, P<0.001), lower hemoglobin (ANCA-ILD: 129±21, CTD-ILD/IPAF: 138±15, IIP: 140±19, H=8.17, P=0.017), higher erythrocyte sedimentation rate (ANCA-ILD:45±35, CTD-ILD/IPAF:26±24,IIP:19±22,H=19.73, P<0.001), lower lung function improvement rate after treatment (ANCA-ILD:31%,CTD-ILD/IPAF:59%,IIP: 39%,χ(2)=11.74,P=0.003), lower absorption rate of CT lesion (ANCA-ILD:61%,CTD-ILD/IPAF:82%,IIP:67%, χ(2)=9.23,P=0.010) and higher death rate(ANCA-ILD:18%,CTD-ILD/IPAF:6%,IIP:12%, χ(2)=7.16,P=0.028). Conclusions: There are significant differences in clinical characteristics between ANCA-positive patients and other types of pulmonary interstitial disease. And both the treatment effect and the prognosis is poor for the ANCA-positive patients.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/sangue , Doenças do Tecido Conjuntivo/diagnóstico , Pneumonias Intersticiais Idiopáticas/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Biomarcadores/sangue , Doenças do Tecido Conjuntivo/sangue , Doenças do Tecido Conjuntivo/imunologia , Doenças do Tecido Conjuntivo/mortalidade , Feminino , Humanos , Pneumonias Intersticiais Idiopáticas/sangue , Pneumonias Intersticiais Idiopáticas/imunologia , Pneumonias Intersticiais Idiopáticas/mortalidade , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/mortalidade , Masculino , Prognóstico , Tomografia Computadorizada por Raios X
2.
Medicine (Baltimore) ; 99(16): e19493, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32311922

RESUMO

BACKGROUND: Past investigations showed inconsistent results for diagnostic and prognostic predictive values of Krebs von den Lungen-6 (KL-6) for interstitial lung disease (ILD). METHODS: Web of Science and PubMed were systematically searched on for articles exploring the association of KL-6 and ILDs published between September 1993 and March 2019. For comparisons between-groups, the standard mean difference and 95% confidence intervals (CIs) were computed as the effect sizes. For diagnostic studies, a summary of sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and diagnostic odds ratio, which indicated the accuracy of KL-6 in the differentiation of ILDs and no ILDs, were calculated from the true positive, true negative, false positive, and false negative of each study. In addition, the summary receive-operating characteristics curve was constructed to summarize the TP and FP rates. For follow-up study, we computed hazard ratios (HRs) and 95% CIs for mortality. ILD patients showed elevated concentrations of KL-6, compared to healthy controls and patients without ILD. RESULTS: The meta-analysis showed a sensitivity (0.85 [95% CI: 0.77-0.91]) and specificity (0.97 [95% CI: 0.90-0.99]) of KL-6 for ILDs. In addition, it showed elevated baseline circulating levels of KL-6 in subsequent active ILD, compared to subsequent inactive ILD. Moreover, there was a significant association between baseline levels of circulating KL-6 and mortality of ILD (HR 2.95, 95% CI 2.45-3.55, I = 65.9%, P = .032). CONCLUSION: In conclusion, the study suggested that circulating KL-6 showed diagnostic and prognostic predictive values for ILDs.


Assuntos
Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/diagnóstico , Mucina-1/sangue , Biomarcadores/sangue , Humanos , Doenças Pulmonares Intersticiais/mortalidade , Valor Preditivo dos Testes , Prognóstico
3.
PLoS One ; 15(3): e0229997, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32163457

RESUMO

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) has a variable clinical course for which predicting prognosis is difficult. However, the role of blood biomarkers in RA-ILD is ill-defined. The aim of this study was to investigate the prognostic value of Krebs von den Lungen-6 (KL-6) levels in RA-ILD patients. The medical records of 84 patients with RA-ILD were retrospectively reviewed. Plasma KL-6 levels were measured by Nanopia KL-6 assay (SEKISUI MEDICAL, Tokyo), using latex-enhanced immunoturbidimetric assay. The median follow-up period was 61 months. Mean age was 61.4 years, 45.2% were men, 44.0% were ever-smokers, and 35.7% showed a usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography. The median KL-6 level at baseline was 741.2 U/mL (interquartile range, 439.7-1308.9 U/mL). On multivariate logistic regression analysis, a high KL-6 level (≥ 640 U/mL) was an independently associated with a UIP pattern (odds ratio [OR], 5.173; P = 0.005) with old age (OR, 1.104, P = 0.005). On multivariate Cox analysis, a high KL-6 level (≥ 685 U/mL) was an independent prognostic factor for the mortality (hazard ratio [HR], 2.984; P = 0.016) with a older age (HR, 1.061; P = 0.030), male sex (HR, 3.610; P = 0.001), lower forced vital capacity (HR, 0.957; P = 0.002), and a UIP pattern (HR, 4.034; P = 0.002). Our results suggest that high KL-6 levels might be useful as a biomarker for the presence of a UIP pattern and prognosis in patients with RA-ILD.


Assuntos
Artrite Reumatoide/patologia , Doenças Pulmonares Intersticiais/patologia , Mucina-1/sangue , Fatores Etários , Idoso , Artrite Reumatoide/complicações , Biomarcadores/sangue , Feminino , Humanos , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/patologia , Modelos Logísticos , Pulmão/fisiologia , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/mortalidade , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Capacidade Vital
4.
Ann Thorac Surg ; 109(4): 1054-1060, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31887276

RESUMO

BACKGROUND: Interstitial pneumonia is linked to lung cancer, and treatment can cause acute exacerbation. We aimed to identify predictors of severe postoperative complications in patients with lung cancer and interstitial pneumonia. METHODS: Between April 2007 and April 2017, 199 patients were diagnosed with primary lung cancer and interstitial pneumonia using high-resolution computed tomography. Multivariable logistic regression analyses were performed to identify independent predictors of severe complications (Clavien-Dindo grade IIIa or higher). RESULTS: Multivariable analyses revealed that severe complications were independently predicted by the percent diffusing capacity of the lungs for carbon monoxide (%Dlco [odds ratio 0.88; 95% confidence interval, 0.82 to 0.95; P < .001]) and surgical procedures (lobectomy, odds ratio 4.49; 95% confidence interval, 1.86 to 23.32; P = .045). Severe complications occurred in 39.2% of patients with low %Dlco (less than 40%) and in 4.2% of patients with high %Dlco (greater than 40%). The rates of severe complications were 11.5% for patients who underwent lobectomy and 9.7% for patients who underwent sublobar resection. For patients with low %Dlco, the rates of severe complications were 85.7% for those undergoing lobectomy and 23.8% for those undergoing sublobar resection (P = .009). Overall survival (OS) was significantly different between patients with low %Dlco (5-year OS 33.5%) and patients with high %Dlco (5-year OS 65.3%; P = .001). Among patients with low %Dlco, there was a significant difference in OS between patients who underwent lobectomy (5-year OS 0%) and those who underwent sublobar resection (5-year OS 49.6%; P = .029). CONCLUSIONS: Severe postoperative complications were predicted by %Dlco and surgery type. Sublobar resection might be a better option for patients with low %Dlco values (less than 40%).


Assuntos
Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/cirurgia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Doenças Pulmonares Intersticiais/mortalidade , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Capacidade de Difusão Pulmonar , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Cirurgia Torácica Vídeoassistida/efeitos adversos
5.
Rheumatology (Oxford) ; 59(1): 112-119, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31382295

RESUMO

OBJECTIVE: To clarify the incidence, risk factors, and impact of malignancy in patients with PM/DM-associated interstitial lung disease (ILD). METHODS: This study used data from 497 patients with PM/DM-associated ILD enrolled in a multicentre, retrospective and prospective cohort of incident cases. Cancer-associated myositis (CAM) was defined as malignancy diagnosed within 3 years before or after PM/DM diagnosis. Demographic and clinical information was recorded at the time of diagnosis, and data about the occurrence of mortality and malignancy was collected. RESULTS: CAM was identified in 32 patients with PM/DM-associated ILD (6.4%). Patients with CAM were older (64 vs 55 years, P < 0.001), presented with arthritis less frequently (24% vs 49%, P = 0.01), and showed a lower level of serum Krebs von den Lungen-6 (687 vs 820 IU/l, P = 0.03) than those without CAM. The distribution of myositis-specific autoantibodies, including anti-melanoma differentiation-associated gene 5, anti-aminoacyl tRNA synthetase, and anti-transcriptional intermediary factor 1-γ antibodies, did not differ between the groups. Survival analysis demonstrated that CAM patients had a poorer survival than non-CAM patients (P = 0.006), primarily due to excess deaths by concomitant malignancy, while mortality due to ILD-related respiratory failure was similar between the groups (P = 0.51). CONCLUSION: Concomitant malignancy can occur in patients with PM/DM-associated ILD, and has significant impact on mortality. Older age, lack of arthritis, and a lower level of serum Krebs von den Lungen-6 at diagnosis are predictors of concomitant malignancy.


Assuntos
Doenças Pulmonares Intersticiais/mortalidade , Miosite/mortalidade , Neoplasias/mortalidade , Fatores Etários , Aminoacil-tRNA Sintetases/imunologia , Autoanticorpos/sangue , Feminino , Humanos , Incidência , Japão/epidemiologia , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Mucina-1/sangue , Miosite/sangue , Miosite/etiologia , Neoplasias/sangue , Neoplasias/complicações , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco
6.
Anticancer Res ; 39(10): 5725-5731, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570474

RESUMO

BACKGROUND/AIM: In lung cancer (LC) patients, pre-existing interstitial lung disease (ILD) is a risk of chemotherapy-associated acute exacerbation of ILD (AE-ILD). AE-ILD shows a diverse clinical course varying from fatal respiratory failure to asymptomatic event, and the prognostic impact is still unclear. MATERIALS AND METHODS: We retrospectively evaluated the association between the prognosis and AE-ILD in 86 LC patients with pre-existing ILD who were treated with cytotoxic chemotherapy, especially focusing on histological types of LC. RESULTS: Thirty (34.9%) patients had AE-ILD, that was significantly associated with a poor prognosis in LC patients with ILD. When analyzed by histological types, a significant association of AE-ILD with shorter survival was observed only in the small cell LC (SCLC) group, but not in the non-small cell LC group. CONCLUSION: The development of AE-ILD by cytotoxic chemotherapy is associated with poor prognosis in LC patients with ILD, especially in patients with SCLC.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Doenças Pulmonares Intersticiais/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/patologia , Masculino , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia
7.
Am J Cardiol ; 124(7): 1133-1139, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31405546

RESUMO

Interstitial lung disease (ILD) is a known risk factor for noncardiac surgery due to acute pulmonary exacerbations but its impact after cardiac surgery is not known. We examined perioperative outcomes and risk factors for long-term survival in ILD patients who underwent cardiac surgery. From January 2002 to June 2017, 294 cardiac surgery patients with a previous ILD diagnosis, including 75 patients with idiopathic pulmonary fibrosis (IPF), were identified. A comparison cohort of 1,481 non-ILD patients was selected based on a priori variables. Long-term survival was evaluated using Cox proportional hazard modeling. Median follow-up was 6.4 years. ILD patients had higher postoperative mortality, reintubation rates, longer intensive care unit stay, and higher 30-day readmission rates (all p <0.05). Kaplan-Meier estimates of survival at 1, 5, and 10 years were 89%, 62%, and 37% for the non-IPF ILD cohort, 89%, 50%, and 13% for the IPF cohort, and 95%, 82%, and 67% for the comparison cohort, respectively (overall p <0.001). These significant differences in survival persisted in our risk-adjusted survival analysis. Adjusted survival analysis identified IPF (hazard ratio 3.04) and ILD (non-IPF; hazard ratio 1.78) as significant contributors to all-cause mortality. However, there were no changes in pulmonary function tests after 48 months postprocedure. In conclusion, ILD patients who underwent cardiac surgery have increased operative mortality, reintubation rates, longer intensive care unit, and higher 30-day readmissions compared with non-ILD patients. Moreover, severity of ILD, especially in IPF, appears to be associated with shorter long-term survival. In these patients, pulmonary risk stratification and multidisciplinary team approach are crucial.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Doenças Pulmonares Intersticiais/complicações , Complicações Pós-Operatórias/epidemiologia , Adulto , Feminino , Hospitalização , Humanos , Doenças Pulmonares Intersticiais/mortalidade , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
8.
Int J Rheum Dis ; 22(9): 1741-1745, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31328423

RESUMO

BACKGROUND: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is associated with high mortality, but there is limited clinical data on AE of interstitial lung disease (ILD) in connective tissue disease-associated ILD (CTD ILD). The present study was conducted to provide prevalence and clinical features of AE, as well as various risk factors associated with mortality among AE CTD ILD patients. METHODS: Between May 2013 and April 2018, 15 patients who developed AE among 105 consecutive patients with CTD with chronic ILD were included. AE was defined using the criteria recently proposed by the IPF net, with slight modification for adaptation to CVD-IP6 (collagen vascular disease-associated interstitial pneumonia), and patients having CTD with AE met all the criteria. RESULTS: Fifteen patients with mean age of 45.8 ± 13.9 years developed AE; the most common subgroup (n = 5, 33%) was systemic sclerosis. The mean duration (months) between diagnosis of ILD and AE was 56.5 ± 38.0 with mean follow-up duration of 24 ± 18.1 months. The baseline arterial oxygen pressure (PaO2 ) was 81.7 ± 8.1 mm Hg and mean forced vital capacity (%) was 57.9 ± 8.9. Five patients requiring mechanical ventilation died. Patients with shorter duration (months) of disease between onset of ILD to AE had higher mortality, 40.4 ± 45.1 vs 64.6 ± 33.6. Those who had significantly lower baseline PaO2 (mean ± SD), 72.6 ± 3.4 vs 86.2 ± 5.3 mm Hg (P = .002) had higher mortality. CONCLUSIONS: In our study, the majority of patients with AE CTD ILD had systemic sclerosis. Patients with lower baseline PaO2 and those requiring mechanical ventilation had higher mortality.


Assuntos
Doenças do Tecido Conjuntivo/epidemiologia , Fibrose Pulmonar Idiopática/epidemiologia , Doenças Pulmonares Intersticiais/epidemiologia , Adulto , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/mortalidade , Doenças do Tecido Conjuntivo/terapia , Progressão da Doença , Feminino , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/terapia , Imunossupressores/uso terapêutico , Índia/epidemiologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/terapia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Prospectivos , Respiração Artificial , Medição de Risco , Fatores de Risco , Fatores de Tempo
9.
BMC Pulm Med ; 19(1): 120, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31272428

RESUMO

BACKGROUND: Patients with interstitial lung disease (ILD) who show features related to autoimmunity without meeting criteria for a defined connective tissue disease are categorized as interstitial pneumonia with autoimmune features (IPAF). The present study compared clinical characteristics and clinical outcomes of patients with IPAF to patients with connective tissue disease related-interstitial lung disease (CTD-ILD) and patients with idiopathic pulmonary fibrosis (IPF). METHODS: ILD patients who were consecutively enrolled in a single institution ILD cohort between 2008 and 2015 were evaluated for the study. Clinical data had been prospectively collected, while radiologic imaging and pathologic findings were re-reviewed for the present study. RESULTS: Out of 305 patients with ILD, 54 (17.7%) patients met the classification of IPAF, 175 (57.4%) patients had IPF, and 76 (24.9%) patients were diagnosed with CTD-ILD. Compared to IPF, incidences of acute exacerbations in 1,3 and 5 years were significantly less in the IPAF group (p = 0.022, p = 0.026 and p = 0.007, respectively). From multivariate analysis for mortality, age (p = 0.034, HR 1.022, 95% CI: 1.002-1.044), FVC (p < 0.001, HR 0.970, 95% CI: 0.955-0.984), ILD exacerbation (p = 0.001, HR 2.074, 95% CI: 1.366-3.148), and ILD type (p = 0.047, HR 0.436, 95% CI: 0.192-0.984 (IPAF vs IPF), respectively) showed significant association. CONCLUSIONS: Compared to the other ILD groups, IPAF showed distinct clinical characteristics. The IPAF group showed better survival and less episodes of exacerbation when compared to the IPF group.


Assuntos
Autoimunidade , Doenças do Tecido Conjuntivo/complicações , Fibrose Pulmonar Idiopática/mortalidade , Doenças Pulmonares Intersticiais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Doenças do Tecido Conjuntivo/imunologia , Bases de Dados Factuais , Feminino , Humanos , Incidência , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , República da Coreia/epidemiologia , Análise de Sobrevida , Tomografia Computadorizada por Raios X
10.
Respir Res ; 20(1): 117, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182103

RESUMO

BACKGROUND: Connective tissue disease associated with interstitial lung disease (CTD-ILD) and interstitial lung disease (ILD) alone have same pathological and imaging backgrounds. However, the differences between lung cancer development and the mortality risk between these two conditions are unclear. Incidence of primary lung cancer and all-cause mortality were studied between interstitial lung disease patients with and without connective tissue disease. METHODS: Data were extracted from the Korean National Health Insurance Research Database in 2009. A total of 12,787 cases of ILD without idiopathic pulmonary fibrosis and 2491 cases of CTD-ILD were diagnosed in 2009. The cohort was followed up until June 30, 2014. Incident lung cancers and all-cause mortality were ascertained. RESULTS: The overall incidence of lung cancer was 165.7 and 161.8 per 10,000 person-years in the CTD-ILD and ILD-only, respectively (rate ratio, 1.08; 95% confidence interval, 0.89-1.30). CTD-ILD patients in the 40-49 and 50-59 years old age groups had lung cancer incidence rates of 92.5 and 139.2, which were 2.0 and 1.7 times higher than those in the ILD-only, respectively. All-cause mortality was significantly higher in the CTD-ILD group compared to ILD-only group in patients aged 50-79 years. All-cause mortality of women in the 50-59, 60-69 and 70-79 age groups was 2.0, 1.8, and 1.4 times higher in the CTD-ILD group than in the ILD-only group, respectively. CONCLUSIONS: CTD-ILD patients aged < 60 years had a higher lung cancer incidence than ILD-only patients in the same age group. Furthermore, CTD-ILD patients aged 50-79 years had higher all-cause mortality than ILD-only patients in the same age group.


Assuntos
Doenças do Tecido Conjuntivo/mortalidade , Doenças Pulmonares Intersticiais/mortalidade , Neoplasias Pulmonares/mortalidade , Vigilância da População , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Doenças do Tecido Conjuntivo/diagnóstico , Feminino , Humanos , Estudos Longitudinais , Doenças Pulmonares Intersticiais/diagnóstico , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Vigilância da População/métodos , República da Coreia/epidemiologia , Fatores de Tempo
11.
Respir Med ; 152: 25-31, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31128606

RESUMO

INTRODUCTION: Evidence about the economic burden related to interstitial lung diseases (ILDs) and the cost-driving factors is sparse. In the knowledge that distinct comorbidities affect the clinical course of ILDs, our study investigates their impact on costs of care within first year after diagnosis. METHODS: Using claims data of individuals diagnosed with Idiopathic Interstitial Pneumonia (IIP) (n = 14 453) or sarcoidosis (n = 9106) between 2010 and 2013, we calculated total and ILD-associated mean annual per capita costs adjusted by age, sex and comorbidity burden via Generalized Linear Gamma models. Then, we assessed the cost impact of chronic obstructive pulmonary disease (COPD), diabetes, coronary artery disease, depression, gastro-esophageal reflux disease, pulmonary hypertension (PH), obstructive sleep apnoea syndrome (OSAS) and lung cancer using the model-based parameter estimates. RESULTS: Total mean annual per capita costs were €11 131 in the pooled cohort, €12 111 in IIP and €8793 in sarcoidosis, each with a 1/3 share of ILD-associated cost. Most comorbidities had a significant cost-driving effect, which was most pronounced for lung cancer in total (1.989 pooled, 2.491 sarcoidosis, 1.696 IIP) and for PH in ILD-associated costs (2.606 pooled, 2.347 IIP, 3.648 sarcoidosis). The lung-associated comorbidities COPD, PH, OSAS more strongly affected ILD-associated than total costs. CONCLUSION: Comorbidities increase the already substantial costs of care in ILDs. To support patient-centred ILD care, not only highly cost-driving conditions that are inherent with high mortality themselves require systematic management. Moreover, conditions that are more rather restricting the patient's activities of daily living should be addressed - despite a low-cost impact.


Assuntos
Comorbidade/tendências , Efeitos Psicossociais da Doença , Doenças Pulmonares Intersticiais/economia , Sarcoidose/economia , Atividades Cotidianas/psicologia , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/economia , Doença da Artéria Coronariana/epidemiologia , Depressão/economia , Depressão/epidemiologia , Diabetes Mellitus/economia , Diabetes Mellitus/epidemiologia , Feminino , Refluxo Gastroesofágico/economia , Refluxo Gastroesofágico/epidemiologia , Humanos , Hipertensão Pulmonar/economia , Hipertensão Pulmonar/epidemiologia , Revisão da Utilização de Seguros/economia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/mortalidade , Neoplasias Pulmonares/economia , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Assistência Centrada no Paciente/economia , Doença Pulmonar Obstrutiva Crônica/economia , Estudos Retrospectivos , Sarcoidose/diagnóstico , Sarcoidose/epidemiologia , Apneia Obstrutiva do Sono/economia , Apneia Obstrutiva do Sono/epidemiologia
12.
Semin Respir Crit Care Med ; 40(2): 208-226, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31137061

RESUMO

Interstitial lung disease (ILD) is a common complication of systemic sclerosis (SSc). SSc-ILD adversely impacts quality of life and is currently the leading cause of death in this multisystem disease. Identifying clinically significant SSc-ILD is critically important. Accurate staging and prognostication remain difficult; however, significant advances have been made in the last decade. Evidence supports the need to treat patients with extensive and/or progressive SSc-ILD, while only a subset of patients with limited ILD may require treatment. Research is urgently required to allow improved prediction of patients at risk of ILD progression at an early point in the disease, and ideally prior to its onset, to allow prevention. The last decade has seen the publication of landmark clinical trials for SSc-ILD. More effective strategies with less toxicity are under investigation. For those with refractory or very advanced disease, studies into disease-specific palliative approaches are in their infancy. Lung transplantation as an option for SSc-ILD remains patient- and center-specific, with data to suggest equivalent outcomes to other fibrotic lung diseases, in carefully selected cases. This review aims to provide a comprehensive overview of all key aspects of SSc-ILD.


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/terapia , Escleroderma Sistêmico/complicações , Progressão da Doença , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Imunossupressores/uso terapêutico , Transplante de Pulmão/tendências , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Rheumatology (Oxford) ; 58(11): 2031-2038, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31089697

RESUMO

OBJECTIVES: Lung involvement in RA has several manifestations and is a major cause of morbidity and mortality. The aim of this study was to characterize the different types of lung disease and response to treatment in a UK cohort of RA patients. METHODS: RA patients who had undergone high resolution CT scans of the lung were identified and scans reviewed. Demographic data, RA features, complementary exams and treatments were recorded for those with radiological evidence of lung involvement. Descriptive analysis was performed, and Mann-Whitney U and χ2 tests were used for comparison between different radiological subtypes. RESULTS: Lung disease was reported in 87 (7.7%) of 1129 RA patients, usually (97.7%) post-dating articular symptoms. Most patients had positive RF (74/84; 88.1%) and ACPA (72/82; 87.7%). Interstitial lung disease (ILD) was the most common pattern, reported in 45 (51.7%) patients. Drug-induced lung disease was reported in 2 of 64 (3.1%) patients treated with MTX. Rituximab was used in 26 (57.8%) patients with ILD, with evidence of disease improvement or stabilization in patients with non-specific interstitial pneumonia and organizing pneumonia. During lung disease follow-up (6.7 ± 4.1 years), 22 (25.3%) patients were admitted to hospital with respiratory infections, with 14 (63.6%) of them having underlying bronchiectasis. Lung disease-related mortality was estimated at 8%. CONCLUSION: ILD was the most prevalent manifestation of lung involvement in RA and was associated with higher mortality. Immunosuppressive drugs used in RA were rarely associated with lung toxicity, and rituximab demonstrated promising results for the treatment of RA-ILD.


Assuntos
Artrite Reumatoide/complicações , Doenças Pulmonares Intersticiais/etiologia , Pneumopatias/etiologia , Tomografia Computadorizada por Raios X , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/mortalidade , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Pneumopatias/mortalidade , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab/uso terapêutico , Reino Unido
14.
World J Surg ; 43(7): 1857-1866, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30937488

RESUMO

BACKGROUND: This study aimed to analyze cause-specific mortality in lung cancer patients over 80 years old undergoing surgery. METHODS: This retrospective, multi-institutional analysis included patients aged ≥ 80 years who underwent radical surgery for primary lung cancer from January 1998 to December 2015. Preoperative clinical data, surgical results, survival, and cause of death were evaluated. Competing risk analysis for cause-specific mortality was performed. RESULTS: Of the 337 patients (median age 82 years) enrolled and analyzed, 68.1% were male. There were 52 and 44 cancer-specific and non-cancer-specific deaths, respectively. On competing risk regression analysis, non-cancer-specific deaths were significantly associated with male sex (hazard ratio [HR]: 3.06, 95% confidence interval [CI]: 1.02-9.12, p = 0.046), coronary artery disease (HR: 2.49, 95% CI: 2.49 [1.14-5.47], p = 0.02), interstitial pneumonia (HR: 3.58, 95% CI: 1.73-7.40, p < 0.001), and pathological stage III (HR: 3.83, 95% CI: 1.44-10.13, p = 0.007). In contrast, cancer-specific deaths were significantly associated with limited resection (HR: 1.99, 95% CI: 1.02-3.89, p = 0.04) and pathological stage III (HR: 3.13, 95% CI: 1.44-6.80, p = 0.004). The 5-year cumulative incidences of lung cancer-specific and non-cancer-specific deaths were 18.0% and 15.9%, respectively. CONCLUSIONS: Prognostic factors for non-cancer-specific death were different from those of cancer-specific death, except for pathological stage. Each prognostic factor should be considered when deciding surgical indication and procedure and monitoring for pulmonary events during outpatient follow-up.


Assuntos
Causas de Morte , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Doenças Pulmonares Intersticiais/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Pneumonectomia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco/métodos , Fatores Sexuais
15.
Respir Med ; 150: 120-125, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30961937

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by irreversible loss of lung function and an unpredictable course of disease progression. METHODS: The safety data for patients with IPF who received placebo in 6 clinical trials were pooled to examine the categories and frequencies of serious adverse events (SAEs) in this population. RESULTS: In 1082 patients with IPF who received placebo, 673 SAEs were reported. Of these, 93 SAEs resulted in death (8.6% of patients). Respiratory-related conditions were the most frequently reported SAE (225 events, 16.33 per 100 patient-exposure years [PEY]), followed by infections and infestations (136 events, 9.87 per 100 PEY) and cardiac disorders (79 events, 5.73 per 100 PEY); these categories also had the most fatal outcomes (60, 10, and 10 deaths, respectively). The most frequently reported fatal respiratory-related SAEs were IPF and respiratory failure (38 and 11 patients, respectively), and the most frequently reported fatal infections and infestations and cardiac disorders were pneumonia (5 patients) and myocardial infarction (3 patients), respectively. CONCLUSIONS: This pooled analysis has value as a comparator for safety in future studies of IPF and provides insights in the natural evolution of both IPF and common comorbidities.


Assuntos
Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/mortalidade , Placebos/efeitos adversos , Segurança/estatística & dados numéricos , Idoso , Comorbidade , Progressão da Doença , Feminino , Cardiopatias/epidemiologia , Humanos , Fibrose Pulmonar Idiopática/epidemiologia , Fibrose Pulmonar Idiopática/fisiopatologia , Infecções/epidemiologia , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/mortalidade , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Placebos/administração & dosagem , Pneumonia/epidemiologia , Testes de Função Respiratória/métodos , Insuficiência Respiratória/epidemiologia
16.
Respir Med ; 150: 126-130, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30961938

RESUMO

BACKGROUND: The clinical characteristics, hemodynamic changes and outcomes of lung disease-associated pulmonary hypertension (LD-PH) are poorly defined. METHODS: A prospective cohort of PH patients undergoing initial hemodynamic assessment was collected, from which 51 patients with LD-PH were identified. Baseline characteristics and long-term survival were compared with 83 patients with idiopathic pulmonary arterial hypertension (iPAH). RESULTS: Mean age (±standard deviation) of LD-PH patients was 64 ±â€¯10 years, 30% were female and 78% were New York Heart Association class III-IV. The LD-PH group was older than the iPAH group (64 ±â€¯10 vs 56 ±â€¯18 years, respectively, P = 0.003) with a lower percentage of women (30% vs 70%, P = 0.007). LD-PH patients had smaller right ventricular sizes (P = 0.02) and less tricuspid regurgitation (P = 0.03) by echocardiogram, and lower mean pulmonary arterial pressures (mPAP) (P = 0.01) and pulmonary vascular resistance (PVR) (P = 0.001) at catheterization. Despite these findings, mortality was equally high in both groups (P = 0.16). 5-year survival was lower in patients with interstitial lung disease compared to those with obstructive pulmonary disease (P = 0.05). Among the LD-PH population, those with mild to moderately elevated mPAP and those with PVR <7 Wood units demonstrated significantly improved survival (P = 0.04 and P = 0.001, respectively). Vasoreactivity was not associated with improved survival (P = 0.64). A PVR ≥7 Wood units was associated with increased risk of mortality (hazard ratio (95% confidence interval), 3.59 (1.27-10.19), P = 0.02). CONCLUSIONS: Despite less severe PH and less right heart sequelae, LD-PH has an equally poor clinical outcome when compared to iPAH. A PVR ≥7 Wood units in LD-PH patients was associated with 3-fold higher mortality.


Assuntos
Hipertensão Pulmonar Primária Familiar/mortalidade , Hipertensão Pulmonar/mortalidade , Pulmão/irrigação sanguínea , Resistência Vascular/fisiologia , Adulto , Idoso , Cateterismo Cardíaco/métodos , Ecocardiografia/métodos , Hipertensão Pulmonar Primária Familiar/epidemiologia , Hipertensão Pulmonar Primária Familiar/fisiopatologia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Hemodinâmica/fisiologia , Humanos , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/fisiopatologia , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/fisiopatologia , Pneumopatias Obstrutivas/epidemiologia , Pneumopatias Obstrutivas/mortalidade , Pneumopatias Obstrutivas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Artéria Pulmonar/fisiopatologia , Análise de Sobrevida , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/epidemiologia
17.
Chin Med J (Engl) ; 132(11): 1283-1292, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31021982

RESUMO

BACKGROUNDS: Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) that develops in response to the inhalation of various antigens. The clinical pathologies are very complex and undetermined. The clinical features and outcomes of HP have not been fully elucidated. The aim of this study was to analyze the incidence, clinical features, and outcomes of HP patients and construct a simple clinical model for diagnosing chronic HP (CHP). METHODS: The cohort study included 101 patients with HP admitted to the Nanjing Drum Tower Hospital from January 2009 to December 2017. The patients were categorized into acute HP (AHP, n = 72) and CHP (n = 29) groups according to the updated international criteria. The clinical, imaging, treatment, and follow-up data were retrospectively reviewed. All patients were followed up until December 31, 2017. Statistical analysis was performed, and a clinical scoring system for CHP was constructed by SPSS 20.0 software. RESULTS: The incidence of HP was 2.4% in ILD inpatients in our center. Patients in the CHP group were older (t = -2.212, P = 0.029), had more smokers (χ = 8.428, P = 0.004), and longer duration of symptoms (t = -4.852, P < 0.001) than those in the AHP group. Weight loss, crackles, digital clubbing, and cyanosis were more common in the CHP group than those in the AHP group (χ = 5.862, P < 0.001; χ = 8.997, P = 0.003; χ = 11.939, P = 0.001; and χ = 4.025, P = 0.045, respectively). On chest high-resolution computed tomography (HRCT), reticular patterns, traction bronchiectasis, and accompanying honeycombing were more common in CHP cases than those in AHP cases (χ = 101.000, P < 0.001; χ = 32.048, P < 0.001; and χ = 36.568, P < 0.001, respectively). The clinical scoring system for CHP was established based on the clinical variables (age [A], duration of symptoms [D], smoking history [S], unidentified exposure [U], and chest HRCT [C]; ADSUC) (area under the curve 0.935, 95% confidence interval: 0.883-0.987, P < 0.001). Eleven patients (15.3%) in the AHP group developed CHP, and unidentified exposure was an independent risk factor for the progression of disease (P = 0.038). The survival of patients with CHP, smoking history, unidentified antigens and fibrosis on Chest HRCT were significantly worse (P = 0.011, P = 0.001, P = 0.005, and P = 0.011, respectively) by Kaplan-Meier analysis. Cox multivariate regression analysis revealed that unidentified exposure and total lung volume (TLC pred%) were independent prognostic predictors for HP patients (P = 0.017 and P = 0.017, respectively). CONCLUSIONS: The clinical features and outcomes of the CHP patients differ from those of the AHP patients. ADSUC is a simple and feasible clinical model for CHP. Unidentified exposure is an independent risk factor for the progression of AHP to CHP. Unidentified exposure and a low baseline TLC pred% are independent predictors for survival in HP patients.


Assuntos
Alveolite Alérgica Extrínseca/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Adulto , Idoso , Alveolite Alérgica Extrínseca/mortalidade , Alveolite Alérgica Extrínseca/fisiopatologia , China , Doença Crônica , Estudos de Coortes , Feminino , Fibrose , Humanos , Estimativa de Kaplan-Meier , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Capacidade Pulmonar Total/fisiologia
18.
Respir Med ; 150: 30-37, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30961948

RESUMO

Interstitial lung disease (ILD) is a category of diffuse parenchymal lung diseases characterized by inflammation and/or fibrosis. The best characterized ILD is idiopathic pulmonary fibrosis (IPF). Acute exacerbation of IPF is a dreaded occurrence with grim prognosis and suboptimal treatment options. There have been recent reports that acute exacerbation can occur in other ILDs (AE-ILD). Of note, some of these acute exacerbations follow lung procedures. This review summarizes the available information on AE-ILD and discusses the procedures reported to cause AE-ILD. We also discuss proposed mechanisms, risk factors, treatment and prognosis. This review should help to inform decision-making about risks versus benefits of procedures that are commonly recommended to diagnose ILD.


Assuntos
Biópsia/efeitos adversos , Fibrose Pulmonar Idiopática/etiologia , Doenças Pulmonares Intersticiais/etiologia , Idoso , Lavagem Broncoalveolar/efeitos adversos , Broncoscopia/efeitos adversos , Progressão da Doença , Feminino , Humanos , Hiperóxia/complicações , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/fisiopatologia , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Testes de Função Respiratória/métodos , Fatores de Risco , Tomografia Computadorizada por Raios X/métodos
19.
Kaohsiung J Med Sci ; 35(6): 365-372, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30913371

RESUMO

Interstitial lung disease (ILD) is a common pulmonary manifestation of connective tissue diseases (CTD). Prognostic effect of radiological usual interstitial pneumonia (UIP) pattern in CTD-associated interstitial lung disease (CTD-ILD) is unknown. This study aimed to investigate the disease progression and mortality of patients with CTD-ILD and idiopathic interstitial pneumonias (IIP) including idiopathic pulmonary fibrosis (IPF) and idiopathic nonspecific interstitial pneumonia and the prognostic impact of the radiological UIP pattern on both disease groups. The medical records of 91 patients (55 with CTD-ILD and 36 with IIP) diagnosed with ILD at pulmonary medicine department, Faculty of Medicine, Gazi University from 2004 to 2014 were retrospectively reviewed. Patients included whose baseline high-resolution computed tomography (HRCT) scans showed either a UIP or non-UIP pattern. While 67.3% (n = 37) of CTD-ILD patients possessed UIP pattern, 38.9% (n = 14) of IIP patients had UIP pattern in HRCT. Respiratory functions including the forced expiratory volume in the first second (FEV1 ), functional vital capacity (FVC), and transfer coefficient for carbon monoxide (diffusing capacity of the lung for carbon monoxide [DLCO]) of IIP group at the time of diagnosis were significantly lower than CTD-ILD group (P = .007, P = .002, and P = .019, respectively). There was no significant survival difference between CTD-ILD and IIP by using the log-rank test (P = .76). Multivariate analysis revealed that UIP pattern in HRCT (Hazard ratio: 1.85; 95% Confidence interval = 1.14-3; P = .013), annual FVC (Hazard ratio: 0.521; 95% Confidence interval = 0.32-0.84; P = .007), and annual DLCO declines (Hazard ratio: 0.943; 95% Confidence interval = 0.897-0.991; P = .02) were independent risk factors for mortality in both CTD-ILD and IIP groups. We found that UIP pattern in HRCT and annual losses in respiratory functions were the main determinants of prognosis of ILDs either idiopathic or CTD-associated.


Assuntos
Pneumonias Intersticiais Idiopáticas/fisiopatologia , Fibrose Pulmonar Idiopática/fisiopatologia , Doenças Pulmonares Intersticiais/fisiopatologia , Pulmão/fisiopatologia , Idoso , Monóxido de Carbono/metabolismo , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Pneumonias Intersticiais Idiopáticas/diagnóstico por imagem , Pneumonias Intersticiais Idiopáticas/mortalidade , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/mortalidade , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Capacidade Vital
20.
Transplant Proc ; 51(2): 372-375, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30879544

RESUMO

BACKGROUND: Patients with diffuse parenchymal lung disease (DPLD) have the poorest survival rates both before and after lung transplantation (LT). Early mortality among LT patients as a result of DLPD is estimated at 10% to 20%. The aim of the study was to assess intrahospital mortality after LT procedures for DLPD and to identify factors in the recipient, donor, intra- and postoperative periods that might improve early outcomes. METHODS: A retrospective, observational, cohort, single-hospital study was conducted. Data from 67 patients with LT patients owing to DPLD were recorded between October 2008 to June 2017 in Madrid, Spain. RESULTS: Out of 67 LT recipients with DPLD, 51 had idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP), 6 nonspecific interstitial pneumonia (NSIP), and 10 other DPLD. Intrahospital mortality took place in 13.4% of patients, with a median survival time of 34 days (interquartile range [IQR], 27.50-66). In the preoperative period, there were no differences in the recipients' demographic and hemodynamic characteristics, respiratory function, or time spent in the waiting list, except higher doses of systemic steroids in nonsurvivors (prednisone 15 vs 10 mg, P = .046). No differences were reported in the donors' characteristics (age, mechanical ventilation hours, PaO2/FiO2). In the intraoperative and postoperative periods, we found differences statistically significant in longer cold ischemia time and development of primary graft dysfunction (PGD) grade 3 in the nonsurvivor group. CONCLUSIONS: The mortality rate in our series was 13.4%, and the main risk factors for intrahospital mortality were longer cold ischemia time and greater incidence of PGD grade 3.


Assuntos
Doenças Pulmonares Intersticiais/mortalidade , Transplante de Pulmão/mortalidade , Adulto , Estudos de Coortes , Isquemia Fria/efeitos adversos , Feminino , Humanos , Incidência , Doenças Pulmonares Intersticiais/cirurgia , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/epidemiologia , Disfunção Primária do Enxerto/mortalidade , Estudos Retrospectivos , Fatores de Risco , Espanha
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