Balanced Solution versus Normal Saline in Predicted Severe Acute Pancreatitis: A Stepped Wedge Cluster Randomized Trial.

OBJECTIVE: To compare the effect of balanced multielectrolyte solutions(BMES) versus normal saline(NS) for intravenous fluid on chloride levels and clinical outcomes.in patients with predicted severe acute pancreatitis (pSAP). SUMMARY BACKGROUND DATA: Isotonic crystalloids are recommended for initial fluid therapy in acute pancreatitis, but whether the use of BMES in preference to NS confers clinical benefits is unknown. METHODS: In this multicenter, stepped-wedge, cluster-randomized trial, we enrolled patients with pSAP (APACHE II score ≥8 and C-reactive protein >150 mg/L) admitted within 72 hours of the advent of symptoms. The study sites were randomly assigned to staggered start dates for one-way crossover from the NS phase (NS for intravenous fluid) to the BMES phase(Sterofudin for intravenous fluid). The primary endpoint was the serum chloride concentration on trial day3. Secondary endpoints included a composite of clinical and laboratory measures. RESULTS: Overall, 259 patients were enrolled from eleven sites to receive NS(n=147) or BMES(n=112). On trial day3, the mean chloride level was significantly lower in patients who received BMES(101.8 mmol/L(SD4.8) versus 105.8 mmol/L(SD5.9), difference -4.3 mmol/L [95%CI -5.6 to -3.0 mmol/L];P<0.001). For secondary endpoints, patients who received BMES had less systemic inflammatory response syndrome(19/112,17.0% versus 43/147,29.3%, P=0.024) and increased organ failure-free days (3.9 d(SD2.7) versus 3.5days(SD2.7), P<0.001) by trial day7. They also spent more time alive and out of ICU(26.4 d(SD5.2) versus 25.0days(SD6.4), P=0.009) and hospital(19.8 d(SD6.1) versus16.3days(SD7.2), P<0.001) by trial day30. CONCLUSIONS: Among patients with pSAP, using BMES in preference to NS resulted in a significantly more physiological serum chloride level, which was associated with multiple clinical benefits(Trial registration number: ChiCTR2100044432).

Associations of Intrapancreatic Fat Deposition With Incident Diseases of the Exocrine and Endocrine Pancreas: A UK Biobank Prospective Cohort Study.

INTRODUCTION: To investigate whether increased intrapancreatic fat deposition (IPFD) heightens the risk of diseases of the exocrine and endocrine pancreas. METHODS: A prospective cohort study was conducted using data from the UK Biobank. IPFD was quantified using MRI and a deep learning-based framework called nnUNet. The prevalence of fatty change of the pancreas (FP) was determined using sex- and age-specific thresholds. Associations between IPFD and pancreatic diseases were assessed with multivariate Cox-proportional hazard model adjusted for age, sex, ethnicity, body mass index, smoking and drinking status, central obesity, hypertension, dyslipidemia, liver fat content, and spleen fat content. RESULTS: Of the 42,599 participants included in the analysis, the prevalence of FP was 17.86%. Elevated IPFD levels were associated with an increased risk of acute pancreatitis (hazard ratio [HR] per 1 quintile change 1.513, 95% confidence interval [CI] 1.179-1.941), pancreatic cancer (HR per 1 quintile change 1.365, 95% CI 1.058-1.762) and diabetes mellitus (HR per 1 quintile change 1.221, 95% CI 1.132-1.318). FP was also associated with a higher risk of acute pancreatitis (HR 3.982, 95% CI 2.192-7.234), pancreatic cancer (HR 1.976, 95% CI 1.054-3.704), and diabetes mellitus (HR 1.337, 95% CI 1.122-1.593, P = 0.001). DISCUSSION: FP is a common pancreatic disorder. Fat in the pancreas is an independent risk factor for diseases of both the exocrine pancreas and endocrine pancreas.

AAV-mediated hepatic LPL expression ameliorates severe hypertriglyceridemia and acute pancreatitis in Gpihbp1 deficient mice and rats.

GPIHBP1 plays an important role in the hydrolysis of triglyceride (TG) lipoproteins by lipoprotein lipases (LPLs). However, Gpihbp1 knockout mice did not develop hypertriglyceridemia (HTG) during the suckling period but developed severe HTG after weaning on a chow diet. It has been postulated that LPL expression in the liver of suckling mice may be involved. To determine whether hepatic LPL expression could correct severe HTG in Gpihbp1 deficiency, liver-targeted LPL expression was achieved via intravenous administration of the adeno-associated virus (AAV)-human LPL gene, and the effects of AAV-LPL on HTG and HTG-related acute pancreatitis (HTG-AP) were observed. Suckling Gpihbp1-/- mice with high hepatic LPL expression did not develop HTG, whereas Gpihbp1-/- rat pups without hepatic LPL expression developed severe HTG. AAV-mediated liver-targeted LPL expression dose-dependently decreased plasma TG levels in Gpihbp1-/- mice and rats, increased post-heparin plasma LPL mass and activity, decreased mortality in Gpihbp1-/- rat pups, and reduced the susceptibility and severity of both Gpihbp1-/- animals to HTG-AP. However, the muscle expression of AAV-LPL had no significant effect on HTG. Targeted expression of LPL in the liver showed no obvious adverse reactions. Thus, liver-targeted LPL expression may be a new therapeutic approach for HTG-AP caused by GPIHBP1 deficiency.

Serum Sulfur-Containing Amino Acids and Risk of Maternal Gestational Diabetes and Adverse Growth Patterns in Offspring.

BACKGROUND: To estimate associations of sulfur-containing amino acids (SAAs) in the early trimester of pregnancy and gestational diabetes mellitus (GDM) and estimate associations of maternal SAAs with adverse growth patterns in offspring. METHODS: We established a 1:1 matched case-control study (n = 486) from our cohort of pregnant women, and 401 children were followed up at ages 1 to 8 years. We conducted binary conditional logistic regression to estimate the risk associations of serum SAAs with GDM. Multinomial logistic regression was implemented to explore associations of maternal SAAs with adverse growth patterns in the offspring. RESULTS: High serum methionine and cystine were independently associated with increased GDM risk (OR: 1.92, 95%CI: 1.18-3.13 and 2.69, 1.59-4.53). Conversely, a low level of serum taurine was independently associated with increased GDM risk (2.61, 1.64-4.16). Maternal high cystine and low taurine were also associated with an increased risk of persistent obesity growth pattern (POGP) in offspring (OR: 2.79, 95%CI: 1.09-7.17 and 3.92, 1.11-13.89) and the effect was largely independent of GDM. CONCLUSIONS: High serum methionine, cystine and low serum taurine in the early trimester of pregnancy were associated with a greatly increased risk of GDM. Maternal high cystine and low taurine were associated with elevated risk of offspring POGP, largely independent of GDM.

Reversible cardiac function and left ventricular hypertrophy in a Chinese man with mitochondrial myopathy: a case report.

BACKGROUND: Mitochondrial myopathies (MMs) are a group of multi-system diseases caused by abnormalities in mitochondrial DNA (mtDNA) or mutations of nuclear DNA (nDNA). The diagnosis of mitochondrial myopathy (MM) is reliant on the combination of history and physical examination, muscle biopsy, histochemical studies, and next-generation sequencing. Patients with MMs have diverse clinical manifestations. In the contemporary literature, there is a paucity of reports on cardiac structure and function in this rare disease. We report a Chinese man with MM accompanied with both acute right heart failure and left ventricular hypertrophy. CASE PRESENTATION: A 49-year-old man presented with clinical features suggestive of MM, i.e., ophthalmoparesis, weakness of the pharyngeal and extremity muscles, and respiratory muscles which gradually progressed to respiratory insufficiency. He had a family history of mitochondrial myopathy. He had increased levels of serum creatine kinase and lactate. Muscle biopsy of left lateral thigh revealed 8% ragged red fibers (RRF) and 42% COX-negative fibers. Gene sequencing revealed a novel heterozygote TK2 variant (NM_001172644: c.584T>C, p.Leu195Pro) and another heterozygous variant (NM_004614.4:c.156+958G>A; rs1965661603) in the intron of TK2 gene. Based on these findings, we diagnosed the patient as a case of MM. Echocardiography revealed right heart enlargement, pulmonary hypertension, left ventricular hypertrophy, and thickening of the main pulmonary artery and its branches. The patient received non-invasive ventilation and coenzyme Q10 (CoQ10). The cardiac structure and function were restored at 1-month follow-up. CONCLUSIONS: This is the first report of reversible cardiac function impairment and left ventricular hypertrophy in a case of adult-onset MM, nocturnal hypoxia is a potential mechanism for left ventricular hypertrophy in patients with MM.

Initial suction drainage decreases severe postoperative complications after pancreatic trauma: A cohort study.

BACKGROUND: Few studies have addressed the question of which drain types are more beneficial for patients with pancreatic trauma (PT). AIM: To investigate whether sustained low negative pressure irrigation (NPI) suction drainage is superior to closed passive gravity (PG) drainage in PT patients. METHODS: PT patients who underwent pancreatic surgery were enrolled consecutively at a referral trauma center from January 2009 to October 2021. The primary outcome was defined as the occurrence of severe complications (Clavien-Dindo grade ≥ Ⅲb). Multivariable logistic regression was used to model the primary outcome, and propensity score matching (PSM) was included in the regression-based sensitivity analysis. RESULTS: In this study, 146 patients underwent initial PG drainage, and 50 underwent initial NPI suction drainage. In the entire cohort, a multivariable logistic regression model showed that the adjusted risk for severe complications was decreased with NPI suction drainage [14/50 (28.0%) vs 66/146 (45.2%); odds ratio (OR), 0.437; 95% confidence interval (CI): 0.203-0.940]. After 1:1 PSM, 44 matched pairs were identified. The proportion of each operative procedure performed for pancreatic injury-related and other intra-abdominal organ injury-related cases was comparable in the matched cohort. NPI suction drainage still showed a lower risk for severe complications [11/44 (25.0%) vs 21/44 (47.7%); OR, 0.365; 95%CI: 0.148-0.901]. A forest plot revealed that NPI suction drainage was associated with a lower risk of Clavien-Dindo severity in most subgroups. CONCLUSION: This study, based on one of the largest PT populations in a single high-volume center, revealed that initial NPI suction drainage could be recommended as a safe and effective alternative for managing complex PT patients.

Catheter-directed thrombolysis versus systemic anticoagulation in the treatment of symptomatic splanchnic venous thrombosis secondary to acute pancreatitis: a retrospective cohort study.

BACKGROUND: Catheter-directed thrombolysis (CDT) has been an important therapy and seems effective in patients with splanchnic venous thrombosis (SVT) secondary to some diseases, but this intervention hasn't been formally evaluated in the setting of acute pancreatitis (AP). METHODS: This was a retrospective study enrolled patients between January 2013 and December 2018. AP patients who developed SVT-induced symptoms, including intractable ascites and/or enteral nutrition intolerance, were included. Demographics, SVT associated parameters, clinical features and outcomes, long-term quality of life evaluated by using SF-36 questionnaire were compared between CDT group and systemic anticoagulation (SAC) group. RESULTS: 6 patients underwent CDT and 17 received SAC. Patients in CDT group had a higher recanalization rate (100% versus 35.3%; p = 0.014) and shorter time to symptoms resolution (median 8 days versus. 31.5 days, p = 0.004). Mortality and length of hospital stay were comparable between two groups. The association analysis indicated that CDT use exerted a significantly beneficial effect on recanalization rate (risk ratio, 2.833; 95% CI, 1.489 to 5.393; p = 0.002) and time to symptoms resolution (mean difference, -33.333; 95% CI, -64.612 to -2.055; p = 0.038). No SVT-related symptoms recurrence was recorded in survivors at six-month follow-up. There was no statistical difference in either item of SF-36 questionnaire between two groups. CONCLUSIONS: Compared with SAC, CDT may facilitate vascular recanalization and shorten symptom resolution for symptomatic SVT.

Recurrence rates and risk factors for recurrence after first episode of acute pancreatitis: A systematic review and meta-analysis.

BACKGROUND: There are a certain number of acute pancreatitis (AP) patients who may suffer from multiple episodes and develop recurrent acute pancreatitis (RAP), but recurrence rates and associated risk factors for RAP vary significantly in the published literature. METHODS: We searched PubMed, Web of Science, Scopus, and Embase databases to identify all publications reporting AP recurrence until October 20th, 2022. Meta-analysis and meta-regression were performed to calculate the pooled estimates using the random-effects model. RESULTS: A total of 36 studies met the inclusion criteria and all were used in pooled analyses. The overall rate of recurrence after first-time AP was 21% (95% CI, 18%- 24%), and pooled rates in biliary, alcoholic, idiopathic, and hypertriglyceridemia etiology patients were 12%, 30%, 25%, and 30%, respectively. After managing underlying causes post-discharge, the recurrence rate decreased (14% versus 4% for biliary, 30% versus 6% for alcoholic, and 30% versus 22% for hypertriglyceridemia AP). An increased risk of recurrence was reported in patients with a smoking history (odds ratio [OR] = 1.99), alcoholic etiology (OR = 1.72), male sex (hazard ratio [HR] = 1.63), and local complications (HR = 3.40), while biliary etiology was associated with lower recurrence rates (OR = 0.38). CONCLUSION: More than one-fifth of AP patients experienced recurrence after discharge, with the highest recurrence rate in alcoholic and hypertriglyceridemia etiologies, and managing underlying causes post-discharge was related to decreased incidence. In addition, smoking history, alcoholic etiology, male gender, and presence of local complications were independent risks for the recurrence.

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.

Association of demographic and clinical factors with risk of acute pancreatitis: An exposure-wide Mendelian randomization study.

BACKGROUND: The incidence of acute pancreatitis (AP) is increasing over years, which brings enormous economy and health burden. However, the aetiologies of AP and underlying mechanisms are still unclear. Here, we performed a two-sample Mendelian randomization (MR) analysis to investigate the associations between all reported possible risk factors and AP using publicly available genome-wide association study summary statistics. METHODS: A series of quality control steps were taken in our analysis to select eligible instrumental single nucleotide polymorphisms which were strongly associated with exposures. To make the conclusions more robust and reliable, we utilized several analytical methods (inverse-variance weighting, MR-PRESSO method, weighted median, MR-Egger regression) that are based on different assumptions of two-sample MR analysis. The MR-Egger intercept test, radial regression and leave-one-out sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on each exposure. A two-step MR method was applied to explore mediators in significant associations. RESULTS: Genetic predisposition to cholelithiasis (effect estimate: 17.30, 95% CI: 12.25-22.36, p = 1.95 E-11), body mass index (0.32, 95% CI: 0.13-0.51, p < 0.001), body fat percentage (0.57, 95% CI: 0.31-0.83, p = 1.31 E-05), trunk fat percentage (0.36, 95% CI: 0.14-0.59, p < 0.005), ever smoked (1.61, 95% CI: 0.45-2.77, p = 0.007), and limbs fat percentage (0.55, 95% CI: 0.41-0.69, p < 0.001) were associated with an increased risk of AP. In addition, whole-body fat-free mass (-0.32, 95% CI: -0.55 to -0.10, p = 0.004) was associated with a decrease risk of AP. CONCLUSION: Genetic predisposition to cholelithiasis, obesity and smoking could be causally associated with an increased risk of AP, and whole body fat-free mass could be associated with a decreased risk of AP.

The effects of bicarbonated versus acetated Ringer's solutions on acid-base status and kidney injury following orthotopic liver transplantation: Protocol for a single-centre, randomised controlled trial (The BETTER trial).

Background: The ideal crystalloid fluid of choice for fluid therapy during liver transplantation is unknown. Conventional balanced crystalloids are buffered with organic anions, which requires liver metabolism to prevent matabolic acidosis and protect renal function. Therefore they can not function properly during liver transplantation. On the contrary, the bicarbonated Ringer's solution (BRS) can maintain acid-base status regardless of liver function. In this study, we aimed to test the hypothesis that, in patients undergoing orthotopic liver transplantation, compared with acetated Ringer's solutions (ARS), perioperative fluid therapy with BRS could better maintain the acid-base status. Methods: This is a prospective, single-centre, randomised controlled trial. 72 eligible patients will be randomised to receive either BRS or ARS perioperatively. The primary endpoint is the difference in standard base excess (SBE) before and after operation. Secondary endpoints include the incidence of acute kidney injury (AKI) within 48 h post operation and free and alive days to day 14 for intensive care admission, invasive ventilation, vasopressors, and renal replacement therapy (RRT). Discussion: Metabolic acidosis is common perioperatively, potentially leading to decreased renal blood flow and reduced glomerular filtration rate. The use of balanced solutions can prevent hyperchloremic metabolic acidosis, thereby avoiding AKI in some patients. However, during liver transplantation, when well-functioning liver metabolism is lacking, the organic anions in conventional balanced solutions may remain strong anions and thus fail to maintain the acid-base status, but no solid clinical evidence exists now. This study will, for the first time, provide evidence on the relative effects of BRS vs. ARS on acid-base status and renal injury in patients undergoing liver transplantation. Clinical Trial Registration: The trial has been registered at the Chinese Clinical Trials Registry (ChiCTR2100046889) on 29 May 2021.

Increased Gestational Weight Gain is Associated with a Higher Risk of Offspring Adiposity Before Five Years of Age: A Population-Based Cohort Study.

Objective: We aim to investigate the influence of weight gain during pregnancy on the risk of offspring adiposity before five years old. Methods: We retrospectively collected health information from the Tianjin mother-child cohort. Offspring outcome was BMI Z-score and prevalence of childhood adiposity from 0.5-5 years old. Gestational weight gain was analyzed using continuous and categorical variables evaluated by the IOM guidelines. Multivariate analysis adjusted maternal age, prepregnancy BMI, maternal height, smoking, cesarean section, gestational age at birth, birth weight, birth length, and mode of infant feeding during 0-6 months. Results: Gestational weight gain contributed to offspring's BMI Z-score from 1-5 years old, and the effect was most obvious in the first half of pregnancy (multivariate analysis, at 1, 2, 2.5, 3, 4, and 5 years of age: ß 0.011, 95% CI 0.008-0.014; ß 0.017, 95% CI 0.015-0.020; ß 0.005, 95%CI 0.002-0.008; ß 0.018, 95% CI 0.015-0.021; ß 0.014, 95% CI 0.009-0.020; ß 0.013, 95% CI 0.005-0.021). Excessive weight gain was associated with a higher prevalence of offspring adiposity before five years, even if prepregnancy BMI is normal. Multivariate regression analysis further confirmed that excessive weight gain during the first half of pregnancy significantly increased the risk of childhood obesity at aged one and three (AOR 1.083, 95% CI 1.003-1.169; AOR 1.158, 95% CI 1.036-1.293). Conclusion: Offspring have a higher risk of preschool adiposity when gestational weight gain was excessive during the first half of pregnancy.

Triphlorethol-A attenuates U251 human glioma cancer cell proliferation and ameliorates apoptosis through JAK2/STAT3 and p38 MAPK/ERK signaling pathways.

Glioma is the foremost recurrent type of brain tumor in humans; in particular, glioblastoma (GBM) is the main form of brain tumor (GBM) that is highly proliferative and impervious to apoptosis. Triphlorethol-A (TA), a phlorotannin isolated from Ecklonia cava, exhibited cytoprotective, antioxidant, and anticancer properties. However, the exact molecular action of TA in the U251 human GBM cells remains unknown. This may be the first report on the antiproliferative and apoptotic mechanisms of TA on GBM. The cytotoxicity, intracellular reactive oxygen species (ROS), matrix metalloproteinase (MMP), and cell apoptosis activity of TA have been evaluated by the MTT assay and by DCFH-DA, Rh-123, AO/EB, and western blot analysis. The results obtained showed that TA abridged the viability of U251 cells, while MMP increased apoptosis by increasing the ROS levels in a time-dependent manner. The results showed that a reduction in U251 cell proliferation was associated with the regulation of JAK2/STAT3 and p38 MAPK/ERK signaling pathways. TA was found to suppress pJAK, pSTAT3, p38 MAPK, and pERK phosphorylation, thereby causing Bax/Bcl-2 imbalance, activating the caspase cascade and cytochrome c, and inducing apoptosis. Our findings showed that the suppression of JAK2/STAT3 and p38 MAPK/ERK signaling by TA results in cell growth arrest and stimulation of apoptosis in GBM cells. These studies justify the protective remedy of TA against GBM.

The clinical outcome from early versus delayed minimally invasive intervention for infected pancreatic necrosis: a systematic review and meta-analysis.

BACKGROUND: While the management of infected pancreatic necrosis (IPN) has evolved in the last two decades with the adoption of minimally invasive interventions (drainage ± debridement), it is unknown whether the principle of delaying intervention inherited from the open surgery era still applies. The aim of the current study was to investigate the impact of the timing of minimally invasive intervention on the outcomes of patients with IPN requiring intervention. METHODS: PubMed, Embase, MEDLINE and Web of Science databases were searched for appropriate studies. The primary outcome of interest was hospital mortality, the secondary outcomes were the incidence of complications during the hospitalization, including new-onset organ failure, gastrointestinal fistula or perforation, bleeding and length of hospital or intensive care unit (ICU) stay. RESULTS: Seven clinical studies were included with a total of 742 patients with IPN requiring intervention, of whom 321 received early intervention and 421 delayed intervention. Results from the meta-analysis showed that early minimally invasive intervention did not increase hospital mortality (odds ratio 1.65, 95% confidence interval 0.97-2.81; p = 0.06) but was associated with a remarkably prolonged hospital stay and an increased incidence of gastrointestinal fistula or perforation when compared with delayed intervention. CONCLUSIONS: Although no firm conclusion can be drawn because of the quality of available studies, it does appear that timing of intervention is a risk factor for adverse outcomes and ought to be investigated more rigorously in prospective studies.

Heparin-binding protein (HBP) worsens the severity of pancreatic necrosis via up-regulated M1 macrophages activation in acute pancreatitis mouse models.

Acute pancreatitis (AP) is one of the most widespread clinical emergencies. Macrophages are the most common immune cells in AP pancreatic tissue and are closely associated with pancreatic necrosis and recovery. The level of heparin-binding protein (HBP) is closely linked to inflammation. In this study, we assessed the effect of HBP on AP tissue necrosis severity and whether HBP is associated with M1 macrophages in pancreatic necrosis. We observed the dynamic changes of HBP levels in the pancreas during acute inflammation in the caerulein-induced AP mice model. We used hematoxylin-eosin staining to evaluate pancreatic edema and necrosis, and to detect infiltration of macrophages by immunohistochemistry. Moreover, expressions of the maker and cytokines of macrophages, including inducible nitric oxide synthase (iNOS), and arginase 1 (Arg-1), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) mRNA, were detected by real-time polymerase-chain reaction (RT-PCR). High levels of HBP in the pancreas were detected at 48 h, and heparin inhibited HBP expression in AP pancreatic tissue. Inhibiting HBP expression by injecting heparin before AP can alleviate pancreatic necrosis and inhibit F4/80 labeled M1 macrophage infiltration and IL-6, TNF-α, and iNOS mRNA expression. Clodronate liposome (CLDL) intraperitoneally treated mice showed no change in pancreatic HBP levels, but pancreatic macrophage-specific antigen F4/80 and TNF-α, IL-1ß, and IL-6 mRNA levels decreased after CLDL treatment. HBP is critical for pancreatic necrosis response in acute pancreatitis by increasing the infiltration of M1 macrophages and promoting the secretion of inflammatory factors, such as TNF-α, IL-6, IL-1ß, which can be reduced by heparin.

Protectin D1 decreases pancreatitis severity in mice by inhibiting neutrophil extracellular trap formation.

BACKGROUND: Docosahexaenoic acid-derived protectin D1 (PD1) was identified critical in the resolution of inflammation in vivo, where it modulates the innate immune response and stimulates resolution. Acute pancreatitis (AP) is characterized by local pancreatic inflammation with mild forms whereas systemic inflammation with severe forms. Herein we investigate the impact of PD1 in murine models of pancreatitis. METHODS: Three independent AP models, which induced in male mice via intraperitoneal injection of caerulein, L-arginine or pancreatic duct ligation, were used to confirm the protective effect of PD1. Infiltrationsof neutrophils and macrophages in pancreas were detected by flow cytometry and immunohistochemistry. In vitro and in vivo neutrophil extracellular traps formation was detected by immunofluorescence staining. Expression of peptidylarginine deiminase 4 (PAD4) in activated neutrophils was evaluated by western blotting. RESULTS: Systemic treatment with PD1 reduced serum activities of amylase and lipase, blunted the concentrations of tumor necrosis factor-α and interleukin-6 in serum and protected against pancreas histologic damage in three AP models. PD1 also prolonged the survival in the pancreatic duct ligation model. Moreover, pancreatic infiltrationofneutrophils and neutrophil CitH3 expression were reduced after PD1 administration. In vitro studies revealed PD1 decreased supernatant cell-free DNA and CitH3 levels and downregulated PAD4 expression in mouse bone-marrow derived neutrophils. However, in the caerulein mice pretreated with GSK484 hydrochloride, an inhibitor of PAD4, PD1 treatment showed no more protective effect. CONCLUSIONS: PD1 ameliorates AP by decreasing early infiltration of neutrophils into the pancreas and neutrophil extracellular traps formation through PAD4. These results supply the foundation to consider PD1 as a therapy for AP.

Sarcopenia associated with 90-day readmission and overall survival after abdominal trauma.

BACKGROUND AND OBJECTIVES: It is widely recognized that sarcopenia increases postoperative complications in trauma patients. However, the effects on prognosis remain unclear. This study aimed to evaluate the impact of sarcopenia on 90-day readmission and overall survival (OS) in abdominal trauma patients. METHODS AND STUDY DESIGN: 485 consecutive patients who underwent abdominal surgery after trauma in our institution were enrolled. Sarcopenia was diagnosed with low muscle mass and low muscle strength-handgrip. Multivariate logistic regression analysis was performed to identify factors that contributed to 90-day readmission and OS. Cox logistic regression analysis was used to assess the relationship between sarcopenia and OS. RESULTS: Sarcopenia was present in 120 of 485 patients (24.7%) with abdominal trauma within one week after admission based on the diagnostic cut-off values (40.9 cm2/m2 for men and 36.8 cm2/m2 for women). 90-day readmission was significantly higher in the sarcopenia group (p=0.019), and OS lower in the sarcopenia group (p=0.025). Sarcopenia was an independent predictor of 90-day readmission [odds ratio (OR): 5.34, 95% confidence interval (CI): 2.52-11.3]. CONCLUSIONS: Sarcopenia was associated with high 90-day readmission and low OS in abdominal trauma patients, and it was an independent risk factor for 90-day readmission.

Exosome-Mediated Transfer of Long Noncoding RNA HOTAIR Regulates Temozolomide Resistance by miR-519a-3p/RRM1 Axis in Glioblastoma.

Background: Chemoresistance obstructs the treatment of glioblastoma (GB). Exosome-mediated transfer of long noncoding RNAs (lncRNAs) was reported to regulate chemoresistance in diverse cancers. The authors aimed to investigate the underlying mechanism of lncRNA HOX transcript antisense intergenic RNA (HOTAIR) in regulating temozolomide (TMZ) resistance in GB. Materials and Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was utilized to check TMZ resistance and cell proliferation. The abilities of cell migration and invasion were evaluated by transwell assay. The protein levels of E-cadherin, N-cadherin, Vimentin, CD63, CD81, and ribonucleoside-diphosphate reductase subunit M1 (RRM1) were measured by western blot. Quantitative real-time polymerase chain reaction was conducted to detect the levels of HOTAIR, microRNA (miR)-519a-3p, and RRM1. The starBase was hired to predict the target sites between miR-519a-3p and HOTAIR or RRM1 and the dual-luciferase reporter assay was performed to verify the interaction. Xenograft tumor model was established to investigate the biological role of HOTAIR in vivo. Results: The high abilities of cell viability and metastasis were observed in TMZ-resistant GB cells. LncRNA HOTAIR was significantly upregulated in TMZ-resistant GB cells and its downregulation inhibited proliferation, migration, invasion, and epithelial/mesenchymal transition in TMZ-resistant GB cells. Further analysis indicated that exosomal lncRNA HOTAIR induced TMZ resistance and modulated TMZ resistance through miR-519a-3p/RRM1 axis. Besides, serum exosomal lncRNA HOTAIR was stable and had diagnostic value. Moreover, knockdown of lncRNA HOTAIR reduced TMZ resistance in vivo. Conclusions: Exosomal lncRNA HOTAIR mediated TMZ resistance through miR-519a-3p/RRM1 axis in GB.

Open necrosectomy combined with continuous positive drainage and prophylactic diverting loop ileostomy for late infected pancreatic necrosis: a retrospective cohort study.

BACKGROUND: To evaluate an innovative open necrosectomy strategy with continuous positive drainage and prophylactic diverting loop ileostomy for the management of late infected pancreatic necrosis (LIPN). METHODS: Consecutive patients were divided into open necrosectomy (ON) group (n = 23), open necrosectomy with colonic segment resection (ON+CSR) group (n = 8) and open necrosectomy with prophylactic diverting loop ileostomy (ON+PDLI) group (n = 11). Continuous positive drainage (CPD) via double-lumen irrigation-suction tube (DLIST) was performed in ON+PDLI group. The primary endpoints were duration of organ failure after surgery, postoperative complication, the rate of re-surgery and mortality. The secondary endpoints were duration of hospitalization, cost, time interval between open surgery and total enteral nutrition (TEN). RESULTS: The recovery time of organ function in ON+PDLI group was shorter than that in other two groups. Colonic complications occurred in 13 patients (56.5%) in the ON group and 3 patients (27.3%) in the ON+PDLI group (p = 0.11). The length of stay in the ON+PDLI group was shorter than the ON group (p = 0.001). The hospitalization cost in the ON+PDLI group was less than the ON group (p = 0.0052). CONCLUSION: ON+PDLI can avoid the intestinal dysfunction, re-ileostomy, the resection of innocent colon and reduce the intraoperative trauma. Despite being of colonic complications before or during operation, CPD + PDLI may show superior effectiveness, safety, and convenience in LIPN.