Value of the biomarker soluble tyrosine kinase 1 type fms (sFLT-1) in the diagnosis and prognosis of sepsis: a systematic review. / Valor del biomarcador tirosina quinasa 1 soluble tipo fms (sFLT-1) en el diagnóstico y pronóstico de la sepsis: una revisión sistemática.

INTRODUCTION: The present systematic review analyses the role of soluble fms-like tyrosine kinase-1 (sFLT-1) as an indirect biomarker of endothelial dysfunction in sepsis or septic shock from articles published in PubMed between 2010 and March 2022. MATERIALS AND METHODS: A systematic review of studies studying sFLT-1 monitoring in intensive care units in adults with sepsis or septic shock vs. controls for sepsis diagnosis and prognosis has been carried out (PROSPERO CRD42023412929 Registry). RESULTS: The endothelial dysfunction of sepsis is one of the keys to the development of the disease. VEGF binds to sFLT-1 acting as a competitive inhibitor of VEGF signalling in endothelial cells and thus neutralizes its pro-inflammatory effects. Endothelial dysfunction is reflected in increased sFLT-1 levels. High values of sFLT-1 were used for the differential diagnosis of sepsis versus other inflammatory pathologies, septic shock versus other types of shock, were elevated over time, estimation of disease prognosis, correlation with sepsis severity, organ dysfunction, and mortality prediction. CONCLUSIONS: It is evident that sepsis is based on endothelial dysfunction. sFLT-1 is one of the main biomarkers of microvascular alteration and is a predictive diagnostic and prognostic biomarker.

Usefulness of Preoperative Determination of Serum MR-ProAdrenomedullin Levels to Predict the Need for Postoperative Organ Support in Abdominal Oncological Surgery.

The need for postoperative organic support is associated with patient outcomes. Biomarkers may be useful for detecting patients at risk. MR-ProADM is a novel biomarker with an interesting profile that can be used in this context. The main objective of this study was to verify whether there was an association between the preoperative serum levels of MR-ProADM and the need for organic support after elective abdominal cancer surgery, and to determine the preoperative MR-ProADM value that predicts the need for postoperative organic support. This was a multicenter prospective observational study conducted by four tertiary hospitals in Spain between 2017 and 2018. Plasma samples were collected for the quantification of MR-ProADM from adults who underwent major abdominal surgery during 2017-2018. The primary outcome was the need for organic support in the first seven postoperative days and its association with the preoperative levels of MR-ProADM, and the secondary outcome was the preoperative levels of MR-ProADM in the study population. This study included 370 patients with a mean age of 67.4 ± 12.9 years. Seventeen percent (63 patients) required some postoperative organic support measures in the first week. The mean preoperative value of MR-ProADM in patients who required organic support was 1.16 ± 1.15 nmol/L. The AUC-ROC of the preoperative MR-ProADM values associated with the need for organic support was 0.67 (95% CI: 0.59-0.75). The preoperative MR-ProADM value, which showed the best compromise in sensitivity and specificity for predicting the need for organic support, was 0.70 nmol/L. The negative predictive value was 91%. A multivariate analysis confirmed that a preoperative level of MR-ProADM ≥ 0.70 nmol/L is an independent factor associated with risk of postoperative organic support (OR 2, 6). Elevated preoperative MR-ProADM levels are associated with the need for postoperative organic support. Therefore, MR-ProADM may be a useful biomarker for perioperative risk assessment.

Postoperative delirium: An independent risk factor for poorer quality of life with long-term cognitive and functional decline after cardiac surgery.

STUDY OBJECTIVE: To evaluate the influence of delirium on the functional and cognitive capacity of patients included in the DELIPRECAS study, as well as on their quality of life, in the 3-4 years after cardiac surgery. DESIGN: Prospective observational study. SETTING: Assessment of cognitive and functional status from hospital discharge to the present, 3 years after cardiac surgery. PATIENTS: 313 patients undergoing cardiac surgery consecutively, aged 18 years or over. MEASUREMENTS: The primary outcome measure was the cognitive and functional status of the patients 3 years after cardiac surgery, evaluated by telephone interview, and the possible influence on them of delirium diagnosed by the Confusion Assessment Method in Intensive Care Units (CAM-ICU) during their stay in the intensive care unit after cardiac surgery. MAIN RESULTS: Postoperative delirium acts as an independent risk factor for the long-term development of memory problems (OR 6.11, 95% CI 2.54 to 14.68, p < 0.001), concentration (OR 11.20, 95% CI 3.58 to 35.09, p > 0.001), confusion/disorientation (OR 10.93, 95% CI 3.61 to 33.12, p > 0.001), sleep problems (OR 5.21, 95% CI 2 0.29 to 11.84, p < 0.001), nightmares (OR 8.99, 95% CI 1.98 to 40.90, p = 0.004), emotional problems (OR 4.30, 95% CI 1.87 to 9.91, p = 0.001) and poorer mobility after hospital discharge (OR 2.436, 95% CI 1.06 to 5.61, p = 0.037). The number of hospital readmissions was also significantly higher in those patients who developed delirium after cardiac surgery (27% vs 13.8%, p = 0.022). CONCLUSION: Postoperative delirium is a risk factor for decreased quality of life in patients 3 years after heart surgery, being associated with greater cognitive and functional deterioration, as well as greater risk of hospital readmission. Therefore, emphasis should be placed on both prevention and early recognition and treatment of delirium to improve long-term outcomes for patients after cardiac surgery.

Influence of Renal Dysfunction on the Differential Behaviour of Procalcitonin for the Diagnosis of Postoperative Infection in Cardiac Surgery.

Background: procalcitonin is a valuable marker in the diagnosis of bacterial infections; however, the impairment of renal function can influence its diagnostic precision. The objective of this study is to evaluate the differential behaviour of procalcitonin, as well as its usefulness in the diagnosis of postoperative pulmonary infection after cardiac surgery, depending on the presence or absence of impaired renal function. Materials and methods: A total of 805 adult patients undergoing cardiac surgery with extracorporeal circulation (CBP) were prospectively recruited, comparing the behaviour of biomarkers between the groups with and without postoperative pneumonia and according to the presence or absence of renal dysfunction. Results: Pulmonary infection was diagnosed in 42 patients (5.21%). In total, 228 patients (28.32%) presented postoperative renal dysfunction. Procalcitonin was significantly higher in infected patients, even in the presence of renal dysfunction. The optimal procalcitonin threshold differed markedly in patients with renal dysfunction compared to patients without renal dysfunction (1 vs. 0.78 ng/mL p < 0.05). The diagnostic accuracy of procalcitonin increased significantly when the procalcitonin threshold was adapted to renal function. Conclusions: Procalcitonin is an accurate marker of postoperative infection in cardiac surgery, even in the presence of renal dysfunction. Renal function is an important determinant of procalcitonin levels and, therefore, its diagnostic thresholds must be adapted in the presence of renal dysfunction.

Development and validation of a delirium risk prediction preoperative model for cardiac surgery patients (DELIPRECAS): An observational multicentre study.

STUDY OBJECTIVE: To develop and validate a delirium risk prediction preoperative model for patients undergoing cardiac surgery. DESIGN: Observational prospective multicentre study. SETTING: Six intensive care units in Spain. PATIENTS: 689 patients undergoing cardiac surgery consecutively, aged ≥18 years. MEASUREMENTS: The primary outcome measure was the development of delirium, diagnosed using the Confusion Assessment Method in Intensive Care Units (CAM-ICU), during the stay in the intensive care unit after cardiac surgery. MAIN RESULTS: The model was developed with 345 consecutive patients undergoing cardiac surgery at six hospitals and validated with another 344 patients from the same hospitals. The prediction model contained four preoperative risk factors: age over 65 years, Mini-Mental State Examination (MMSE) score of 25-26 points (possible impairment of cognitive function) or < 25 (impairment of cognitive function), insomnia needing medical treatment and low physical activity (walk less than 30 min a day). The model had an area under the receiver operating characteristics curve of 0.825 (95% confidence interval: 0.76-0.89). The validation resulted in an area under the curve of 0.79 (0.73-0.85) and the pooled area under the receiver operating characteristics curve (n = 689) was 0.81 (0.76-0.85). We stratified patients in groups of low (0%-20%), moderate (> 20%-40%), high (> 40%-60%) and very high (> 60%) risk of developing delirium, with a positive and negative predictive value for the very high risk group of 70.97% and 85.56%, respectively. CONCLUSION: The DELIPRECAS model (DELIrium PREvention CArdiac Surgery), consisting of four well-defined clinical risk factors, can predict in the preoperative period the risk of developing postoperative delirium in patients undergoing cardiac surgery. An automatic version of the risk calculator is available.

Impact of nosocomial infections on patient mortality following cardiac surgery.

STUDY OBJECTIVE: To determine the rate of nosocomial infection among patients undergoing cardiac surgery and to identify risk factors and the impact of these infections on patient mortality. DESIGN: Prospective observational study. SETTING: Intensive Care Unit (ICU). PATIENTS: 1097 adult patients who underwent cardiac surgery at Hospital Clínico Universitario de Valladolid between January 2011 and January 2016. INTERVENTIONS: None. MEASUREMENTS: Preoperative, intraoperative and postoperative medical, surgical and anaesthetic variables. MAIN RESULTS: A total of 111 patients (10.1%) acquired a nosocomial infection in the postoperative period. Pneumonia was the most frequent (4.2%) nosocomial infection. Three independent risk factors for the development of a nosocomial infection were identified: cardiopulmonary bypass time, kidney failure and emergency surgery. The stay in the ICU was significantly higher in patients who developed a nosocomial infection (16.6 ±â€¯38.8 vs. 4.4 ±â€¯17.8, P < 0.001). The mortality rate of patients who acquired a nosocomial infection was significantly greater (18%) than that of patients who did not acquire a nosocomial infection (5%) (P < 0.001). The 90-day survival was greater in the group of patients without nosocomial infection (log rank 27.55, P < 0.001). The dynamic modelling of 90-day mortality revealed that in the first week, cardiopulmonary bypass time (HR = 1.00, 95% CI 1.00-1.02, P < 0.001) and emergency surgery (HR = 0.12, 95% CI 0.04-0.37, P < 0.001) were the most important risk factors for mortality, while after the first week, nosocomial infection (HR = 6.23, 95% CI 2.49-15.63, P < 0.001) was the main risk factor, followed by cardiopulmonary bypass time (HR = 1.01, 95% CI 1.00-1.01, P = 0.001) and EuroSCORE (HR = 1.03, 95% CI 1.00-1.06, P = 0.008). CONCLUSIONS: Nosocomial infections after cardiac surgery constitute the main independent risk factor for mortality after the first week of surgery. These data suggest that its prevention following cardiac surgery must be prioritised to improve patient outcomes.

The Overlooked Immune State in Candidemia: A Risk Factor for Mortality.

Lymphopenia has been related to increased mortality in septic patients. Nonetheless, the impact of lymphocyte count on candidemia mortality and prognosis has not been addressed. We conducted a retrospective study, including all admitted patients with candidemia from 2007 to 2016. We examined lymphocyte counts during the first 5 days following the diagnosis of candidemia. Multivariable logistic regression analysis was performed to determine the relationship between lymphocyte count and mortality. Classification and Regression Tree analysis was used to identify the best cut-off of lymphocyte count for mortality associated with candidemia. From 296 cases of candidemia, 115 died, (39.8% 30-day mortality). Low lymphocyte count was related to mortality and poor outcome (p < 0.001). Lymphocyte counts <0.703 × 109 cells/L at diagnosis (area under the curve (AUC)-ROC, 0.783 ± 0.042; 95% confidence interval (CI), 0.700-0.867, p < 0.001), and lymphocyte count <1.272 × 109 cells/L five days later (AUC-ROC, 0.791 ± 0.038; 95%CI, 0.716-0.866, p < 0.001) increased the odds of mortality five-fold (odds ratio (OR), 5.01; 95%CI, 2.39-10.93) at time of diagnosis, and three-fold (OR, 3.27; 95%CI, 1.24-8.62) by day 5, respectively. Low lymphocyte count is an independent predictor of mortality in patients with candidemia and might serve as a biomarker for predicting candidemia-associated mortality and poor outcome.