Clinical characteristics of postoperative necrotizing enterocolitis in patients with congenital jejunoileal atresia and its risk factors.

Objective: To review postoperative necrotizing enterocolitis (NEC) in patients with jejunoileal atresia (JIA) and to explore the potential risk factors related to the concurrence of NEC. Methods: Patients diagnosed with JIA who received surgical treatment from January 2016 to June 2021 were enrolled. Demographics, viral infection of the fetus, transfusion within 48 hours before NEC, sepsis before JIA repair, pathological and anatomical classification of JIA, combined malformation, occurrence time of NEC after the operation, treatment, and prognosis of patients were analyzed. Patients were divided into NEC group and non-NEC group, and all patients were followed up for 3-6 months to observe for complications. Results: A total of 180 patients with JIA were included, of whom 12 were diagnosed with NEC after surgery and 1 patient with NEC died during follow-up. The average age, birth weight, gestational age, proportion of premature infants, proportion of preoperative infections, and pathological classification of JIA did not significantly differ between the two groups. The probability of patients with proximal jejunal atresia (PJA) in the NEC group (58.3%) was higher than that in the non-NEC group (22.6%) (p=0.011), and patients with PJA had longer parenteral nutrition time than patients without PJA (26.64±9.21 days vs 15.11±6.58 days, p<0.001). Conclusion: PJA was more likely to be associated with concurrent NEC after surgery, which is a highly NEC-related risk factor inherent in JIA.

Head-to-head comparison of 18F-FDG PET/CT and 18F-FDG PET/MRI for lymph node metastasis staging in non-small cell lung cancer: a meta-analysis.

PURPOSE: The current meta-analysis aimed to compare the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) with 18F-FDG PET/magnetic resonance imaging (MRI) in non-small cell lung cancer (NSCLC) lymph node metastasis staging. METHODS: We searched the PubMed, Web of Science, and Embase databases for relevant articles between November 1992 and September 2022. Studies evaluating the head-to-head comparison of 18F-FDG PET/CT and 18F-FDG PET/MRI for lymph node metastasis in patients with NSCLC were included. The quality of each study was assessed using the Quality Assessment of Diagnostic Performance Studies-2 tool. RESULTS: The analysis includes six studies with a total of 434 patients. The pooled sensitivity of 18F-FDG PET/CT and 18F-FDG PET/MRI was 0.78 [95% confidence interval (CI): 0.59-0.90] and 0.84 (95% CI: 0.68-0.93), and the pooled specificity was 0.87 (95% CI: 0.72-0.94) and 0.87 (95% CI: 0.80-0.92), respectively. The accuracy of 18F-FDG PET/CT and 18F-FDG PET/MRI was 0.81 (95% CI: 0.71-0.90) and 0.84 (95% CI: 0.75-0.92), respectively. When the pre-test probability was set at 50%, the post-test probability for 18F-FDG PET/CT could increase to 85%, and the post-test probability for 18F-FDG PET/MRI could increase to 87%. CONCLUSION: 18F-FDG PET/CT and 18F-FDG PET/MRI have similar diagnostic performance in detecting lymph node metastasis in NSCLC. However, the results of this study were from a small sample study, and further studies with larger sample sizes are needed.

Diagnostic potential of [18F]FDG PET/MRI in non-small cell lung cancer lymph node metastasis: a meta-analysis.

PURPOSE: This meta-analysis evaluated the diagnostic accuracy and diagnostic value of [18F]FDG PET/MRI for mediastinal lymph node staging of NSCLC. METHODS: Relevant articles in PubMed, Embase, Web of Science, and the Cochrane Library were searched until January 2023. Research evaluating [18F]FDG PET/MRI for mediastinal lymph node staging of NSCLC was included. Pooled estimates of sensitivity, specificity, PLR, and NLR were calculated by the "Stata" software. RESULTS: Nine researches were included, containing 618 patients. The pooled sensitivity of [18F]FDG PET/MRI for detecting mediastinal lymph node staging of NSCLC was 0.82 (0.70-0.90), and the pooled specificity was 0.88 (0.82-0.93). PLR and NLR were 7.38 (4.73-11.52) and 0.20 (0.11-0.36), respectively. The AUC value of this imaging modality was 0.92 (0.90-0.94). The post-test probability for [18F]FDG PET/MRI might rise to 88% when the pre-test probability was set at 50%. CONCLUSIONS: We considered [18F]FDG PET/MRI as an effective imaging tool with relatively high specificity and sensitivity. It has great potential to be used in the clinical management of patients in NSCLC who are amenable to early surgery. More studies with large sample sizes in the same direction are needed in future to obtain more reliable evidence-based support.

The safety and effectiveness of Santulli enterostomy in neonatal intestinal conditions.

Background: As an end stoma, Santulli enterostomy provides early restoration of intestinal continuity without formal laparotomy. Short amputation of the common limb enables closure on a side to restore anatomic continuity without sacrificing valuable intestine; additionally, the procedure is simple and safe. Most newborns who require enterostomy might benefit from Santulli enterostomy; however, several pediatric surgeons lack information regarding this procedure. Therefore, we have reviewed our experience about Santulli enterostomy and explore the advantages and indications in neonatal intestinal conditions. Methods: The clinical data of 76 neonates who underwent enterostomywere obtained. The patients were divided into two groups: the Santulli group with 33 cases who underwent Santulli enterostomy, and the control group with 43 cases who underwent double- or single-lumen ostomy. The general data of the two groups were analyzed, and the perioperative/postoperative complications, clinical data and the long-term outcomes were compared. Results: There was no difference in the demographic informations, the level of enterostomy, the rate of high-sight stoma, the operative time and bleeding of enterostomy between the two groups. Compared to the control group, the operative time of ostomy closure was less in the Santulli group (53.00 vs. 152.47, P < 0.001). The duration of parenteral nutrition (27.45 vs. 44.56, P = 0.010), the mean interval of initial enterostomy to stomal closure (131.21 vs. 216.42, P < 0.001), and length of stay (46.00 vs. 67.60, P = 0.007) were shorter, while the incidence of postoperative complications and hospitalization costs (11.21 vs. 15.49, P = 0.006) were lower. The Santulli procedure can reduce the morbidity of high output ostomy (2 vs. 10, P = 0.042) and short bowel syndrome (3 vs. 132, P = 0.025), shorten the discrepancy of diameter between the proximal and distal segments, maximize the available intestine, and monitor the movement of the distal bowel. The length of incision was shorter, and the catch-up growth was significantly faster in the Santulli group. Conclusion: Santulli enterostomy is a superior procedure in the treatment of neonatal intestinal conditions, in terms of fewer complications, faster catch-up growth, shorter hospitalization time and treatment duration. It should be the procedure of choice in several newborns with intestinal conditions that require ostomy.

TNF-α induces autophagy through ERK1/2 pathway to regulate apoptosis in neonatal necrotizing enterocolitis model cells IEC-6.

Necrotizing enterocolitis (NEC) is a potentially fatal illness in premature neonates. Tumor necrosis factor-α (TNF-α) and autophagy are associated with the pathogenesis of NEC. This study aimed to explore whether TNF-α might regulate apoptosis in neonatal NEC model cells IEC-6 via regulation of autophagy. NEC rat model was induced by hand feeding and exposure to asphyxia/cold-stress for histologic examination. The NEC in vitro model (IEC-6/NEC cells) was established by stimulating the intestinal epithelial cell line IEC-6 with lipopolysaccharide (LPS, 100 µg/mL) for 3 h to investigate the effects of TNF-α on IEC-6 proliferation and apoptosis. In this study, NEC rats showed decreased proliferating cell nuclear antigen (PCNA) expression, increased TUNEL-positive cells, higher expression of TNF-α, p-ERK1/2, and autophagy-related proteins in rat small intestine compared with their controls. Additionally, the LPS-stimulated IEC-6/NEC cells showed a significantly decreased proliferation and increased apoptosis compared with the control cells. Furthermore, the LPS-stimulated IEC-6/NEC cells exhibited enhanced autophagy level, as evidenced by a dose-dependent increase in Beclin-1 protein expression, LC3II/LC3I ratio and accumulation of MDC-positive autophagic vacuoles. Moreover, inhibition of autophagy by wortmannin or LY294002 significantly abolished the LPS-mediated decreased proliferation and increased apoptosis of IEC-6/NEC cells. Results also showed that inhibition of ERK1/2 pathway using U0126 significantly inhibited TNF-α-induced autophagy. Furthermore, the TNF-α-mediated inhibition of IEC-6 proliferation and promotion of IEC-6 apoptosis was abolished by U0126. Our findings demonstrated that TNF-α might induce autophagy through ERK1/2 pathway to regulate apoptosis in neonatal NEC cells IEC-6. Our study enhances our understanding of neonatal NEC pathogenesis.

Gene expression profile of TLR7 signaling pathway in the liver of rhesus rotavirus-induced murine biliary atresia.

PURPOSE: To identify genes potentially involved in the pathogenesis of bile duct obstruction in biliary atresia (BA). METHODS: We used rhesus rotavirus (RRV) Balb/c mouse BA model to study BA. Liver and serum samples were harvested from BA and normal control (NC) groups at 1, 3, 5, 7, 10 and 14 days postinoculation. Serum total bilirubin (STB) and conjugated bilirubin (CB) were measured. Livers of each group at day 7 were used for a genome-wide expression analysis. Expression of TLR7 signaling pathway in liver was measured by immunohistochemical staining and western blotting, including expression of TLR7, activation of phosphorylated IRF7 and secretion of IFN-ß, IL-1α and IL-6. Cell viability and survival rate after RRV infection were measured by using TLR7 knockdown human cholangiocarcinoma cell RBE. RESULTS: STB was significantly elevated from day 5 postinoculation and CB was from day 7 postinoculation, while CK19 (the biomarker of biliary epithelial cells) expression by western blotting was decreased. By microarray analysis of liver tissues at day 7 postinoculation, TLR7 signaling pathway was up-regulated in BA mice. Based on the results of microarray analysis, the protein expression of TLR7 in the liver tissues of BA groups were found to be up-regulated from day 5 comparing to respective NC groups, although it was increased as pups aged in NC groups. And the level of p-IRF7 and secretion of cytokines were also statistically significant in BA groups. In vitro, TLR7 knockdown cell line showed less cellular proliferation and more susceptible to RRV infection. CONCLUSION: By in vivo study, TLR7 signal pathway was up-regulated in BA group; by additional in vitro study, intact TLR7 signal pathway might have some protective abilities in BA pathogenesis.

Anorectal malformation associated with a mutation in the P63 gene in a family with split hand-foot malformation.

PURPOSE: The aims of this study were to identify the mutation gene of a Chinese family with anorectal malformation (ARM) associated with split hand-foot malformation and to determine the spatiotemporal expression of the mutated gene during hindgut and anorectum development in human embryos. METHOD: A Chinese family with intrafamilial clinically variable manifestation was analyzed and primers were designed for exons 3-14 of P63, DLX5, DLX6, DAC, and HOXD13 as candidate genes and direct sequence analysis of the exons was performed. Immunohistochemical study of mutated gene in the hindgut and anorectum of human embryos of 4th-10th weeks was performed. RESULT: Affected individuals were found to have an Arg227Gln P63 gene mutation. From the 4th-10th weeks of gestation of the human embryo, the P63-positive cells were mainly located on the epithelium of the apical urorectal septum, hindgut, and cloacal membrane. After the anorectum ruptured during the 8th week, the P63 remained strongly immunoreactive on the epithelium of the anal canal and urethra, but the mucous membrane of the rectum exhibited no reaction. CONCLUSIONS: The mutation identified strongly suggests a causal relationship between the ARM phenotype and P63. The expression of P63 was persistently active during the dynamic and incessant septation of the cloaca and hindgut, suggesting that P63 may play a pivotal role in the morphogenesis of the hindgut and anorectum.