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BACKGROUND: Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS. METHODS: Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. RESULTS: The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297-311 of DIDO1, 426-440 of FOXJ2, and 607-621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case-control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS. CONCLUSIONS: Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.
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Anticuerpos , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Anticuerpos/sangre , Isquemia Encefálica/diagnóstico , Estudios de Casos y Controles , Factor de Especificidad de Desdoblamiento y Poliadenilación/inmunología , Proteínas de Unión al ADN/inmunología , Factores de Transcripción Forkhead/inmunología , Humanos , Accidente Cerebrovascular/diagnósticoRESUMEN
BACKGROUND: Noninvasive estimation of the actual systolic pulmonary artery pressure measured via right-sided heart catheterization (sPAPRHC) is vital for the management of pulmonary hypertension, including chronic thromboembolic pulmonary hypertension (CTEPH). Evaluation related to the interventricular septum (IVS) is generally performed with only visual assessment and has been rarely assessed quantitatively in the field of echocardiography. Thus, this study aimed to investigate the utility of echocardiographic IVS curvature to estimate sPAPRHC in patients with CTEPH. METHODS: Medical records of 72 patients with CTEPH were studied retrospectively. We estimated sPAPRHC using echocardiographic IVS curvature (esPAPcurv) and left ventricular eccentricity index (esPAPLVEI), and compared their ability to predict sPAPRHC with estimated sPAPRHC using tricuspid regurgitant pressure gradient (esPAPTRPG). RESULTS: IVS curvature and LVEI were significantly correlated with sPAPRHC (r = - 0.52 and r = 0.49, respectively). Moreover, the IVS curvature was effective in estimating the sPAPRHC of patients with trivial tricuspid regurgitation (r = - 0.56) and in determining patients with sPAPRHC ≥ 70 mmHg with higher sensitivity (77.0%) compared to those with esPAPTRPG and esPAPLVEI. CONCLUSION: Our results indicate that the echocardiographic IVS curvature could be a useful additional tool for estimating sPAPRHC in CTEPH patients for whom accurate estimation of sPAPRHC using tricuspid regurgitant pressure gradient is challenging.
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Ecocardiografía/métodos , Hipertensión Pulmonar/diagnóstico por imagen , Embolia Pulmonar/diagnóstico por imagen , Anciano , Femenino , Humanos , Hipertensión Pulmonar/fisiopatología , Masculino , Persona de Mediana Edad , Arteria Pulmonar/diagnóstico por imagen , Embolia Pulmonar/fisiopatología , Estudios RetrospectivosRESUMEN
Macrophages endocytose modified low-density lipoproteins (LDL) vigorously via scavenger receptor A (SR-A) to become foam cells. In the present study, we found that Sac1, a member of the Sac family of phosphoinositide phosphatases, increases the protein level of SR-A and upregulates foam cell formation. Mouse macrophages (RAW264.7) were transfected with short hairpin RNAs (shRNAs) against Sac1. Sac1 knockdown decreased cell surface SR-A levels and impaired acetylated LDL-induced foam cell formation. Transfection of Sac1-knockdown cells with shRNA-resistant flag-Sac1 effectively rescued the expression of SR-A. Glycosylation of SR-A was largely attenuated by Sac1 knockdown, but neither mRNA expression nor protein degradation of SR-A were affected. These results suggest that Sac1 maintains SR-A protein levels by modulating SR-A glycosylation.
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Células Espumosas/metabolismo , Proteínas de la Membrana/metabolismo , Fosfoinosítido Fosfatasas/metabolismo , Receptores Depuradores de Clase A/metabolismo , Animales , Lipoproteínas LDL/metabolismo , Proteínas de la Membrana/genética , Ratones , Fosfoinosítido Fosfatasas/genética , Células RAW 264.7 , ARN Mensajero , ARN Interferente Pequeño , Receptores Depuradores de Clase A/genéticaRESUMEN
The findings of this study suggest that the phosphoinositide phosphatase Sac3 maintains the protein level of scavenger receptor A (SR-A) and regulates foam cell formation. RAW264.7 macrophages were transfected with short hairpin RNAs that target Sac3. The knockdown decreased the level of the cell surface SR-A and suppressed the acetylated low density lipoprotein-induced foam cell formation. The associated regulator of PIKfyve (ArPIKfyve) is a scaffold protein that protects Sac3 from proteasome-dependent degradation. The knockdown of ArPIKfyve decreased Sac3, cell surface SR-A, and foam cell formation. The knockdown of PIKfyve had no effect on SR-A protein levels. These results suggest that the ArPIKfyve-Sac3 complex regulates SR-A protein levels independently of its effect on PIKfyve activity.
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Flavoproteínas/metabolismo , Gotas Lipídicas/metabolismo , Macrófagos/metabolismo , Fosfoinosítido Fosfatasas/metabolismo , Monoéster Fosfórico Hidrolasas/metabolismo , Receptores Depuradores/metabolismo , Animales , Membrana Celular/metabolismo , Flavoproteínas/genética , Técnicas de Silenciamiento del Gen/métodos , Humanos , Ratones , Fosfoinosítido Fosfatasas/genética , Monoéster Fosfórico Hidrolasas/genética , Células RAW 264.7 , Receptores Depuradores de Clase A/metabolismoRESUMEN
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: Currently, it is unknown whether polyglycolic acid (PGA) felt staplers can reduce the occurrence of intraoperative air leaks. We investigated whether staplers with bioabsorbable PGA felt reduced intraoperative air leakage compared to the conventional stapler in patients undergoing lung resection. Methods: From 2013 to 2021, 211 patients diagnosed with lung cancer or pulmonary metastasis underwent lung resection using only PGA felt (n=88) or conventional (n=123) staplers at Tokyo Rosai Hospital. One-to-one propensity score matching was used to compare intraoperative air leak rates, operation time, and intraoperative bleeding between the two groups. Results: The PGA felt group required more staples than the conventional stapler group. The forced expiratory volume in one second percentage of predicted in the PGA felt stapler group was lower than that in the conventional stapler group. In the PGA felt stapler group, 56.8% of patients had undergone anatomic lung resection, whereas 29.3% of patients in the conventional stapler group had undergone wedge resection. In a propensity-matched analysis of 67 pairs, the occurrence of intraoperative air leaks was significantly lower in the PGA felt stapler group than in the conventional stapler group (16.4% vs. 56.7%, P<0.001). The operation time was significantly shorter and intraoperative bleeding was significantly lower in the PGA felt stapler group than in the conventional stapler group (P=0.001 and P=0.016, respectively). Conclusions: Pulmonary resection using staplers with a PGA felt could reduce the occurrence of intraoperative air leaks among patients undergoing lung resection.
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An 87-year-old man presented with dyspnea. Computed tomography revealed progressive subpleural consolidation in the apex, reticular shadows in the lower lobes, and bilateral ground glass opacifications. He died of respiratory failure on day 3. The post-mortem examination showed exudative stage diffuse alveolar damage and pulmonary edema. Intraalveolar collagenous fibrosis and subpleural elastosis were observed in the upper lobes, accompanied by interlobular septal and pleural thickening and lung architecture remodeling in the lower lobes. He was diagnosed with acute exacerbation of pleuroparenchymal fibroelastosis with lower lobe usual interstitial pneumonia, which can be fatal.
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Biomarkers are not available for monitoring the onset and progression of coronary artery disease (CAD) in patients with obstructive sleep apnea (OSA), a major risk factor for arteriosclerotic cardiovascular diseases. This study aimed to test for correlation between circulating anti-Sorting Nexins 16 antibody (SNX16-Ab) levels, CAD history and clinical parameters of patients with OSA. Sixty-four healthy donors, 82 adults with OSA, and 96 with acute coronary syndrome (ACS) were studied. Serum samples were collected at diagnostic polysomnography in the OSA group or at the disease onset in the ACS group. Serum SNX16-Ab levels were measured by amplified luminescence proximity homogeneous assay (AlphaLISA), and correlation between SNX16-Ab levels and clinical parameters was analyzed. SNX16-Ab levels and apnea-hypopnea index (AHI) were weakly correlated. Additionally, logistic regression analyses of OSA group identified that elevated SNX16-Ab level associated with the history of CAD. Circulating SNX16-Ab could increase during CAD pathogenesis in patients with OSA. Further prospective studies are required to prove the predictive potential of SNX16-Ab level in CAD onset of patients with OSA.
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PURPOSE: Although patients with suspected obstructive sleep apnea (OSA) might suffer difficulty in falling asleep during overnight polysomnography (PSG), standard hypnotics to obtain sleep during PSG have not been established. The aim of this study was to investigate the safety and efficacy of a new hypnotic agent, suvorexant, a dual orexin receptor antagonist, for insomnia in suspected OSA patients during in-laboratory PSG. PATIENTS AND METHODS: An observational study was conducted during PSG for 149 patients with suspected OSA who had no insomnia at home. Patients with difficulty in falling asleep during PSG were optionally permitted to take single-use suvorexant. Patients with residual severe insomnia (>1 hour) after taking suvorexant were permitted to take an add-on use zolpidem. Clinical data and sleep questionnaire results were analyzed between a no insomnia group (without hypnotics) and an insomnia group (treated with suvorexant). RESULTS: Among 84 patients who experienced insomnia during PSG and required hypnotics (the insomnia group; treated with suvorexant), 44 (52.4%) achieved sufficient subjective sleep with single-use of suvorexant, while the other 40 (47.6%) required suvorexant plus zolpidem. An apnea hypopnea index (AHI) of ≥5 was observed in 144 out of 149 patients with predominantly obstructive respiratory events. Among those patients, 70.8% in the no insomnia group and 63.1% in the insomnia group had severe OSA. Regarding both subjective sleep time and morning mood, significant differences between the no insomnia group and the insomnia group were not observed. No patient taking suvorexant had an adverse event, such as delirium or falling. CONCLUSION: Single-use suvorexant seems to be a safe and effective (but mild) hypnotic agent for suspected OSA patients with insomnia during in-laboratory PSG.
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Azepinas/administración & dosificación , Azepinas/uso terapéutico , Polisomnografía/métodos , Fármacos Inductores del Sueño/administración & dosificación , Fármacos Inductores del Sueño/uso terapéutico , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/diagnóstico , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Triazoles/administración & dosificación , Triazoles/uso terapéutico , Azepinas/efectos adversos , Humanos , Fármacos Inductores del Sueño/efectos adversos , Triazoles/efectos adversosRESUMEN
STUDY OBJECTIVES: The WatchPAT is a wrist-worn portable device that creates integration data regarding peripheral arterial tone (PAT), oxyhemoglobin saturation, heart rate, and actigraphy to diagnose or screen for obstructive sleep apnea (OSA). Previous studies have demonstrated the efficacy and validity of respiratory variables measured by the WatchPAT compared to those using polysomnography (PSG). However, the effects of arterial stiffness or atherosclerosis on WatchPAT parameters remain to be elucidated. METHODS: Sixty-one consecutive patients with suspected OSA who underwent home-based testing with the WatchPAT 200, standard in-laboratory overnight polysomnography (PSG), and pulse wave velocity (PWV) as an index of arterial stiffness were studied. All PSG recordings were scored manually using the American Academy of Sleep Medicine criteria, whereas WatchPAT data were analyzed by an automatic algorithm. We evaluated how arterial stiffness affected respiratory event index data in WatchPAT (WP-AHI), because WP-AHI could be partly influenced by PAT, comparing WP-AHI and the apneahypopnea index measured by PSG (PSG-AHI) in consideration of PWV result. RESULTS: Overall, WP-AHI was moderately correlated to PSG-AHI, but WP-AHI was significantly lower than PSG-AHI (28.4 ± 19.2 versus 53.6 ± 30.2 events/h, P < .0001). For the lower PWV group, there was a significant correlation and good agreement between the WP-AHI and PSG-AHI, but as the PWV increased, there was low correlation between the WP-AHI and PSG-AHI. CONCLUSIONS: Arterial stiffness may affect the respiratory variables measured by WatchPAT in patients with OSA. COMMENTARY: A commentary on this article appears in this issue on page 301.
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Monitoreo Ambulatorio/métodos , Apnea Obstructiva del Sueño/fisiopatología , Rigidez Vascular , Dispositivos Electrónicos Vestibles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Ambulatorio/instrumentación , Polisomnografía , Reproducibilidad de los Resultados , MuñecaRESUMEN
INTRODUCTION: The prognosis of patients with an acute exacerbation of interstitial pneumonia (AE-IP) is poor. Pirfenidone (PFD) reduces the disease progression in idiopathic pulmonary fibrosis. OBJECTIVES: The purpose of this study was evaluating whether the administration of PFD improved the outcomes of AE-IP. METHODS: We conducted a retrospective study of 31 patients with AE-IP who did not recover between 7 and 14 days after an initial treatment. Fourteen patients received PFD within 2 weeks (PFD group) of the AE, while 17 patients were treated without PFD (non-PFD group). The patients' clinical data and computed tomography (CT) scores were analyzed. RESULTS: The survival rate in the PFD group was not significantly different from non-PFD group at 30 (78.6% vs 64.7%, P = .46) and 90 days (64.3% vs 52.9%, P = .72). The white blood cell counts in the PFD group were significantly lower on PFD day 14 than on PFD days 1 and 7. The C-reactive protein levels in the PFD group were also significantly lower on PFD day 7 than on PFD day 1. There were no significant differences regarding the changes of the CT scores. CONCLUSIONS: PFD may reduce the inflammation in AE-IP patients undergoing corticosteroid treatment.
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Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Piridonas/administración & dosificación , Tomografía Computarizada por Rayos X/métodos , Enfermedad Aguda , Anciano , Antiinflamatorios no Esteroideos/administración & dosificación , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/mortalidad , Japón/epidemiología , Masculino , Pronóstico , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Factores de Tiempo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfaRESUMEN
OBJECTIVE: Although severe obstructive sleep apnea (OSA) is an important risk factor for atherosclerosis-related diseases including coronary artery disease (CAD), there is no reliable biomarker of CAD risks in patients with OSA. This study aimed to test our hypothesis that circulating autoantibodies against neuroblastoma suppressor of tumorigenicity 1 (NBL1-Abs) are associated with the prevalence of CAD in patients with OSA. METHODS: Eighty-two adults diagnosed with OSA by polysomnography, 96 patients with a diagnosis of acute coronary syndrome (ACS) and 64 healthy volunteers (HVs) were consecutively enrolled. Serum samples were collected from patients with OSA at diagnostic polysomnography and from patients with ACS at disease onset. Serum NBL1-Ab level was measured by amplified luminescence proximity homogeneous assay and its association with clinical variables related to atherosclerosis was evaluated. RESULTS: NBL1-Ab level was significantly elevated in patients with both OSA and ACS compared with HVs. Subgroup analyses showed that NBL1-Ab level was markedly higher in patients with severe OSA and OSA patients with a history of CAD. Weak associations were observed between NBL1-Ab level and apnea-hypopnea index, age, mean SpO2 and arousal index, whereas significantly higher NBL1-Ab levels were observed in OSA patients with a history of CAD than in those without a history of CAD. Sensitivity analysis using a logistic regression model also demonstrated that increased NBL1-Ab levels were associated with the previous history of CAD in patients with OSA. CONCLUSIONS: Elevated NBL1-Ab levels may be associated with the prevalence of CAD in patients with OSA, which needs to be confirmed further.
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Autoanticuerpos/sangre , Enfermedad de la Arteria Coronaria/complicaciones , Proteínas/inmunología , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/complicaciones , Adulto , Anciano , Autoanticuerpos/inmunología , Biomarcadores/sangre , Proteínas de Ciclo Celular , Femenino , Humanos , Masculino , Persona de Mediana Edad , Apnea Obstructiva del Sueño/inmunologíaRESUMEN
Background: Pirfenidone is one of the anti-fibrotic drugs used for patients with idiopathic pulmonary fibrosis. Pirfenidone exerts anti-inflammatory effects by inhibiting the influx of inflammatory cells. Objectives: The purpose of this study was to clarify the differences in the baseline parameters in responsive and unresponsive patients, and to assess the clinical and radiological changes after pirfenidone therapy. Methods: Patients with idiopathic pulmonary fibrosis who were treated with pirfenidone from April 2009 to March 2014 were retrospectively analyzed. The enrolled patients were classified into a good response group if they showed inhibition of progression, or were classified into a slowly progressive group on the basis of a decline in the vital capacity over a six-month interval after beginning treatment. The parameters of pulmonary function tests and laboratory findings were compared before and after treatment. The chest computed tomography findings were evaluated using the Sumikawa score. Results: Twenty patients were classified into seven good responders and eight cases with inhibition of progression. These groups had higher antinuclear antibody and autoimmune antibody values, and less ground glass attenuation at baseline. A chest computed tomography assessment at six-months after beginning pirfenidone administration showed a reduction of the ground glass attenuation findings in the good response group and an increase in airspace consolidation in the slowly progressing group compared with the baseline. Conclusions: Higher positive values for antinuclear antibodies and autoimmune antibodies at baseline and the location of ground glass attenuation at baseline, which indicates inflammatory lesions, may predict the efficacy of pirfenidone. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 290-299).
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STUDY OBJECTIVES: Although moderate to severe obstructive sleep apnea (OSA) is an independent risk factor for severe arteriosclerotic diseases such as cardiovascular disease (CVD) and stroke, the development of atherosclerosis-related diseases cannot yet be predicted in patients with OSA. In a pilot study, we identified autoantibodies against the coatomer protein complex, subunit epsilon [circulating anti-coatomer protein complex subunit epsilon autoantibody (COPE-Ab)], a cytosolic complex that mediates protein transport in the Golgi compartment, as a potential novel biomarker of atherosclerosis. This study aimed to evaluate whether COPE-Ab levels had an association with cardiovascular and cerebrovascular events in patients with OSA. METHODS: Eighty-two adult patients with a diagnosis of OSA via polysomnography and 64 healthy donors were studied. Serum COPE-Ab levels were measured using an amplified luminescence proximity homogeneous assay. Then, clinical factors related to atherosclerosis were evaluated with respect to COPE-Ab levels. RESULTS: Significant differences in COPE-Ab levels were observed in terms of OSA severity. COPE-Ab levels were significantly higher in patients with OSA and also CVD and/or stroke, hypertension, and a high body mass index. Univariate and multivariate logistic regression analyses of patients with OSA identified elevated COPE-Ab level as a significant predictor of CVD and/or stroke. CONCLUSIONS: An elevated COPE-Ab level may be a potential predictor of the risks of cardiovascular and cerebrovascular events in patients with OSA. Therefore, patients with higher COPE-Ab levels may require more careful and intensive treatment. COMMENTARY: A commentary on this article appears in this issue on page 361.
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Autoanticuerpos/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/complicaciones , Proteína Coatómero/sangre , Apnea Obstructiva del Sueño/complicaciones , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/complicaciones , Adulto , Anciano , Biomarcadores/sangre , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Proyectos Piloto , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
PURPOSE: Acute exacerbation (AE) is an important outcome of idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP). Recombinant human soluble thrombomodulin (rhTM) is a new drug for the treatment of disseminated intravascular coagulation in Japan. The objective of this study was to evaluate the efficacy of rhTM for AE of IPF/NSIP. METHODS: Twenty-two patients with AE-idiopathic interstitial pneumonia (16 patients with IPF and six patients with NSIP) were enrolled in our study. Among them, eleven patients were treated with rhTM (rhTM group), and eleven patients were treated without rhTM (non-rhTM group). Patients admitted to our hospital prior to December 2013 were treated with rhTM, while those admitted after January 2014 were treated without rhTM. The primary endpoint was mortality at 90 days after AE treatment. The secondary endpoint was the safety of rhTM for AE-IPF/AE-NSIP. In addition, we examined prognostic factors of AE-IPF/AE-NSIP. RESULTS: The mortality rate was significantly lower in the rhTM group than in the non-rhTM group (mortality rate at 90 days: 36% vs 90%, P=0.023; median survival time: not reached vs 15.0 days, P=0.019). A univariate analysis revealed the respiratory rate (hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.00-1.18, P=0.039) and rhTM administration (HR 0.21, 95% CI 0.06-0.77, P=0.013) as predictors of mortality at 90 days, and a multivariate analysis identified rhTM administration (HR 0.025, 95% CI 0.0006-0.94, P=0.046) as an independent predictor of mortality at 90 days. No serious adverse events were observed. CONCLUSION: The administration of rhTM is associated with reductions in mortality in patients with AE-IPF/NSIP, without causing adverse events.
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Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Fármacos del Sistema Respiratorio/uso terapéutico , Trombomodulina/uso terapéutico , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/mortalidad , Estimación de Kaplan-Meier , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Proteínas Recombinantes/uso terapéutico , Fármacos del Sistema Respiratorio/efectos adversos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Limitations in airflow are detected in some patients with sarcoidosis in association with a poor prognosis. The impulse oscillation system (IOS) is used to treat patients with obstructive lung disease, as it can sensitively detect increased airway resistance. OBJECTIVES: To investigate the characteristics of parameters obtained with IOS in patients with sarcoidosis. METHODS: Forty-six pulmonary sarcoidosis patients at Chiba University Hospital and 20 healthy controls were enrolled. The subjects underwent IOS, pulmonary function testing and multidetector computed tomography. We evaluated the correlations between these indices in the pulmonary sarcoidosis patients and compared the pulmonary sarcoidosis patients with the healthy controls. RESULTS: The ratio of V50/V25, percentage of wall area (WA%), resistance at 5 Hz (R5) and difference between the R5 and R20 (R5-R20) values of the patients with pulmonary sarcoidosis were significantly increased compared to those observed in the controls. Inverse weak correlations were observed between the R5-R20 values and the forced expiratory volume in one second (r = -0.56; p <0.001). The R5-R20 values were correlated with the V50/V25 (r = 0.42; p < 0.005) and WA% (r = 0.43; p < 0.05) values. The WA% values were also significantly correlated with the V50/V25 (r = 0.32; p < 0.05) and R5 (r = 0.33; p < 0.05) values. CONCLUSIONS: IOS parameters were found to be significantly correlated with pulmonary function parameters and the airway wall thickness in pulmonary sarcoidosis patients. IOS is considered to be useful for detecting early manifestations of airflow limitation in pulmonary sarcoidosis patients.
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Resistencia de las Vías Respiratorias/fisiología , Oscilometría/métodos , Sarcoidosis Pulmonar/diagnóstico , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado , Hospitales Universitarios , Humanos , Japón , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector/métodos , Valor Predictivo de las Pruebas , Valores de Referencia , Análisis de Regresión , Estudios Retrospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Estadísticas no ParamétricasRESUMEN
The prevention of encapsulating peritoneal sclerosis (EPS) and the enhancement of dialysis efficiency are two important strategies that can improve the quality of life of patients undergoing peritoneal dialysis. We have thus far developed bionanoparticles that effectively scavenge reactive oxygen species (redox nanoparticles; RNPs). The objective of this study was to apply RNPs as a component of dialysate to reduce oxidative stress. Porous silica nanoparticles were combined with RNPs to enhance the effective adsorption capacity of low-molecular weight (LMW) compounds. The silica-containing RNPs (siRNPs) were confirmed to statistically decrease the level of creatinine and blood urea nitrogen in vivo. EPS model rats that underwent an intraperitoneal injection of chlorhexidine gluconate exhibited dysfunction of the peritoneal membrane. siRNP administration did not result in dysfunction of the peritoneal membrane. An LMW nitroxide compound, TEMPOL, also showed a weak peritoneal protective effect, although its efficiency was limited. No blood uptake of siRNPs was observed when they were administered into the peritoneal cavity. However, LMW-TEMPOL diffused into the blood stream, which might have decreased its effective concentration in the peritoneal cavity and led to adverse effects across the entire body. Considering these results, siRNPs are expected to be a new multi-functional nanomaterial for high performance peritoneal dialysis.
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A 52-year-old Japanese woman presented with optical symptoms, including left-sided myodesopsia, blurred vision, narrowed visual field, and diminished visual acuity. Ocular evaluation revealed a metastatic tumor in the choroid. Further examinations identified pulmonary adenocarcinoma as the primary tumor. Because an epidermal growth factor receptor gene (EGFR) mutation was detected in a biopsy specimen, gefitinib treatment was initiated. Dramatic responses were obtained in the primary tumor and metastatic foci. Optical symptoms improved and remained stable for 5 months during the treatment, until relapse. This report demonstrates that gefitinib is effective for choroidal metastasis of pulmonary adenocarcinoma harboring an EGFR mutation.