Indirectly determined hematology reference intervals for pediatric patients in Berlin and Brandenburg

Objectives Establishing direct reference intervals (RIs) for pediatric patients is a very challenging endeavor. Indirectly determined RIs can address this problem by utilization of existing clinical laboratory databases. In order to provide better laboratory services to the local pediatric population, we established population-specific hematology RIs via data mining. Methods Our laboratory information system (LIS) was searched for pediatric blood counts of patients aged from 0 days to 18 years, performed from 1st of January 2018 until 31st of March 2021. In total, 27,554 blood counts on our SYSMEX XN-9000 were initially identified. After application of pre-defined exclusion criteria, 18,531 sample sets remained. Age- and sex-specific RIs were established in accordance with International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and Clinical & Laboratory Standards Institute (CLSI) recommendations. Results When compared to pediatric RIs supplied by other authors, the RIs determined specifically for pediatric patients from Berlin and Brandenburg showed several relevant differences, especially with regard to white blood cell counts (WBCs), red blood cell counts (RBCs), red cell distribution widths (RDW) and platelet counts (PLTs) within the distinct age groups. Additionally, alterations to several published age-specific partitions had to be made, while new sex-specific partitions were introduced for WBCs and PLTs. Conclusions Generic RIs from textbooks, manufacturer information and medical publications – even from nationwide or multicenter studies – commonly used in many laboratories might not reflect the specifics of local patient populations properly. RIs should be tailored to the serviced patient population whenever possible. Careful data mining appears to be suitable for this task.

Prospective urinary albumin/creatinine ratio for diagnosis, staging, and organ response assessment in renal AL amyloidosis: results from a large cohort of patients

Objectives Quantification of 24 h-proteinuria is the gold standard for diagnosing, staging, and monitoring of patients with renal AL amyloidosis. However, 24 h-urine collection is cumbersome and may result in preanalytical error. In this prospective study, we investigated the role of urinary albumin/creatinine ratio (UACR) (cut-off: 300 mg/g) identifying renal involvement, evaluated a UACR-based staging system (UACR cut-off: 3,600 mg/g) and assessed whether UACR response (UACR decrease >30% without worsening in eGFR >25%) predicts renal outcome in 531 patients with newly-diagnosed AL amyloidosis. Methods From October 2013 paired 24 h-proteinuria and UACR (on first morning void) were measured in all newly-diagnosed patients with AL amyloidosis. Correlation between 24 h-proteinuria and UACR at baseline was assessed by Pearson’s r test. Impact of UACR response on renal outcome was assessed in randomly created testing (n=354) and validation (n=177) cohorts. Results A strong linear correlation was found between 24 h-proteinuria and UACR at baseline (r=0.90; p<0.001). After a median follow-up of 31 months, 57 (11%) patients required dialysis. A UACR-based renal staging system identified three stages with significantly higher dialysis rate at 36 months comparing stage I with stage II and stage II with stage III. Achieving a renal response, according to a UACR-based criterion, resulted in lower dialysis rate in both testing and validation cohorts. Conclusions UACR is a reliable marker for diagnosis, prognosis, and organ response assessment in renal AL amyloidosis and can reliably replace 24 h-proteinuria in clinical trials and individual patients’ management.

Monocyte distribution width (MDW): a useful biomarker to improve sepsis management in Emergency Department

Objectives Sepsis is a time-dependent and life-threating condition. Despite several biomarkers are available, none of them is completely reliable for the diagnosis. This study aimed to evaluate the diagnostic utility of monocyte distribution width (MDW) to early detect sepsis in adult patients admitted in the Emergency Department (ED) with a five part differential analysis as part of the standard clinical practice. Methods A prospective cohort study was conducted on 985 patients aged from 18 to 96 and included in the study between November 2019 and December 2019. Enrolled subjects were classified into four groups based on sepsis-2 diagnostic criteria: control, Systemic Inflammatory Response Syndrome (SIRS), infection and sepsis. The hematology analyzer DxH 900 (Beckman Coulter Inc.) provides the new reportable parameter MDW, included in the leukocyte 5 part differential analysis, cleared by Food and Drug administration (FDA) and European Community In-Vitro-Diagnostic Medical Device (CE IVD) marked as early sepsis indicator (ESId). Results MDW was able to differentiate the sepsis group from all other groups with Area Under the Curve (AUC) of 0.849, sensitivity of 87.3% and specificity of 71.7% at cut-off of 20.1. MDW in combination with white blood cell (WBC) improves the performance for sepsis detection with a sensitivity increased up to 96.8% when at least one of the two biomarkers are abnormal, and a specificity increased up to 94.6% when both biomarkers are abnormal. Conclusions MDW can predict sepsis increasing the clinical value of Leukocyte 5 Part Differential analysis and supporting the clinical decision making in sepsis management at the admission to the ED.

S100B in cardiac surgery brain monitoring: friend or foe?

Recent advances in perioperative management of adult and pediatric patients requiring open heart surgery (OHS) and cardiopulmonary bypass (CPB) for cardiac and/or congenital heart diseases repair allowed a significant reduction in the mortality rate. Conversely morbidity rate pattern has a flat trend. Perioperative period is crucial since OHS and CPB are widely accepted as a deliberate hypoxic-ischemic reperfusion damage representing the cost to pay at a time when standard of care monitoring procedures can be silent or unavailable. In this respect, the measurement of neuro-biomarkers (NB), able to detect at early stage perioperative brain damage could be especially useful. In the last decade, among a series of NB, S100B protein has been investigated. After the first promising results, supporting the usefulness of the protein as predictor of short/long term adverse neurological outcome, the protein has been progressively abandoned due to a series of limitations. In the present review we offer an up-dated overview of the main S100B pros and cons in the peri-operative monitoring of adult and pediatric patients.