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The multisystem inflammatory syndrome in children (MIS-C) is a novel and concerning entity related to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Although MIS-C has been the subject of intensive research efforts, its pathophysiology and optimal treatment remain elusive. We studied the clinical features, laboratory findings, and immunoinflammatory profiles of seven children prospectively admitted to a pediatric intensive care unit (PICU) during the first wave of the pandemic. All patients had immunoglobulin (Ig)-G against SARS-CoV-2, four of seven patients had both IgM and IgG, and in one of the 7 SARS-CoV-2 was detected in a respiratory sample. All patients received intravenous fluid boluses (median: 15 mL/kg) and norepinephrine. The most common form of respiratory support was supplemental oxygen via nasal cannula. None of the patients needed mechanical ventilation. The cardiovascular system was frequently involved. All patients had an elevated troponin-I (median: 107.3 ng/L). Four out of seven patients had coronary artery abnormalities, and two of seven had both abnormal electrocardiogram (EKG) findings and evidence of left ventricular dysfunction on echocardiogram. Ig levels and complement function were normal. Peripheral blood phenotyping with flow cytometry showed decreased T-cell numbers at the expense of CD8+ T-cells. Cytokine profiling showed a heterogeneous increase in interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-18, IL-2Ra, IL-10, and IL-1Ra that tended to normalize after treatment. Our study shows that children with MIS-C have elevated plasma levels of pro- and anti-inflammatory cytokines in the acute phase of the disease without other relevant immunologic disturbances. These findings suggest the presence of a mixed antagonist response syndrome (MARS) similar to that present in pediatric sepsis. Combining a meticulous differential diagnosis with cautiously coordinated immunomodulatory therapy and high-quality supportive care can help clinicians avoid causing iatrogenic harm in patients with MIS-C.
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Aim: T2Bacteria® Panel detects six ESKAPE pathogens in around 3.5 h directly in whole blood. Our aim was to compare T2Bacteria with simultaneous blood culture in critically ill children with suspected bloodstream infection. Materials & methods: Retrospective study of critically ill children admitted to our tertiary-care center (2018-2020). Results: A total of 60 patients were recruited, including 63 episodes and 75 T2Bacteria/blood cultures were performed. Overall agreement between T2Bacteria and blood culture was 78.7% with a discordance of 21.3% (16/75 samples). Conclusion: T2Bacteria Panel may be useful in critically ill children providing an accurate and fast diagnosis of bacteremia directly from blood sample and detecting pathogens not recovered in blood cultures.
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Bacteriemia , Enfermedad Crítica , Bacteriemia/diagnóstico , Bacteriemia/microbiología , Cultivo de Sangre , Niño , Humanos , Unidades de Cuidados Intensivos , Unidades de Cuidado Intensivo Pediátrico , Estudios RetrospectivosRESUMEN
We evaluated in this randomised, double-blind clinical trial the efficacy of melatonin as a prophylactic treatment for prevention of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Healthcare workers fulfilling inclusion criteria were recruited in five hospitals in Spain and were randomised 1:1 to receive melatonin 2 mg administered orally for 12 weeks or placebo. The main outcome was the number of SARS-CoV-2 infections. A total of 344 volunteers were screened, and 314 were randomised: 151 to placebo and 163 to melatonin; 308 received the study treatment (148 placebo; 160 melatonin). We detected 13 SARS-CoV-2 infections, 2.6% in the placebo arm and 5.5% in the melatonin arm (p = 0.200). A total of 294 adverse events were detected in 127 participants (139 in placebo; 155 in melatonin). We found a statistically significant difference in the incidence of adverse events related to treatment: 43 in the placebo arm and 67 in the melatonin arm (p = 0.040), and in the number of participants suffering from somnolence related to treatment: 8.8% (n = 14) in the melatonin versus 1.4% (n = 2) in the placebo arm (p = 0.008). No severe adverse events related to treatment were reported. We cannot confirm our hypothesis that administration of melatonin prevents the development of SARS-CoV-2 infection in healthcare workers.
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The aim of this study was to investigate the effect of tobacco smoke exposure among severely pediatric ICU patients. A prospective epidemiological observational study was conducted among children with bronchiolitis younger than 2 years of age admitted to the Pediatric Intensive Care Unit of Children's University Hospital La Paz during the October 2017 to March 2018 outbreak. On admission, parents were asked whether they smoked. In children who required invasive mechanical ventilation, endotracheal aspirate was collected at the time of intubation. A total of 102 patients with bronchiolitis were studied. Among these, 14 (47%) of 30 infants whose parents smoked required invasive mechanical ventilation vs. 14 (19%) of 72 whose parents were nonsmokers (p = 0.007). Among patients on invasive mechanical ventilation, 10 (71%) of 14 infants with secondhand smoke exposure presented pulmonary bacterial superinfection vs. 3 (21%) of 14 in the unexposed (p = 0.012).Conclusion: Secondhand smoke exposure is an additional high risk for pulmonary bacterial superinfection and invasive mechanical ventilation in infants with severe acute bronchiolitis What is known: â¢Environmental tobacco smoke exposure is known to be an important risk factor for childhood lower respiratory tract infections. â¢Tobacco smoke makes structural changes in the respiratory tract and reduces the immune response. What in new: â¢Secondhand smoke exposure showed to be associated with the increased need and duration of invasive mechanical ventilation, and pediatric intensive care length of stay. â¢Tobacco smoke exposure is an additional risk factor for the presence of bacteria in the endotracheal aspirate.
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Bronquiolitis , Infecciones por Virus Sincitial Respiratorio , Bronquiolitis/epidemiología , Bronquiolitis/etiología , Niño , Hábitos , Humanos , Lactante , Padres , Estudios Prospectivos , NicotianaRESUMEN
OBJECTIVES: Early diagnosis of invasive Candida infections is a challenge for pediatricians, intensivists, and microbiologists. To fill this gap, a new nanodiagnostic method has been developed using manual application of T2 nuclear magnetic resonance to detect Candida species. The aim of this study was to evaluate, prospectively, the usefulness as a tool diagnosis of the T2Candida panel in pediatric patients admitted at the PICU compared with blood culture. DESIGN: This is a prospective, observational, and unicentric study to compare T2Candida results with simultaneous blood cultures for candidemia diagnose. SETTING: This study was carried out in a 1,300-bed tertiary care hospital with a 16-bed medical-surgical PICU. PATIENTS: Sixty-three patients from 0 to 17 years old were enrolled in this study, including those undergoing solid organ transplantation (kidney, liver, pulmonary, multivisceral, intestinal, and heart) and hematopoietic stem cell transplantation. MEASUREMENTS AND MAIN RESULTS: Seven patients were positive by the T2Candida test. Only two of them had the simultaneous positive blood culture. T2Candida yielded more positive results than blood cultures. CONCLUSIONS: T2Candida might be useful for the diagnosis of candidemia in PICUs. The prevalence of candidemia might be underestimated in this pediatric population. The use of this diagnostic tool in these units may help clinicians to start adequate and timely antifungal treatments.
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Candidemia , Adolescente , Candida , Candidemia/diagnóstico , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Pediátrico , Espectroscopía de Resonancia Magnética , Estudios ProspectivosRESUMEN
OBJECTIVES: ⢠Primary objective: to evaluate the effect of intravenous melatonin (IVM) on mortality in adult patients admitted to the intensive care unit (ICU) with COVID-19. ⢠Secondary objectives: ⦠To evaluate the effect of IVM on ICU length of stay. ⦠To evaluate the effect of IVM on the length of mechanical ventilation (MV). ⦠To evaluate if the use of IVM is associated with an increase in the number of ventilator-free days. ⦠To evaluate if the use of IVM is associated with a reduced number of failing organs as determined by the sequential organ failure assessment (SOFA) scale. ⦠To evaluate if the use of IVM is associated with a reduction of the frequency and severity of COVID-19-associated thromboembolic phenomena. ⦠To evaluate if the use of IVM is associated with a decreased systemic inflammatory response assessed by plasma levels of ferritin, D-dimer, C-reactive protein, procalcitonin and interleukin-6. ⦠To evaluate if the use of IVM is associated with an improvement in hematologic parameters. ⦠To evaluate if the use of IVM is associated with an improvement in biochemical parameters. ⦠To evaluate if the use of IVM is associated with an improvement in blood gas analysis parameters. ⦠To evaluate adverse events during the 28 day study period. TRIAL DESIGN: Phase II, single center, double-blind, placebo-controlled randomized trial with a two-arm parallel group design and 2:1 allocation ratio. PARTICIPANTS: Only critically ill adult patients that fulfill all of the inclusion criteria and none of the exclusion criteria will be included. The study will be conducted in a mixed ICU of a publicly funded tertiary referral center in Madrid, Spain with a 30-bed capacity and 1100 admissions per year. ⢠Inclusion criteria: ⦠Patient, family member or legal guardian has provided written Informed Consent. ⦠Age ε 18 years. ⦠Confirmed SARS-CoV-2 infection with compatible symptoms AND a positive RT-PCR. ⦠Admission to the ICU with acute hypoxemic respiratory failure attributed to SARS-CoV-2 infection. ⦠ICU length of stay of less than 7 days prior to randomization with or without MV and without signs of improvement in respiratory failure (MURRAY score at randomization greater or equal to the MURRAY score at ICU admission). ⢠Exclusion criteria: ⦠Participant in a different COVID-19 study in which the study drug is under clinical development and hasn't been previously authorized for commercialization. ⦠Liver enzymes > 5 times the upper normal range. ⦠Chronic kidney disease with GFR < 30 mL/min/1.73 m2 (stage 4 or greater) or need for hemodialysis. ⦠Pregnancy. A pregnancy test will be performed on every woman younger than 55 years of age prior to inclusion. ⦠Terminal surgical or medical illness. ⦠Autoimmune disease. ⦠Any patient condition that can prevent the study procedures to be carried out at the treating physician's judgement. INTERVENTION AND COMPARATOR: All patients will receive standard-of-care treatment according to the current institutional protocols. In addition, patients will be randomized in a 2:1 ratio to receive: ⢠Experimental group (12 patients): 7 days of 5 mg per Kg of actual body weight per day of intravenous melatonin every 6 hours. Maximum daily dose 500 mg per day. ⢠Control group (6 patients): 7 days of 5 mg per Kg of actual body weight per day of intravenous identically-looking placebo every 6 hours. After 3 days of treatment, 3 intensive care physicians will evaluate the participant and decide whether or not to complete the treatment based on their clinical assessment: ⢠If objective or subjective signs of improvement or no worsening of the general clinical condition, respiratory failure, inflammatory state or multi-organ failure are observed, the participant will continue the treatment until completion. ⢠If an adverse effect or clinical impairment is observed that is objectively or subjectively attributable to the study drug the treatment will be stopped. MAIN OUTCOME: Mortality in each study group represented in frequency and time-to-event at day 28 after randomization RANDOMIZATION: The randomization sequence was created using SAS version 9.4 statistical software (programmed and validated macros) with a 2:1 allocation. No randomization seed was pre-specified. The randomization seed was generated using the time on the computer where the program was executed. BLINDING (MASKING): Participants, caregivers and study groups will be blinded to arm allocation. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 18 patients will be randomized in this trial: 12 to the experimental arm and 6 to the control arm. TRIAL STATUS: Protocol version 2.0, June 5th 2020. Trial status: recruitment not started. The first patient is expected to be recruited in October 2020. The last patient is anticipated to be recruited in August 2021. TRIAL REGISTRATION: EU Clinical Trials Register. Date of trial registration: 10 July 2020. URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001808-42/ES FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Melatonina/administración & dosificación , Neumonía Viral/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Administración Intravenosa , COVID-19 , Método Doble Ciego , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Melatonina/efectos adversos , Pandemias , SARS-CoV-2RESUMEN
The pharmacological properties of melatonin are well known. However, there is noticeable the lack of clinical trials that confirm the efficacy, security, absence of side effects in the short and long term, and the effective doses of melatonin. This point is especially important in diseases with high morbidity and mortality including COVID-19. There is not treatment for COVID-19, and several anti-inflammatory and antiviral molecules are being tested, and different vaccines are in preparation. Although the SARS-CoV-2 pandemic is apparently improving, it is expected new resurges next fall. Thus, looking for an effective treatment of COVID-19 is mandatory. Melatonin has significant anti-inflammatory, antioxidant, and mitochondrial protective effects, and its efficacy has been demonstrated in multiple experimental models of disease and in a clinical trial in sepsis. Because COVID-19 courses with a severe septic response, multiple reviews proposing melatonin as a treatment for COVID-19 have been published. Nevertheless, there is a lack of experimental and clinical data on the use of melatonin on SARS-CoV-2 infection. Accordingly, we designed a clinical trial with an injectable formulation of melatonin for intravenous perfusion in ICU patients suffering from COVID-19 that has been just approved by the Spanish Agency of Medicines and Medical Devices (AEMPS). The trial will allow by the first time understand the doses and efficacy of melatonin against COVID-19.
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Antioxidantes/administración & dosificación , Infecciones por Coronavirus/tratamiento farmacológico , Melatonina/administración & dosificación , Neumonía Viral/tratamiento farmacológico , Betacoronavirus , COVID-19 , Humanos , Infusiones Intravenosas , Pandemias , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19RESUMEN
BACKGROUND: Fewer children than adults have been affected by the COVID-19 pandemic, and the clinical manifestations are distinct from those of adults. Some children particularly those with acute or chronic co-morbidities are likely to develop critical illness. Recently, a multisystem inflammatory syndrome (MIS-C) has been described in children with some of these patients requiring care in the pediatric ICU. METHODS: An international collaboration was formed to review the available evidence and develop evidence-based guidelines for the care of critically ill children with SARS-CoV-2 infection. Where the evidence was lacking, those gaps were replaced with consensus-based guidelines. RESULTS: This process has generated 44 recommendations related to pediatric COVID-19 patients presenting with respiratory distress or failure, sepsis or septic shock, cardiopulmonary arrest, MIS-C, those requiring adjuvant therapies, or ECMO. Evidence to explain the milder disease patterns in children and the potential to use repurposed anti-viral drugs, anti-inflammatory or anti-thrombotic therapies are also described. CONCLUSION: Brief summaries of pediatric SARS-CoV-2 infection in different regions of the world are included since few registries are capturing this data globally. These guidelines seek to harmonize the standards and strategies for intensive care that critically ill children with COVID-19 receive across the world. IMPACT: At the time of publication, this is the latest evidence for managing critically ill children infected with SARS-CoV-2. Referring to these guidelines can decrease the morbidity and potentially the mortality of children effected by COVID-19 and its sequalae. These guidelines can be adapted to both high- and limited-resource settings.
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Betacoronavirus , Infecciones por Coronavirus/terapia , Cuidados Críticos/normas , Unidades de Cuidado Intensivo Pediátrico/normas , Pandemias , Neumonía Viral/terapia , Adolescente , África/epidemiología , Américas/epidemiología , Antivirales/uso terapéutico , Asia/epidemiología , COVID-19 , Reanimación Cardiopulmonar/métodos , Reanimación Cardiopulmonar/normas , Niño , Preescolar , Terapia Combinada , Comorbilidad , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Cuidados Críticos/métodos , Infección Hospitalaria/prevención & control , Europa (Continente)/epidemiología , Oxigenación por Membrana Extracorpórea/normas , Femenino , Humanos , Lactante , Recién Nacido , Control de Infecciones/métodos , Control de Infecciones/normas , Masculino , Neumonía Viral/complicaciones , Neumonía Viral/epidemiología , Respiración Artificial/normas , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/terapia , SARS-CoV-2 , Choque/etiología , Choque/terapia , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Síndrome de Respuesta Inflamatoria Sistémica/terapia , Tratamiento Farmacológico de COVID-19RESUMEN
OBJECTIVES: Primary objective: to evaluate the efficacy of melatonin as a prophylactic treatment on prevention of symptomatic SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Secondary objectives: To evaluate the efficacy of melatonin as a prophylactic treatment on prevention of asymptomatic SARS-CoV-2 infection.To evaluate the efficacy of melatonin to prevent the development of severe COVID-19 in the participants enrolled in this study who develop SARS-CoV-2 infection along the trial.To evaluate the duration of COVID-19 symptoms in participants receiving melatonin before the infection.To evaluate seroconversion timing post-symptom onset. Exploratory objectives:To compare severity of COVID-19 between men and women.To evaluate the influence of sleep and diet on prevention from SARS-CoV-2 infection.To evaluate the effect of melatonin on the incidence and characteristics of lymphopenia and increase of inflammatory cytokines related to COVID-19. TRIAL DESIGN: This is a two-arm parallel randomised double-blind controlled trial to evaluate the efficacy of melatonin versus placebo in the prophylaxis of coronavirus disease 2019 among healthcare workers. PARTICIPANTS: Inclusion Criteria: Male or female participants ≥ 18 and ≤ 80 years of age.Healthcare workers from the public and private Spanish hospital network at risk of SARS-CoV 2 infection.Not having a previous COVID19 diagnosis.Understanding the purpose of the trial and not having taken any pre-exposure prophylaxis (PrEP) including HIV PrEP from March 1st 2020 until study enrolment.Having a negative SARS-CoV 2 reverse-transcription PCR (RT-PCR) result or a negative serologic rapid test (IgM/IgG) result before randomization.Premenopausal women must have a negative urinary pregnancy test in the 7 days before starting the trial treatment.Premenopausal women and males with premenopausal couples must commit to using a high efficiency anticonceptive method. EXCLUSION CRITERIA: HIV infection.Active hepatitis B infection.Renal failure (CrCl < 60 mL/min/1.73 m2) or need for hemodialysis.Osteoporosis.Myasthenia gravis.Pre-existent maculopathy.Retinitis pigmentosa.Bradycardia (less than 50 bpm).Weight less than 40 Kg.Participant with any immunosuppressive condition or hematological disease.Treatment with drugs that may prolong QT in the last month before randomization for more than 7 days including: azithromycin, chlorpromazine, cisapride, clarithromycin, domperidone, droperidol, erythromycin, halofantrine, haloperidol, lumefantrine, mefloquine, methadone, pentamidine, procainamide, quinidine, quinine, sotalol, sparfloxacin, thioridazine, amiodarone.Hereditary intolerance to galactose, Lapp lactase deficiency or glucose or galactose malabsorption.Treatment with fluvoxamine.Treatment with benzodiazepines or benzodiazepine analogues such as zolpidem, zopiclone or zaleplon.Pregnancy.Breastfeeding.History of potentially immune derived diseases such as: lupus, Crohn's disease, ulcerative colitis, vasculitis or rheumatoid arthritis.Insulin-dependent diabetes mellitus.Known history of hypersensitivity to the study drug or any of its components.Patients that should not be included in the study at the judgment of the research team. Participants will be recruited from the following eight hospitals in Madrid, Spain: Hospital Universitario La Paz, Hospital Ramón y Cajal, Hospital Infanta Sofía, Hospital 12 de Octubre, Hospital Clínico San Carlos, Hospital Central de la defensa Gómez Ulla,Hospital de La Princesa and Hospital Infanta Leonor. INTERVENTION AND COMPARATOR: Experimental: Melatonin (Circadin®, Exeltis Healthcare, Spain): 2 mg of melatonin orally before bedtime for 12 weeks. Comparator: Identical looking placebo (Laboratorios Liconsa, Spain) orally before bedtime for 12 weeks. MAIN OUTCOMES: Number of SARS-CoV-2 (COVID-19) symptomatic infections confirmed by polymerase chain reaction (PCR) test or serologic test or according to each centre diagnosis protocol. Primary outcome will be measured until the end of treatment for each participant (until the date of the last dose taken by each patient). RANDOMISATION: Patients who meet all inclusion and no exclusion criteria will be randomised, stratified by centres, sex and age (<50 and ≥ 50 years old). The randomisation sequence was created using SAS version 9.4 statistical software (procedure 'PROC PLAN') with a 1:1 allocation. No randomisation seed was specified. The randomisation seed was generated taking the hour of the computer where the program was executed. Randomization will be done centrally through the electronic system RedCAP® in order to conceal the sequence until interventions are assigned BLINDING (MASKING): Participants, caregivers, and those assessing the outcomes are blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 450 participants are planned to be enrolled in this clinical trial, 225 in the experimental arm and 225 in the placebo arm. TRIAL STATUS: Protocol version 3.0, 17th of April 2020. Recruitment ongoing. First participant was recruited on the 21st of April 2020. The final participant is anticipated to be recruited on the 31st of May 2020. As of May 18th, 2020, a total of 312 participants have been enrolled (154 at Hospital La Paz, 85 at Hospital Infanta Sofía and 73 at Hospital 12 de Octubre). TRIAL REGISTRATION: EU Clinical Trials Register: 2020-001530-35; Date of trial registration: 13th of April 2020; https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001530-35/ES FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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Antivirales/administración & dosificación , Betacoronavirus/efectos de los fármacos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Melatonina/administración & dosificación , Exposición Profesional/efectos adversos , Salud Laboral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , Antivirales/efectos adversos , Betacoronavirus/inmunología , Betacoronavirus/patogenicidad , COVID-19 , Quimioprevención , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Método Doble Ciego , Femenino , Humanos , Masculino , Melatonina/efectos adversos , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Pandemias , Neumonía Viral/sangre , Neumonía Viral/diagnóstico , Neumonía Viral/transmisión , Neumonía Viral/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , SARS-CoV-2 , Seroconversión , España , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression. Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from <1/3,300 in patients with anti-John Cunninghan virus antibody indices <0.9 and relapse rate >0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from <1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices <0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case. Conclusions: In a perspective of personalized medicine, disease activity, anti-lipid specific IgM oligoclonal bands, anti Jonh Cunninghan virus antibody levels, and age can help tailor natalizumab therapy in multiple sclerosis patients, as predictors of progressive multifocal leucoencephalopathy.
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Extracellular vesicles (EV) are small membrane structures released by cells that act as potent mediators of intercellular communication. The study of EV biology is important, not only to strengthen our knowledge of their physiological roles, but also to better understand their involvement in several diseases. In the field of biomedicine they have been studied as a novel source of biomarkers and drug delivery vehicles. The most commonly used method for EV enrichment in crude pellet involves serial centrifugation and ultracentrifugation. Recently, different protocols and techniques have been developed to isolate EV that imply less time and greater purification. Here we carry out a comparative analysis of three methods to enrich EV from plasma of healthy controls: ultracentrifugation, ExoQuickTM precipitation solution (System Biosciences), and Total Exosome Isolation kit (Invitrogen). Our results show that commercial precipitation reagents are more efficient and enable higher EV enrichment factors compared with traditional ultracentrifugation, although subsequent imaging analysis is not possible with some of them. We hope that this work will contribute to the current research on isolation techniques to assist the progress of clinical applications with diagnostic or therapeutic objectives.
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A case of 1-year- old male multivisceral transplant recipient with candidemia diagnosed by the T2Candida® test is presented. Optimal management of the candidemia complemented the treatment of the global clinical episode. Duration of treatment might be established much more precisely with the T2Candida® test than with blood cultures.
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A paediatric intensive care unit (PICU) is a separate physical facility or unit specifically designed for the treatment of paediatric patients who, because of the severity of illness or other life-threatening conditions, require comprehensive and continuous inten-sive care by a medical team with special skills in paediatric intensive care medicine. Timely and personal intervention in intensive care reduces mortality, reduces length of stay, and decreases cost of care. With the aim of defending the right of the child to receive the highest attainable standard of health and the facilities for the treatment of illness and rehabilitation, as well as ensuring the quality of care and the safety of critically ill paediatric patients, the Spanish Association of Paediatrics (AEP), Spanish Society of Paediatric Intensive Care (SECIP) and Spanish Society of Critical Care (SEMICYUC) have approved the guidelines for the admission, discharge and triage for Spanish PICUs. By using these guidelines, the performance of Spanish paediatric intensive care units can be optimised and paediatric patients can receive the appropriate level of care for their clinical condition.
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Unidades de Cuidado Intensivo Pediátrico/normas , Admisión del Paciente/normas , Alta del Paciente/normas , Triaje/normas , Niño , Humanos , EspañaRESUMEN
La unidad de cuidados intensivos pediátricos (UCIP) es una unidad física asistencial hospitalaria independiente especialmente diseñada para el tratamiento de pacientes pediátricos quienes debido su gravedad o condiciones potencialmente letales requieren observación y asistencia médica intensiva integral y continua por un equipo médico que haya obtenido competencia especial en medicina intensiva pediátrica. La aplicación oportuna de terapia intensiva a los pacientes críticos reduce la mortalidad, el tiempo de estancia y los costes asistenciales. Con los objetivos de respetar el derecho del niño al disfrute del más alto nivel posible de salud y a servicios para el tratamiento de las enfermedades y la rehabilitación de la salud y de garantizar la calidad asistencial y la seguridad de los pacientes pediátricos críticos, la Asociación Española de Pediatría (AEP), la Sociedad Española de Cuidados Intensivos Pediátricos (SECIP) y la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) han desarrollado y aprobado las guías de ingreso, alta y triage para las UCIP en España. Mediante la aplicación de estas guías se puede optimizar el uso de las UCIP españolas de forma que los pacientes pediátricos reciban el nivel de cuidados médicos más apropiado para su situación clínica
A paediatric intensive care unit (PICU) is a separate physical facility or unit specifically designed for the treatment of paediatric patients who, because of the severity of illness or other life-threatening conditions, require comprehensive and continuous inten-sive care by a medical team with special skills in paediatric intensive care medicine. Timely and personal intervention in intensive care reduces mortality, reduces length of stay, and decreases cost of care. With the aim of defending the right of the child to receive the highest attainable standard of health and the facilities for the treatment of illness and rehabilitation, as well as ensuring the quality of care and the safety of critically ill paediatric patients, the Spanish Association of Paediatrics (AEP), Spanish Society of Paediatric Intensive Care (SECIP) and Spanish Society of Critical Care (SEMICYUC) have approved the guidelines for the admission, discharge and triage for Spanish PICUs. By using these guidelines, the performance of Spanish paediatric intensive care units can be optimised and paediatric patients can receive the appropriate level of care for their clinical condition
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Humanos , Niño , Admisión del Paciente , Alta del Paciente/normas , Triaje/normas , Unidades de Cuidados Intensivos/normas , Cuidados Críticos , Seguridad del Paciente , EspañaRESUMEN
La unidad de cuidados intensivos pediátricos (UCIP) es una unidad física asistencial hospitalaria independiente especialmente diseñada para el tratamiento de pacientes pediátricos quienes debido su gravedad o condiciones potencialmente letales requieren observación y asistencia médica intensiva integral y continua por un equipo médico que haya obtenido competencia especial en medicina intensiva pediátrica. La aplicación oportuna de terapia intensiva a los pacientes críticos reduce la mortalidad, el tiempo de estancia y los costes asistenciales. Con los objetivos de respetar el derecho del niño al disfrute del más alto nivel posible de salud y a servicios para el tratamiento de las enfermedades y la rehabilitación de la salud y de garantizar la calidad asistencial y la seguridad de los pacientes pediátricos críticos, la Asociación Española de Pediatría (AEP), la Sociedad Española de Cuidados Intensivos Pediátricos (SECIP) y la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) han desarrollado y aprobado las guías de ingreso, alta y triage para las UCIP en España. Mediante la aplicación de estas guías se puede optimizar el uso de las UCIP españolas de forma que los pacientes pediátricos reciban el nivel de cuidados médicos más apropiado para su situación clínica
A paediatric intensive care unit (PICU) is a separate physical facility or unit specifically designed for the treatment of paediatric patients who, because of the severity of illness or other life-threatening conditions, require comprehensive and continuous intensive care by a medical team with special skills in paediatric intensive care medicine. Timely and personal intervention in intensive care reduces mortality, reduces length of stay, and decreases cost of care. With the aim of defending the right of the child to receive the highest attainable standard of health and the facilities for the treatment of illness and rehabilitation, as well as ensuring the quality of care and the safety of critically ill paediatric patients, the Spanish Association of Paediatrics (AEP), Spanish Society of Paediatric Intensive Care (SECIP) and Spanish Society of Critical Care (SEMICYUC) have approved the guidelines for the admission, discharge and triage for Spanish PICUs. By using these guidelines, the performance of Spanish paediatric intensive care units can be optimised and paediatric patients can receive the appropriate level of care for their clinical condition
Asunto(s)
Humanos , Niño , Unidades de Cuidado Intensivo Pediátrico/organización & administración , Triaje/métodos , Resumen del Alta del Paciente/normas , Servicio de Admisión en Hospital/organización & administración , Hospitalización/tendencias , Cuidados Críticos/métodos , Calidad de la Atención de Salud/tendencias , Seguridad del PacienteRESUMEN
A paediatric intensive care unit (PICU) is a separate physical facility or unit specifically designed for the treatment of paediatric patients who, because of the severity of illness or other life-threatening conditions, require comprehensive and continuous inten-sive care by a medical team with special skills in paediatric intensive care medicine. Timely and personal intervention in intensive care reduces mortality, reduces length of stay, and decreases cost of care. With the aim of defending the right of the child to receive the highest attainable standard of health and the facilities for the treatment of illness and rehabilitation, as well as ensuring the quality of care and the safety of critically ill paediatric patients, the Spanish Association of Paediatrics (AEP), Spanish Society of Paediatric Intensive Care (SECIP) and Spanish Society of Critical Care (SEMICYUC) have approved the guidelines for the admission, discharge and triage for Spanish PICUs. By using these guidelines, the performance of Spanish paediatric intensive care units can be optimised and paediatric patients can receive the appropriate level of care for their clinical condition.
Asunto(s)
Unidades de Cuidado Intensivo Pediátrico/organización & administración , Admisión del Paciente/normas , Alta del Paciente/normas , Triaje/normas , Niño , Toma de Decisiones Clínicas , Grupos Diagnósticos Relacionados , Adhesión a Directriz , Humanos , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Política Organizacional , Pase de Guardia/normas , EspañaRESUMEN
Bronchospasm appears in up to 4% of patients with obstructive lung disease or respiratory infection undergoing general anesthesia. Clinical examination alone may miss bronchospasm. As a consequence, subsequent (mis)treatment and ventilator settings could lead to pulmonary hyperinflation, hypoxia, hypercapnia, hypotension, patient-ventilator asynchrony, volutrauma, or barotrauma. Electrical impedance tomography (EIT), a new noninvasive technique, can potentially identify bronchospasms by determining regional expiratory time constants (τ) for each one of the pixels of a functional EIT image. We present the first clinical case that highlights the potential of breath-wise EIT-based τ images of the lung to quickly identify bronchospasm at the bedside, which could improve perioperative patient management and safety.