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BACKGROUND: Pulmonary hypertension (PH) is defined by elevated mean pulmonary arterial pressure (MPAP), and elevated pulmonary vascular resistance (PVR) reflects pulmonary vascular abnormalities. The clinical significance of non-severe PH in patients with various interstitial lung diseases (ILDs) has not been fully elucidated. We aimed to investigate the clinical significance of MPAP and PVR for mortality in patients with newly diagnosed ILD. METHODS: We retrospectively analysed consecutive patients with ILD at initial evaluations that included right heart catheterisation from 2007 to 2018. These patients were classified by MPAP and PVR using the 2022 the European Society of Cardiology (ESC)/the European Respiratory Society (ERS) guidelines for PH. The clinical significance of MPAP and PVR for mortality was analysed. RESULTS: Among 854 patients, 167 (19.6%) had MPAP>20 mm Hg. The proportion of patients with PVR>2 Wood units (WU) among those with MPAP≤20 mm Hg, 20
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Hipertensión Pulmonar , Enfermedades Pulmonares Intersticiales , Humanos , Arteria Pulmonar , Estudios Retrospectivos , Resistencia Vascular/fisiología , Enfermedades Pulmonares Intersticiales/diagnóstico , Pulmón , Hipertensión Pulmonar/diagnósticoRESUMEN
BACKGROUND AND OBJECTIVE: The relative effectiveness of initial non-invasive respiratory strategies for acute respiratory failure using continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC) is unclear. METHODS: We conducted a multicenter, open-label, parallel-group randomized controlled trial to compare the efficacy of CPAP and HFNC on reducing the risk of meeting the prespecified criteria for intubation and improving clinical outcomes of acute hypoxemic respiratory failure. The primary endpoint was the time taken to meet the prespecified criteria for intubation within 28 days. RESULTS: Eighty-five patients were randomly assigned to the CPAP or HFNC group. Eleven (28.9%) in the CPAP group and twenty (42.6%) in the HFNC group met the criteria for intubation within 28 days. Compared with HFNC, CPAP reduced the risk of meeting the intubation criteria (hazard ratio [HR], 0.327; 95% CI, 0.148-0.724; p = 0.006). There were no significant between-group differences in the intubation rates, in-hospital and 28-day mortality rates, ventilator-free days, duration of the need for respiratory support, or duration of hospitalization for respiratory illness. Pulmonary oxygenation was significantly better in the CPAP group, with significantly lower pH and higher partial pressure of carbon dioxide, but there were no differences in the respiratory rate between groups. CPAP and HFNC were associated with few possibly causal adverse events. CONCLUSION: CPAP is more effective than HFNC at reducing the risk of meeting the intubation criteria in patients with acute hypoxemic respiratory failure.
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Presión de las Vías Aéreas Positiva Contínua , Insuficiencia Respiratoria , Humanos , Presión de las Vías Aéreas Positiva Contínua/efectos adversos , Cánula , Terapia por Inhalación de Oxígeno , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/etiología , OxígenoRESUMEN
BACKGROUND AND OBJECTIVE: Reference values of physical activity to interpret longitudinal changes are not available in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to define the minimal clinical important difference (MCID) of longitudinal changes in physical activity in patients with IPF. METHODS: Using accelerometry, physical activity (steps per day) was measured and compared at baseline and 6-months follow-up in patients with IPF. We calculated MCID of daily step count using multiple anchor-based and distribution-based methods. Forced vital capacity and 6-minute walk distance were applied as anchors in anchor-based methods. Effect size and standard error of measurement were used to calculate MCID in distribution-based methods. RESULTS: One-hundred and five patients were enrolled in the study (mean age: 68.5 ± 7.5 years). Step count significantly decreased from baseline to 6-months follow-up (-461 ± 2402, p = .031). MCID calculated by anchor-based and distribution-based methods ranged from 570-1358 steps. CONCLUSION: Daily step count significantly declined over 6-months in patients with IPF. MCID calculated by multiple anchor-based and distribution-based methods was 570 to 1358 steps/day. These findings contribute to interpretation of the longitudinal changes of physical activity that will assist its use as a clinical and research outcome in patients with IPF.
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Fibrosis Pulmonar Idiopática , Diferencia Mínima Clínicamente Importante , Humanos , Persona de Mediana Edad , Anciano , Ejercicio Físico , Caminata , AcelerometríaRESUMEN
BACKGROUND AND OBJECTIVE: The development of clinically progressive fibrosis complicates a wide array of interstitial lung diseases (ILDs). However, there are limited data regarding its prevalence and prognosis. METHODS: We analysed consecutive patients seen for initial evaluation of a fibrosing form of ILD (FILD). Patients were evaluated for evidence of progressive fibrosis over the first 24 months of follow-up. We defined a progressive phenotype as the presence of at least one of the following: a relative decline in forced vital capacity (FVC) of ≥10%; a relative decline in FVC of ≥5%-<10% with a relative decline in diffusing capacity of the lung for carbon monoxide of ≥15%, increased fibrosis on HRCT or progressive symptoms. RESULTS: Eight hundred and forty-four patients (397 with idiopathic pulmonary fibrosis [IPF] and 447 non-IPF FILD) made up the final analysis cohort. Three hundred and fifty-five patients (42.1%) met the progressive phenotype criteria (59.4% of IPF patients and 26.6% of non-IPF FILD patients, p <0.01). In both IPF and non-IPF FILD, transplantation-free survival differed between patients with a progressive phenotype and those without (p <0.01). Multivariable analysis showed that a progressive phenotype was an independent predictor of transplantation-free survival (hazard ratio [HR]: 3.36, 95% CI: 2.68-4.23, p <0.01). Transplantation-free survival did not differ between non-IPF FILD with a progressive phenotype and IPF (HR: 1.12, 95% CI: 0.85-1.48, p = 0.42). CONCLUSION: Over one-fourth of non-IPF FILD patients develop a progressive phenotype compared to approximately 60% of IPF patients. The survival of non-IPF FILD patients with a progressive phenotype is similar to IPF.
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Fibrosis Pulmonar Idiopática , Enfermedades Pulmonares Intersticiales , Progresión de la Enfermedad , Fibrosis , Humanos , Fibrosis Pulmonar Idiopática/epidemiología , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/epidemiología , Fenotipo , Prevalencia , Pronóstico , Capacidad VitalRESUMEN
INTRODUCTION: Monoclonal antibody therapy has been reported to be highly effective for preventing hospitalisation and severe cases in patients with Coronavirus Disease 2019 (COVID-19). However, since the drug is not readily available, it is important to rapidly and appropriately identify high-risk patients who can benefit most from therapy. Therefore, we designed a risk scoring system to identify at-risk COVID-19 patients in our region during the largest surge of COVID-19, from July to September 2021. METHODS: According to the risk scores, confirmed COVID-19 patients were introduced to receive REGN-CoV-2 to our hospital by regional health centre from 18th August (Term 3). The primary outcome was the comparison of the number of hospitalisation and severe condition with other periods, the 4th wave (Term 1) and the early part of the 5th wave (Term 2) in Japan. RESULTS: During Term 3, 115 patients were stratified with the scoring system and administered REGN-COV-2. The number of hospitalisation vs severe cases were 60 (5.2%) vs 14 (1.2%), 8 (1.5%) vs 3 (0.6%) and 21 (1.2%) vs 2 (0.1%), in term 1, 2 and 3, respectively. Among those aged <60 years, compared with term 1, the relative risk of hospitalisation and severe condition were 0.25 (95% CI: 0.12-0.53) and 0.10 (95% CI: 0.01-0.80), respectively, in term 3. Drug adverse events were fever (3: 2.6%), headache (1: 0.9%) and neck rash (1: 0.9%), all events were resolved within 24 h wth no serious adverse event. CONCLUSIONS: The administration of monoclonal antibody therapy using a risk scoring system significantly reduced the number of hospitalisation and disease severity of COVID-19 without any serious adverse events and avoided regional medical collapse.
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COVID-19 , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Anticuerpos Neutralizantes , Combinación de Medicamentos , Humanos , Factores de Riesgo , SARS-CoV-2RESUMEN
BACKGROUND AND AIM OF THE STUDY: To assess the validity and long-term outcomes of direct bilateral axillary arterial cannulation for acute type A aortic dissection. METHODS: Between 2003 and 2020, 208 consecutive patients with acute type A aortic dissection underwent emergency surgical repair. Cardiopulmonary bypass was attempted to establish direct bilateral axillary arterial cannulation and bicaval drainage. Antegrade selective cerebral perfusion was established by axillary perfusion and direct cannulation of the left common carotid artery. RESULTS: Ascending aortic, partial arch, and extended total aortic arch replacement were performed in 50 (24.0%), 7 (3.4%), and 151 (72.6%) patients, respectively. Aortic root surgery and coronary artery bypass grafting were performed concomitantly in 23 and seven patients, respectively. Cardiopulmonary bypass was attempted only through bilateral axillary cannulation in all patients but was successful in 13 (6.3%) patients without bilateral axillary cannulation. No postoperative complications occurred related to this technique. There were seven hospital deaths (early mortality rate, 3.4%). Five patients had postoperative reoperation for bleeding, and nine (4.3%) were transferred to other hospitals due to postoperative permanent cerebral infarction, particularly two with arm ischemia. The 10-year survival rate of patients who underwent emergency surgical repair with this technique was 71.4%. CONCLUSIONS: Direct bilateral axillary arterial cannulation followed by selective cerebral perfusion was successful in 93.7% of patients and this may be an optimal solution for providing stable outcomes after emergency surgery for acute type A aortic dissection. However, we experienced two complications of arm ischemia, attention should be paid to potential arm ischemia.
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Disección Aórtica , Arteria Axilar , Humanos , Resultado del Tratamiento , Disección Aórtica/cirugía , Cateterismo , Aorta/cirugía , Puente Cardiopulmonar/métodosRESUMEN
BACKGROUND AND AIMS: The optimal procedure for reconstructing the dissected aortic stump for acute type A dissection remains controversial. We routinely used the intimal-protected adventitial inversion technique (iPAIT), a modified adventitial inversion technique, to protect the fragile intima by inserting a graft and assessed the safety and efficacy of this technique. METHODS: Between August 2008 and April 2020, 146 consecutive patients with acute type A dissections underwent thoracic aortic surgery in our hospital. Extended total aortic arch replacement was performed in 119 patients (81.5%). Sixty-nine patients underwent treatment for distal aortic anastomosis with the iPAIT. To compare the iPAIT to a historical control, we assessed 69 iPAIT patients and 25 patients who underwent total arch replacement using gelatin-resorcinol-formaldehyde (GRF) glue. RESULTS: Hospital mortality was 2.9% in the iPAIT group and 8.0% in the GRF group. Perioperative characteristics were similar between the two groups. However, postoperative computed tomography revealed that the obliteration rate was significantly higher in the iPAIT group (60/66, 90.9%) than in the GRF group (15/23, 65.2%) (p = .01), not including the patients who had died or developed severe renal dysfunction. The 8-year aortic event-free survival rate in the iPAIT group (81.3%) was significantly higher than that in the GRF group (47.4%). CONCLUSIONS: The use of this technique for acute type A dissections resulted in a low mortality rate and demonstrated promising midterm survival and may accelerate the obliteration of a patent false lumen and prevent late aortic events.
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Aneurisma de la Aorta Torácica , Disección Aórtica , Enfermedad Aguda , Anastomosis Quirúrgica/métodos , Disección Aórtica/etiología , Aorta/cirugía , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/etiología , Grosor Intima-Media Carotídeo , Humanos , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/métodosRESUMEN
BACKGROUND: Although physical activity is associated with mortality in patients with idiopathic pulmonary fibrosis (IPF), reference values to interpret levels of physical activity are lacking. OBJECTIVES: This study aimed to investigate the prognostic significance of physical activity assessed by step count and its cutoff points for all-cause mortality. METHODS: We measured physical activity (steps per day) using an accelerometer in patients with IPF at the time of diagnosis. Relationships among physical activity and mortality, as well as cutoff points of daily step count to predict all-cause mortality were examined. RESULTS: Eighty-seven patients (73 males) were enrolled. Forty-four patients (50.1%) died during the follow-up (median 54 months). In analysis adjusting for Gender-Age-Physiology stage and 6-min walk distance, daily step count was an independent predictor of all-cause mortality (hazard ratio (HR) = 0.820, 95% confidence interval (CI) = 0.694-0.968, p = 0.019). The optimal cutoff point (receiving operating characteristic analysis) for 1-year mortality was 3,473 steps per day (sensitivity = 0.818 and specificity = 0.724). Mortality was significantly lower in patients with a daily step count exceeding 3,473 steps than in those whose count was 3,473 or less (HR = 0.395, 95% CI = 0.218-0.715, p = 0.002). CONCLUSIONS: Step count, an easily interpretable measurement, was a significant predictor of all-cause mortality in patients with IPF. At the time of diagnosis, a count that exceeded the cutoff point of 3,473 steps/day more than halved mortality. These findings highlight the importance of assessing physical activity in this patient population.
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Fibrosis Pulmonar Idiopática , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Masculino , Pronóstico , Modelos de Riesgos Proporcionales , Caminata/fisiologíaRESUMEN
BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) is a severe complication of idiopathic pulmonary fibrosis (AE-IPF). In 2016, an international working group revised its definition and diagnostic criteria; however, few studies have assessed the frequency and prognosis of AE in patients with other fibrotic interstitial lung diseases (FILD). METHODS: We used data from 1019 consecutive interstitial lung disease (ILD) patients initially evaluated between January 2008 and July 2015. All subject diagnoses were made by multidisciplinary discussion in December 2018. ILD was categorized as IPF (n = 462) and other FILD which included non-specific interstitial pneumonia (n = 22), chronic hypersensitivity pneumonitis (n = 29), connective tissue disease-associated ILD (n = 205) and unclassifiable ILD (n = 209). Using the 2016 definition of AE-IPF, we identified all subjects with an AE. RESULTS: During the observational period, 193 patients experienced a first AE (AE-FILD n = 69, AE-IPF n = 124). The time to first AE was significantly longer in FILD than IPF (log-rank test, P < 0.001). After adjusting for potentially influential confounders, FILD remained a significant predictor of longer time to first AE compared with IPF (hazard ratio: 0.453; 95% CI: 0.317-0.647, P = 0.006). In a multivariate Cox proportional analysis, baseline disease severity was closely associated with the incidence of AE-ILD. Even after adjustment for other clinical variables, AE had a negative impact on overall survival. AE-FILD and AE-IPF showed similar poor short-term outcomes. CONCLUSION: All forms of ILD are at risk of AE and have a similar outcome to AE-IPF.
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Alveolitis Alérgica Extrínseca/diagnóstico , Fibrosis Pulmonar Idiopática , Enfermedades Pulmonares Intersticiales/diagnóstico , Fibrosis Pulmonar/clasificación , Brote de los Síntomas , Diagnóstico Diferencial , Femenino , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/epidemiología , Fibrosis Pulmonar Idiopática/fisiopatología , Japón/epidemiología , Masculino , Persona de Mediana Edad , Pronóstico , Medición de Riesgo , Índice de Severidad de la Enfermedad , Terminología como AsuntoRESUMEN
BACKGROUND: Patients with fibrotic interstitial lung disease (FILD) often experience gas exchange abnormalities and ventilatory limitations, resulting in reduced exercise capacity. High-flow nasal cannula (HFNC) oxygen therapy is a novel treatment, whose physiological beneficial effects have been demonstrated in various clinical settings. We hypothesized that HFNC oxygen therapy might be superior to conventional oxygen therapy for improving exercise capacity in FILD patients. METHODS: We performed a prospective randomized controlled crossover trial with a high-intensity constant work-rate endurance test (CWRET) using HFNC (50 L/min, FiO2 0.5) and a venturi mask (VM) (15 L/min, FiO2 0.5) for oxygen delivery in FILD patients. The primary outcome variable was endurance time. The secondary outcome variables were SpO2, heart rate, Borg scale (dyspnea and leg fatigue), and patient's comfort. RESULTS: Seven hundred and eleven patients were screened and 20 eligible patients were randomized. All patients completed the trial. The majority of patients were good responders to VM and HFNC compared with the baseline test (VM 75%; HFNC 65%). There was no significant difference in endurance time between HFNC and VM (HFNC 6.8 [95% CI 4.3-9.3] min vs VM 7.6 [95% CI 5.0-10.1] min, p = 0.669). No significant differences were found in other secondary endpoints. Subgroup analysis with HFNC good responders revealed that HFNC significantly extended the endurance time compared with VM (VM 6.4 [95%CI 4.5-8.3] min vs HFNC 7.8 [95%CI 5.8-9.7] min, p = 0.046), while no similar effect was observed in the VM good responders. CONCLUSIONS: HFNC did not exceed the efficacy of VM on exercise capacity in FILD, but it may be beneficial if the settings match. Further large studies are needed to confirm these findings. TRIAL REGISTRATION: UMIN-CTR: UMIN000021901.
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Tolerancia al Ejercicio , Enfermedades Pulmonares Intersticiales/fisiopatología , Enfermedades Pulmonares Intersticiales/terapia , Terapia por Inhalación de Oxígeno/métodos , Fibrosis Pulmonar/fisiopatología , Fibrosis Pulmonar/terapia , Anciano , Anciano de 80 o más Años , Cánula , Estudios Cruzados , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/complicaciones , Masculino , Persona de Mediana Edad , Prueba de Estudio Conceptual , Estudios Prospectivos , Fibrosis Pulmonar/complicacionesRESUMEN
BACKGROUND AND OBJECTIVE: Drug-induced lung injury (DLI) can result from a vast number of agents, and sometimes presents findings similar to those of acute respiratory distress syndrome (ARDS). Previous studies have reported that circulating levels of soluble thrombomodulin (TM) reflect endothelial injuries, which play key roles in the development of ARDS. We hypothesized that endothelial injuries are an important aspect of pathogenesis in severe DLI. The primary aim of this study was to examine the associations between soluble TM and disease severity in DLI patients. METHODS: Of the 2580 patients who underwent a bronchoalveolar lavage (BAL) procedure at Tosei General Hospital between May 2007 and February 2015, we retrospectively analysed the data of 68 DLI patients. Soluble TM in plasma and BAL fluid (BALF), and other biomarkers were included in our analysis. RESULTS: At the time of diagnosis, 39 patients (57%) had respiratory failure (partial pressure of oxygen/inspiratory oxygen fraction ratio, PaO2 /FiO2 ratio < 300). There was a significant negative linear correlation between the PaO2 /FiO2 ratio and soluble TM in BALF (r = -0.448, P < 0.001). In a stepwise multiple regression analysis, soluble TM in BALF and surfactant protein D (SP-D) were the only independent determinants of the PaO2 /FiO2 ratio. Additionally, in a multivariate logistic regression model, soluble TM in BALF (adjusted OR (aOR): 7.48, 95% CI: 1.60-34.98) and SP-D (aOR: 5.31, 95% CI: 1.40-20.15) was an independent predictor of respiratory failure (PaO2 /FiO2 ratio < 300). CONCLUSION: Soluble TM in BALF is an independent predictor of severe DLI. These findings underscore the importance of pulmonary endothelial injuries in the pathogenesis of severe DLI.
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Líquido del Lavado Bronquioalveolar/química , Lesión Pulmonar/diagnóstico , Trombomodulina/metabolismo , Adulto , Anciano , Biomarcadores/metabolismo , Lavado Broncoalveolar/métodos , Femenino , Humanos , Lesión Pulmonar/inducido químicamente , Masculino , Persona de Mediana Edad , Estudios RetrospectivosAsunto(s)
Alveolitis Alérgica Extrínseca/clasificación , Alveolitis Alérgica Extrínseca/diagnóstico , Técnicas de Diagnóstico del Sistema Respiratorio/normas , Fibrosis Pulmonar Idiopática/clasificación , Fibrosis Pulmonar Idiopática/diagnóstico , Guías de Práctica Clínica como Asunto , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Our previous animal and preliminary human studies indicated that bronchoscopy-guided cooled radiofrequency ablation (RFA) for the lung is a safe and feasible procedure without major complications. OBJECTIVES: The present study was performed to evaluate the safety, effectiveness and feasibility of computed tomography (CT)-guided bronchoscopy cooled RFA in patients with medically inoperable non-small-cell lung cancer (NSCLC). METHODS: Patients with pathologically diagnosed NSCLC, who had no lymph node involvement or distant metastases (T1-2aN0M0) but were not surgical candidates because of comorbidities (e.g., synchronous multiple nodules, advanced age, cardiovascular disease, poor pulmonary function, etc.) were enrolled in the present study. The diagnosis and location between the nearest bronchus and target tumor were made by CT-guided bronchoscopy before the treatment. A total of 28 bronchoscopy-guided cooled RFA procedures were performed in 20 patients. After treatment, serial CT imaging was performed as follow-up. RESULTS: Eleven lesions showed significant reductions in tumor size and 8 lesions showed stability, resulting in a local control rate of 82.6%. The median progression-free survival was 35 months (95% confidence interval: 22-45 months), and the 5-year overall survival was 61.5% (95% confidence interval: 36-87%). Three patients developed an acute ablation-related reaction (fever, chest pain) and required hospitalization but improved with conservative treatment. There were no other adverse events in the present study. CONCLUSIONS: CT-guided bronchoscopy cooled RFA is applicable for only highly selected subjects; however, our trial may be an alternative strategy, especially for disease local control in medically inoperable patients with stage I NSCLC.
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Adenocarcinoma/cirugía , Broncoscopía/métodos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Escamosas/cirugía , Ablación por Catéter/métodos , Neoplasias Pulmonares/cirugía , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Estudios de Factibilidad , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Cirugía Asistida por Computador/métodos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: The presence of EGFR (epidermal growth factor receptor) mutations is a robust predictor of EGFR tyrosine kinase inhibitor (TKI) responsiveness. Predictors of EGFR-TKI responsiveness in EGFR-mutant non-small cell lung cancer (NSCLC) patients, however, have not been well investigated. The purpose of this study is to examine predictors of EGFR-TKI responsiveness in EGFR-mutant NSCLC patients. PATIENTS AND METHODS: Seventy EGFR-mutant NSCLC patients who received EGFR-TKIs in our institution between April 2007 and March 2013 were analyzed retrospectively. RESULTS: The objective response rate was 50.0% (95% confidence interval, CI, 38.6-61.4%) and the disease control rate was 91.4% (95% CI, 82.5-96.0%). The median progression-free survival (PFS) and overall survival were 9.0 (95% CI, 3.92-14.08) and 20.8 months (95% CI, 14.56-27.04), respectively. In multivariate analysis, adenocarcinoma (hazard ratio, HR, 12.25; 95% CI, 37.7-41.10; p < 0.001) and major mutations (deletions in exon 19 and L858R point mutation in exon 21; HR, 2.46; 95% CI, 1.14-5.28; p = 0.022) were significant predictors of longer PFS. CONCLUSION: Major mutations and adenocarcinoma histology were independent predictors of better treatment outcome in EGFR-mutant NSCLC patients who received EGFR-TKIs. Further well-controlled prospective studies are warranted to confirm our findings.
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Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Quinazolinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Análisis Mutacional de ADN , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Clorhidrato de Erlotinib , Femenino , Gefitinib , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación Missense , Modelos de Riesgos Proporcionales , Quinazolinas/farmacología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: The mortality of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is high. Anticoagulation therapy (recombinant human soluble thrombomodulin (rhTM)) is recognized as a potential new strategy for treating disseminated intravascular coagulation in Japan. This preliminary study was to evaluate whether the coagulation factors increase or decrease in AE-IPF-patients, and whether the additional administration of rhTM for AE-IPF-patients has any beneficial effects on inflammatory mediators and activated coagulation. METHODS: We retrospectively compared the clinical data of AE-IPF-patients, idiopathic pulmonary fibrosis (IPF) with pneumonia-patients and slowly progressive IPF-patients. As a subsequent study, AE-IPF-patients were prospectively treated with a bolus of rhTM intravenously for six days under mechanical ventilation. We historically investigated the improvement of the serial clinical data in both oxygenation and intravascular coagulation disturbance between treated AE-IPF-patients and untreated AE-IPF-patients. RESULTS: Eleven AE-IPF, 21 IPF with pneumonia and 16 slowly progressive IPF-patients were enrolled, and the coagulatory levels of the AE-IPF-patients were found to be significantly higher than in the other patients. In 20 treated AE-IPF-patients, the 28-day mortality and in-hospital mortality were 35% and 45%, respectively. The levels of oxygenation rapidly increased on day 1 and continued to improve until day 7 in the survival AE-IPF-patients. The thrombin-antithrombin complex levels and inflammatory cytokine levels in the survivors on day 7 were significantly different from those observed in the nonsurvivors. CONCLUSION: AE-IPF-patients were found to have significantly higher levels of coagulation. The rhTM administration in the surviving AE-IPF-patients led to significant differences in the oxygenation and intravascular coagulation disturbance.
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Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Trombomodulina/uso terapéutico , Enfermedad Aguda , Anciano , Proteína C-Reactiva/análisis , Coagulación Intravascular Diseminada/tratamiento farmacológico , Coagulación Intravascular Diseminada/etiología , Femenino , Humanos , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/mortalidad , L-Lactato Deshidrogenasa/sangre , Recuento de Leucocitos , Masculino , Estudios Prospectivos , Proteínas Recombinantes , Estudios RetrospectivosRESUMEN
BACKGROUND: Little is known about the annual change in Krebs von Lungen-6 (KL-6) and its correlation with forced vital capacity (FVC) in limited cutaneous systemic sclerosis-associated interstitial lung disease (lcSSc-ILD). We aimed to clarify the correlation during the clinical course. METHODS: We retrospectively reviewed data from consecutive patients with lcSSc-ILD. We measured FVC and KL-6 annually and calculated their annual changes using the difference in absolute values. Decline in FVC was defined as annual decline in FVC ≥5 %. RESULTS: Thirty-eight patients with SSc-ILD were included. The median age was 62 years and 58 % were female. The median FVC was 87.3 % and the median KL-6 was 1629 U/ml. The median observation period was 55.2 months and the annual changes in FVC and KL-6 were evaluated 151 times simultaneously. The annual change in KL-6 had a significant negative correlation with that in FVC in the first year from the initial evaluation (from the baseline to one-year follow-up) (r = -0.819, p < 0.01), but not after the first year. In the multivariable analysis adjusted by age, sex, and FVC at each year, the annual change of KL-6 (per 100 U/ml) was significantly associated with decline in FVC in the first year (odds ratio: 3.03, 95 % confidence interval: 1.21-7.59, p = 0.02), but not after the first year. CONCLUSIONS: Only in the first year from the initial evaluation, there was negative correlation between the annual change in FVC and that in KL-6 and the annual elevation in KL-6 was associated with decline in FVC in patients with lcSSc-ILD.
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Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Esclerodermia Sistémica/complicaciones , Mucina-1 , Enfermedades Pulmonares Intersticiales/complicaciones , Progresión de la EnfermedadRESUMEN
Background: Coronavirus disease 2019 (COVID-19) features a hypercoagulable state, but therapeutic anticoagulation effectiveness varies with disease severity. We aimed to evaluate the dynamics of the coagulation profile and its association with COVID-19 severity, outcomes, and biomarker trajectories. Methods: This multicenter, prospective, observational study included patients with COVID-19 requiring respiratory support. Rotational thromboelastometry findings were evaluated for coagulation and fibrinolysis status. Hypercoagulable status was defined as supranormal range of maximum clot elasticity in an external pathway. Longitudinal laboratory parameters were collected to characterize the coagulation phenotype. Results: Of 166 patients, 90 (54%) were severely ill at inclusion (invasive mechanical ventilation, 84; extracorporeal membrane oxygenation, 6). Higher maximum elasticity (P=0.02) and lower maximum lysis in the external pathway (P=0.03) were observed in severely ill patients compared with the corresponding values in patients on non-invasive oxygen supplementation. Hypercoagulability components correlated with platelet and fibrinogen levels. Hypercoagulable phenotype was associated with favorable outcomes in severely ill patients, while normocoagulable phenotype was not (median time to recovery, 15 days vs. 27 days, P=0.002), but no significant association was observed in moderately ill patients. In patients with severe COVID-19, lower initial C3, minimum C3, CH50, and greater changes in CH50 were associated with the normocoagulable phenotype. Changes in complement components correlated with dynamics of coagulation markers, hematocrit, and alveolar injury markers. Conclusions: While hypercoagulable states become more evident with increasing severity of respiratory disease in patients with COVID-19, normocoagulable phenotype is associated with triggered by alternative pathway activation and poor outcomes.
Asunto(s)
COVID-19 , Trombofilia , Humanos , Estudios Prospectivos , Trombofilia/etiología , Coagulación Sanguínea , FenotipoRESUMEN
BACKGROUND: Therapeutic strategies in patients with interstitial pneumonia with autoimmune features (IPAF) and histological usual interstitial pneumonia (UIP) pattern (IPAF-UIP) have not been thoroughly evaluated. We compared the therapeutic efficacy of anti-fibrotic therapy with that of immunosuppressive treatment for patients with IPAF-UIP. METHODS: In this retrospective case series, we identified consecutive IPAF-UIP patients treated with anti-fibrotic therapy or immunosuppressive therapy. Clinical characteristics, one-year treatment response, acute exacerbation, and survival were studied. We performed a stratified analysis by the pathological presence or absence of inflammatory cell infiltration. RESULTS: Twenty-seven patients with anti-fibrotic therapy and 29 with immunosuppressive treatment were included. There was a significant difference in one-year forced vital capacity (FVC) change between patients with anti-fibrotic treatment (4 in 27 improved, 12 stable, and 11 worsened) and those with immunosuppressive treatment (16 in 29 improved, eight stable, and five worsened) (p = 0.006). There was also a significant difference in one-year St George's Respiratory Questionnaire (SGRQ) change between patients with anti-fibrotic therapy (2 in 27 improved, ten stable, and 15 worsened) and those with immunosuppressive treatment (14 in 29 improved, 12 stable, and worsened) (p < 0.001). There was no significant difference in survival between the groups (p = 0.32). However, in the subgroup with histological inflammatory cell infiltration, survival was significantly better with immunosuppressive therapy (p = 0.02). CONCLUSION: In IPAF-UIP, immunosuppressive therapy seemed to be superior to anti-fibrotic treatment in terms of therapeutic response, and provided better outcomes in the histological inflammatory subgroup. Further prospective studies are needed to clarify the therapeutic strategy in IPAF-UIP.