RESUMEN
Mode decomposition is a method for extracting the characteristic intrinsic mode function (IMF) from various multidimensional time-series signals. Variational mode decomposition (VMD) searches for IMFs by optimizing the bandwidth to a narrow band with the [Formula: see text] norm while preserving the online estimated central frequency. In this study, we applied VMD to the analysis of electroencephalogram (EEG) recorded during general anesthesia. Using a bispectral index monitor, EEGs were recorded from 10 adult surgical patients (the median age: 47.0, and the percentile range: 27.0-59.3 years) who were anesthetized with sevoflurane. We created an application named EEG Mode Decompositor, which decomposes the recorded EEG into IMFs and displays the Hilbert spectrogram. Over the 30-min recovery from general anesthesia, the median (25-75 percentile range) bispectral index increased from 47.1 (42.2-50.4) to 97.4 (96.5-97.6), and the central frequencies of IMF-1 showed a significant change from 0.4 (0.2-0.5) Hz to 0.2 (0.1-0.3) Hz. IMF-2, IMF-3, IMF-4, IMF-5, and IMF-6 increased significantly from 1.4 (1.2-1.6) Hz to 7.5 (1.5-9.3) Hz, 6.7 (4.1-7.6) Hz to 19.4 (6.9-20.0) Hz, 10.9 (8.8-11.4) Hz to 26.4 (24.2-27.2) Hz, 13.4 (11.3-16.6) Hz to 35.6 (34.9-36.1) Hz, and 12.4 (9.7-18.1) Hz to 43.2 (42.9-43.4) Hz, respectively. The characteristic frequency component changes in specific IMFs during emergence from general anesthesia were visually captured by IMFs derived using VMD. EEG analysis by VMD is useful for extracting distinct changes during general anesthesia.
Asunto(s)
Anestesia General , Electroencefalografía , Adulto , Humanos , Persona de Mediana Edad , Sevoflurano , Monitores de ConcienciaRESUMEN
We previously reported that extracellular vesicles (EVs) released during Escherichia coli (E. coli) bacterial pneumonia were inflammatory, and administration of high molecular weight hyaluronic acid (HMW HA) suppressed several indices of acute lung injury (ALI) from E. coli pneumonia by binding to these inflammatory EVs. The current study was undertaken to study the therapeutic effects of HMW HA in ex vivo perfused human lungs injured with Pseudomonas aeruginosa (PA)103 bacterial pneumonia. For lungs with baseline alveolar fluid clearance (AFC) <10%/h, HMW HA 1 or 2 mg was injected intravenously after 1 h (n = 4-9), and EVs released during PA pneumonia were collected from the perfusate over 6 h. For lungs with baseline AFC > 10%/h, HMW HA 2 mg was injected intravenously after 1 h (n = 6). In vitro experiments were conducted to evaluate the effects of HA on inflammation and bacterial phagocytosis. For lungs with AFC < 10%/h, administration of HMW HA intravenously significantly restored AFC and numerically decreased protein permeability and alveolar inflammation from PA103 pneumonia but had no effect on bacterial counts at 6 h. However, HMW HA improved bacterial phagocytosis by human monocytes and neutrophils and suppressed the inflammatory properties of EVs released during pneumonia on monocytes. For lungs with AFC > 10%/h, administration of HMW HA intravenously improved AFC from PA103 pneumonia but had no significant effects on protein permeability, inflammation, or bacterial counts. In the presence of impaired alveolar epithelial transport capacity, administration of HMW HA improved the resolution of pulmonary edema from Pseudomonas PA103 bacterial pneumonia.
Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Ácido Hialurónico/farmacología , Neumonía Bacteriana/tratamiento farmacológico , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Edema Pulmonar/tratamiento farmacológico , Lesión Pulmonar Aguda/microbiología , Lesión Pulmonar Aguda/patología , Adulto , Vesículas Extracelulares/patología , Femenino , Humanos , Pulmón/efectos de los fármacos , Pulmón/microbiología , Pulmón/patología , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Neutrófilos/inmunología , Técnicas de Cultivo de Órganos , Fagocitosis/efectos de los fármacos , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/patología , Edema Pulmonar/microbiología , Edema Pulmonar/patología , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/microbiología , Síndrome de Dificultad Respiratoria/patologíaRESUMEN
Rationale: Recent studies have demonstrated that extracellular vesicles (EVs) released during acute lung injury (ALI) were inflammatory.Objectives: The current study was undertaken to test the role of EVs induced and released from severe Escherichia coli pneumonia (E. coli EVs) in the pathogenesis of ALI and to determine whether high-molecular-weight (HMW) hyaluronic acid (HA) administration would suppress lung injury from E. coli EVs or bacterial pneumonia.Methods:E. coli EVs were collected from the perfusate of an ex vivo perfused human lung injured with intrabronchial E. coli bacteria for 6 hours by ultracentrifugation and then given intrabronchially or intravenously to naive human lungs. One hour later, HMW HA was instilled into the perfusate (n = 5-6). In separate experiments, HMW HA was given after E. coli bacterial pneumonia (n = 6-10). In vitro experiments were conducted to evaluate binding of EVs to HMW HA and uptake of EVs by human monocytes.Measurements and Main Results: Administration of HMW HA ameliorated the impairment of alveolar fluid clearance, protein permeability, and acute inflammation from E. coli EVs or pneumonia and reduced total bacteria counts after E. coli pneumonia. HMW HA bound to E. coli EVs, inhibiting the uptake of EVs by human monocytes, an effect associated with reduced TNFα (tumor necrosis factor α) secretion. Surprisingly, HMW HA increased E. coli bacteria phagocytosis by monocytes.Conclusions: EVs induced and released during severe bacterial pneumonia were inflammatory and induced ALI, and HMW HA administration was effective in inhibiting the uptake of EVs by target cells and decreasing lung injury from E. coli EVs or bacterial pneumonia.
Asunto(s)
Lesión Pulmonar Aguda/terapia , Adyuvantes Inmunológicos/uso terapéutico , Infecciones por Escherichia coli/terapia , Ácido Hialurónico/uso terapéutico , Neumonía Bacteriana/terapia , Lesión Pulmonar Aguda/etiología , Infecciones por Escherichia coli/complicaciones , Vesículas Extracelulares , Humanos , Neumonía Bacteriana/etiología , Técnicas de Cultivo de TejidosRESUMEN
An effective vaccine against Pseudomonas aeruginosa would be hugely beneficial to people who are susceptible to the serious infections it can cause. Vaccination against PcrV of the P. aeruginosa type III secretion system is a potential prophylactic strategy for improving the incidence and prognosis of P. aeruginosa pneumonia. Here, the effect of nasal PcrV adjuvanted with CpG oligodeoxynucleotide (CpG) was compared with a nasal PcrV/aluminum hydroxide gel (alum) vaccine. Seven groups of mice were vaccinated intranasally with one of the following: 1, PcrV-CpG; 2, PcrV-alum; 3, PcrV alone; 4, CpG alone; 5, alum alone; 6 and 7, saline control. Fifty days after the first immunization, anti-PcrV IgG, IgA and IgG isotype titers were measured; significant increases in these titers were detected only in the PcrV-CpG vaccinated mice. The vaccinated mice were then intratracheally infected with a lethal dose of P. aeruginosa and their body temperatures and survival monitored for 24 hr, edema, bacteria, myeloperoxidase activity and lung histology also being evaluated at 24 hr post-infection. It was found that 73% of the PcrV-CpG-vaccinated mice survived, whereas fewer than 30% of the mice vaccinated with PcrV-alum or adjuvant alone survived. Lung edema and other inflammation-related variables were less severe in the PcrV-CpG group. The significant increase in PcrV-specific IgA titers detected following PcrV-CpG vaccination is probably a component of the disease protection mechanism. Overall, our data show that intranasal PcrV-CpG vaccination has potential efficacy for clinical application against P. aeruginosa pneumonia.
Asunto(s)
Antígenos Bacterianos/inmunología , Toxinas Bacterianas/inmunología , Oligodesoxirribonucleótidos/inmunología , Neumonía/prevención & control , Proteínas Citotóxicas Formadoras de Poros/inmunología , Infecciones por Pseudomonas/prevención & control , Vacunas contra la Infección por Pseudomonas/inmunología , Pseudomonas aeruginosa/efectos de los fármacos , Vacunación , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Animales , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Antígenos Bacterianos/genética , Toxinas Bacterianas/genética , Temperatura Corporal , Modelos Animales de Enfermedad , Edema , Pulmón/inmunología , Pulmón/patología , Masculino , Ratones , Oligodesoxirribonucleótidos/genética , Peroxidasa/análisis , Proteínas Citotóxicas Formadoras de Poros/genética , Infecciones por Pseudomonas/inmunología , Infecciones por Pseudomonas/microbiología , Vacunas contra la Infección por Pseudomonas/administración & dosificación , Pseudomonas aeruginosa/patogenicidad , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Tasa de Supervivencia , Sistemas de Secreción Tipo III/inmunologíaRESUMEN
Antimicrobial-resistant isolates of Pseudomonas aeruginosa collected from 2005 to 2014 in a university hospital in Kyoto, Japan, were retrospectively analyzed by multilocus sequence typing (MLST), exoenzyme genotype determination, integron characterization, and clinical associations. During the study, 1573 P. aeruginosa isolates were detected, and 41 of these were resistant to more than two classes of antimicrobial agents. Twenty-five (61.0%) isolates were collected from urine. All isolates were resistant to ciprofloxacin, 8 (19.5%) isolates showed resistance to imipenem/cilastatin, and 8 (19.5%) isolates showed resistance to meropenem. None of the isolates fulfilled the clinical criteria for multidrug-resistant P. aeruginosa. All isolates were negative in the metallo-ß lactamase test. Thirty-six (87.8%) isolates were of the exoS-exoU+ genotype and 5 (12.2%) isolates were of the exoS+exoU- genotype. Among 36 exoS-exoU+ isolates, 33 (80.5%) were ST357, and 3 (7.3%) were ST235. Five isolates of exoS+exoU- were ST186, ST244, ST314, ST508, and ST512. Thirty-three isolates were positive for class 1 integrons and four different class 1 integrons were detected: aminoglycoside (2') adenyltransferase and chloramphenicol transporter (AadB+CmlA6), OXA-4 ß-lactamase and aminoglycoside 3'-adenyltransferase (OXA4+AadA2), AadB alone, and aminoglycoside acetyltransferase alone (AacA31). Among the 41 patients from which the isolates originated, the most common underlying disease was cancer in 16 patients (39%), and 9 patients (22.0%) died during the hospitalization period. There was no statistical correlation between MLST, exoenzyme genotype, and patient mortality. The results indicated outbreaks of fluoroquinolone-resistant P. aeruginosa in immunocompromised patients mainly due to the propagation of potentially virulent ST357 isolates possessing the exoU+ genotype.
Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/genética , Brotes de Enfermedades , Farmacorresistencia Bacteriana/genética , Fluoroquinolonas/farmacología , Infecciones por Pseudomonas/epidemiología , Pseudomonas aeruginosa/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aminoglicósidos/farmacología , Aminoglicósidos/uso terapéutico , Antibacterianos/uso terapéutico , Femenino , Fluoroquinolonas/uso terapéutico , Genotipo , Humanos , Huésped Inmunocomprometido , Integrones/genética , Japón/epidemiología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Tipificación de Secuencias Multilocus , Infecciones por Pseudomonas/inmunología , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/aislamiento & purificación , Pseudomonas aeruginosa/patogenicidad , Adulto JovenRESUMEN
Vaccination against the type III secretion system of P. aeruginosa is a potential prophylactic strategy for reducing the incidence and improving the poor prognosis of P. aeruginosa pneumonia. In this study, the efficacies of three different adjuvants, Freund's adjuvant (FA), aluminum hydroxide (alum) and CpG oligodeoxynucleotide (ODN), were examined from the viewpoint of inducing PcrV-specific immunity against virulent P. aeruginosa. Mice that had been immunized intraperitoneally with recombinant PcrV formulated with one of the above adjuvants were challenged intratracheally with a lethal dose of P. aeruginosa. The PcrV-FA immunized group attained a survival rate of 91%, whereas the survival rates of the PcrV-alum and PcrV-CpG groups were 73% and 64%, respectively. In terms of hypothermia recovery after bacterial instillation, PcrV-alum was the most protective, followed by PcrV-FA and PcrV-CpG. The lung edema index was lower in the PcrV-CpG vaccination group than in the other groups. PcrV-alum immunization was associated with the greatest decrease in myeloperoxidase in infected lungs, and also decreased the number of lung bacteria to a similar number as in the PcrV-FA group. There was less neutrophil recruitment in the lungs of mice vaccinated with PcrV-alum or PcrV-CpG than in those of mice vaccinated with PcrV-FA or PcrV alone. Overall, in terms of mouse survival the PcrV-CpG vaccine, which could be a relatively safe next-generation vaccine, showed a comparable effect to the PcrV-alum vaccine.
Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Antígenos Bacterianos/inmunología , Toxinas Bacterianas/inmunología , Neumonía Bacteriana/prevención & control , Proteínas Citotóxicas Formadoras de Poros/inmunología , Infecciones por Pseudomonas/prevención & control , Vacunas contra la Infección por Pseudomonas/inmunología , Pseudomonas aeruginosa/inmunología , Hidróxido de Aluminio/administración & dosificación , Animales , Carga Bacteriana , Adyuvante de Freund/administración & dosificación , Pulmón/microbiología , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos ICR , Oligodesoxirribonucleótidos/administración & dosificación , Vacunas contra la Infección por Pseudomonas/administración & dosificación , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Vector flow mapping, a novel flow visualization echocardiographic technology, is increasing in popularity. Energy loss reference values for children have been established using vector flow mapping, but those for adults have not yet been provided. We aimed to establish reference values in healthy adults for energy loss, kinetic energy in the left ventricular outflow tract, and the energetic performance index (defined as the ratio of kinetic energy to energy loss over one cardiac cycle). METHODS: Transthoracic echocardiography was performed in fifty healthy volunteers, and the stored images were analyzed to calculate energy loss, kinetic energy, and energetic performance index and obtain ranges of reference values for these. RESULTS: Mean energy loss over one cardiac cycle ranged from 10.1 to 59.1 mW/m (mean ± SD, 27.53 ± 13.46 mW/m), with a reference range of 10.32 ~ 58.63 mW/m. Mean systolic energy loss ranged from 8.5 to 80.1 (23.52 ± 14.53) mW/m, with a reference range of 8.86 ~ 77.30 mW/m. Mean diastolic energy loss ranged from 7.9 to 86 (30.41 ± 16.93) mW/m, with a reference range of 8.31 ~ 80.36 mW/m. Mean kinetic energy in the left ventricular outflow tract over one cardiac cycle ranged from 200 to 851.6 (449.74 ± 177.51) mW/m with a reference range of 203.16 ~ 833.15 mW/m. The energetic performance index ranged from 5.3 to 37.6 (18.48 ± 7.74), with a reference range of 5.80 ~ 36.67. CONCLUSIONS: Energy loss, kinetic energy, and energetic performance index reference values were defined using vector flow mapping. These reference values enable the assessment of various cardiac conditions in any clinical situation.
Asunto(s)
Circulación Coronaria , Ecocardiografía Doppler en Color/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Contracción Miocárdica , Imagen de Perfusión Miocárdica/métodos , Función Ventricular Izquierda , Adulto , Fenómenos Biomecánicos , Transferencia de Energía , Femenino , Voluntarios Sanos , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Valores de Referencia , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Arterial pulse waveform analysis (APWA) with a semi-invasive cardiac output monitoring device is popular in perioperative hemodynamic and fluid management. However, in APWA, evaluation of hemodynamic data is not well discussed. In this study, we analyzed how we visually interpret hemodynamic data, including stroke volume variation (SVV) and stroke volume (SV) derived from APWA. We performed arithmetic estimation of the SVV-SV relationship and applied measured values to this estimation. We then collected measured values in six anesthesia cases, including three liver transplantations and three other types of surgeries, to apply them to this SVV-SVI (stroke volume variation index) plot. Arithmetic analysis showed that the relationship between SVV and SV can be drawn as hyperbolic curves. Plotting SVV-SV values in the semi-logarithmic scale showed linear correlations, and the slopes of the linear regression lines theoretically represented average mean cardiac contractility. In clinical measurements in APWA, plotting SVV and SVI values in the linear scale and the semi-logarithmic scale showed the correlations represented by hyperbolic curves and linear regression lines. The plots approximately shifted on the rectangular hyperbolic curves, depending on blood loss and blood transfusion. Arithmetic estimation is close to real measurement of the SVV-SV interaction in hyperbolic curves. In APWA, using SVV as an index of preload and the cardiac index or SVI derived from arterial pressure-based cardiac output as an index of cardiac function, is likely to be appropriate for categorizing hemodynamic stages as a substitute for Forrester subsets.
Asunto(s)
Fluidoterapia , Hemodinámica , Monitoreo Fisiológico/métodos , Volumen Sistólico , Adulto , Anciano , Anestesia , Presión Arterial , Arterias , Presión Sanguínea , Gasto Cardíaco , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Curva ROC , Respiración Artificial , Procesamiento de Señales Asistido por Computador , Volumen de Ventilación Pulmonar , Signos Vitales , Adulto JovenRESUMEN
Of the various virulence mechanisms of the opportunistic pathogen Pseudomonas aeruginosa, the type III secretion system (TTSS) has been characterized as a major factor associated with acute lung injury, bacteremia and mortality. In addition, PcrV, a component protein of the TTSS, has been characterized as a protective antigen against infection with P. aeruginosa. This study comprised an epidemiological analysis of serum anti-PcrV titers in a cohort of Japanese adults. From April 2012 to March 2013, serum anti-PcrV titers of 198 volunteer participants undergoing anesthesia for scheduled surgeries were measured. The median, minimum and maximum serum anti-PcrV titers among the 198 participants were 4.09 nM, 1.01 nM and 113.81 nM, respectively. The maximum peaks in the histogram were within the anti-PcrV 2.00-4.99 nM titer range; values for 115 participants (58.1%) were within this range. Anti-PcrV titers were more than approximately three-fold greater (>12 nM) than the median value in 21 participants (10.6%). Ten-year interval age increases, history of treatment for traffic trauma, and a history of past surgery each showed statistically significant associations with higher anti-PcrV titers (i.e., >10 nM) than did the other factors assessed by binomial analysis. This study revealed a considerable variation in anti-PcrV titers in adult subjects without any obvious histories of infection with P. aeruginosa.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Infecciones por Pseudomonas/epidemiología , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antibacterianos/inmunología , Anticuerpos Monoclonales/sangre , Anticuerpos Monoclonales/inmunología , Antígenos Bacterianos/sangre , Antígenos Bacterianos/inmunología , Bacteriemia/sangre , Bacteriemia/epidemiología , Bacteriemia/inmunología , Bacteriemia/microbiología , Toxinas Bacterianas/sangre , Toxinas Bacterianas/inmunología , Estudios de Cohortes , Femenino , Humanos , Inmunoglobulina G/inmunología , Japón/epidemiología , Masculino , Persona de Mediana Edad , Proteínas Citotóxicas Formadoras de Poros/sangre , Proteínas Citotóxicas Formadoras de Poros/inmunología , Infecciones por Pseudomonas/sangre , Infecciones por Pseudomonas/inmunología , Pseudomonas aeruginosa/aislamiento & purificación , Sistemas de Secreción Tipo III/inmunología , Adulto JovenRESUMEN
Multi-drug resistant Pseudomonas aeruginosa causes the type of acute lung injury that is strongly associated with bacteremia, sepsis, and mortality, especially under immunocompromised conditions. Although administration of immunoglobulin solution is an applicable immunotherapy in immunocompromised patients, efficacy of immunoglobulin administration against multi-drug resistant P. aeruginosa pneumonia has not been well evaluated. In this study, we investigated the effectiveness of prophylactic administration of immunoglobulin solution (IVIG) in comparison with that of other types of antimicrobial agents, such as anti-PcrV IgG, piperacillin/tazobactam, or colistin in an immunocompromised mouse model of P. aeruginosa pneumonia. Colistin was the most effective agent for preventing acute lung injury, bacteremia, cytokinemia, and sepsis. Among the four tested antimicrobial agents, after colistin, anti-PcrV IgG and IVIG were the most effective at protecting mice from mortality. Piperacillin/tazobactam did not prevent acute lung injury or bacteremia; rather, it worsened lung histology. The data suggest that using an agent for which a positive result in an in vitro susceptibility test has been obtained may not always prevent acute lung injury in a leukopenic host infected with P. aeruginosa. Clinicians should consider the possibility of discrepancies between in vitro and in vivo tests because the absence of in vitro bactericidal activity in an antimicrobial agent is not always a reliable predictor of its lack of ability to eradicate bacteria in vivo, even in immunocompromised hosts. Based on our findings, the potential protective effects of IVIG against the acute lung injury induced by P. aeruginosa should be reevaluated.
Asunto(s)
Antibacterianos/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Leucopenia/tratamiento farmacológico , Neumonía Bacteriana/tratamiento farmacológico , Sustancias Protectoras/uso terapéutico , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa , Animales , Temperatura Corporal , Colistina/uso terapéutico , Citocinas/metabolismo , Edema , Inmunoglobulina G/uso terapéutico , Leucopenia/complicaciones , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos ICR , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/uso terapéutico , Peroxidasa/metabolismo , Piperacilina/uso terapéutico , Neumonía Bacteriana/complicaciones , Neumonía Bacteriana/mortalidad , Profilaxis Pre-Exposición , Infecciones por Pseudomonas/complicaciones , Infecciones por Pseudomonas/mortalidad , TazobactamRESUMEN
BACKGROUND: Mediastinoscopic surgery for esophageal cancer facilitates early postoperative recovery. However, it can occasionally cause serious complications. Here, we present the case of a patient with a tracheal injury diagnosed by a sudden increase in end-tidal carbon dioxide (EtCO2) during mediastinoscopic subtotal esophagectomy. CASE PRESENTATION: A 52-year-old man diagnosed with esophageal cancer was scheduled to undergo mediastinoscopic subtotal esophagectomy. During the mediastinoscopic procedure, the EtCO2 level suddenly increased above 200 mmHg, and the blood pressure dropped below 80 mmHg. We immediately asked the operator to stop insufflation and found a tracheal injury on the right side of the trachea near the carina by bronchoscopy. The endotracheal tube was replaced with a double-lumen tube, and the trachea was repaired via right thoracotomy. There were no further intraoperative complications. After surgery, the patient was extubated and admitted to the intensive care unit. CONCLUSIONS: Monitoring EtCO2 levels and close communication with the operator is important for safely managing sudden tracheal injury during mediastinoscopic esophagectomy.
RESUMEN
Acute lung injury caused by Pseudomonas aeruginosa is attributed to the translocation of cytotoxin into pulmonary epithelial cells via the P. aeruginosa type III secretion system. This virulence can be blocked with a specific antibody against PcrV in this secretion system. However, because anti-PcrV antibodies do not have bactericidal activity, the treatment of bacteria depends on the phagocytic system of the host. In this study, we investigated the therapeutic effect of combination therapy with an anti-PcrV antibody and bactericidal bacteriophages on acute lung injury and subsequent death in mice compared with a single treatment. After the mice intratracheally received a lethal dose of the cytotoxic P. aeruginosa strain, a second instillation was performed with saline, anti-PcrV IgG, bacteriophages, or a mixture of anti-PcrV and bacteriophages. The survival rates 24 h after infection were as follows: 7.1% in the saline group, 26.7% in the anti-PcrV group, 41.2% in the phage group, and 66.7% in the anti-PcrV + phage group (P < 0.001 vs saline-treated group). The activity of surviving mice in the anti-PcrV + phage group was significantly greater than that in the saline group. The lung weight in the anti-PcrV + phage group was significantly lower than that in the anti-PcrV group. In conclusion, combination therapy with an anti-PcrV antibody and a bacteriophage reduces acute lung injury and suggests improved survival compared with each treatment alone. This combination therapy, which does not rely on conventional antibiotics, could constitute a new strategy for treating multidrug-resistant P. aeruginosa infections.IMPORTANCECombination therapy with either bacteriophages alone or in combination with anti-PcrV antibodies in a mouse model of Pseudomonas aeruginosa pneumonia may reduce the acute lung injury and improve survival. This combination therapy, which does not rely on conventional antibiotics, may be a new strategy to treat multidrug-resistant Pseudomonas aeruginosa infections.
RESUMEN
PURPOSE: Left atrial enlargement correlates with the severity of diastolic dysfunction and is a predictor of cardiovascular complications such as atrial fibrillation. Aortic valve stenosis (AS) causes left atrial enlargement and progression of diastolic dysfunction. The aim of this study was to investigate the efficacy of the preoperative left atrial volume index (LAVI) in predicting postoperative outcome in patients with severe AS. METHODS: Forty-seven patients with severe AS who underwent aortic valve replacement were examined. Transthoracic echocardiography and LAVI measurement were performed on admission. Patients were divided into two groups according to optimal cut-off values of LAVI derived from receiver operating characteristic curves for postoperative atrial fibrillation (POAF) (group S: LAVI <52 ml/m(2), group L: LAVI ≥52 ml/m(2)). The incidence of POAF, ventilation time, inotropic support time, duration of stay in intensive care, and overall duration of hospital stay were evaluated. RESULTS: By univariate analysis, the incidence of POAF in group S was significantly lower than that in group L (25.9 and 65.0%, respectively; P < 0.01). Values for other parameters were higher in group L, although the differences were insignificant. CONCLUSION: In patients with severe AS, a preoperative LAVI of ≥52 ml/m(2) may be a useful predictor of POAF, although the efficacy of this index for predicting other postoperative outcomes has yet to be determined.
Asunto(s)
Estenosis de la Válvula Aórtica/fisiopatología , Válvula Aórtica/fisiopatología , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Corazón/fisiopatología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/fisiopatología , Anciano , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Ecocardiografía/métodos , Femenino , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Atrios Cardíacos/cirugía , Humanos , Incidencia , Masculino , Complicaciones Posoperatorias/diagnóstico por imagen , Periodo Preoperatorio , Pronóstico , Curva ROC , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
An effective vaccine against Pseudomonas aeruginosa would benefit people susceptible to severe infection. Vaccination targeting V antigen (PcrV) of the P. aeruginosa type III secretion system is a potential prophylactic strategy for reducing P. aeruginosa-induced acute lung injury and acute mortality. We created a recombinant protein (designated POmT) comprising three antigens: full-length PcrV (PcrV#1-#294), the outer membrane domain (#190-342) of OprF (OprF#190-#342), and a non-catalytic mutant of the carboxyl domain (#406-613) of exotoxin A (mToxA#406-#613(E553Δ)). In the combination of PcrV and OprF, mToxA, the efficacy of POmT was compared with that of single-antigen vaccines, two-antigen mixed vaccines, and a three-antigen mixed vaccine in a murine model of P. aeruginosa pneumonia. As a result, the 24 h-survival rates were 79%, 78%, 21%, 7%, and 36% in the POmT, PcrV, OprF, mTox, and alum-alone groups, respectively. Significant improvement in acute lung injury and reduction in acute mortality within 24 h after infection was observed in the POmT and PcrV groups than in the other groups. Overall, the POmT vaccine exhibited efficacy comparable to that of the PcrV vaccine. The future goal is to prove the efficacy of the POmT vaccine against various P. aeruginosa strains.
Asunto(s)
Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Velocidad del Flujo Sanguíneo/fisiología , Ecocardiografía Transesofágica/métodos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Estenosis de la Válvula Aórtica/fisiopatología , Preescolar , Ecocardiografía Transesofágica/tendencias , Implantación de Prótesis de Válvulas Cardíacas/tendencias , Humanos , Masculino , Trasplante Autólogo/métodos , Trasplante Autólogo/tendenciasAsunto(s)
Estenosis de la Válvula Aórtica/diagnóstico por imagen , Complicaciones Intraoperatorias/diagnóstico por imagen , Monitoreo Intraoperatorio/métodos , Vectorcardiografía/métodos , Disfunción Ventricular Izquierda/diagnóstico por imagen , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/cirugía , Velocidad del Flujo Sanguíneo/fisiología , Femenino , Humanos , Disfunción Ventricular Izquierda/cirugíaRESUMEN
Lung endothelial permeability is a key pathological feature of acute respiratory distress syndrome. Hyaluronic acid (HA), a major component of the glycocalyx layer on the endothelium, is generated by HA synthase (HAS) during inflammation and injury and is critical for repair. We hypothesized that administration of exogenous high molecular weight (HMW) HA would restore protein permeability across human lung microvascular endothelial cells (HLMVEC) injured by an inflammatory insult via upregulation of HAS by binding to CD44. A transwell coculture system was used to study the effects of HA on protein permeability across HLMVEC injured by cytomix, a mixture of IL-1ß, TNFα, and IFNγ, with or without HMW or low molecular weight (LMW) HA. Coincubation with HMW HA, but not LMW HA, improved protein permeability following injury at 24 h. Fluorescence microscopy demonstrated that exogenous HMW HA partially prevented the increase in "actin stress fiber" formation. HMW HA also increased the synthesis of HAS2 mRNA expression and intracellular HMW HA levels in HLMVEC following injury. Pretreatment with an anti-CD44 antibody or 4-methylumbelliferone, a HAS inhibitor, blocked the therapeutic effects. In conclusion, exogenous HMW HA restored protein permeability across HLMVEC injured by an inflammatory insult in part through upregulation of HAS2.
RESUMEN
ABSTRACT: Extracellular vesicles (EVs) have now been recognized as important mediators of cellular communication during injury and repair. We previously found that plasma EVs isolated from ex vivo perfused human lungs injured with Escherichia coli bacterial pneumonia were inflammatory, and exogenous administration of high molecular weight (HMW) hyaluronic acid (HA) as therapy bound to these EVs, decreasing inflammation and injury. In the current study, we studied the role of EVs released during severe Pseudomonas aeruginosa (PA) pneumonia in mice and determined whether intravenous administration of exogenous HMW HA would have therapeutic effects against the bacterial pneumonia. EVs were collected from the bronchoalveolar lavage fluid (BALF) of mice infected with PA103 by ultracentrifugation and analyzed by NanoSight and flow cytometry. In a cytotoxicity assay, administration of EVs released from infected mice (I-EVs) decreased the viability of A549 cells compared to EV isolated from sham control mice (C-EVs). Either exogenous HMW HA or an anti-CD44 antibody, when co-incubated with I-EVs, significantly improved the viability of the A549 cells. In mice with PA103 pneumonia, administration of HMW HA improved pulmonary edema and bacterial count in the lungs and decreased TNF-α and caspase-3 levels in the supernatant of lung homogenates. In conclusion, EVs isolated from BALF of mice with P. aeruginosa pneumonia were cytotoxic and inflammatory, and intravenous HMW HA administration was protective against P. aeruginosa pneumonia.
Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Vesículas Extracelulares/efectos de los fármacos , Ácido Hialurónico/uso terapéutico , Neumonía Bacteriana/tratamiento farmacológico , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa , Animales , Líquido del Lavado Bronquioalveolar/citología , Citotoxicidad Inmunológica/efectos de los fármacos , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Neumonía Bacteriana/etiología , Infecciones por Pseudomonas/complicacionesRESUMEN
BACKGROUND: There is currently no subjective, definitive evaluation method for therapeutic indication other than symptoms in aortic regurgitation. Energy loss, a novel parameter of cardiac workload, can be visualized and quantified using echocardiography vector flow mapping. The purpose of the present study was to evaluate whether energy loss in patients with chronic aortic regurgitation can quantify their subjective symptoms more clearly than other conventional metrics. METHODS: We studied 15 patients undergoing elective aortic valve surgery for aortic regurgitation. We divided the patients into symptomatic and asymptomatic groups using their admission records. We analyzed the mean energy loss in one cardiac cycle using transesophageal echocardiography during the preoperative period. The relationships between symptoms, energy loss, and other conventional metrics were statistically analyzed. RESULTS: There were seven and eight patients in the symptomatic and asymptomatic groups, respectively. The mean energy loss of one cardiac cycle was higher in the symptomatic group (121 mW/m [96-184]) than in the asymptomatic group (87 mW/m [80-103]) (p = 0.040), whereas the diastolic diameter was higher in the asymptomatic group (65 mm [59-78]) than in the symptomatic group (57 mm [51-57]) (p = 0.040). There was no significant difference between the symptomatic and asymptomatic groups in terms of other conventional metrics. CONCLUSIONS: An energy loss can quantify patients' subjective symptoms more clearly than other conventional metrics. The small sample size is the primary limitation of our study, further studies assessing larger cohort of patients are warranted to validate our findings.