A Dynamic Approach for Early Risk Prediction of Gram-Negative Bloodstream Infection and Systemic Inflammatory Response Syndrome in Febrile Pediatric Hemato-Oncology Patients.

Background: The aim of this study was to evaluate the usefulness of C-Reactive Protein (CRP), Procalcitonin (PCT), and Interleukine 6 (IL6) biomarkers in predicting the existence of high-risk episodes (HRE) during the first 24 h of fever in pediatric cancer patients. HRE were defined as the presence of Gram-negative bloodstream infections or Systemic Inflammatory Response Syndrome. Methods: The study included 103 consecutive fever episodes in 44 hemato-oncological pediatric patients, from whom samples for biomarkers were taken upon initial evaluation (CRP-1, PCT-1 and IL6-1) and then between 12 and 24 h afterward (CRP-2, PCT-2 and IL6-2). Results: An IL6-1 value higher than 164 pg/mL showed an area under the curve (AUC) of 0.890 (0.791−0.989) and OR of 48.68 (7.92−951.42, p < 0.001) to detect HRE in multivariate analysis. A PCT-1 higher than 0.32 ng/mL showed an AUC of 0.805 (0.700−0.910) and OR of 4.55 (0.90−27.84, p = 0.076). A PCT-2 higher than 0.94 ng/mL showed an AUC of 0.836 (0.725−0.947) and OR of 13.01 (1.82−149.13, p = 0.018), and an increase in CRP between the first and second sample (CRP-2vs1) higher than 291% also showed an AUC of 0.785 (0.655−0.915) and OR of 31.09 (4.87−355.33, p = 0.001). Conclusions: IL6-1, PCT-2, and CRP-2vs1 showed a strong and independent correlation with HREs in pediatric cancer patients. CRP variations over the first 24 h provide an improvement in predictive models that are especially useful if IL-6 and PCT are not available.

Biomarkers and Fever in Children with Cancer: Kinetics and Levels According to Final Diagnosis.

We investigated the kinetics of CRP, PCT, IL-6 and MR-proADM in a cohort of consecutive febrile patients with cancer in order to test the hypothesis that higher plasma concentrations and the absence of a rapid decrease in peak values would be associated with disease severity. (1) Method: A prospective descriptive and analytical study of patients with cancer and fever (≤18 years of age) at a University Hospital was carried out between January 2018 and December 2019. Information collected: sex, age, diagnosis, date and symptoms at diagnosis and medical history. The episodes were classified into three groups: bacterial infection, non-bacterial infection and systemic inflammatory response syndrome (SIRS). (2) Results: One hundred and thirty-four episodes were included. Bacterial infection criteria were met in 38 episodes. Biomarkers were measured at four different points: baseline, at 12-24 h, at 25-48 h and at 49-72 h. All the biomarkers evaluated decreased after the peak level was reached. IL-6 and MR-proADM showed a trend towards higher levels in the SIRS group although this rise was statistically significant only for IL-6 (p < 0.005). Bacterial infections more frequently presented values of PCT above the cut-off point (>0.5 ng/mL) at 12-24 h. (3) Conclusion: In our experience, IL-6 kinetics is faster than PCT kinetics and both are faster than CRP in patients with fever and cancer who present a good outcome. Patients with a good evolution show a rapid increase and decrease of PCT and particularly of IL-6 levels.

Performance of plasma free metanephrines in diagnosis of pheochromocytomas and paragangliomas in the population of Asturias. / Rendimiento de las metanefrinas libres plasmáticas en el diagnóstico de los feocromocitomas y paragangliomas en la población asturiana.

INTRODUCTION: Pheochromocytoma and paraganglioma are uncommon tumors whose best known symptoms include high blood pressure, palpitations, headache, and sweating. Clinical identification is not easy, however, and requires biochemical tests that allow for early diagnosis, including measurement of metanephrines levels. The aim of this study was to assess the diagnostic performance of plasma free metanephrines (PMETs) and to verify the transferability of the reference values used. METHODS: PMETs levels were measured by liquid chromatography coupled to tandem mass spectrometry. Other biochemical tests evaluated (plasma catecholamine, urine metanephrine, catecholamine and vanilmandelic acid levels) were performed by liquid chromatography with electrochemical detection. Requests of these tests from 01/09/2015 to 31/10/2017 were reviewed, and both the reference values (document EP28-A3c) and the parameters of biological variation (Fraser method) for PMETs were estimated. RESULTS: The study sample consisted of 1,279 patients (61.3% females) aged 0-90 years, including 19 with pheochromocytoma/paraganglioma. Tests requested included: PMETs (n=662), catecholamines (n=589), metanephrines (n=586), and vanilmandelic acid (n=513) in urine, and plasma catecholamines (n=228). Tests with higher sensitivity were urinary fractionated metanephrines (91.7%) and PMETs (82.4%). When performance was compared in patients with both tests (n=243), they detected the same number of tumors (90.9%), but PMETs showed greater specificity (93.5% vs 88.8%). Plasma normetanephrine levels showed a significant association with age (rho=0.19, P<.0001). CONCLUSION: PMETs and urinary fractionated metanephrines are the biochemical tests with better performance in diagnosis of pheochromocytomas/paragangliomas.

Cell-free DNA as a noninvasive acute rejection marker in renal transplantation.

BACKGROUND: Acute rejection (AR) is a key conditioning factor for long-term graft function and survival in renal transplantation patients. The standard care with creatinine measurements and biopsy upon allograft dysfunction implies that AR is usually detected at advanced stages. Rapid noninvasive biomarkers of rejection are needed to improve the management of these patients. We assessed whether total cell-free DNA (tCF-DNA) and donor-derived cell-free DNA (ddCF-DNA) were useful markers for this purpose, both in plasma and in urine. METHODS: Plasma and urine samples from 100 renal transplant recipients were obtained during the first 3 months after transplantation. tCF-DNA and ddCF-DNA were analyzed by quantitative PCR for the HBB (hemoglobin, beta) and the TSPY1 (testis specific protein, Y-linked 1) genes, respectively. We observed 19 episodes of AR, as well as other complications, such as acute tubular necrosis, nephrotoxicity, and infections. RESULTS: Plasma tCF-DNA concentrations increased markedly during AR episodes, often before clinical diagnosis, and returned to reference values after antirejection treatment. A cutoff plasma tCF-DNA concentration of 12 000 genome equivalents/mL correctly classified AR and non-AR episodes in 86% of posttransplantation complications (diagnostic sensitivity, 89%; specificity, 85%). Although similar increases were observed during severe posttransplantation infections, use of the combination of plasma tCF-DNA and procalcitonin (PCT), a specific marker of sepsis, significantly improved the diagnostic specificity (to 98%; 95% CI, 92%-100%), with 97% of the episodes being correctly classified. Use of transrenal DNA and ddCF-DNA concentrations did not add relevant information. CONCLUSIONS: Given that renal biopsy is the gold standard for detecting AR, analysis of both plasma tCF-DNA and PCT could permit a more selective use of this invasive procedure.