Thursday, December 9, 2010

Use of Procalcitonin in Newborn to determine length of antibiotic therapy

BMC Pediatrics 2010

Martin Stocker , Wim JJ Hop and Annemarie MC van Rossum

BMC Pediatrics 2010, 10:89

Published:8 December 2010

Abstract (provisional)


Early diagnosis and treatment of the newborn infant with suspected sepsis are essential to prevent severe and life threatening complications. Diagnosis of neonatal sepsis is difficult because of the variable and nonspecific clinical presentation. Therefore, many newborns with nonspecific symptoms are started on antibiotic treatment before the presence of sepsis has been proven. With our recently published single-centre intervention study we were able to show that Procalcitonin determinations allowed to shorten the duration of antibiotic therapy in newborns with suspected early-onset sepsis.


The study is designed as randomized controlled international multicenter intervention trial on the efficacy and safety of Procalcitonin guided treatment. Term and near-term infants (gestational age greater than or equal to 34 0/7 weeks) with suspected sepsis in the first 3 days of life requiring empiric antibiotic therapy will be included. The duration of antibiotic therapy in the standard group is based on the attending physician's assessment of the likelihood of infection (infection unlikely, possible, probable or proven). In the Procalcitonin group, if infection is considered to be unlikely or possible, antibiotic therapy is discontinued when two consecutive Procalcitonin values are within the normal range. Co-primary outcome measures are the duration of antibiotic therapy (superiority aspect of the trial) and the proportion of infants with a recurrence of infection requiring additional courses of antibiotic therapy and/or death in the first month of life (safety of study intervention, non-inferiority aspect of the trial). The number of infants to be included equals 800 per arm. With these numbers the power of the study to demonstrate superiority for duration of antibiotic therapy as well as non-inferiority regarding safety, i.e. excluding a disadvantage difference larger than 2% for the experimental arm, will both be greater than 80%.


Benefit of the study is a possible limitation of unnecessary use of antibiotics. The results of our first study suggest that there is a low risk on discontinuing antibiotic treatment too early, resulting in the development of a neonatal infection with its morbidity and mortality. Trial registration: This trial is registered in the U.S. National Institutes of Health's register, located at (NCT00854932).

From Introduction:

Another biomarker that has been discovered more recently, PCT, is proven to be a good marker of severe, invasive bacterial infections in children. All studies on severe, invasive bacterial infections in children report higher sensitivities and specificities of PCT than for CRP [12-16]. PCT is a 116–aminoacid peptide and one of the precursors of calcitonin. The physiological function of calcitonin remains unknown. No disorders attributable to either an excess or a deficiency of calcitonin have been identified. Most microbial infections induce a ubiquitous increase in CALC1 gene expression and a subsequent release of calcitonin precursors from all tissues and cell types throughout the body [17]. In bacterial infections, PCT increases from concentrations in the picogram range (below the detection level of current PCT assays) to plasma concentrations ranging from 1 to 1000 ng/ml. This increase often correlates with the severity of the disease and with mortality [18-21]. Increases in PCT occur more rapidly than increases in CRP. PCT can be detected in the plasma 2 hours after the injection of endotoxins. Within 6–8 hours, PCT concentrations rise and a plateau is reached after approximately 12 hours [22]. CRP can be detected in the plasma after 12 h and reaches a plateau after 20–72 hours. PCT and CRP decrease to their normal values after 2–3 days and 3–7 days, respectively [23-25].

The use of PCT as a marker of neonatal bacterial infection is complicated by several factors. First, infants with respiratory distress syndrome, hemodynamic failure, perinatal asphyxia, intracranial hemorrhage, pneumothorax, or after resuscitation have raised serum PCT concentrations that do not differ from those of septic neonates up to 48 h after onset of clinical signs of distress or infection [26-28]. Second, a physiological increase of PCT has been reported up to 48 h post partum [29]. Third, prepartum and intrapartum administration of antibiotics may affect PCT concentrations in the umbilical cord [30], and postnatal administration of antibiotics will decrease PCT concentrations more rapidly than CRP concentrations [31,32]. When these pitfalls are taken into account, PCT performs better than CRP in diagnosing neonatal bacterial infection.

Chiesa et al developed a nomogram for PCT [33] and Assumma and colleagues performed a longitudinal study on PCT values in healthy neonates [34]. In his findings Chiesa was able to report two major differences in between healthy and septic neonates which formed the basis of his nomogram. Firstly, the level of elevation in PCT was much higher in septic neonates versus healthy newborns and secondly, the absence of a decrease of PCT values after the initial cytokine release post-partum is indicative of a bacterial infection. With all PCT values being increased during the first two days of life, a reference range covering this time period with intervals of several hours is a tool to identify septic neonates. The adult reference ranges apply from three days after birth. Using PCT in this manner has been proven extensively to be a very reliable marker for the diagnosis of neonatal sepsis [35-39].

In recent years a novel indication for the use of PCT has been discovered, related to its described high negative value. It has been reported in many interventional trials [40-44] that a low PCT indicates the absence of a need for antimicrobial therapy. In several countries the recent adult intensive care guidelines have been altered to the extent that PCT has displaced CRP in the recommendations [45,46]. Applying this principle to neonatology, we performed a single-centre intervention trial in Lucerne, Switzerland that showed that serial PCT determinations allowed to shorten the duration of antibiotic therapy in term and near-term infants with suspected early-onset sepsis [47]. This study is designed to test the reliability of a PCT-based strategy in a larger cohort of neonates.

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Tuesday, December 7, 2010

22q11 microdeletion

requency of 22q11.2 microdeletion in children with congenital heart defects in Western Poland

Anna Wozniak email, Danuta Wolnik-Brzozowska email, Marzena Wisniewska email, Renata Glazar email, Anna Materna-Kiryluk email, Tomasz Moszura email, Magdalena Badura-Stronka email, Joanna Skolozdrzy email, Maciej Krawczynski email, Joanna Zeyland email, Waldemar Bobkowski email, Ryszard Slomski email, Anna Latos-Bielenska email and Aldona Siwinska email

BMC Pediatrics 2010, 10:88doi:10.1186/1471-2431-10-88

Published:6 December 2010

Abstract (provisional)


The 22q11.2 microdeletion syndrome (22q11.2 deletion syndrome -22q11.2DS) refers to congenital abnormalities, including primarily heart defects and facial dysmorphy, thymic hypoplasia, cleft palate and hypocalcaemia. Microdeletion within chromosomal region 22q11.2 constitutes the molecular basis of this syndrome. The 22q11.2 microdeletion syndrome occurs in 1/4000 births. The aim of this study was to determine the frequency of 22q11.2 microdeletion in 87 children suffering from a congenital heart defect (conotruncal or non-conotruncal) coexisting with at least one additional 22q11.2DS feature and to carry out 22q11.2 microdeletion testing of the deleted children's parents. We also attempted to identify the most frequent heart defects in both groups and phenotypic traits of patients with microdeletion to determine selection criteria for at risk patients.


The analysis of microdeletions was conducted using fluorescence in situ hybridization (FISH) on metaphase chromosomes and interphase nuclei isolated from venous peripheral blood cultures. A molecular probe (Tuple) specific to the HIRA (TUPLE1, DGCR1) region at 22q11 was used for the hybridisation.


Microdeletions of 22q11.2 region were detected in 13 children with a congenital heart defect (14.94% of the examined group). Microdeletion of 22q11.2 occurred in 20% and 11.54% of the conotruncal and non-conotruncal groups respectively. Tetralogy of Fallot was the most frequent heart defect in the first group of children with 22q11.2 microdeletion, while ventricular septal defect and atrial septal defect/ventricular septal defect were most frequent in the second group. The microdeletion was also detected in one of the parents of the deleted child (6.25%) without congenital heart defect, but with slight dysmorphism. In the remaining children, 22q11.2 microdeletion originated de novo.


Patients with 22q11.2DS exhibit wide spectrum of phenotypic characteristics, ranging from discreet to quite strong. The deletion was inherited by one child. Our study suggests that screening for 22q11.2 microdeletion should be performed in children with conotruncal and non-conotruncal heart defects and with at least one typical feature of 22q11.2DS as well as in the deleted children's parents.

Saturday, December 4, 2010

Rivaroxabon - Oral factor Xa inhibitor

NEJM dt. 12/04/10:
The EINSTEIN Investigators
Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the need for laboratory monitoring.


We conducted an open-label, randomized, event-driven, noninferiority study that compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months in patients with acute, symptomatic DVT. In parallel, we carried out a double-blind, randomized, event-driven superiority study that compared rivaroxaban alone (20 mg once daily) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism. The primary efficacy outcome for both studies was recurrent venous thromboembolism. The principal safety outcome was major bleeding or clinically relevant nonmajor bleeding in the initial-treatment study and major bleeding in the continued-treatment study.


The study of rivaroxaban for acute DVT included 3449 patients: 1731 given rivaroxaban and 1718 given enoxaparin plus a vitamin K antagonist. Rivaroxaban had noninferior efficacy with respect to the primary outcome (36 events [2.1%], vs. 51 events with enoxaparin–vitamin K antagonist [3.0%]; hazard ratio, 0.68; 95% confidence interval [CI], 0.44 to 1.04; P<0.001). p="0.11).


Rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation. (Funded by Bayer Schering Pharma and Ortho-McNeil; numbers, NCT00440193and NCT00439725.)