Aim:To investigate discharge readiness among older adult sepsis survivors and its influencing factors, and to explore the relationship with 30-day unplanned readmission. Methods:From May 2024 to May 2025, a cohort of 330 older adult sepsis survivors was recruited from an infectious disease center in China. Before discharge, participants completed questionnaires on demographic and disease characteristics, the Readiness for Hospital Discharge Scale (RHDS), and the Quality of Discharge Teaching Scale (QDTS). A follow-up survey on the 30-day unplanned readmission was subsequently conducted. The data were analyzed using Spearman correlation and multiple linear regression. Results:The mean scores for RHDS and QDTS were 93.54 ± 19.96 and 155.21 ± 24.57. RHDS was primarily influenced by the QDTS, length of hospitalization, medical expenses payment, and general self-efficacy, which together explained 43.0% of the variance. Lower discharge readiness was associated with a higher risk of unplanned readmission within 30 days. Conclusion:The readiness for hospital discharge of older adult sepsis survivors is moderate and influenced by multiple factors, with the quality of discharge teaching being particularly significant. Higher levels of discharge readiness are associated with a lower rate of unplanned readmission.

BACKGROUND & AIMS:Dysregulation of the von Willebrand factor and its protease, a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13, has been implicated in the pathogenesis of pancreatic necrosis during acute pancreatitis, but the underlying mechanisms remain incompletely understood. NETosis and their enzyme component, peptidylarginine deiminase type IV, have been proposed to inhibit a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13. We aimed to determine whether peptidylarginine deiminase type IV-mediated inhibition of a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 contributes to the progression of pancreatic injury in acute pancreatitis. METHODS:Serum a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 activity and peptidylarginine deiminase type IV levels were prospectively assessed in 30 patients with acute pancreatitis. Peptidylarginine deiminase type IV-a disintegrin and a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 interactions were examined in vitro and in vivo. Experimental acute pancreatitis was induced in mice using cerulein plus lipopolysaccharide or L-arginine, with interventions including recombinant human a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13, the peptidylarginine deiminase type IV inhibitor Cl-amidine, and genetic knockout models (Pad4-/- and Adamts13-/-). RESULTS:Patients with acute pancreatitis and >30% pancreatic necrosis exhibited significantly reduced a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 activity, elevated peptidylarginine deiminase type IV levels, and accumulation of large von Willebrand factor multimers. In mouse acute pancreatitis models, a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 deficiency worsened pancreatic necrosis and systemic injury, whereas recombinant human a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 treatment conferred protection. Mechanistically, peptidylarginine deiminase type IV suppressed a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 activity both in vitro and in vivo; this inhibition was reversed by Cl-amidine. Peptidylarginine deiminase type IV inhibition attenuated acute pancreatitis severity, but this effect was abolished in Adamts13-/- mice, demonstrating that peptidylarginine deiminase type IV aggravates acute pancreatitis primarily through a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 suppression. CONCLUSIONS:An early imbalance in the von Willebrand factor-a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 axis and peptidylarginine deiminase type IV activation is a hallmark of both clinical and experimental acute pancreatitis. By inhibiting a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 activity, peptidylarginine deiminase type IV promotes pancreatic necrosis and exacerbates disease severity. Targeting peptidylarginine deiminase type IV or restoring a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 activity may represent a promising therapeutic strategy to protect against pancreatic injury in acute pancreatitis.

BACKGROUND:Infected necrotizing pancreatitis (INP) patients requiring open necrosectomy (ON) as part of the step-up approach generally face high postoperative mortality. Our center proposed the step-cross approach as a supplement, but supporting evidence remains limited. This study aimed to compare clinical outcomes between the step-cross and step-up approaches in INP patients. METHODS:This retrospective cohort study included adult INP patients admitted to our center from 2017 to 2022. The step-cross approach consisted of percutaneous catheter drainage, followed by accelerated focused ON and personalized drainage or debridement as needed. Propensity score matching (PSM) was used to adjust for confounders. RESULTS:Of 509 included patients (median age 46 [34-55] years, 67.6 % male), 454 (89.2 %) and 55 (10.8 %) underwent the step-up and step-cross approach respectively. Overall, 180-day mortality was 20.2 % (103/509): 83 (18.3 %) in the step-up group and 20 (36.4 %) in step-cross group. After PSM (53 matched pairs), 180-day mortality did not differ significantly (35.9 %vs 49.1 %, relative risk [RR] and 95 % confidence interval [CI] with the step-cross approach = 0.73 [0.46-1.15], P = 0.169), but the step-cross group was associated with lower CRRT duration (2 [0, 16] vs 15 [3.5, 22] days, P = 0.005) and fewer minimally invasive necrosectomy procedures. Complications, hospital stays and costs were comparable between groups. CONCLUSIONS:The step-cross approach is a safe complementary strategy to the step-up approach, demonstrating trends toward lower mortality and reduced organ support requirements in selected INP patients. Nevertheless, these findings require validation through large-scale prospective studies.

This study investigates the role of trehalose in modulating gut microbiota metabolism and alleviating symptoms of severe acute pancreatitis (SAP). Here, we found that gut microbial metabolism was imbalanced in SAP. In particular, we observed increased lipid metabolism and decreased carbohydrate and amino acid metabolism, which were reversed by gut microbiota depletion. Moreover, the production of trehalose was significantly increased after gut microbiota depletion. Interestingly, trehalose treatment effectively reduced pancreatic injury and ameliorated the SAP-induced microbial metabolism imbalance by promoting carbohydrate metabolism and suppressing lipid metabolism. The effect of trehalose was depend on the gut microbiota, especially the expansion of Muribaculaceae. Mechanistically, trehalose-remodelled gut microbiota suppressed SAP-induced increases in serum TG, IL-6, IL-17A, and TNF-α levels, inhibited caspase-3-mediated apoptosis, and reduced macrophage infiltration into the pancreas. Overall, our study revealed that trehalose ameliorates SAP by modulating gut microbial metabolism homeostasis, providing new insights into the “microbial metabolism‒gut‒pancreatic axis”.

BACKGROUND:Esophageal stricture (ES), a common complication after endoscopic submucosal dissection (ESD), is the consequence of excessive fibrosis and scar formation. The fibroblast-to-myofibroblast differentiation is a key characteristic in the pathogenesis of ES, but the molecular basis remains poorly understood. METHODS:According to the human transcriptome sequencing analysis, which utilized different expression gene analysis and weighted gene co-expression network analysis, the potential gene associated with ES was explored. Furthermore, we utilized the rat model of ES and the temporal progression of ES after drug treatment to elucidate the role of DPP4 in ES. Subsequently, we identified a significant association between DPP4 and the progression of ES. Finally, we validated our conclusions through experiments on Bama pigs. RESULTS:DPP4 expression was consistently elevated in both human ES tissues and the rat ES model. Upon inhibition of DPP4, the proliferative activity of ES primary cells and the expression of fibrosis-related genes were markedly suppressed. In rats, treatment with a DPP4 inhibitor significantly alleviated ES, which was accompanied by a significant reduction in collagen content and downregulation of fibrosis-related targets. These effects were observed in conjunction with changes in the Hippo-YAP pathway, although the data primarily support a parallel association rather than a hierarchical regulatory relationship between DPP4 and this pathway. CONCLUSIONS:Our findings suggest that DPP4 may contribute to the remodeling of the regenerative microenvironment in ES, with its expression and function occurring in parallel with alterations in the Hippo-YAP pathway. Direct mechanistic evidence establishing a linear upstream-downstream relationship between DPP4 and Hippo-YAP signaling remains to be further elucidated.

Objective:To evaluate critical care professionals' perceptions of the burden of metabolic acidosis (MA) in the intensive care unit (ICU), and assess agreement on indications, modalities, risks, and benefits of sodium bicarbonate therapy. Design:A multinational, web-based survey administered at different times to Chinese and international ICU practitioners. Main outcome measures:The survey comprised 20 items across four domains: 1) perceived epidemiology and research relevance of MA; 2) rationale, indications, and treatment modalities; 3) potential benefits of sodium bicarbonate; and 4) potential adverse effects of sodium bicarbonate. Responses were recorded on a 5-point Likert scale and classified as "Agreed", "Disagreed", or "Uncertain". Results:A total of 1279 responses from 20 countries were analysed. MA was widely recognised as common, clinically relevant, a frequent cause of ICU admission, and an area requiring further research. Most clinicians supported targeted therapy beyond treating underlying causes, though uncertainty remained regarding sodium bicarbonate. Chinese respondents favoured early correction and continuous infusion, while international opinions varied on timing and approach. Perceived benefits, such as reduced vasopressor use and respiratory workload, were supported by Chinese clinicians, whereas international ones remained uncertain. Opinions on adverse effects also diverged. Chinese physicians highlighted risks of hypernatraemia, severe alkalosis, and hypokalemia, while international respondents viewed sodium bicarbonate as safe regarding the risk of fluid overload or pulmonary oedema. Conclusions:This international survey shows broad agreement that MA is a clinically important and understudied condition in the ICU but reveals substantial variability and uncertainty in clinicians' perceptions of sodium bicarbonate therapy, with notable differences between Chinese and international respondents. These findings underscore key knowledge gaps and the need for well-designed clinical trials.

Transpapillary therapy remains a critical treatment modality for main pancreatic duct (MPD) injury after acute necrotizing pancreatitis. This study aimed to verify the factors linked to the technical success of transpapillary drainage by endoscopic retrograde cholangiopancreatography (ERCP) in managing MPD injury, and the impact of technical success on tube duration and overall survival. A retrospective analysis was conducted on patients who underwent ERCP for MPD injuries following acute pancreatitis from May 2019 to April 2021. Univariate and multivariate logistic regression analyses were employed to identify factors associated with successful treatment. Kaplan–Meier curves were used to analyze the impact of technical success on tube duration and overall survival. We included 63 patients in whom MPD opacification was achieved (43 technical successes and 20 failures). The technical success group had a significantly higher proportion of patients whose interval from onset of acute pancreatitis to endoscopic transpapillary drainage (IOP) was less than 90 days (58.14

IntroductionEnteral nutrition (EN) is the preferred route of medical nutrition therapy for critically ill patients. However, enteral feeding intolerance remains a frequent challenge when implementing EN. Pectin, a water-soluble dietary fiber, has been shown to reduce diarrhea and improve feeding tolerance, but existing evidence remains inconsistent. The PROMOTE trial aims to evaluate whether EN supplemented with pectin, compared to usual care, improves EN delivery in critically ill patients.MethodsThis is a multicenter, open-label, randomized, parallel-controlled trial, conducted in 10 centers across China. Newly admitted adult critically ill patients who received invasive mechanical ventilation for less than 72 h and had an indication for EN via gastric access will be enrolled. In addition to standard care, patients assigned to the intervention group will receive EN supplemented with 90 g of pectin per 500 mL of EN solution. The study intervention will be discontinued 7 days after randomization, upon discharge from the study site, upon death, or upon cessation of gastric feeding, whichever occurs first. The primary outcome is the ratio of EN energy intake to the prescribed target energy on Day 5 after randomization. Secondary outcomes include daily energy and protein intake, the incidence of enteral feeding intolerance, duration of ICU stay, duration of mechanical ventilation, duration of hospital stay, 28-day mortality, ICU-free, hospital-free and ventilation-free days to 28 days.DiscussionThis study investigates whether pectin-supplemented EN enhances gastric feeding tolerance and clinical outcomes in critically ill patients. The finding will provide evidence on pectin’s efficacy in optimizing EN delivery and guide early gastric feeding strategies in critical care.Clinical trial registrationhttps://www.chictr.org.cn, identifier ChiCTR2300078477.

BackgroundThis study aimed to investigate whether neutrophil elastase inhibitor (sivelestat sodium) was associated with decreased duration of organ failure in patients with acute pancreatitis (AP) and early organ failure.MethodsBetween January 2022 and December 2024, patients who were diagnosed with AP and early organ failure were included. The primary outcome was organ failure-free days (OFFD) to Day 14 after admission. Propensity score matching (PSM) analysis was performed to control confounders. Multivariate zero-inflated negative binomial regression model was used to evaluate the association between sivelestat sodium and OFFD. An exploratory mediation analysis was carried out to evaluate whether day 3 C-reactive protein partly accounted for the association.Results340 patients were enrolled in this study. After PSM, patients receiving sivelestat sodium had significantly more OFFD than those who did not (median [IQR], 9 [5 to 13] vs. 6 [1 to 10], p = 0.040). Using sivelestat sodium was associated with increased OFFD (Incidence rate ratio = 1.21, p = 0.001) after adjusting for covariates. The exploratory mediation analysis suggested that this association was primarily direct (1.28 days, p = 0.036), with a marginally significant component mediated through day 3 C-reactive protein reduction (0.13 days, p = 0.068).ConclusionSivelestat sodium use was associated with more organ failure-free days in patients with AP and early organ failure, particularly in those with respiratory failure. These findings require confirmation in future prospective randomized trials.

Dysbiosis of the oral microbiome has been associated with esophageal squamous cell carcinoma (ESCC), but how it impacts ESCC remains largely unknown. Surprisingly, we find that the oral microbiota derived from ESCC patients-not that from healthy controls-exhibits potent inhibitory and cytotoxic effects on ESCC cells. This anti-tumor effect is attributable to Veillonella, which is enriched in the ESCC-associated microbiota. Mechanistically, Veillonella produces valeric acid, which is transported into cells via MCT1 and inhibits the GTPase activity of eEF1A1, thereby suppressing protein translation. These findings identify valeric acid as a potential postbiotic for ESCC treatment and underscore the necessity of functional validation beyond observational and correlative studies.

Serum triglycerides have been believed to play a key role in the pathophysiology of hypertriglyceridemia-associated acute pancreatitis (HTG-AP). However, mechanistic studies have shown that high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) may also be involved. We aimed to investigate whether admission levels of HDL-C and ApoA-I were associated with adverse outcomes in HTG-AP. Participants enrolled in the national PERFORM registry between November 2020 and November 2023, with available HDL-C and ApoA-I levels at enrollment, were retrospectively analyzed. The primary outcome was persistent organ failure (POF) within 14 days. Multivariable logistic regression models were used to examine the association of tertiles of HDL-C and ApoA-I with POF risk. Cochran–Armitage trend test and restricted cubic splines were performed to explore the dose–response relationship. Among the 325 patients eventually included, 52 (16.0

Elevated heart rate is associated with poor clinical outcomes across various patient populations, including acute pancreatitis. This study aimed to assess whether trajectories of daily highest heart rate during the acute phase were associated with prolonged organ failure in patients with predicted severe acute pancreatitis (pSAP). This was a secondary analysis of data from a multicenter, randomized, controlled trial that assessed the effects of different crystalloids in patients with pSAP. Based on the daily highest heart rate trajectories over the first five days, patients were categorized into two groups: persistent high (PH) and transient high (TH). The primary outcome was the presence of organ failure or death on day 7. The association between different heart rate trajectories and the primary outcome was modeled with selected confounders (age, gender, BMI, etiologies, and the presence of necrosis at admission). The Multivariable Cox regression model was used to evaluate the association between heart rate trajectories and time to alive and full organ failure resolution. Overall, 183 patients were included in the analysis, of whom 41 (22.4%) were categorized in the PH group and 142 (77.6%) in the TH group. The incidence of organ failure or death on day 7 in the PH group was more than twice as high as that in the TH group (56.1% vs. 23.0%; p < 0.001). After adjustment, the results remained significant (odds ratio 3.85; 95% CIs 1.70–8.99; p = 0.001). Compared to the TH group, patients in the PH group also had a lower cumulative probability of alive and full organ failure resolution within 7 days of enrollment (hazard ratio 0.33; 95% CIs 0.14–0.77; log-rank p = 0.004). Persistent elevated heart rate during the acute phase is associated with more prolonged organ failure in patients with pSAP, indicating that early heart rate control may be a potential therapeutic strategy to improve clinical outcomes.

Currently, tools to dynamically monitor pathogen load and guide antibiotic adjustment in suspected sepsis are limited. In this prospective, multicenter randomized trial (3:1, ddPCR vs standard care), 1,373 patients were followed for 90 days. The primary outcome was diagnostic efficacy; secondary outcomes included mortality and SOFA. ddPCR showed higher detection positivity (54.1% vs 21.6%, p < 2 × 10−16), faster turnaround, and sensitivity of 80.6%. It increased appropriate antimicrobial coverage (12.91% vs 6.1%, p = 0.0039), and sufficient coverage within 0–3 days was associated with improved outcomes (p = 0.026). Baseline pathogen load >3051 copies/mL, day 3 > 404.1 copies/mL, and day 7 > 1348 copies/mL predicted 28-day mortality. Furthermore, ddPCR-guided early, precision-based adjustment of antimicrobial therapy significantly increased the rate of appropriate antimicrobial coverage, thereby translating into a meaningful improvement in survival outcomes among patients with sepsis. ClinicalTrials.gov: NCT05190861. In a multicenter randomized trial of patients with suspected sepsis, droplet digital PCR identified bloodstream pathogens faster and more often than blood culture and guided earlier, better-targeted antibiotics linked to improved survival.

The enteric microbiome and nutrient sensing within the small intestine play critical roles in maintaining host metabolic homeostasis. Although various bacteria and some fungi have established functions in nutrient metabolism, the role of the enteric virome remains poorly understood. Here, we demonstrate that the enteric virome significantly influences carbohydrate digestion and absorption independently of the bacteriome. Furthermore, the virome elicits distinct responses across different intestinal cell types. Specifically, it activates programs for carbohydrate digestion and absorption in intestinal epithelial cells while simultaneously stimulating antigen-presenting cells-Th17 cells-to produce interleukin-22, a cytokine that curbs excessive carbohydrate uptake. The virome's effect on carbohydrate digestion and absorption-whether suppressive or stimulatory-depends on the presence or absence of immune surveillance. This intricate interplay between metabolic and immune pathways establishes the enteric virome as a pivotal regulator of metabolism and reveals the virome's intrinsic capacity to autonomously modulate vertebrate intestinal physiology.

Although insulin is widely used for early lipid lowering in hypertriglyceridemic acute pancreatitis, the clinical benefit of heparin combined with insulin remains unclear. To examine whether low-molecular-weight heparin (LMWH) combined with insulin is superior to insulin alone in improving clinical outcomes in hypertriglyceridemic acute pancreatitis. This multicenter, open-label, parallel-group, superiority randomized clinical trial was conducted from September 21, 2019, to April 2, 2023, across 13 tertiary hospitals in China. The duration of follow-up was 30 days after randomization. Patients aged 18 to 85 years were eligible if they met the diagnostic criteria for acute pancreatitis, presented with baseline serum triglyceride levels between 1000 and 3550 mg/dL, and were admitted within 48 hours of symptom onset. Participants received either subcutaneous LMWH (4000 IU every 12 hours for 3 days) plus insulin (LMWH plus insulin group) or insulin alone (insulin group). The primary end point was a composite of new-onset organ failure (defined as organ failure occurring after randomization but absent during the 24-hour prerandomization period) and/or all-cause mortality within 30 days after randomization. Among 533 randomized patients (median [IQR] age, 39 [33-46] years; 406 [76.2%] male), 264 were randomized to LMWH plus insulin and 269 to insulin alone. The primary end point occurred in 66 (25.0%) of the LMWH and insulin group vs 76 (28.3%) of the insulin group (relative risk [RR], 0.89; 95% CI, 0.67-1.17; P = .40). Both groups achieved the triglyceride target (<500 mg/dL) in a median (IQR) of 2 (1-3) days ( P = .94). Safety outcomes were similar between groups, including new-onset bleeding events (RR, 0.61; 95% CI, 0.15-2.53; P = .73), triglyceride rebound (RR, 0.53; 95% CI, 0.28-1.01; P = .05), and drug-related adverse events (RR, 0.79; 95% CI, 0.30-2.10; P = .64). In this randomized clinical trial, the combination of LMWH and insulin failed to demonstrate superior efficacy vs insulin alone in patients with hypertriglyceridemic acute pancreatitis. LMWH might not be necessary for early lipid-lowering in hypertriglyceridemic acute pancreatitis. ChiCTR.org.cn Identifier: ChiCTR1900023640

To develop contrast-enhanced CT-based nomograms for predicting early intervention efficacy and in-hospital mortality in acute necrotizing pancreatitis (ANP) with persistent organ failure (POF). This retrospective study analyzed 164 ANP patients with POF (110 in the training cohort, 54 in the validation cohort). The Sequential Organ Failure Assessment (SOFA) score was used to evaluate organ dysfunction severity. Contrast-enhanced CT parameters included mean and range CT numbers (HU) of acute necrotic collections (ANC) across anatomical regions, as well as pancreatic necrosis volume (PNV). LASSO regression identified predictors for early intervention efficacy and mortality. Nomograms were assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. Early intervention efficacy predictors included intra-abdominal pressure, cardiovascular hemodynamic changes, and PNV increase. The model demonstrated good predictive performance, with an area under the ROC curve (AUC) of 0.848 (95

Radiation colitis is an inflammatory response induced by damage to colonic tissue from radiation therapy that primarily affects patients undergoing abdominal or pelvic radiation treatments. In this study, we designed a selenium-loaded probiotic (EcN-Se@SA) encapsulated in sodium alginate gel for the oral treatment of radiation colitis. Selenium nanoparticles (Se NPs) exhibit antioxidant, anti-inflammatory, ferroptosis, and tissue repair-promoting properties. To enhance the therapeutic efficacy of Se NPs for radiation-induced colitis, we combined Se NPs with Escherichia coli Nissle 1917 and encapsulated them in sodium alginate hydrogel. The resulting EcN-Se@SA formulation not only withstands gastric acid and intestinal fluids but also remains in the colon and cecum for extended periods. Oral administration of EcN-Se@SA attenuates X-ray-induced colitis in mice through its antioxidant and anti-inflammatory effects, macrophage reprogramming, and inhibition of ferroptosis in histiocytes. This work introduces a promising therapeutic candidate for the treatment of radiation colitis.

AbstractThis study investigated the genetic basis of spontaneous intraabdominal hemorrhage (SIH) in severe acute pancreatitis (SAP) to facilitate the development of more effective treatments for this life‐threatening complication. A four‐phase study was conducted with a large cohort of acute pancreatitis (AP) patients (n = 600). In the first phase, whole‐exome sequencing identified a specific exonic variant (rs1326680184) in the human Fc gamma binding protein (FCGBP) gene consistently associated with SIH. The second phase employed serum ELISA tests, revealing that this variant altered FCGBP protein levels, increasing susceptibility to SIH. In the third phase, functional validation was performed through: (i) in vivo experiments using a Fcgbp‐knockdown mouse model demonstrated that reduced Fcgbp expression exacerbated AP severity and increased the risk of hemorrhage; and (ii) in vitro experiments with FCGBP‐knockdown in human vascular fibroblasts showed that decreased FCGBP expression destabilized the vascular wall, leading to vascular injury in SAP. Finally, the fourth phase compared clinical characteristics of FCGBP rs1326680184 carriers and non‐carriers, finding that carriers exhibited higher risks of severe complications, worse AP prognosis, and demonstrated enhanced diagnostic utility as a predictive indicator. These findings provide critical insights into the genetic basis of SIH in SAP, paving the way for precision therapies and effective prognostic tools to improve AP management and early intervention.

Importance:Although insulin is widely used for early lipid lowering in hypertriglyceridemic acute pancreatitis, the clinical benefit of heparin combined with insulin remains unclear. Objective:To examine whether low-molecular-weight heparin (LMWH) combined with insulin is superior to insulin alone in improving clinical outcomes in hypertriglyceridemic acute pancreatitis. Design, Setting, and Participants:This multicenter, open-label, parallel-group, superiority randomized clinical trial was conducted from September 21, 2019, to April 2, 2023, across 13 tertiary hospitals in China. The duration of follow-up was 30 days after randomization. Patients aged 18 to 85 years were eligible if they met the diagnostic criteria for acute pancreatitis, presented with baseline serum triglyceride levels between 1000 and 3550 mg/dL, and were admitted within 48 hours of symptom onset. Interventions:Participants received either subcutaneous LMWH (4000 IU every 12 hours for 3 days) plus insulin (LMWH plus insulin group) or insulin alone (insulin group). Main Outcomes and Measures:The primary end point was a composite of new-onset organ failure (defined as organ failure occurring after randomization but absent during the 24-hour prerandomization period) and/or all-cause mortality within 30 days after randomization. Results:Among 533 randomized patients (median [IQR] age, 39 [33-46] years; 406 [76.2%] male), 264 were randomized to LMWH plus insulin and 269 to insulin alone. The primary end point occurred in 66 (25.0%) of the LMWH and insulin group vs 76 (28.3%) of the insulin group (relative risk [RR], 0.89; 95% CI, 0.67-1.17; P = .40). Both groups achieved the triglyceride target (<500 mg/dL) in a median (IQR) of 2 (1-3) days (P = .94). Safety outcomes were similar between groups, including new-onset bleeding events (RR, 0.61; 95% CI, 0.15-2.53; P = .73), triglyceride rebound (RR, 0.53; 95% CI, 0.28-1.01; P = .05), and drug-related adverse events (RR, 0.79; 95% CI, 0.30-2.10; P = .64). Conclusions and Relevance:In this randomized clinical trial, the combination of LMWH and insulin failed to demonstrate superior efficacy vs insulin alone in patients with hypertriglyceridemic acute pancreatitis. LMWH might not be necessary for early lipid-lowering in hypertriglyceridemic acute pancreatitis. Trial Registration:ChiCTR.org.cn Identifier: ChiCTR1900023640.