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1.
Int J Infect Dis ; 2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33647515

RESUMEN

BACKGROUND: The role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear. METHODS: We conducted a retrospective single-center study including consecutive patients ≥65 years that developed severe COVID-19 between March 3 and May 1, 2020 and were treated with corticosteroids at various doses (methylprednisolone [0.5 mg/Kg/12 hours to 250 mg/24 hours]), either alone ("CS group") or associated to intravenous tocilizumab (400-600 mg, one to three doses) ("CS-TCZ group"). Primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2-point decrease on a six-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied. RESULTS: Overall, 181 and 80 patients were included in the CS and CS-TCZ groups. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17 - 0.68; P-value = 0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21 - 0.68; P-value = 0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21 - 0.72; P-value = 0.003). Clinical improvement by day +14 was higher in the CS-TCZ group in the IPTW analysis only (OR: 2.26; 95% CI: 1.49 - 3.41; P-value <0.001). The occurrence of secondary infection was similar between both groups. CONCLUSIONS: The combination of corticosteroids and TCZ was associated with better outcomes among patients ≥65 years with severe COVID-19.

2.
Artículo en Inglés | MEDLINE | ID: mdl-33409832

RESUMEN

The aim of our study was to elucidate if SARS-CoV-2 viral load on admission, measured by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) cycle threshold (Ct) value on nasopharyngeal samples, was a marker of disease severity. All hospitalized adult patients with a diagnosis of SARS-CoV-2 infection by rRT-PCR performed on a nasopharingeal sample from March 1 to March 18 in our institution were included. The study population was divided according to the Ct value obtained upon admission in patients with high viral load (Ct < 25), intermediate viral load (Ct: 25-30) and low viral load (Ct > 30). Demographic, clinical and laboratory variables of the different groups were analyzed to assess the influence of viral load on the development of respiratory failure during admission. Overall, 455 sequential patients were included. The median Ct value was 28 (IQR: 24-32). One hundred and thirty patients (28.6%) had a high viral load, 175 (38.5%) an intermediate viral load and 150 (33%) a low viral load. Advanced age, male sex, presence of cardiovascular disease and laboratory markers such as lactate dehydrogenase, lymphocyte count and C-reactive protein, as well as a high viral load on admission, were predictive of respiratory failure. A Ct value < 25 was associated with a higher risk of respiratory failure during admission (OR: 2.99, 95%IC: 1.57-5.69). SARS-CoV-2 viral load, measured through the Ct value on admission, is a valuable tool to predict the development of respiratory failure in COVID-19 inpatients.

3.
J Med Virol ; 2020 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-32672860

RESUMEN

Coronavirus disease 2019 (COVID-19) can lead to a massive cytokine release. The use of the anti-interleukin-6 receptor monoclonal antibody tocilizumab (TCZ) has been proposed in this hyperinflammatory phase, although supporting evidence is limited. We retrospectively analyzed 88 consecutive patients with COVID-19 pneumonia that received at least one dose of intravenous TCZ in our institution between 16 and 27 March 2020. Clinical status from day 0 (first TCZ dose) through day 14 was assessed by a 6-point ordinal scale. The primary outcome was clinical improvement (hospital discharge and/or a decrease of ≥2 points on the 6-point scale) by day 7. Secondary outcomes included clinical improvement by day 14 and dynamics of vital signs and laboratory values. Rates of clinical improvement by days 7 and 14 were 44.3% (39/88) and 73.9% (65/88). Previous or concomitant receipt of subcutaneous interferon-ß (adjusted odds ratio [aOR]: 0.23; 95% confidence interval [CI]: 0.06-0.94; P = .041) and serum lactate dehydrogenase more than 450 U/L at day 0 (aOR: 0.25; 95% CI: 0.06-0.99; P = .048) were negatively associated with clinical improvement by day 7. All-cause mortality was 6.8% (6/88). Body temperature and respiratory and cardiac rates significantly decreased by day 1 compared to day 0. Lymphocyte count and pulse oximetry oxygen saturation/FiO2 ratio increased by days 3 and 5, whereas C-reactive protein levels dropped by day 2. There were no TCZ-attributable adverse events. In this observational single-center study, TCZ appeared to be useful and safe as immunomodulatory therapy for severe COVID-19 pneumonia.

4.
Int J Chron Obstruct Pulmon Dis ; 15: 3433-3445, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33447021

RESUMEN

Objective: To describe the characteristics and prognosis of patients with COPD admitted to the hospital due to SARS-CoV-2 infection. Methods: The SEMI-COVID registry is an ongoing retrospective cohort comprising consecutive COVID-19 patients hospitalized in Spain since the beginning of the pandemic in March 2020. Data on demographics, clinical characteristics, comorbidities, laboratory tests, radiology, treatment, and progress are collected. Patients with COPD were selected and compared to patients without COPD. Factors associated with a poor prognosis were analyzed. Results: Of the 10,420 patients included in the SEMI-COVID registry as of May 21, 2020, 746 (7.16%) had a diagnosis of COPD. Patients with COPD are older than those without COPD (77 years vs 68 years) and more frequently male. They have more comorbidities (hypertension, hyperlipidemia, diabetes mellitus, atrial fibrillation, heart failure, ischemic heart disease, peripheral vascular disease, kidney failure) and a higher Charlson Comorbidity Index (2 vs 1, p<0.001). The mortality rate in COPD patients was 38.3% compared to 19.2% in patients without COPD (p<0.001). Male sex, a history of hypertension, heart failure, moderate-severe chronic kidney disease, presence of cerebrovascular disease with sequelae, degenerative neurological disease, dementia, functional dependence, and a higher Charlson Comorbidity Index have been associated with increased mortality due to COVID-19 in COPD patients. Survival was higher among patients with COPD who were treated with hydroxychloroquine (87.1% vs 74.9%, p<0.001) and with macrolides (57.9% vs 50%, p<0.037). Neither prone positioning nor non-invasive mechanical ventilation, high-flow nasal cannula, or invasive mechanical ventilation were associated with a better prognosis. Conclusion: COPD patients admitted to the hospital with SARS-CoV-2 infection have more severe disease and a worse prognosis than non-COPD patients.


Asunto(s)
/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/terapia , Anciano , Femenino , Humanos , Masculino , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/mortalidad , Neumonía Viral/terapia , Neumonía Viral/virología , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , España/epidemiología , Tasa de Supervivencia
5.
BMJ Open ; 9(5): e025744, 2019 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-31129580

RESUMEN

INTRODUCTION: Pseudomonas aeruginosa (PA) has historically been one of the major causes of severe sepsis and death among neutropenic cancer patients. There has been a recent increase of multidrug-resistant PA (MDRPA) isolates that may determine a worse prognosis, particularly in immunosuppressed patients. The aim of this study is to establish the impact of antibiotic resistance on the outcome of neutropenic onco-haematological patients with PA bacteraemia, and to identify the risk factors for MDRPA bacteraemia and mortality. METHODS AND ANALYSIS: This is a retrospective, observational, multicentre, international study. All episodes of PA bacteraemia occurring in neutropenic onco-haematological patients followed up at the participating centres from 1 January 2006 to 31 May 2018 will be retrospectively reviewed. The primary end point will be overall case-fatality rate within 30 days of onset of PA bacteraemia. The secondary end points will be to describe the following: the incidence and risk factors for multidrug-resistant and extremely drug-resistant PA bacteraemia (by comparing the episodes due to susceptible PA with those produced by MDRPA), the efficacy of ceftolozane/tazobactam, the rates of persistent bacteraemia and bacteraemia relapse and the risk factors for very early (48 hours), early (7 days) and overall (30 days) case-fatality rates. ETHICS AND DISSEMINATION: The Clinical Research Ethics Committee of Bellvitge University Hospital approved the protocol of the study at the primary site. To protect personal privacy, identifying information of each patient in the electronic database will be encrypted. The processing of the patients' personal data collected in the study will comply with the Spanish Data Protection Act of 1998 and with the European Directive on the privacy of data. All data collected, stored and processed will be anonymised. Results will be reported at conferences and in peer-reviewed publications.


Asunto(s)
Bacteriemia/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple , Neoplasias/complicaciones , Neutropenia/complicaciones , Infecciones por Pseudomonas/tratamiento farmacológico , Antibacterianos/uso terapéutico , Bacteriemia/mortalidad , Cefalosporinas/uso terapéutico , Humanos , Cooperación Internacional , Modelos Logísticos , Estudios Multicéntricos como Asunto , Estudios Observacionales como Asunto , Pseudomonas aeruginosa/aislamiento & purificación , Proyectos de Investigación , Estudios Retrospectivos , Tazobactam/uso terapéutico , Factores de Tiempo
6.
J Clin Microbiol ; 57(2)2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30463889

RESUMEN

The objective of the present study was to evaluate the value of the PCR cycle threshold (CT ) for predicting the recurrence/severity of infection compared to that of toxin detection plus clinical variables. First episodes of Clostridium difficile infection (CDI) diagnosed during 2015 at our institution were included. Samples were tested for glutamate dehydrogenase (GDH) and toxin A/B by use of a single enzyme immunoassay (EIA). The Xpert C. difficile PCR assay was performed on GDH-positive samples. Medical data were reviewed by investigators blinded to diagnostic results for comparison of patients with and without recurrence or a poor outcome (severe/severe-complicated CDI episodes and all-cause death). We generated two sets of predictive models by incorporating the presence of a positive toxin EIA ("EIA-including model") or the optimal PCR CT cutoff value ("PCR-including model") into the clinical variables. Among 227 episodes of CDI included in the study, the rates of recurrence and poor outcome were 15.8% and 30.8%, respectively. The mean PCR CT was lower for episodes with recurrence (24.00 ± 3.28 versus 26.02 ± 4.54; P = 0.002) or a poor outcome (24.9 ± 4.24 versus 26.05 ± 4.47; P = 0.07). The optimal cutoff value for recurrence was 25.65 (sensitivity, 77.8% [95% confidence interval {CI}, 60.9 to 89.9]; and specificity, 46.6% [95% CI, 39.4 to 53.9]). The area under the receiver operator characteristics curve (auROC) for the "PCR-including model" was similar to that for the "EIA-including model" (0.785 versus 0.775, respectively). The optimal PCR CT value for poor outcome was 27.55 (sensitivity, 78.6% [95% CI, 67.1 to 87.5]; and specificity, 35.7% [95% CI, 28.2 to 43.7]). The auROC of the "PCR-including model" was again similar to that of the "EIA-including model" (0.804 versus 0.801). Despite the inverse correlation between PCR CT and the risk of CDI recurrence/severity, this determination does not meaningfully increase the predictive value of clinical variables plus toxin EIA.


Asunto(s)
Proteínas Bacterianas/genética , Toxinas Bacterianas/genética , Reglas de Decisión Clínica , Infecciones por Clostridium/diagnóstico , Infecciones por Clostridium/patología , Reacción en Cadena de la Polimerasa/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Técnicas para Inmunoenzimas/métodos , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Recurrencia , Estudios Retrospectivos , Sensibilidad y Especificidad , Resultado del Tratamiento , Adulto Joven
7.
Atherosclerosis ; 269: 204-210, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29407595

RESUMEN

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is a leading cause of mortality after kidney transplantation (KT). The potential role of the complement system in the pathogenesis of post-transplant CVD remains unexplored. METHODS: Serum complement (C3 and C4) levels were measured at baseline and post-transplant months 1 and 6 in 447 kT recipients. The study outcome was post-transplant atherothrombotic event (PAE), a composite of acute coronary syndrome, critical peripheral arterial disease, stroke and/or transient ischemic attack. RESULTS: After a median follow-up of 4.2 years, 48 PAEs occurred in 43 patients (cumulative incidence: 9.6%; incidence rate: 2.6 events per 100 transplant-years). No differences were found in C3 and C4 levels at baseline or month 1 between patients with or without PAE. However, C3 levels at month 6 were significantly lower in patients developing PAE beyond that point (i.e., late PAE) (96.9 ±â€¯22.3 vs. 109.6 ±â€¯24.0 mg/dL; p = 0.013). The presence of C3 hypocomplementemia at month 6 was associated with a lower PAE-free survival (p = 0.002). After adjusting for conventional CVD risk factors and acute graft rejection, C3 hypocomplementemia at month 6 remained as an independent risk factor for late PAE in all the exploratory models (minimum hazard ratio: 3.24; p = 0.011). With respect to a model exclusively based on clinical variables, the inclusion of C3 levels at month 6 improved predictive capacity (areas under ROC curves: 0.788 and 0.812, respectively). CONCLUSIONS: Post-transplant monitoring of serum C3 levels might be useful to identify KT recipients at increased risk of CVD.


Asunto(s)
Enfermedades Cardiovasculares/inmunología , Complemento C3/deficiencia , Complemento C4/deficiencia , Trasplante de Riñón/efectos adversos , Adulto , Anciano , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Monitorización Inmunológica , Supervivencia sin Progresión , Estudios Prospectivos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , España/epidemiología , Factores de Tiempo
8.
Artículo en Inglés | MEDLINE | ID: mdl-28584145

RESUMEN

ß-Lactam/ß-lactamase inhibitors (BLBLIs) were compared to carbapenems in two cohorts of hematological neutropenic patients with extended-spectrum-ß-lactamase (ESBL) bloodstream infection (BSI): the empirical therapy cohort (174 patients) and the definitive therapy cohort (251 patients). The 30-day case fatality rates and other secondary outcomes were similar in the two therapy groups of the two cohorts and also in the propensity-matched cohorts. BLBLIs might be carbapenem-sparing alternatives for the treatment of BSI due to ESBLs in these patients.


Asunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Enterobacteriaceae/efectos de los fármacos , Neutropenia/complicaciones , Inhibidores de beta-Lactamasas/uso terapéutico , Adulto , Bacteriemia/complicaciones , Bacteriemia/microbiología , Bacteriemia/mortalidad , Carbapenémicos/uso terapéutico , Estudios de Cohortes , Enterobacteriaceae/enzimología , Infecciones por Enterobacteriaceae/complicaciones , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , beta-Lactamasas/metabolismo , beta-Lactamas/uso terapéutico
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