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Background: SeptiCyte RAPID is a molecular test for distinguishing sepsis from non-infectious systemic inflammation. The objective of this study was the clinical validation of SeptiCyte RAPID, based on testing retrospective (banked) and prospectively collected patient samples. Methods: The cartridge-based SeptiCyte RAPID assay accepts a PAXgene blood RNA sample and provides sample-to-answer processing in about 1 hour. The test output (SeptiScore, range 0-15) falls into four interpretation bands, with higher scores indicating higher probabilities of sepsis. Retrospective (banked) and prospective samples from adult patients in ICU either having systemic inflammatory response syndrome (SIRS), or suspected of sepsis under either the Sepsis-2 or Sepsis-3 definition were tested, and results were compared to a gold standard of clinical evaluation by a blinded, three-physician external panel. A multivariable analysis was performed, in which SeptiScore was combined with other clinical variables. Results: With adjudication under the Sepsis-2 definition, SeptiCyte RAPID performance for the complete cohort (356 retrospective + 63 prospective patients) had Area Under the ROC Curve (AUC) ranging from 0.82-0.85, negative predictive value 0.91 (sensitivity 0.94) for SeptiScores between 0.1 and 5.0 (Band 1, lowest risk of sepsis), and positive predictive value 0.81 (specificity 0.90) for SeptiScores between 7.4 and 15 (Band 4, highest risk of sepsis). Performance estimates for the prospective cohort ranged from AUC 0.86-0.95. For physician-adjudicated sepsis cases that were blood culture (+) or blood, urine culture (+)(+), 43/48 (90%) of SeptiCyte scores fell in bands 3 or 4. In multivariable analysis with up to 14 additional clinical variables, SeptiScore was the most important variable for sepsis diagnosis. Comparable results were obtained when the data were reanalyzed under the Sepsis-3 definition. Conclusions: This study validates SeptiCyte RAPID for differentiating patients with sepsis vs. SIRS, on the first day of ICU admission. Trial Registration:NCT01905033(MARS),NCT02127502(VENUS),NCT05469048(NEPTUNE, retrospectively registered) at clinicaltrials.gov. Keywords: sepsis, diagnosis, host response, SIRS, sepsis scoring systems

A molecular test to distinguish between sepsis and systemic inflammation of noninfectious etiology could potentially have clinical utility.This study evaluated the diagnostic performance of a molecular host response assay (SeptiCyte LAB) designed to distinguish between sepsis and noninfectious systemic inflammation in critically ill adults.The study employed a prospective, observational, noninterventional design and recruited a heterogeneous cohort of adult critical care patients from seven sites in the United States (n = 249). An additional group of 198 patients, recruited in the large MARS (Molecular Diagnosis and Risk Stratification of Sepsis) consortium trial in the Netherlands ( www.clinicaltrials.gov identifier NCT01905033), was also tested and analyzed, making a grand total of 447 patients in our study. The performance of SeptiCyte LAB was compared with retrospective physician diagnosis by a panel of three experts.In receiver operating characteristic curve analysis, SeptiCyte LAB had an estimated area under the curve of 0.82-0.89 for discriminating sepsis from noninfectious systemic inflammation. The relative likelihood of sepsis versus noninfectious systemic inflammation was found to increase with increasing test score (range, 0-10). In a forward logistic regression analysis, the diagnostic performance of the assay was improved only marginally when used in combination with other clinical and laboratory variables, including procalcitonin. The performance of the assay was not significantly affected by demographic variables, including age, sex, or race/ethnicity.SeptiCyte LAB appears to be a promising diagnostic tool to complement physician assessment of infection likelihood in critically ill adult patients with systemic inflammation. Clinical trial registered with www.clinicaltrials.gov (NCT01905033 and NCT02127502).

A sensitive system has been presented for the isolation of erythrocyte membrane and the separation of its solubilized components by acrylamide gel electrophoresis. Comparisons were made between the membrane from both normal patients and patients with hereditary spherocytosis. While variation in a specific band on electrophoresis could be correlated with the disease state, no such variation existed among the normal membrane samples. The possible reasons for these observations are discussed.

The objectives of this research were to separate and partially characterize the components of rat liver cell plasma membranes. The plasma membranes of liver cells obtained from normal Wistar male rats were isolated using density gradients. The purified membrane was then solubilized in phenol-urea-acetic acid and gel electrophoresis was performed on the solubilized membrane components. Samples of the eluate collected following preparative gel electrophoresis were phosphorus positive-ninhydrin positive; phosphorus negative-ninhydrin positive; phosphorus po6itive-ninhydrin negative; and phosphorus negative-ninhydrin negative. The amino acid analyses showed that the proteins of the separated components were different and that no one component contained more than 6% of the total membrane protein. Liver cell plasma membranes contain components that differ from those of red blood cell plasma membranes. These components can be further divided into subgroups of proteins, i.e., phospholipoproteins and prot...

We studied the value of transcutaneous carbon dioxide (PtcCO2) monitoring during neonatal transport. Thirty-two neonates with respiratory distress were alternately enrolled in an experimental group (results of PtcO2 and PtcCO2 available for clinical management) and a control group (results of only PtcO2 available). Although differences were not significant, infants in the experimental group had more changes in the intermittent mandatory ventilation (IMV) settings during transport, and more such infants arrived at the receiving hospital with acceptable pH and PCO2 values. On arrival at the receiving hospital, two patients in the control group had acidosis and hypercarbia and were placed on IMV immediately on arrival. No such patients were encountered in the experimental group. For patients needing IMV during transport, the percentage of study time spent with PtcCO2 measurements in the normal range (35 to 45 torr) was greater for the experimental group (p less than .02). Continuous PtcCO2 monitoring during transport offers the opportunity to further decrease the risks of transporting a critically ill neonate.

Sequential bleeding times were performed on 25 preterm infants receiving intravenous indomethacin for closure of the patent ductus arteriosus. Prolongation of bleeding time was observed after the initial dose of indomethacin, with an increase from a pretreatment mean of 3.6 minutes to 8.7 minutes. The bleeding time was not further prolonged at the end of the three-dose course of indomethacin, but was still elevated 48 hours after the completion of therapy. Clinical bleeding developed in six of the patients, but was generally limited to occult hematuria. Serial echoencephalography during indomethacin therapy showed progression from mild periventricular-intraventricular hemorrhage to moderate or severe grades in five of 21 infants at risk for this complication. However, no clear temporal relationship between indomethacin administration and intraventricular hemorrhage extension was observed, and no difference in the degree of bleeding time prolongation was noted between infants with and without hemorrhage extension. Other factors, including surfactant deficiency, amount of volume expansion used, and lowest Po 2 in the first day of life, did distinguish those with hemorrhage extension. The results suggest that indomethacin-induced platelet dysfunction is not associated with major hemorrhagic complications in the majority of preterm infants with patent ductus arteriosus.

Combined high-frequency oscillatory ventilation (HFOV) and intermittent mandatory ventilation (IMV) was used in 12 neonates with inadequate gas exchange with conventional IMV. Diagnoses included diaphragmatic hernia with hypoplastic lungs, pneumonia, persistent fetal circulation, and severe respiratory distress syndrome. In most patients there was severe air leak. Within 10 hours of beginning HFOV-IMV the mean arterial PCO2 fell from 60 +/- 5 (means +/- SEM) to 38 +/- 2 mm Hg (P less than 0.01) and the mean IMV rate was reduced from 96 +/- 8 to 17 +/- 4 breaths per minute (P less than 0.001). The mean arterial-alveolar oxygen tension ratio rose from 0.05 +/- 0.01 to 0.09 +/- 0.01 (P less than 0.005). Mean airway pressure in the trachea was reduced from 16 +/- 2 to 10 +/- 3 cm H2O (P less than 0.05). Four patients died, three of whom had diaphragmatic hernias with hypoplastic lungs. Five of the eight survivors had mild bronchopulmonary dysplasia requiring supplemental oxygen. These studies demonstrate that in some neonates with respiratory failure who fail to respond to conventional IMV, combined HFOV-IMV can be successful.

Previous reports of hypocalcemia and hyperphosphatemia following use of phosphate enemas have either been in patients with renal disease or followed prolonged abuse of these products. The two patients described here had marked elevation of serum phosphate and concomitant lowering of serum calcium secondary to absorption of phosphate from a single administered enema. Associated moderate dehydration resulted in poor renal excretion of the absorbed phosphate and prolongation of hypocalcemia. Hydration was effective in permitting clearance of phosphate and restoration of normocalcemia.

TIMING & INCIDENCE OF INTRAVENTRICULAR-SUBEPENDYMAL HEMORRHAGES (IVH/SEH) IN INBORN PRETERM INFANTS