Association of genetic variation in IKZF1, ARID5B,CDKN2A,and CEBPE with the risk of acute lymphoblastic leukemia in Tunisian children and their contribution to racial differences in leukemia incidence

Recent genome-wide association studies (GWAS) focusing on pediatric acute lymphoblastic leukemia (ALL), the most common malignancy in children younger than 15 years old, have found evidence that single-nucleotide polymorphisms (SNPs) in IKZF1 (7p12.2), ARID5B (10q21.2), CDKN2A (9p21.3), and CEBPE (14q11.2) are strongly associated to the risk of developing pediatric ALL. These studies have been conducted in European and Thai populations, and it is unclear whether these observations generalize to other populations with a lower incidence of pediatric ALL. In order to explore the impact of these variants on pediatric ALL risk in the Tunisian population, we genotyped 58 cases of pediatric ALL and 150 controls for SNPs rs4132601 (7p12.2), rs7089424 (10q21.2), rs3731217 (9p21.3), and rs2239633 (14q11.2). Our results, which are consistent with findings in European populations, show that 3 SNPs, i.e., rs4132601 (P = .00116, odds ratio [OR] = 2.78, 95% confidence interval [CI] = [1.42, 5.87]), rs7089424 (P = .0022, OR = 0.49, 95% CI = [0.31, 0.79]), and rs2239633 (P = .0010, OR = 0.47, 95% CI = [0.29, 0.75]) are significantly associated with a higher risk of developing pediatric ALL (P < .05). Furthermore, we show differences in allele frequencies in SNPs between Tunisian and Caucasian and/or Thai populations (e.g., CEBPE, rs2239633; population attributable risk [PAR] ～15-fold the PAR of Thai population). These differences, combined with differences in linkage disequilibrium structure between populations and differences in size between populations, may contribute to racial differences in pediatric ALL incidence.     

Coffin-Siris syndrome with bilateral macular dysplasia caused by a novel exonic deletion in ARID1B

Coffin-Siris syndrome (CSS) is a congenital anomaly syndrome characterized by developmental delay, coarse facial features, and hypoplasia of the fifth digit's nail or phalanges. Herein, we report a case of the 8-year-old female patient who showed developmental delay associated with dysplasia in the macular and large toe area. Comprehensive genomic analysis showed no possible candidate variants, but the subsequent genomic copy number analysis revealed a novel exonic deletion in the coding region of AT-rich interactive domain-containing protein 1B (ARID1B), a gene responsible for CSS. Genomic copy number analysis can aid in diagnosing CSS by confirming undiagnosed exonic deletions in ARID1B. Furthermore, this is the first report of CSS associated with bilateral macular dysplasia.     

Association of -24CT, 1249GA,and 3972CT ABCC2 Gene Polymorphisms with Methotrexate Serum Levels and Toxic Side Effects in Children with Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia patients after being treated with methotrexate, have differences in methotrexate serum levels and toxic side effects. One of the main determinants of these toxic side effects is the host pharmacogenetics. The aim of this study was to evaluate the association of -24CT, 1249GA, and 3972CT ABCC2 gene polymorphisms with serum levels, and toxic side effects of methotrexate in childhood acute lymphoblastic leukemia. Applying polymerase chain reaction and restriction fragment length polymorphism techniques, the prevalence of -24CT, 1249GA, and 3972CT ABCC2 gene polymorphisms was evaluated in 65 acute lymphoblastic leukemia patients. The relationship between polymorphisms and methotrexate serum levels and toxicities was studied. A reverse significant relationship was detected between 3972T allele carriers and hepatotoxicity (P = 0.01, OR = 0.25, 95% CI = 0.09–0.72). Also, 1249A allele carriers had increased rate of gastrointestinal toxicity (P = 0.05, OR = 3.47, 95% CI = 1.04–11.57). No significant relationship was detected between -24CT polymorphism and methotrexate toxic side effects. There was no significant relationship between these three polymorphisms and methotrexate serum levels. Genotyping for 3972CT and 1249GA ABCC2 gene variants maybe useful in acute lymphoblastic leukemia to optimize methotrexate therapy and reducing the associated toxicity.     

Serum Fructosamine and Retinopathy of Prematurity

Objective

To determine whether serum fructosamine which is a good marker for detecting hyperglycemia during the previous 2 to 3 wk in infants could predict the development of retinopathy of prematurity in very low birth weight infants.

Methods

One hundred sixty seven premature infants who had a birth weight of <1500 g and a gestational age of less than 32 wk were investigated in the present study. Blood glucose was measured at the bedside and infants were recorded as hyperglycemic if their mean blood glucose levels were higher than 150 mg/dL. Serum corrected fructosamine level was obtained from the cord blood at birth and after the first month of life. The infants’ eyes were examined by ophthalmologists to detect retinopathy of prematurity at the gestational age of 32 wk or at four wk after birth, whichever came first.

Results

Corrected fructosamine was 319.6?±?59.6 and 272.8?±?50.6 mmol/l for group1 on 1^st and 30^th day respectively; 320?±?61.7 and 268.2?±?47.3 mmol/l for groups 2?+?3 on 1^st and 30^th day respectively which did not differ between groups (p?=?0.766 and p?=?0.665), whereas duration of hyperglycemia was 1.69?±?1.1 day in group 1 compared with 3.05?±?2.4 day in groups 2?+?3 which was significantly different (p?=?0.019). The multivariate regression analysis indicated that the duration of hyperglycemia in days was significantly correlated with the development of retinopathy of prematurity (OR 3.26; 95% CI 1.09–9.80; p?=?0.035).

Conclusions

Although the duration of hyperglycemia may contribute to the development of retinopathy of prematurity, serum corrected fructosamine does not have a good predictive value in developing retinopathy of prematurity in very-low-birth-weight (VLBW) infants.     

IRF‐1 SNPs influence the risk for childhood allergic asthma: A critical role for pro‐inflammatory immune regulation

Background

Allergic and non‐allergic childhood asthma has been characterized by distinct immune mechanisms. While interferon regulating factor 1 (IRF‐1) polymorphisms (SNPs) influence atopy risk, the effect of SNPs on asthma phenotype‐specific immune mechanisms is unclear. We assessed whether IRF‐1 SNPs modify distinct immune‐regulatory pathways in allergic and non‐allergic childhood asthma (AA/NA).

Methods

In the CLARA study, asthma was characterized by doctor's diagnosis and AA vs NA by positive or negative specific IgE. Children were genotyped for four tagging SNPs within IRF‐1 (n = 172). mRNA expression was measured with qRT‐PCR. Gene expression was analyzed depending on genetic variants within IRF‐1 and phenotype including haplotype estimation and an allelic risk score.

Results

Carrying the risk alleles of IRF‐1 in rs10035166, rs2706384, or rs2070721 was associated with increased risk for AA. Carrying the non‐risk allele in rs17622656 was associated with lower risk for AA but not NA. In AA carrying the risk alleles, an increased pro‐inflammatory expression of ICAM3, IRF‐8, XBP‐1, IFN‐γ, RGS13, RORC, and TSC2 was observed. NOD2 expression was decreased in AA with risk alleles in rs2706384 and rs10035166 and with risk haplotype. Further, AA with risk haplotype showed increased IL‐13 secretion. NA with risk allele in rs2070721 compared to non‐risk allele in rs17622656 showed significantly upregulated calcium, innate, mTOR, neutrophil, and inflammatory‐associated genes.

Conclusion

IRF‐1 polymorphisms influence the risk for childhood allergic asthma being associated with increased pro‐inflammatory gene regulation. Thus, it is critical to implement IRF‐1 genetics in immune assessment for childhood asthma phenotypes.     

Association of high ventilator pressures with the development of chronic pulmonary hypertension in congenital diaphragmatic hernia patients requiring ECMO

Purpose

Congenital diaphragmatic hernia (CDH) patients requiring extracorporeal membrane oxygenation (ECMO) were examined to determine, if aspects of their complex ventilatory management were associated with the development of chronic pulmonary hypertension (cPH).

Methods

CDH patients requiring ECMO from 1992 to 2007 were retrospectively reviewed. cPH was defined as pulmonary hypertension at 3?months of age. Demographic and clinical variables including peak ventilatory pressures (PVP) and mean airway pressures (MAP) were tabulated.

Results

10/31 (32?%) patients developed cPH. Gestational age, birth weight, inborn status, CDH side and liver position were not different between cPH and non-cPH patients. Pre-ECMO, both groups required statistically similar ventilatory support, though there was a trend toward higher oxygenation index and higher PVP for cPH patients. While ECMO duration was similar between groups, cPH patients required significantly higher PVP (30.0 vs. 25.0?cmH₂O, p?=?0.01) and MAP (11.5 vs. 9.0?cmH₂O, p?=?0.02) for ECMO decannulation. Post-ECMO, maximum PVP (50.0 vs. 26.0?cmH₂O, p?p?=?0.001), HFV requirement (90 vs. 10?%, p?p?Conclusion Not until after ECMO decannulation do we see clinical differences separating patients who ultimately develop cPH. Although the degree of pulmonary hypoplasia may ultimately dictate ECMO decannulation criteria, perhaps greater physiologic optimization before decannulation could decrease the incidence of cPH.     

Polymorphisms in the promoter region of <Emphasis Type="Italic">IL10</Emphasis> gene are associated with virus etiology of infant bronchiolitis

Background

Bronchiolitis is the most common infection leading to hospitalization in infancy. Interleukin-10 (IL-10) is an anti-inflammatory cytokine, and in our previous study, IL10 gene rs1800896 (??1082A/G) polymorphism was associated with viral etiology of infant bronchiolitis. The objective of this study was to evaluate the associations between IL10 single nucleotide polymorphisms (SNPs) at rs1800890 (??3575A/T), rs1800871 (??819C/T) or rs1800872 (??592C/A) either alone or combined with the SNP at rs1800896 (??1082G/A), and the etiology and severity of infant bronchiolitis.

Methods

Data on four IL10 SNPs were available from 135 full-term infants, hospitalized for bronchiolitis at age less than 6 months, and from 378 to 400 controls. Viral etiology was studied, and oxygen support, feeding support and the length of stay in hospital were recorded during bronchiolitis hospitalization.

Results

Infants with rhinovirus bronchiolitis had the IL10 rs1800890 variant AT or TT genotype less often (18.2%) than controls (63.3%, P?=?0.03), and likewise, had the IL10 rs1800896 variant AG or GG genotype less often (27.3%) than controls (65.5%, P?=?0.009). Twenty-eight infants with bronchiolitis had the variant–variant G_rs1800896T_rs1800890 haplotype, and none of them had rhinovirus infection. The IL10 rs1800871 or rs1800872 genotypes showed no associations with viruses. No association was found between any genotypes and bronchiolitis severity measures.

Conclusion

IL10 rs1800890 and rs1800896 polymorphisms differed between infants with rhinovirus bronchiolitis and controls, but not between infants with respiratory syncytial virus bronchiolitis and controls.

     

Differential manifestations of prepubescent, pubescent and postpubescent pediatric patients with systemic lupus erythematosus: A retrospective study of 96 Chinese children and adolescents

Background

Children represent 10-20% of all systemic lupus erythematosus (SLE) patients. Their clinical manifestations and outcomes vary with age. We aim to clarify the relationship between pubescent status and the clinical manifestations of pediatric SLE.

Methods

In this study, pediatric SLE patients were divided into three groups, based on age at disease onset (?Q8, 8?C13 &; 13?C18?years), defined as prepubescent, pubescent and postpubescent, respectively. Initial clinical manifestations and laboratory characteristics at diagnosis were analyzed.

Results

Ninety-six patients were entered into the study: 8 had disease onset before age 8, while 49 were between 8?C13 and 39 of them were 13?C18. Female predominance was noted in all three groups (2.5-7.0:1). Postpubescents showed significantly more renal involvement and lymphopenia, along with lower levels of C3 and C4, when compared with prepubescents. They also showed significantly more lymphopenia when compared with pubescents. Pubescents showed significantly more renal involvement, leukopenia and lupus anticoagulant (LAC) positivity, along with lower C3 and C4 levels, when compared with prepubescents. Pubescents also showed significantly higher anti-Sm antibody positivity when compared with postpubescents. Prepubescents showed significantly more splenomegaly and anti-Jo-1 antibody positivity when compared with those of pubescents. The results showed that the disease activity (SLEDAI-2K score) correlated positively with age at disease onset and negatively with disease duration before diagnosis (p?=?0.011).

Conclusions

Age at disease onset is related to initial manifestations in pediatric SLE patients at our center. Certain parameters such as renal involvement, splenomegaly, low C3 level, low C4 level, lymphopenia, leukopenia, and anti-Sm &; anti-Jo-1 antibody were found to be significantly different among the age groups. Renal involvement might be the key symptom that varies with age.     

Association between toll-like receptor 10 (TLR10) gene polymorphisms and childhood IgA nephropathy

Toll-like receptors (TLRs) play an important role in the induction and regulation of the innate immune system and adaptive immune responses. TLR10 gene polymorphisms have been reported to be associated with a range of immune-related diseases. In this study, we investigated the association of TLR10 gene polymorphisms with immunoglobulin A nephropathy (IgAN) in Korean children. To examine the association, we genotyped one promoter single nucleotide polymorphisms (SNP) [rs10004195 (−113T/A)] and three missense SNPs [rs11096957 (Asn241His), rs11096955 (Ile369Leu), and rs4129009 (Ile775Val)] using direct sequencing in 199 IgAN patients and 289 control subjects. Our case–control analysis showed that rs10004195 was associated with IgAN (codominant model, p = 0.016 in TT vs. TA; p = 0.044 in TT vs. AA; dominant model, p = 0.0068). In addition, when comparing the proteinuria level of IgAN patients according to the genotypes of each SNP, we found that in dominant model of rs1004195, the level of proteinuria of patients with TA or AA genotypes (median, 4.01 mg/m²/h) was higher than that of patients with TT genotype (2.00 mg/m²/h, p = 0.033). In conclusion, these results suggest that TLR10 gene may be associated with susceptibility to IgAN in Korean children.     

Predictors of Mortality in Hospitalized Children with Pandemic H1N1 Influenza 2009 in Pune, India

Objective

To analyse the factors associated with increased mortality among Indian Children with H1N1.

Methods

Data were abstracted from available hospital records of children less than 12?y of age, who were admitted to Sassoon General Hospital in Pune, India, with confirmed pandemic 2009 H1N1 influenza infection from August 2009 through January 2010. Logistic regression analysis was used to identify clinical characteristics associated with mortality.

Results

Of 775 pediatric cases admitted with Influenza Like Illness (ILI), 92 (11.8%) had confirmed H1N1 influenza infection. The median age of HIN1 cases was 2.5?y; 13 (14%) had an associated co-morbid condition. Median duration of symptoms was 4?d (interquartile range (IQR), 3?C7?d). All 92 H1N1 cases received oseltamivir and empiric antimicrobials on admission. Intensive care unit (ICU) admission was required for 88 (96%) children, and 20 (23%) required mechanical ventilation.Fifteen children (16%) died; mortality was associated with presence of diffuse alveolar infiltrate on admission chest radiography (odds ratio (OR) 45, 95%CI :5.4?C370; p?p?=?0.001), SpO₂ <80% on admission (OR 32.8, 95% CI: 5.8?C185.5; p?p?n?=?4 each, 27%) with gram positive organisms consistent with severe viral and bacterial co-infection.

Conclusions

Hypoxia, ARDS and use of corticosteroids in children with ARDS who were mechanically ventilated were the factors associated with increased odds of mortality. Necropsy also suggested bacterial co-infection as a risk factor.     

Safety of cardiac magnetic resonance and contrast angiography for neonates and small infants: a 10-year single-institution experience

Background

With increasing applications of cardiac magnetic resonance (CMR) and magnetic resonance angiography (MRA) for evaluation of congenital heart disease (CHD), safety of this technology in the very young is of particular interest.

Objective

We report our 10-year experience with CMR in neonates and small infants with particular focus on the safety profile and incidence of adverse events (AEs).

Materials and methods

We reviewed clinical, anesthesia and nursing records of all children ≤120?days of age who underwent CMR. We recorded variables including cardiac diagnosis, study duration, anesthesia type and agents, prostaglandin E1 (PGE1) dependence and gadolinium (Gd) use. Serially recorded temperature, systemic saturation (SpO₂) and cardiac rhythm were analyzed. Primary outcome measure was any AE during or <24?h after the procedure, including minor AEs such as hypothermia (axillary temperature ≤95 °F), desaturation (SpO₂ drop ≥10% below baseline) and bradycardia (heart rate ≤100?bpm). Secondary outcome measure was unplanned overnight hospitalization of outpatients.

Results

Children (n?=?143; 74 boys, 69 girls) had a median age of 6?days (1–117), and 98 were ≤30?days at the time of CMR. The median weight was 3.4?kg (1.4–6?kg) and body surface area 0.22?m² (0.13–0.32?m²). There were 118 (83%) inpatients (108 receiving intensive care) and 25 (17%) outpatients. Indications for CMR were assessment of aortic arch (n?=?57), complex CHD (n?=?41), pulmonary veins (n?=?15), vascular ring (n?=?8), intracardiac mass (n?=?8), pulmonary artery (n?=?7), ventricular volume (n?=?4), and systemic veins (n?=?3). CMR was performed using a 1.5-T scanner and a commercially available coil. CMR utilized general anesthesia (GA) in 86 children, deep sedation (DS) in 50 and comforting methods in seven. MRA was performed in 136 children. Fifty-nine children were PGE1-dependent and 39 had single-ventricle circulation. Among children on PGE1, 43 (73%) had GA and 10 (17%) had DS. Twelve children (9%) had adverse events (AEs)—one major and 11 minor. Of those 12, nine children had GA (10%) and three had DS (6%). The single major AE was respiratory arrest after DS in a neonate (resuscitated without sequelae). Minor AEs included desaturations (n?=?2), hypothermia (n?=?5), bradycardia (n?=?2), and bradycardia with hypoxemia (n?=?2). Incidence of minor AEs was 9% for inpatients (vs. 4% for outpatients), and 8% for neonates (vs. 9% for age ≥30?days). Incidence of minor AEs was similar between PGE1-dependent infants and the non-PGE1 group. There were no adverse events related to MRA. Of 25 outpatients, 5 (20%) were admitted for overnight observation due to desaturations.

Conclusion

CMR and MRA can be accomplished safely in neonates and infants ≤120?days old for a wide range of pre-surgical cardiac indications. Adverse events were unrelated to patient age, complexity of heart disease, type of anesthesia or PGE1 dependence.     

Trends in the treatment and outcome of congenital diaphragmatic hernia over the last decade

Purpose

Congenital diaphragmatic hernia (CDH) remains a challenging and life-threatening congenital anomaly. The aim was to evaluate whether treatment and survival has changed during the last decade.

Methods

We retrospectively analysed all consecutive infants with CDH referred to two European tertiary paediatric surgical centres over 11?years (January 1999 to December 2009). Minimum follow-up was 1?year. ??² test for trend was used to evaluate significance.

Results

There were 234 infants. There was no significant variation over time in the proportion of infants receiving high frequency oscillatory ventilation (HFOV) (p?=?0.89), inhaled nitric oxide (iNO) (p?=?0.90) or extracorporeal membrane oxygenation (ECMO) (p?=?0.22). 205 infants (88?%) were stabilised and underwent surgical repair; of these, 186 (79?%) survived after surgery. Over time there was a significant increase in the proportion of infants undergoing surgical repair (p?=?0.018) without a concomitant significant improvement in survival (p?=?0.099).

Conclusion

This multicentre analysis indicates that the survival rate of infants with CDH referred to two European paediatric surgical centres is high (79?%). The use of HFOV, iNO and ECMO has not changed in recent years. We observed a significant increase in the proportion of infants who undergo surgery but this has not resulted in a significant increase in the overall survival rate.     

IL1R1基因多态性与儿童哮喘的相关性

目的 探讨我国中部地区儿童IL1R1 基因的两个SNP 位点(rs1558641 和rs949963)的多态性与哮喘易感性的相关性。方法 采用病例-对照的研究方法,选取来自于我国中部地区的208 例哮喘患儿(哮喘组)和223 例同时期体检正常的儿童(健康对照组)作为研究对象。利用限制性片段长度多态性分析(PCRRFLP)的方法检测IL1R1 基因两个SNP 位点(rs1558641 和rs949963)的多态性分布;酶联免疫吸附试验(ELISA)测定血清中IL1R1 的水平。结果 哮喘组患儿SNP 位点(rs1558641)的基因型及等位基因频率与健康对照组相比差异无统计学意义。而哮喘组患儿SNP 位点(rs949963)GG 基因型的比例显著高于健康对照组(P=0.031),且两组等位基因频率差异也有统计学意义(P=0.018)。哮喘组血清IL1R1 的水平明显高于健康对照组(P=0.011),且SNP 位点(rs949963)GG 基因型的患儿血清IL1R1 水平高于其他基因型(AA+AG)的患儿(P=0.028)。结论 IL1R1 基因SNP 位点(rs949963)的多态性与我国中部地区儿童哮喘的易感性相关,且该位点的多态性可能影响患儿血清中IL1R1 的表达水平。     

Nephrolithiasis in pediatric hematopoietic cell transplantation with up to 40 years of follow‐up

Background

Kidney stones have been reported to occur after childhood cancer, but little is known about kidney stones in children following hematopoietic cell transplantation (HCT). The objective of this retrospective study was to determine risk factors for the development of kidney stones and to describe the prevalence among survivors.

Procedure

The study included 1,343 childhood HCT patients. Mean follow‐up was 15.8 (1.0–40.0) years. Patients were treated with total body irradiation (TBI) (n = 948) or non‐TBI regimens. Methotrexate (MTX) for acute graft‐versus‐host disease (GVHD) prophylaxis was given as long‐course (n = 360), short‐course (n = 626), or none (n = 357). Prednisone for chronic GVHD therapy was received by 525 patients. Multivariate Cox regression models were used to estimate the hazard ratio (HR) of risk factors associated with kidney stones.

Results

Kidney stones developed in 51 patients, a median of 9.9 (0.2–29.4) years after first HCT, with a 30‐year cumulative incidence of 7.4%. Risk factors associated with kidney stones were TBI (HR = 2.2; P = 0.03), age at HCT (12–18 vs. <6 years, HR = 2.7; P = 0.01), MTX (long vs. none, HR = 3.6; P = 0.02), and prednisone (HR = 2.2; P = 0.008). Among 868 survivors, the prevalence of a history of kidney stones was 4.7%.

Conclusions

Survivors of childhood HCT have an increased risk of developing kidney stones. Pediatr Blood Cancer 2014;61:417–423. © 2013 Wiley Periodicals, Inc.     

Slow-transit constipation with concurrent upper gastrointestinal dysmotility and its response to transcutaneous electrical stimulation

Purpose

Transcutaneous electrical stimulation (TES) speeds up colonic transit in children with slow-transit constipation (STC). This study examined if concurrent upper gastrointestinal dysmotility (UGD) affected response to TES.

Methods

Radio-nuclear transit studies (NTS) were performed before and after TES treatment of STC as part of a larger randomised controlled trial. UGD was defined as delayed gastric emptying and/or slow small bowel transit. Improvement was defined as increase of ??1 Geometric Centre (median radiotracer position at each time [small bowel?=?1, toilet?=?6]).

Results

Forty-six subjects completed the trial, 34 had NTS after stimulation (21?M, 8?C17?years, mean 11.3?years; symptoms >9?years). Active stimulation increased transit in >50% versus only 25% with sham (p?=?0.04). Seventeen children also had UGD. In children with STC and either normal upper GI motility (NUGM) and UGD, NTS improved slightly after 1?month (57 vs. 60%; p?=?0.9) and more after 2?months (88 vs. 40%; p?=?0.07). However, mean transit rate significantly increased with NUGM, but not UGD (5.0?±?0.2: 3.6?±?0.6, p?<?0.01).

Conclusion

Transcutaneous electrical stimulation was beneficial for STC, with response weakly associated with UGD. As measured by NTS, STC children with NUGM responded slightly more, but with significantly greater increased transit compared to those with UGD. Higher numbers are needed to determine if the difference is important.     

MRI diffusion-weighted imaging (DWI) in pediatric small bowel Crohn disease: correlation with MRI findings of active bowel wall inflammation

Background

Restricted diffusion on diffusion-weighted imaging (DWI) sequences during magnetic resonance enterography (MRE) has been shown in segments of bowel affected by Crohn disease. However, the exact meaning of this finding, particularly within the pediatric Crohn disease population, is poorly understood.

Objective

The purpose of this study was to determine the significance of bowel wall restricted diffusion in children with small bowel Crohn disease by correlating apparent diffusion coefficient (ADC) values with other MRI markers of disease activity.

Materials and methods

A retrospective review of pediatric patients (≤ 18 years of age) with Crohn disease terminal ileitis who underwent MRE with DWI at our institution between May 1, 2009 and May 31, 2011 was undertaken. All of the children had either biopsy-proven Crohn disease terminal ileitis or clinically diagnosed Crohn disease, including terminal ileal involvement by imaging. The mean minimum ADC value within the wall of the terminal ileum was determined for each examination. ADC values were tested for correlation/association with other MRI findings to determine whether a relationship exists between bowel wall restricted diffusion and disease activity.

Results

Forty-six MRE examinations with DWI in children with terminal ileitis were identified (23 girls and 23 boys; mean age, 14.3 years). There was significant negative correlation or association between bowel wall minimum ADC value and established MRI markers of disease activity, including degree of bowel wall thickening (R?=?(?)0.43; P?=?0.003), striated pattern of arterial enhancement (P?=?0.01), degree of arterial enhancement (P?=?0.01), degree of delayed enhancement (P?=?0.045), amount of mesenteric inflammatory changes (P?<?0.0001) and presence of a stricture (P?=?0.02). ADC values were not significantly associated with bowel wall T2-weighted signal intensity, length of disease involvement or mesenteric fibrofatty proliferation.

Conclusion

Increasing bowel wall restricted diffusion (lower ADC values) is associated with multiple MRI findings that are traditionally associated with active inflammation in pediatric small bowel Crohn disease.     

Association between adenosine receptor gene polymorphism and response to caffeine citrate treatment in apnea of prematurity; An Egyptian single-center study

Background

Caffeine citrate is the methyl-xanthine of choice used in controlling apnea of prematurity (AOP). Caffeine central effect is mediated via non-selective (A₁) and selective (A_2a) adenosine receptors antagonism. Variability in caffeine response had been frequently noticed in AOP, suggesting underlying genetic predisposition.

New Biomarkers to Diagnose Ventilator Associated Pneumonia: Pentraxin 3 and Surfactant Protein D

Objective

To detect the most effective biomarker to confirm ventilator associated pneumonia (VAP).

Methods

Fifty patients with VAP suspicious diagnosis and 30 healthy patients were recruited. Suspicion of VAP was established if patients met the modified CPIS score?≥?6 points. The confirmation of VAP was defined by the quantitative culture of nonbronchoscopic bronchoalveolar lavage (BAL) >10⁵ CFU/ml of pathogenic microorganism. Serum samples for determination of C-reactive protein (CRP), procalcitonin (PCT), pentraxin 3 (PTX3), surfactant protein D (SPD) were collected on suspected VAP.

Results

Twenty seven of 50 patients were accepted as confirmed VAP group whose nonbronchoscopic BAL cultures were positive and rest of them were accepted as unconfirmed VAP group. PTX3, PCT and SPD levels were significantly higher in confirmed VAP group, (P?=?0.021, P?=?0.007, P?<?0.001 respectively). There were no significant differences in CRP levels between the two groups (P?=?0.062). The most sensitive marker for diagnosing VAP was SPD (P?<?0.001). Receiver operating characteristic (ROC) curve for modified clinical pulmonary infection score (CPIS) to confirm VAP was evaluated (AUC 0.741?±?0.07, P?<?0.001) and the optimal cutoff value was >7 with a sensitivity of 51.85% and a specificity of 91.3%. SPD levels were significantly higher in Acinetobacter baumannii and Pseudomonas aeruginosa infected patients than culture negative patients (P?<?0.001).

Conclusions

The index findings suggest that serum SPD is the most sensitive biomarker in diagnosis of VAP and it can be used as an early and organism specific marker for Acinetobacter baumannii and Pseudomonas aeruginosa.

     

Measurement of cardiac output in children by bioreactance

The objective of this study was to evaluate a new bioreactance method for noninvasive cardiac output (CO) measurement (NICOM) in children. Ten patients between 1 and 144?months of age and with no hemodynamic disturbances were studied. Using bioreactance, heart rate (HR), mean arterial pressure (MAP), and cardiac index (CI) measurements were made every 6?C8?h. CI was 2.4?±?1.03?l/min/1.73?m² (range 1?C4.9?l/min/1.73?m²); There were significant correlations between CI and age (r?=?0.50, P?=?0.003), weight (r?=?0.66, P?<?0.001), and MAP (r?=?0.369, P?=?0.037). Significant differences in CI (P?<?0.001) were detected between children weighing <10?kg (1.9?±?0.73?l/min/1.73?m²; range 1?C3.2), 10?C20?kg (2.07?±?0.7?l/min/1.73?m²; range 1?C3.6), and >20?kg (3.7?±?0.8?l/min/1.73?m²; range 2.4?C4.9). We conclude that the CI measured by bioreactance in children varies with the age and weight of the patients and is lower than the normal range in a large percentage of measurements. These data suggest that this method is not useful for evaluating CI in small children.     

Single-nucleotide and copy-number variance related to severity of hypospadias

Background

The genetic association of hypospadias-risk studies has been conducted in Caucasians, Chinese-Han populations and few in Indian populations. However, no comprehensive approach has been followed to assess genetic involvement in the severity of the disorder.

Methods

The study evaluated to establish the correlation between genotyped single nucleotide and copy number variants (SNPs/CNVs) and severity of hypospadias by an association in a total 30 SNPs in genes related to sex hormone-biosynthesis and metabolism; embryonic-development and phospholipase-d-signalling pathways on 138 surgery-confirmed hypospadias-cases from North India (84 penile and 28 cases of penoscrotal-hypospadias as compared with 31 cases of glanular?+?coronal), and analyzed and identified CNVs in four familial cases (18 members) and three paired-sporadic cases (6 members) using array-based comparative-genomic-hybridization and validated in 32 hypospadias samples by TaqMan assay.

Results

Based on odds ratio at 95% CI, Z Statistic and Significance Levels, STS gene-rs17268974 was associated with Penile-Hypospadias and 9-SNPs [seven-SNPs (rs5934740; rs5934842; rs5934913; rs6639811; rs3923341; rs17268974; rs5934937)] of STS gene; rs7562326-SRD5A2 and rs1877031-STARD3 were associated with penoscrotal-hypospadias. On aggregate analysis with p?<?0.001, we identified homozygous-loss of Ch7:q34 (PRSS3P2, PRSS2). On validation in previously CNV-characterized and new (32 hypospadias cases), we identified PRSS3P2-loss in most of the grade 3 and 4 hypospadias. Hence, Grade 1 and 2 (coronal and granular) show no-PRSS3P2-loss and no-association with SNPs in STS; SRD5A2; STARD3-gene but Grade 3 and 4 (Penile and Penoscrotal) show PRSS3P2-loss accompanied with the association of SNPs in STS; SRD5A2; STARD3.

Conclusions

Hence, homozygous-loss of PRSS3P2 accompanied with the association of STS; SRD5A2; STARD3 may link to the severity of the disease.