Hypertriglyceridemic acute pancreatitis (HTG-AP) progresses rapidly with poor prognosis. Intestinal barrier dysfunction and excessive oxidative stress contribute to its pathogenesis, but specific mediators linking gut injury, oxidative stress and pancreatic damage remain unclear. Here, we identify endogenous phenyllactic acid (PLA) as a critical metabolite regulating intestinal barrier integrity and oxidative homeostasis in HTG-AP. We noted serum PLA, a disease-associated metabolite whose reduction correlates with gut dysbiosis and pancreatic inflammation in HTG-AP. PLA supplementation in HTG-AP mice attenuated intestinal barrier dysfunction and mitigated intestinal oxidative stress, as evidenced by improved gut dysbiosis, reduced reactive oxygen species accumulation, restored superoxide dismutase activity, restored barrier integrity, reduced bacterial translocation to the pancreas, and decreased serum lipopolysaccharide levels, ultimately mitigating pancreatic injury. RNA sequencing of colonic tissue revealed peroxisome proliferator-activated receptor (PPAR) signaling as one of the most significantly altered pathways in HTG-AP. PPARγ expression was markedly reduced in colonic epithelial cells and upregulated upon PLA treatment. Knockdown of colonic epithelial PPARγ via adeno-associated virus abrogated the beneficial effects of PLA on intestinal barrier integrity, oxidative stress and pancreatic injury in HTG-AP mice. The protective effects of PLA were phenocopied by the PPARγ agonist rosiglitazone. Collectively, these findings identified gut microbiota-derived PLA as an endogenously derived metabolite modulating intestinal oxidative stress and barrier function. Using male C57BL/6J mice to establish an HTG-AP model, we further revealed that PLA exerts protective effects against HTG-AP by targeting colonic PPARγ to modulate the gut-pancreas axis, highlighting PLA as a promising candidate for targeted intervention in HTG-AP.

Objective: To investigate the therapeutic efficacy of surgical rescue (SR) in patients with severe acute pancreatitis (SAP) complicated by infected pancreatic necrosis (IPN) and sepsis,and to identify the risk factors associated with SR failure. Methods: Clinical data were retrospectively collected from 130 patients with SAP complicated by IPN who developed sepsis and were admitted to the First Affiliated Hospital of Harbin Medical University between January 2019 and October 2025. The cohort included 86 males and 44 females,with an age(M(IQR)) of 47(21) years (range:22 to 74 years). Patients were divided into an SR group (n=86) and a non-SR group (n=44) based on whether SR was performed. Significant differences were observed between the two groups in age,Balthazar-CTSI score,and creatinine and urea nitrogen levels at the onset of sepsis (all P<0.05). After propensity score matching (PSM) with a 1∶1 nearest-neighbor method and a caliper value of 0.2 to balance baseline characteristics,76 patients were included (38 in each group). Patients were also divided into an SR success group (n=52) and an SR failure group (n=34). Univariate analysis was performed using independent sample t-test,Mann-Whitney U test,chi-square test,or Fisher's exact test as appropriate. Variables with P<0.05 in univariate analysis were included in a multivariate logistic regression model. The predictive value of the model for SR failure was assessed using receiver operating characteristic (ROC) curve analysis. Results: Multivariate logistic regression analysis identified SR as an independent protective factor for survival (OR=0.184,95%CI: 0.063 to 0.537,P<0.05). Kaplan-Meier survival curves showed that the 28 d cumulative survival rate was higher in the SR group than that in the non-SR group (χ²=14.950,P<0.05). Multivariate Logistic analysis identified age (OR=1.188, 95%CI: 1.068 to 1.322),acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) score (OR=1.303,95%CI: 1.043 to 1.628),sequential organ failure assessment (SOFA) score at the onset of sepsis (OR=1.840,95%CI: 1.205 to 2.811), and timing of first SR (OR=3.004, 95%CI: 1.208 to 7.469) as independent risk factors for SR failure (all P<0.05). The area under the ROC curve was 0.950 (95%CI: 0.903 to 0.997). Conclusions: SR can prolong survival time in SAP patients with IPN who develop sepsis. Age, higher APACHE Ⅱ score,higher SOFA score at initial sepsis diagnosis,and delayed time to first SR are independent prognostic factors for SR failure.

The Adult Chronic Pancreatitis (CP) Working Group, formed at inception of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC), has developed a robust framework and infrastructure to conduct clinical, translational, and mechanistic studies of CP. At its core is PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies (PROCEED), the first longitudinal cohort study of CP in US adults, launched in 2017. PROCEED has developed a well annotated clinical dataset of over 2,000 deeply-phenotyped participants, a biorepository and an imaging repository. Investigators have published promising data on blood- and imaging- based biomarkers of CP diagnosis and pain, which are awaiting validation. Clinical observations include classification of patients into mechanism-based pain phenotypes using responses to PROMIS questionnaires, prevalence and predictors of opioid use, prevalence of psychological comorbidity, and osteopathy in CP patients. Pilot clinical trials have evaluated the effect of oral indomethacin on pancreas fluid prostaglandin E2 levels, and Internet-based cognitive behavioral therapy (CBT) for chronic pain. Results of pilot trials have led to an ongoing definitive randomized clinical trial for CBT. The rich environment and resources have facilitated mentorship and academic development of many early-stage investigators. Investigators outside of the consortium have opportunities for collaboration. In the next 5 years, the Working Group plans to further strengthen the research platform, complete primary and key secondary analyses of PROCEED and ancillary studies, continue efforts to develop biomarkers for diagnosis and prognosis of CP, and complete ongoing clinical trials to address unanswered questions in the field.

Small intestinal bacterial overgrowth (SIBO) refers to an abnormal increase in the number of bacteria in the small intestine and is observed in various diseases. SIBO can also develop after long-term use of proton pump inhibitors (drug-induced SIBO), bariatric surgery, gastrectomy, and other surgeries (postoperative SIBO). The aim of this narrative review is to summarize all of the published information on the treatment of SIBO in as much detail as possible and present it separately for each specific disease and intervention associated with SIBO. The most extensively studied drug for the treatment of SIBO is rifaximin. It eliminates SIBO in 63% of cases; however, most studies lack a control group. Small RCTs assessing the effects of this antibiotic on SIBO have reported conflicting results, and a meta-analysis showed no effect. A large RCT is required to verify the results of uncontrolled studies. Neomycin and norfloxacin showed efficacy in the treatment of SIBO in single RCTs, with elimination rates of 20 and 100%, respectively. Ciprofloxacin, rifamycin, metronidazole, and other antibiotics, as well as ursodeoxycholic acid, showed positive effects for the treatment of SIBO, but only in uncontrolled studies or in comparison with rifaximin or other drugs. The reported elimination rates were 54%, 67%, 79%, and 75%, respectively. Eradication therapy for Helicobacter pylori infection eliminated SIBO at a rate of approximately 70%. Probiotics have been tested for treatment of SIBO in various diseases. VSL#3 and Saccharomyces boulardii CNCM I-745 were effective in RCTs, with elimination rates of 58% and 80%, respectively. In conclusion, when selecting SIBO treatment regimens, those that have demonstrated the greatest efficacy for a specific concomitant disease should be preferred, despite the generally low level of evidence supporting these approaches in most cases.

This report describes a 59-year-old woman with a history of malignancy and post-tuberculosis lung disease complicated by chronic cavitary pulmonary aspergillosis. She was admitted with worsening hemoptysis and underwent bronchial artery embolization. However, she subsequently developed massive post-procedural hemoptysis, requiring mechanical ventilation. Sputum metagenomic next-generation sequencing detected SARS-CoV-2 and bacterial pathogens, prompting Paxlovid treatment for COVID-19 pneumonia. While her respiratory symptoms improved, epigastric pain developed. Based on elevated serum amylase/lipase and CT-confirmed peripancreatic inflammation, she was diagnosed with acute pancreatitis. One year later, pulmonary tuberculosis and liver metastasis recurred. This case highlights acute pancreatitis temporally associated with COVID-19 pneumonia in a patient with multiple competing risk factors. Further, this case underscores the diagnostic complexity of structural lung disease with overlapping infections such as COVID-19 and stresses on the need for long-term surveillance.

Regulatory T cells (Tregs) are essential for maintaining immune tolerance and limiting collateral tissue injury during inflammation. In pancreatic diseases, however, Treg function is highly context-dependent: protective in acute inflammatory settings by restraining excessive immune activation, yet potentially pathogenic by fostering immunosuppression and immune escape in pancreatic ductal adenocarcinoma (PDAC). Acute pancreatitis (AP), chronic pancreatitis (CP), and PDAC share overlapping immune microenvironmental features, including cytokine-driven T-cell reprogramming, barrier dysfunction-associated microbial translocation, and stromal-immune crosstalk. Understanding Treg behaviour along the pancreatitis-PDAC continuum requires deciphering context-dependent immune microenvironmental mechanisms that shift from protective regulation to tumour-promoting immunosuppression. Recent evidence highlights that indiscriminate Treg depletion may paradoxically accelerate pancreatic tumorigenesis in specific settings, underscoring the need to resolve Treg heterogeneity, tissue residency, and stage-specific roles. In this review, we summarise current mechanistic insights into Treg-mediated regulation in AP and CP (including Th17/Treg balance and fibrosis-associated immune networks) and in PDAC (including Treg phenotypic diversity and interactions with myeloid cells and stroma). We further discuss emerging therapeutic strategies that modulate Tregs directly or indirectly, and propose a translational framework for aligning Treg-targeted interventions with disease stage and immune context to improve outcomes in pancreatic inflammation and cancer.

Although individual complications of pancreatic pseudocysts are well-documented, the occurrence of multiple complications from a single pseudocyst is exceptionally rare. This report illustrates the surgical management of a cascade of life-threatening complications arising from a single pancreatic pseudocyst of gastric fistulization, intraperitoneal rupture, and splenic involvement following intracystic hemorrhage. A 42-year-old female patient with chronic alcoholic pancreatitis and a known pancreatic tail pseudocyst presented with severe abdominal pain and emesis. The workup revealed active extravasation from a splenic artery branch that was managed with arterial embolization. The patient returned three days following embolization with sepsis and peritonitis. An emergent exploratory laparotomy revealed an infected hematoma and intraperitoneal rupture of the pseudocyst that had fistulized into the stomach with splenic involvement, requiring a distal pancreatectomy, splenectomy, and wedge gastrectomy. Postoperatively, the patient's nasogastric tube (NG) perforated the suture line, necessitating further repair, but she otherwise recovered uneventfully. Arterial embolization can achieve hemostasis in cases of hemorrhagic pseudocysts, but patients remain vulnerable to further pseudocyst complications. Definitive management involves drainage or resection. The management of ruptured pseudocysts should be determined based on patient stability and involvement of surrounding structures.