Progranulin mitigates intestinal injury in a murine model of necrotizing enterocolitis by suppressing M1 macrophage polarization.

Neonatal necrotizing enterocolitis (NEC) is a critical digestive disorder frequently affecting premature infants. Characterized by intestinal inflammation caused by activated M1 macrophages, modulation of macrophage polarization is considered a promising therapeutic strategy for NEC. It has been demonstrated that the growth factor-like protein progranulin (PGRN), which plays roles in a number of physiological and pathological processes, can influence macrophage polarization and exhibit anti-inflammatory characteristics in a number of illnesses. However, its role in NEC is yet to be investigated. Our research showed that the levels of PGRN were markedly elevated in both human and animal models of NEC. PGRN deletion in mice worsens NEC by encouraging M1 polarization of macrophages and escalating intestinal damage and inflammation. Intravenous administration of recombinant PGRN to NEC mice showed significant survival benefits and protective effects, likely due to PGRN's ability to inhibit M1 polarization and reduce the release of pro-inflammatory factors. Our findings shed new light on PGRN's biological role in NEC and demonstrate its potential as a therapeutic target for the disease.

A comprehensive scoring system for the better prediction of bowel resection in pediatric intussusception.

BACKGROUND: Intussusception presents a significant emergency that often necessitates bowel resection, leading to severe complications and management challenges. This study aims to investigate and establish a scoring system to enhance the prediction of bowel resection necessity in pediatric intussusception patients. METHODS: This retrospective study analyzed 660 hospitalized patients with intussusception who underwent surgical management at a pediatric hospital in Southwest China from April 2008 to December 2020. The necessity of bowel resection was assessed and categorized in this cohort. Variables associated with bowel resection were examined using univariate and multivariate logistic regression analyses. Based on these analyses, a scoring system was developed, grounded on the summation of the coefficients (ß). RESULTS: Among the 660 patients meeting the inclusion criteria, 218 required bowel resection during surgery. Bowel resection occurrence was linked to an extended duration of symptoms (Odds Ratio [OR] = 2.14; 95% Confidence Interval [CI], 1.03-5.23; P = 0.0015), the presence of gross bloody stool (OR = 8.98; 95% CI, 1.76-48.75, P < 0.001), elevated C-reactive protein levels (OR = 4.79; 95% CI, 1.12-28.31, P = 0.0072), lactate clearance rate (LCR) (OR = 17.25; 95% CI, 2.36-80.35; P < 0.001), and the intussusception location (OR = 12.65; 95% CI, 1.46-62.67, P < 0.001), as determined by multivariate logistic regression analysis. A scoring system (totaling 14.02 points) was developed from the cumulative ß coefficients, with a threshold of 5.22 effectively differentiating infants requiring surgical intervention from others with necrotizing enterocolitis (NEC), exhibiting a sensitivity of 78.3% and a specificity of 71.9%. CONCLUSIONS: This study successfully identified multiple risk factors for bowel resection and effectively used a scoring system to identify patients for optimal clinical management.

Lymphoma-related intussusception in children: diagnostic challenges and clinical characteristics.

Intussusception is a common cause of acute abdominal pain in children and the most frequent cause of intestinal obstruction in infants. Although often idiopathic, it can stem from conditions like lymphoma. This study delves into lymphoma-related intussusception in children, aiming to enhance early detection and management. A retrospective review encompassed children admitted from 2012 to 2023 with intussusception due to intestinal lymphoma. Demographic, clinical, and imaging data were meticulously extracted and analyzed. The study included 31 children in the lymphoma-related intussusception group. Contrasted with non-lymphoma-related cases, the patients of lymphoma-related intussusception were notably older (median age: 87 months vs. 18.5 months), predominantly male, and demonstrated protracted abdominal pain. Ultrasound unveiled mesenteric lymph node enlargement and distinct intra-abdominal masses; enema reduction success rates were notably diminished. Detecting lymphoma-related intussusception remains intricate. Age, prolonged symptoms, and distinctive ultrasound findings can arouse suspicion. Timely surgical intervention, based on preoperative imaging, proves pivotal for accurate diagnosis. CONCLUSION:  Swift identification of lymphoma-related intussusception, distinguished by unique clinical and ultrasound features, is imperative for timely intervention and treatment. Further research is warranted to refine diagnostic approaches. WHAT IS KNOWN: • Intussusception in pediatric patients can be caused by a wide spectrum of underlying diseases including lymphoma. • Early Identifying the exact underlying cause of intussusception is crucial for tailored therapy, however often challenging and time-consuming. WHAT IS NEW: • Lymphoma-related intussusception may present with increased abdominal fluid accumulation, intestinal obstruction, and a higher likelihood of failed reduction during enema procedures. • For high-risk children, repeated ultrasound examinations or further investigations may be necessary to confirm the diagnosis.

Involvement of HIF1 stabilization and VEGF signaling modulated by Grx-1 in murine model of bronchopulmonary dysplasia.

Hypoxia inducible factor (HIF)-1α could be stabilized by Grx1 deletion, which is implicated critical in the pathogenesis of bronchopulmonary dysplasia (BPD). Until now, the stabilization of HIF-1α by glutathionylation to regulate the pulmonary microcirculation in BPD is not well addressed. In this study, we investigated whether the HIF-1α stabilization modulated by Grx1 ablation could ameliorate the pathological changes in the mouse model of BPD, including angiogenesis and alveolar formation. We found that depletion of Grx1 increased levels of GSH-protein adducts, which was associated with the improvement in the numbers of alveoli, the capillary density in the pulmonary microcirculation and the survival rate in the littermates with hyperoxic exposure. Grx1 ablation could promote HIF-1α glutathionylation by increasing GSH adducts to stabilize HIF-1α and to induce VEGF-A production in the lung tissue. The above phenotype of capillary density and VEGF-A production was removed by the pharmacological administration of YC-1, the HIF-1α inhibitor, suggesting the HIF-1α dependent manner for pulmonary microcirculatory perfusion. These data indicate that HIF-1α stabilization plays an critical role in modification pulmonary microcirculatory perfusion, which is associated with the pathological damage under hyperoxic conditions, suggesting that targeting with HIF-1α stabilization should be a potential clinical and therapeutic strategy for BPD treatment.

Regular use of low-dose of opioids after gastrointestinal surgery may lead to postoperative gastrointestinal tract dysfunction in children: a Chinese national regional health center experience sharing.

BACKGROUND: The need for pain management is increasing in pediatrics, but the side effects of overuse or abuse of analgesics can be harmful to children's health and even life-threatening in severe cases. METHODS: Patients who underwent resection of Meckel's diverticulum at the Children's Hospital of Chongqing Medical University from July 1, 2019, to July 1, 2022, were included in this study. Opioids were administered through patient-controlled analgesia (PCA). Based on the preoperative choices made by the legal guardians, patients were stratified into two groups: PCA Group (PCAG) and Non-PCA Group (NPCAG). Data pertaining to the clinical characteristics and prognoses of these patients were subsequently collected and analyzed to assess the impact of opioid administration. RESULTS: In the study, a total of 126 patients were enrolled, with 72 allocated to the Patient-Controlled Analgesia Group (PCAG) and 54 to the Non-Patient-Controlled Analgesia Group (NPCAG). When compared to the NPCAG, the PCAG exhibited a longer duration of postoperative fasting (median 72 vs. 62 h, p = 0.044) and increased utilization of laxatives (12[16.7%] vs. 2[3.7%], p = 0.022). However, the PCAG also experienced higher incidences of intestinal stasis and abnormal intestinal dilation (13[18.1%] vs. 3[5.6%], p = 0.037). No statistically significant differences were observed in pain assessments at the conclusion of the surgical procedure (0 vs. 1[1.9%], p = 0.429) or within the first 24 h postoperatively (16[22.2%] vs. 18[33.3%], p = 0.164). Additionally, NPCAG patients did not necessitate increased administration of rescue analgesics (2[2.8%] vs. 4[7.4%], p = 0.432). CONCLUSIONS: The administration of opioids did not demonstrably ameliorate postoperative pain but was associated with a heightened incidence of postoperative gastrointestinal tract dysfunction. The retrospective nature of the current research should be considered and should be clarified further.

Potential and Limitations of ChatGPT 3.5 and 4.0 as a Source of COVID-19 Information: Comprehensive Comparative Analysis of Generative and Authoritative Information.

BACKGROUND: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has necessitated reliable and authoritative information for public guidance. The World Health Organization (WHO) has been a primary source of such information, disseminating it through a question and answer format on its official website. Concurrently, ChatGPT 3.5 and 4.0, a deep learning-based natural language generation system, has shown potential in generating diverse text types based on user input. OBJECTIVE: This study evaluates the accuracy of COVID-19 information generated by ChatGPT 3.5 and 4.0, assessing its potential as a supplementary public information source during the pandemic. METHODS: We extracted 487 COVID-19-related questions from the WHO's official website and used ChatGPT 3.5 and 4.0 to generate corresponding answers. These generated answers were then compared against the official WHO responses for evaluation. Two clinical experts scored the generated answers on a scale of 0-5 across 4 dimensions-accuracy, comprehensiveness, relevance, and clarity-with higher scores indicating better performance in each dimension. The WHO responses served as the reference for this assessment. Additionally, we used the BERT (Bidirectional Encoder Representations from Transformers) model to generate similarity scores (0-1) between the generated and official answers, providing a dual validation mechanism. RESULTS: The mean (SD) scores for ChatGPT 3.5-generated answers were 3.47 (0.725) for accuracy, 3.89 (0.719) for comprehensiveness, 4.09 (0.787) for relevance, and 3.49 (0.809) for clarity. For ChatGPT 4.0, the mean (SD) scores were 4.15 (0.780), 4.47 (0.641), 4.56 (0.600), and 4.09 (0.698), respectively. All differences were statistically significant (P<.001), with ChatGPT 4.0 outperforming ChatGPT 3.5. The BERT model verification showed mean (SD) similarity scores of 0.83 (0.07) for ChatGPT 3.5 and 0.85 (0.07) for ChatGPT 4.0 compared with the official WHO answers. CONCLUSIONS: ChatGPT 3.5 and 4.0 can generate accurate and relevant COVID-19 information to a certain extent. However, compared with official WHO responses, gaps and deficiencies exist. Thus, users of ChatGPT 3.5 and 4.0 should also reference other reliable information sources to mitigate potential misinformation risks. Notably, ChatGPT 4.0 outperformed ChatGPT 3.5 across all evaluated dimensions, a finding corroborated by BERT model validation.

Efficacy of Probiotic Consortium Transplantation on Experimental Necrotizing Enterocolitis.

INTRODUCTION: Fecal microbiota transplantation (FMT) is a promising therapy, but it has not been used to treat neonatal necrotizing enterocolitis (NEC) due to reports of adverse side effects. Probiotics are considered relatively safe with practicable administrative procedures; however, no systematic research has compared the results of FMT and probiotic consortium transplantation (PCT) on oxidative stress in the intestines of patients with NEC. We conducted this study to provide a basis for optimizing NEC therapy. METHODS: Eight-day-old newborn C57BL/6 mice were randomly divided into the following four groups: the dam-fed group (control group); the NEC induction group (NEC group); the NEC induction and transplantation of Lactobacillus reuteri and Bifidobacterium infantis consortium group (NEC + PCT group); and the NEC induction and the FMT group (NEC + FMT). Intestinal injury, oxidative stress indexes, intestinal barrier function, and inflammatory cytokines were assessed in the terminal ileum. RESULTS: FMT more effectively modulates oxidative stress in the intestine than does PCT; however, the difference between the effects of PCT and FMT was not significant. The protective effect was associated with enhanced antioxidant capacity, regulation of the main components of the mucus layer, reduced inflammatory reactions, and improved intestinal integrity. CONCLUSIONS: Intestinal dysbiosis affects oxidative stress, inflammatory response, and mucosal integrity. Although FMT is more effective than PCT in regulating oxidative stress, PCT may be preferred in pediatrics because the proportion and dose of transplanted bacteria can be standardized and individualized according to individual conditions.

Hypoxia-Inducible Factor 1α Stability Modified by Glutaredoxin-1 in Necrotizing Enterocolitis.

INTRODUCTION: Hypoxia-inducible factor (HIF) 1α is essential for the pathogenesis of necrotizing enterocolitis (NEC). HIF-1α is stabilized by glutaredoxin-1 (Grx1) deletion. The precise role of HIF-1α in the intestinal microcirculation in NEC is not well defined. We aimed to determine the role of HIF-1α in the regulation of the intestinal microcirculation during the development of NEC. METHODS: Experimental NEC was induced in full-term C57BL/6 mice and Grx1-/- pups through the formula gavage and hypoxia technique. HIF-1α signaling was blocked using the HIF-1α inhibitor, YC-1 [3-(5-hydroxymethyl-2-furyl)-1-benzyl indazole]. Intestinal tissues were collected at predetermined time points for the assessment of the intestinal microcirculation and HIF-1α activity and signaling. RESULTS: We found that NEC induction impaired the intestinal microcirculation, but the impairment of the intestinal blood flow and capillary density was ameliorated in Grx1-/- mice. This amelioration was associated with tripeptide glutathione-protein adducts in the intestinal tissue. Grx1 ablation also promoted vascular endothelial growth factor A production in the intestinal tissue. This intestinal microvascular improvement was not found in HIF-1α-inhibited mice, suggesting that HIF-1α was involved in the intestinal microcirculatory perfusion. CONCLUSIONS: The current data demonstrated that HIF-1α signaling is involved in the intestinal microvascular modification during the pathogenesis of NEC, suggesting that targeting HIF-1α might be a promising strategy for NEC treatment.

NF-κB inactivation attenuates the M1 macrophage polarization in experimental necrotizing enterocolitis by glutaredoxin-1 deficiency.

The pathogenesis of necrotizing enterocolitis (NEC) is severe inflammatory injury in preterm infants, which resulted from macrophage polarization. Nuclear factor-κB (NF-κB) is implicated to be involved in macrophage polarization. We here evaluated the essential role of NF-κB in macrophage polarization in NEC in human samples from neonates with NEC and the mouse experimental NEC model. Enhanced intestinal macrophage (IM) infiltration was presented in human neonates with NEC, the majority of which were M1 macrophages. Meanwhile, NF-κB was activated in the IMs in human NEC samples. NF-κB inhibition by BAY promoted the M1 to M2 macrophage polarization. Furthermore, glutaredoxin-1 (Grx1) deficiency promoted M2 polarization via NF-κB inactivation from the lipopolysaccharide-induced proinflammatory macrophages. The IMs isolated from Grx1- / - mice presented with decreases in total numbers and less macrophage differentiation. Grx1- / - derived IM were effective in the increased survival in experimental NEC through inflammation blocking. Our study provides evidence that NF-κB inactivation by Grx1 depletion contributed to the alleviation of NEC via inhibiting M1 macrophage polarization. The modulation to alternative macrophages in the intestines may provide a promising benefits for NEC treatment.

Value of abdominal ultrasonography in predicting intestinal resection for premature infants with necrotizing enterocolitis.

BACKGROUND: Abdominal ultrasonography (AUS) has been suggested to be valuable in the early detection of necrotizing enterocolitis (NEC). OBJECTIVE: Here, we intended to assess the efficiency of abdominal ultrasound in terms of predicting bowel resection in infants with NEC. METHODS: From January 2018 to March 2021, 164 hospitalized children with NEC who underwent surgical management were enrolled. The enrolled infants were separated into two groups according to whether they underwent bowel resection. We reviewed the clinical data, as well as dynamic sonographic and abdominal radiographic (AR) parameters. The potential performance of AUS parameters was identified and compared with that of AR using a logistic regression analysis and receiver operating characteristic (ROC) curve analysis. RESULTS: Several parameters were detected to be statistically significant in predicting the occurrence of bowel resection, including thick to thin transformation [p < 0.001, odds ratios (OR), 4.38; 95% confidence interval (CI) 2.26-8.52], absence of peristalsis certain areas (p = 0.001, OR, 2.99; 95% CI 1.53-5.86), absence of bowel wall perfusion (p < 0.001, OR 10.56; 95% CI 5.09-21.90), and portal venous gas (p = 0.016, OR, 2.21; 95% CI 1.12-4.37). Furthermore, the ROC curve analysis showed significant differences (p = 0.0021) in the area under the receiver operating curve (AUROC) for the logistic models of AUS (AUROC: 0.755, 95% CI 0.660-0.849) and AR (AUROC: 0.693, 95% CI 0.597-0.789) for the prediction of intestinal resection. CONCLUSIONS: A dynamic AUS examination play an important role to indicate the potential for bowel loss during the surgery.

Clinical characteristics of immune tolerance after pediatric liver transplantation.

BACKGROUND: Clinical operational tolerance is the ultimate goal for liver transplantation. This study aimed to investigate the clinical characteristics of immune tolerance after pediatric liver transplantation and to identify the possible predictors. METHODS: The clinical data from 37 cases of pediatric patients 2 year later after liver transplantation surgery in the Children's Hospital of Chongqing Medical University, China, were retrospectively analyzed. According to the status of the current immunosuppressant medications of the patients, they were divided into tolerance (n = 15) and Control (n = 22) groups. The current status regarding prope/operational tolerance was reviewed and screened based on the immunosuppressant medications. RESULTS: The patients in the tolerance group were younger than that of Controls (p < 0.001). The children in the tolerance group experienced no acute rejection episode and exhibited no obvious abnormalities in the liver function during the continuous follow-up period. The primary disease of the tolerance group were more often diagnosed with biliary atresia (p = 0.011), and received with a living donor liver graft (p = 0.005). There were less glomerular function, diabetes mellitus, arterial hypertension events presented in the tolerance group compared with the control group, indicating low toxicity profile. CONCLUSION: In the current study, there were really certain quantity of recipients following liver transplantation attained long term immune tolerance, with low toxicity and satisfied liver graft function. The younger age of the recipient and maternal donor seems to promote long-term clinical immune tolerance. Further work in larger series should be required to describe the overall perspective of tolerance.

A promising new predictive factor for detecting bowel resection in childhood intussusception: the lymphocyte-C-reactive protein ratio.

BACKGROUND: The most critical concern for the management of childhood intussusception is bowel resection due to intestinal ischemia and necrosis. The early prediction of this problem is of great importance. We investigated the value of various combinations of inflammatory factors to predict intestinal necrosis and resection. METHODS: We retrospectively reviewed the medical records of pediatric patients with intussusception who underwent surgical management. During the research period, 47 patients who underwent intestinal resection due to intestinal necrosis and 68 patients who did not undergo intestinal resection were enrolled. We evaluated the diagnostic value of various combinations of inflammatory markers from preoperative laboratory analyses using the receiver operating characteristic (ROC) method. RESULTS: In the current cohort, 115 patients underwent operations for intussusception; among them, 47 patients (40.9%) underwent intestinal resections. In the patients with intestinal resection, the neutrophil count(p = 0.013), CRP level(p = 0.002), platelet-lymphocyte ratio (PLR, p = 0.008), NLR (neutrophil-lymphocyte ratio, p = 0.026), and LCR (lymphocyte-CRP ratio, p < 0.001) values were significantly higher than those in the patients without any resection. The receiver operating characteristic (ROC) analysis results showed that the combination of lymphocytic count along with C-reactive protein levels (LCR) demonstrated the highest correlation with intestinal resection due to intussusception compared with other parameters in the patients, with a sensitivity of 0.82 (0.73-0.86) and specificity of 0.80 (0.57-0.94) for the diagnosis of strangulation. CONCLUSION: The preoperative LCR level is a useful marker to predict the need for intestinal resection due to intestinal necrosis in patients with intussusception.

Ablation of glutaredoxin 1 promotes pulmonary angiogenesis and alveolar formation in hyperoxia-injured lungs by modifying HIF-1α stability and inhibiting the NF-κB pathway.

Glutaredoxin 1 (Grx1) is an important thiol transferase that catalyses the deglutathionylation of proteins through its active site. Deletion of Grx1 increases levels of glutathione-protein adducts and improves ischaemic revascularization. In this study, we investigated whether the absence of Grx1 ameliorates pathological changes in blood vessels and alveoli in a mouse model exposed to hyperoxic conditions. High oxygen exposure for three consecutive weeks increased the levels of Grx1 in the lungs of hyperoxic mice from control levels, while Grx1 levels in Grx1 knockout (KO) mice were significantly reduced under high oxygen conditions. Exposure to 85% oxygen for 21 days reduced alveolarization in wild-type (WT) mice but increased the numbers of alveoli and the survival rate of Grx1 KO littermates. Importantly, vascular endothelial growth factor receptor 2 (VEGFR2) and vascular endothelial growth factor A (VEGFA) expressions were increased in Grx1 KO mice after hyperoxia treatment, and these effects were probably attributable to increased hypoxia-inducible factor (HIF)-1α expression. On the other hand, in response to nuclear factor (NF)-κB inhibition by Grx1 ablation, chemokine and caspase-3 levels were reduced, although the Bcl-2:Bax ratio was increased. Here, we provide evidence that Grx1 plays an important role in regulating pathological damage under hyperoxic conditions by promoting HIF-1α stability and inhibiting the NF-κB pathway in vivo. Our study highlights the functional importance of the Grx1/protein S-glutathionylation (PSSG) redox module in the regulation of ischaemic revascularization, indicating potential clinical and therapeutic applications.

Thromboelastography Detects Possible Coagulation Disturbance in Pediatric Patients with Portal Cavernoma.

BACKGROUND: Thromboelastography (TEG) allows a dynamic assessment of clot formation and dissolution that might be useful for assessing the relative contribution of the coagulation components to overall clot formation and dissolution, but it has not been fully defined in patients with portal cavernoma (PC). METHODS: We retrospectively recruited consecutive patients with PC between July 2006 and June 2016 who had no abdominal malignancy or liver cirrhosis. Blood samples were drawn on admission and were subjected to coagulation parameter assessment, including conventional coagulation tests, measurement of the circulating levels of procoagulant and anticoagulant factors, and TEG assessment. RESULTS: Compared with controls, patients with PC showed significant reductions in the serum levels of procoagulant factors and anticoagulants factors, whereas factor VIII was slightly elevated. TEG showed clot formation (α-angle), and the maximal clot strength (MA) was higher in patients with PC than in controls, indicating a hypercoagulable state. Thrombocytopenia decreased both clot formation (α-angle) and the maximal clot strength (MA) but was still significantly higher than the control. Furthermore, patients with PC had a higher level of D-dimer and LY30 than did controls, indicating the in vivo activation of coagulation and fibrinolysis. CONCLUSION: TEG analysis showed that patients with PC were in a hypercoagulable state that could be partially masked by thrombocytopenia secondary to splenomegaly and hypersplenism in these patients, which indicates that our current prophylaxis and therapy regimen could be improved.

Evaluation for Perioperative Blood Transfusion during Major Abdominal Procedures in a Pediatric Population: A Retrospective Observation Cohort Study.

OBJECTIVES: The purpose of this study was to examine modifiable factors and their impact on perioperative blood transfusion for pediatric patients with major abdominal procedures. METHODS: This is a retrospective review of 1,506 patients who underwent major abdominal surgical procedures in a tertiary medical center from January 2008 to June 2018. Clinical data about blood administration including triggers and targets for intra- or postoperative transfusion were collected and analyzed. The inappropriate transfusion (transfusion > 8.0 g/dL of hemoglobin [Hb] trigger) and overtrans-fusion criteria (target transfusion > 10.0 g/dL or > 2 g/dL of target minus trigger level) were applied to examine the intraoperative factors with the intraoperative transfusion practice. Perioperative morbidity was further assessed based on the inappropriate transfusion and overtransfusion status. RESULTS: Intraoperative transfusion was used in 468 (31.1%) of the 1,506 patients included in the study. Among them, 212 (45.3%) intraoperative transfusion episodes were classified as inappropriate, and 135 cases (28.8%) were confirmed as overtransfusion. On univariate analysis, inappropriate transfusions were observed more commonly among patients with younger age (p < 0.001) and who underwent hepatic resection (p < 0.001) or intestinal resection (p < 0.001). Overtransfusion was also associated with elevated trigger of 8.0 g/dL Hb (p = 0.006) and younger age (p = 0.003). No perioperative complications were associated with inappropriate transfusions and overtransfusion under multivariate analysis. CONCLUSIONS: Overtransfusion was common in hepatic resection and younger age, but to definitely prove this hypothesis, a prospective randomized trial needs to be performed.

High-mobility group box-1 inhibition stabilizes intestinal permeability through tight junctions in experimental acute necrotizing pancreatitis.

BACKGROUND: In acute necrotizing pancreatitis (ANP), bacterial translocation (BT) from the gastrointestinal tract is the essential pathogenesis in the development of septic complications. Although high-mobility group box-1 (HMGB1) is associated with BT and organ dysfunction in ANP, the mechanism of HMGB1 in the intestinal barrier dysfunction and BT has not been well addressed. In this study, we intend to address the role of HMGB1 in ANP involving BT and intestinal barrier dysfunction. METHODS: Experimental ANP was achieved in male Sprague-Dawley rats through a retrograde injection of taurocholate into the common biliopancreatic duct following a laparotomy operation. HMGB1 blockade intervention was conducted with a subcutaneous injection of anti-HMGB1 antibody immediately before the laparotomy procedure. Twenty-four hours after ANP induction, pancreatic and intestinal tissues and blood samples were collected for a histopathological assessment and lipid peroxidation or glutathione (GSH) evaluation. AP-induced barrier dysfunction was determined by an intestinal permeability assessment. Tight junction proteins and autophagy regulators were investigated by western blotting, immunohistological analysis and confocal immunofluorescence imaging. RESULTS: ANP developed as indicated by microscopic parenchymal necrosis and fat necrosis, which were associated with intestinal mucosal barrier dysfunction. HMGB1 inhibition played a protective role in intestinal mucosal barrier dysfunction, protected against microbiome changes in ANP, and relieved intestinal oxidative stress. Additionally, HMGB1 inhibition attenuated intestinal permeability; preserved the expression of TJs, such as claudin-2 and occludin; and decreased autophagy. Furthermore, the autophagy regulator LC3 and TJ protein claudin-2 were both upregulated in ANP according to dual immunofluorescence analysis. CONCLUSION: HMGB1 inhibition ameliorated the severity of experimental ANP though beneficial effects on BT, mainly involving in TJ function.

Clinical benefit of oral lactulose for postoperative care of pateints with complicated appendicitis using propensity score matching analysis.

OBJECTIVE: The aim of this study was to investigate the effect of oral lactulose for pediatric patients with complicated appendicitis, who underwent appendectomy. BACKGROUND: Oral lactulose was widely used for gastrointestinal function regulation. However, clinical benefit for oral lactulose regarding its effects on recent postoperative gastrointestinal (GI) recovery and long term adhesive small bowel obstruction (ASBO) incidence, especially in the postoperative pediatric population has not yet defined. METHODS: A total of 525 pediatric patients with complicated appendicitis underwent appendectomy were retrospectively reviewed. Among them, 317 cases were subjected to oral lactulose management and 208 patients without, served as control. Propensity score 1:1 matching was carried out to adjust for any potential baseline variables. In 189 paired patients, clinical outcomes, including gastrointestinal recovery variables, incidence of ABSO, as well as adverse events, were compared according to the oral lactulose administration or not. RESULTS: Patients who received oral lactulose administration achieved early gastrointestinal function recovery, including, first bowel movement (Risk ratio [RR], 1.34; 95% confidence interval [CI] 1.02-2.63, p = 0.005) and first solid feeding (RR, 1.26; 95% CI, 1.01-1.92, p = 0.012). A lower occurrence of ASBO (OR, 0.47; 95% CI, 0.25-0.87; p = 0.011) and lower constipation (Odds ratio [OR], 0.25; 95% CI, 0.13-0.46; p < 0.001), were noted in patients received oral lactulose than in patients without. Furthermore, significantly fewer patients required readmission (OR, 0.56; 95% CI, 0.32-0.99; p = 0.031) and reoperation (OR, 0.29; 95% CI, 0.09-0.92; p = 0.022) in the patients who received oral lactulose administration. CONCLUSIONS: Beneficial effects of oral lactulose administration in pediatric patients undergone appendectomy were indicated, such as accelerating gastrointestinal function recovery, reducing the postoperative incidence of ASBO and constipation, so reduced readmission and reoperation.

Prediction of perioperative outcome after hepatic resection for pediatric patients.

BACKGROUND: Hepatic resection is associated with significant risk of morbidity and mortality. Optimising the surgical techniques and perioperative management may improve in operative morbidity and mortality. However, perioperative variables involved in the improvement for postoperative outcomes in pediatric hepatectomy have not been defined. METHODS: We retrospectively reviewed 156 consecutive pediatric patients who underwent hepatectomy at our center (an academic tertiary care hospital) between 2006 and 2016. Baseline demographic variables, intraoperative variables, complications, and hospital stay were explored. The patients were further investigated using univariate and multivariate analysis for the factors involved in the postoperative outcomes. RESULTS: Of the conditions requiring resections, malignant and benign liver diseases accounted for 47.4% (74/156) and 52.6% (82/156), respectively. The overall hospital mortality was 1.9% (3/156) and the overall postoperative complication rate was 44.2% (69/156). Anatomical resections were performed in 128 patients (82.1%), including 14(9.0%) extended hepatectomies. Eighty percent of patients had three or more segments resected. The median operative time was 167.7 (65-600) minutes and median estimated blood loss was 320.1(10-1600) mL. On multivariate analysis, the estimated blood loss (EBL) (mL) (OR, 2.19; 95CI, 1.18-3.13; p = 0.016), extent of hepatectomy (OR, 1.81; 95CI, 1.06-2.69; p = 0.001) and pringle maneuver (OR, 1.38; 95CI, 1.02-1.88; p = 0.038) were the independent predictors of postoperative complications. CONCLUSIONS: Extent of hepatectomy and estimated blood loss are largely responsible for the perioperative complications. With the surgical devices and management amelioration, like pringle maneuver, the treatment planning may be optimize in pediatric liver resection.

Understanding unplanned readmissions for children undergoing surgery in a single pediatric general surgical department.

BACKGROUND: The aim of the current research was to investigate the unplanned readmission rates and identify the risk factors of unplanned readmissions in pediatric general surgical specialties. METHODS: A retrospective review of unplanned readmissions following initial surgery from July 1, 2010, to June 30, 2017, in the general surgical specialties at an academic tertiary care hospital was performed. The main outcome of interest was unplanned readmission rates, the common causes for readmission. The risk factors involved in the unplanned readmissions were further investigated using univariate and multivariate analyses. RESULTS: Of the 3263 patients who underwent surgery and discharge, 176 (9%) were unplanned readmissions. The most frequent surgical operation related to readmission was appendectomy, and the common readmission causes were associated with treatment of gastrointestinal complaints/complications. Multivariable analysis demonstrated that emergency surgery (p = 0.016, odds ratio [OR] = 2.73; 95% CI = 1.35-6.19), major complications (p = 0.042, OR = 2.43; 95% CI = 1.12-4.71) and the initial hospital length of stay (p = 0.036, OR = 3.46; 95% CI = 1.67-7.53) were independent risk factors for readmission. CONCLUSIONS: This study identified potential risks for readmission, which should be targeted for interventions to improve quality and resource allocation.

Application of the cerebral edema monitor on cardiopulmonary bypass in infants.

A diagnostic accuracy study was adopted to evaluate the ability of Cerebral edema monitor by comparing the index test results with those of the reference standard. The serum levels of astrocyte S100 protein and neuron-specific enolase (NSE) were determined. Changes in the cerebral electrical impedance coefficient (CEIC) was detected with the BORN-BE monitor. The left- and right-sided CEIC values, serum levels of S100, and serum NSE in the CPB group significantly increased from the beginning to the end of the operation (P < .05). Furthermore, left and right-sided CEIC values, serum levels of S100, and serum NSE in the CPB-B group were significantly higher than those of the CPB-A group (P < .05). Detection rates of cerebral edema in the CPB-B group at the 24 h post-operative time point were significantly higher than those in the CPB-A group (P < .05). The degree of brain damage is positively correlated with the CPB and aortic cross-clamping. CEIC is a sensitive index reflecting brain damage during CPB in infants.