Serum salicylic acid levels in children with Kawasaki disease.

BACKGROUND: This study aimed to clarify serum salicylic acid (SA) levels in patients with Kawasaki disease (KD) after the administration of moderate-dose acetylsalicylic acid (ASA) and their relationship with the therapeutic effect. METHODS: We retrospectively analyzed the clinical data of 142 children with KD. We measured serum SA trough levels during the acute and recovery periods and determined their relationship with clinical and laboratory parameters. RESULTS: The median age of patients was 2.4 years. Thirty-one patients had incomplete KD, 29 were intravenous immunoglobulin (IVIG) non-responders, and one patient had coronary artery lesions. The median ASA dose was 49.7 mg/kg/day. The median serum SA level was 22 µg/mL in the acute period and 15 µg/mL in the recovery period, with 45 (33%) in the acute period and 60 (44%) in the recovery period below the limit of measurement (< 10 µg/mL). Serum SA levels during the recovery period were significantly lower in patients who received steroids. There were no significant differences in IVIG responsiveness based on serum SA levels. CONCLUSIONS: Serum SA trough levels in KD patients treated with moderate-dose ASA were highly variable and did not reach sufficient levels. Serum SA levels were not associated with IVIG responsiveness.

Determining the Treatment Strategy for Refractory Ulcerative Colitis Using Prostaglandin E-major Urinary Metabolite (PGE-MUM) Measurement.

Prostaglandin E-major urinary metabolite (PGE-MUM) is a valuable biomarker reflecting the cytokine profile. We encountered a case of a 14-year-old boy with pan-colitis-type ulcerative colitis who was unresponsive to steroids and infliximab. The patient's clinical symptoms gradually deteriorated and surgical treatment was strongly considered because anti-inflammatory therapy was unlikely to be effective. PGE-MUM levels were markedly elevated, indicating a T-helper 17 (Th17)-like cytokine profile. Because an antibody against interleukin 23 (IL-23) was presumed to be effective, the patient was treated with mirikizumab, after which he achieved remission. In the present case, measurement of PGE-MUM levels was useful in selecting anti-cytokine treatments for severe ulcerative colitis.

Importance of preoperative total colonoscopy and endoscopic resection after self-expandable metallic stent placement for obstructive colorectal cancer as a bridge-to-surgery.

BACKGROUND AND AIM: Colonic self-expandable metallic stent (SEMS) placement enables preoperative total colonoscopy (TCS) in patients with obstructive colorectal cancer. Following SEMS placement, it is possible to assess the presence or absence of synchronous proximal colon cancers and perform preoperative endoscopic resection (ER) for neoplastic lesions proximal to the primary lesion. The objective of this study was to determine the usefulness and safety of preoperative TCS and ER after SEMS placement in patients with obstructive colorectal cancer. METHODS: From April 2016 to March 2022, we enrolled 100 patients with obstructive colorectal cancer who underwent SEMS placement, including 86 patients who underwent preoperative TCS after SEMS placement. Complications associated with preoperative TCS and ER after SEMS placement and the characteristics of the neoplastic lesions were assessed. RESULTS: The success rate of SEMS placement as bridge-to-surgery was 98.0%; six patients had associated complications. Preoperative TCS was performed 8 (range: 1-30) days after SEMS placement. Four patients had synchronous advanced cancers. Nine non-advanced synchronous cancers, 116 adenomas, and 18 sessile-serrated lesions were treated by preoperative TCS and ER after SEMS placement. No procedure-related complications, namely stent migration, bleeding, and perforation were observed. Forty-five patients underwent follow-up TCS 1 year after surgery. Only one patient with submucosal invasive cancer required a second surgery. CONCLUSIONS: Preoperative TCS and ER after SEMS placement was performed with no complications. This approach allows preoperative evaluation of the entire colon and the treatment of precancerous lesions. (240 words).

Utility of a rapid assay for prostaglandin E-major urinary metabolite as a biomarker in pediatric ulcerative colitis.

Prostaglandin E-major urinary metabolite (PGE-MUM) is a urinary biomarker reflecting ulcerative colitis (UC) activity. This prospective observational study aimed to evaluate the usefulness of PGE-MUM via rapid chemiluminescent enzyme immunoassay in detecting endoscopic remission (ER) and histologic remission (HR) in pediatric UC (6-16 years) in comparison with fecal calprotectin (FCP). ER and HR were defined as Mayo endoscopic score (MES) of 0 and Matts' histological grades (Matts) of 1 or 2, respectively. A total of 104 UC and 39 functional gastrointestinal disorder (FGID) were analyzed. PGE-MUM levels were significantly higher in the UC group than in the FGID group (P < 0.001). FCP levels were significantly elevated in the group without ER and HR than in the group with ER and HR (P < 0.001 and P = 0.001), whereas PGE-MUM levels were significantly higher in the group without ER compared to the group with ER (P < 0.001). No significant differences were noted in the AUCs for PGE-MUM and FCP in detecting ER and HR. Although PGE-MUM was inferior to FCP for the detection of HR, it might have the potential for application as a biomarker of endoscopic activity in pediatric UC owing to its noninvasive and rapid method.

Bacteremia Caused by Kalamiella piersonii Found in an Infant During the Course of Gastrointestinal Food Allergy.

Kalamiella piersonii is rare pathogen, and its pathogenicity to humans has been unknown. We describe an infant with bacteremia caused by Kalamiella piersonii. The patient was a 2-month-old girl presented with diarrhea, poor oral intake, and vomiting. The patient was tentatively diagnosed with acute enterocolitis. After admission, the patient developed a fever and blood culture yielded Gram-negative cocci, first determined to be Pantoea septica by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. However, genetic analysis of 16S rRNA allowed its identification as Kalamiella piersonii (GenBank accession number is OQ547240). Other housekeeping genes such as gyrB, rpoB, and atpD also identified the isolated strain as Kalamiella piersonii. The patient was successfully treated with cefotaxime without sequelae. Later, the patient was diagnosed as non-IgE-mediated gastrointestinal food allergy. Our experience indicated that Kalamiella piersonii is a potential human pathogen that can cause invasive infections even in infants and children. Identification of Kalamiella piersonii is difficult with routine conventional tests, and detailed studies including genetic analyses are necessary to clarify the pathogenicity of Kalamiella piersonii in humans.

Radial nerve palsy caused by a rapidly growing intramuscular hematoma in an infant with biliary atresia: a case report.

BACKGROUND: Biliary atresia (BA) is a rare cause of persistent jaundice in infants that can result in vitamin K malabsorption and vitamin K deficiency bleeding (VKDB). We present an infant with BA who developed a rapidly growing intramuscular hematoma in her upper arm after a vaccination which caused a radial nerve palsy. CASE PRESENTATION: An 82-day-old girl was referred to our hospital because of a rapidly growing left upper arm mass. She had received three doses of oral vitamin K before age 1 month. At age 66 days, she received a pneumococcal vaccination in her left upper arm. On presentation, she showed no left wrist or finger extension. Blood examination revealed direct hyperbilirubinemia, liver dysfunction, and coagulation abnormalities, indicating obstructive jaundice. Magnetic resonance imaging showed a hematoma in the left triceps brachii. Abdominal ultrasonography revealed an atrophic gallbladder and the triangular cord sign anterior to the portal vein bifurcation. BA was confirmed on cholangiography. VKDB resulting from BA in conjunction with vaccination in the left upper arm were considered the cause of the hematoma. The hematoma was considered the cause of her radial nerve palsy. Although she underwent Kasai hepatic portoenterostomy at age 82 days, the obstructive jaundice did not sufficiently improve. She then underwent living-related liver transplantation at age 8 months. The wrist drop was still present at age 1 year despite hematoma resolution. CONCLUSIONS: Delayed detection of BA and inadequate prevention of VKDB can result in permanent peripheral neuropathy.

Safety and efficacy of the endoscopic delivery of capsule endoscopes in adult and pediatric patients: Multicenter Japanese study (AdvanCE-J study).

BACKGROUND AND AIM: We retrospectively determined the safety and efficacy of the endoscopic delivery (ED) of capsule endoscopes. METHODS: We enrolled 10,156 patients who underwent small bowel capsule endoscopy (SBCE), 3182 who underwent patency capsule (PC), and 1367 who underwent colon capsule endoscopy (CCE), at 11 gastroenterological and nine pediatric centers. RESULTS: Small bowel capsule endoscopies, PCs, and CCEs were endoscopically delivered to 546 (5.4%), 214 (6.7%), and 14 (1.0%) patients, respectively. Only mild complications occurred for 21.6% (167/774), including uneventful mucosal damage, bleeding, and abdominal pain. Successful ED of SBCE to the duodenum or jejunum occurred in 91.8% and 90.7% of patients aged <16 years and ≥16 years, respectively (P = 0.6661), but the total enteroscopy rate was higher in the first group (91.7%) than in the second (76.2%, P < 0.0001), for whom impossible ingestion (87.3%) was significantly more common than prolonged lodging in the stomach (64.2%, P = 0.0010). Successful PC and CCE delivery to the duodenum occurred in 84.1% and 28.6%, thereafter the patency confirmation rate and total colonoscopy rate was 100% and 61.5%, respectively. The height, weight, and age cutoff points in predicting spontaneous ingestion were 132 cm, 24.8 kg, and 9 years 2 months, respectively, in patients aged <16 years. Patients aged ≥16 years could not swallow the SBCEs mainly due to dysphagia (75.0%); those who retained it in the esophagus due to cardiac disease (28.6%), etc. and in the stomach due to diabetes mellitus (15.7%), etc. CONCLUSIONS: This large-scale study supports the safety and efficacy of ED in adult and pediatric patients. UMIN000042020.

Constitutional mismatch repair deficiency in childhood colorectal cancer harboring a de novo variant in the MSH6 gene: a case report.

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is caused by biallelic pathogenic variants in one of the mismatch repair genes, and results in early onset colorectal cancer, leukemia, brain tumors and other childhood malignancies. Here we report a case of CMMRD with compound heterozygous variants in the MSH6 gene, including a de novo variant in multiple colorectal cancers. CASE PRESENTATION: An 11-year-old girl, who presented with multiple spots resembling café-au-lait macules since birth, developed abdominal pain, diarrhea and bloody stool over two months. Colonoscopy revealed multiple colonic polyps, including a large epithelial tumor, and pathological examination revealed tubular adenocarcinoma. Brain magnetic resonance imaging (MRI) showed an unidentified bright object (UBO), commonly seen in neurofibromatosis type 1 (NF1). Genetic testing revealed compound heterozygous variants, c. [2969T > A (p.Leu990*)] and [3064G > T (p.Glu1022*)] in the MSH6 gene; c.2969T > A (p.Leu990*) was identified as a de novo variant. CONCLUSIONS: We present the first report of a CMMRD patient with a de novo variant in MSH6, who developed colorectal cancer in childhood. CMMRD symptoms often resemble NF1, as observed here. Physicians should become familiar with CMMRD clinical phenotypes for the screening and early detection of cancer.

Intussusception Caused by Percutaneous Endoscopic Gastrostomy With Jejunal Extension in Patients With Severe Motor and Intellectual Disabilities.

The risk of intussusception related to percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) in patients with severe motor and intellectual disabilities (SMID) remains unknown. In a cross-sectional study, a review of 26 patients (mean age, 11.6 ± 6.4 years) with SMID who underwent PEG-J was performed. During the follow-up period, 6 of 26 (23%) patients developed intussusception. The median period from PEG-J to the onset of intussusception was 364 (range, 8-1344) days. No significant difference was observed in the Cobb angle between the intussusception and nonintussusception groups; however, body mass index at the time of PEG-J was significantly lower in the intussusception group. Intussusception related to PEG-J occurs relatively frequently in patients, and it is possibly attributable to factors such as deformity caused by undernutrition and weight loss. If enteral nutrition via PEG-J has been established, earlier enterostomy can be recommended because of the high risk of intussusception in patients with SMID.

A novel de novo SLC26A3 mutation causing congenital chloride diarrhea in a Japanese neonate.

BACKGROUND: Congenital chloride diarrhea (CCD) is characterized by persistent chloride (Cl)-rich diarrhea evident from birth. CCD is a rare autosomal recessive disorder caused by defects in the solute carrier family 26 member 3 (SLC26A3) gene, which encodes an intestinal Cl- /HCO3- , Na+ -independent exchanger. Various mutations of SLC26A3 have been described in CCD. However, no de novo mutations have been found to be responsible for CCD. Here we report the first such occurrence. METHODS: Clinical and laboratory findings during the perinatal period were obtained retrospectively from medical records. Mutations involving SLC26A3 were detected by Sanger sequencing. RESULTS: The male infant reported here was delivered at 29 weeks of gestation. Just after birth, he had watery diarrhea without meconium passage. High chloride concentrations in the diarrhea led to a diagnosis of CCD. Direct sequencing of all coding exons in SLC26A3 including exon-intron boundaries disclosed 2 compound heterozygous mutations: c.382G>A, p.G128S and c.2063-1g>t. The c. 2063-1g>t mutation was confirmed in his mother's DNA, but c.382G>A, p.G128S was absent in both mother and father. CONCLUSION: We concluded that c.382G>A, p.G128S represented a de novo mutation of SLC26A3, a very rare event in autosomal recessive disorders. To our knowledge, this is the first CCD case involving a de novo novel mutation of SLC26A3.

Efficacy and safety of a capsule endoscope delivery device in children.

OBJECTIVES: This multicenter, cross-sectional study aimed to elucidate the efficacy and safety of the AdvanCE capsule endoscope delivery device for children in Japan. METHODS: The present study analyzed 183 cases of small bowel capsule endoscope (SBCE) insertion performed using the AdvanCE in 154 patients aged less than 18 years at participating institutions between 2013 and 2017. Statistical analyses were conducted to identify factors contributing to the completion rate for the entire small intestine examination, small intestine transit time, adverse events and technical issues. RESULTS: The commonest reason for using the AdvanCE was the patient's inability to swallow the SBCE, which was attributed to young age. SBCE was successfully delivered into the stomach or duodenum in 180 cases and was placed in the duodenum in 90% patients. In 89% patients, the entire small intestine was completely examined, and in 63% patients, findings leading to a new diagnosis or involving changing or maintaining the treatment strategy were obtained. No severe adverse events were observed; however, mild adverse events were observed in 35% patients. No factors considerably contributed to the completion rate for the entire small intestine examination or small intestine transit time and onset of technical issues. The factors that contributed to mild adverse events included intravenous anesthesia, technical issue, and absence of prior insertion of a patency capsule using the AdvanCE. CONCLUSION: The AdvanCE is well tolerated and effective for children.

Significance of Molecular Monitoring of T Cells for the Decision of Treatment Strategy for Epstein-Barr Virus-associated Hemophagocytic Lymphohistiocytosis.

A 17-year-old patient with Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis achieved first remission after immunochemotherapy (ICT). However, he had fever with an increase in soluble interleukin-2 receptor, but not in ferritin. Molecular analysis revealed augmented plasma and T-cell EBV loads and reappearance of clonal T cells. Despite achieving second remission, the T-cell EBV load at week 8 after second ICT was almost similar to that at week 8 after first ICT. Hence, cyclosporine was decreased over a 9-month period, with molecular monitoring of plasma and T cells. In this article, we describe how useful molecular monitoring was for detecting relapse and resuming ICT.

Clinical features of Helicobacter pylori antibody-positive junior high school students in Nagano Prefecture, Japan.

BACKGROUND: Previously, we conducted an epidemiological study screening for Helicobacter pylori antibody positivity among Japanese junior high school students. In this study, we updated the epidemiological data and assessed the clinical features of H pylori antibody-positive junior high school students. MATERIALS AND METHODS: We assessed H pylori antibody-positive subjects who were identified between 2012 and 2015 at four junior high schools in Nagano Prefecture, Japan. H pylori infection was confirmed by urea breath test (UBT) or endoscopic examination. Endoscopy was performed after obtaining consent from the subject and their guardians. Eradication therapy consisted of triple therapy with proton pump inhibitor (PPI), amoxicillin (AMPC), and clarithromycin (CAM) or metronidazole (MNZ) for seven days. Eradication of H pylori was confirmed by UBT. We reviewed subjects' characteristics, endoscopic findings, histological findings, eradication regimes, outcomes, and adverse effects. RESULTS: The overall prevalence of H pylori antibody positivity was 3.2% (42/1298). We assessed thirteen H pylori antibody-positive subjects. Eight subjects had a family history of H pylori infection. Six subjects had abdominal pain, and two subjects had iron deficiency anemia (IDA). Twelve subjects underwent endoscopy; one subject had duodenal ulcer, eleven subjects had antral nodular gastritis, and six subjects showed grade 2 closed type atrophic border according to the Kimura-Takemoto classification. All subjects received eradication therapy; CAM was used in five subjects with CAM susceptibility as well as in three subjects with unknown information on CAM susceptibility, and MNZ was used in five subjects with CAM resistance. Eradication was successful in twelve subjects (one unconfirmed). There were three mild adverse effects (abdominal pain or diarrhea). CONCLUSIONS: Helicobacter pylori test for junior high school students represents an opportunity to diagnose the peptic ulcer, iron deficiency anemia, and gastric atrophy.

Vaccine-associated paralytic poliomyelitis in an infant with perianal abscesses.

We describe a case of vaccine-associated paralytic poliomyelitis (VAPP) in a 7-month-old infant with perianal abscesses. The infant had suffered from perianal abscesses from 3 weeks after birth. The abscesses repeatedly developed and spontaneously drained through the orifice. Twenty-seven days before admission, a live attenuated oral poliovirus vaccine (OPV) was given to the infant for the first time for routine immunization. His body temperature rose to 38°C 19 days after receiving the OPV and fell 4 days later. Flaccid paralysis of the right leg appeared 26 days after receipt of the OPV. A Sabin type 3 poliovirus was isolated from a stool obtained at admission. The DNA sequences of the VP1 region of the isolated virus were more than 99% identical with those of the vaccine strain. Mild muscle atrophy with moderate motor impairment in the right leg persisted at 18 months of age. One VAPP case provoked by a perianal abscess has been reported from the United Kingdom. Database search revealed that one of nine VAPP cases reported during 2003-2008 in Japan had a perianal abscess. Taken together, these reports and our case imply that we should give OPV with caution to infants with a perianal abscess.