Targeted LC-MS/MS profiling of bile acids reveals primary/secondary bile acid ratio as a novel biomarker for necrotizing enterocolitis.

Bile acids (BAs) are involved in the development of necrotizing enterocolitis (NEC), which mainly occurs in preterm infants. We aim to identify the change of BAs in preterm infants and validate its potential value in the detection of NEC. Targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to measure the plasma BAs in healthy preterm infants and patients with NEC. By analyzing the level of BAs in healthy preterm infants, we found that the plasma concentrations of BAs were related to sex, gestational/postnatal age, birth weight, mode of birth, and feeding type after birth. The plasma levels of TCA, GCA, TCDCA, GCDCA, primary BAs, and total BAs and the primary/secondary BA ratio were decreased, while DCA, UDCA, and secondary BAs were increased in NEC. The primary/secondary BA ratio (cutoff point 62.9) can effectively differentiate NEC from healthy preterm infants, with an AUC of 0.9, a sensitivity of 94.5%, and a specificity of 78.1%. Combining the ratio with high-risk factors of NEC can better distinguish between NEC and control, with an AUC of 0.95. Importantly, significantly lower levels of primary/secondary BA ratio were found in infants with surgical NEC than in nonsurgical NEC cases. The cutoff point of 28.7 identified surgical NEC from nonsurgical NEC with sensitivity and specificity of 76.9% and 100%. Thus, our study identified that the primary/secondary BA ratio in the plasma can differentiate NEC from healthy preterm infants and effectively differentiate the surgical NEC from nonsurgical NEC. Therefore, LC-MS/MS was expected to be a novel measurement platform used to distinguish infants who are most in need of close monitoring or early surgical intervention.

Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis.

Epigenetic alterations are especially important in necrotizing enterocolitis (NEC). Here, we reported that histone deacetylase 8 (HDAC8) plays a previously unknown role in modulating arginine metabolism via acetylation of histone 3 lysine 9 (acetyl-H3K9) regulation during the pathogenesis of NEC. We found that HDAC8 was upregulated in humans and mice intestinal samples with NEC, while selective inhibition of HDAC8 expression ameliorated NEC. HDAC8 regulates enzymes involved in the metabolic conversion of proline to arginine (PRODH, PRODH2, OAT, and OTC) and arginine to ornithine (ARG1). The results showed that H3K9ac signal in the PRODH/PRODH2 promoter region was mediated by HDAC8. Additionally, the decreased concentration of butyric acid was strongly correlated with elevated HDAC8 levels and circulating arginine, which may result from an unbalanced Firmicutes/Bacteroidetes ratio. These results reveal previously underappreciated roles of microbial metabolites and HDAC8 to coordinate the arginine metabolism during NEC development.

Primary omental torsion in children: single-center experience of 17 cases.

OBJECTIVE: Primary omental torsion (POT) is a rare condition in children often misdiagnosed because of a lack of clinical manifestations. Here we present insights gained from the treatment of pediatric POT cases at a single center over 8 years and summarize some influencing factors found in diagnosis and treatment, in order to reduce the misdiagnosis of POT in children in the future. METHODS: Demographic and clinical data of 17 children with POT treated in Shanghai Children's Hospital, Shanghai Jiaotong University from June 2012 to December 2020 were reviewed. RESULTS: The mean age of the 17 pediatric patients was 7.65 ± 2.12 years (range: 4-12 years), sixteen were male. The average time from the pain onset to operation was 73.82 ± 47.21 h (range: 21-144 h). In 5 cases, the ultrasound scan revealed a low-intensity inflammatory mass in the abdominal cavity. Only 1 of the 17 patients had normal body mass index, while others were overweight or obese. The mean computed tomography (CT) value of the mass in the lower right abdomen was - 58.74 ± 10.32 HU (range: - 70 to - 46 HU), which is close to that of its own abdominal wall fat [- 46.29 ± 9.45 HU (range: - 62 to - 32 HU)]. The location of the mass was located in front of the right colon in ten cases, except for two cases near the ligamentum teres. Five patients had whirl sign on CT images and 8 patients had pelvic fluid. Five cases were diagnosed as acute appendicitis and 12 were diagnosed as POT, the preoperative diagnosis was correct in 70.59% of cases. All 17 patients were treated with laparoscopic omentectomy. The average duration of hospitalization was 5.53 ± 1.12 days (range: 4-8 days). All cases were followed up. 1 case relapsed 8 months post operation, while the remaining cases had no complications. CONCLUSION: POT is rare in children with acute abdominal pain, which is more common in obese boys. The fatty mass in front of colon and between rectus abdominis sheath in CT image is specific, which is helpful for diagnosis of POT. Laparoscopy is an effective method for the treatment of POT in children.

Primary cutaneous lymphoma in children: A report of four cases.

Chen F, Liu J, Lv Z, Huang Y, Wu Y. Primary cutaneous lymphoma in children: A report of four cases. Turk J Pediatr 2018; 60: 739-743. Primary cutaneous lymphoma (CL) is a malignant lymphoma presenting in the skin. Primary CL is rare in children and difficult to clinically diagnose. We report four pediatric cases of primary CL with tumors in different body area: case 1, on the face and left thigh; case 2, on the left side of the neck; case 3, on the left side of the back; and case 4, on the left buttock. The first diagnoses of these children were rash, abscess, lymphadenitis, and fever, respectively in local hospitals. All 4 patients were diagnosed as primary CL by histopathologic examination in our hospital. Three patients (case 1, case 2 and case 4) were treated with chemotherapy. The size of tumor and degree of cutaneous lesion were alleviated after chemotherapy. Case 3 refused to receive chemotherapy, and died. The cases indicated the importance of early diagnosis of primary CL to guide appropriate therapy.