ABSTRACT
Objective:To establish the cut-off value of tetradecenoyl carnitine (C14∶1)/dodecenoyl carnitine(C12∶1) based on non-derivatized tandem mass spectrometry (MS/MS), and to explore the application value of C14∶1/C12∶1 to screen newborns for very long chain acyl-CoA dehydrogenase deficiency (VLCADD), determining the best combination of indicators for screening VLCADD.Methods:This retrospective study included data from 17 newborns with VLCADD detected by MS/MS and confirmed by acyl-CoA dehydrogenase very long chain ( ACADVL) gene detection, and 423 507 newborns with normal MS/MS results. The data from these newborns were collected from January 2014 to December 2021 as the newborns received neonatal screening in Nanjing Neonatal Disease Screening Center and Suzhou Neonatal Disease Screening Center. All newborns were divided into 3 groups: all newborns group, full-term newborns group and normal-birth-weight newborns group, and the cut-off values of C14∶1/C12∶1 for VLCADD in these 3 groups were determined by their receiver operating characteristic (ROC) curves individually. With these results, a total of 5 interpretation schemes were composed using different indicators alone or jointly: scheme 1 being C14∶1/C12∶1, scheme 2 being C14∶1, scheme 3 being C14∶1+C14∶1/C2+C14∶1/C16, scheme 4 being C14∶1/C12∶1+C14∶1, and scheme 5 being C14∶1/C12∶1+C14∶1+C14∶1/C2+C14∶1/C16. The detection rate, false-positive rate and positive predictive value of each scheme were calculated, and their screening efficiencies were statistically compared by Chi-square tests. Results:The cut-off values of C14∶1/C12∶1 for VLCADD in the 3 newborn groups were all 2.80. The detection rates of VLCADD with all 5 interpretation schemes were 17/17. Scheme 1 had the highest false positive rate [26.15‰ (11 075/423 524)] and the lowest positive predictive value [0.15% (17/11 092)]. Scheme 4 (Scheme 5) had the lowest false positive rate [0.02‰ (10/423 524)] and the highest positive predictive value [62.96% (17/27)]. Comparing scheme 4 (Scheme 5) with scheme 1, scheme 2 and scheme 3, the differences of false positive rate (χ2=302.30,11 191.50,32.06) and positive predictive value (χ2=102.51,3 485.61,13.83) were statistically significant (all P<0.001). Conclusion:C14∶1/C12∶1 was an effective auxiliary interpretive indicator for VLCADD in newborn screening, and the combination of C14∶1/C12∶1+C14∶1 was tested to be the best indicator for VLCADD screening based on non-derivatized tandem mass spectrometry.
ABSTRACT
Objective To establish a discriminant method based on clinical and laboratory data and common examinations for early predicting the severity of pediatric infection. Methods Consecutive hospitalized patients diag-nosed as septic shock were included who were admitted between June 2014 and May 2015 retrospectively. Gender (male - female ratio:1. 25∶ 1. 00)and age(1 month to 6 years old)were matched in all of 18 patients with septic shock,and 27 patients diagnosed as systemic inflammatory response syndrome(SIRS),sepsis and severe sepsis on ad-mission were included respectively in order of sequential admission number during the same period. Additional 36 gen-der - and age - matched children with common infection(non - SIRS)were enrolled as controls. The clinical and labo-ratory examination data of all the included patients were collected and then the pediatric critical illness scores(PCIS) were made according to the worst condition within 24 hours of hospitalization. The parameters correlated with the severi-ty of infection were evaluated by rank correlation and Logistic regression analysis. The discriminant models were estab-lished based on κth - nearest - neighbor analysis and evaluated with clinical diagnosis by interrater agreement test. Results Except for platelet count,the other indexes including PCIS,neutrophil count,C - reactive protein,procalcito-nin(PCT),international normalized ratio of prothrombin time,activated partial thromboplastin time,thrombin time,fi-brinogen,fibrin/ fibrinogen degradation product(FDP)and D - dimer(D - D)all had differences among groups with varying infection severity(all P ﹤ 0. 001). The Spearman's coefficient ρ of PCIS,PCT,D - D and FDP correlated to in-fection severity were - 0. 837,0. 680,0. 679 and 0. 648,respectively(all P ﹤ 0. 001). Multivariate cumulative odds Lo-gistic regression analysis showed PCIS,D - D and PCT were related to infection severity(all P ﹤ 0. 05). The total error rate of discriminant models based on 3 - index combination(Mahalanobis transformation,k = 2)was 0. 091 that was lower than any models based on 2 - index combination or single - index. Using the discriminant model based on three -index combination,the infection severity of 26 patients admitted during June 2015 were predicted with a high interrater a-greement(weighted Kappa coefficient:0. 670,P ﹤ 0. 001)compared to clinical diagnosis. Conclusion The discriminant model based on combination of PCIS,D - D and PCT could assist predicting the severity of pediatric infection earlier.