The heart rate variability-derived Newborn Infant Parasympathetic Evaluation (NIPE (TM)) Index in pediatric surgical patients from 0 to 2 years under sevoflurane anesthesia

Abstract Background The heart rate variability‐derived Newborn Infant Parasympathetic Evaluation (NIPE™) Index is a continuous noninvasive tool to assess pain and discomfort in infants <2 years. Initial studies focused on pain monitoring in the neonatal intensive care unit environment. Aims The aim of this study was to investigate the performance of the NIPE in infants under sevoflurane anesthesia. The primary objective of this study was to compare the NIPE and heart rate as tools to help recognize the need for additional opioid drugs. Secondary objectives were the course of the NIPE and heart rate around specific standardized noxious procedural mile‐stones. Methods NIPE and heart rate values recorded during a 120 seconds interval before the anesthetist's decision to administer additional opioid due to the perceived insufficient antinociception and during a 120 seconds interval after drug administration were analyzed by means of a repeated measures ANOVA. The same analyses were performed for datasets around per protocol administration of morphine for postoperative analgesia, performance of a caudal block and surgical incision. Results In patients with a NIPE value <50, an additional opioid drug administration resulted in a rise of NIPE values, reaching a maximum increase of 5.1 (95% CI: 0.22‐9.99) units 120 seconds after drug administration (P = 0.041). There was no evidence of a change in heart rate during these two 120 seconds periods. Per protocol administration of morphine, caudal block, and surgical incision did not result in changes of the NIPE, which was around 65 units on these occasions, and heart rate. Conclusion In infants anesthetized with sevoflurane, NIPE values <50 might be indicative of insufficient antinociception. The results of this observational pilot study might suggest that the NIPE could be a better measure of the nociception/antinociception balance than heart rate

Получение полуизолирующего кремния для высоковольтных приборов

Исследовано влияние условий осаждения на структуру и электрофизические свойства пленок поликристаллического кремния, легированного кислородом. Результаты использованы при изготовлении изделий силовой электроники

The predictive value of the heart rate variability-derived Analgesia Nociception Index in children anaesthetized with sevoflurane: An observational pilot study

Background The heart rate variability (HRV)‐derived Analgesia Nociception Index (ANI™) is a continuous noninvasive tool to assess the nociception/antinociception balance in unconscious patients. It has been shown to be superior to haemodynamic variables in detecting insufficient antinociception in children, while little is known about its predictive value. Methods The primary objective of this prospective observational pilot study in paediatric surgical patients under sevoflurane anaesthesia was to compare the predictive value of the ANI and heart rate to help decide to give additional opioids. The paediatric anaesthesiologist in charge was blinded to ANI values. Results In patients with an ANI value <50 (indicating insufficient antinociception) at the moment of decision, ANI values dropped from ±55 (indicating sufficient antinociception) to ±35, starting 60 s before decision. Within 120 s after administration of fentanyl (1 μg/kg), ANI values returned to ±60. This phenomenon was only observed in the ANI values derived from HRV data averaged over 2 min. Heart rate remained unchanged. In patients with ANI values ≥50 at the time of decision, opioid administration had no effect on ANI or heart rate. The same accounts for morphine for postoperative analgesia and fentanyl in case of intraoperative movement. Conclusions This study provides evidence of a better predictive value of the ANI in detecting insufficient antinociception in paediatric surgical patients than heart rate. The same accounts for depicting re‐establishment of sufficient antinociception after opioid drug administration

Genetic and nongenetic etiology of nonsyndromic anorectal malformations: A systematic review

Item does not contain fulltextCongenital anorectal malformations (ARMs) are one of the most frequently observed birth defects of the digestive system. However, their etiology remains elusive. Therefore, we aim to summarize and critically appraise all existing literature on the genetic and nongenetic etiology of nonsyndromic ARM and to conclude with unifying hypotheses and directions for future research. A structured literature search on English language human studies was conducted in PubMed and Embase up to October 1, 2013, resulting in 112 included articles. Research on the identification of genes underlying nonsyndromic ARM is remarkably scarce. Most studies were focused on screening of candidate genes for mutations or single-nucleotide polymorphisms, which did not yield any substantial evidence. Nongenetic factors fairly consistently found to be associated with ARM are assisted reproductive techniques, multiple pregnancy, preterm delivery, low birth weight, maternal overweight or obesity, and preexisting diabetes. This review provides indications for the involvement of both genes and nongenetic risk factors in the etiology of ARM. In future studies, large cohorts of patients with ARM from national and international collaborations are needed to acquire new hypotheses and knowledge through hypothesis-generating approaches. Challenges for future studies may also lie in the investigation of gene-gene and gene-environment interactions. Birth Defects Research (Part C) 102:382-400, 2014. (c) 2014 Wiley Periodicals, Inc

Genetic and nongenetic etiology of nonsyndromic anorectal malformations: A systematic review

Congenital anorectal malformations (ARMs) are one of the most frequently observed birth defects of the digestive system. However, their etiology remains elusive. Therefore, we aim to summarize and critically appraise all existing literature on the genetic and nongenetic etiology of nonsyndromic ARM and to conclude with unifying hypotheses and directions for future research. A structured literature search on English language human studies was conducted in PubMed and Embase up to October 1, 2013, resulting in 112 included articles. Research on the identification of genes underlying nonsyndromic ARM is remarkably scarce. Most studies were focused on screening of candidate genes for mutations or single-nucleotide polymorphisms, which did not yield any substantial evidence. Nongenetic factors fairly consistently found to be associated with ARM are assisted reproductive techniques, multiple pregnancy, preterm delivery, low birth weight, maternal overweight or obesity, and preexisting diabetes. This review provides indications for the involvement of both genes and nongenetic risk factors in the etiology of ARM. In future studies, large cohorts of patients with ARM from national and international collaborations are needed to acquire new hypotheses and knowledge through hypothesis-generating approaches. Challenges for future studies may also lie in the investigation of gene-gene and gene-environment interactions. Birth Defects Research (Part C) 102:382-400, 2014. (c) 2014 Wiley Periodicals, Inc

Parental subfertility, fertility treatment, and the risk of congenital anorectal malformations

Item does not contain fulltextBACKGROUND: Fertility treatment seems to play a role in the etiology of congenital anorectal malformations, but it is unclear whether the underlying parental subfertility, ovulation induction, or the treatment itself is involved. Therefore, we investigated the odds of anorectal malformations among children of subfertile parents who conceived with or without treatment compared with fertile parents. METHODS: We performed a case-control study among 380 cases with anorectal malformations treated at 3 departments of pediatric surgery in The Netherlands and 1973 population-based controls born between August 1988 and August 2012. Parental questionnaires were used to obtain information on fertility-related issues and potential confounders. RESULTS: In singletons, increased risks of anorectal malformations were observed for parents who underwent intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF) treatment compared with fertile parents (odds ratio = 2.4 [95% confidence interval = 1.0-5.9] and 4.2 [1.9-8.9], respectively). For subfertile parents who conceived after IVF treatment, an elevated risk was also found when they were compared with subfertile parents who conceived without treatment (3.2 [1.4-7.2]). Among children of the latter category of parents, only the risk of anorectal malformations with other major congenital malformations was increased compared with fertile parents (2.0 [1.3-3.3]). No associations were found with intrauterine insemination or use of hormones for ovulation induction. CONCLUSIONS: We found evidence of a role of ICSI and IVF treatments in the etiology of anorectal malformations. However, subfertility without treatment increased only the risk of anorectal malformations with additional congenital malformations

Comparison of surveillance and retroperitoneal lymph node dissection in Stage I nonseminomatous germ cell tumors.

Item does not contain fulltextOBJECTIVES: To compare retrospectively the treatment results of surveillance and primary retroperitoneal lymph node dissection (RPLND) of patients with clinical Stage I nonseminomatous germ cell tumors of the testis (NSGCT) in two institutions in The Netherlands. METHODS: From 1982 to 1994, 90 consecutive patients with clinical Stage I NSGCT were prospectively entered in a surveillance protocol in Amsterdam (group 1). In the same period, 101 patients with clinical Stage I NSGCT underwent primary RPLND in Nijmegen (group 2). Both patient populations were comparable for patient age, presence of vascular invasion, and embryonal cell components in the primary tumor. All patients in group 1 with relapse, except for 2, were treated with cisplatin-based chemotherapy. All patients in group 2 with vital tumor in the RPLND specimen were treated with two adjuvant courses of combined chemotherapy (cisplatin, etoposide, and bleomycin). RESULTS: In group 1, at a median follow-up of 7.7 years, 23 patients (26%) had relapse. The median time to relapse was 12 months. Relapses were located retroperitoneally (n = 18, 78%), in the lung (n = 3, 13%), scrotally (n = 1, 4%), and combined in the liver, lung, and pleura (n = 1, 4%). After treatment of relapses (chemotherapy in 21 and/or surgery in 11), only 1 patient died of disseminated disease. A disease-free survival rate of 98.5% was achieved at the median follow-up. The main toxicities consisted of short-lasting leukopenia, accompanied by infection (13%). Four patients reported cardiovascular and four neuropathy complaints. In group 2, the median follow-up was 6.9 years. In 31 patients (30.7%), vital tumor was found retroperitoneally; after two courses of combined chemotherapy, none of them had a relapse. Seven patients with pathologic Stage I disease (6.4%) had a pulmonary relapse within 1 year after surgery. No retroperitoneal relapses were found. After chemotherapy, 6 patients with relapse were salvaged, and 1 died of disseminated disease. The disease-specific survival rate in group 2 was 98% at the median follow-up. The most frequent surgical complications were lymphocele (n = 3), small bowel obstruction (n = 3), and abdominal pain (n = 3). The antegrade ejaculation rate was 94%. CONCLUSIONS: Excellent treatment results in terms of disease-free survival can be achieved in Stage I NSGCT with both surveillance and primary RPLND. Patients with pathologic Stage II disease adjuvantly treated with chemotherapy did not have any relapse and consequently all survived. Most complications after both treatment strategies are reversible. The choice of treatment should be based on balanced information and not on dogmatic principles

A Genetics-First Approach Revealed Monogenic Disorders in Patients With ARM and VACTERL Anomalies

Contains fulltext : 221455.pdf (publisher's version ) (Open Access

Sequencing of the DKK1 gene in patients with anorectal malformations and hypospadias

Contains fulltext : 153944.pdf (publisher's version ) (Closed access)Anorectal malformations (ARM) are rare congenital malformations of the gastrointestinal tract. Approximately 60% of the patients have additional congenital malformations, such as hypospadias. A recently published article showed that deletion of one single gene, dickkopf WNT signaling pathway inhibitor-1 (Dkk1), resulted in an imperforate anus with rectourinary fistula and preputial hypospadias in mice. To determine whether DKK1 also plays a role in the etiology of ARM and hypospadias in humans, we sequenced the four exons of the DKK1 gene in 17 patients affected with both ARM and hypospadias. No new potential disease-causing variant was identified. However, we detected a known non-synonymous variant in one patient, which was predicted in silico to be damaging, and the corresponding unaffected amino acid is highly conserved. CONCLUSION: In this human study, a potential interesting non-synonymous variant was found in the DKK1 gene. Whether this variant plays a contributory role in the genesis of ARM or hypospadias would require a much larger study

No major role for periconceptional folic acid use and its interaction with the MTHFR C677T polymorphism in the etiology of congenital anorectal malformations

Item does not contain fulltextBackground: Both genetic and nongenetic factors are suggested to be involved in the etiology of congenital anorectal malformations (ARM). Maternal periconceptional use of folic acid supplements were inconsistently suggested to play a role in the prevention of ARM. Therefore, we investigated independent associations and interactions of maternal periconceptional folic acid supplement use and the infant and maternal MTHFR (methylenetetrahydrofolate reductase) C677T polymorphisms with the risk of ARM and subgroups of ARM. Methods: A case-control study was conducted among 371 nonsyndromic ARM cases and 714 population-based controls born between 1990 and 2012 using maternal questionnaires and DNA samples from mother and child. Cases were treated for ARM at departments of Pediatric Surgery of the Radboud university medical center, Sophia Children's Hospital-Erasmus MC Rotterdam, and the University Medical Center Groningen in The Netherlands and hospitals throughout Germany. Results: No association with folic acid use was present (odds ratio = 1.1; 95% confidence interval: 0.8-1.4) for ARM as a group. Infant and maternal MTHFR C677T polymorphisms were weakly associated with isolated ARM in particular. Lack of folic acid supplement use in combination with infants or mothers carrying the MTHFR C677T polymorphism did not seem to increase the risk of ARM or subgroups of ARM. The relative excess risks due to interaction did not clearly indicate interaction on an additive scale either. Conclusion: This first study investigating interactions between periconceptional folic acid supplement use and infant and maternal MTHFR C677T polymorphisms in the etiology of ARM did not provide evidence for a role of this gene-environment interaction. Birth Defects Research (Part A) 100:483-492, 2014. (c) 2014 Wiley Periodicals, Inc