RESUMEN
PURPOSE: Postoperative complications increase mortality, disability and costs. Advanced understanding of the risk factors for postoperative complications is needed to improve surgical outcomes. This paper discusses the rationale and profile of the BIGPROMISE (biomarkers to guide perioperative management and improve outcome in high-risk surgery) cohort, that aims to investigate risk factors, pathophysiology and outcomes related to postoperative complications. PARTICIPANTS: Adult patients undergoing major surgery in two tertiary teaching hospitals. Clinical data and blood samples are collected before surgery, at the end of surgery and on the first, second and third postoperative day. At each time point a panel of cardiovascular, inflammatory, renal, haematological and metabolic biomarkers is assessed. Aliquots of plasma, serum and whole blood of each time point are frozen and stored. Data on severe complications are prospectively collected during 30 days after surgery. Functional status is assessed before surgery and after 120 days using the WHO Disability Assessment Schedule (WHODAS) 2.0. Mortality is followed up until 2 years after surgery. FINDINGS TO DATE: The first patient was enrolled on 8 October 2021. Currently (1 January 2024) 3086 patients were screened for eligibility, of whom 1750 (57%) provided informed consent for study participation. Median age was 66 years (60; 73), 28% were female, and 68% of all patients were American Society of Anaesthesiologists (ASA) physical status class 3. Most common types of major surgery were cardiac (49%) and gastro-intestinal procedures (26%). The overall incidence of 30-day severe postoperative complications was 16%. FUTURE PLANS: By the end of the recruitment phase, expected in 2026, approximately 3000 patients with major surgery will have been enrolled. This cohort allows us to investigate the role of pathophysiological perioperative processes in the cause of postoperative complications, and to discover and develop new biomarkers to improve risk stratification for adverse postoperative outcomes. TRIAL REGISTRATION NUMBER: NCT05199025.
Asunto(s)
Biomarcadores , Complicaciones Posoperatorias , Humanos , Femenino , Masculino , Complicaciones Posoperatorias/epidemiología , Anciano , Persona de Mediana Edad , Biomarcadores/sangre , Factores de Riesgo , Bancos de Muestras Biológicas , Estudios Prospectivos , Procedimientos Quirúrgicos Operativos/efectos adversosRESUMEN
BACKGROUND: Acute kidney injury (AKI) is associated with mortality after cardiac surgery. Novel risk factors may improve identification of patients at risk for renal injury. The authors evaluated the association between preoperative biomarkers that reflect cardiac, inflammatory, renal, and metabolic disorders and cardiac surgery-associated AKI (CSA-AKI) in elderly patients. METHODS: This was a secondary analysis of the 2-center prospective cohort study "Anesthesia Geriatric Evaluation." Twelve biomarkers were determined preoperatively in 539 patients. Primary outcome was CSA-AKI. The association between biomarkers and CSA-AKI was investigated with multivariable logistic regression analysis. Secondary outcomes were 1-year mortality and patient-reported disability and were assessed with relative risks (RR) between patients with and without CSA-AKI. RESULTS: CSA-AKI occurred in 88 (16.3%) patients and was associated with increased risk of mortality (RR, 6.70 [95% confidence interval {CI}, 3.38-13.30]) and disability (RR, 2.13 [95% CI, 1.53-2.95]). Preoperative concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitive C-reactive protein (hs-CRP), hemoglobin, and magnesium had the strongest association with CSA-AKI. Identification of patients with CSA-AKI improved when a biomarker panel was used (area under the curve [AUC] 0.75 [95% CI, 0.69-0.80]) compared to when only clinical risk factors were used (European System for Cardiac Operative Risk Evaluation [EuroSCORE II] AUC 0.67 [95% CI, 0.62-0.73]). CONCLUSIONS: Preoperative cardiac, inflammatory, renal, and metabolic biomarkers are associated with CSA-AKI and may improve identification of patients at risk.
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Lesión Renal Aguda/etiología , Biomarcadores/sangre , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/mortalidad , Factores de Edad , Anciano , Proteína C-Reactiva/análisis , Procedimientos Quirúrgicos Cardíacos/mortalidad , Evaluación de la Discapacidad , Femenino , Estado Funcional , Evaluación Geriátrica , Hemoglobinas/análisis , Humanos , Magnesio/sangre , Masculino , Péptido Natriurético Encefálico/sangre , Países Bajos , Fragmentos de Péptidos/sangre , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Lesión Renal Aguda/fisiopatología , Tasa de Filtración Glomerular/fisiología , Hipotensión/fisiopatología , Complicaciones Intraoperatorias/fisiopatología , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Procedimientos Quirúrgicos del Sistema Digestivo/tendencias , Femenino , Humanos , Hipotensión/diagnóstico , Hipotensión/epidemiología , Complicaciones Intraoperatorias/diagnóstico , Complicaciones Intraoperatorias/epidemiología , Masculino , Estudios Prospectivos , Procedimientos Quirúrgicos TorácicosRESUMEN
OBJECTIVE: To assess the association of systemic inflammation and outcome after major abdominal surgery. BACKGROUND: Major abdominal surgery carries a high postoperative morbidity and mortality rate. Studies suggest that inflammation is associated with unfavorable outcome. METHODS: Levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α and the systemic inflammatory response syndrome (SIRS) were assessed in 137 patients undergoing major abdominal surgery. Blood samples were drawn on days 0, 1, 3, and 7, and SIRS was scored during 48âhours after surgery. Primary outcome was a composite of mortality, pneumonia, sepsis, anastomotic dehiscence, wound infection, noncardiac respiratory failure, atrial fibrillation, congestive heart failure, myocardial infarction, and reoperation within 30 days of surgery. RESULTS: An IL-6 level more than 432âpg/mL on day 1 was associated with an increased risk of complications (adjusted odds ratio: 3.3; 95% confidence interval [CI]: 1.3-8.5) and a longer median length of hospital stay (7 vs 12 days, P < 0.001). As a single test, an IL-6 cut-off level of 432âpg/mL on day 1 yielded a specificity of 70% and a sensitivity of 64% for the prediction of complications (area under the curve: 0.67; 95% CI: 0.56-0.77). Levels of CRP started to discriminate from day 3 onward with a specificity of 87% and a sensitivity of 58% for a cut-off level of 203 mg/L (AUC: 0.73; 95% CI: 0.63-0.83). CONCLUSIONS: A high IL-6 level on day 1 is associated with postoperative complications. Levels of IL-6 help distinguish between patients at low and high risk for complications before changes in levels of CRP.
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Abdomen/cirugía , Interleucina-6/sangre , Complicaciones Posoperatorias/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Diagnóstico Precoz , Procedimientos Quirúrgicos Electivos/mortalidad , Femenino , Humanos , Masculino , Complicaciones Posoperatorias/mortalidad , Estudios Prospectivos , Factores de Riesgo , Síndrome de Respuesta Inflamatoria Sistémica/mortalidad , Factor de Necrosis Tumoral alfa/sangreAsunto(s)
Neoplasias Abdominales/sangre , Neoplasias Abdominales/cirugía , Enfermedad de la Arteria Coronaria/sangre , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Troponina T/sangre , Neoplasias Abdominales/epidemiología , Biomarcadores/sangre , Caquexia/sangre , Caquexia/epidemiología , Estudios de Cohortes , Enfermedad de la Arteria Coronaria/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fuerza Muscular/fisiología , Factores de RiesgoRESUMEN
Insulin can be measured by immunochemical methods using polyclonal or monoclonal antibodies. Monoclonal antibodies are specific in the detection of pure human insulin, and may show little to no cross reactivity with pro-insulin or recombinant insulin. Polyclonal antibodies, however, do show such cross reactivity. Most medical laboratories use commercial (monoclonal) methods to measure insulin 75% of which are not capable of detecting pro-insulin or exogenous insulin. This pitfall in diagnostics may lead to prolonged uncertainty for both patient and physician, which we illustrate with two patients. The first patient was a 45-year-old woman with DM type 1 who for years suffered from hypoglycaemic attacks. Factitious hypoglycaemia went undiagnosed because our monoclonal assay did not detect the overdose insulin analogues. The second patient was a 47-year-old woman with recurrent hypoglycaemic attacks. An insulinoma, which produced pro-insulin, was only detected after using polyclonal insulin and specific pro-insulin assays.
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Hipoglucemia/diagnóstico , Hipoglucemiantes/análisis , Insulina/análisis , Insulinoma/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Anticuerpos Monoclonales/inmunología , Diagnóstico Diferencial , Femenino , Humanos , Hipoglucemia/etiología , Insulina/análogos & derivados , Insulinoma/metabolismo , Persona de Mediana Edad , Neoplasias Pancreáticas/metabolismoRESUMEN
Whenever neurons in the CNS are injured, microglia become activated. In addition to local activation, microglia remote from the primary lesion site are stimulated. Because this so-called secondary activation of microglia is instrumental for long-term changes after neuronal injury, it is important to understand how microglia activity is controlled. The remote activation of microglia implies that the activating signals are transported along neuronal projections. However, the identity of these signals has not yet been identified. It is shown here that glutamate-treated neurons rapidly express and release the chemokine CCL21. We also provide evidence that neuronal CCL21 is packed in vesicles and transported throughout neuronal processes to reach presynaptic structures. Chemotaxis assays show that functional CCL21 is released from endangered neurons and activate microglia via the chemokine receptor CXCR3. Based on these findings, we suggest that neuronal CCL21 is important in directed neuron-microglia signaling and that this communication could account for the remote activation of microglia, far distant from a primary lesion.