BACKGROUND: In cystic fibrosis newborn screening (CFNBS), immunoreactive trypsinogen (IRT) and pancreatitis-associated protein (PAP) can be used as screening parameters. We evaluated the IRT×PAP product as second-tier parameter in CFNBS in newborns with elevated IRT. METHODS: Data on 410,111 screened newborns including 78 patients with classical cystic fibrosis (CF) from two European centers were retrospectively analyzed by discrimination analysis to identify a screening protocol with optimal cutoffs. We also studied differences in PAP measurement methods and the association of IRT and PAP with age. RESULTS: PAP values differed systematically between fluorometric and photometric assays. The IRT×PAP product showed better discrimination for classical CF than PAP only as second-tier screening parameter (p<0.001). In CF patients, IRT decreased while PAP values remained high over years. In newborns without CF, IRT decreased after birth over weeks while PAP increased within days. CONCLUSIONS: The IRT×PAP product performs well as second-tier cutoff parameter for CFNBS. Screening quality parameters depend on the analytic method and on age at blood collection.
- MeSH
- Chemistry Techniques, Analytical MeSH
- Cystic Fibrosis * blood diagnosis MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Neonatal Screening methods MeSH
- Pancreatitis-Associated Proteins analysis MeSH
- Retrospective Studies MeSH
- Sensitivity and Specificity MeSH
- Trypsinogen * analysis immunology MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: In recent years different IRT/PAP protocols have been evaluated, but the individual performance remains unclear. To optimize the IRT/PAP strategy we compared protocols from three regional CF newborn screening centers (Heidelberg, Dresden, and Prague). METHODS: We evaluated the effect of elevating the IRT-cut-off from 50 to 65 μg/l (~97.5th to ~99.0th percentile), the need of a failsafe protocol (FS, IRT ≥ 99.9th percentile) and the relative performance using either two IRT-dependent PAP-cut-offs or one PAP-cut-off. FINDINGS: Elevation of the IRT cut-off to 65 μg/l (~99.0th percentile) increased the PPV significantly (Dresden: 0.065 vs. 0.080, p < 0.0001, Prague: 0.052 vs. 0.074, p < 0.0001) without reducing sensitivity. All three IRT/PAP protocols showed a trend towards a higher sensitivity with FS than without and when using one PAP-cut-off instead of two IRT-dependent PAP-cut-offs. CONCLUSIONS: For best performance we suggest an IRT/PAP protocol with an IRT-cut-off close to the 99.0th percentile, FS, and a single PAP-cut-off.
- MeSH
- Antigens, Neoplasm analysis blood genetics MeSH
- Cystic Fibrosis blood diagnosis genetics MeSH
- Genetic Testing methods standards MeSH
- Chemistry, Clinical methods standards MeSH
- Lectins, C-Type analysis blood genetics MeSH
- Humans MeSH
- Biomarkers, Tumor analysis blood genetics MeSH
- Infant, Newborn MeSH
- Neonatal Screening methods standards MeSH
- Prospective Studies MeSH
- Cystic Fibrosis Transmembrane Conductance Regulator genetics MeSH
- Retrospective Studies MeSH
- Sensitivity and Specificity MeSH
- Dried Blood Spot Testing methods standards MeSH
- Trypsinogen analysis blood genetics MeSH
- Check Tag
- Humans MeSH
- Infant, Newborn MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Geographicals
- Europe MeSH
Cíl studie:Výskyt pooperační hyperamylazémie po kardiochirurgických výkonech je v literatuře udáván ve 30–70%případů. Příčiny zvýšené hladiny amylázy v séru nejsou dosud zcela objasněny. Na souboru 110 pacientů jsme se pokusili zjistit možnou příčinu a důsledky zvýšené pooperační aktivity amyláz v séru. Typ studie: Prospektivní studie. Název a sídlo pracoviště: Klinika kardiovaskulární chirurgie UK, 1. LF a VFN, Praha. Soubor a metodika: Do studie bylo náhodným výběrem zařazeno 110 pacientů, u kterých byly sledovány peroperační rizikové faktory iritace pankreatu, pooperační hladiny pankreatického izoenzymu amylázy a kreatininu v séru a v moči 1. a 2. pooperační den. K vyloučení významného pankreatického poškození byl použit semikvantitativní test stanovení hladiny trypsinogenu 2 v moči. U pooperačního průběhu byl sledován klinický stav, čas zahájení výživy perorální cestou a doba pobytu na oddělení intenzivní pooperační péče. Výsledky: Zvýšená hladina pankreatického izoenzymu amylázy v séru byla zjištěna u 22 pacientů (20 %). Akutní pankreatitida jako pooperační komplikace se nevyskytla u žádného pacienta. Jako nezávislé prediktory pooperační hyperamylazémie byly identifikovány předoperační zvýšení amylázy a peroperační hemodynamický inzult, vedoucí zřejmě k hypoperfuzi splanchniku. Závěr: Zvýšená hodnota pankreatického izoenzymu v séru časně po kardiochirurgickém výkonu zřejmě neznamená významné postižení buněk pankreatu a podle našich výsledků nemá vliv na mortalitu a morbiditu pacientů.
Objective: Hyperamylasemia is reported in 30–70% of cardiac surgery patients. The exact cause of elevated serum levels of amylase remains unclear. The goal of our study was to find out the possible cause of amylase elevation and evaluate the influence of increased levels of serum amylase on the postoperative course and clinical outcome of 110 cardiac surgical patients. Design: Prospective study. Setting: Cardiac Surgery Department, Prague General Hospital, 1st Medical Faculty of Charles University, Prague, the Czech Republic. Material and methods: The cohort of 110 randomly selected patients who underwent cardiac surgery at our institution was studied prospectively. Serial blood and urine samples were obtained on the 1st and 2nd morning after the operation. Pancreatic isoamylase, creatinine, the fractional clearence of pancreatic isoamylase (in relation to creatinine clearence) were measured. To preclude an important pancreatic cellular injury we used the semiquantitative urinary trypsinogen-2 dipstick test. Postoperatively we studied a clinical course of illness, start of feeding by oral route and time to discharge from postoperative ICU. Results: 22 out of 110 patients (20%) had at least one serum sample with elevated pancreatic isoamylase concentration.We observed no acute pancreatitis in our patients. Preoperative hyperamylasemia and perioperative hemodynamic insult were identified as independent predictors of postoperative hyperamylasemia leading probably to splanchnic hypoperfusion. Conclusion: Early elevation of pancreatic isoamylase after cardiac surgery procedure probably could not be interpreted as a sign of pancreatic cells injury and does not affect mortality or morbidity.
