Tenofovir alafenamide or tenofovir disoproxil fumarate in pregnancy to prevent HBV transmission: Maternal ALT trajectory and infant outcomes.

BACKGROUND: The use of antiviral agents, specifically tenofovir disoproxil fumarate (TDF), in pregnant women to prevent mother-to-child HBV transmission is a key step towards hepatitis elimination. However, data on using tenofovir alafenamide (TAF) is insufficient. The frequent occurrence of postpartum ALT flares may impact the clinical implementation. METHODS: The maternal and infant outcomes were compared in multi-centre trials of high viral load HBsAg/HBeAg+ pregnant women receiving TAF or TDF from the third trimester until 2 weeks postpartum with intensive follow-ups. To explore the dynamic pre- and postpartum changes in ALT levels, we used a group-based trajectory model for analysing data of 332 women from three prospective studies. RESULTS: After treatment, the maternal HBV DNA levels significantly decreased from baseline to delivery: 7.87 ± 0.59 to 3.99 ± 1.07 Log10 IU/mL TAF (n = 78) and 8.30 ± 0.36 to 4.47 ± 0.86 Log10 IU/mL (TDF, n = 53), with viral load reductions of 3.87 versus 3.83 Log10 IU/mL. The HBsAg-positive rates among 12-month-old infants were 1.28% (1/78) versus 1.82% (1/55) respectively (p = 1.00). Of the TAF or TDF-treated mothers, 25.64% versus 16.98% experienced ALT > 2X ULN, and 11.54% versus 1.89% received extended antiviral treatment. Our model revealed four distinct ALT patterns: stable ALT (87.2%), moderate (8.0%) or marked (2.4%) postpartum flares, or prepartum elevations (2.4%). CONCLUSIONS: TAF effectively reduces mother-to-child HBV transmission, but prophylaxis failure still occurred in few cases. Postpartum ALT flares are common in women receiving TAF or TDF during pregnancy. Approximately 12.8% of mothers may require extended postpartum antiviral treatment. CLINICAL TRIAL NUMBER: NCT03695029 (ClinicalTrials.gov).

Characterization of Hepatitis B Virus in Tenofovir-Treated and Untreated Chronically Infected Mothers and Their Immunoprophylaxis Failure Infants.

BACKGROUND: Maternal tenofovir disoproxil fumarate (TDF) therapy during late pregnancy can reduce mother-to-infant transmission of hepatitis B virus (HBV). We investigated HBV mutations associated with maternal TDF therapy and their role in infant immunonophylaxis failure (IPF). METHODS: Serum samples from untreated (n = 89) and TDF-treated (n = 68), highly viremic, chronically infected mothers and their infants were analyzed for HBV DNA by nested polymerase chain reaction (PCR) and direct sequencing. RESULTS: At delivery, compared with untreated mothers, TDF-treated mothers had a lower HBV DNA titer and a higher frequency of basal core promoter (BCP) gene mutations, but they had similar frequencies in pre-S/S and pre-core/core mutations. The 14 mothers harboring surface "a" determinant mutants did not transmit the mutants to their immunized infants. Such mutants were found in 3 of 13 IPF infants; the 13 mothers had wild-type hepatitis B surface antigen (HBsAg). In univariable analysis, maternal HBV DNA titer (odds ratio [OR]: 1.54; 95% confidence intervals [CI]: 1.02-2.33; P = .039), genotype C (OR: 4.18; 95% CI: 1.28-13.62; P = .018) and pre-S1 wild-type sequence (OR: 6.33; 95% CI: 1.85-21.68; P = .003) at delivery were associated with infant IPF. Multivariable analyses showed that maternal genotype C (OR: 3.71; 95% CI: 1.11-12.36; P = .033) and pre-S1 wild-type (OR: 6.34; 95% CI: 1.79-22.44; P = .004) were associated with infant IPF independently of maternal viremia. CONCLUSIONS: Along with high maternal HBV DNA titer at delivery, maternal genotype C and pre-S1 wild-type sequence were potential risk factors for infant IPF, although BCP mutations were not. The offspring of pregnant women harboring "a" determinant mutants as major strains seemed to be protected by immunoprophylaxis. CLINICAL TRIALS REGISTRATION: NCT01312012.

Occult Hepatitis B Virus Infection in Immunized Infants Born to Untreated and Tenofovir-Treated Highly Viremic Mothers.

Tenofovir disoproxil fumurate (TDF) therapy during late pregnancy in highly viremic mothers can reduce residual overt hepatitis B virus (HBV) infections of their infants that occur despite immunoprophylaxis.1,2 Occult HBV infection (OBI) has been defined as the presence of HBV DNA in liver or sera in subjects seronegative for hepatitis B surface antigen (HBsAg).3 OBI has been found in varying proportions of immunized infants born to HBsAg-positive mothers.4-6 We aimed to investigate the impact of maternal TDF therapy during pregnancy on vertically acquired OBI.

High-flow nasal cannula in children with asthma exacerbation: A review of current evidence.

Asthma is the commonest obstructive airway disease and the leading cause of morbidity in children. In the pediatric population, acute exacerbations of asthma are a frequent cause of presentations and hospital admissions. An acute asthma exacerbation is potentially life-threatening; it is predominantly treated using conventional oxygen therapy with bronchodilators and systemic corticosteroids. The treatment of those who do not respond to conventional therapy is escalated to noninvasive positive pressure ventilation (NIPPV) before invasive ventilation. Although NIPPV has demonstrated benefits and safety, it still has limitations such as treatment intolerance caused mainly by discomfort and complications. High-flow oxygen therapy administered through a nasal cannula (HFNC) provides respiratory support with adequate airway humidity and has demonstrated safety and benefits in clinical practice. In the present review, we discuss HFNC and variations in HFNC use, focusing on its feasibility and current evidence of using it on children with asthma exacerbations.

Long-term growth and bone development in children of HBV-infected mothers with and without fetal exposure to tenofovir disoproxil fumarate.

BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF) is the preferred treatment to prevent maternal transmission of HBV, owing to its efficacy and safety. However, data are lacking on the long-term safety outcomes in children following fetal exposure to TDF. METHODS: Children participating in a prospective, multisite trial of maternal TDF treatment during late pregnancy were recruited for follow-up visits once a year. Growth parameters, serum biochemistry, HBV serology, and bone mineral density (BMD) by dual-energy x-ray absorptiometery scan were measured. RESULTS: One hundred and twenty-eight children, 71 in the TDF and 57 in the control group, completed 255 follow-up visits at the age of 2 to 7 (median, 4.08) years. No differences in z-scores for weight-for-age (0.26 ± 0.90 vs. 0.22 ± 0.99, p = 0.481), z-scores for height-for-age (0.20 ± 1.02 vs. 0.25 ± 0.98, p = 0.812), and estimated glomerular filtration rate (169.12 ± 50.48 vs. 169.06 ± 34.46 ml/min/1.73m2, p = 0.479) were detected. After adjustment for age, sex and HBV status by multiple linear regression, children in the TDF and control group had comparable levels of serum calcium, phosphorus, bone-specific alkaline phosphatase, calcidiol and BMD of lumbar spines (0.55 ± 0.01 vs. 0.57 ± 0.01 g/cm2, p = 0.159) and left hip (0.56 ± 0.01 vs. 0.56 ± 0.01 g/cm2, p = 0.926). CONCLUSIONS: Children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery. CLINICAL TRIAL NUMBER: NCT01312012 (ClinicalTrials.gov) LAY SUMMARY: Currently there are insufficient long-term safety data in children born to mothers who took antiviral agents during pregnancy to prevent mother-to-infant transmission of hepatitis B virus (HBV). In this study, we found that children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery.

Sustained inflation: The lung recruitment maneuvers for neonates.

Establishing effective respiration is vital in the transition from fetal to neonatal life. Respiratory support mainly facilitates and creates functional residual capacity and maintains adequate gas exchange. Sustained inflation (SI) delivers prolonged inflation and rapidly creates and establishes the functional residual capacity. The use of SI in preterm infants in the delivery room is still controversial. The optimum settings of SI remain unknown. Animal studies and clinical reports have demonstrated the advantages and disadvantages of SI. In this article, the current literature was reviewed to examine the efficacy of SI in infants.

Combined effect of polymorphisms of MTHFR and MTR and arsenic methylation capacity on developmental delay in preschool children in Taiwan.

Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are related to cognitive dysfunction and mental disability. These genes, along with folate and vitamin B12 levels, are regulators of one-carbon metabolism, which synthesizes S-adenosylmethionine (SAM) as a methyl donor for arsenic methylation. The aim of this study was to explore whether polymorphisms of MTHFR and MTR influence arsenic methylation capacity and plasma folate and vitamin B12 levels and if these influences cause developmental delay in preschool children. A total of 178 children with developmental delay and 88 without developmental delay were recruited from August 2010 to March 2014. A high-performance liquid chromatography-hydride generator and atomic absorption spectrometer were used to determine urinary arsenic species. Plasma folate and vitamin B12 concentrations were measured by SimulTRAC-SNB radioassay. Polymorphisms of MTHFR C677T, MTHFR A1298C, and MTR A2756G were examined by polymerase chain reaction and restriction fragment length variation. The results show that MTHFR C677T C/T and T/T genotypes had a lower risk of developmental delay than the C/C genotype (odds ratio [OR] = 0.47; 95% confidence interval, 0.26-0.85). Subjects with the MTHFR C677T C/C genotype had significantly lower plasma folate and vitamin B12 levels than those with the MTHFR C677T C/T and T/T genotype. The MTHFR C677T C/C genotype combined with high total urinary arsenic and poor arsenic methylation capacity indices significantly increased the OR of developmental delay in a dose-response manner. This is the first study to show the combined effect of MTHFR C677T genotype and poor arsenic methylation capacity on developmental delay.

Plasma selenium influences arsenic methylation capacity and developmental delays in preschool children in Taiwan.

Inefficient arsenic methylation capacity has been associated with developmental delay in preschool children. Selenium has antioxidant and anti-inflammatory properties that protect experimental animals from chemically induced neurotoxicity. The present study was designed to explore whether plasma selenium levels affects arsenic methylation capacity related to developmental delay in preschool children. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 178 children with a developmental delay and 88 children without a delay were recruited. High-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry were used to determine urinary arsenic species, including arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV). Plasma selenium levels were measured by inductively coupled plasma mass spectrometry. As results, plasma selenium concentration was significantly inversely associated with the odds ratio (OR) of developmental delay. Plasma selenium concentration was positively associated with arsenic methylation capacity [percentage of inorganic arsenic and percentage of MMAV (MMAV%) decreased, and percentage of DMAV (DMAV%) increased]. High plasma selenium concentration and high DMA% significantly and additively interacted to decrease the OR of developmental delay; the OR and 95% confidence interval were 0.40 (0.18-0.90). This is the first study to show a combined dose-response effect of plasma selenium concentration and that efficient arsenic methylation capacity decreased the OR of developmental delay in preschool children.

Association of plasma folate, vitamin B12 levels, and arsenic methylation capacity with developmental delay in preschool children in Taiwan.

Developmental delay has been associated with inefficient arsenic methylation capacity in preschool children. Folate and vitamin B12 are important nutrients that produce s-adenosylmethionine during single-carbon metabolism and provide methyl groups for arsenic methylation. The aim of the present study was to explore whether plasma folate and vitamin B12 levels influence arsenic methylation capacity and in turn are related to developmental delay in preschool children. A case-control study was conducted in 178 children with developmental delay and 88 normal children, who were recruited from Shin Kong Wu Ho-Su Memorial Teaching Hospital from August 2010 to March 2014. Arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) in the urine was determined by high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Plasma folate and vitamin B12 levels were measured using a SimulTRAC-SNB radioassay. The results show that the combination of high plasma folate and high vitamin B12 levels were correlated with efficient arsenic methylation capacity (low MMAV %, low InAs %, and high DMAV %). High MMAV % significantly increased and high DMAV % and secondary methylation index decreased the odds ratio (OR) of developmental delay in a dose-dependent manner in both low plasma folate and low vitamin B12 (low/low) groups; the multivariate OR and 95% confidence interval were 5.01 (0.83-30.06), 0.21 (0.04-1.23), and 0.20 (0.03-1.20), respectively. This is the first study to show that the combination of high plasma folate and high vitamin B12 levels increases arsenic methylation capacity and indirectly decreases the OR of developmental delay in preschool children.

Relation of polymorphism of arsenic metabolism genes to arsenic methylation capacity and developmental delay in preschool children in Taiwan.

Inefficient arsenic methylation capacity has been associated with developmental delay in children. The present study was designed to explore whether polymorphisms and haplotypes of arsenic methyltransferase (AS3MT), glutathione-S-transferase omegas (GSTOs), and purine nucleoside phosphorylase (PNP) affect arsenic methylation capacity and developmental delay. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 179 children with developmental delay and 88 children without delay were recruited. Urinary arsenic species, including arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) were measured using a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphisms of AS3MT, GSTO, and PNP were performed using the Sequenom MassARRAY platform with iPLEX Gold chemistry. Polymorphisms of AS3MT genes were found to affect susceptibility to developmental delay in children, but GSTO and PNP polymorphisms were not. Participants with AS3MT rs3740392 A/G+G/G genotype, compared with AS3MT rs3740392 A/A genotype, had a significantly lower secondary methylation index. This may result in an increased OR for developmental delay. Participants with the AS3MT high-risk haplotype had a significantly higher OR than those with AS3MT low-risk haplotypes [OR and 95% CI, 1.59 (1.08-2.34)]. This is the first study to show a joint dose-response effect of this AS3MT high-risk haplotype and inefficient arsenic methylation capacity on developmental delay. Our data provide evidence that AS3MT genes are related to developmental delay and may partially influence arsenic methylation capacity.

Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-to-infant transmission of hepatitis B virus.

UNLABELLED: The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in reducing mother-to-infant hepatitis B virus (HBV) transmissions is not clearly understood. We conducted a prospective, multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)- and hepatitis B e antigen-positive pregnant women with HBV DNA ≥7.5 log10 IU/mL. The mothers received no medication (control group, n = 56, HBV DNA 8.22 ± 0.39 log10 IU/mL) or TDF 300 mg daily (TDF group, n = 62, HBV DNA 8.18 ± 0.47 log10 IU/mL) from 30-32 weeks of gestation until 1 month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery, the TDF group had lower maternal HBV DNA levels (4.29 ± 0.93 versus 8.10 ± 0.56 log10 IU/mL, P < 0.0001). Of the 121/123 newborns, the TDF group had lower rates of HBV DNA positivity at birth (6.15% versus 31.48%, P = 0.0003) and HBsAg positivity at 6 months old (1.54% versus 10.71%, P = 0.0481). Multivariate analysis revealed that the TDF group had lower risk (odds ratio = 0.10, P = 0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P = 0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal alanine aminotransferase (ALT) levels above two times the upper limit of normal for ≥3 months (3.23% versus 14.29%, P = 0.0455), a lesser extent of postpartum elevations of ALT (P = 0.007), and a lower rate of ALT over five times the upper limit of normal (1.64% versus 14.29%, P = 0.0135) at 2 months postpartum. Maternal creatinine and creatinine kinase levels, rates of congenital anomaly, premature birth, and growth parameters in infants were comparable in both groups. At 12 months, one TDF-group child newly developed HBsAg positivity, presumably due to postnatal infection and inefficient humoral responses to vaccines. CONCLUSIONS: Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations. (Hepatology 2015;62:375-386.

Rare type of tracheal agenesis: Unexpected presentation and immediate consideration of emergent esophageal intubation in neonatal resuscitation program. Case reports and review of the literature.

BACKGROUND: Tracheal agenesis, or tracheal atresia, is a rare congenital anomaly. The presence of a tracheoesophageal fistula (TEF) can help with breathing for newborns with tracheal agenesis. In this article, we presented three unique cases and outcomes of neonates with tracheal agenesis along with a review of the literature. METHODS: This study consisted of a single center case series followed by a review of literature. Case reports were generated using both written and electronic medical records from a single hospital. We summarized three unique cases and outcomes of neonates with tracheal agenesis and performed a review of the literature. RESULTS: We identified three cases of tracheal agenesis presented with severe cyanosis without spontaneous crying upon birth. Experienced pediatricians attempted to intubate the babies but were unsuccessful. Endotracheal tubes were subsequently either accidentally or purposely placed into the esophagus, and oxygen saturation levels improved. This suggested tracheal agenesis with TEF. Two cases underwent surgical intervention after resuscitation with esophageal intubation. CONCLUSION: Esophageal intubation may be a life-sustaining ventilation support for patients with tracheal agenesis and TEF at initial resuscitation. Clinicians should suspect tracheal agenesis when a newborn presents with severe cyanosis and voiceless crying upon birth, and esophageal intubation should be immediately attempted.

Early oral-motor management on feeding performance in premature neonates.

BACKGROUND/PURPOSE: Poor oral-motor developments in premature infants are common. From the viewpoint of developmental care, most of the infants required individualized therapy. The specific aim of our study was to evaluate the effectiveness and impact of early intervention of oral-motor management on feeding pattern and the neonatal outcomes in premature neonates. METHODS: The study enrolled 68 preterm infants with birth weight less than 1500 g or gestational age less than 32 weeks. We tried to strengthen the sucking ability of infants with poor oral-motor coordination. RESULTS: There were significant differences in the body weight (g) while feeding up to 45 mL (1916 ± 156 vs. 2003 ± 191 g, p = 0.002) and hospital stay (46.3 ± 25.3 vs. 54.7 ± 23.5 days, p = 0.003) between the study and control groups. CONCLUSION: Abnormal brain sonography [odds ratio (OR): 2.222, p = 0.047) and necrotizing enterocolitis (NEC) (OR: 2.857, p = 0.017) did affect the first trial in the study group. Early intervention of oral-motor management in very-low-birth-weight premature infants improved feeding performance and neonatal outcome in terms of shorter hospital days. Abnormal brain image and NEC could interfere with the success rate of initial challenge of transitioning from tube to oral feeding in the study group.

Naturally occurring hepatitis B virus B-cell and T-cell epitope mutants in hepatitis B vaccinated children.

To control hepatitis B virus (HBV) infection, a universal HBV vaccination program for infants was launched in Taiwan in 1984. The aim of this study was to investigate the role of B-cell and T-cell epitope variations of HBsAg and polymerase in HBV infection in vaccinated children. One hundred sixty-three sera from vaccinated children were enrolled randomly. HBV serum markers, including hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) and core antigen (anti-HBc), were detected by ELISA. Nucleotide sequences encoding the S and the pre-S regions of HBsAg were analyzed in all HBsAg positive sera. Five children were HBsAg positive. Sequence analysis of S, pre-S, and overlapped polymerase (P) genes showed that HBV isolates of HBsAg-positive vaccinees were variants; no G145R but G145A and other substitutions were found in the "a" determinant. Fifteen, six, and eight amino acid substitutions within B-cell and T-cell epitopes of S, pre-S, and P regions were detected, respectively. Several immune-epitope mutants, such as S45T/A, N131T, I194V, and S207N in S, were detected in all isolates. In conclusion, our results suggested that these naturally occurring immunoepitope mutants, which changed their immunogenicity leading to escape from immune response, might cause HBV infection.

Corrigendum: Helmet ventilation for pediatric patients during the COVID-19 pandemic: A narrative review.

[This corrects the article DOI: 10.3389/fped.2022.839476.].

Helmet Ventilation for Pediatric Patients During the COVID-19 Pandemic: A Narrative Review.

The air dispersion of exhaled droplets from patients is currently considered a major route of coronavirus disease 2019 (COVID-19) transmission, the use of non-invasive ventilation (NIV) should be more cautiously employed during the COVID-19 pandemic. Recently, helmet ventilation has been identified as the optimal treatment for acute hypoxia respiratory failure caused by COVID-19 due to its ability to deliver NIV respiratory support with high tolerability, low air leakage, and improved seal integrity. In the present review, we provide an evidence-based overview of the use of helmet ventilation in children with respiratory failure.

Medicinal Components in Edible Mushrooms on Diabetes Mellitus Treatment.

Mushrooms belong to the family "Fungi" and became famous for their medicinal properties and easy accessibility all over the world. Because of its pharmaceutical properties, including anti-diabetic, anti-inflammatory, anti-cancer, and antioxidant properties, it became a hot topic among scientists. However, depending on species and varieties, most of the medicinal properties became indistinct. With this interest, an attempt has been made to scrutinize the role of edible mushrooms (EM) in diabetes mellitus treatment. A systematic contemporary literature review has been carried out from all records such as Science Direct, PubMed, Embase, and Google Scholar with an aim to represents the work has performed on mushrooms focuses on diabetes, insulin resistance (IR), and preventive mechanism of IR, using different kinds of mushroom extracts. The final review represents that EM plays an important role in anticipation of insulin resistance with the help of active compounds, i.e., polysaccharide, vitamin D, and signifies α-glucosidase or α-amylase preventive activities. Although most of the mechanism is not clear yet, many varieties of mushrooms' medicinal properties have not been studied properly. So, in the future, further investigation is needed on edible medicinal mushrooms to overcome the research gap to use its clinical potential to prevent non-communicable diseases.

Clinical Manifestations of Pediatric Food Allergy: a Contemporary Review.

Food allergies (FAs) are an emerging health care issue, and a "second wave of the allergy epidemic" was named. There are extensive data that documented the prevalence rate as high as approximately 10%. FAs are immunological adverse reactions, including IgE-mediated mechanisms, cell-mediated mechanisms, or mixed IgE- and cell-mediated mechanisms. A diagnosis of FA is made by specific symptoms encounter with food, detailed past history, sensitization tests, and oral food challenges (OFCs) if necessary. The component-resolved diagnostics (CRD) test can distinguish true or cross-reaction. "Minimal elimination" from the results of CRD and OFC could avoid unnecessary food restriction. Strict food limitation is harsh and stressful on patients and their families. Children with FAs experience a higher rate of post-traumatic stress symptoms (PTSS) and bullying than others. In the last 20 years, oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) are treatment strategies. OIT and EPIT are the most two encouraging treatments for FA. This review aims to introduce FAs in diverse clinical disorders, new perspectives, and their practical implications in diagnosing and treating FA.

Pediatric sigmoid colonic perforation with Campylobacter enterocolitis: a case report and review of the literature.

BACKGROUND: Campylobacter-related infectious gastroenteritis is common and usually self-limited. Intestinal perforation is a rare complication of the infectious colitis caused by Campylobacter, and only handful of cases have been reported. This is the first published case report of pediatric Campylobacter intestinal perforation located in the sigmoid colon. CASE PRESENTATION: A 15-year-old previously Taiwanese healthy boy presented with 5 days of fever up to 39.8 °C, with right lower quadrant abdominal pain and watery diarrhea. Although he received antimotility agents and antipyretics at a local clinic to relieve symptoms, he came to the emergency department with signs of shock manifesting as hypothermia to 35.2 °C, tachycardia, and low blood pressure. Laboratory testing demonstrated leukocytosis with left shift and significant elevation of C-reactive protein. Stool and blood cultures were obtained, and he was admitted for fluid challenge and antibiotic treatment. On the second day of admission, he suffered from sudden onset of severe, diffuse abdominal pain. Physical examination revealed muscle guarding, rebounding tenderness, and silent bowel sound. Abdominal X-ray showed subdiaphragmatic free air at standing view. The patient underwent emergent exploratory laparotomy, which revealed sigmoid colon perforation about 0.5 cm. Enterolysis and repair of sigmoid colon were performed. Intraoperative stool specimen nucleic acid amplification testing had turned positive for Campylobacter spp. with negative results for other bacterial pathogens. His symptoms improved and he tolerated food well, and was discharged 15 days after admission. CONCLUSIONS: We present this case because of the rarity of Campylobacter-induced sigmoid colon perforation in the pediatric population. It is important to keep in mind that sigmoid colon perforation can be due to an infectious cause, and one of the culprits can be Campylobacter. Infectious colitis caused by Campylobacter spp. should be managed cautiously and the use of antimotility agents in such conditions should be considered judiciously.

The combined effects of nucleotide-binding domain-like receptor protein 3 polymorphisms and levels of blood lead on developmental delays in preschool children.

Nucleotide-binding domain-like receptors protein 3 (NLRP3) inflammasomes are associated with neuroinflammation and multiple NLRP3 genes regulate NLRP3 expression. Our study aimed to investigate the association of NLRP3 polymorphisms with developmental delay in preschool children. We also explored whether NLRP3 polymorphisms modified the effects of total urinary arsenic and blood cadmium and lead to developmental delays. A total of 178 children with developmental delays and 88 healthy children were analyzed for urinary arsenic concentrations and red blood cell lead and cadmium concentrations. We examined the genotypes of fifteen common single-nucleotide polymorphisms in NLRP3. We observed that levels of total urinary arsenic and blood lead were significantly associated with developmental delay. The NLRP3rs10754555 CG versus CC/GG, NLRP3rs12048215 AG versus AA/GG, and NLRP3rs12137901 TC/TT versus CC genotype showed a lower odds of developmental delay, with the odds ratio (OR) and 95% confidence interval (CI) = 0.38 (0.19-0.75), 0.52 (0.27-0.99), and 0.33 (0.12-0.90), respectively. Children with the NLRP3rs10754555 CC/GG genotype and high blood lead levels had a significant multiplicative interaction with developmental delay [OR (95% CI) = 9.74 (3.59-26.45)]. This study found evidence that suggested the joint effects of NLRP3rs10754555 CC/GG genotype and high blood lead levels on developmental delays.