Endotoxin Induced Chorioamnionitis Prevents Intestinal Development during Gestation in Fetal Sheep

Chorioamnionitis is the most significant source of prenatal inflammation and preterm delivery. Prematurity and prenatal inflammation are associated with compromised postnatal developmental outcomes, of the intestinal immune defence, gut barrier function and the vascular system. We developed a sheep model to study how the antenatal development of the gut was affected by gestation and/or by endotoxin induced chorioamnionitis

Developmental changes in mesenteric artery reactivity in embryonic and newly hatched chicks

At birth, the intestine becomes the sole site for nutrient absorption requiring a dramatic increase in blood flow. The vascular changes accompanying this transition have been partly characterized in mammals. We investigated, using wire myography, the developmental changes in chick mesenteric artery (MA) reactivity. Rings of the MA from 15-day (E15) and 19-day (E19) chicken embryos (total incubation 21 days) as well as non-fed 0–3-h-old (NH3h) and first-fed 1-day-old (NH1d) newly hatched chicks contracted in response to KCl, norepinephrine (NE), U46619, and endothelin (ET)-1 and relaxed in response to acetylcholine (ACh), sodium nitroprusside (SNP), and forskolin indicating the presence of electro- and pharmaco-mechanical coupling as well as cGMP- and cAMP-mediated relaxation. In ovo development and transition to ex ovo life was accompanied by alterations in the response of the MAs, but a different developmental trajectory was observed for each reactivity pathway tested. Thus, the contractile efficacy of KCl underwent a linear increase (E15 < E19 < NH3h < NH1d). The efficacy of NE and U46619 increased in ovo, but not ex ovo (E15 < E19 = NH3h = NH1d) and the efficacy of ET-1 peaked at E19 (E15 < E19 > NH3h = NH1d). The relaxations elicited by ACh (endothelium-dependent), SNP, and forskolin did not undergo significant developmental changes. In conclusion, the ability of chick MAs to constrict in response to pharmacological stimuli increases during the embryonic period, but no dramatic changes are induced by hatching or the first feeding. Maturation of vasodilator mechanisms precedes that of vasoconstrictor mechanisms. Alterations of the delicate balance between vasoconstrictors and vasodilators may play an important role in perinatal intestinal diseases

The T1405N Carbamoyl Phosphate Synthetase Polymorphism Does Not Affect Plasma Arginine Concentrations in Preterm Infants

A C-to-A nucleotide transversion (T1405N) in the gene that encodes carbamoyl-phosphate synthetase 1 (CPS1) has been associated with changes in plasma concentrations of L-arginine in term and near term infants but not in adults. In preterm infants homozygosity for the CPS1 Thr1405 variant (CC genotype) was associated with an increased risk of having necrotizing enterocolitis (NEC). Plasma L-arginine concentrations are decreased in preterm infants with NEC.To examine the putative association between the CPS1 T1405N polymorphism and plasma arginine concentrations in preterm infants.Prospective multicenter cohort study. Plasma and DNA samples were collected from 128 preterm infants (<30 weeks) between 6 and 12 hours after birth. Plasma amino acid and CPS1 T1405N polymorphism analysis were performed.Distribution of genotypes did not differ between the preterm (CC:CA:AA = 55.5%:33.6%:10.9%, n = 128) and term infants (CC:CA:AA = 54.2%:35.4%:10.4%, n = 96). There was no association between the CPS1 genotype and plasma L-arginine or L-citrulline concentration, or the ornithine to citrulline ratio, which varies inversely with CPS1 activity. Also the levels of asymmetric dimethylarginine, and symmetric dimethylarginine were not significantly different among the three genotypes.The present study in preterm infants did not confirm the earlier reported association between CPS1 genotype and L-arginine levels in term infants

Cost impact of procalcitonin-guided decision making on duration of antibiotic therapy for suspected early-onset sepsis in neonates

Abstract Backgrounds The large, international, randomized controlled NeoPInS trial showed that procalcitonin (PCT)-guided decision making was superior to standard care in reducing the duration of antibiotic therapy and hospitalization in neonates suspected of early-onset sepsis (EOS), without increased adverse events. This study aimed to perform a cost-minimization study of the NeoPInS trial, comparing health care costs of standard care and PCT-guided decision making based on the NeoPInS algorithm, and to analyze subgroups based on country, risk category and gestational age. Methods Data from the NeoPInS trial in neonates born after 34 weeks of gestational age with suspected EOS in the first 72 h of life requiring antibiotic therapy were used. We performed a cost-minimization study of health care costs, comparing standard care to PCT-guided decision making. Results In total, 1489 neonates were included in the study, of which 754 were treated according to PCT-guided decision making and 735 received standard care. Mean health care costs of PCT-guided decision making were not significantly different from costs of standard care (€3649 vs. €3616). Considering subgroups, we found a significant reduction in health care costs of PCT-guided decision making for risk category ‘infection unlikely’ and for gestational age ≥ 37 weeks in the Netherlands, Switzerland and the Czech Republic, and for gestational age < 37 weeks in the Czech Republic. Conclusions Health care costs of PCT-guided decision making of term and late-preterm neonates with suspected EOS are not significantly different from costs of standard care. Significant cost reduction was found for risk category ‘infection unlikely,’ and is affected by both the price of PCT-testing and (prolonged) hospitalization due to SAEs

Machine learning used to compare the diagnostic accuracy of risk factors, clinical signs and biomarkers and to develop a new prediction model for neonatal early-onset sepsis

Background: Current strategies for risk stratification and prediction of neonatal early-onset sepsis (EOS) are inefficient and lack diagnostic performance. The aim of this study was to use machine learning to analyze the diagnostic accuracy of risk factors (RFs), clinical signs and biomarkers and to develop a prediction model for culture-proven EOS. We hypothesized that the contribution to diagnostic accuracy of biomarkers is higher than of RFs or clinical signs. Study Design: Secondary analysis of the prospective international multicenter NeoPInS study. Neonates born after completed 34 weeks of gestation with antibiotic therapy due to suspected EOS within the first 72 hours of life participated. Primary outcome was defined as predictive performance for culture-proven EOS with variables known at the start of antibiotic therapy. Machine learning was used in form of a random forest classifier. Results: One thousand six hundred eighty-five neonates treated for suspected infection were analyzed. Biomarkers were superior to clinical signs and RFs for prediction of culture-proven EOS. C-reactive protein and white blood cells were most important for the prediction of the culture result. Our full model achieved an area-under-the-receiver-operating-characteristic-curve of 83.41% (±8.8%) and an area-under-the-precision-recall-curve of 28.42% (±11.5%). The predictive performance of the model with RFs alone was comparable with random. Conclusions: Biomarkers have to be considered in algorithms for the management of neonates suspected of EOS. A 2-step approach with a screening tool for all neonates in combination with our model in the preselected population with an increased risk for EOS may have the potential to reduce the start of unnecessary antibiotics

Pentalogy of Cantrell: two patients and a review to determine prognostic factors for optimal approach

Two patients with incomplete pentalogy of Cantrell are described. The first was a girl with a large omphalocele with evisceration of the heart, liver and intestines with an intact sternum. Echocardiography showed profound intracardiac defects. The girl died 33 h after birth. The second patient was a female fetus with ectopia cordis (EC) without intracardiac anomalies; a large omphalocele with evisceration of the heart, stomach, spleen and liver; a hypoplastic sternum and rib cage; and a scoliosis. The pregnancy was terminated. A review of patients described in the literature is presented with the intention of finding prognostic factors for an optimal approach to patients with the pentalogy of Cantrell. In conclusion the prognosis seems to be poorer in patients with the complete form of pentalogy of Cantrell, EC, and patients with associated anomalies. Intracardial defects do not seem to be a prognostic factor

C-Reactive Protein, Procalcitonin, and White Blood Count to Rule Out Neonatal Early-onset Sepsis Within 36 Hours: A Secondary Analysis of the Neonatal Procalcitonin Intervention Study.

BACKGROUND: Neonatal early-onset sepsis (EOS) is one of the main causes of global neonatal mortality and morbidity, and initiation of early antibiotic treatment is key. However, antibiotics may be harmful. METHODS: We performed a secondary analysis of results from the Neonatal Procalcitonin Intervention Study, a prospective, multicenter, randomized, controlled intervention study. The primary outcome was the diagnostic accuracy of serial measurements of C-reactive protein (CRP), procalcitonin (PCT), and white blood count (WBC) within different time windows to rule out culture-positive EOS (proven sepsis). RESULTS: We analyzed 1678 neonates with 10 899 biomarker measurements (4654 CRP, 2047 PCT, and 4198 WBC) obtained within the first 48 hours after the start of antibiotic therapy due to suspected EOS. The areas under the curve (AUC) comparing no sepsis vs proven sepsis for maximum values of CRP, PCT, and WBC within 36 hours were 0.986, 0.921, and 0.360, respectively. The AUCs for CRP and PCT increased with extended time frames up to 36 hours, but there was no further difference between start to 36 hours vs start to 48 hours. Cutoff values at 16 mg/L for CRP and 2.8 ng/L for PCT provided a sensitivity of 100% for discriminating no sepsis vs proven sepsis. CONCLUSIONS: Normal serial CRP and PCT measurements within 36 hours after the start of empiric antibiotic therapy can exclude the presence of neonatal EOS with a high probability. The negative predictive values of CRP and PCT do not increase after 36 hours

Smart and sustainable supply Chains

Over the last decades, companies have utilized supply chain management principles and practices as instruments to gain advantage in competition between business networks. In this chapter, we explore the use of Information and Communication Technologies to make supply chains smart and sustainable.</p

Evaluating medical residents as managers of care: a critical appraisal of assessment methods

INTRODUCTION: The increasing demands for effective and efficient health care delivery systems worldwide have resulted in an expansion of the desired competencies that physicians need to possess upon graduation. Presently, medical residents require additional professional competencies that can prepare them to practice adequately in a continuously changing health care environment. Recent studies show that despite the importance of competency-based training, the development and evaluation of management competencies in residents during residency training is inadequate. The aim of this literature review was to find out which assessment methods are currently being used to evaluate trainees' management competencies and which, if any, of these methods make use of valid and reliable instruments. METHODS: In September 2012, a thorough search of the literature was performed using the PubMed, Cochrane, Embase®, MEDLINE®, and ERIC databases. Additional searches included scanning the references of relevant articles and sifting through the "related topics" displayed by the databases. RESULTS: A total of 25 out of 178 articles were selected for final review. Four broad categories emerged after analysis that best reflected their content: 1) measurement tools used to evaluate the effect of implemented curricular interventions; 2) measurement tools based on recommendations from consensus surveys or conventions; 3) measurement tools for assessing general competencies, which included care-management; and 4) measurement tools focusing exclusively on care-management competencies. CONCLUSION: Little information was found about (validated) assessment tools being used to measure care-management competence in practice. Our findings suggest that a combination of assessment tools should be used when evaluating residents' care-management competencies

Smart and sustainable supply Chains

Over the last decades, companies have utilized supply chain management principles and practices as instruments to gain advantage in competition between business networks. In this chapter, we explore the use of Information and Communication Technologies to make supply chains smart and sustainable