Gene polymorphisms of IL-6<Superscript>−174</Superscript> G/C and IL-1Ra VNTR in asthmatic children

Objective  To check for the association of genetic polymorphisms of IL-6-⁻¹⁷⁴G/C and IL-1RaVNTR with the susceptibility and severity of asthma in Egyptian children. Methods  Subjects included 69 asthmatic children and 98 healthy unrelated controls from the Nile Delta of Egypt. Cases consisted of 20 males and 49 females with an age mean± SD is 7.5 ± 2.1 ranging between 2-13 years. DNA amplification using PCR with sequence-specific primers was done for detection of promotor single nucleotide polymorphism of IL-6 gene as well as intron 2 VNTR of IL-1Ra gene. Frequency of case-genotypes or alleles were compared to controls using Fisher exact test and Odds ratio. Results  Cases showed significant higher frequency of the genotypes: IL-6-174 GG (P<0.05, OR=3.2, 95% CI=1.09–10) that was evident mainly in the uncontrolled asthma subgroup indicative of the possibility of being a severity genotype. All cases as well as case-subgroups showed high significant frequency of IL-1Ra A1A1 (p<0.0001, OR=1.5, 95% CI=1.3–1.8). This may be considered a susceptibility genotype. Cases have also shown significant lower frequency of IL-6⁻¹⁷⁴ GC and IL-1Ra A1A2 genotypes (P<0.001 and P<0.0001 respectively). Conclusion  IL-6 and IL-1Ra polymorphisms can be considered genetic markers for bronchial asthma susceptibility and/or severity among Egyptian children. This may have a potential impact on family counseling and management.     

Novel <Emphasis Type="Italic">UBR1</Emphasis> gene mutation in a patient with typical phenotype of Johanson–Blizzard syndrome

Johanson–Blizzard syndrome is a rare autosomal recessive disorder, characterized by exocrine pancreatic deficiency and a wide range of other abnormalities. We present here an infant with failure to thrive, exocrine pancreatic deficiency, short stature and developmental delay, cutis aplasia on the scalp, aplasia of alae nasi, hypospadias, hypothyroidism, myxomatous mitral valve, and patent ductus arteriosus. Molecular studies revealed a novel homozygous nonsense mutation in exon 38 of the UBR1 gene, which confirmed the diagnosis of Johanson–Blizzard syndrome. It should be acknowledged that the combination of exocrine pancreatic insufficiency and nasal wing hypo-aplasia is pathognomonic for this syndrome. Prompt diagnosis and exact monitoring of the patients with JBS are required to avoid further complications.     

The use of Surgisis<Superscript><Emphasis Type="Bold">®</Emphasis></Superscript> for abdominal wall reconstruction in the separation of omphalopagus conjoined twins

Abdominal wall reconstruction in omphalopagus twins poses a difficult reconstructive challenge, as separation often results in a large abdominal wall defect. A number of options are available for closure, including tissue flaps, expanders and patches made of foreign material. Surgisis is a new biodegradable small intestine scaffolding substrate that permits tissue in-growth and results in a permanent durable scar. We describe its use in abdominal wall reconstruction after separation of a set of conjoined twins. A set of omphalopagus conjoined twins shared liver and abdominal wall. After separation at 6 months of age, Twin A's abdomen could be closed primarily, but Twin B could not. A 4-ply Surgisis mesh was used in the upper abdominal closure, and a skin flap was created, to completely cover the patch. Both twins survived the operation. A small portion of the skin flap over the Surgisis broke down, healing by secondary intention. In follow up of over 18 months post procedure, there have been no wound infections and the abdominal wall is intact with no evidence of a hernia. Surgisis can be successfully used for the reconstruction of complex abdominal wall defects in the pediatric patient, including reconstruction after separation of conjoined twins.     

Ranitidine-enhanced <Superscript>99m </Superscript>technetium pertechnetate imaging in children improves the sensitivity of identifying heterotopic gastric mucosa in Meckel’s diverticulum

Meckels diverticulum is the most common congenital gastrointestinal anomaly. ^99m Technetium pertechnetate imaging (Meckels scan) is the best noninvasive method used to diagnose this condition when heterotopic gastric mucosa (HGM) is present. Although cimetidine enhancement has been shown to improve sensitivity of the Meckels scan, ranitidine enhancement has also been advocated; however, this recommendation is based on unpublished data. Thirty-seven children with confirmed Meckels diverticulum were reviewed retrospectively. Of eight children with HGM in the Meckels diverticulum who presented with profuse rectal bleeding and underwent the conventional Meckels scan, three of them (37.5%) had a false negative study. Ranitidine, when administered either intravenously or orally for 24 h prior to the Meckels scan, enhanced the sensitivity of this test to 87.5% in our patient cohort.     

A novel <Emphasis Type="BoldItalic">WT1</Emphasis> gene mutation in a patient with Wilms’ tumor and 46, XY gonadal dysgenesis

Denys–Drash syndrome (DDS) is a rare genetic disorder featuring the triad of Wilms' tumor, early-onset renal failure, and 46, XY disorder of sex development. DDS is usually caused by heterozygous missense mutations in the zinc-finger region of the WT1 gene. The most frequent constitutional WT1 mutations in DDS patients are missense mutations in exons 8 and 9. We present a new case of variable DDS in a child who was found to have a novel heterozygous missense mutation in exon 7 (c.905G>T) and a splicing mutation in exon 6 (IVS6-1G>T).     

Gene Polymorphisms of TNF-α<Superscript>−308</Superscript>, IL-10<Superscript>−1082</Superscript>, IL-6<Superscript>−174</Superscript>, and IL-1Ra<Superscript>VNTR</Superscript> Related to Susceptibility and Severity of Rheumatic Heart Disease

Rheumatic heart disease (RHD) is an inflammatory disease of the heart tissues caused by interactive immune, genetic, and environmental factors. The objective of this study is to test for the association of polymorphisms related to cytokine genes with susceptibility and severity of RHD among affected children from the Nile Delta region of Egypt. The study included 50 children with chronic RHD (29 males and 21 females), with a mean age of 12.2 years, in addition to 98 healthy unrelated controls. Cases were further classified on the basis of echocardiographic findings into those with only mitral valve disease (MVD) or multivalvular lesions (MVLs) and also as mild, moderate, or severe valve lesions. For all cases and controls, DNA was extracted and amplified using polymerase chain reaction with sequence-specific primers for detection of single nucleotide polymorphisms (SNPs) in the promoter regions of cytokine genes tumor necrosis factor (TNF)-alpha(-308 )G/A, interleukin (IL)-10(-1082 )G/A, and IL-6(-174 )G/C as well as a variable number of tandem repeats (VNTRs) in intron 2 of the IL-1Ra gene. All cases showed a significantly higher frequency of homozygous genotypes of TNF-alpha(-308 )A/A [odds ratio (OR) = 5.7, p < 0.001], IL-10(-1082) A/A (OR = 3.1, p < 0.05), IL-10(-1082) G/G (OR = 5.2, p < 0.05), and IL-1Ra A1/A1 (OR = 2.2, p < 0.05). Cases with MVD showed higher frequencies of genotypes TNF-alpha(-308 )A/A, G/G; IL-10(-1082) G/G; and IL-1Ra(VNTR) A1/A1 (p < 0.05). Cases with MVL showed a significantly higher frequency of homozygous A/A genotype of both TNF-alpha(-308 )(OR = 10.6, p < 0.05) and IL-10(-1082) (OR = 5.2, p < 0.05). The same was observed for cases with severe valve lesions. On the other hand, all studied groups showed significantly lower frequency of heterozygous genotypes of TNF-alpha(-308 )G/A, IL-10(-1082) G/A, and IL-1Ra(VNTR) A1/A2. No significant difference was found regarding the frequency of IL-6(-174 )G/C polymorphisms in total cases or subgroups compared to controls (p > 0.05). Predisposition to RHD is influenced by genetic factors including cytokine gene polymorphisms, with possible susceptibility to severe disease with multivalvular affection among cases with composite polymorphism (TNF-alpha(-308 )A/A and IL-10(-1082) A/A) and (TNF-alpha(-308 )A/A and IL-10(-1082) G/G).     

Selective deficiency of naïve CD4<Superscript>+</Superscript> T-lymphocytes in a child with congenital lymphoedema

We describe the first known case of congenital lymphoedema associated with selective deficit of naïve CD4⁺ T-lymphocytes. A high proportion of naïve CD4⁺ T-lymphocytes was found in the ascitic fluid, supporting the hypothesis of extra-vascular sequestration of these cells into lymphoedematous tissue.Abbreviation ICL idiopathic CD4⁺ lymphocytopenia     

Disseminated Bacillus Calmette-Guérin lymphadenitis in a patient with gp91<Emphasis Type="Italic">phox</Emphasis><Superscript>−</Superscript> chronic granulomatous disease 25 years after vaccination

A boy developed ipsilateral axillary lymphadenitis after Bacillus Calmette-Guérin (BCG) inoculation at the age of 5 months. Subsequently, he was diagnosed with X-linked chronic granulomatous disease (CGD) by the nitroblue tetrazolium assay when he was 4 years old. Body computerized tomography (CT) performed at the age of 25 years showed enlarged lymph nodes in the left periclavicular and axillary regions, and was confirmed by gallium scintigraphy. Mycobacterial culture, smear, and polymerase chain reaction (PCR) of the sputum and gastric fluid were negative. Whole-blood IFN-γ assay was negative as well. Mycobacterium bovis BCG was isolated from the lymph node biopsy by PCR amplification and culture. No mutation of the IFN-γ receptor 1 could be identified. In conclusion, CGD can be the underlying condition for BCG-itis; whole-blood IFN-γ assay might be useful in differentiating BCG infection and tuberculosis in CGD patients; BCG vaccination is contraindicated in X-linked CGD.     

Incorporation of Integra<Superscript>®</Superscript> in tissue defects: a pilot study in the rat model

Integra has been shown to be very useful in accelerating the growth of neodermis. It has found extensive use in case of burns as a primary dressing immediately after a burn, after release of contractures and following scar revision. It has been used to achieve cover after the debridement of extensive infective processes involving the skin. Encouraged by these results we have assessed the application of Integra to augment and/or patch defects of the urinary bladder, diaphragm and the abdominal wall in the rat model. This was a pilot study and involved the incorporation of Integra in the diaphragm, the urinary bladder (extramucosal) and the muscle layer of the abdominal wall. Eight adult Wistar rats were given general anaesthesia and Integra was implanted with absorbable sutures at the sites mentioned. The omentum was hitched to the collagen matrix surface to revascularise the graft. The silicone was left in situ. The operative period was covered with antibiotics. The anaesthesia was then reversed. Postoperatively the rats were given analgesia and feeds started immediately. The rats were sacrificed after 3 weeks. The abdominal cavity was examined for adhesions. The Integra implant along with adjacent tissue was harvested and examined histologically. There were no visible intra-abdominal adhesions. The histology revealed good degree of neovascularisation and fibrosis in and adjacent to the implant. This was comparable to the changes seen in the skin. This pilot study has shown that implanting Integra invokes a similar response in deeper tissues and it can develop neovascularisation from the omentum. Hence, this could find some application in treating congenital conditions such as diaphragmatic hernias, abdominal wall defects and for bladders requiring augmentation. Our initial results are quite encouraging and we feel that this field should be further explored.     

Hematopoietic stem cell transplantation for children with <Emphasis Type="Italic">β</Emphasis>-thalassemia major: multicenter experience in China

Background

β-Thalassemia major (β-TM) has become a public health problem in mainland China. Hematopoietic stem cell transplantation (HSCT) has remained the only cure for β-TM in mainland China since 1998.

Methods

This multicenter retrospective study provides a comprehensive review of the outcomes of 50 pediatric patients with β-TM who received HSCT between 1998 and 2009 at five centers in mainland China. Both related (n = 35) and unrelated donors (n = 15) with complete human leukocyte antigen matches were included. The stem cell sources included bone marrow (BM), peripheral blood stem cells, umbilical cord blood (UCB) and a combination of BM and UCB or a combination of BM and peripheral blood stem cells from a single sibling donor.

Results

The probabilities of 5-year overall survival (OS) and thalassemia-free survival (TFS) after the first HSCT were 83.1 and 67.3%, respectively. Graft failure (GF) occurred in 17 patients. Univariate analyses showed that umbilical cord blood transplantation (UCBT) was one of the potential risk factors for decreased OS (P = 0.051), and that UCBT (P = 0.002) was potentially related to TFS. GF incidence was distinct between the UCBT and non-UCBT groups (P = 0.004). Four cases of UCB-BM combined transplantation led to decreased risks of mortality and recurrence. In the UCBT group, related donor transplantation produced more favorable results than unrelated donor transplantation in OS (P = 0.009) but not in TFS (P = 0.217).

Conclusions

GF was the primary cause of UCBT failure. Though UCBT from related donors was not favorable, the combined transplantation of UCB and BM could improve the prognosis of UCBT.

     

A novel <Emphasis Type="Italic">SOX10</Emphasis> mutation in a patient with PCWH who developed hypoxic–ischemic encephalopathy after <Emphasis Type="Italic">E. coli</Emphasis> sepsis

We describe a male infant with a novel SOX10 mutation and a severe course of PCWH—a special phenotype of Shah-Waardenburg syndrome involving peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung’s disease. The patient had severe hypoplastic hypoganglionosis of the small and total colonic intestine together with peripheral and central dysmyelination. The patient was completely dependent on parenteral nutrition. We identified a novel frameshift mutation, p.Asp293GlyfsX10, in the SOX10 gene of this patient. The mutation would encode a protein that lacked the transactivation domain and resulted in the largest duplication described to date. At the age of 20 months, the boy presented with a severe complication with a translocation of Escherichia coli and developed sepsis leading to severe hypoxic–ischemic encephalopathy with persistent vegetative state (PVS). The boy died at the age of 24 months. Conclusion: Septic encephalopathy with hypoxic–ischemic encephalopathy can be a serious complication in severe sepsis. It is unknown to what extent the mutant SOX10 protein influenced the degree of brain injury—for example central nervous system susceptibility to hypoxia—during sepsis, which may explain the severe encephalopathy with clinical signs of PVS the boy developed.     

Matriderm<Superscript>®</Superscript> 1 mm versus Integra<Superscript>®</Superscript> Single Layer 1.3 mm for one-step closure of full thickness skin defects: a comparative experimental study in rats

Purpose

Dermal templates, such as Matriderm^® and Integra^®, are widely used in plastic and reconstructive surgery, often as two-step procedures. A recent development is the application of thin dermal templates covered with split thickness skin grafts in one-step procedures. In this experimental study, we compare the two thin matrices Matriderm^® 1 mm and Integra^® Single Layer in a one-step procedure with particular focus on neodermis formation.

Methods

Matriderm^® 1 mm and Integra^® Dermal Regeneration Template—Single Layer (1.3 mm) were compared in a rat model. In three groups of five animals each, a full thickness wound was covered with (a) Matriderm^® 1 mm and neonatal rat epidermis, (b) Integra^® Single Layer and neonatal rat epidermis, or, (c) neonatal rat epidermis only (control). Histological sections 2 weeks post transplantation were analyzed with regard to take of template and epidermis, neodermal thickness, collagen deposition, vascularization, and inflammatory response.

Results

Take of both templates was complete in all animals. The Matriderm^®-based neodermis was thinner but showed a higher cell density than the Integra^®-based neodermis. The other parameters were similar in both matrices.

Conclusion

The two templates demonstrate a comparable biological behavior early after transplantation. The only difference was found regarding neodermal thickness, probably resulting from faster degradation of Matriderm^®. These preliminary data suggest that both dermal templates appear similarly suitable for transplantation in a one-step procedure.

     

Comparison of the Occlutech<Superscript>®</Superscript> Figulla<Superscript>®</Superscript> Septal Occluder and Amplatzer<Superscript>®</Superscript> Septal Occluder for Atrial Septal Defect Device Closure

The Occlutech^® Figulla^® septal occluder (OFSO) is a later-generation double-disk device with few reports of its success rates and complications compared with the Amplatzer^® septal occluder (ASO), which is the worldwide standard device in percutaneous atrial septal defect (ASD) closure. We recruited and compared the results in 149 patients (76.5 % female) who underwent ASD device closure in our center between January 2003 and June 2012. The patients ranged in age from 2.3 to 77.2 years. There were no statistically significant differences between the two groups regarding patient baseline characteristics and procedure variables. The success rate using either device was excellent (ASO 94.4 % and OFSO 97.4 %; p = 0.43). Although the diameter of the ASD and the pulmonary arterial pressure in the OFSO group were slightly higher than in the ASO group, the median fluoroscopic time in the OFSO group was significantly shorter (ASO 13.7 min; OFSO 9.0 min; p < 0.001). The overall median follow-up time was 3.6 years (interquartile range 2.1–9.0 years). There were no significant differences between the major and minor complications when comparing the two devices. Both devices were safe and effective for percutaneous ASD closures. The OFSO had the benefit of a shorter fluoroscopic time.     

Mechanism of Rho-kinase-mediated Ca<Superscript>2+</Superscript>-independent contraction in aganglionic smooth muscle in a rat model of Hirschsprung’s disease

Purpose  

Lack of ganglion cells is the main cause of bowel movement disorder in Hirschsprung’s disease. Because smooth muscle is the primary organ, the properties of intestinal smooth muscle need to be investigated. We therefore investigated the reactivity of the contractile system and the mechanism of contraction in aganglionic intestinal smooth muscle.     

Influencing factors for the development and severity of bronchopulmonary dysplasia in preterm infants with a gestational age of <32 weeks and a birth weight of <1 500 g北大核心CSCD

Objective To study the influencing factors for the development and severity of bronchopulmonary dysplasia (BPD) in preterm infants with a gestational age of <32 weeks and a birth weight of <1 500 g. Methods A retrospective analysis was performed on the medical data of preterm infants with a gestational age of <32 weeks and a birth weight of <1 500 g who were admitted to Women and Children's Hospital Affiliated to Xiamen University from January 1, 2017 to December 31, 2021. According to oxygen dependence on day 28 after birth, they were divided into two groups: BPD (n=218) and non-BPD (n=142). According to disease severity based on oxygen concentration required at the corrected age of 36 weeks or at discharge, the infants with BPD were divided into two groups: mild BPD (n=154) and moderate/severe BPD (n=64). Indices such as perinatal data and nutritional status were compared between groups. The multivariate logistic regression analysis was used to determine the influencing factors for BPD and its severity. Results The incidence rate and severity of BPD increased with the reduction in gestational age and birth weight (P<0.05). The multivariate logistic regression analysis showed that a long duration of invasive mechanical ventilation (OR=1.320, P <0.05), hemodynamically significant patent ductus arteriosus (OR=2.032, P<0.05), and a prolonged time to reach oral calorie goal of 110 kcal/(kg·d) (OR=1.041, P<0.05) were risk factors for BPD, while an older gestational age was a protective factor against BPD (OR=0.535, P<0.05). Early-onset sepsis (OR=2.524, P<0.05) and a prolonged time to reach oral calorie goal of 110 kcal/(kg·d) (OR=1.029, P<0.05) were risk factors for moderate/severe BPD, while a high mean weight growth velocity was a protective factor against moderate/severe BPD (OR=0.906, P<0.05). Conclusions The incidence rate and severity of BPD in preterm infants with a gestational age of <32 weeks and a birth weight of <1 500 g can be reduced by shortening the duration of invasive mechanical ventilation, giving early treatment of early-onset sepsis and hemodynamically significant patent ductus arteriosus, adopting active enteral nutritional strategies, and increasing mean weight growth velocity. © 2022 Xiangya Hospital of CSU. All rights reserved.     

High mortality due to congenital malformations in children aged &lt; 1 year in French Guiana

Background

In French Guiana, pregnant women may be exposed to infectious, environmental, and social risks leading to congenital malformation. The objective of the study was to study mortality rates from congenital malformations among infants <?1?year and to compare them with those in mainland France.

Methods

We used the CEPI DC (INSERM) database, which compiles annual data from death certificates in all French territories using the International Classification of Diseases. Annual deaths for French Guiana and mainland France between 2005 and 2015 were compiled. The age category studied was children less than 1?year and deaths from congenital malformations, deformations and chromosomal abnormalities were compiled. Crude risk ratios and 95% confidence intervals were calculated to quantify the excess risk of disease in French Guiana.

Results

In French Guiana between 2005 and 2015 there were 666 deaths of children aged <?1?year, among which, 132 (19.8%) were due to congenital malformations and chromosomal anomalies. Overall the risk ratio of death from congenital malformations and chromosomal anomalies between French Guiana and mainland France was 2.7 (1.5–4.7), P?<?0.001 for neurological congenital malformations it was 4.8 (1.2–19.7), P?=?0.01 and for congenital malformations of the circulatory system it was 3.3 (1.5–6.9), P?=?0.001.

Conclusions

The incidence of death from congenital malformations or chromosomal anomalies in French Guiana was significantly higher than in mainland France. Explanations for this may be infections, genetic causes, nutritional causes, and toxic causes that are prevalent. There is a need to identify factors that predispose children born in French Guiana to having a higher risk of congenital malformations and chromosomal anomalies.