Early systemic anticoagulation reduces hospital readmission in acute necrotizing pancreatitis patients: A retrospective cohort study.

BACKGROUND: Early systemic anticoagulation (SAC) is a common practice in acute necrotizing pancreatitis (ANP), and its impact on in-hospital clinical outcomes had been assessed. However, whether it affects long-term outcomes is unknown. This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients. METHODS: During January 2013 and December 2018, ANP patients admitted within 7 days from the onset of abdominal pain were screened. The primary outcome was 90-day readmission after discharge. Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission. RESULTS: A total of 241 ANP patients were enrolled, of whom 143 received early SAC during their hospitalization and 98 did not. Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis (SVT) [risk ratio (RR) = 0.40, 95% CI: 0.26-0.60, P < 0.01] and lower 90-day readmission with an RR of 0.61 (95% CI: 0.41-0.91, P = 0.02) than those who did not. For the quality of life, patients who received early SAC had a significantly higher score in the subscale of vitality (P = 0.03) while the other subscales were all comparable between the two groups. Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57 (95% CI: 0.34-0.96, P = 0.04). Mediation analysis showed that SVT mediated 37.0% of the early SAC-90-day readmission causality. CONCLUSIONS: The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients, and reduced SVT incidence might be the primary contributor.

Frameshift coding sequence variants in the LPL gene: identification of two novel events and exploration of the genotype-phenotype relationship for variants reported to date.

BACKGROUND: Lipoprotein lipase (LPL) is the rate-limiting enzyme for triglyceride hydrolysis. Homozygous or compound heterozygous LPL variants cause autosomal recessive familial chylomicronemia syndrome (FCS), whereas simple heterozygous LPL variants are associated with hypertriglyceridemia (HTG) and HTG-related disorders. LPL frameshift coding sequence variants usually cause complete functional loss of the affected allele, thereby allowing exploration of the impact of different levels of LPL function in human disease. METHODS: All exons and flanking intronic regions of LPL were Sanger sequenced in patients with HTG-related acute pancreatitis (HTG-AP) or HTG-AP in pregnancy. Previously reported LPL frameshift coding sequence variants were collated from the Human Gene Mutation Database and through PubMed keyword searching. Original reports were manually evaluated for the following information: zygosity status of the variant, plasma LPL activity of the variant carrier, disease referred for genetic analysis, patient's age at genetic analysis, and patient's disease history. SpliceAI was employed to predict the potential impact of collated variants on splicing. RESULTS: Two novel rare variants were identified, and 53 known LPL frameshift coding sequence variants were collated. Of the 51 variants informative for zygosity, 30 were simple heterozygotes, 12 were homozygotes, and 9 were compound heterozygotes. Careful evaluation of the 55 variants with respect to their clinical and genetic data generated several interesting findings. First, we conclude that 6-7% residual LPL function could significantly delay the age of onset of FCS and reduce the prevalence of FCS-associated syndromes. Second, whereas a large majority of LPL frameshift coding sequence variants completely disrupt gene function through their "frameshift" nature, a small fraction of these variants may act wholly or partly as "in-frame" variants, leading to the generation of protein products with some residual LPL function. Third, we identified two candidate LPL frameshift coding sequence variants that may retain residual function based on genotype-phenotype correlation or SpliceAI-predicted data. CONCLUSIONS: This study reported two novel LPL variants and yielded new insights into the genotype-phenotype relationship as it pertains to LPL frameshift coding sequence variants.

Nomogram development and validation for predicting minimally invasive step-up approach failure in infected necrotizing pancreatitis patients: a retrospective cohort study.

BACKGROUND: Previous studies have shown that minimally invasive treatment for infected necrotizing pancreatitis (INP) may be safer and more effective than open necrosectomy (ON), but ON is still irreplaceable in a portion of INP patients. Furthermore, there is a lack of tools to identify INP patients at risk of minimally invasive step-up approach failure (eventually received ON or died), which may enable appropriate treatment for them. Our study aims to identify risk factors that can predict minimally invasive step-up approach failure in INP patients and to develop a nomogram for early prediction. METHODS: Multivariate logistic regression was performed to evaluate the association between minimally invasive step-up approach failure and factors regarding demographics, disease severity, laboratory index, and the location of extrapancreatic necrotic collections. A novel nomogram was developed, and its performance was validated both internally and externally by its discrimination, calibration, and clinical usefulness. RESULTS: There were 267, 89, and 107 patients in the training, internal, and external validation cohorts, respectively. Multivariate logistic regression demonstrated that the computed tomography severity index (CTSI) greater than 8 points, Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 16 points or more, early spontaneous bleeding, fungi infection, granulocyte and platelet decrease within 30 days of acute pancreatitis onset, and extrapancreatic necrosis collection located in small bowel mesentery were independent risk factors for minimally invasive step-up approach failure. The area under the curve and coefficient of determination ( R2 ) of the nomogram constructed from the above factors were 0.920 and 0.644, respectively. The Hosmer-Lemeshow test showed that the model had good fitness ( P =0.206). In addition, the nomogram performed well in both the internal and external validation cohorts. CONCLUSIONS: The nomogram had a good performance in predicting minimally invasive step-up approach failure, which may help clinicians distinguish INP patients at risk of minimally invasive step-up approach failure early.

Osteolectin increases bone elongation and body length by promoting growth plate chondrocyte proliferation.

Osteolectin is a recently identified osteogenic growth factor that binds to Integrin α11 (encoded by Itga11), promoting Wnt pathway activation and osteogenic differentiation by bone marrow stromal cells. While Osteolectin and Itga11 are not required for the formation of the skeleton during fetal development, they are required for the maintenance of adult bone mass. Genome-wide association studies in humans reported a single-nucleotide variant (rs182722517) 16 kb downstream of Osteolectin associated with reduced height and plasma Osteolectin levels. In this study, we tested whether Osteolectin promotes bone elongation and found that Osteolectin-deficient mice have shorter bones than those of sex-matched littermate controls. Integrin α11 deficiency in limb mesenchymal progenitors or chondrocytes reduced growth plate chondrocyte proliferation and bone elongation. Recombinant Osteolectin injections increased femur length in juvenile mice. Human bone marrow stromal cells edited to contain the rs182722517 variant produced less Osteolectin and underwent less osteogenic differentiation than that of control cells. These studies identify Osteolectin/Integrin α11 as a regulator of bone elongation and body length in mice and humans.

The molecular mechanism of γ-aminobutyric acid against AD: the role of CEBPα/circAPLP2/miR-671-5p in regulating CNTN1/2 expression.

The expression levels of the synaptic-related proteins contactin 1/2 (CNTN1/2) are down-regulated in the brain of Alzheimer's disease (AD), but the mechanism has not been clarified. γ-Aminobutyric acid (GABA) is considered a biologically active ingredient in food. Our previous research revealed that GABA can regulate CEBPα expression in Aß-treated U251 cells. However, it is uncertain whether GABA can antagonize the pathogenesis of AD. Whether GABA can inhibit the reduction in CNTN1/2 expression by regulating CEBPα/circAPLP2/miR-671-5p in the AD brain remains unclear yet. Here, we demonstrate that GABA could attenuate the deposition of Aß in the brain and ameliorate cognitive impairments in AD model mice. The expressions of CEBPα, circAPLP2, and CNTN1/2 were decreased and that of miR-671-5p was increased in AD model mouse brains and Aß-induced SH-SY5Y cells. These alterations were partly reversed by GABA. The CNTN1/2 expression was down-regulated and up-regulated in SH-SY5Y cells treated with miR-671-5p mimics and miR-671-5p inhibitors, respectively. The results from the luciferase reporter assay revealed that miR-671-5p could bind to the 3'-untranslated region of circAPLP2. The silencing of circAPLP2 with the siRNA duplex caused an up-regulation of miR-671-5p and a down-regulation of CNTN1/2 in SH-SY5Y cells. The silencing of CEBPα with the siRNA duplex caused a down-regulation of circAPLP2 or CNTN1/2 and an up-regulation of miR-671-5p. In conclusion, GABA may decrease the deposition of Aß in the brain, inhibit the down-regulation of CNTN1/2 expression, and ameliorate the cognitive deficits of AD model mice. The CEBPα/circAPLP2/miR-671-5p pathway plays a role in regulating CNTN1/2 expression by GABA in AD.

Detection of potential pathogen in pancreatic fluid aspiration with metagenomic next-generation sequencing in patients with suspected infected pancreatic necrosis.

BACKGROUND: Timely and accurate microbial diagnosis is important in managing patients with infected pancreatic necrosis (IPN). AIMS: To evaluate the diagnostic performance of Metagenomic next-generation sequencing (mNGS) in patients with suspected IPN. METHODS: The clinical data of 40 patients with suspected IPN who underwent CT-guided pancreatic fluid aspiration were retrospectively analyzed. Microbial culture and mNGS were simultaneously applied to identify the potential pathogens. The diagnostic performance of the mNGS was assessed by sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: The mNGS report can be obtained significantly earlier than culture methods (42 (36-62 h) vs. 60 (42-124 h), P = 0.032). Across all the study samples, seven species of bacteria and two species of fungi were reported accordingly to the culture results, while 22 species of bacteria and two species of fungi were detected by mNGS. The sensitivity, specificity, NPV, and PPV of mNGS were 88.0%, 100%, 83.33%, and 100%, respectively. CONCLUSIONS: The diagnostic accuracy of mNGS in patients with suspected IPN is satisfactory. Moreover, mNGS may broaden the range of identifiable infectious pathogens and provide a more timely diagnosis.

GPIHBP1 autoantibody is an independent risk factor for the recurrence of hypertriglyceridemia-induced acute pancreatitis.

BACKGROUND: GPIHBP1, a glycolipid-anchored protein of capillary endothelial cells, is a crucial partner for lipoprotein lipase (LPL) in plasma triglyceride metabolism. GPIHBP1 autoantibodies block LPL binding to GPIHBP1 and lead to severe hypertriglyceridemia (HTG) and HTG-induced acute pancreatitis (HTG-AP). We sought to define the incidence of GPIHBP1 autoantibodies in patients with HTG-AP. OBJECTIVE: We determined the incidence of GPIHBP1 autoantibody in HTG-AP patients, and compared the clinical features and long-term outcomes between GPIHBP1 autoantibody-positive and negative groups. METHODS: An enzyme-linked immunosorbent assay was used to screen for GPIHBP1 autoantibody in 116 HTG-AP patients hospitalized from Jan 1, 2015 to Aug 31, 2019. All patients were followed up for 24 months. The primary outcome was the recurrence rate of HTG-AP during the two-year follow-up period. The incidence of recurrent episodes was analyzed by the Kaplan-Meier method and multivariable Cox regression was used to identify risk factors. RESULTS: GPIHBP1 autoantibodies were present in 17 of 116 study patients (14.66%). The 2-year recurrence rate of HTG-AP was much higher in the GPIHBP1 autoantibody-positive group (35%, 6 in 17) than in the negative group (4%, 4 in 99). The multivariable Cox regression analysis showed that GPIHBP1 autoantibody was an independent risk factor for HTG-AP recurrence in two years. CONCLUSIONS: The presence of GPIHBP1 autoantibody is common in patients with HTG-AP, and is an independent risk factor for two-year recurrence of HTG-AP.

Plasma metagenomic next-generation sequencing of microbial cell-free DNA detects pathogens in patients with suspected infected pancreatic necrosis.

BACKGROUND: Infected pancreatic necrosis (IPN) is a life-threatening complication of acute pancreatitis (AP). Timely diagnosis of IPN could facilitate appropriate treatment, but there is a lack of reliable non-invasive screening tests. In this study, we aimed to evaluate the diagnostic value of plasma metagenomic next-generation sequencing (mNGS) based on circulating microbial cell-free DNA in patients with suspected IPN. METHODS: From October 2020 to October 2021, 44 suspected IPN patients who underwent plasma mNGS were reviewed. Confirmatory diagnosis of IPN within two weeks after the index blood sampling was considered the reference standard. The confirmation of IPN relied on the microbiological results of drains obtained from the necrotic collections. The distribution of the pathogens identified by plasma mNGS was analyzed. Positive percent agreement (PPA) and negative percent agreement (NPA) were evaluated based on the conformity between the overall mNGS results and culture results of IPN drains. In addition, the clinical outcomes were compared between mNGS positive and negative patients. RESULTS: Across all the study samples, thirteen species of bacteria and five species of fungi were detected by mNGS. The positivity rate of plasma mNGS was 54.55% (24/44). Of the 24 mNGS positive cases, twenty (83.33%, 95% CI, 68.42-98.24%) were consistent with the culture results of IPN drains. The PPA and NPA of plasma mNGS for IPN were 80.0% (20/25; 95% CI, 64.32-95.68%) and 89.47% (17/19; 95% CI, 75.67-100%), respectively. Compared with the mNGS negative group, patients in the positive group had more new-onset septic shock [12 (50.0%) vs. 4 (20.0%), p = 0.039]. CONCLUSION: IPN relevant pathogens can be identified by plasma mNGS, potentially facilitating appropriate treatment. The clinical application of mNGS in this cohort appears feasible.

IL-1ß expression in bone marrow dendritic cells is induced by TLR2 agonists and regulates HSC function.

Hematopoietic stem/progenitor cells (HSPCs) reside in localized microenvironments, or niches, in the bone marrow that provide key signals regulating their activity. A fundamental property of hematopoiesis is the ability to respond to environmental cues such as inflammation. How these cues are transmitted to HSPCs within hematopoietic niches is not well established. Here, we show that perivascular bone marrow dendritic cells (DCs) express a high basal level of Toll-like receptor-1 (TLR1) and TLR2. Systemic treatment with a TLR1/2 agonist induces HSPC expansion and mobilization. It also induces marked alterations in the bone marrow microenvironment, including a decrease in osteoblast activity and sinusoidal endothelial cell numbers. TLR1/2 agonist treatment of mice in which Myd88 is deleted specifically in DCs using Zbtb46-Cre show that the TLR1/2-induced expansion of multipotent HPSCs, but not HSPC mobilization or alterations in the bone marrow microenvironment, is dependent on TLR1/2 signaling in DCs. Interleukin-1ß (IL-1ß) is constitutively expressed in both murine and human DCs and is further induced after TLR1/2 stimulation. Systemic TLR1/2 agonist treatment of Il1r1-/- mice show that TLR1/2-induced HSPC expansion is dependent on IL-1ß signaling. Single-cell RNA-sequencing of low-risk myelodysplastic syndrome bone marrow revealed that IL1B and TLR1 expression is increased in DCs. Collectively, these data suggest a model in which TLR1/2 stimulation of DCs induces secretion of IL-1ß and other inflammatory cytokines into the perivascular niche, which in turn, regulates multipotent HSPCs. Increased DC TLR1/2 signaling may contribute to altered HSPC function in myelodysplastic syndrome by increasing local IL-1ß expression.

Major adverse kidney events within 30 days in patients with acute pancreatitis: a tertiary-center cohort study.

BACKGROUND: To evaluate the event rate of major adverse kidney events within 30 days (MAKE30) in acute pancreatitis (AP) and its potential risk factors. METHODS: A retrospective analysis of a tertiary center data on all AP patients admitted within 72 h after onset of abdominal pain between June 2015 and June 2019 was conducted. MAKE30 - a composite of death, new renal replacement therapy (RRT), or persistent renal dysfunction (PRD) - and its individual components were retrieved at discharge or 30 days. Logistic regression analysis was used to assess the risk factors for MAKE30. RESULTS: 295 patients were enrolled and 16% experienced MAKE30. For individual components, the incidence was 3% for death, 15% for new RRT, and 5% for PRD. In multivariate logistic regression analysis, hyperchloremia at admission [OR = 8.38 (1.07-65.64); P = 0.043] and SOFA score [OR 1.63 (1.18-2.26); P = 0.003] were independent risk factors in predicting MAKE30. Further analysis showed that patients with hyperchloremia had more requirements of RRT (57% vs. 10%, P < 0.001), more PRD (14% vs. 4%, P = 0.034). CONCLUSION: MAKE30 is a common event in AP patients. Hyperchloremia and SOFA score at admission were two independent risk factors for MAKE30.

Risk Factors for Fetal Death and Maternal AP Severity in Acute Pancreatitis in Pregnancy.

Background: Acute pancreatitis in pregnancy is a rare but highly life-threatening gestational and perinatal disease. Objective: This study aimed to identify the risk factors for fetal death and acute pancreatitis severity. Methods: This retrospective cohort study enrolled patients with acute pancreatitis in pregnancy in our center from January 1, 2012, to August 1, 2020, and classified them according to two clinical endpoints, fetal outcome and disease severity. The groups were examined and compared according to gestational week, etiology, gravidity and parity, complications in pre- and post-delivery, and medical history. Logistic regression analysis was performed to identify the independent risk factors for fetal death and acute pancreatitis severity. Results: Of the 90 enrolled patients, 28 (31.1%) had fetal death and 43 (47.8%) had severe acute pancreatitis. Logistic regression analysis showed that pre-delivery acute respiratory distress syndrome (OR, 5.8; 95% CI, 1.5-22.4; p = 0.010) and gestational week (OR, 0.9; 95% CI, 0.8-1.0; p = 0.011) were risk factors for fetal death. Gestation week (OR, 1.2; 95% CI, 1.1-1.3; p = 0.003) and fetal intrauterine death (OR, 5.9; 95% CI, 1.8-19.4; p = 0.003) were risk factors for severe acute pancreatitis. Conclusions: Pre-delivery acute respiratory distress syndrome and gestational week were independent risk factors for fetal death. Fetal intrauterine death and gestational week were independent risk factors for severe acute pancreatitis.

The Involvement of Renal Capsule Is Associated With Acute Kidney Injury in Patients With Acute Pancreatitis.

Background: Acute pancreatitis (AP) is characterized by pancreatic/peripancreatic inflammation. Involvement of renal capsule refers to peripancreatic inflammation extending beyond the Gerota fascia and disappearance of renal rim sign (+) on CT images. However, its association with acute kidney injury (AKI), an important complication of AP, was rarely studied. Aim: This study aimed to assess the relationship between the involvement of renal capsule and AKI in a cohort of patients with AP. Methods: We retrospectively screened all the patients admitted for AP from January 2018 to December 2019. The involvement of renal capsule was judged by experienced radiologists according to the CT imaging. Propensity score matching (PSM) was used to control for biases in group sizes and baseline characteristics. The primary outcome was the development of AKI during the index admission. We also categorized the pararenal inflammation with the renal rim grade (RRG) and compared the incidence of AKI among different grades. Results: Involvement of renal capsule was identified in 71 of 503 patients (14.1%). The incidence of AKI was significantly higher in these patients when compared with the matched controls (43/71, 60.6% vs. 12/71, 16.9%, p < 0.001). Moreover, mortality also differed between groups (12.7% vs. 1.4%, p = 0.017). Multivariable logistic regression showed that renal capsule involvement is an independent risk factor of AKI (odds ratio, 4.355; 95% confidence interval, 1.434, 13.230, p = 0.009). Patients with RRG grade III had a significantly higher incidence of AKI than the other two grades (60.6% for Grade III, 17.1% for Grade II, and 3.8% for Grade I, p < 0.001). Conclusion: Involvement of renal capsule is associated with higher AKI incidence and mortality.

The effect of parathyroid hormone on osteogenesis is mediated partly by osteolectin.

We previously described a new osteogenic growth factor, osteolectin/Clec11a, which is required for the maintenance of skeletal bone mass during adulthood. Osteolectin binds to Integrin α11 (Itga11), promoting Wnt pathway activation and osteogenic differentiation by leptin receptor+ (LepR+) stromal cells in the bone marrow. Parathyroid hormone (PTH) and sclerostin inhibitor (SOSTi) are bone anabolic agents that are administered to patients with osteoporosis. Here we tested whether osteolectin mediates the effects of PTH or SOSTi on bone formation. We discovered that PTH promoted Osteolectin expression by bone marrow stromal cells within hours of administration and that PTH treatment increased serum osteolectin levels in mice and humans. Osteolectin deficiency in mice attenuated Wnt pathway activation by PTH in bone marrow stromal cells and reduced the osteogenic response to PTH in vitro and in vivo. In contrast, SOSTi did not affect serum osteolectin levels and osteolectin was not required for SOSTi-induced bone formation. Combined administration of osteolectin and PTH, but not osteolectin and SOSTi, additively increased bone volume. PTH thus promotes osteolectin expression and osteolectin mediates part of the effect of PTH on bone formation.

The Proresolving Lipid Mediator Maresin1 Alleviates Experimental Pancreatitis via Switching Macrophage Polarization.

METHOD: Repeated caerulein injection was used to induce AP and chronic pancreatitis (CP) models in mice. The histopathological and serological changes were examined for evaluating the severity of the AP model, and flow cytometry was used for detecting macrophage phagocytosis and phenotype. Meanwhile, clodronate liposomes were used for macrophage depletion in mice. Finally, the CP model was adopted to further observe the protective effect of MaR1. RESULT: MaR1 administration manifested the improved histopathological changes and the lower serum levels of amylase and lipase. However, MaR1 played no protective role in the pancreatic acinar cell line in vitro. It obviously reduced the macrophage infiltration in the injured pancreas, especially M1-type macrophages. After macrophage clearance, MaR1 showed no further protection in vivo. This study also demonstrated that MaR1 could alleviate fibrosis to limit AP progression in the CP model. CONCLUSION: Our data suggests that MaR1 was a therapeutic and preventive target for AP in mice, likely operating through its effects on decreased macrophage infiltration and phenotype switch.

A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis.

Stromal cells in adult bone marrow that express leptin receptor (LEPR) are a critical source of growth factors, including stem cell factor (SCF), for the maintenance of haematopoietic stem cells and early restricted progenitors1-6. LEPR+ cells are heterogeneous, including skeletal stem cells and osteogenic and adipogenic progenitors7-12, although few markers have been available to distinguish these subsets or to compare their functions. Here we show that expression of an osteogenic growth factor, osteolectin13,14, distinguishes peri-arteriolar LEPR+ cells poised to undergo osteogenesis from peri-sinusoidal LEPR+ cells poised to undergo adipogenesis (but retaining osteogenic potential). Peri-arteriolar LEPR+osteolectin+ cells are rapidly dividing, short-lived osteogenic progenitors that increase in number after fracture and are depleted during ageing. Deletion of Scf from adult osteolectin+ cells did not affect the maintenance of haematopoietic stem cells or most restricted progenitors but depleted common lymphoid progenitors, impairing lymphopoiesis, bacterial clearance, and survival after acute bacterial infection. Peri-arteriolar osteolectin+ cell maintenance required mechanical stimulation. Voluntary running increased, whereas hindlimb unloading decreased, the frequencies of peri-arteriolar osteolectin+ cells and common lymphoid progenitors. Deletion of the mechanosensitive ion channel PIEZO1 from osteolectin+ cells depleted osteolectin+ cells and common lymphoid progenitors. These results show that a peri-arteriolar niche for osteogenesis and lymphopoiesis in bone marrow is maintained by mechanical stimulation and depleted during ageing.

Clinical characteristics and management of gastric outlet obstruction in acute pancreatitis.

OBJECTIVE: The aim of this study was to describe the clinical characteristics and management of gastric outlet obstruction following acute pancreatitis(AP). BACKGROUND: Gastric outlet obstruction (GOO) is not uncommon in acute pancreatitis (AP) and can occur throughout the course. However, the clinical features and related treatment of GOO is rarely reported. METHODS: A retrospective review of AP patients with a diagnosis of GOO from March 2017 to June 2020 was performed. The diagnosis and management of GOO, as well as the demographic characteristics and clinical outcomes of the study patients, were collected and analyzed. RESULTS: Over the three years, there were 60 AP patients developed GOO, constituting an incidence of 5.7%. Thirty-three patients (55.0%, 33/60) developed GOO in the first 4 weeks and 27 patients (45.0%, 27/60) after 4 weeks from onset. Pancreatic necrosis compression (60.6%; 20/33), gastric outlet gastrointestinal edema (27.3%, 9/33) are the main causes of early-onset GOO (≤4 weeks), while wall-off necrosis (92.6%, 25/27) is the leading cause in the late phase (>4 weeks). The management of GOO incorporates both supportive and specific treatment like gastric decompression, gastric juice reinfusion, percutaneous catheter drainage, etc. The mortality of AP patients with GOO (≤4 weeks) was 21.2% and none patients who developed GOO (>4 weeks) died. CONCLUSIONS: GOO, as a gastrointestinal complication developed in AP patients, has two peak incidences in the duration of AP and needs to be paid more attention to.

Comparison of pancreatic function and quality of life between patients with infected pancreatitis necrosis undergoing open necrosectomy and minimally invasive drainage: A long-term study.

The present study aimed to determine whether a difference in pancreatic function and quality of life (QoL) is present between patients with infected pancreatitis necrosis (IPN) undergoing open necrosectomy (ON) and minimally invasive drainage (MID). The medical records of patients with IPN discharged from Jinling Hospital were retrospectively analyzed. Pancreatic function and QoL were compared between patients treated with ON and MID. Pancreatic endocrine and exocrine function were assessed using the oral glucose tolerance test and fecal elastase-1 (FE-1) test, respectively. The standard Short Form 36 health questionnaire was used to evaluate the QoL of patients. The analysis included 101 patients who underwent either ON (n=40, 39.6%) or MID (n=61, 60.4%). There were no significant differences in exocrine and endocrine pancreatic function between the two groups evaluated based on FE-1, fasting blood glucose, glycated hemoglobin and 2-h plasma glucose (P<0.05). The scores of the QoL questionnaire were significantly higher in patients treated with MID than in patients treated with ON, including the scores of general health perception (19.39±3.07 vs. 17.37±3.63, P=0.003), vitality (18.93±2.88 vs. 17.57±3.47, P=0.035), social role functioning (8.85±1.43 vs. 8.15±1.98, P=0.042), emotional role functioning (5.33±1.07 vs. 4.82±1.25, P=0.034), mental health (24.21±3.31 vs. 22.57±3.91, P=0.026) and the total QoL score (125.12±13.16 vs. 116.50±16.94, P=0.005). In conclusion, although the initial health of the patient may have influenced the treatment provided, patients with IPN who received MID achieved a better post-treatment QoL than those treated with ON. No significant differences between the two groups were observed regarding the endocrine and exocrine functions of the pancreas.

Efficacy and Safety of Early Systemic Anticoagulation for Preventing Splanchnic Thrombosis in Acute Necrotizing Pancreatitis.

OBJECTIVES: Splanchnic venous thrombosis (SVT) is a relevant complication in patients with acute necrotizing pancreatitis. So far, no specific treatment for preventing development of SVT exists, and the effect of systemic anticoagulation (SAC) is unclear. METHODS: Patients with acute necrotizing pancreatitis admitted to our center within 7 days from onset of abdominal pain were screened. In the historic group, during which period, most patients received no SAC. Patients in the study group received SAC therapy considering the risk of deep vein thrombosis and SVT. The primary outcome measure was the incidence of SVT. RESULTS: Splenic vein was involved in 71% of all 84 SVT patients. Compared with the historic cohort, patients who received SAC experienced lower incidence of SVT (P < 0.001), especially for splenic venous thrombosis (P = 0.002). Patients in the study group also showed lower mortality (P = 0.04) and incidence of new-onset organ failure (P = 0.03). The incidence of bleeding shows no statistical significance between 2 groups. CONCLUSIONS: Application of SAC seems to reduce the incidence of SVT and improve clinical outcomes without increasing the risk of bleeding. Randomized clinical trials are needed to confirm our findings.

Up-regulation of neprilysin mediates the protection of fructo-oligosaccharides against Alzheimer's disease.

Fructo-oligosaccharides (FOS), an important prebiotic, have been proved to have a beneficial effect on Alzheimer's disease (AD); however, the specific mechanism remains to be confirmed. Senile plaques are one of the main neuropathological features of AD and the core of senile plaques mainly consists of extracellular beta-amyloid (Aß). Reducing Aß accumulation in the brain is an important therapeutic strategy for AD. Neprilysin (NEP), a major Aß-degrading enzyme, has been found to be decreased in the AD brain. Evidence has shown that the expression of NEP is associated with histone acetylation levels. Histone deacetylases (HDACs) are the key enzymes in the modulation of histone acetylation modification. Importantly, several metabolites of FOS have been demonstrated to be pan-HDAC inhibitors. In this study, we demonstrate that FOS ameliorate cognitive impairment and alleviate Aß accumulation in the brain of AD model mice. The regulation of HDAC2 on NEP plays an important role in the anti-AD effect of FOS.