RESUMEN
BACKGROUND: Up to 6% of kidney transplant recipients (KTRs) experience life-threatening complications requiring intensive care unit (ICU) admission, and one of the most common medical complications requiring ICU admission is infection. This study aimed to evaluate the effect of immunosuppressive therapy (IST) modification on prognosis of KTRs with sepsis. METHODS: We conducted a multicenter retrospective study in 4 university-affiliated hospitals to evaluate the effect of adjusting the IST in KTRs with sepsis. Only patients who either maintained IST after ICU admission or those who underwent immediate (within 24â h of ICU admission) reduction or withdrawal of IST following ICU admission were included in this study. "Any reduction" was defined as a dosage reduction of any IST or discontinuation of at least 1 IST. "Complete withdrawal of IST" was defined as concomitant discontinuation of all ISTs, except steroids. RESULTS: During the study period, 1596 of the KTRs were admitted to the ICU, and 112 episodes of sepsis or septic shock were identified. The overall in-hospital mortality rate was 35.7%. In-hospital mortality was associated with higher sequential organ failure assessment score, simplified acute physiology score 3, non-identical human leukocyte antigen relation, presence of septic shock, and complete withdrawal of IST. After adjusting for potential confounding factors, complete withdrawal of IST remained significantly associated with in-hospital mortality (adjusted coefficient, 1.029; 95% confidence interval, 0.024-2.035) and graft failure (adjusted coefficient, 2.001; 95% confidence interval, 0.961-3.058). CONCLUSIONS: Complete IST withdrawal was common and associated with worse outcomes in critically ill KTRs with sepsis.
Asunto(s)
Mortalidad Hospitalaria , Inmunosupresores , Unidades de Cuidados Intensivos , Trasplante de Riñón , Sepsis , Humanos , Estudios Retrospectivos , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Sepsis/mortalidad , Sepsis/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Unidades de Cuidados Intensivos/estadística & datos numéricos , Adulto , Anciano , Puntuaciones en la Disfunción de Órganos , Receptores de Trasplantes/estadística & datos numéricos , PronósticoRESUMEN
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has changed respiratory infection patterns globally. However, its impact on community-acquired pneumonia (CAP) in high-risk patients with haematological malignancies (HM) is uncertain. We aimed to examine how community-acquired pneumonia aetiology in patients with haematological malignancies changed during the COVID-19 pandemic. METHODS: This was a retrospective study that included 524 patients with haematological malignancies hospitalised with community-acquired pneumonia between March 2018 and February 2022. Patients who underwent bronchoscopy within 24 h of admission to identify community-acquired pneumonia aetiology were included. Data on patient characteristics, laboratory findings, and results of bronchioalveolar lavage fluid cultures and polymerase chain reaction tests were analysed and compared to identify changes and in-hospital mortality risk factors. RESULTS: Patients were divided into the 'pre-COVID-19 era' (44.5%) and 'COVID-19 era' (55.5%) groups. The incidence of viral community-acquired pneumonia significantly decreased in the COVID-19 era, particularly for influenza A, parainfluenza, adenovirus, and rhinovirus (pre-COVID-19 era vs. COVID-19 era: 3.0% vs. 0.3%, P = 0.036; 6.5% vs. 0.7%, P = 0.001; 5.6% vs. 1.4%, P = 0.015; and 9.5% vs. 1.7%, P < 0.001, respectively), whereas that of bacterial, fungal, and unknown community-acquired pneumonia aetiologies remain unchanged. Higher Sequential Organ Failure Assessment scores and lower platelet counts correlated with in-hospital mortality after adjusting for potential confounding factors. CONCLUSIONS: In the COVID-19 era, the incidence of community-acquired pneumonia with viral aetiologies markedly decreased among patients with haematological malignancies, with no changes in the incidence of bacterial and fungal pneumonia. Further studies are required to evaluate the impact of COVID-19 on the prognosis of patients with haematological malignancies and community-acquired pneumonia.
Asunto(s)
COVID-19 , Infecciones Comunitarias Adquiridas , Neoplasias Hematológicas , Humanos , COVID-19/epidemiología , COVID-19/complicaciones , Masculino , Femenino , Estudios Retrospectivos , Neoplasias Hematológicas/complicaciones , Persona de Mediana Edad , Infecciones Comunitarias Adquiridas/epidemiología , Anciano , Mortalidad Hospitalaria , SARS-CoV-2 , Factores de Riesgo , Incidencia , Adulto , Hospitalización/estadística & datos numéricos , Neumonía Viral/epidemiología , Neumonía Viral/complicacionesRESUMEN
BACKGROUND: In patients with sepsis, timely risk stratification is important to improve prognosis. Although several clinical scoring systems are currently being used to predict the outcome of sepsis, but they all have certain limitations. The objective of this study was to evaluate the prognostic value of estimated plasma volume status (ePVS) in patients admitted to the intensive care unit (ICU) with sepsis or septic shock. METHODS: This single-center, prospective observational study, included 100 patients admitted to the ICU with sepsis or septic shock. Informed consent, blood samples, and co-morbidity data were obtained from the patients on admission, and the severity of sepsis was recorded. The primary outcome was in-hospital mortality and multivariable logistic regression analysis was used to adjust for confounding factors to determine the significant prognostic factor. RESULTS: The in-hospital mortality was 47%. The ePVS was correlated with the amount of total fluids administered 24 hours before the ICU admission. The mean ePVS in patients who died was higher than in those who survived (7.7 ± 2.1 dL/g vs. 6.6 ± 1.6 dL/g, P = 0.003). To evaluate the utility of ePVS in predicting in-hospital mortality, a receiver operating characteristic curve was produced. Sensitivity and specificity were optimal at a cut-off point of 7.09 dL/g, with an area under the curve of 0.655. In the multivariate analysis, higher ePVS was significantly associated with higher in-hospital mortality (adjusted odds ratio, 1.39; 95% confidence interval, 1.04-1.85, P = 0.028). The Kaplan-Meier curve showed that an ePVS value above 7.09 was associated with an increased risk of in-hospital mortality compared with the rest of the population (P = 0.004). CONCLUSION: The ePVS was correlated with the amount of intravenous fluid resuscitation and may be used as a simple and novel prognostic factor in patients with sepsis or septic shock who are admitted to the ICU.
Asunto(s)
Sepsis , Choque Séptico , Humanos , Unidades de Cuidados Intensivos , Volumen Plasmático , Pronóstico , Curva ROC , Estudios Retrospectivos , Sepsis/diagnóstico , Choque Séptico/diagnósticoRESUMEN
OBJECTIVES: To investigate the impact of normothermia on compliance with sepsis bundles and in-hospital mortality in patients with sepsis who present to emergency departments. DESIGN: Retrospective multicenter observational study. PATIENTS: Nineteen university-affiliated hospitals of the Korean Sepsis Alliance participated in this study. Data were collected regarding patients who visited emergency departments for sepsis during the 1-month period. The patients were divided into three groups based on their body temperature at the time of triage in the emergency department (i.e., hypothermia [< 36°C] vs normothermia [36-38°C] vs hyperthermia [> 38°C]). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 64,021 patients who visited emergency departments, 689 with community-acquired sepsis were analyzed (182 hyperthermic, 420 normothermic, and 87 hypothermic patients). The rate of compliance with the total hour-1 bundle was lowest in the normothermia group (6.0% vs 9.3% in hyperthermia vs 13.8% in hypothermia group; p = 0.032), the rate for lactate measurement was lowest in the normothermia group (62.1% vs 73.1% vs 75.9%; p = 0.005), and the blood culture rate was significantly lower in the normothermia than in the hyperthermia group (p < 0.001). The in-hospital mortality rates in the hyperthermia, normothermia, and hypothermia groups were 8.5%, 20.6%, and 30.8%, respectively (p < 0.001), but there was no significant association between compliance with sepsis bundles and in-hospital mortality. However, in a multivariate analysis, compared with hyperthermia, normothermia was significantly associated with an increased in-hospital mortality (odds ratio, 2.472; 95% CI, 1.005-6.080). This association remained significant even after stratifying patients by median lactate level. CONCLUSIONS: Normothermia at emergency department triage was significantly associated with an increased risk of in-hospital mortality and a lower rate of compliance with the sepsis bundle. Despite several limitations, our findings suggest a need for new strategies to improve sepsis outcomes in this group of patients.
Asunto(s)
Temperatura Corporal , Servicio de Urgencia en Hospital/estadística & datos numéricos , Mortalidad Hospitalaria/tendencias , Paquetes de Atención al Paciente/estadística & datos numéricos , Sepsis/mortalidad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Concentración de Iones de Hidrógeno , Hipertermia/epidemiología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , República de Corea/epidemiología , Estudios Retrospectivos , Sepsis/microbiología , Choque Séptico/microbiología , Choque Séptico/mortalidadRESUMEN
PURPOSE: The aim of the present study was to demonstrate the role of insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase inhibitors (TKIs) in IGF-1R expressed epidermal growth factor receptor (EGFR) mutant cells. MATERIALS AND METHODS: Human lung adenocarcinoma PC9, HCC827, and H1975 cells were exposed to a combination of IGF-1, gefitinib, or linsitinib. Cell viability was assessed by the MTT assay. The expression of EGFR, IGF-1R, AKT, extracellular regulated kinases 1 and 2 (ERK1/2), cleaved poly ADP ribose polymerase (PARP), cleaved caspase 3, and hypoxia-inducible factor (HIF)-1α were measured by Western blot. The concentrations of vascular endothelial growth factor (VEGF) were measured using an enzyme-linked immunosorbent assay kit. RESULTS: Cell growth in PC9 and HCC827 cells was synergistically suppressed by co-treatment with gefitinib and linsitinib. Gefitinib did not affect H1975 cell growth; however, linsitinib suppressed cell proliferation. Co-treatment with gefitinib and linsitinib inhibited pAKT and pERK, and linsitinib treatment profoundly reduced IGF-1-induced pIGF-1R expression in PC9 and HCC827 cells. Dual treatment increased the number of Annexin-V-positive HCC827 and H1975 cells, and expression of cleaved caspase 3 and cleaved PARP increased in H1975 cells following linsitinib treatment. Gefitinib inhibited HIF-1α and VEGF expression in HCC827 cells, and linsitinib inhibited VEGF production in H1975 cells. CONCLUSION: IGF-1R TKIs had modest anti-tumor efficacy and their effects were explained by blocking the EGFR and IGF-1R pathway in IGF-1R expressing EGFR-sensitive cells. IGF-1R TKI had pro-apoptotic activity and inhibited cellular growth in EGFR-resistant cells.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Inhibidores de Proteínas Quinasas/farmacología , Receptor IGF Tipo 1/antagonistas & inhibidores , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Inhibidores de Proteínas Quinasas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacosRESUMEN
BACKGROUND: Modern treatments have improved the survival rate following cardiac arrest, but prognostication remains a challenge. We examined the prognostic value of continuous electroencephalography according to time by performing amplitude-integrated electroencephalography on patients with cardiac arrest receiving therapeutic hypothermia. METHODS AND RESULTS: We prospectively studied 130 comatose patients treated with hypothermia from September 2010 to April 2013. We evaluated the time to normal trace (TTNT) as a neurological outcome predictor and determined the prognostic value of burst suppression and status epilepticus, with a particular focus on their time of occurrence. Fifty-five patients exhibited a cerebral performance category score of 1 to 2. The area under the curve for TTNT was 0.97 (95% confidence interval, 0.92-0.99), and the sensitivity and specificity of TTNT<24 hours after resuscitation as a threshold for predicting good neurological outcome were 94.6% (95% confidence interval, 84.9%-98.9%) and 90.7% (95% confidence interval, 81.7%-96.2%), respectively. The threshold displaying 100% specificity for predicting poor neurological outcome was TTNT>36 hours. Burst suppression and status epilepticus predicted poor neurological outcome (positive predictive value of 98.3% and 96.4%, respectively). The combination of these factors predicted a negative outcome at a median of 6.2 hours after resuscitation (sensitivity and specificity of 92.0% and 96.4%, respectively). CONCLUSIONS: A TTNT<24 hours was associated with good neurological outcome. The lack of normal trace development within 36 hours, status epilepticus, and burst suppression were predictors of poor outcome. The combination of these negative predictors may improve their prognostic performance at an earlier stage.
Asunto(s)
Electroencefalografía/métodos , Paro Cardíaco/diagnóstico , Paro Cardíaco/terapia , Hipotermia Inducida/métodos , Monitoreo Fisiológico/métodos , Adulto , Anciano , Coma/complicaciones , Comorbilidad , Femenino , Paro Cardíaco/fisiopatología , Hemodinámica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Sensibilidad y Especificidad , Estado Epiléptico/complicaciones , Resultado del TratamientoRESUMEN
OBJECTIVES: We investigated the effect of long-term treatment with azithromycin on the pathogenesis of chronic asthma with airway remodeling. METHODS: Six-week-old-BALB/c mice were sensitized with ovalbumin (OVA) combined with lipopolysaccharide (LPS) for 1 month, then challenged with OVA for 3 months. Azithromycin at 75 mg/kg was administered via oral gavage five times a week during the challenge period. Inflammatory cells, T helper 2 cytokines in bronchoalveolar lavage fluid (BAL) fluid, and airway hyperresponsiveness (AHR) were measured. Parameters related to airway remodeling were evaluated. The levels of neutrophil elastase, Interleukin (IL)-8, and BRP-39 (human homologue YKL-40) were assessed. The expression of MAPK and NF-κB signaling were investigated. RESULTS: Long-term treatment with azithromycin improved AHR and airway inflammation compared with the OVA and the OVA/LPS groups. The concentrations of IL-5 and IL-13 in the OVA/LPS group decreased significantly after azithromycin administration. The levels of neutrophil elastase and IL-8, as surrogate markers of neutrophil activation, were reduced in the azithromycin group compared with the OVA/LPS group. Goblet cell hyperplasia and the smooth muscle thickening of airway remodeling were attenuated after azithromycin treatment. The expression of MAPK/NF-kappaB signal and the level of BRP-39 in the lung decreased remarkably in the OVA/LPS with azithromycin-treated group. CONCLUSIONS: This study suggests that in a murine model of chronic asthma, long-term azithromycin treatment ameliorates not only airway inflammation but also airway remodeling by influencing on neutrophilc-related mediators, BRP-39 and MAPK/NF-κB signal pathways. Macrolide therapy might be an effective adjuvant therapy in a chronic, severe asthma with remodeling airway.
Asunto(s)
Antibacterianos/uso terapéutico , Asma/tratamiento farmacológico , Asma/patología , Azitromicina/uso terapéutico , Neumonía/tratamiento farmacológico , Neumonía/patología , Animales , Asma/inducido químicamente , Hiperreactividad Bronquial/tratamiento farmacológico , Hiperreactividad Bronquial/patología , Hiperreactividad Bronquial/fisiopatología , Líquido del Lavado Bronquioalveolar/citología , Femenino , Interleucinas/metabolismo , Elastasa de Leucocito/metabolismo , Lipopolisacáridos , Ratones , Ratones Endogámicos BALB C , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Ovalbúmina , Neumonía/inducido químicamente , Linfocitos T Colaboradores-Inductores/efectos de los fármacosRESUMEN
Pulmonary infections are a major cause of morbidity and mortality in patients with hematologic malignancy. Bronchoscopy is at present still the traditional first investigation in immunosuppressed patients that have developed pulmonary infiltrates. There is limited data available on the validity of fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) to determine the etiology of pulmonary infiltrates with concurrent hematologic malignancy. We retrospectively analyzed the microbiological results of 206 bronchoscopic examinations and treatment changes used in 187 patients with hematologic malignancy and pulmonary infiltrates. Bacteria, fungi, and viruses were found in 85 (41.3 %), 49 (23.8 %), and 55 (28.6 %) of cases, respectively, and overall yield of bronchoscopy was 65.0 %. We compared the microbiological findings with respect to neutropenia, hematopoietic stem cell transplantation (HSCT) status, and the type of malignancy. There were significantly more bacterial and viral infections detected in post-HSCT patients, and more viruses were detected in patients without neutropenia. Galactomannan (GM) was measured in 149 BAL samples. With a GM index threshold of ≥0.5, the sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) of the BAL GM assay were 93.94 %, 86.21 %, 65.96 %, and 98.04 %, respectively. Treatment was modified in 62 cases (30.1 %). There was no significant relationship of treatment modification with the underlying disease, HSCT, or neutropenia. Bronchoscopy with BAL is a valuable diagnostic tool to determine the etiology and appropriate treatment in patients with hematologic malignancy and pulmonary infiltrates. A BAL GM test is recommended when invasive pulmonary aspergillosis is suspected.
Asunto(s)
Lavado Broncoalveolar/métodos , Broncoscopía/métodos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/microbiología , Pulmón/microbiología , Pulmón/virología , Adolescente , Adulto , Anciano , Líquido del Lavado Bronquioalveolar/microbiología , Líquido del Lavado Bronquioalveolar/virología , Femenino , Humanos , Aspergilosis Pulmonar Invasiva/diagnóstico , Aspergilosis Pulmonar Invasiva/microbiología , Pulmón/patología , Masculino , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/microbiología , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: Peptide nucleic acid (PNA)-mediated real-time polymerase chain reaction clamping was recently developed to improve mutation detection sensitivity. Pleural effusion could be a good sample candidate for mutation analysis. To establish if PNA clamping could be used to detect KRAS mutation in particular in pleural effusion, we analysed its diagnostic performance. METHODS: We studied 57 patients with malignant effusion. KRAS mutation was evaluated in samples of matched tumour tissue, cell block, pleural effusion and serum using PNA clamping and direct sequencing. RESULTS: The detection rate of KRAS mutation using pleural effusion was 14% for PNA clamping and 10.5% for direct sequencing. The κ coefficient between the two methods was 0.76 (P value < 0.0001), 1.00 (P value < 0.0001) and 0.87 (P value < 0.0001) in pleural effusion, tissue and cell block, respectively. The diagnostic performance of KRAS mutation detection from pleural effusion compared with the results obtained for all samples combined showed that the sensitivity, specificity, positive predictive value and negative predictive value were as follows: 89, 100, 100 and 98%, respectively for PNA clamping; 67, 100, 100 and 94%, respectively for directing sequencing. CONCLUSIONS: The current study suggests that PNA clamping had a good concordance with direct sequencing for the detection of KRAS mutation in patients with malignant effusion. Furthermore, the good diagnostic performance obtained from pleural effusion samples provides evidence that pleural effusion can be a useful source for detecting KRAS mutation in a clinical setting, in which the collection of tumour tissues is challenging.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Derrame Pleural Maligno , Proteínas Proto-Oncogénicas/genética , Proteínas ras/genética , Anciano , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/patología , Análisis Mutacional de ADN/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Ácidos Nucleicos de Péptidos/metabolismo , Derrame Pleural Maligno/etiología , Derrame Pleural Maligno/genética , Derrame Pleural Maligno/patología , Valor Predictivo de las Pruebas , Proteínas Proto-Oncogénicas p21(ras) , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The role of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) as a prognostic factor in patients admitted to the intensive care unit (ICU) is not yet fully established. We aimed to determine whether NT-pro-BNP is predictive of ICU mortality in a multicenter cohort of critically ill patients. METHODS: A total of 1440 patients admitted to 22 ICUs (medical, 14; surgical, six; multidisciplinary, two) in 15 tertiary or university-affiliated hospitals between July 2010 and January 2011 were assessed. Patient data, including NT-pro-BNP levels and Simplified Acute Physiology Score (SAPS) 3 scores, were recorded prospectively in a web-based database. RESULTS: The median age was 64 years (range, 53-73 years), and 906 (62.9%) patients were male. The median NT-pro-BNP level was 341 pg/mL (104-1,637 pg/mL), and the median SAPS 3 score was 57 (range, 47-69). The ICU mortality rate was 18.9%, and hospital mortality was 24.5%. Hospital survivors showed significantly lower NT-pro-BNP values than nonsurvivors (245 pg/mL [range, 82-1,053 pg/mL] vs. 875 pg/mL [241-5,000 pg/mL], respectively; p < 0.001). In prediction of hospital mortality, the area under the curve (AUC) for NT-pro-BNP was 0.67 (95% confidence interval [CI], 0.64-0.70) and SAPS 3 score was 0.83 (95% CI, 0.81-0.85). AUC increment by adding NT-pro-BNP is minimal and likely no different to SAPS 3 alone. CONCLUSIONS: The NT-pro-BNP level was more elevated in nonsurvivors in a multicenter cohort of critically ill patients. However, there was little additional prognostic power when adding NT-pro-BNP to SAPS 3 score.
Asunto(s)
Enfermedad Crítica , Mortalidad Hospitalaria/tendencias , Unidades de Cuidados Intensivos/tendencias , Péptido Natriurético Encefálico/sangre , Admisión del Paciente/tendencias , Fragmentos de Péptidos/sangre , Anciano , Biomarcadores/sangre , Enfermedad Crítica/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Patients admitted to medical intensive care unit (MICU) are at increased risk for venous thromboembolism (VTE); and prophylaxis is recommended. However, the actual range and frequency of VTE prophylaxis administered to MICU patients are not well defined. Patients over 40 yr of age and expected MICU stay of more than 48 hr were eligible for this observational cohort study of 23 MICUs in Korea. Patients already on anticoagulation therapy or those requiring anticoagulation for reasons other than VTE were excluded. Among 830 patients, VTE prophylaxis was given to 560 (67.5%) patients. Among 560 patients, 323 (38.9%) received pharmacoprophylaxis, 318 (38.4%) received mechanical prophylaxis and 81 (9.8%) received both forms of prophylaxis. About 74% of patients in the pharmacoprophylaxis group received low molecular weight heparin and 53% of the patients in the mechanical prophylaxis group used intermittent pneumatic compression. Most of the patients (90%) had more than one risk factor for VTE and the most common risk factor was old age, followed by heart and respiratory failure. In this observational cohort study of 23 MICUs in Korea, 67.5% of patients received thromboprophylaxis. Further studies are needed to clarify the role and efficacy of VTE prophylaxis in Korean critically ill patients.
Asunto(s)
Unidades de Cuidados Intensivos , Tromboembolia Venosa/prevención & control , Adulto , Factores de Edad , Anciano , Estudios de Cohortes , Femenino , Insuficiencia Cardíaca/complicaciones , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Tiempo de Internación , Masculino , Trombolisis Mecánica , Persona de Mediana Edad , República de Corea , Insuficiencia Respiratoria/complicaciones , Estudios Retrospectivos , Factores de Riesgo , Tomografía Computarizada por Rayos X , Tromboembolia Venosa/complicaciones , Tromboembolia Venosa/terapiaRESUMEN
Surfactants, a group of amphiphilic molecules (i.e. with hydrophobic(water insoluble) as well as hydrophilic(water soluble) properties) can modulate interfacial tension. Currently, the majority of surfactants depend on petrochemical feedstocks (such as oil and gas). However, deployment of these petrochemical surfactants produces high toxicity and also has poor biodegradability which can cause more environmental issues. To address these concerns, the current research is moving toward natural resources to produce sustainable surfactants. Among the available natural resources, Cashew Nut Shell Liquid (CNSL) is the preferred choice for industrial scenarios to meet their goals of sustainability. CNSL is an oil extracted from non-edible cashew nut shells, which doesn't affect the food supply chain. The unique structural properties and diverse range of use cases of CNSL are key to developing eco-friendly surfactants that replace petro-based surfactants. Against this backdrop, this article discusses various state-of-the-art developments in key cardanol-based surfactants such as anionic, cationic, non-ionic, and zwitterionic. In addition to this, the efficiency and characteristics of these surfactants are also analyzed and compared with those of the synthetic surfactants (petro-based). Furthermore, the present paper also focuses on various market aspects and different applications in various industries. Finally, this article describes various future research perspectives including Artificial Intelligence technology which, of late, is having a huge impact on society.
RESUMEN
OBJECTIVE: The aim of this study was to measure the level of nerve growth factor (NGF) in bronchial specimens from humans and to determine whether it correlated with not only clinical characteristics of asthma such as percent eosinophils, Th2 cytokine levels, and pulmonary function, but also metallopeptidase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1). METHODS: Fifty-three people participated; 42 had asthma. The participants underwent bronchoscopy and the specimens were analyzed. The participants' clinical data including pulmonary function tests were reviewed. RESULTS: Bronchoalveolar lavage fluid (BALF) from patients with asthma had a significantly higher level of NGF compared with that from participants without asthma. NGF level showed a positive correlation with the percentage of eosinophils in both BALF and serum. The concentration of NGF did not correlate with that of Th2 cytokines interleukin (IL)-4, IL-5, and IL-13 in BALF or parameters of pulmonary function including degree of airway hyperresponsiveness (ARH). The levels of MMP-9 and TIMP-1 in BALF were higher in asthma patients than in participants without asthma. The levels of NGF correlated with TIMP-1 levels but not with MMP-9 in the whole participants. CONCLUSIONS: This study shows that NGF correlates with levels of eosinophils, a major effector cell in asthma. The high expression of NGF and TIMP-1 in asthma patients and the moderate correlation between NGF and TIMP-1 in the entire group of asthma subjects suggest a possible association between NGF and TIMP-1, which may influence asthma pathogenesis.
Asunto(s)
Asma/metabolismo , Metaloproteinasa 9 de la Matriz/biosíntesis , Factor de Crecimiento Nervioso/biosíntesis , Inhibidor Tisular de Metaloproteinasa-1/biosíntesis , Adolescente , Adulto , Anciano , Asma/sangre , Asma/enzimología , Asma/inmunología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Eosinofilia/inmunología , Eosinofilia/metabolismo , Femenino , Humanos , Inmunohistoquímica , Interleucinas/inmunología , Masculino , Metaloproteinasa 9 de la Matriz/inmunología , Persona de Mediana Edad , Factor de Crecimiento Nervioso/inmunología , Estudios Prospectivos , Pruebas de Función Respiratoria , Estadísticas no Paramétricas , Inhibidor Tisular de Metaloproteinasa-1/inmunología , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: To externally validate the simplified acute physiology score 3 (SAPS3) and to customize it for use in Korean intensive care unit (ICU) patients. METHODS: This is a prospective multicentre cohort study involving 22 ICUs from 15 centres throughout Korea. The study population comprised patients who were consecutively admitted to participating ICUs from 1 July 2010 to 31 January 2011. RESULTS: A total of 4617 patients were enrolled. ICU mortality was 14.3%, and hospital mortality was 20.6%. The patients were randomly assigned into one of two cohorts: a development (n = 2309) or validation (n = 2308) cohort. In the development cohort, the general SAPS3 had good discrimination (area under the receiver operating characteristics curve = 0.829), but poor calibration (Hosmer-Lemeshow goodness-of-fit test H = 123.06, P < 0.001, C = 118.45, P < 0.001). The Australasia SAPS3 did not improve calibration (H = 73.53, P < 0.001, C = 70.52, P < 0.001). Customization was achieved by altering the logit of the original SAPS3 equation. The new equation for Korean ICU patients was validated in the validation cohort, and demonstrated both good discrimination (area under the receiver operating characteristics curve = 0.835) and good calibration (H = 4.61, P = 0.799, C = 5.67, P = 0.684). CONCLUSIONS: General and regional Australasia SAPS3 admission scores showed poor calibration for use in Korean ICU patients, but the prognostic power of the SAPS3 was significantly improved by customization. Prediction models should be customized before being used to predict mortality in different regions of the world.
Asunto(s)
Cuidados Críticos , Hospitalización/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Anciano , Estudios de Cohortes , Femenino , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Corea (Geográfico) , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Pronóstico , Estudios ProspectivosRESUMEN
INTRODUCTION: Advances in critical care management have led to the recent increase in the use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation (LT). Patients with respiratory failure requiring venovenous ECMO usually experience progressive right ventricular (RV) failure. Diagnosis and treatment of RV failure during ECMO are essential for improving the prognosis of patients. PATIENT CONCERNS: A 28-year-old female patient underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor for acute myeloid leukemia presenting with progressive dyspnea. DIAGNOSES: Computed tomography revealed multifocal patchy peribronchial and subpleural ground-glass opacities in both lungs, and the patient was clinically diagnosed with cryptogenic organizing pneumonia. INTERVENTIONS AND OUTCOMES: Despite intensifying systemic corticosteroid therapy, her symptoms deteriorated, and mechanical ventilation and ECMO were applied. During treatment, her respiratory failure continued to progress, and systemic hypotension developed. An echocardiogram showed evidence of RV failure, and percutaneous atrial septostomy was performed for RV decompression. After a balloon atrial septostomy was performed, RV failure of the patient improved, and LT was successfully performed. LESSONS: We report the first case of atrial septostomy as a successful bridge to LT in a HSCT recipient with venovenous ECMO. Atrial septostomy could be an option for management of RV failure during ECMO. Further studies need to be conducted to validate the effect of atrial septostomy in patients with RV failure during ECMO.
Asunto(s)
Oxigenación por Membrana Extracorpórea , Insuficiencia Cardíaca , Trasplante de Pulmón , Insuficiencia Respiratoria , Adulto , Oxigenación por Membrana Extracorpórea/métodos , Femenino , Insuficiencia Cardíaca/etiología , Humanos , Pericardiectomía , Insuficiencia Respiratoria/cirugía , Insuficiencia Respiratoria/terapiaRESUMEN
In the Concealed Information Test (CIT), differential responses between crime-relevant and crime-irrelevant items are indicative of concealed knowledge of a crime, and are used to classify an individual as either "guilty" or "innocent". However, when crime-relevant items are leaked before the test, an innocent examinee can exhibit enhanced responses to the crime-relevant items, thus causing such examinee to be wrongly classified as guilty. In an attempt to solve this problem, we examined the role of retroactive memory interference (RI) in differentiating informed innocents from guilty participants, using a P300-based CIT. Participants acquired crime-related knowledge either by committing a mock crime (guilty group) or reading a paper that described a mock crime (informed innocent group). Subsequently, the participants within each condition were randomly assigned to either an RI group, where they were exposed to new crime-related details before the CIT, or a control group. We found an interaction between guilty and RI groups: in the guilty group, there was a significant difference in P300 amplitude between the probe and irrelevant items, regardless of RI manipulation, whereas in the informed innocent group, a difference in P300 amplitude between the probe and irrelevant items was significant only in the control group, but not in the RI group. This led to an improved detection rate of the informed innocents (31% for the control group vs. 77% for the RI group). These results suggest that RI manipulation could be used to reduce the false positive outcomes of informed innocents without affecting the detection rate of guilty participants.
Asunto(s)
Detección de Mentiras , Decepción , Potenciales Relacionados con Evento P300/fisiología , Respuesta Galvánica de la Piel , Culpa , Humanos , Memoria/fisiologíaRESUMEN
Background: There have been few studies to verify factors associated with a false-negative interferon-gamma release assay (IGRA) in patients with tuberculous pleurisy. We investigated the clinical relevance of false-negative results of the blood QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and its risk factors in patients diagnosed with pleural tuberculosis (TB). Methods: Medical records of 650 pleural TB patients in a tertiary hospital between January 2009 and December 2020 were reviewed retrospectively. Patients who underwent the blood QFT-GIT assay and pleural fluid analysis before starting anti-TB medication were included. Results: Of 199 patients with pleural TB who were performed QFT-GIT assay, 36 (18.1%) were false-negative results. These patients tended to be older than those with a positive result (P=0.060). The QFT-GIT-false-negative group of had significantly more comorbidities such as end-stage renal disease (ESRD), haematological cancer or pneumoconiosis than the QFT-GIT-positive group. Hypoproteinaemia and pH >6 in pleural fluid were associated with a false-negative QFT-GIT. Of the 199 patients, 163 (81.9%) were cured or completed anti-TB treatment; 13 patients (6.5%) died. The QFT-GIT-negative patients had significantly worse outcomes including mortality [unfavourable outcome: 33.3% (12/36 patients) in QFT-GIT-negative groups vs. 14.7% (24/163 patients) in QFT-GIT-positive groups, P<0.017; overall mortality: 16.7% (6/36 patients) vs. 4.3% (7/163 patients), respectively, P<0.015]. Conclusions: In pleural TB, a false-negative QFT-GIT result was 18.1% in a country of intermediate TB incidence. This discordant result in GFT-GIT was associated with ESRD, pneumoconiosis, hypoproteinaemia and a poor outcome. Clinicians should keep in mind the possibility of false-negativity in the blood IGRA test, especially in specific situations and its impact on TB outcome in managing patients with pleural TB.
RESUMEN
We conducted a series of experiments to investigate the neural basis of the immediate extinction deficit, the lack of extinction when the interval between fear memory acquisition and extinction is short. In experiment 1, rats were given extinction training composed of 15 conditioned stimuli (CSs) either 15 min (immediate extinction: I-EXT) or 24 h (delayed extinction: D-EXT) after five tone-shock pairings. In the retention test performed 48 h after conditioning, I-EXT group exhibited significantly higher freezing than D-EXT group. In experiment 2, functional activation in the medial prefrontal cortex (mPFC) was detected using c-fos immunoreactivity. The number of Fos-positive neurons in the mPFC was significantly lower in I-EXT group than in D-EXT group. In experiment 3, rats received immediate extinction with microstimulation of the infralimbic region (IL) of the mPFC, either contingently paired or unpaired with the CS. In a subsequent retention test, the paired stimulation group exhibited decreased freezing relative to the unpaired stimulation group. Together, our results suggest that the immediate extinction deficit may be linked to the lack of neuronal activity in the IL.
Asunto(s)
Condicionamiento Clásico/fisiología , Extinción Psicológica/fisiología , Corteza Prefrontal/metabolismo , Estimulación Acústica/efectos adversos , Vías Aferentes/fisiología , Análisis de Varianza , Animales , Recuento de Células/métodos , Electrochoque/efectos adversos , Regulación de la Expresión Génica/fisiología , Indoles , Sistema Límbico/fisiología , Proteínas Oncogénicas v-fos/metabolismo , Ratas , Tiempo de Reacción/fisiología , Factores de TiempoRESUMEN
BACKGROUND: Asthma is characterized by airway hyperresponsiveness (AHR), inflammation and remodeling. The tyrosine kinase inhibitor imatinib mesylate was developed to inhibit BCR-ABL kinase activity; however, it also has potent inhibitory activity against the c-Kit and platelet-derived growth factor receptors. The present study aimed to determine whether imatinib suppresses airway smooth muscle (ASM) remodeling and whether its effect is associated with growth factors such as transforming growth factor (TGF)-ß1 and stem cell factor (SCF). METHODS: We developed a mouse model of airway remodeling, which includes smooth muscle thickening, in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration twice a week for 3 months. Mice were treated with imatinib during the OVA challenge. RESULTS: Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation and AHR compared with control mice. In addition, the mice chronically exposed to OVA developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of imatinib significantly inhibited the development of AHR, eosinophilic inflammation and, importantly, ASM remodeling in mice chronically exposed to OVA. Imatinib treatment significantly reduced the levels of interleukin-4, -5 and -13. In addition, TGF-ß1 and SCF were significantly reduced in the imatinib-treated animals. CONCLUSIONS: These results suggest that imatinib administration can prevent not only airway inflammation, but also airway remodeling associated with chronic allergen challenge. Imatinib may provide a clinically attractive therapy for chronic severe asthma.
Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Asma/tratamiento farmacológico , Músculo Liso/efectos de los fármacos , Piperazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Animales , Asma/patología , Benzamidas , Enfermedad Crónica , Femenino , Mesilato de Imatinib , Interleucinas/biosíntesis , Ratones , Ratones Endogámicos BALB C , Músculo Liso/patología , Ovalbúmina/farmacología , Índice de Severidad de la Enfermedad , Factor de Células Madre/biosíntesis , Factor de Crecimiento Transformador beta1/biosíntesisRESUMEN
BACKGROUND: The tyrosine kinase inhibitor imatinib mesylate was developed as an inhibitor of the kinase activity of BCR-ABL. However, imatinib also has potent inhibitory activity against the platelet-derived growth factor receptor (PDGFR). Nilotinib is approved for treating patients with chronic myeloid leukemia showing resistance or intolerance to imatinib. Like imatinib, nilotinib selectively inhibits the tyrosine kinase activity of PDGFR. OBJECTIVES: We examined the effect of imatinib and nilotinib on acute lung injury and pulmonary fibrosis in a mouse model. METHODS: Mice were treated by intratracheal instillation of bleomycin. Imatinib or nilotinib were administered by oral gavage. To study the early inflammatory and late fibrotic phases of lung injury, mice were sacrificed on days 3, 7, 14 and 21 after bleomycin instillation. RESULTS: Histopathology showed that imatinib and nilotinib attenuated the extent of lung injury and fibrosis. The numbers of inflammatory cells and levels of IL-6, IL-1ß and tumor necrosis factor-α were decreased in the imatinib and nilotinib groups on days 3 and 7. Imatinib and nilotinib therapy significantly reduced the levels of hydroxyproline on days 14 and 21, which was accompanied by decreased expression levels of transforming growth factor (TGF)-ß1 and PDGFR-ß. Imatinib and nilotinib also significantly reduced the expression levels of the genes for TGF-ß1 and platelet-derived growth factor (PDGF). Imatinib and nilotinib treatment also significantly inhibited the PDGF-induced proliferation of lung fibroblasts in vitro. When imatinib or nilotinib was given 7 days after the instillation of bleomycin, only nilotinib attenuated pulmonary fibrosis. CONCLUSIONS: Imatinib and nilotinib attenuated bleomycin-induced acute lung injury and pulmonary fibrosis in mice. In a therapeutic model, nilotinib showed more potent antifibrotic effects than imatinib.