Monocyte distribution width (MDW) parameter as a sepsis indicator in intensive care units.

Abstract Objectives Patients in Intensive Care Units (ICU) are a high-risk population for sepsis, recognized as a major cause of admission and death. The aim of the current study was to evaluate the diagnostic accuracy and prognostication of monocyte distribution width (MDW) in sepsis for patients admitted to ICU. Methods Between January and June 2020, we conducted a prospective observational study during the hospitalization of 506 adult patients admitted to the ICU. MDW was evaluated in 2,367 consecutive samples received for routine complete blood counts (CBC) performed once a day and every day during the study. Sepsis was diagnosed according to Sepsis-3 criteria and patients enrolled were classified in the following groups: no sepsis, sepsis and septic shock. Results MDW values were significantly higher in patients with sepsis or septic shock in comparison to those within the no sepsis group [median 26.23 (IQR: 23.48–29.83); 28.97 (IQR: 21.27–37.21); 21.99 (IQR: 19.86–24.36) respectively]. ROC analysis demonstrated that AUC is 0.785 with a sensitivity of 66.88% and specificity of 77.79% at a cut-off point of 24.63. In patients that developed an ICU-acquired sepsis MDW showed an increase from 21.33 [median (IQR: 19.47–21.72)] to 29.19 [median (IQR: 27.46–31.47)]. MDW increase is not affected by the aetiology of sepsis, even in patients with COVID-19. In sepsis survivors a decrease of MDW values were found from the first time to the end of their stay [median from 29.14 (IQR: 26.22–32.52) to 25.67 (IQR: 22.93–30.28)]. Conclusions In ICU, MDW enhances the sepsis detection and is related to disease severity

Performance criteria and quality indicators for the post-analytical phase

Background: Quality indicators (QIs) used as performance measurements are an effective tool in accurately estimating quality, identifying problems that may need to be addressed, and monitoring the processes over time. In Laboratory Medicine, QIs should cover all steps of the testing process, as error studies have confirmed that most errors occur in the pre- and post-analytical phase of testing. Aim of the present study is to provide preliminary results on QIs and related performance criteria in the post-analytical phase. Methods: This work was conducted according to a previously described study design based on the voluntary -participation of clinical laboratories in the project on QIs of the Working Group "Laboratory Errors and Patient Safety" (WG-LEPS) of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Results: Overall, data collected highlighted an improvement or stability in performances over time for all reported indicators thus demonstrating that the use of QIs is-effective in the quality improvement strategy. Moreover, QIs data are an important source for defining the state-of- the-art concerning the error rate in the total testing process. The definition of performance specifications based on the state-of-the-art, as suggested by consensus documents, is a valuable benchmark point in evaluating the performance of each laboratory. Conclusions: Laboratory tests play a relevant role in the monitoring and evaluation of the efficacy of patient outcome thus assisting clinicians in decision-making. Laboratory performance evaluation is therefore crucial to providing patients with safe, effective and efficient care

Inflammation and pancreatic cancer: molecular and functional interactions between S100A8, S100A9, NT-S100A8 and TGFβ1

BACKGROUND: In order to gain further insight on the crosstalk between pancreatic cancer (PDAC) and stromal cells, we investigated interactions occurring between TGF\u3b21 and the inflammatory proteins S100A8, S100A9 and NT-S100A8, a PDAC-associated S100A8 derived peptide, in cell signaling, intracellular calcium (Cai2+) and epithelial to mesenchymal transition (EMT). NF-\u3baB, Akt and mTOR pathways, Cai2+ and EMT were studied in well (Capan1 and BxPC3) and poorly differentiated (Panc1 and MiaPaCa2) cell lines. RESULTS: NT-S100A8, one of the low molecular weight N-terminal peptides from S100A8 to be released by PDAC-derived proteases, shared many effects on NF-\u3baB, Akt and mTOR signaling with S100A8, but mainly with TGF\u3b21. The chief effects of S100A8, S100A9 and NT-S100A8 were to inhibit NF-\u3baB and stimulate mTOR; the molecules inhibited Akt in Smad4-expressing, while stimulated Akt in Smad4 negative cells. By restoring Smad4 expression in BxPC3 and silencing it in MiaPaCa2, S100A8 and NT-S100A8 were shown to inhibit NF-\u3baB and Akt in the presence of an intact TGF\u3b21 canonical signaling pathway. TGF\u3b21 counteracted S100A8, S100A9 and NT-S100A8 effects in Smad4 expressing, not in Smad4 negative cells, while it synergized with NT-S100A8 in altering Cai2+ and stimulating PDAC cell growth. The effects of TGF\u3b21 on both EMT (increased Twist and decreased N-Cadherin expression) and Cai2+ were antagonized by S100A9, which formed heterodimers with TGF\u3b21 (MALDI-TOF/MS and co-immuno-precipitation). CONCLUSIONS: The effects of S100A8 and S100A9 on PDAC cell signaling appear to be cell-type and context dependent. NT-S100A8 mimics the effects of TGF\u3b21 on cell signaling, and the formation of complexes between TGF\u3b21 with S100A9 appears to be the molecular mechanism underlying the reciprocal antagonism of these molecules on cell signaling, Cai2+ and EMT

A Randomized Trial of Pharmacogenetic Warfarin Dosing in Naive Patients with Non-Valvular Atrial Fibrillation

Genotype-guided warfarin dosing have been proposed to improve patient's management. This study is aimed to determine whether a CYP2C9- VKORC1- CYP4F2-based pharmacogenetic algorithm is superior to a standard, clinically adopted, pharmacodynamic method. Two-hundred naive patients with non-valvular atrial fibrillation were randomized to trial arms and 180 completed the study. No significant differences were found in the number of out-of-range INRs (INR3.0) (p = 0.79) and in the mean percentage of time spent in the therapeutic range (TTR) after 19 days in the pharmacogenetic (51.9%) and in the control arm (53.2%, p = 0.71). The percentage of time spent at INR>4.0 was significantly lower in the pharmacogenetic (0.7%) than in the control arm (1.8%) (p = 0.02). Genotype-guided warfarin dosing is not superior in overall anticoagulation control when compared to accurate clinical standard of care

Laboratory critical values: automated notification supports effective clinical decision making.

Failure to adequately communicate a laboratory critical value (CV) is a potential cause of adverse events. The harmonization of CV reporting is increasingly recognized as a key issue in ensuring patient care and minimizing harm. With ongoing improvements in CV reporting, the patient's outcome should be audited to assess the effectiveness of CV notification. DESIGN AND METHODS: We report the data audited throughout a six month-period during which an analysis was made of CVs, and we describe the approach of clinicians and general practitioners (GPs), and their decision making following CV reporting. RESULTS: CV notification led to a change of treatment in 98.0% of patients admitted to surgical and in 90.6% of those admitted to medical wards. Clinicians made a further evaluation of new complications in patients in 70.0% and 60.4% of cases, in surgical and medical wards respectively. In more than 40.0% of cases, CVs were unexpected findings. In the primary care setting, critical hyperkalemia was managed by GPs in 55% of patients, thus sparing patient's hospitalization. For all outpatients with critical INR (international normalized ratio), the GPs changed or stopped warfarin dosage. Twenty-four percent of patients were checked for an additional INR, whereas a further medical examination by a consultant in the hospital setting was requested for 5% of patients. CONCLUSIONS: The laboratory plays a key role in ensuring patient safety, especially in CV reporting. An evaluation should be made of the patient's outcome and clinical decision making in order to assess the effectiveness of the CV process

AUTOMATED IT-BASED INTERVAL POP-UP (POP-UP) HAS LITTLE IMPACT ON VITAMIN D (VITD) APPROPRIATE MINIMUM RETESTING

Background: Based on the UK National Minimum Retesting Interval Project Recommendations, we verified whether POP-UP allows appropriate VitD retesting (minimum = 90 days). Materials and methods: POP-UP was applied for one year to inpatients. One year VitD free (FREE-YEAR) and one year POP-UP (POPUP-YEAR) VitD requests were collected (LIS), comparing outpatients and inpatients. These were further classified as coming from medical, surgical, or maternal and child area. The number of patients with repeated VitD was identified for each area. Results: VitD was requested once/year in 11.6% and in 13.1% and at least twice in 3.7% and 4.1% inpatients in FREE-YEAR and POPUP-YEAR respectively. Considering both in- and out-patients, VitD assay was offered to 35564 and 38217 patients in FREE-YEAR and POPUP-YEAR, being repeated at least twice in 15% and 13% (X2 = 42, p < 0.0001). This reduction was confirmed among outpatients (from 11.3% to 9.4%), not among inpatients (24% unchanged). The time interval between repeated testing was shorter in POPUP-YEAR (128\ub11 days) than in FREE-YEAR (179\ub12 days, mean\ub1SE) (t = 25.5, p < 0.0001). Time interval between two repeated VitD measures was dependent on POP-UP (p < 0.0001), medical area (p < 0.0001), gender (p = 0.02) and on VitD result (p = 0.0005), not on age (p = 0.308) (multivariate ANOVA). VitD retesting was classified as appropriate ( 90 days). A significant decrease in inappropriate retesting was observed in POPUP-YEAR for inpatients belonging to medical (p < 0.0001) or surgical (p = 0.003) areas, while it increased in the maternal and child area or remained unchanged among outpatients (p = 0.089). For 4 months POP-UP was replaced by an IT-block for inpatients or a clinical comment for outpatients, and this caused a fall in retesting to 2.5%. Conclusion: although POP-UP might determine a slight reduction in inappropriate VitD retesting, this approach does not render appropriateness a routine. Minimal retesting interval rejection rules appear a cheap and sustainable method toward more appropriate retesting