ABSTRACT
Abstract Objective: The objectives of this study were to evaluate an automated device for ventilatory support based on AMBU manufactured in March 2020. Methods: The ESSI-1 INC was evaluated through pulmonary mechanics and physiology parameters through compensatory spirometer tests (TISSOTs), and an artificial lung Model5600i Dual Adult PNEU VIEW SYSTEM; it was also compared to the anesthetic ventilatory support equipment (AEONMED 7500) in porcine models, measuring ventilatory, hemodynamic and gasometric parameters. Results: This equipment (ESSI-1 INC) was successfully tested by mechanical and biological models, such as pigs in which its performance was evaluated in terms of variability of tidal volume, ventilation frequency, and I/E relationship versus the manual performance of two medical interns. All the results turned out as expected and were satisfactory. Conclusions: It is safe and effective equipment and should be tested and used in diverse clinical conditions to standardize the ventilatory safety and care of patients who require it.
Resumen Objetivo: Evaluar un dispositivo automatizado para la asistencia ventilatoria basado en un AMBU manufacturado en Marzo del 2020. Métodos: El ESSI-1 INC fue evaluado por medio de parámetros fisiológicos y mecánica pulmonar a través de pruebas de espirómetro compensatorios (TISSOT); pulmón artificial (Modelo 5600i Dual Adult PNEU VIEW SYSTEM); así como su desempeño comparado a la máquina de anestesia (AEONMED 7500) en modelos porcinos, midiendo criterios ventilatorios, hemodinámicos y gasométricos. Resultados: Este equipo (ESSI-1 INC) fue exitosamente probado por modelos mecánicos y biológicos, tales como cerdos donde su desempeño fue evaluado en términos de la variabilidad del volumen tidal, frecuencia ventilatoria, y relación I/E versus el desempeño manual de dos médicos. Todos los resultados finalizaron como se esperaba de forma satisfactoria. Conclusiones: Es un equipo seguro y efectivo, el cual debería ser probado y usado en distintas condiciones clínicas para estandarizar la seguridad ventilatoria y cuidado de pacientes que lo requieran.
ABSTRACT
OBJECTIVE: The objectives of this study were to evaluate an automated device for ventilatory support based on AMBU manufactured in March 2020. METHODS: The ESSI-1 INC was evaluated through pulmonary mechanics and physiology parameters through compensatory spirometer tests (TISSOTs), and an artificial lung Model5600i Dual Adult PNEU VIEW SYSTEM; it was also compared to the anesthetic ventilatory support equipment (AEONMED 7500) in porcine models, measuring ventilatory, hemodynamic and gasometric parameters. RESULTS: This equipment (ESSI-1 INC) was successfully tested by mechanical and biological models, such as pigs in which its performance was evaluated in terms of variability of tidal volume, ventilation frequency, and I/E relationship versus the manual performance of two medical interns. All the results turned out as expected and were satisfactory. CONCLUSIONS: It is safe and effective equipment and should be tested and used in diverse clinical conditions to standardize the ventilatory safety and care of patients who require it.
OBJETIVO: Evaluar un dispositivo automatizado para la asistencia ventilatoria basado en un AMBU manufacturado en Marzo del 2020. MÉTODOS: El ESSI-1 INC fue evaluado por medio de parámetros fisiológicos y mecánica pulmonar a través de pruebas de espirómetro compensatorios (TISSOT); pulmón artificial (Modelo 5600i Dual Adult PNEU VIEW SYSTEM); así como su desempeño comparado a la máquina de anestesia (AEONMED 7500) en modelos porcinos, midiendo criterios ventilatorios, hemodinámicos y gasométricos. RESULTADOS: Este equipo (ESSI-1 INC) fue exitosamente probado por modelos mecánicos y biológicos, tales como cerdos donde su desempeño fue evaluado en términos de la variabilidad del volumen tidal, frecuencia ventilatoria, y relación I/E versus el desempeño manual de dos médicos. Todos los resultados finalizaron como se esperaba de forma satisfactoria. CONCLUSIONES: Es un equipo seguro y efectivo, el cual debería ser probado y usado en distintas condiciones clínicas para estandarizar la seguridad ventilatoria y cuidado de pacientes que lo requieran.
Subject(s)
Cardiology , Respiration, Artificial , Animals , Humans , Swine , Spirometry , Respiration, Artificial/instrumentationABSTRACT
BACKGROUND: In the setting of hepatitis C virus (HCV) active infection, liver stiffness (LS)-based strategies identify patients with low risk of developing esophageal variceal bleeding (VB) episodes, in whom unnecessary upper esophagogastroduodenoscopy (UGE) screening can be safely avoided. However, after sustained virological response (SVR), data on the accuracy of the criteria predicting this outcome in HCV-infected patients with cirrhosis, with or without human immunodeficiency virus (HIV) coinfection, are very limited. METHODS: This was a multicenter prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they had (1) SVR with direct-acting antiviral-based therapy; (2) LS ≥9.5 kPa previous to treatment; and (3) LS measurement at the SVR time-point ≥14 kPa. Diagnostic accuracy of HEPAVIR, expanded Baveno VI, and HIV cirrhosis criteria, at the time of SVR, was evaluated. Missed VB episodes, negative predictive values (NPVs), and number of spared UGEs were specifically assessed. RESULTS: Four hundred thirty-five patients were included, 284 (65%) coinfected with HIV. Seven (1.6%) patients developed a first episode of VB after SVR. In patients without a previous VB episode, HEPAVIR, expanded Baveno VI and HIV cirrhosis criteria achieved NPV for first VB episode after SVR of 99.5% (95% confidence interval [CI], 97.1%-100%), 100% (95% CI 97.8%-100%), and 100% (95% CI 98%-100%) while sparing 45%, 39%, and 44% of UGEs, respectively. When considering HIV coinfection, the performance of the 3 criteria was similar, both in HCV-monoinfected and HIV/HCV-coinfected individuals. CONCLUSIONS: After SVR, predictive LS-based strategies accurately identify HCV-infected patients, HIV coinfected or not, with low risk of developing VB during follow-up. In these specific patients, using HIV cirrhosis criteria maximize the number of spared UGEs while missing no VB episode.
Subject(s)
Coinfection , Esophageal and Gastric Varices , HIV Infections , Hepatitis C, Chronic , Hepatitis C , Antiviral Agents/therapeutic use , Coinfection/drug therapy , Esophageal and Gastric Varices/drug therapy , Esophageal and Gastric Varices/etiology , Gastrointestinal Hemorrhage/drug therapy , HIV , HIV Infections/complications , HIV Infections/drug therapy , Hepacivirus , Hepatitis C/complications , Hepatitis C/drug therapy , Hepatitis C, Chronic/drug therapy , Humans , Liver Cirrhosis/drug therapy , Prospective Studies , Treatment OutcomeABSTRACT
INTRODUCTION: A drug-eluting coronary stent is being developed at the National Institute of Cardiology of Mexico for the treatment of ischemic heart disease. OBJECTIVE: To establish the best animal model for the tests, to show the advances in the drug-eluting stent prototype, to assess two drugs' antiproliferative activity and histological results. METHOD: Smooth muscle cell culture tests were performed in order to assess sirolimus and paclitaxel antiproliferative properties. The drugs were encapsulated inside the polymeric matrix of the stents. Rabbits and pigs were used as animal models. RESULTS: Sirolimus and paclitaxel showed an inhibitory effect, which was higher for the latter. Infrared spectroscopy and light and optical microscopy showed that the drug/polymer layer properly adhered to the stent. At a four-week follow-up, both animal models showed satisfactory clinical evolution and adequate histological response, although the porcine model was shown to be more suitable for future protocols. CONCLUSIONS: Preliminary tests of the drug-eluting stent provided bases for the development of a study protocol with an adequate number of pigs and with clinical angiographic and histopathological three-month follow-up.
INTRODUCCIÓN: En el Instituto Nacional de Cardiología de México se desarrolla una endoprótesis (stent) coronaria liberadora de fármacos para el tratamiento de la cardiopatía isquémica. OBJETIVO: Establecer el mejor modelo animal para las pruebas, mostrar los avances en el prototipo del stent liberador de fármacos, evaluar la actividad antiproliferativa de dos fármacos y los resultados histológicos. MÉTODO: Se realizaron cultivos de células de músculo liso para evaluar las propiedades antiproliferativas de sirolimus y paclitaxel. Los fármacos fueron encapsulados en el interior de la matriz polimérica de los stents. Se emplearon conejos y cerdos como modelos animales. RESULTADOS: Sirolimus y paclitaxel mostraron efecto inhibitorio, mayor en el segundo. La espectroscopia infrarroja y la microscopia óptica y electrónica mostraron que la capa del polímero con el fármaco se adhería adecuadamente al stent. A las cuatro semanas de seguimiento, ambos modelos animales mostraron evolución clínica satisfactoria y adecuada respuesta histológica, si bien el modelo porcino resultó más conveniente para protocolos futuros. CONCLUSIONES: Las pruebas preliminares del stent liberador de fármaco brindó bases para desarrollar el protocolo con un número adecuado en cerdos y con seguimiento clínico angiográfico e histopatológico a tres meses.
Subject(s)
Drug-Eluting Stents , Paclitaxel/administration & dosage , Sirolimus/administration & dosage , Animals , Disease Models, Animal , Female , Follow-Up Studies , Male , Microscopy , Prosthesis Design , Rabbits , Spectrophotometry, Infrared , SwineABSTRACT
Abstract Introduction: A drug-eluting coronary stent is being developed at the National Institute of Cardiology of Mexico for the treatment of ischemic heart disease. Objective: To establish the best animal model for the tests, to show the advances in the drug-eluting stent prototype, to assess two drugs antiproliferative activity and histological results. Method: Smooth muscle cell culture tests were performed in order to assess sirolimus and paclitaxel antiproliferative properties. The drugs were encapsulated inside the polymeric matrix of the stents. Rabbits and pigs were used as animal models. Results: Sirolimus and paclitaxel showed an inhibitory effect, which was higher for the latter. Infrared spectroscopy and light and optical microscopy showed that the drug/polymer layer properly adhered to the stent. At a four-week follow-up, both animal models showed satisfactory clinical evolution and adequate histological response, although the porcine model was shown to be more suitable for future protocols. Conclusions: Preliminary tests of the drug-eluting stent provided bases for the development of a study protocol with an adequate number of pigs and with clinical angiographic and histopathological three-month follow-up.
Resumen Introducción: En el Instituto Nacional de Cardiología de México se desarrolla una endoprótesis (stent) coronaria liberadora de fármacos para el tratamiento de la cardiopatía isquémica. Objetivo: Establecer el mejor modelo animal para las pruebas, mostrar los avances en el prototipo del stent liberador de fármacos, evaluar la actividad antiproliferativa de dos fármacos y los resultados histológicos. Método: Se realizaron cultivos de células de músculo liso para evaluar las propiedades antiproliferativas de sirolimus y paclitaxel. Los fármacos fueron encapsulados en el interior de la matriz polimérica de los stents. Se emplearon conejos y cerdos como modelos animales. Resultados: Sirolimus y paclitaxel mostraron efecto inhibitorio, mayor en el segundo. La espectroscopia infrarroja y la microscopia óptica y electrónica mostraron que la capa del polímero con el fármaco se adhería adecuadamente al stent. A las cuatro semanas de seguimiento, ambos modelos animales mostraron evolución clínica satisfactoria y adecuada respuesta histológica, si bien el modelo porcino resultó más conveniente para protocolos futuros. Conclusiones: Las pruebas preliminares del stent liberador de fármaco brindó bases para desarrollar el protocolo con un número adecuado en cerdos y con seguimiento clínico angiográfico e histopatológico a tres meses.
Subject(s)
Animals , Male , Female , Rabbits , Paclitaxel/administration & dosage , Sirolimus/administration & dosage , Drug-Eluting Stents , Prosthesis Design , Spectrophotometry, Infrared , Swine , Follow-Up Studies , Disease Models, Animal , MicroscopyABSTRACT
BACKGROUND: Previous studies have suggested that hepatocellular carcinoma (HCC) has an aggressive presentation and a shorter survival in people with HIV (PWH). This could be due to later diagnosis or lower rates of HCC treatment, and not to HIV infection itself. AIM: :: To assess the impact of HIV on HCC survival in hepatitis C virus (HCV)-infected patients. METHODS: Multicenter cohort study (1999-2018) of 342 and 135 HCC cases diagnosed in HIV/HCV-infected and HCV-monoinfected patients. Survival after HCC diagnosis and its predictors were assessed. RESULTS: HCC was at Barcelona-Clinic Liver-Cancer (BCLC) stage 0/A in 114 (33%) HIV/HCV-coinfected and in 76 (56%) HCV-monoinfected individuals (Pâ<â0.001). Of them, 97 (85%) and 50 (68%) underwent curative therapies (Pâ=â0.001). After a median (Q1-Q3) follow-up of 11 (3-31) months, 334 (70%) patients died. Overall 1 and 3-year survival was 50 and 31% in PWH and 69 and 34% in those without HIV (Pâ=â0.16). Among those diagnosed at BCLC stage 0/A, 1 and 3-year survival was 94 and 66% in PWH whereas it was 90 and 54% in HIV-negative patients (Pâ=â0.006). Independent predictors of mortality were age, BCLC stage and α-fetoprotein levels. HIV infection was not independently associated with mortality [adjusted hazard ratio (AHR) 1.57; 95% confidence interval: 0.88-2.78; Pâ=â0.12]. CONCLUSION: HIV coinfection has no impact on the survival after the diagnosis of HCC in HCV-infected patients. Although overall mortality is higher in HIV/HCV-coinfected patients, this seem to be related with lower rates of early diagnosis HCC in HIV-infected patients and not with HIV infection itself or a lower access to HCC therapy.
Subject(s)
Carcinoma, Hepatocellular/mortality , Coinfection , HIV Infections , Hepatitis C, Chronic , Liver Neoplasms/mortality , Cohort Studies , HIV Infections/complications , Hepacivirus , Hepatitis C, Chronic/complications , Humans , Liver Neoplasms/virology , Survival RateABSTRACT
BACKGROUND: The left atrial appendage (LAAp) resection is an effective treatment approach to reduce the risk of thromboembolism in patients with atrial fibrillation. OBJECTIVE: To study was to study the impact of removing atrial appendages in the production of natriuretic peptides (NPs) in conditions of volume overload and to develop an experimental model of LAAp resection. MATERIALS AND METHODS: In a swine model of ischemic heart failure (HF), serum NP levels were measured before (Basal-1A) and after (Basal-1B) a fluid overload. Animals were grouped as follows: (0) preserved appendages, (1) resected LAAp, and (2) both atrial appendages resected. Levels of NP were measured before (2A) and after a fluid overload (2B). RESULTS: Furin levels were higher in Group 0-2A than in Group 2-2A, and a significant increase was found in Group 0-2B compared to Groups 1-2B and 2-2B. Corin levels increased in Basal-1B versus Basal-1A. Atrial NP (ANP) decreased in Basal-1B compared to Basal-1A. After HF induction, ANP increased in Groups 2-2A and 2-2B. CONCLUSIONS: Resection of atrial appendages drastically modifies the natriuretic mechanisms of cardiac homeostasis, especially after a fluid overload challenge. Herein, we describe the face and predictive validation of an animal model of atrial appendage resection useful to investigations in translational medicine.
Subject(s)
Atrial Appendage/metabolism , Atrial Appendage/surgery , Disease Models, Animal , Heart Failure/metabolism , Heart Failure/surgery , Homeostasis , Natriuretic Peptides/biosynthesis , Natriuretic Peptides/physiology , Academic Medical Centers , Animals , Male , SwineABSTRACT
ABSTRACT Background: The left atrial appendage (LAAp) resection is an effective treatment approach to reduce the risk of thromboembolism in patients with atrial fibrillation. Objective: To study was to study the impact of removing atrial appendages in the production of natriuretic peptides (NPs) in conditions of volume overload and to develop an experimental model of LAAp resection. Materials and Methods: In a swine model of ischemic heart failure (HF), serum NP levels were measured before (Basal-1A) and after (Basal-1B) a fluid overload. Animals were grouped as follows: (0) preserved appendages, (1) resected LAAp, and (2) both atrial appendages resected. Levels of NP were measured before (2A) and after a fluid overload (2B). Results: Furin levels were higher in Group 0-2A than in Group 2-2A, and a significant increase was found in Group 0-2B compared to Groups 1-2B and 2-2B. Corin levels increased in Basal-1B versus Basal-1A. Atrial NP (ANP) decreased in Basal-1B compared to Basal-1A. After HF induction, ANP increased in Groups 2-2A and 2-2B. Conclusions: Resection of atrial appendages drastically modifies the natriuretic mechanisms of cardiac homeostasis, especially after a fluid overload challenge. Herein, we describe the face and predictive validation of an animal model of atrial appendage resection useful to investigations in translational medicine.
Subject(s)
Animals , Male , Atrial Appendage/surgery , Atrial Appendage/metabolism , Disease Models, Animal , Heart Failure/surgery , Heart Failure/metabolism , Homeostasis , Swine , Natriuretic Peptides/biosynthesis , Natriuretic Peptides/physiology , Academic Medical CentersABSTRACT
OBJECTIVE: Test anxiety (TA) is a construct that has scarcely been studied based on Lang's three-dimensional model of anxiety. The objective of this article is to investigate the repercussion of sociodemographic and academic variables on different responses for each component of anxiety and for the type of test in adolescent students. METHOD: A total of 1181 students from 12 to 18 years old (M = 14.7 and SD = 1.8) participated, of whom 569 were boys (48.2%) and 612 girls (51.8%). A sociodemographic questionnaire and the Cuestionario de Ansiedad ante los examenes-Adaptado (CAEX-A) [Test Anxiety Questionnaire-Adapted] an adaptation for Spanish secondary school levels (ESO) and Bachillerato were administered. RESULTS: Girls scored higher on the cognitive and physiological components of TA than boys, the intensity of the physiological response increasing with age. Bachillerato level students reported more physiological anxiety than those of ESO level. Students with better marks in the previous year presented more anxiety in the cognitive component, while those who obtained the lower mark presented higher anxiety values in the behavioral component. Participants reported that the types of tests that cause them more anxiety were oral tests in front of the class, oral presentation in front of a panel, and mathematics tests. CONCLUSION: Adolescents show a differential response of TA based on the physiological, cognitive and motor components, mediated by the variables of gender, age, grade, academic performance and type of exam. These results serve to design specific intervention programs to manage anxiety in situations of academic assessment.
ABSTRACT
Interleukin-7 receptor subunit alpha (IL7RA) rs6897932 polymorphism is related to CD4+ recovery after combination antiretroviral therapy (cART), but no studies so far have analyzed its potential impact in patients with very low CD4+ T-cells count. We aimed to analyze the association between IL7RA rs6897932 polymorphism and CD4+ T-cells count restoration in HIV-infected patients starting combination antiretroviral therapy (cART) with CD4+ T-cells count <200 cells/mm3. We performed a retrospective study in 411 patients followed for 24 months with a DNA sample available for genotyping. The change in CD4+ T-cells count during the follow-up was considered as the primary outcome. The rs6897932 polymorphism had a minimum allele frequency (MAF) >20% and was in Hardy-Weinberg equilibrium (p = 0.550). Of 411 patients, 256 carried the CC genotype, while 155 had the CT/TT genotype. The CT/TT genotype was associated with a higher slope of CD4+ T-cells recovery (arithmetic mean ratio; AMR = 1.16; p = 0.016), higher CD4+ T-cells increase (AMR = 1.19; p = 0.004), and higher CD4+ T-cells count at the end of follow-up (AMR = 1.13; p = 0.006). Besides, rs6897932 CT/TT was related to a higher odds of having a value of CD4+ T-cells at the end of follow-up ≥500 CD4+ cells/mm3 (OR = 2.44; p = 0.006). After multiple testing correction (Benjamini-Hochberg), only the increase of ≥ 400 CD4+ cells/mm3 lost statistical significance (p = 0.052). IL7RA rs6897932 CT/TT genotype was related to a better CD4+ T-cells recovery and it could be used to improve the management of HIV-infected patients starting cART with CD4+ T-cells count <200 cells/mm3.
Subject(s)
Anti-Retroviral Agents/pharmacology , HIV Infections/drug therapy , HIV Infections/genetics , Polymorphism, Single Nucleotide , Receptors, Interleukin-7/genetics , Adult , Anti-Retroviral Agents/therapeutic use , CD4 Lymphocyte Count , Drug Interactions , Female , Genotype , HIV Infections/immunology , Humans , Male , Middle AgedABSTRACT
OBJECTIVES: To compare the efficacy of sofosbuvir/ledipasvir (SOF/LDV) for 8 weeks (SL8) versus a 12-week course of SOF/LDV (SL12) among HIV/HCV-coinfected patients in clinical practice. In addition we compared sustained virological response (SVR) rates achieved with SL8 in HCV-monoinfected and HIV/HCV-coinfected patients in a real life setting. METHODS: HCV-infected patients were retrospectively selected from the HEPAVIR-DAA and GEHEP-MONO real-life prospective cohorts if they fulfilled the following criteria: 1) Infected with genotype 1; 2) Treatment with SL8 or SL12; 3) Treatment naïve prior to receiving SL8 or SL12; 4) Absence of cirrhosis; 5) Baseline HCV RNA<6â¯×â¯106 IU/mL; 6) Reached the scheduled time-point for SVR (SVR12) assessment. SVR12 and relapse rates of HCV-monoinfected and HIV/HCV-coinfected patients were compared on an intention to treat basis. The responses with SL8 and SL12 were also compared. RESULTS: In the SL8 group, 107 (51%) HCV-monoinfected and 102 (49%) HIV/HCV-coinfected patients were included. One hundred and sixty-four (43%) HCV-monoinfected subjects and 220 (57%) HIV/HCV-coinfected patients received SL12. SVR12 rates for HIV/HCV-coinfected patients treated with SL8 vs SL12 were SVR12 92.2% vs. 97.3% (pâ¯=â¯0.044) and the respective relapse rates were 4.9% vs. 0.5% (pâ¯=â¯0.013). SVR12 rates for SL8 among HCV-monoinfected and HIV/HCV-coinfected patients were: 96.3% vs. 92.2% (pâ¯=â¯0.243), respectively. The corresponding relapse rates were 0.9% vs. 4.9% (pâ¯=â¯0.112). CONCLUSION: HIV/HCV-coinfected patients reach high rates of SVR12 with SL8, although lower than with SL12, mainly due to a higher probability of relapse. SVR12 rates with SL8 are numerically lower and the proportion of relapses higher in HIV/HCVcoinfected patients than in HCV-monoinfected subjects.
Subject(s)
Antiviral Agents/therapeutic use , Benzimidazoles/therapeutic use , Coinfection/drug therapy , Fluorenes/therapeutic use , HIV Infections/complications , Hepatitis C, Chronic/drug therapy , Recurrence , Sofosbuvir/therapeutic use , Female , Humans , Male , Middle Aged , Retrospective Studies , Sustained Virologic Response , Treatment OutcomeABSTRACT
OBJECTIVE: To assess the performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma (HCC) in HIV-infected patients. METHODS: The GEHEP-002 cohort recruits HCC cases diagnosed in HIV-infected patients from 32 centers across Spain. The proportion of 'ultrasound lack of detection', defined as HCC diagnosed within the first 3 months after a normal surveillance ultrasound, and the proportion of 'surveillance failure', defined as cases in which surveillance failed to detect HCC at early stage, were assessed. To assess the impact of HIV, a control population of 104 HCC cases diagnosed in hepatitis C virus-monoinfected patients during the study period was used. RESULTS: A total of 186 (54%) out of 346 HCC cases in HIV-infected patients were diagnosed within an ultrasound surveillance program. Ultrasound lack of detection occurred in 16 (8.6%) of them. Ultrasound surveillance failure occurred in 107 (57%) out of 186 cases diagnosed by screening, whereas this occurred in 18 (29%) out of 62 diagnosed in the control group (Pâ<â0.0001). HCC cases after ultrasound surveillance failure showed a lower frequency of undetectable HIV viral load at diagnosis. The probability of 1-year and 2-year survival after HCC diagnosis among those diagnosed by screening was 56 and 45% in HIV-infected patients, whereas it was 79 and 64% in HIV-negative patients (Pâ=â0.038). CONCLUSION: The performance of ultrasound surveillance of HCC in HIV-infected patients is very poor and worse than that shown outside HIV infection. A HCC surveillance policy based on ultrasound examinations every 6 months might be insufficient in HIV-infected patients with cirrhosis.
Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , HIV Infections/complications , Liver Neoplasms/diagnostic imaging , Ultrasonography/methods , Aged , Carcinoma, Hepatocellular/epidemiology , Epidemiological Monitoring , Female , Humans , Liver Neoplasms/epidemiology , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Spain/epidemiologyABSTRACT
OBJECTIVE: To assess the possible association between the use of direct antiviral agents (DAA) and the risk of hepatocellular carcinoma (HCC) in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS: The GEHEP-002 cohort recruits HCC cases in HIV-infected patients from 32 centers from Spain. Three analyses were performed: the proportion of HCC cases after sustained virological response (SVR) and the evolution of this proportion over time, the frequency of HCC after SVR in HIV/HCV-coinfected patients with cirrhosis, and the probability of HCC recurrence after curative therapies among those undergoing HCV therapy. RESULTS: Forty-two (13%) out of 322 HCC cases in HIV/HCV-coinfected patients occurred after SVR. Twenty-eight (10%) out of 279 HCC cases diagnosed during the years of use of IFN-based regimens occurred after SVR whereas this occurred in 14 (32.6%) out of the 43 HCC cases diagnosed in the all-oral DAA period (Pâ<â0.0001). One thousand, three hundred and thirty-seven HIV/HCV-coinfected patients with cirrhosis achieved SVR in the cohort. The frequency of HCC after SVR declined from 15% among those cured with pegylated-IFN with ribavirin to 1.62 and 0.87% among those cured with DAA with and without IFN, respectively. In patients with previous HCC treated with curative therapies, HCC recurrence occurred in two (25%) out of eight patients treated with IFN-based regimens and four (21%) out of 19 treated with DAA-IFN-free regimens (Pâ=â1.0). CONCLUSION: The frequency of HCC emergence after SVR has not increased after widespread use of DAA in HIV/HCV-coinfected patients. DAA do not seem to impact on HCC recurrence in the short-term among those with previously treated HCC.
Subject(s)
Antiviral Agents/administration & dosage , Carcinoma, Hepatocellular/epidemiology , Coinfection/complications , Coinfection/drug therapy , HIV Infections/complications , Hepatitis C, Chronic/drug therapy , Sustained Virologic Response , Female , Hepatitis C, Chronic/complications , Humans , Male , Middle Aged , Prevalence , Risk Assessment , Spain/epidemiologyABSTRACT
A Streptomyces sp. isolated from a patient who had had breast reconstruction after a mastectomy was identified at the species level by comparative sequence analysis of 16S ribosomal DNA (rDNA) and the hypervariable alpha-region of the 16S rDNA.
Subject(s)
Breast Implantation/adverse effects , Gram-Positive Bacterial Infections/diagnosis , Streptomyces/classification , Streptomyces/genetics , Surgical Wound Infection/microbiology , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , Female , Genes, rRNA , Gram-Positive Bacterial Infections/microbiology , Humans , Middle Aged , Molecular Sequence Data , Phylogeny , RNA, Bacterial/genetics , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Sequence Homology, Nucleic Acid , Silicones , Streptomyces/isolation & purificationABSTRACT
Recombinant antibodies such as Fab and scFv are monovalent and small in size, although their functional affinity can be improved through tag-specific immobilization. In order to find the optimum candidate for oriented immobilization, we generated Fab and scFv fragments derived from an anti-pneumolysin monoclonal antibody PLY-7, with histidine and cysteine residues added in diverse arrangements. Tagged antibody fragments scFv-Cys7-His6, His6-scFv-Cys7, and Fab-Cys7 lost considerable affinity for the antigen; however, Fab-His6, Fab-Cys1, and scFv-His6-Cys1 were able to detect immobilized antigen, revealing that the position and number of histidine and cysteine residues are involved differently in the reactivity of antibody fragments. Random and orientated immobilizations were carried out using conventional polystyrene and commercial surface-pretreated ELISA plates. The best orientation performance was obtained with Fab-Cys1-biotin on streptavidin-coated plates with increased signal levels of 62%, while oriented immobilization of Fab-His6 and scFv-His6-Cys1 on nickel- and maleimide-coated plates failed to improve the ELISA sensitivity.
Subject(s)
Immunoglobulin Fragments/chemistry , Streptolysins/immunology , Bacterial Proteins/chemistry , Bacterial Proteins/immunology , Immunoglobulin Fragments/genetics , Immunoglobulin Fragments/immunology , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Streptolysins/chemistrySubject(s)
Gonorrhea/complications , Meningitis, Bacterial/complications , Meningitis, Bacterial/microbiology , Pregnancy Complications, Infectious/microbiology , Adolescent , Anti-Bacterial Agents/pharmacology , Base Sequence , Ciprofloxacin/pharmacology , DNA Primers/genetics , Drug Resistance, Multiple, Bacterial , Female , Gonorrhea/drug therapy , Gonorrhea/microbiology , Humans , Meningitis, Bacterial/drug therapy , Neisseria gonorrhoeae/drug effects , Neisseria gonorrhoeae/genetics , Neisseria gonorrhoeae/isolation & purification , Pregnancy , Pregnancy Complications, Infectious/drug therapy , RNA, Bacterial/genetics , RNA, Ribosomal, 16S/genetics , Tetracycline/pharmacologyABSTRACT
Streptomyces cinereoruber isolated from a patient with severe respiratory failure that could not be identified by culture was correctly identified at the species level by comparative sequence analysis of 16S rDNA and the hypervariable alpha-region of 16S rDNA. Restriction fragment length polymorphism, morphologic, and biochemical characteristics have confirmed their identity.
Subject(s)
Haemophilus Infections/complications , Haemophilus influenzae/isolation & purification , Pulmonary Disease, Chronic Obstructive/microbiology , Streptomyces/isolation & purification , Aged , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Bacterial Typing Techniques , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , Haemophilus Infections/drug therapy , Haemophilus influenzae/genetics , Humans , Male , Polymorphism, Restriction Fragment Length , Prednisone/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , RNA, Ribosomal, 16S/genetics , Radiography, Thoracic , Streptomyces/genetics , Sulfamethoxazole/therapeutic use , Tomography, X-Ray Computed , Trimethoprim/therapeutic useABSTRACT
A pneumolysin-specific enzyme-linked immunosorbent assay (PLY-ELISA) for the detection of pneumolysin in urine was developed and evaluated in comparison with the commercially available Binax Now Streptococcus pneumoniae test (Binax, Portland, ME) for the diagnosis of pneumococcal infections. Assay sensitivity was evaluated using urine from 108 patients with culture-confirmed pneumococcal infections. In adults, the sensitivity and specificity of the PLY-ELISA were 56.6% and 92.2%, respectively. In children with nasopharyngeal pneumococcal carriage, PLY-ELISA and Binax Now S. pneumoniae test sensitivities were 62.5% and 87.5%, respectively, while specificities were 94.4% and 27.8%, respectively. In children with nonnasopharyngeal pneumococcal carriage, PLY-ELISA and Binax Now S. pneumoniae test sensitivities were 68.7% and 93.7%, respectively, and test specificities were 94.1% and 41.2%, respectively. The persistence of pneumolysin in urine of pneumococcal pneumonia patients decreased significantly after 4 to 6 days of treatment. Our data suggest that combining the high specificity of the PLY-ELISA with the high sensitivity of the Binax Now S. pneumoniae test would enable pneumococcal infections to be accurately diagnosed in children.
Subject(s)
Enzyme-Linked Immunosorbent Assay/methods , Pneumococcal Infections/diagnosis , Streptolysins/urine , Adolescent , Adult , Aged , Aged, 80 and over , Bacterial Proteins/urine , Female , Humans , Male , Middle Aged , Pneumococcal Infections/urine , Sensitivity and SpecificityABSTRACT
BACKGROUND: Intranasal inoculation of Streptococcus pneumoniae D39 serotype 2 causes fatal pneumonia in mice. The cytotoxic and inflammatory properties of pneumolysin (PLY) have been implicated in the pathogenesis of pneumococcal pneumonia. METHODS: To examine the role of PLY in this experimental model we performed ELISA assays for PLY quantification. The distribution patterns of PLY and apoptosis were established by immunohistochemical detection of PLY, caspase-9 activity and TUNEL assay on tissue sections from mice lungs at various times, and the results were quantified with image analysis. Inflammatory and apoptotic cells were also quantified on lung tissue sections from antibody treated mice. RESULTS: In bronchoalveolar lavages (BAL), total PLY was found at sublytic concentrations which were located in alveolar macrophages and leukocytes. The bronchoalveolar epithelium was PLY-positive, while the vascular endothelium was not PLY reactive. The pattern and extension of cellular apoptosis was similar. Anti-PLY antibody treatment decreased the lung damage and the number of apoptotic and inflammatory cells in lung tissues. CONCLUSION: The data strongly suggest that in vivo lung injury could be due to the pro-apoptotic and pro-inflammatory activity of PLY, rather than its cytotoxic activity. PLY at sublytic concentrations induces lethal inflammation in lung tissues and is involved in host cell apoptosis, whose effects are important to pathogen survival.
