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1.
ESMO Open ; 9(8): 103667, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39121815

RESUMEN

BACKGROUND: This is a multicentre, single-arm, phase II study aimed at further exploring the activity of trabectedin as second-/further-line treatment in retroperitoneal leiomyosarcoma (LMS) and well-differentiated/dedifferentiated liposarcoma (LPS). MATERIALS AND METHODS: The primary endpoint was the growth modulation index (GMI) defined as the ratio between PFS under trabectedin (PFS) and during previous chemotherapy treatment: time to progression (TTP-1). Secondary endpoints were objective response rate (ORR) and PFS. As per protocol, patients were considered responders if the GMI was >1.33, non-responders if <0.75 and neither if 0.76-1.32. RESULTS: Overall 91 patients were assessable for the primary endpoint (32 patients with LMS and 59 patients with LPS): the median number of cycles received was 6.0 (Q1-Q3 3.0-12.0), and the main reason for treatment discontinuation was disease progression in 72% of patients. The median PFS was 6.0 months, while the median TTP1 was 7.5 months (8.1 and 6.4 months for LMS and LPS, respectively). Thirty-three patients [52%, 95% confidence interval (CI) 36% to 58%, P = 0.674, odds of response 1.1] had a GMI >1.33 (LMS 46%, 95% CI 26% to 67%, odds of response 0.85; LPS 56%, 95% CI 40% to 72%, odds of response 1.3). Overall, in LPS we observed 15/47 patients with a GMI <0.5 and 15/47 patients with a GMI >2. Among LMS patients, 9/26 had a GMI <0.5 and 10/26 had a GMI >2. Overall, ORR (complete response + partial response) was 16% (24% for LMS and 12% for LPS). CONCLUSIONS: While the primary endpoint of the study was not met, we noticed a subgroup of patients with a markedly discrepant TTP with trabectedin in comparison to previous therapy (GMI <0.5 or >2, the latter including some patients with a long TTP with trabectedin). A mismatch between PFS and overall survival was observed, possibly due to the natural history of the two different histologies and the availability of further lines in LMS.

2.
Pulmonology ; 28(6): 419-420, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36180351

Asunto(s)
Vacunación , Humanos
4.
Respir Res ; 22(1): 156, 2021 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-34020646

RESUMEN

BACKGROUND: Although cardiac autonomic modulation has been studied in several respiratory diseases, the evidence is limited on lung transplantation, particularly on its acute and chronic effects. Thus, we aimed to evaluate cardiac autonomic modulation before and after bilateral lung transplantation (BLT) through a prospective study on patients enrolled while awaiting transplant. METHODS: Twenty-two patients on the waiting list for lung transplantation (11 women, age 33 [24-51] years) were enrolled in a prospective study at Ospedale Maggiore Policlinico Hospital in Milan, Italy. To evaluate cardiac autonomic modulation, ten minutes ECG and respiration were recorded at different time points before (T0) and 15 days (T1) and 6 months (T2) after bilateral lung transplantation. As to the analysis of cardiac autonomic modulation, heart rate variability (HRV) was assessed using spectral and symbolic analysis. Entropy-derived measures were used to evaluate complexity of cardiac autonomic modulation. Comparisons of autonomic indices at different time points were performed. RESULTS: BLT reduced HRV total power, HRV complexity and vagal modulation, while it increased sympathetic modulation in the acute phase (T1) compared to baseline (T0). The HRV alterations remained stable after 6 months (T2). CONCLUSION: BLT reduced global variability and complexity of cardiac autonomic modulation in acute phases, and these alterations remain stable after 6 months from surgery. After BLT, a sympathetic predominance and a vagal withdrawal could be a characteristic autonomic pattern in this population.


Asunto(s)
Sistema Nervioso Autónomo/fisiopatología , Frecuencia Cardíaca , Corazón/inervación , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón , Pulmón/cirugía , Respiración , Adulto , Electrocardiografía , Femenino , Humanos , Pulmón/fisiopatología , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/fisiopatología , Trasplante de Pulmón/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
6.
Clin Microbiol Infect ; 26(7): 880-894, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32360444

RESUMEN

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has rapidly become epidemic in Italy and other European countries. The disease spectrum ranges from asymptomatic/mildly symptomatic presentations to acute respiratory failure. At the present time the absolute number of severe cases requiring ventilator support is reaching or even surpassing the intensive care unit bed capacity in the most affected regions and countries. OBJECTIVES: To narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and frontline opinions and to provide balanced answers to pressing clinical questions. SOURCES: Inductive PubMed search for publications relevant to the topic. CONTENT: The available literature and the authors' frontline-based opinion are summarized in brief narrative answers to selected clinical questions, with a conclusive statement provided for each answer. IMPLICATIONS: Many off-label antiviral and anti-inflammatory drugs are currently being administered to patients with COVID-19. Physicians must be aware that, as they are not supported by high-level evidence, these treatments may often be ethically justifiable only in those worsening patients unlikely to improve only with supportive care, and who cannot be enrolled onto randomized clinical trials. Access to well-designed randomized controlled trials should be expanded as much as possible because it is the most secure way to change for the better our approach to COVID-19 patients.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Uso Fuera de lo Indicado/ética , Neumonía Viral/tratamiento farmacológico , COVID-19 , Infecciones por Coronavirus/epidemiología , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Italia/epidemiología , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/patología , Enfermedades Pulmonares/virología , Pandemias , Neumonía Viral/epidemiología , Respiración Artificial/métodos , SARS-CoV-2
7.
Eur J Clin Microbiol Infect Dis ; 39(8): 1513-1525, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32242314

RESUMEN

An accurate knowledge of the epidemiology of community-acquired pneumonia (CAP) is key for selecting appropriate antimicrobial treatments. Very few etiological studies assessed the appropriateness of empiric guideline recommendations at a multinational level. This study aims at the following: (i) describing the bacterial etiologic distribution of CAP and (ii) assessing the appropriateness of the empirical treatment recommendations by clinical practice guidelines (CPGs) for CAP in light of the bacterial pathogens diagnosed as causative agents of CAP. Secondary analysis of the GLIMP, a point-prevalence international study which enrolled adults hospitalized with CAP in 2015. The analysis was limited to immunocompetent patients tested for bacterial CAP agents within 24 h of admission. The CAP CPGs evaluated included the following: the 2007 and 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA), the European Respiratory Society (ERS), and selected country-specific CPGs. Among 2564 patients enrolled, 35.3% had an identifiable pathogen. Streptococcus pneumoniae (8.2%) was the most frequently identified pathogen, followed by Pseudomonas aeruginosa (4.1%) and Klebsiella pneumoniae (3.4%). CPGs appropriately recommend covering more than 90% of all the potential pathogens causing CAP, with the exception of patients enrolled from Germany, Pakistan, and Croatia. The 2019 ATS/IDSA CPGs appropriately recommend covering 93.6% of the cases compared with 90.3% of the ERS CPGs (p < 0.01). S. pneumoniae remains the most common pathogen in patients hospitalized with CAP. Multinational CPG recommendations for patients with CAP seem to appropriately cover the most common pathogens and should be strongly encouraged for the management of CAP patients.


Asunto(s)
Infecciones Comunitarias Adquiridas/epidemiología , Adhesión a Directriz , Neumonía Bacteriana/epidemiología , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Pseudomonas aeruginosa , Streptococcus pneumoniae , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/microbiología , Femenino , Salud Global , Hospitalización , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiología , Prevalencia
8.
COPD ; 16(1): 72-74, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30786778

RESUMEN

The increasing prevalence and incidence of bronchiectasis leads to a substantial health care burden. Quality standards for the management of bronchiectasis were formulated by the British Thoracic Society following publication of guidelines in 2010. They can be used as a benchmark for quality of care. It is, however, unclear how and whether they apply outside of the UK. Between May and November 2017, we conducted an online survey among respiratory physicians caring for adult bronchiectasis patients in Belgium. About 186 cases were submitted by 117 treating physicians. Patients were mostly female (58%), of Caucasian descent (84%) with a remarkably low median age of 59.8 (IQR 47-73) years. 41% had Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus and/or Enterobacteriaceae isolated from respiratory samples in the past. 21% had three or more exacerbations, however, more than 58% were receiving long-term oral antibiotics (of which 90% azithromycin). In 40% of patients the diagnostic testing was insufficient. Surveillance of sputum bacteriology in stable patients and composing a self-management plan was missing in 53% and 68% of patients, respectively. Airway clearance techniques were implemented in 84%. Respiratory physicians complied with 60% or more to five out of the eight applicable quality standards, which is encouraging. Increasing educational act could further raise awareness and increase quality of care.


Asunto(s)
Antibacterianos/uso terapéutico , Bronquiectasia/terapia , Adhesión a Directriz/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Neumología/estadística & datos numéricos , Esputo/microbiología , Adulto , Anciano , Antibacterianos/administración & dosificación , Azitromicina/uso terapéutico , Bélgica , Bronquiectasia/diagnóstico por imagen , Bronquiectasia/microbiología , Bronquiectasia/rehabilitación , Progresión de la Enfermedad , Enterobacteriaceae/aislamiento & purificación , Femenino , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Persona de Mediana Edad , Planificación de Atención al Paciente , Grupo de Atención al Paciente , Educación del Paciente como Asunto/normas , Guías de Práctica Clínica como Asunto , Pseudomonas aeruginosa/aislamiento & purificación , Autocuidado , Encuestas y Cuestionarios
9.
J Prev Med Hyg ; 59(2): E128-E131, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30083619

RESUMEN

INTRODUCTION: Influenza epidemics are one of the main causes of morbidity and mortality worldwide. Influenza vaccination is considered the most important public health intervention to prevent seasonal influenza infection. European health authority policies focus on patient protection by vaccinating both these subjects and their care-givers, including health-care workers (HCWs). The aim of this survey is to investigate knowledge about influenza vaccination and intention to get vaccinated among Italian HCWs who take care patients with respiratory disease. METHODS: An anonymous web-based survey was addressed to members of the Italian Respiratory Society (IRS). RESULTS: Among the 1,776 IRS members who have been invited to the survey, 144 (8.1%) completed the survey (97 men; median age 59 years; 85.4% Respiratory Disease). The vast majority recommended vaccination to all their patients (81%). More than two thirds of respondents considered influenza vaccination safe for immunocompromised patients. More than 50% of respondents underwent seasonal influenza vaccination in 2015 and 68% declared the intention to undergo vaccination in 2016 epidemic season. Reasons for having vaccination mainly referred to 'protect oneself from influenza' (63%), 'protect patients' (31%) or household members' (6%). The main reasons for vaccination refusal were 'lack of time' (45%), 'concerns about side effects' (22%), 'do not get influenza easily and/or not afraid of influenza infection' (22%) and 'disagreement with indication of vaccination for HCWs' (9%). CONCLUSIONS: The promotion of better knowledge and attitude towards influenza vaccination among Italian specialists remains an unmet goal and should be addressed by appropriate multifaceted interventions.


Asunto(s)
Actitud del Personal de Salud , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Internet , Médicos/psicología , Anciano , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Italia , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios
10.
J Hosp Infect ; 99(4): 413-418, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29621600

RESUMEN

AIM: To describe the phenotypic and genotypic profiles of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) strains isolated from patients with invasive infections at an Italian university hospital in order to assess the epidemiological trend. METHODS: An observational prospective study was undertaken at the University Hospital of Sassari, Italy to detect KPC-Kp strains in patients with invasive bacteraemia. Isolates were identified phenotypically; carbapenemase production was assessed using phenotypic and genotypic methods. Sequencing of blaKPC genes, pulsed-field gel electrophoresis and multi-locus sequence typing were performed. RESULTS: During the period 2015-2017, 46 cases of invasive infection with K. pneumoniae were recorded. Two-thirds (67.4%) of the patients were male, and the mean age was 69.4 years. Most patients had at least one comorbidity (56.5%) and/or had been hospitalized previously (70.5%), 81.8% had current or recent medical device use, and 85.4% had recent antibiotic exposure. The mortality rate was 52.3%. A multi-drug-resistant pattern (including carbapenems, fluoroquinolones, third-/fourth-generation cephalosporins) was shown for all K. pneumoniae isolates. KPC-3 and -2 were produced by all strains. The most common sequence types were 512 (91.3%) and 101 (8.7%), grouped into three clusters (A, A1 and B). CONCLUSIONS: A high incidence of KPC-Kp in patients with invasive infections was recorded at an Italian university hospital compared with the incidence measured before 2015. This study confirmed the importance of the KPC-3 carbapenemase variant, as reported by other Italian studies. High mortality and comorbidity rates appear to be associated with KPC-Kp infection.


Asunto(s)
Bacteriemia/transmisión , Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación , Infección Hospitalaria/transmisión , Transmisión de Enfermedad Infecciosa , Genotipo , Infecciones por Klebsiella/transmisión , Klebsiella pneumoniae/aislamiento & purificación , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Bacteriemia/epidemiología , Bacteriemia/microbiología , Bacteriemia/mortalidad , Enterobacteriaceae Resistentes a los Carbapenémicos/clasificación , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Infección Hospitalaria/mortalidad , Farmacorresistencia Bacteriana Múltiple , Electroforesis en Gel de Campo Pulsado , Femenino , Hospitales Universitarios , Humanos , Incidencia , Italia/epidemiología , Infecciones por Klebsiella/epidemiología , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/mortalidad , Klebsiella pneumoniae/clasificación , Klebsiella pneumoniae/genética , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Epidemiología Molecular , Tipificación de Secuencias Multilocus , Estudios Prospectivos , Análisis de Secuencia de ADN , Análisis de Supervivencia
11.
Lung ; 195(5): 679-682, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28668972

RESUMEN

Alpha-1-antitrypsin deficiency (AATD) is a genetic condition caused by SERPINA1 mutations, which culminates into lower protease inhibitor activity in the serum and predisposes to emphysema. Clinical manifestations of AATD are often associated to ZZ (p.Glu342Lys) and SZ (p.Glu264Val) genotypes and less frequently to rare deficiency or null alleles in heterozygous and homozygous states. We report a case of a 52-year-old woman with bronchiectasis without other potential causes other than an electrophoresis that showed a decrease of alpha-1 globin band and AAT levels below the normal value (78 mg/dl; v.n. 90-200 mg/dl). No S or Z mutation was identified, but sequencing analysis found a novel missense variant Ile74Asn (c.221T > A) in heterozygous state on an M3 allele (Glu400Asp) in the exon 2 of the SERPINA-1gene, probably leading to a dysfunctional protein. This mutation has never been previously identified, and it is interesting to note the association with bronchiectasis in the absence of emphysema.


Asunto(s)
Bronquiectasia/genética , Pulmón/diagnóstico por imagen , Mutación Missense , Deficiencia de alfa 1-Antitripsina/genética , alfa 1-Antitripsina/genética , Bronquiectasia/sangre , Bronquiectasia/diagnóstico por imagen , Bronquiectasia/fisiopatología , Monóxido de Carbono , Femenino , Volumen Espiratorio Forzado , Genotipo , Heterocigoto , Humanos , Pulmón/fisiopatología , Persona de Mediana Edad , Capacidad de Difusión Pulmonar , Volumen Residual , Análisis de Secuencia de ADN , Tomografía Computarizada por Rayos X , Capacidad Pulmonar Total , Capacidad Vital , alfa 1-Antitripsina/sangre , Deficiencia de alfa 1-Antitripsina/sangre , Deficiencia de alfa 1-Antitripsina/diagnóstico , Deficiencia de alfa 1-Antitripsina/fisiopatología
12.
Transplant Proc ; 49(4): 702-706, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28457376

RESUMEN

Lung transplantation is a well-established treatment for selected patients with advanced chronic respiratory insufficiency. Recognizing those patients with end-stage lung disease who might benefit from lung transplantation is a crucial task. Considering the presence of inadequate evidence-based practice, international and national scientific societies provided consensus opinions regarding the appropriate timing of listing. The Study Group for Thoracic Organs Transplantation (branch of the Italian Society for Organs Transplantation) promoted and realized a Delphi conference among the Italian lung transplantation centers to provide guidance to clinical practice based on international recommendations. The experts from the nine Italian centers completed two rounds of standardized questionnaires (answer rate, 100%): 42 statements received a consensus ≥80%. The selected statements presented in this article are intended to assist Italian clinicians in selecting patients for lung transplantation.


Asunto(s)
Trasplante de Pulmón/métodos , Selección de Paciente , Técnica Delphi , Humanos , Italia
13.
Thorax ; 71(12): 1110-1118, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27516225

RESUMEN

INTRODUCTION: Bronchiectasis is a multidimensional disease associated with substantial morbidity and mortality. Two disease-specific clinical prediction tools have been developed, the Bronchiectasis Severity Index (BSI) and the FACED score, both of which stratify patients into severity risk categories to predict the probability of mortality. METHODS: We aimed to compare the predictive utility of BSI and FACED in assessing clinically relevant disease outcomes across seven European cohorts independent of their original validation studies. RESULTS: The combined cohorts totalled 1612. Pooled analysis showed that both scores had a good discriminatory predictive value for mortality (pooled area under the curve (AUC) 0.76, 95% CI 0.74 to 0.78 for both scores) with the BSI demonstrating a higher sensitivity (65% vs 28%) but lower specificity (70% vs 93%) compared with the FACED score. Calibration analysis suggested that the BSI performed consistently well across all cohorts, while FACED consistently overestimated mortality in 'severe' patients (pooled OR 0.33 (0.23 to 0.48), p<0.0001). The BSI accurately predicted hospitalisations (pooled AUC 0.82, 95% CI 0.78 to 0.84), exacerbations, quality of life (QoL) and respiratory symptoms across all risk categories. FACED had poor discrimination for hospital admissions (pooled AUC 0.65, 95% CI 0.63 to 0.67) with low sensitivity at 16% and did not consistently predict future risk of exacerbations, QoL or respiratory symptoms. No association was observed with FACED and 6 min walk distance (6MWD) or lung function decline. CONCLUSION: The BSI accurately predicts mortality, hospital admissions, exacerbations, QoL, respiratory symptoms, 6MWD and lung function decline in bronchiectasis, providing a clinically relevant evaluation of disease severity.


Asunto(s)
Bronquiectasia/diagnóstico , Índice de Severidad de la Enfermedad , Anciano , Bronquiectasia/mortalidad , Bronquiectasia/fisiopatología , Progresión de la Enfermedad , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado/fisiología , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Calidad de Vida , Medición de Riesgo/métodos
14.
Infection ; 43(6): 729-38, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26424683

RESUMEN

PURPOSE: Further examination of clinical outcomes and inflammatory response of bacteremic pneumococcal community-acquired pneumonia (CAP) is of great interest to enhance the care of patients with pneumococcal CAP. METHODS: This is a secondary analysis of the Community Acquired Pneumonia Organization (CAPO) to compare the time to clinical stability (TCS), length of hospital stay (LOS), and in-hospital mortality of hospitalized pneumococcal CAP patients with and without bacteremia. To measure the effect of bacteremia in pneumococcal CAP patients on outcomes, we modeled all-cause in-hospital mortality using a Poisson regression model, and TCS and LOS using Cox proportional hazards models. Adjusted multivariate regression models were also used to predict the probability of occurrence of each of the study outcomes. To investigate the inflammatory response, we measured the plasma levels of pro- and anti-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1rα, IL-6, IL-8, IL-10], inflammatory biomarkers [C-reactive protein (CRP), pro-calcitonin (PCT), and B-type natriuretic peptide (BNP)], and peripheral blood neutrophil responses in 10 patients, 4 bacteremic and 6 non-bacteremic pneumococcal CAP, upon admission and every other day during the first 6 days of hospitalization. Functional data were presented as median and standard error of the median (SEM); due to small number of samples no statistical comparisons were performed between groups. RESULTS: From 833 pneumococcal CAP patients, 394 patients (47 %) were bacteremic. Bacteremic pneumococcal CAP were less likely to reach TCS with an adjusted hazard ratio (AHR) of 0.82 (95 % CI 0.69-0.97; p = 0.02) and had higher in-hospital mortality with an AHR of 1.63 (95 % CI 1.06-2.50, p = 0.026). Bacteremic pneumococcal CAP patients had a longer LOS than non-bacteremic pneumococcal CAP (p < 0.003). Higher plasma levels of CRP, PCT, and BNP were found in bacteremic than in non-bacteremic patients. The bacteremic group had consistently higher plasma levels of both pro- and anti-inflammatory cytokines. The blood neutrophil functional responses were similar in both groups of patients. CONCLUSIONS: Bacteremic pneumococcal CAP patients were significantly associated with higher in-hospital mortality, lower TCS, and longer LOS. HIV-infected patients showed a greater mortality which was not statistically significant. Bacteremic pneumococcal CAP patients had higher levels of biomarkers and systemic cytokines.


Asunto(s)
Bacteriemia/diagnóstico , Bacteriemia/patología , Infecciones Comunitarias Adquiridas/patología , Neumonía Neumocócica/complicaciones , Neumonía Neumocócica/patología , Streptococcus pneumoniae/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/mortalidad , Proteína C-Reactiva/análisis , Calcitonina/sangre , Infecciones Comunitarias Adquiridas/microbiología , Citocinas/sangre , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Plasma/química , Estudios Prospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Adulto Joven
15.
Clin Microbiol Infect ; 21(10): 936.e11-8, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26115864

RESUMEN

There is no evidence supporting the use of de-escalation therapy (DET) among patients with community-acquired pneumonia (CAP). We assessed the outcomes associated with DET among bacteraemic CAP patients. We performed a secondary analysis of the Community-Acquired Pneumonia Organization database, which contains data on 660 bacteraemic patients hospitalized because of CAP in 35 countries (2001-2013). Exclusion criteria were death within 72 h from admission and an inappropriate empirical antibiotic regimen. DET was defined as changing an appropriate empirical broad-spectrum regimen to a narrower-spectrum regimen according to culture results within 7 days from hospital admission. Two study groups were identified: patients whose antibiotic therapy was de-escalated (the DET group), and patients whose antibiotic therapy was not de-escalated (the N-DET group). The primary study outcome was 30-day mortality. Two hundred and sixty-one bacteraemic CAP patients were included. Gram-positive bacteria were responsible for 88.1% of the cases (Streptococcus pneumoniae, 75.9%). Gram-negative bacteria were responsible for for 7.3% of the cases. DET was performed in 165 patients (63.2%). The N-DET group was characterized by a more severe presentation at admission. After adjustment for confounders, DET was not associated with an increased risk of 30-day mortality. DET seems to be safe among bacteraemic patients with CAP. Randomized clinical trials are warranted to further explore these findings.


Asunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Neumonía Bacteriana/complicaciones , Neumonía Bacteriana/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/mortalidad , Infecciones Comunitarias Adquiridas/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Resultado del Tratamiento , Adulto Joven
16.
Leukemia ; 29(6): 1390-401, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25533804

RESUMEN

Although anaplastic large-cell lymphomas (ALCL) carrying anaplastic lymphoma kinase (ALK) have a relatively good prognosis, aggressive forms exist. We have identified a novel translocation, causing the fusion of the TRAF1 and ALK genes, in one patient who presented with a leukemic ALK+ ALCL (ALCL-11). To uncover the mechanisms leading to high-grade ALCL, we developed a human patient-derived tumorgraft (hPDT) line. Molecular characterization of primary and PDT cells demonstrated the activation of ALK and nuclear factor kB (NFkB) pathways. Genomic studies of ALCL-11 showed the TP53 loss and the in vivo subclonal expansion of lymphoma cells, lacking PRDM1/Blimp1 and carrying c-MYC gene amplification. The treatment with proteasome inhibitors of TRAF1-ALK cells led to the downregulation of p50/p52 and lymphoma growth inhibition. Moreover, a NFkB gene set classifier stratified ALCL in distinct subsets with different clinical outcome. Although a selective ALK inhibitor (CEP28122) resulted in a significant clinical response of hPDT mice, nevertheless the disease could not be eradicated. These data indicate that the activation of NFkB signaling contributes to the neoplastic phenotype of TRAF1-ALK ALCL. ALCL hPDTs are invaluable tools to validate the role of druggable molecules, predict therapeutic responses and implement patient specific therapies.


Asunto(s)
Resistencia a Antineoplásicos , Linfoma Anaplásico de Células Grandes/genética , FN-kappa B/metabolismo , Proteínas Tirosina Quinasas Receptoras/genética , Factor 1 Asociado a Receptor de TNF/genética , Translocación Genética/genética , Quinasa de Linfoma Anaplásico , Animales , Western Blotting , Citometría de Flujo , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunoprecipitación , Hibridación Fluorescente in Situ , Linfoma Anaplásico de Células Grandes/tratamiento farmacológico , Linfoma Anaplásico de Células Grandes/mortalidad , Ratones , Ratones Endogámicos NOD , FN-kappa B/genética , Factor 1 de Unión al Dominio 1 de Regulación Positiva , Inhibidores de Proteasoma/farmacología , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteínas Tirosina Quinasas Receptoras/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Factor 1 Asociado a Receptor de TNF/metabolismo , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Clin Microbiol Infect ; 20 Suppl 5: 52-8, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24410778

RESUMEN

Pneumococcal infections, including pneumonia and invasive disease, are major sources of morbidity and mortality worldwide. Prevention of the first acquisition of Streptococcus pneumoniae through the use of vaccines represents an effective method to reduce the burden of the disease in both children and adults. Two vaccines are currently available in adults: a pneumococcal polysaccharide vaccine (PPV23) that includes 23 purified capsular polysaccharide antigens and a pneumococcal protein-conjugate vaccine (PCV13) that includes capsular polysaccharide antigens covalently linked to a non-toxic protein. The PPV23 induces a humoral immune response and since it has been licensed has been the subject of debates and controversies. Numerous studies and meta-analyses have shown that PPV23 protects against invasive pneumococcal disease, although there are conflicting data regarding its efficacy for the prevention of pneumonia. Vaccination with PCV13 stimulates good antibody responses as well as mucosal immunity and suppresses colonization. A conjugate vaccine can be expected to have benefits over a polysaccharide vaccine because of the characteristics of a T-cell-dependent response in terms of affinity, maturation of antibodies with repeated exposure, induction of immunological memory and long-lasting immunity. PCV13 has demonstrated all of these characteristics in children and fundamental differences in adults are not expected. The efficacy in adults is currently being investigated and results will be available soon.


Asunto(s)
Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico , Vacunación/métodos , Europa (Continente) , Humanos , Memoria Inmunológica , Metaanálisis como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Streptococcus pneumoniae , Vacunas Conjugadas/uso terapéutico
18.
Cytopathology ; 25(4): 231-40, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23866000

RESUMEN

OBJECTIVE: Lymphoid proliferations of the salivary glands can be either reactive or malignant. Diagnosis based solely on fine needle aspiration (FNA) cytology may be troublesome in view of the difficulty in distinguishing low-grade B-cell and mucosa-associated lymphoid tissue (MALT) lymphomas from reactive lymphoid proliferations. We report our experience with FNA cytology combined with flow cytometry (FC) immunophenotyping for the diagnosis of lymphoproliferative processes affecting the salivary glands. METHODS: Sixty-one FNA specimens, obtained from salivary glands over a 10-year period, were analysed by cytology and FC. The results were correlated with histological follow-up if available. RESULTS: A diagnosis of lymphoma was given in 37 of 61 (61%) specimens; 22 of 61 (36%) specimens were considered as benign/reactive or non-lymphomatous processes; two of 61 (3%) specimens were considered as suspicious for lymphoma on cytological analysis and negative on FC. Histological control was available in 23 malignant, four non-lymphomatous and one cytologically suspicious case. Data obtained by the combination of cytology and FC were confirmed in all but one case: the case suspicious on cytology received a histological diagnosis of carcinoma. Four of seven cases with small populations of clonal cells (less than 15%) were histologically confirmed as lymphoma, whereas two remain under surveillance and one was reactive. Correlation with histological data showed a sensitivity of 100% and a specificity of 83% for the combination of cytology and FC. CONCLUSIONS: FC is fundamental for the diagnosis of lymphoproliferative lesions of the salivary glands. It may solve cytologically suspicious cases and detect the presence of neoplastic B or T cells. This combined approach reduces the time to therapy and may prevent unnecessary surgical biopsies.


Asunto(s)
Biopsia con Aguja Fina , Citodiagnóstico , Linfoma no Hodgkin/diagnóstico , Trastornos Linfoproliferativos/diagnóstico , Adulto , Anciano , Femenino , Citometría de Flujo , Humanos , Linfoma no Hodgkin/patología , Trastornos Linfoproliferativos/patología , Masculino , Persona de Mediana Edad , Glándulas Salivales/patología
19.
Braz. j. med. biol. res ; 45(9): 806-810, Sept. 2012. ilus, tab
Artículo en Inglés | LILACS | ID: lil-646325

RESUMEN

The aim of this study was to investigate the influence of image resolution manipulation on the photogrammetric measurement of the rearfoot static angle. The study design was that of a reliability study. We evaluated 19 healthy young adults (11 females and 8 males). The photographs were taken at 1536 pixels in the greatest dimension, resized into four different resolutions (1200, 768, 600, 384 pixels) and analyzed by three equally trained examiners on a 96-pixels per inch (ppi) screen. An experienced physiotherapist marked the anatomic landmarks of rearfoot static angles on two occasions within a 1-week interval. Three different examiners had marked angles on digital pictures. The systematic error and the smallest detectable difference were calculated from the angle values between the image resolutions and times of evaluation. Different resolutions were compared by analysis of variance. Inter- and intra-examiner reliability was calculated by intra-class correlation coefficients (ICC). The rearfoot static angles obtained by the examiners in each resolution were not different (P > 0.05); however, the higher the image resolution the better the inter-examiner reliability. The intra-examiner reliability (within a 1-week interval) was considered to be unacceptable for all image resolutions (ICC range: 0.08-0.52). The whole body image of an adult with a minimum size of 768 pixels analyzed on a 96-ppi screen can provide very good inter-examiner reliability for photogrammetric measurements of rearfoot static angles (ICC range: 0.85-0.92), although the intra-examiner reliability within each resolution was not acceptable. Therefore, this method is not a proper tool for follow-up evaluations of patients within a therapeutic protocol.


Asunto(s)
Adulto , Femenino , Humanos , Masculino , Pie/anatomía & histología , Pie/fisiología , Variaciones Dependientes del Observador , Fotogrametría , Valores de Referencia , Reproducibilidad de los Resultados
20.
Braz J Med Biol Res ; 45(9): 806-10, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22911379

RESUMEN

The aim of this study was to investigate the influence of image resolution manipulation on the photogrammetric measurement of the rearfoot static angle. The study design was that of a reliability study. We evaluated 19 healthy young adults (11 females and 8 males). The photographs were taken at 1536 pixels in the greatest dimension, resized into four different resolutions (1200, 768, 600, 384 pixels) and analyzed by three equally trained examiners on a 96-pixels per inch (ppi) screen. An experienced physiotherapist marked the anatomic landmarks of rearfoot static angles on two occasions within a 1-week interval. Three different examiners had marked angles on digital pictures. The systematic error and the smallest detectable difference were calculated from the angle values between the image resolutions and times of evaluation. Different resolutions were compared by analysis of variance. Inter- and intra-examiner reliability was calculated by intra-class correlation coefficients (ICC). The rearfoot static angles obtained by the examiners in each resolution were not different (P > 0.05); however, the higher the image resolution the better the inter-examiner reliability. The intra-examiner reliability (within a 1-week interval) was considered to be unacceptable for all image resolutions (ICC range: 0.08-0.52). The whole body image of an adult with a minimum size of 768 pixels analyzed on a 96-ppi screen can provide very good inter-examiner reliability for photogrammetric measurements of rearfoot static angles (ICC range: 0.85-0.92), although the intra-examiner reliability within each resolution was not acceptable. Therefore, this method is not a proper tool for follow-up evaluations of patients within a therapeutic protocol.


Asunto(s)
Pie/anatomía & histología , Adulto , Femenino , Pie/fisiología , Humanos , Masculino , Variaciones Dependientes del Observador , Fotogrametría , Valores de Referencia , Reproducibilidad de los Resultados
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