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.

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).

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.

Early versus delayed intervention in necrotizing acute pancreatitis complicated by persistent organ failure.

BACKGROUND: Current guidelines for the treatment of patients with necrotizing acute pancreatitis (NAP) recommend that invasive intervention for pancreatic necrosis should be deferred to 4 or more weeks from disease onset to allow necrotic collections becoming "walled-off". However, for patients showing signs of clinical deterioration, especially those with persistent organ failure (POF), it is controversial whether this delayed approach should always be adopted. In this study, we aimed to assess the impact of differently timed intervention on clinical outcomes in a group of NAP patients complicated by POF. METHODS: All NAP patients admitted to our hospital from January 2013 to December 2017 were screened for potential inclusion. They were divided into two groups based on the timing of initial intervention (within 4 weeks and beyond 4 weeks). All the data were extracted from a prospectively collected database. RESULTS: Overall, 131 patients were included for analysis. Among them, 100 (76.3%) patients were intervened within 4 weeks and 31 (23.7%) underwent delayed interventions. As for organ failure prior to intervention, the incidences of respiratory failure, renal failure and cardiovascular failure were not significantly different between the two groups (P > 0.05). The mortality was not significantly different between the two groups (35.0% vs. 32.3%, P = 0.83). The incidences of new-onset multiple organ failure (8.0% vs. 6.5%, P = 1.00), gastrointestinal fistula (29.0% vs. 12.9%, P = 0.10) and bleeding (35.0% vs. 35.5%, P = 1.00), and length of ICU (30.0 vs. 22.0 days, P = 0.61) and hospital stay (42.5 vs. 40.0 days, P = 0.96) were comparable between the two groups. CONCLUSION: Intervention within 4 weeks did not worsen the clinical outcomes in NAP patients complicated by POF.

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.

Lacticaseibacillus rhamnosus TR08 alleviated intestinal injury and modulated microbiota dysbiosis in septic mice.

BACKGROUND: Probiotics are widely used in intestinal microbiota imbalance caused by sepsis, however, the protective mechanism is still unclear. This study aimed to explore protective effect of Lacticaseibacillus rhamnosus TR08 on intestinal injury in septic mice. RESULTS: The levels of serum inflammatory factors were reduced significantly in septic mice treated with L. rhamnosus TR08. The levels of sIgA in terminal ileum were significantly higher in probiotic treatment group than sepsis group. Intestinal pathological damage in septic mice improved and the expression of tight junction proteins increased after probiotic treatment. Sequencing of fecal microbiota showed that the abundance and diversity of probiotic treatment group were significantly better than those of sepsis group, and beneficial bacteria increased while some bacteria decreased in the phylum level. CONCLUSION: L. rhamnosus TR08 could improve the integrity of intestinal barrier, enhance the intestinal mucosal immunity in septic mice, and rebalance the intestinal microecosystem.

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.

Increased circulating total bile acid levels were associated with organ failure in patients with acute pancreatitis.

BACKGROUND: Recent studies have shown that bile acids (BAs) are closely related to metabolic and inflammatory diseases. Our study aimed to investigate whether circulating total bile acid (TBA) levels were associated with the severity of acute pancreatitis (AP). METHODS: We retrospectively collected data on patients diagnosed with AP in a tertiary center from 01 January 2014 to 31 December 2016. The highest TBA value during the first 1,2,3,5,7 days after admission was determined as D1, D2, D3, D5, D7 TBAmax. Patients were divided into the high TBA (HTBA) group and the normal TBA (NTBA) group according to whether the TBAmax was ≥10 µmol/L. The prognosis and complications, including death, organ failure (OF) and pancreatic necrosis, were compared between the two groups. Logistic regression analysis and receiving operating characteristic (ROC) curve were used to evaluate the relationship between circulating TBA and organ failure in AP patients. RESULTS: Through stratified analysis of each time period, we found that the incidence of OF in the HTBA group was significantly higher than that in the NTBA group, and the AP severity classification in the HTBA group was more serious than that in the NTBA group. In addition, according to the D7 TBAmax values, the pancreatic necrosis rate, percutaneous catheter drainage (PCD) rate and mortality in the HTBA group were higher than those in the NTBA group. Multivariate regression analysis showed that HTBA (odds ratio (OR), 4.894; P = 0.002) was an independent risk factor for AP complicated with OF, which was verified in the grouping based on D7 TBAmax. ROC analysis revealed that a circulating D7 TBAmax cutoff point of 6.450 umol/L had optimal predictive value for the development of OF in AP patients with an area under the curve of the ROC curve (AUCROC) of 0.777. CONCLUSIONS: The increase of circulating TBA in early stage of AP is independently related to organ failure, which indicates the adverse prognosis of AP patients.

Protective effects of HTD4010, a Reg3α/PAP-derived peptide, in mouse model of acute pancreatitis via toll-like receptor 4 pathway.

Acute pancreatitis (AP) is one of the most common digestive tract diseases, but effective drug therapy is still lack. Regenerating gene protein 3α (Reg3α) administration significantly reduced the severity of AP in mice. HTD4010 is a new 15 amino acid long synthetic peptide and its biological activities are similar to Reg3α. This study aimed to explore whether HTD4010 could protect pancreatic acinar cells against necrosis and decrease the inflammatory response in AP, and thus to explore underlying mechanisms. It was shown that administration of HTD4010 alleviated significantly the severity of biliary AP (BAP), characterized as less degree of pancreatic histological damage and acinar cell injury (both apoptosis and necroptosis), lower levels of serum amylase and pro-inflammatory cytokines. Moreover, HTD4010 down-regulated the expression of toll-like receptor 4 (TLR4) protein, and TLR4 deficiency eliminated the protective effect of HTD4010 on BAP in mice. In conclusion, these results showed that HTD4010 could alleviate the severity of pancreatitis, reduce the acinar cells necrosis and inflammatory response possibly by TLR4 signaling pathway in AP.

Increase in serum chloride and chloride exposure are associated with acute kidney injury in moderately severe and severe acute pancreatitis patients.

OBJECTIVE: We aimed to evaluate whether early (first 48 h) hyperchloremia and/or the change of serum chloride concentration are associated with acute kidney injury (AKI) in patients with moderately severe and severe acute pancreatitis (MSAP and SAP). METHODS: We retrospectively collected the data of patients with a primary diagnosis of MSAP or SAP from a tertiary center between January 2014 and June 2017. Consecutive chloride levels within the first 48 h after admission were retrieved for further calculation. Logistic regression analysis and receiving operating characteristic (ROC) curve were used to assess the relationship between hyperchloremia and AKI. RESULTS: 145 patients were enrolled for analysis, of whom 33.5% (47/145) developed hyperchloremia during the observation period. The incidence of AKI was significantly higher in the hyperchloremia group (40.4% vs 7.1%; p < 0.001). On multivariate analysis, the increase in serum chloride (Δ[Cl-]) was independently associated with AKI [OR = 1.32 (1.00-1.74)], as was chloride exposure [OR = 1.01 (1.00-1.02)], and these associations were found to be stronger in patients identified as predicted SAP (PSAP). Moreover, even in patients without hyperchloremia, increase in serum chloride (Δ[Cl-]) was still associated with AKI [OR = 1.65 (1.18-2.32)]. Area under the curve of the ROC curve (AUCROC) analysis found that Δ[Cl-] is a good predictor of AKI with an optimal cutoff point at 3.5 mmol/L, showing an AUCROC of 0.81. CONCLUSION: Hyperchloremia is common in patients with AP and Δ[Cl-] and chloride exposure during the first 48 h were independent risk factors for AKI in MSAP and SAP patients.

Aggressive Resuscitation Is Associated with the Development of Acute Kidney Injury in Acute Pancreatitis.

INTRODUCTION: The association between early resuscitation volume and clinical outcomes remains controversial in acute pancreatitis. In the present study, we aimed to identify the association between resuscitation volume and the development of acute kidney injury (AKI) and other clinical outcome metrics. METHODS: Patients admitted to our center with moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) from January 2009 to December 2013 were reviewed retrospectively. Patients were stratified into two groups on the basis of the volume of fluid infused during the first 24 h. The primary clinical endpoint was incidence of AKI. Moreover, AKI lasting time, utilization of continuous renal replacement therapy and lasting time, creatinine increase, and other clinical metrics were also compared. The potential risk factors of new-onset AKI were also analyzed. RESULTS: A total of 179 patients were included, and aggressive fluid resuscitation (≥ 4 l) was associated with increased incidence of AKI compared with nonaggressive group (53.12% vs. 25.64%, p = 0.008), longer AKI lasting time (p = 0.038), and increased creatinine increase (p < 0.001) during hospitalization. Moreover, utilization of continuous renal replacement therapy was more frequent in aggressive group (40.63% vs. 24.36%, p = 0.108), and the lasting time of continuous renal replacement therapy was also longer (p = 0.181), though both not statistically different. Moreover, in multivariate analysis, aggressive resuscitation [OR 4.36 (1.52-13.62); p = 0.001] and chloride exposure [OR 2.53 (1.26-5.21); p = 0.012] in the first 24 h were risk factors of new-onset AKI. CONCLUSION: In patients with MSAP and SAP, aggressive fluid resuscitation was associated with increased incidence and longer duration of AKI. Moreover, aggressive resuscitation and chloride exposure in the first 24 h were risk factors of new-onset AKI.

Stent-Assisted Percutaneous Endoscopic Necrosectomy for Infected Pancreatic Necrosis: Technical Report and a Pilot Study.

BACKGROUND AND AIMS: A variety of minimally invasive techniques have been proposed to replace open surgery for the treatment of infected pancreatic necrosis (IPN). In this study, we evaluate the feasibility and safety of the stent-assisted percutaneous endoscopic necrosectomy (SAPEN) procedure. METHODS: Data were collected on all patients who underwent the SAPEN procedure between October 2017 and March 2018. The demographic and clinical characteristics of the study patients were analyzed. A composite primary endpoint of major complications and/or death was used. Three different cases were selected to illustrate different technical aspects of the SAPEN procedure. RESULTS: The placement of a percutaneous stent was successful in all of the 23 patients (17 males, six females). IPN was successfully managed in 16/23 (70%) patients, with the need for open surgery in seven patients (30%), with a median of two (range 1-5) SAPEN procedures. No significant procedure-related complications occurred. Overall 11/23 (48%) patients had a major complication and/or death. CONCLUSIONS: In conclusion, the SAPEN procedure was effective in treating IPN without adding extra procedural risk. The role and benefits of the SAPEN procedure now need to be demonstrated in larger controlled study.

Real-time full-field optical angiography utilizing principal component analysis.

We develop a real-time full-field optical angiography method using principal component analysis (PCA). In our approach, an undersampled laser Doppler method is used to record the raw images. Considering the difference in the signal component contributions, PCA is used to separate the dynamic blood flow and static background signals. The principal advantage of the PCA method is that the choice of a high pixel number can aid in efficiently extracting the blood flow signal with finite frame raw images, which can greatly improve the temporal resolution. Our phantom experimental results validate our choice of the optimal frame number for reconstructing an angiographic image. A vascular occlusion test on a rabbit ear demonstrates that global and simultaneous hemodynamic processes of vessels can be monitored.

Significantly different clinical features between hypertriglyceridemia and biliary acute pancreatitis: a retrospective study of 730 patients from a tertiary center.

BACKGROUND: Unlike western world, gallstones and hypertriglyceridemia (HTG) are among the first two etiologies of acute pancreatitis (AP) in China. But yet, detailed differences in clinical features and outcomes between hypertriglyceridemia and biliary acute pancreatitis have not been well described. METHODS: This retrospective study enrolled 730 acute pancreatitis patients from July 1, 2013 to October 1, 2016 in Jinling Hospital. The causes of the study patients were defined according to specific diagnostic criteria. The clinical features and outcomes of patients with hypertriglyceridemia acute pancreatitis (HTG-AP) and biliary acute pancreatitis (BAP) were compared in terms of general information, disease severity, laboratory data, system complications, local complications, and clinical outcome. RESULTS: In the enrolled 730 AP patients, 305 (41.8%) were HTG-AP, and 425 (58.2%) were BAP. Compared to BAP, the HTG-AP patients were found to be younger, with higher body mass Index (BMI), and much higher proportion of diabetes, fatty liver and high fat diet. Besides that, HTG-AP patients had significantly higher C-reactive protein (CRP) (p<0.01) and creatinine (p = 0.031), together with more acute respiratory distress syndrome (ARDS) (p = 0.039), acute kidney injury (AKI) (p<0.001), deep venous thrombosis (p = 0.008) and multiple organ dysfunction syndrome (MODS) (p = 0.032) in systematic complications. As for local complications, HTG-AP patients had significantly less infected pancreatitis necrosis (p = 0.005). However, there was no difference in mortality, hospital duration and costs between the groups. CONCLUSION: HTG-AP patients were younger, more male, having high fat diet and with higher BMI compared to BAP patients. The prevalence of AKI/ARDS/DVT/MODS in HTG-AP patients was higher than BAP patients, while BAP patients had a greater possibility in development of infected pancreatitis necrosis (IPN). According to the multivariate analysis, only the complication of AKI was independently related with the etiology of HTG, however, BMI contributes to AKI, ARDS and DVT.

Full-field functional optical angiography.

We propose full-field functional optical angiography for a live biological specimen based on the absorption intensity fluctuation modulation (AIFM) effect. Because of the difference in absorption between red blood cells (RBCs) and the background tissue under low-coherence light illumination, the moving RBCs, which discontinuously pass though the capillary vessels, generate an AIFM effect. This effect offers high contrast of absorption imaging and sensitivity of low-coherence interference between RBCs and the background tissue. It is used to distinguish the signal of RBCs from that of the background tissue. The averaged and real-time modulation depths are computed to obtain full-field label-free optical angiography and measure blood flow velocity simultaneously. The AIFM method could potentially be applied to study the physiological mechanisms of blood circulation systems of near-transparent live biologic samples.

Nutrition therapy in critically ill patients with severe acute pancreatitis.

A significant proportion of patients (10%-20%) with acute pancreatitis develop severe acute pancreatitis characterized by pancreatic necrosis, systemic inflammation, and organ failure, commonly requiring intensive care unit (ICU) admission. In this specific population, nutrition therapy is more challenging than that in the general ICU population, primarily because of inevitable gastrointestinal involvement by pancreatic inflammation. In this review, we discussed several key aspects of nutrition therapy in this population, including key pathophysiology that may impede nutrition therapy, the timing and implementation of enteral nutrition and parenteral nutrition, the importance of specific nutrient supplements, and the long-term outcomes that may be addressed by nutrition therapy.

Quantification of the effect of biochar application on heavy metals in paddy systems: Impact, mechanisms and future prospects.

Biochar (BC) has shown great potential in remediating heavy metal(loid)s (HMs) contamination in paddy fields. Variation in feedstock sources, pyrolysis temperatures, modification methods, and application rates of BC can result in great changes in its effects on HM bioavailability and bioaccumulation in soil-rice systems and remediation mechanisms. Meanwhile, there is a lack of application guidelines for BC with specific properties and application rates when targeting rice fields contaminated with certain HMs. To elucidate this topic, this review focuses on i) the effects of feedstock type, pyrolysis temperature, and modification method on the properties of BC; ii) the changes in bioavailability and bioaccumulation of HMs in soil-rice systems applying BC with different feedstocks, pyrolysis temperatures, modification methods, and application rates; and iii) exploration of potential remediation mechanisms for applying BC to reduce the mobility and bioaccumulation of HMs in rice field systems. In general, the application of Fe/Mn modified organic waste (OW) derived BC for mid-temperature pyrolysis is still a well-optimized choice for the remediation of HM contamination in rice fields. From the viewpoint of remediation efficiency, the application rate of BC should be appropriately increased to immobilize Cd, Pb, and Cu in rice paddies, while the application rate of BC for immobilizing As should be <2.0 % (w/w). The mechanism of remediation of HM-contaminated rice fields by applying BC is mainly the direct adsorption of HMs by BC in soil pore water and the mediation of soil microenvironmental changes. In addition, the application of Fe/Mn modified BC induced the formation of iron plaque (IP) on the root surface of rice, which reduced the uptake of HM by the plant. Finally, this paper describes the prospects and challenges for the extension of various BCs for the remediation of HM contamination in paddy fields and makes some suggestions for future development.

Investigation of the migration of natural organic matter-iron-antimony nano-colloids in acid mine drainage.

Colloids can potentially affect the efficacy of traditional acid mine drainage (AMD) treatment methods such as precipitation and filtration. However, it is unclear how colloids affect antimony (Sb) migration in AMD, especially when natural organic matter (NOM) is present. To conduct an in-depth investigation on the formation and migration behavior of NOM, iron (Fe), Sb and NOM-Fe-Sb colloids in AMD, experiments were performed under simulated AMD conditions. The results demonstrate significant variations in the formation of NOM-Fe-Sb colloids (1-3-450 nm) as the molar ratio of carbon to iron (C/Fe) increases within acidic conditions (pH = 3). Increasing the C/Fe molar ratio from 0.1 to 1.2 resulted in a decrease in colloid formation but an increase in particulate fraction. The distribution of colloidal Sb, Sb(III), and Fe(III) within the NOM-Fe-Sb colloids decreased from 68 % to 55 %, 72 % to 57 %, and 68 % to 55 %, respectively. Their distribution in the particulate fraction increased from 28 % to 42 %, 21 % to 34 %, and 8 % to 27 %. XRD, FTIR, and SEM-EDS analyses demonstrated that NOM facilitates the formation and crystallization of Fe3O4 and FeSbO4 crystalline phases. The formation of the colloids depended on pH. Our results indicate that NOM-Fe-Sb colloids can form when the pH ≤ 4, and the proportion of colloidal Sb fraction within the NOM-Fe-Sb colloids increased from 9 % to a maximum of 73 %. Column experiments show that the concentration of NOM-Fe-Sb colloids reaches its peak and remains stable at approximately 3.5 pore volumes (PVs), facilitating the migration of Sb in the porous media. At pH ≥ 5, stable NOM-Fe-Sb colloids do not form, and the proportion of colloidal Sb fraction decreases from 7 % to 0 %. This implies that as pH increases, the electrostatic repulsion between colloidal particles weakens, resulting in a reduction in the colloidal fraction and an increase in the particulate fraction. At higher pH values (pH ≥ 5), the repulsive forces between colloidal particles nearly disappear, promoting particle aggregation. The findings of this study provide important scientific evidence for understanding the migration behavior of NOM-Fe-Sb colloids in AMD. As the pH gradually shifts from acidic to near-neutral pH during the remediation process of AMD, these results could be applied to develop new strategies for this purpose.

Recurrence of hypertriglyceridemia-associated acute pancreatitis: A multicenter, prospective cohort study.

OBJECTIVES: There are scarce prospective data on recurrent hypertriglyceridemia-associated acute pancreatitis (HTG-AP). This study aimed to investigate the incidence, potential prognostic factors, and clinical relevance of recurrent HTG-AP. METHODS: This study is a multicenter, prospective cohort study. Adult patients with the first HTG-AP attack enrolled in the PERFORM registry between November 2020 and December 2021 were involved. All the study patients were followed up for more than two years with a two-round schedule. The Cox proportional-hazards model was applied to analyze the potential factors. Quality of life was evaluated using the EuroQol five-dimensional five-level health scale (EQ-5D-5L). RESULTS: A total of 184 patients from 25 sites were included in the study, and 161 patients completed the two-round follow-up. Among them, the mean follow-up time for the study patients was 31±4 months, and the incidence rate of recurrent HTG-AP attack was 23 % (37/161). All patients with recurrent episodes required readmission to the hospital. The EQ visual analog scale (VAS) score was significantly lower in patients with recurrent episodes compared to those without (76±10 vs. 82±12; P = 0.02) at the latest follow-up. Age <40 years old (hazard ratio [HR], 3.6; 95 % confidence interval [CI], 1.5-8.7; P = 0.004) and a history of diabetes (HR, 2.6; 95 %CI, 1.3-5.1; P = 0.005) were identified as potential predictor factors for recurrence. CONCLUSIONS: Recurrence of HTG-AP is common, especially for younger patients with diabetes. Recurrence necessitated additional hospital readmissions and was associated with compromised quality of life.

Immune-Enhancing Treatment among Acute Necrotizing Pancreatitis Patients with Metabolic Abnormalities: A Post Hoc Analysis of a Randomized Clinical Trial.

Background/Aims: : Metabolic syndrome is common in patients with acute pancreatitis and its components have been reported to be associated with infectious complications. In this post hoc analysis, we aimed to evaluate whether metabolic abnormalities impact the effect of immune-enhancing thymosin alpha-1 (Tα1) therapy in acute necrotizing pancreatitis (ANP) patients. Methods: : All data were obtained from the database for a multicenter randomized clinical trial that evaluated the efficacy of Tα1 in ANP patients. Patients who discontinued the Tα1 treatment prematurely were excluded. The primary outcome was 90-day infected pancreatic necrosis (IPN) after randomization. Three post hoc subgroups were defined based on the presence of hyperglycemia, hypertriglyceridemia, or both at the time of randomization. In each subgroup, the correlation between Tα1 and 90-day IPN was assessed using the Cox proportional-hazards regression model. Multivariable propensity-score methods were used to control potential bias. Results: : Overall, 502 participants were included in this post hoc analysis (248 received Tα1 treatment and 254 received matching placebo treatment). Among them, 271 (54.0%) had hyperglycemia, 371 (73.9%) had hypertriglyceridemia and 229 (45.6%) had both. Tα1 therapy was associated with reduced incidence of IPN among patients with hyperglycemia (18.8% vs 29.7%: hazard ratio, 0.80; 95% confidence interval, 0.37 to 0.97; p=0.03), but not in the other subgroups. Additional multivariate regression models using three propensity-score methods yielded similar results. Conclusions: : Among ANP patients with hyperglycemia, immune-enhancing Tα1 treatment was associated with a reduced risk of IPN (ClinicalTrials.gov, Registry number: NCT02473406).