Impact of metabolic syndrome components on clinical outcomes in hypertriglyceridemia-induced acute pancreatitis.

BACKGROUND: The incidence of hypertriglyceridemia (HTG)-induced acute pancreatitis (AP) is steadily increasing in China, becoming the second leading cause of AP. Clinical complications and outcomes associated with HTG-AP are generally more severe than those seen in AP caused by other etiologies. HTG-AP is closely linked to metabolic dysfunction and frequently coexists with metabolic syndrome or its components. However, the impact of metabolic syndrome components on HTG-AP clinical outcomes remains unclear. AIM: To investigate the impact of metabolic syndrome component burden on clinical outcomes in HTG-AP. METHODS: In this retrospective study of 255 patients diagnosed with HTG-AP at the First Affiliated Hospital of Guangxi Medical University, we collected data on patient demographics, clinical scores, complications, and clinical outcomes. Subsequently, we analyzed the influence of the presence and number of individual metabolic syndrome components, including obesity, hyperglycemia, hypertension, and low high-density lipoprotein cholesterol (HDL-C), on the aforementioned parameters in HTG-AP patients. RESULTS: This study found that metabolic syndrome components were associated with an increased risk of various complications in HTG-AP, with low HDL-C being the most significant risk factor for clinical outcomes. The risk of complications increased with the number of metabolic syndrome components. Adjusted for age and sex, patients with high-component metabolic syndrome had significantly higher risks of renal failure [odds ratio (OR) = 3.02, 95%CI: 1.12-8.11)], SAP (OR = 5.05, 95%CI: 2.04-12.49), and intensive care unit admission (OR = 6.41, 95%CI: 2.42-16.97) compared to those without metabolic syndrome. CONCLUSION: The coexistence of multiple metabolic syndrome components can synergistically worsen the clinical course of HTG-AP, making it crucial to monitor these components for effective disease management.

Effectiveness and safety of low molecular weight heparin in the management of acute pancreatitis: a systematic review and meta-analysis.

BACKGROUND: Recent studies suggest that low-molecular-weight heparin (LMWH) may play a role in mitigating the severity of acute pancreatitis (AP). This systematic review and meta-analysis aims to synthesise existing evidence on the effectiveness and safety of LMWH in the treatment of moderately-severe and severe AP. METHODS: This systematic review and meta-analysis was conducted in accordance with the 2020 update of the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The systematic search was conducted in MEDLINE, the Cochrane Central Register of Controlled Trials, Scopus, and EMBASE, covering studies published up to February 2024. Randomised controlled trials (RCTs) and observational studies (n-RCTs) that reported the differences in the outcomes of AP for patients receiving LMWH in addition to the standard treatment (Intervention), compared to patients managed by standard treatment without LMWH (Control) were eligible. A random-effects model was used to calculate the pooled relative risk (RR) and mean differences (MD) with the corresponding 95% CI. RESULTS: Thirteen studies were included in the meta-analysis, all published between 2004 and 2022. Eight studies were RCTs, and five were n-RCTs. Data from 13,709 patients (6.971 Interventions and 6.738 Controls) were analysed. The comparison of Intervention and Control groups showed the superiority of LMWH to standard treatments in terms of overall mortality (RR = 0.44, 95% CI = 0.31; 0.64, P < 0.0001, I2 = 51%), acute necrotic collections (RR = 0.24, 95% CI = 0.09; 0.62, P = 0.003, I2 = 0%), and organ failure (RR = 0.67, 95% CI = 0.48; 0.93, P = 0.02, I2 = 78%). The Intervention group showed superior outcomes compared with the Control group for gastrointestinal bleeding (RR = 0.64, 95% CI = 0.44; 0.94, P = 0.02, I2 = 0%), length of hospital stay (MD= - 6.08, 95% CI = - 10.08; - 2.07, P = 0.003, I2 = 98%), need for operative interventions (RR = 0.50, 95% CI = 0.29; 0.87, P = 0.01, I2 = 61%), and vascular thrombosis (RR = 0.43, 95% CI = 0.31; 0.61, P < 0.00001, I2 = 0%). CONCLUSIONS: Moderate to high-quality evidence suggests that early intervention with LMWH could improve the prognosis of non-mild AP in terms of mortality, organ failure, and decreased incidence of vascular thrombosis. In light of our findings, integrating LMWH into the treatment regimen for moderate-severe to severe AP is advocated.

DGA ameliorates severe acute pancreatitis through modulating macrophage pyroptosis.

Severe acute pancreatitis (SAP) is an inflammatory disease with varying severity, ranging from mild local inflammation to severe systemic disease, with a high incidence rate and mortality. Current drug treatments are not ideal. Therefore, safer and more effective therapeutic drugs are urgently needed. 7α,14ß-dihydroxy-ent-kaur-17-dimethylamino-3,15-dione DGA, a diterpenoid compound derivatized from glaucocalyxin A, exhibits anti-inflammatory activity. In this study, we demonstrated the therapeutic potential of DGA against SAP and elucidated the underlying mechanisms. Treatment with DGA markedly (1) inhibited death of RAW264.7 and J774a.1 cells induced by Nigericin and lipopolysaccharide, (2) alleviated edema, acinar cell vacuolation, necrosis, and inflammatory cell infiltration of pancreatic tissue in mice, and (3) inhibited the activity of serum lipase and the secretion of inflammatory factor IL-1ß. DGA significantly reduced the protein expression of IL-1ß and NLRP3 and inhibited the phosphorylation of NF-κB. However, DGA exhibited no inhibitory effect on the expression of caspase-1, gasdermin D (GSDMD), NF-κB, TNF-α, or apoptosis-associated speck-like protein (ASC) and on the cleavage of caspase-1 or GSDMD. Molecular docking simulation confirmed that DGA can bind to TLR4 and IL-1 receptor. In conclusion, DGA may effectively alleviate the symptoms of SAP in mice and macrophages by inhibiting the binding of TLR4 and IL-1 receptor to their ligands; therefore, DGA is a promising drug candidate for the treatment of patients with SAP.

Efficacy of Topical Epinephrine in Preventing Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Meta-analysis.

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication of ERCP. As the clinical effectiveness of topical epinephrine in preventing PEP is elusive, this work attempts to assess its impact on PEP prevention. The databases Embase, Web of Science, PubMed, and Cochrane Library were searched for randomized controlled trials (RCTs) and retrospective cohort studies (RCSs) on topical epinephrine in PEP prevention (data cutoff, November 2022). This study included a total of 10 research articles, involving 5683 patients, comprising 7 RCTs and 3 RCSs. The results of the meta-analysis indicated that epinephrine had no significant effect on preventing PEP or improving its severity. The meta-analysis results of RCTs subgroup revealed no significant difference in the incidence of PEP between patients receiving epinephrine treatment [alone/in combination with nonsteroidal anti-inflammatory drugs (NSAIDs)] vs. without epinephrine treatment (control group) (P = .23). However, patients treated with epinephrine alone experience a lower incidence of PEP compared to the control group (risk ratio [RR] = 0.28, 95% CI = 0.14-0.56, P = .0004). The treatment with epinephrine+NSAIDs vs. NSAIDs showed no significant difference (P = .95). The meta-analysis results of RCSs subgroup demonstrated a significant reduction in the incidence of PEP with the epinephrine+NSAIDs vs. NSAIDs (P < .05). Regarding the severity of PEP [mild, and moderate to severe (M-S)] in the RCT subgroup, the incidence of PEP was not reduced with epinephrine treatment (alone/in combination with NSAIDs) vs. control group. In the RCS subgroup, receiving epinephrine (alone/in combination with NSAIDs) reduced the incidence of mild PEP, while it had no effect on the incidence of M-S PEP. Epinephrine was not significantly effective in preventing PEP and improving its severity. The combined use of NSAIDs and epinephrine as a possible preventive measure requires further investigation into its efficacy.

Possible omadacycline induce acute pancreatitis: a case report and literature review.

BACKGROUND: Omadacycline is a new generation of tetracycline antibiotics, and its clinical application is increasing. We report the first case of acute pancreatitis possibly induced by omadacycline. CASE PRESENTATION: The patient was admitted to the emergency intensive care unit due to community-acquired pneumonia. The initial treatment consisted of meropenem combined with levofloxacin, and the regimen was subsequently switched to omadacycline combined with cefoperazone/sulbactam due to sputum culture showing carbapenem-resistant Acinetobacter baumannii. Seven days after the administration of omadacycline, abdominal tenderness occurred, and CT scan revealed an enlarged gallbladder with exudation from the pancreatic head. The patient was diagnosed with acute pancreatitis and improved after dis-continuing omadacycline. CONCLUSIONS: Omadacycline, like other tetracycline antibiotics, may cause pancreatitis. Combination medications can be an important factor in this adverse reaction.

An Unusual Presentation of Fatal Acute Haemorrhagic Pancreatitis in a Young Adult.

Acute haemorrhagic pancreatitis is a medical emergency and the most severe form of Acute Pancreatitis. It is characterized by severe epigastric pain that radiates to the back and is associated with vomiting. If not diagnosed and managed promptly, it may result in sudden, unexpected, unexplained deaths which fall within the medicolegal domain. In such cases, the role of an autopsy is of paramount importance to determine the cause of death. Here we report a young adult, who presented to the local hospital with vague abdominal discomfort and vomiting following alcohol intake and referred to our tertiary care center for further management. But he was received dead on arrival at our hospital. The diagnosis of acute haemorrhagic pancreatitis was made only after the post mortem examination. Awareness of the physicians about the unusual symptoms in acute haemorrhagic pancreatitis and the need for pancreas examination at autopsy of all sudden deaths is emphasised.

Clinical efficacy of ilaprazole combined with somatostatin on severe acute pancreatitis and the effects on oxidative stress and inflammatory response.

This study investigates the clinical efficacy of ilaprazole combined with somatostatin on severe acute pancreatitis (SAP) and the effects on oxidative stress and inflammatory response. Seventy SAP patients were randomized to the control and observation groups, which received the somatostatin treatment and ilaprazole combined with somatostatin treatment for seven days, respectively. Results found that, the time of abdominal pain relief, time of serum amylase recovery, time of urinary amylase recovery and time of defecation recovery in the observation group were shorter than those in the control group (P<0.05). After the treatment, comparing to the control group, in the observation group the heart rate decreased (P<0.05), the mean arterial pressure and the central venous pressure increased (P<0.05), the serum levels of super oxide dismutase and glutathione peroxidase increased (P<0.05) and the serum levels of malondialdehyde, tumor necrosis factor α, interleukin-6, C-reactive protein decreased (P<0.05). In treatment of SAP, ilaprazole combined with somatostatin can enhance the curative efficacy and decrease the oxidative stress and the inflammatory response in patients. In addition, it cannot increase the adverse reactions, with good safety.

Evaluating the prognostic performance of the novel ERAP score in Vietnamese acute pancreatitis patients.

Early recognition of severe acute pancreatitis (AP) is crucial for timely intervention. This study aims to evaluate the prognostic accuracy of the Emergency Room Assessment of AP (ERAP) score and compare it with the Bedside Index for Severity in AP (BISAP) score in predicting severe AP, mortality, and persistent multiple organ failure (MOF) in Vietnamese patients. This prospective cohort study included AP patients admitted to Cho Ray Hospital between August 2021 and May 2022. Patient data, including demographics, clinical presentations, and laboratory results, were collected upon admission. The ERAP and BISAP scores were calculated from these admission data. The prognostic accuracy for severe AP, mortality, and persistent MOF was assessed via the area under the receiver-operating characteristic curve (AUC). Among 167 AP patients (mean age 41.5 ±â€…12.0 years), hypertriglyceridemia (34.7%) and alcohol (22.2%) were the most prevalent etiologies. Severe AP accounted for 33.5% of the patients. Mortality rates were higher in persistent MOF patients (42.9%) than in persistent single-organ failure patients (3.6%), with a P value <.001. The ERAP score had AUCs for predicting severe AP, mortality, and persistent MOF of 0.899, 0.817, and 0.867, respectively, with an optimal cutoff of ≥2. The ERAP score had a better prognostic value than the BISAP score in predicting severe AP (AUC: 0.899 vs 0.820; P = .0072) and persistent MOF (AUC: 0.867 vs 0.785; P = .0193) but had a similar prognostic value for mortality (AUC: 0.817 vs 0.728; P = .0628). The ERAP score has strong predictive value for severe AP and persistent MOF, surpassing the BISAP score in these categories while maintaining similar accuracy for mortality prediction in the Vietnamese population. The ERAP score can be a valuable tool for the early identification of high-risk AP patients, enabling timely and appropriate clinical interventions.

Emodin alleviates lung injury via the miR-217-5p/Sirt1 axis in rats with severe acute pancreatitis.

Acute lung injury (ALI) is closely related to high mortality in severe acute pancreatitis (SAP). This study unveils the therapeutic effect and mechanism of miR-217-5p on SAP-associated ALI. The miR-217-5p RNA expression was significantly up-regulated in lipopolysaccharide (LPS)-stimulated primary rat alveolar epithelial type II cells (AEC II) and sodium taurocholate-treated pancreas and lung in SAP rats. miR-217 inhibition protected AEC II from LPS-induced damage by inhibiting apoptosis and reducing the TNF-α, IL-6, and ROS levels. miR-217 inhibition suppressed apoptosis and alleviated mitochondrial damage through mitochondria-mediated apoptotic pathway in vitro. Sirt1 is a direct target of miR-217-5p. Dual-luciferase reporter assay confirmed the binding of miR-217-5p to Sirt1 mRNA 3'-UTR. The rescue experiment identified that the anti-apoptotic, anti-inflammatory, and anti-oxidative effects of miR-217 inhibition were mediated by Sirt1 in vitro. Emodin (EMO) protected AEC II from LPS-induced damage and alleviated pancreatic and lung tissue injuries. EMO exerted similar effects as miR-217 inhibition in vitro and in vivo. The effects of EMO were abolished by miR-217 overexpression. In conclusion, miR-217-5p inhibition exerts protective effects on SAP-ALI in vitro and in vivo by repressing apoptosis, inflammation, and oxidative stress through Sirt1 activation. EMO protects against lung injuries in SAP-associated ALI rats through miR-217-5p/Sirt1 axis.

The BRD4 Inhibitor I-BET-762 Reduces HO-1 Expression in Macrophages and the Pancreas of Mice.

In pancreatic cancer, the tumor microenvironment (TME) accounts for up to 90% of the tumor mass. Pancreatitis, characterized by the increased infiltration of macrophages into the pancreas, is a known risk factor for pancreatic cancer. The NRF2 (nuclear factor erythroid 2-related factor 2) transcription factor regulates responses to oxidative stress and can promote cancer and chemoresistance. NRF2 also attenuates inflammation through the regulation of macrophage-specific genes. Heme oxygenase 1 (HO-1) is expressed by anti-inflammatory macrophages to degrade heme, and its expression is dependent on NRF2 translocation to the nucleus. In macrophages stimulated with conditioned media from pancreatic cancer cells, HO-1 protein levels increased, which correlated with higher NRF2 expression in the nuclear fraction. Significant differences in macrophage infiltration and HO-1 expression were detected in LSL-KrasG12D/+; Pdx-1-Cre (KC) mice, Nrf2 whole-body knockout (KO) mice and wildtype mice with pancreatitis. Since epigenetic modulation is a mechanism used by tumors to regulate the TME, using small molecules as epigenetic modulators to activate immune recognition is therapeutically desirable. When the bromodomain inhibitor I-BET-762 was used to treat macrophages or mice with pancreatitis, high levels of HO-1 were reduced. This study shows that bromodomain inhibitors can be used to prevent physiological responses to inflammation that promote tumorigenesis.