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1.
Eur Rev Med Pharmacol Sci ; 25(2): 1146-1157, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33577071

RESUMEN

OBJECTIVE: Many studies have been published recently on the characteristics of the clinical manifestations of COVID-19 in children. The quality scores of literature are different, and the incidence of clinical manifestations and laboratory tests results vary greatly. Therefore, a systematic retrospective meta-analysis is needed to determine the incidence of the clinical manifestations of COVID-19 in children. MATERIALS AND METHODS: Data from databases, such as PubMed, Web of science, EMBASE, Johns Hopkins University, and Chinese databases were analysed from January 31, 2020 to October 20, 2020. High-quality articles were selected for analysis based on a quality standard score. A meta-analysis of random effects was used to determine the prevalence of comorbidities and subgroup meta-analysis to examine the changes in the estimated prevalence in different subgroups. RESULTS: Seventy-one articles involving 11,671 children were included in the study. The incidence of fever, respiratory symptoms, gastrointestinal symptoms, asymptomatic patients, nervous system symptoms, and chest tightness was 55.8%, 56.8%, 14.4%, 21.1%, 6.7%, and 6.1%, respectively. The incidence of multisystem inflammatory syndrome was 6.2%. Laboratory examination results showed that lymphocytes decreased in 12% and leukocytes decreased in 8.8% of patients, whereas white blood cells increased in 7.8% of patients. Imaging showed abnormalities in 66.5%, and ground-glass opacities were observed in 36.9% patients. Epidemiological history was present in 85.2% cases; severe disease rate was 3.33%. The mortality rate was 0.28%. CONCLUSIONS: The clinical symptoms of COVID-19 in children are mild, and laboratory indicators and imaging manifestations are atypical. While screening children for COVID-19, in addition to assessing patients for symptoms as the first step of screening, the epidemiological history of patients should be obtained.


Asunto(s)
/sangre , /diagnóstico por imagen , /complicaciones , Niño , Preescolar , Humanos , Estudios Retrospectivos , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico por imagen , Síndrome de Respuesta Inflamatoria Sistémica/etiología
2.
Ann Surg ; 272(4): 604-610, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32932316

RESUMEN

OBJECTIVES: Sepsis and sterile both release "danger signals' that induce the systemic inflammatory response syndrome (SIRS). So differentiating infection from SIRS can be challenging. Precision diagnostic assays could limit unnecessary antibiotic use, improving outcomes. METHODS: After surveying human leukocyte cytokine production responses to sterile damage-associated molecular patterns (DAMPs), bacterial pathogen-associated molecular patterns, and bacteria we created a multiplex assay for 31 cytokines. We then studied plasma from patients with bacteremia, septic shock, "severe sepsis," or trauma (ISS ≥15 with circulating DAMPs) as well as controls. Infections were adjudicated based on post-hospitalization review. Plasma was studied in infection and injury using univariate and multivariate means to determine how such multiplex assays could best distinguish infective from noninfective SIRS. RESULTS: Infected patients had high plasma interleukin (IL)-6, IL-1α, and triggering receptor expressed on myeloid cells-1 (TREM-1) compared to controls [false discovery rates (FDR) <0.01, <0.01, <0.0001]. Conversely, injury suppressed many mediators including MDC (FDR <0.0001), TREM-1 (FDR <0.001), IP-10 (FDR <0.01), MCP-3 (FDR <0.05), FLT3L (FDR <0.05), Tweak, (FDR <0.05), GRO-α (FDR <0.05), and ENA-78 (FDR <0.05). In univariate studies, analyte overlap between clinical groups prevented clinical relevance. Multivariate models discriminated injury and infection much better, with the 2-group random-forest model classifying 11/11 injury and 28/29 infection patients correctly in out-of-bag validation. CONCLUSIONS: Circulating cytokines in traumatic SIRS differ markedly from those in health or sepsis. Variability limits the accuracy of single-mediator assays but machine learning based on multiplexed plasma assays revealed distinct patterns in sepsis- and injury-related SIRS. Defining biomarker release patterns that distinguish specific SIRS populations might allow decreased antibiotic use in those clinical situations. Large prospective studies are needed to validate and operationalize this approach.


Asunto(s)
Citocinas/sangre , Sepsis/sangre , Sepsis/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Informes Anuales como Asunto , Diagnóstico Diferencial , Cirugía General , Pruebas Hematológicas/métodos , Humanos , Estudios Prospectivos , Sepsis/inmunología , Sociedades Médicas , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Estados Unidos
3.
J Pediatric Infect Dis Soc ; 9(5): 622-625, 2020 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-32951037

RESUMEN

The pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 infection is a severe complication of coronavirus disease 2019. Since impaired coagulation and thrombosis/endotheliitis are suspected pathomechanisms, we treated 2 patients with defibrotide, a profibrinolytic, antithrombotic, antiinflammatory oligonucleotide. Symptoms resolved during treatment. Moreover, coagulation parameters indicating hypofibrinolysis and complement activation normalized. The pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 infection is a severe complication of coronavirus disease 2019. Since impaired coagulation and thrombosis/endotheliitis are suspected pathomechanisms, 2 patients received defibrotide, a profibrinolytic, antithrombotic, antiinflammatory oligonucleotide. Symptoms resolved and hypofibrinolysis/complement activation normalized during treatment.


Asunto(s)
Infecciones por Coronavirus/complicaciones , Inhibidores de Agregación Plaquetaria/uso terapéutico , Neumonía Viral/complicaciones , Polidesoxirribonucleótidos/uso terapéutico , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Dolor Abdominal/etiología , Adolescente , Betacoronavirus , Factores de Coagulación Sanguínea/análisis , Niño , Infecciones por Coronavirus/diagnóstico , Femenino , Fiebre/etiología , Humanos , Pandemias , Neumonía Viral/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Linfocitos T/inmunología
5.
J Clin Invest ; 130(11): 5967-5975, 2020 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-32730233

RESUMEN

BACKGROUNDInitial reports from the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic described children as being less susceptible to coronavirus disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed multisystem inflammatory syndrome in children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology.METHODSWe prospectively enrolled hospitalized patients with evidence of SARS-CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data.RESULTSTwenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8, and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. The presence of burr cells on blood smears, as well as Cts, differentiated between patients with severe COVID-19 and those with MIS-C.CONCLUSIONPediatric patients with SARS-CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and those with severe COVID-19.FUNDINGFinancial support for this project was provided by CHOP Frontiers Program Immune Dysregulation Team; National Institute of Allergy and Infectious Diseases; National Cancer Institute; the Leukemia and Lymphoma Society; Cookies for Kids Cancer; Alex's Lemonade Stand Foundation for Childhood Cancer; Children's Oncology Group; Stand UP 2 Cancer; Team Connor; the Kate Amato Foundations; Burroughs Wellcome Fund CAMS; the Clinical Immunology Society; the American Academy of Allergy, Asthma, and Immunology; and the Institute for Translational Medicine and Therapeutics.


Asunto(s)
Betacoronavirus/metabolismo , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Infecciones por Coronavirus , Citocinas/sangre , Pandemias , Neumonía Viral , Síndrome de Respuesta Inflamatoria Sistémica , Adolescente , Niño , Preescolar , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/epidemiología , Femenino , Humanos , Masculino , Neumonía Viral/sangre , Neumonía Viral/epidemiología , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología
6.
J Clin Neurosci ; 78: 108-113, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32600972

RESUMEN

Subarachnoid hemorrhage (SAH) can trigger immune activation sufficient to induce systematic inflammatory response syndrome (SIRS). Serum inflammatory biomarkers and SIRS can predict a poor outcome. The relationship between surgical stress and inflammatory response is well known but described in few reports in the neurosurgical population. We aimed to ascertain whether postoperative SIRS and initial serum biomarkers were associated with outcomes and evaluate whether the postoperative SIRS score differed between those with clipping and coil embolization. We evaluated 87 patients hospitalized within 24 h from onset of nontraumatic SAH. Serum biomarkers, such as levels of C-reactive protein (CRP), white blood cells (WBC), and D-dimer, as well as stress index (SI: blood sugar/K ratio) were obtained at admission. SIRS scores 3 days after admission were derived by adding the number of variables meeting the standard criteria (heart rate [HR] >90, respiratory rate [RR] >20, temperature >38 °C or <36 °C, and WBC count <4000 or >12,000). Clinical variables were compared according to whether they were associated with poor outcomes. Coil embolization was performed in 30 patients and clipping in 57. WBC, SI, D-dimer levels, and SIRS scores were significantly higher in patients with poor-grade SAH and were associated with poor outcomes. SIRS scores were significantly higher with clipping than with coil embolization among patients with good-grade SAH without intracerebral hemorrhage. Acute SIRS and serum biomarkers predict outcomes after SAH. Moreover, our study suggests the influence of surgical invasion via clipping on SIRS after SAH.


Asunto(s)
Proteína C-Reactiva/metabolismo , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Hemorragia Subaracnoidea/sangre , Hemorragia Subaracnoidea/cirugía , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Humanos , Leucocitos/metabolismo , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Hemorragia Subaracnoidea/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Resultado del Tratamiento
7.
J Clin Invest ; 130(11): 5942-5950, 2020 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-32701511

RESUMEN

BACKGROUNDPediatric SARS-CoV-2 infection can be complicated by a dangerous hyperinflammatory condition termed multisystem inflammatory syndrome in children (MIS-C). The clinical and immunologic spectrum of MIS-C and its relationship to other inflammatory conditions of childhood have not been studied in detail.METHODSWe retrospectively studied confirmed cases of MIS-C at our institution from March to June 2020. The clinical characteristics, laboratory studies, and treatment response were collected. Data were compared with historic cohorts of Kawasaki disease (KD) and macrophage activation syndrome (MAS).RESULTSTwenty-eight patients fulfilled the case definition of MIS-C. Median age at presentation was 9 years (range: 1 month to 17 years); 50% of patients had preexisting conditions. All patients had laboratory confirmation of SARS-CoV-2 infection. Seventeen patients (61%) required intensive care, including 7 patients (25%) who required inotrope support. Seven patients (25%) met criteria for complete or incomplete KD, and coronary abnormalities were found in 6 cases. Lymphopenia, thrombocytopenia, and elevation in inflammatory markers, D-dimer, B-type natriuretic peptide, IL-6, and IL-10 levels were common but not ubiquitous. Cytopenias distinguished MIS-C from KD and the degree of hyperferritinemia and pattern of cytokine production differed between MIS-C and MAS. Immunomodulatory therapy given to patients with MIS-C included intravenous immune globulin (IVIG) (71%), corticosteroids (61%), and anakinra (18%). Clinical and laboratory improvement were observed in all cases, including 6 cases that did not require immunomodulatory therapy. No mortality was recorded in this cohort.CONCLUSIONMIS-C encompasses a broad phenotypic spectrum with clinical and laboratory features distinct from KD and MAS.FUNDINGThis work was supported by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Institute of Allergy and Infectious Diseases; Rheumatology Research Foundation Investigator Awards and Medical Education Award; Boston Children's Hospital Faculty Career Development Awards; the McCance Family Foundation; and the Samara Jan Turkel Center.


Asunto(s)
Corticoesteroides/administración & dosificación , Betacoronavirus/metabolismo , Inmunoglobulinas Intravenosas/administración & dosificación , Inmunomodulación , Proteína Antagonista del Receptor de Interleucina 1/administración & dosificación , Síndrome de Respuesta Inflamatoria Sistémica , Adolescente , Biomarcadores/sangre , Niño , Preescolar , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Humanos , Lactante , Interleucina-10/sangre , Interleucina-6/sangre , Síndrome de Activación Macrofágica/sangre , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/tratamiento farmacológico , Síndrome de Activación Macrofágica/inmunología , Masculino , Síndrome Mucocutáneo Linfonodular/sangre , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Síndrome Mucocutáneo Linfonodular/inmunología , Péptido Natriurético Encefálico/sangre , Estudios Retrospectivos , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Síndrome de Respuesta Inflamatoria Sistémica/inmunología
10.
Int J Med Sci ; 17(9): 1281-1292, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32547323

RESUMEN

Rationale: Up to date, the exploration of clinical features in severe COVID-19 patients were mostly from the same center in Wuhan, China. The clinical data in other centers is limited. This study aims to explore the feasible parameters which could be used in clinical practice to predict the prognosis in hospitalized patients with severe coronavirus disease-19 (COVID-19). Methods: In this case-control study, patients with severe COVID-19 in this newly established isolation center on admission between 27 January 2020 to 19 March 2020 were divided to discharge group and death event group. Clinical information was collected and analyzed for the following objectives: 1. Comparisons of basic characteristics between two groups; 2. Risk factors for death on admission using logistic regression; 3. Dynamic changes of radiographic and laboratory parameters between two groups in the course. Results: 124 patients with severe COVID-19 on admission were included and divided into discharge group (n=35) and death event group (n=89). Sex, SpO2, breath rate, diastolic pressure, neutrophil, lymphocyte, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and D-dimer were significantly correlated with death events identified using bivariate logistic regression. Further multivariate logistic regression demonstrated a significant model fitting with C-index of 0.845 (p<0.001), in which SpO2≤89%, lymphocyte≤0.64×109/L, CRP>77.35mg/L, PCT>0.20µg/L, and LDH>481U/L were the independent risk factors with the ORs of 2.959, 4.015, 2.852, 3.554, and 3.185, respectively (p<0.04). In the course, persistently lower lymphocyte with higher levels of CRP, PCT, IL-6, neutrophil, LDH, D-dimer, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), and increased CD4+/CD8+ T-lymphocyte ratio and were observed in death events group, while these parameters stayed stable or improved in discharge group. Conclusions: On admission, the levels of SpO2, lymphocyte, CRP, PCT, and LDH could predict the prognosis of severe COVID-19 patients. Systematic inflammation with induced cardiac dysfunction was likely a primary reason for death events in severe COVID-19 except for acute respiratory distress syndrome.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Causas de Muerte , Infecciones por Coronavirus/mortalidad , Insuficiencia Cardíaca/mortalidad , Neumonía Viral/mortalidad , Síndrome de Respuesta Inflamatoria Sistémica/mortalidad , Anciano , Betacoronavirus/patogenicidad , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , China/epidemiología , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/virología , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/virología , Humanos , L-Lactato Deshidrogenasa/sangre , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Neutrófilos , Oximetría , Oxígeno/sangre , Pandemias , Neumonía Viral/sangre , Neumonía Viral/complicaciones , Neumonía Viral/virología , Polipéptido alfa Relacionado con Calcitonina/sangre , Pronóstico , Curva ROC , Factores de Riesgo , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/virología
11.
Circ J ; 84(4): 592-600, 2020 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-32147633

RESUMEN

BACKGROUND: Recent insights have emphasized the importance of inflammatory response in takotsubo syndrome (TTS). We sought to evaluate the predictors of systemic inflammatory response syndrome (SIRS) and its impact on cardiovascular mortality after TTS.Methods and Results:The 215 TTS patients were retrospectively included between September 2008 and January 2018. SIRS was diagnosed in 96 patients (44.7%). They had lower left ventricular ejection fraction (LVEF) on admission (34.5% vs. 41.9%; P<0.001) and higher peak brain natriuretic peptide and troponin. At a median follow-up of 518 days, SIRS was associated with increased in-hospital mortality (14.6% vs. 5.0%; P=0.019), overall mortality (29.4% vs. 10.8%; P=0.002), and cardiovascular mortality (10.6% vs. 2.1%; P=0.026). A history of cancer (OR, 3.36; 95% CI: 1.54-7.31; P=0.002) and LVEF <40% at admission (OR, 2.31; 95% CI: 1.16-4.58; P=0.017) were identified as independent predictors of SIRS. On multivariate Cox regression analysis, SIRS (HR, 12.8; 95% CI: 1.58-104; P=0.017), age (HR, 1.09; 95% CI: 1.02-1.16; P=0.01), and LVEF <40% at discharge (HR, 9.88; 95% CI: 2.54-38.4; P=0.001) were independent predictors of cardiovascular death. CONCLUSIONS: SIRS was found in a large proportion of TTS patients and was associated with enhanced myocardial damage and adverse outcome in the acute phase. At long-term follow-up, SIRS remained an independent factor of cardiovascular death.


Asunto(s)
Mortalidad Hospitalaria , Síndrome de Respuesta Inflamatoria Sistémica/mortalidad , Cardiomiopatía de Takotsubo/mortalidad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Admisión del Paciente , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Volumen Sistólico , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/fisiopatología , Cardiomiopatía de Takotsubo/sangre , Cardiomiopatía de Takotsubo/diagnóstico , Cardiomiopatía de Takotsubo/fisiopatología , Factores de Tiempo , Troponina/sangre , Función Ventricular Izquierda
12.
J Surg Res ; 249: 104-113, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31926397

RESUMEN

BACKGROUND: Hemorrhagic shock (HS) caused by rapid loss of a large amount of blood is the leading cause of early death after severe injury. When cells are damaged during HS, many intracellular components including DNA are released into the circulation and function as endogenous damage-associated molecular patterns (DAMPs) that can trigger excessive inflammatory response and subsequently multiple organ dysfunction. We hypothesized that the administration of deoxyribonuclease I (DNase I) could reduce cell-free DNA and attenuate tissue damage in HS. METHODS: Eight-week-old male C57BL/6 mice underwent HS by controlled bleeding from the femoral artery for 90 min, followed by resuscitation with Ringer's lactate solution (vehicle) or DNase I (10 mg/kg BW). RESULTS: At 20 h after HS, serum levels of cell-free DNA were increased by 7.6-fold in the vehicle-treated HS mice compared with sham, while DNase I reduced its levels by 47% compared with the vehicle group. Serum levels of tissue injury markers (lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase) and proinflammatory cytokine interleukin 6 were significantly reduced in the DNase I-treated mice. In the lungs, messenger RNA levels of proinflammatory cytokines (interleukin 6 and interleukin 1 ß), chemoattractant macrophage inflammatory protein - 2, and myeloperoxidase activity were significantly decreased in HS mice after DNase I. Finally, DNase I significantly improved the 10-day survival rate in HS mice. CONCLUSIONS: Administration of DNase I attenuates tissue damage and systemic and lung inflammation, leading to improvement of survival in HS mice. Thus, DNase I may potentially serve as an adjunct therapy for managing patients with HS.


Asunto(s)
Ácidos Nucleicos Libres de Células/sangre , Desoxirribonucleasa I/administración & dosificación , Resucitación/métodos , Choque Hemorrágico/terapia , Síndrome de Respuesta Inflamatoria Sistémica/terapia , Animales , Ácidos Nucleicos Libres de Células/metabolismo , Ácidos Nucleicos Libres de Células/toxicidad , Desoxirribonucleasa I/farmacología , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Choque Hemorrágico/sangre , Choque Hemorrágico/etiología , Choque Hemorrágico/mortalidad , Tasa de Supervivencia , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Síndrome de Respuesta Inflamatoria Sistémica/mortalidad , Heridas y Traumatismos/complicaciones
13.
Heart Vessels ; 35(1): 46-51, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31278424

RESUMEN

Our prospective study was therefore designed to determine which part of the systemic inflammatory response after cardiac operations resulted from Cardiopulmonary bypass (CPB) in neonates and infants. After approval by the human ethical committee of the Gunma Children's Medical Center (GCMC) and informed consent of the parents, 40 consecutive term congenital heart disease patients aged until 1 year who underwent long CPB time (> 3 h) at surgery were included in the prospective study between January 2012 and December 2014. C1 esterase inhibitor (C1-inh) drug (@Berinert) was generously provided by CSL Behring (King of Prussia, PA). The C1-inh (20 IU/kg) was given intravenously 60 min after CPB. Blood samples for complement factors were obtained before and 48 h after administration of C1-inh. Six patients did not survive and their data were not included. Of 34 patients included, median age was 6.5 months, median body weight was 6050 g, and 16 (47%) were female. According to the Mann-Whitney U test, there were no differences between the two groups concerning demographic and intraoperative data, postoperative chemical data. C1q concentration was only significant lower in patients with C1-inh non-treated group than in patients with C1-inh treated group. But, the consumption of C1q, C3, C4, CH50, and C1-inh in patients with C1-inhibitor non-treated group was observed early postoperatively. There is a significant difference in the values before and after C1-inh treatment between the two groups. The lower value in the C1-inh-treated group is explained by the activation of the classical pathway through the replenishment of complements by C1-inh treatment. This study proposes the administration of C1-inh is an effective therapy to reduce the activation and improve the clinical capillary leak syndrome.


Asunto(s)
Síndrome de Fuga Capilar/prevención & control , Procedimientos Quirúrgicos Cardíacos , Puente Cardiopulmonar , Activación de Complemento/efectos de los fármacos , Proteína Inhibidora del Complemento C1/administración & dosificación , Inactivadores del Complemento/administración & dosificación , Cardiopatías Congénitas/cirugía , Síndrome de Respuesta Inflamatoria Sistémica/prevención & control , Administración Intravenosa , Síndrome de Fuga Capilar/sangre , Síndrome de Fuga Capilar/diagnóstico , Síndrome de Fuga Capilar/inmunología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Puente Cardiopulmonar/efectos adversos , Proteína Inhibidora del Complemento C1/efectos adversos , Inactivadores del Complemento/efectos adversos , Femenino , Cardiopatías Congénitas/sangre , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/inmunología , Humanos , Lactante , Recién Nacido , Japón , Masculino , Estudios Prospectivos , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Factores de Tiempo , Resultado del Tratamiento
14.
Neurochirurgie ; 66(1): 29-35, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31634507

RESUMEN

OBJECTIVE: The mechanisms underlying epileptogenesis are still a focus of experimental and clinical research. Inflammation and angiogenesis are the two main topics that have been an area of interest recently. The present study assessed serum levels of endocan, an inflammatory and angiogenesis-promoting molecule, and of preoperative inflammatory markers (neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR)) in adult patients undergoing epilepsy surgery. METHODS: Twenty-one patients with epilepsy and 21 healthy controls were included. From patients, serum was collected twice: before and within a week after surgery. From controls, serum was collected once. Serum endocan was studied by ELISA and preoperative NLR and PLR were obtained from preoperative hemogram parameters. RESULTS: Preoperative serum endocan levels in patients were significantly higher than in controls. There was no difference between patients and controls regarding preoperative NLR and PLR. After surgery, serum endocan levels decreased in patients, with no further difference compared to controls. Serum endocan levels, NLR and PLR correlated positively, but not significantly, with epilepsy duration and seizure frequency. CONCLUSIONS: Angiogenesis and low-grade inflammation may play a role in the development and progression of epilepsy. We suggest that larger cohort of epilepsy patients with longer-term follow-up should be studied.


Asunto(s)
Biomarcadores/sangre , Epilepsia/sangre , Epilepsia/cirugía , Proteínas de Neoplasias/sangre , Proteoglicanos/sangre , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Adulto , Estudios de Cohortes , Femenino , Humanos , Recuento de Leucocitos , Linfocitos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Neutrófilos , Recuento de Plaquetas , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Convulsiones/cirugía , Resultado del Tratamiento , Adulto Joven
15.
Gastroenterology ; 158(1): 253-269.e14, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31593700

RESUMEN

BACKGROUND & AIMS: Pancreatitis starts with primarily sterile local inflammation that induces systemic inflammatory response syndrome, followed by compensatory anti-inflammatory response syndrome (CARS). We investigated the mechanisms of these processes in mice and human serum. METHODS: We induced severe acute pancreatitis by partial duct ligation with caerulein stimulation or intraperitoneal injection of l-arginine in mice with deletion of interleukin (IL)12B, NLRP3, or IL18 and in mice given MCC950, a small molecule inhibitor of the NLRP3-inflammasome. Pancreata were collected from mice and analyzed by histology, and cytokine levels were measured in serum samples. We measured activation of adaptive immune responses in mice with pancreatitis by flow cytometry analysis of T cells (CD25 and CD69) isolated from the spleen. Differentiation of T-helper (Th1) cells, Th2 cells, and T-regulatory cells was determined by nuclear staining for TBET, GATA3, and FOXP3. We performed transcriptome analysis of mouse lymph nodes and bone marrow-derived macrophages after incubation with acini. We measured levels of cytokines in serum samples from patients with mild and severe acute pancreatitis. RESULTS: Activation of the adaptive immune response in mice was initiated by macrophage-derived, caspase 1-processed cytokines and required activation of NLRP3 (confirmed in serum samples from patients with pancreatitis). Spleen cells from mice with pancreatitis had increases in Th2 cells but not in Th1 cells. Bone marrow-derived macrophages secreted IL1B and IL18, but not IL12, after co-incubation with pancreatic acini. T-cell activation and severity of acute pancreatitis did not differ significantly between IL12B-deficient and control mice. In contrast, NLRP3- or IL18-deficient mice had reduced activation of T cells and no increase in Th2 cell-mediated responses compared with control mice. The systemic type 2 immune response was mediated by macrophage-derived cytokines of the IL1 family. Specifically, IL18 induced a Th2 cell-mediated response in the absence of IL12. MCC950 significantly reduced neutrophil infiltration, T-cell activation, and disease severity in mice. CONCLUSIONS: In mice with severe pancreatitis, we found systemic inflammatory response syndrome and compensatory anti-inflammatory response syndrome developed in parallel. Infiltrating macrophages promote inflammation and simultaneously induce a Th2 cell-mediated response via IL18. Inhibition of NLRP3 reduces systemic inflammatory response syndrome and compensatory anti-inflammatory response syndrome and might be used to treat patients with severe pancreatitis.


Asunto(s)
Furanos/administración & dosificación , Inflamasomas/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , Pancreatitis/inmunología , Sulfonamidas/administración & dosificación , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Células Acinares , Inmunidad Adaptativa , Animales , Arginina/toxicidad , Células Cultivadas , Ceruletida/toxicidad , Citocinas/sangre , Citocinas/inmunología , Modelos Animales de Enfermedad , Compuestos Heterocíclicos de 4 o más Anillos , Humanos , Inyecciones Intraperitoneales , Interleucina-18/inmunología , Interleucina-18/metabolismo , Macrófagos/inmunología , Ratones , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Páncreas/citología , Páncreas/inmunología , Páncreas/patología , Pancreatitis/inducido químicamente , Pancreatitis/tratamiento farmacológico , Cultivo Primario de Células , Sulfonas , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Células Th2/inmunología , Células Th2/metabolismo
16.
Gut ; 69(1): 103-111, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31023832

RESUMEN

OBJECTIVE: We assessed the effect of surgical resection of colorectal cancer (CRC) on perioperative plasma vitamin D (25OHD) and C-reactive protein (CRP) level. We investigated the relationship between circulating vitamin D level and CRC survival. DESIGN: We sequentially sampled 92 patients undergoing CRC resection, and measured plasma 25OHD and CRP. For survival analyses, we assayed 25OHD and CRP in two temporally distinct CRC patient cohorts (n=2006, n=2100) and investigated the association between survival outcome, circulating vitamin D and systemic inflammatory response. RESULTS: Serial sampling revealed a postoperative fall (mean 17.3 nmol/L; p=3.6e-9) in plasma 25OHD (nadir days 1-2). CRP peaked 3-5 days postoperatively (143.1 mg/L; p=1.4e-12), yet the postoperative fall in 25OHD was independent of CRP. In cohort analyses, 25OHD was lower in the 12 months following operation (mean=48.8 nmol/L) than preoperatively (54.8 nmol/L; p=1.2e-5) recovering after 24 months (52.2 nmol/L; p=0.002). Survival analysis in American Joint Committee on Cancer stages I-III demonstrated associations between 25OHD tertile and CRC mortality (HR=0.69; 95% CI 0.46 to 0.91) and all-cause mortality (HR=0.68; 95% CI 0.50 to 0.85), and was independent of CRP. We observed interaction effects between plasma 25OHD and rs11568820 genotype (functional VDR polymorphism) with a strong protective effect of higher 25OHD only in patients with GG genotype (HR=0.51; 95% CI 0.21 to 0.81). We developed an online tool for predicted survival (https://apps.igmm.ed.ac.uk/mortalityCalculator/) that incorporates 25OHD with clinically useful predictive performance (area under the curve 0.77). CONCLUSIONS: CRC surgery induces a fall in circulating 25OHD. Plasma 25OHD level is a prognostic biomarker with low 25OHD associated with poorer survival, particularly in those with rs11568820 GG genotype. A randomised trial of vitamin D supplementation after CRC surgery has compelling rationale.


Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias Colorrectales/cirugía , Vitamina D/análogos & derivados , Anciano , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/genética , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Pronóstico , Receptores de Calcitriol/genética , Análisis de Supervivencia , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Vitamina D/sangre
17.
S Afr Med J ; 110(12): 1180-1185, 2020 10 23.
Artículo en Inglés | MEDLINE | ID: mdl-33403962

RESUMEN

COVID-19 severity appears to lie in its propensity to cause a hyperinflammatory response, attributed to the cytokine release syndrome (CRS) or 'cytokine storm', although the exact role of the CRS remains to be fully elucidated. Hyperinflammation triggers a hypercoagulable state, also thought to play a key role in COVID-19 pathogenesis. Disease severity is linked to age, sex and comorbid conditions, which in turn may be linked to oxidative stress and pre-existing depletion of nicotinamide adenine dinucleotide (NAD+). There is increasing evidence that the host genome may determine disease outcome. Since most information pertaining to COVID-19 has thus far been extrapolated from the 'global North', similar studies in African populations are warranted. Many studies are aimed at finding a therapeutic strategy based on scientific rationale. Some promising results have emerged, e.g. the use of corticosteroids in severe acute respiratory distress syndrome (ARDS).


Asunto(s)
/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Inflamación/inmunología , Trombofilia/sangre , Corticoesteroides/uso terapéutico , Factores de Edad , Antiinflamatorios/uso terapéutico , Anticoagulantes/uso terapéutico , Antivirales/uso terapéutico , /tratamiento farmacológico , /terapia , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Antígenos HLA/genética , Humanos , Inmunización Pasiva , Inflamación/sangre , Inflamación/tratamiento farmacológico , NAD , Estrés Oxidativo , /inmunología , Índice de Severidad de la Enfermedad , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/fisiopatología , Síndrome de Respuesta Inflamatoria Sistémica/terapia , Trombofilia/tratamiento farmacológico , Trombofilia/fisiopatología , Vitaminas/uso terapéutico
18.
Sci Rep ; 9(1): 18340, 2019 12 04.
Artículo en Inglés | MEDLINE | ID: mdl-31798002

RESUMEN

Pentraxin 3 (PTX3) is an acute phase protein. Our goal was to assess PTX3 as a predictor of systemic inflammatory response syndrome (SIRS), death and disease severity in acute pancreatitis (AP) in comparison to C-reactive protein (CRP) and the APACHE II score. From April 2011 to January 2015, 142 patients with AP were included in this single center post hoc analysis of prospectively collected data at the University Hospital Basel, Switzerland. Disease severity was rated by the revised Atlanta criteria (rAC). Inflammatory response was measured by the SIRS criteria. PTX3, CRP and APACHE II score were measured. Patients median PTX3 plasma concentrations in AP were higher in moderate (3.311 ng/ml) and severe (3.091 ng/ml) than in mild disease (2.461 ng/ml). Overall, 59 occurrences of SIRS or death were observed. In the prediction of SIRS or death, PTX3 was inferior to CRP and APACHE II, with modest predictive discriminatory ability of all three markers and AUC of 0.54, 0.69 and 0.69, respectively. Upon combination of CRP with PTX3, AUC was 0.7. PTX3 seems to be inferior to CRP and APACHE II in the prediction of SIRS or death in AP and does not seem to improve the predictive value of CRP upon combination of both parameters.


Asunto(s)
Proteína C-Reactiva/genética , Pancreatitis/sangre , Componente Amiloide P Sérico/genética , Síndrome de Respuesta Inflamatoria Sistémica/sangre , APACHE , Adulto , Anciano , Biomarcadores/sangre , Muerte , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis/diagnóstico , Pancreatitis/patología , Índice de Severidad de la Enfermedad , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/patología
19.
Int J Mol Sci ; 20(23)2019 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-31795299

RESUMEN

This review aims to briefly discuss a short list of a broad variety of inflammatory cytokines. Numerous studies have implicated that inflammatory cytokines exert important effects with regard to various inflammatory diseases, yet the reports on their specific roles are not always consistent. They can be used as biomarkers to indicate or monitor disease or its progress, and also may serve as clinically applicable parameters for therapies. Yet, their precise role is not always clearly defined. Thus, in this review, we focus on the existing literature dealing with the biology of cytokines interleukin (IL)-6, IL-1, IL-33, tumor necrosis factor-alpha (TNF-α), IL-10, and IL-8. We will briefly focus on the correlations and role of these inflammatory mediators in the genesis of inflammatory impacts (e.g., shock, trauma, immune dysregulation, osteoporosis, and/or critical illness).


Asunto(s)
Citocinas/metabolismo , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Animales , Citocinas/genética , Humanos , Linfocitos/inmunología , Monocitos/inmunología , Neutrófilos/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/sangre
20.
PLoS One ; 14(12): e0225525, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31790441

RESUMEN

The Systemic Inflammatory Response Syndrome (SIRS), a sepsis related inflammatory state, is a self-defense mechanism against specific and nonspecific stimuli. The six most extensively studied inflammatory biomarkers for the clinical diagnosis of SIRS are interleukin 4 (hIL-4), interleukin 6 (hIL-6), interleukin 10 (hIL-10), tumor necrosis factor alpha (hTNF-α), interferon gamma (hIFN-γ) and procalcitonin (hPCT). These biomarkers are naturally present (but usually only at low concentration) in SIRS infected patients [1, 2] and thus the development of a highly sensitive detection method is of major clinical interest. However, the existing analytical techniques are lacking in required analytical sensitivity and parallel determination of these biomarkers. We developed a fast, easy and cost-efficient protein microarray biochip where the capture molecules are attached on hydrogel spots, enabling SIRS diagnosis by parallel detection of these six clinically relevant biomarkers with a sample volume of 25 µl. With our hydrogel based protein microarray biochip we achieved a limit of detection for hIL-4 of 75.2 pg/ml, for hIL-6 of 45.1 pg/ml, for hIL-10 of 71.5 pg/ml, for hTNF-α of 56.7 pg/ml, for IFN-γ of 46.4 pg/ml and for hPCT of 1.1 ng/ml in spiked human serum demonstrating sufficient sensitivity for clinical usage. Additionally, we demonstrated successful detection of two relevant SIRS biomarkers in clinical patient samples with a turnaround time of the complete analysis from sample-to-answer in less than 200 minutes.


Asunto(s)
Citocinas/sangre , Análisis por Matrices de Proteínas/instrumentación , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Anticuerpos/química , Anticuerpos/inmunología , Biomarcadores/sangre , Carbocianinas/química , Colorantes Fluorescentes/química , Fluoroinmunoensayo/instrumentación , Fluoroinmunoensayo/métodos , Humanos , Hidrogeles/química , Análisis por Matrices de Proteínas/métodos , Estreptavidina/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Factores de Tiempo
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