Chronic pancreatitis (CP) is a chronic inflammatory disease caused by multiple factors. Numerous studies have found that implementing surgical drainage in the early stages of CP can help alleviate pain and improve prognosis in patients. However, there is currently no consensus on clinical indications for surgical drainage in the early stages of CP, making it difficult to determine whether surgical drainage is necessary. This study aims to use metabolomics methods to identify potential biomarkers that can differentiate whether CP patients require surgical drainage.

This study included two cohorts. The training cohort consisted of 32 serum samples from CP patients and 31 serum samples from healthy controls. The validation cohort comprised 73 serum samples from CP patients and 27 serum samples from healthy controls. All serum samples from CP patients were collected within 24 h of hospital admission. Liquid chromatography-tandem mass spectrometry (LC-MS) was used to perform metabolomic analysis on all collected serum samples.

Based on the validation cohort, 24 differential metabolites, including 1-(6-[3]-ladderane-hexanyl)-2-(8-[3]-ladderane-octanyl)-sn-glycerophosphocholine, PE(18:1(9Z)/20:4(5Z,8Z,11Z,14Z)), and PGP(16:0/20:4(5Z,8Z,11Z,14Z)), were identified as potential biomarkers for distinguishing whether CP patients require surgical drainage. Among these, the combination of 1-(6-[3]-ladderane-hexanyl)-2-(8-[3]-ladderane-octanyl)-sn-glycerophosphocholine and PE(18:1(9Z)/20:4(5Z,8Z,11Z,14Z)) demonstrated improved diagnostic value in joint ROC analysis, with an AUC value of 0.819 (95% CI: 0.691-0.924).

This study represents the first prospective cohort research to identify 24 differential metabolites in serum through metabolomic profiling, which can be used for the early diagnosis of whether CP patients require surgical drainage.

AMP-activated protein kinase (AMPK) is the master regulator of cellular energy which gets activated during energy stress and restores tissue homeostasis. AMPK is widely expressed in the pancreas and is involved in protein synthesis. In cerulein-induced acute pancreatitis (AP), diminished AMPK activity in the pancreatic tissue may be associated with pancreatic inflammation and oxidative stress. Our results demonstrated that berberine (BR) treatment produced significant decrease in plasma amylase and lipase levels and improved histopathological features in AP mice model. Myeloperoxidase (MPO) activity indicated that BR suppressed the infiltration of neutrophils in pancreas. BR treatment markedly decreased the levels of proinflammatory cytokines including interleukins (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α) via inhibition of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression. In addition, BR activates the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling and inhibits cerulein-induced oxidative-nitrosative stress. Mechanistically, we found inhibition of AMPK activity in cerulein-induced AP, while BR-treated animals showed marked increase in the AMPK expression. Together, our study indicated that BR-mediated AMPK activation in pancreatic tissues demonstrated attenuation of cerulein-induced oxidative stress and inflammation. Based on our observations, further exploration of this promising natural product against AP and associated complications may lead to promising therapeutic options.

Severe sepsis with septic shock (SSWSS) is a potential and severe complication that can arise among patients hospitalized for acute biliary pancreatitis.

We queried the 2018-2021 National Inpatient Sample for adults with a primary diagnosis code of acute biliary pancreatitis without necrosis or infection. Baseline characteristics of the patients were studied and multivariate regression models were used to appraise the roles of different factors for events of SSWSS.

We evaluated 136,140 adults who had acute biliary pancreatitis without necrosis or infection on admission; their median age was 57.0 years, and the majority were female (60.6%). Of these, 435 patients developed SSWSS. Higher odds were seen in cases with coexisting chronic kidney disease (P<0.001), liver cirrhosis (P<0.001), and human immunodeficiency virus infection (P<0.001). Races other than White/Black/Hispanics had higher odds (P<0.001) than Whites. Females were less likely to report SSWSS (P<0.001) than males. Moreover, patients from the 26th-50th median household quartiles had lower odds of SSWSS than those in the 0-25th quartiles. Medium (P<0.001) and large (P<0.001) hospitals reported more cases than small hospitals. Admissions in the southern areas of the United States also exhibited higher odds (P=0.026), than Northeast regions. Lower odds were noted in smokers (P<0.001) and cases with dyslipidemia (P=0.048). SSWSS led to higher mortality rates (65.5% vs. 0.4%).

In our nationwide analysis, we found that episodes of SSWSS among patients with acute biliary pancreatitis were influenced by several factors. SSWSS patients also had higher mortality.

The rising prevalence of overweight and obesity across the globe is a major threat both to public health and economic development. This is mainly due to the link of obesity with the development and outcomes of non-communicable diseases (NCDs). NCDs are a leading cause of global death and disability, and reducing the burden of NCDs on patients and healthcare systems is of critical importance to improve public health. Obesity is projected to be the number one preventable risk factor for NCDs by 2035, and there is an urgent need to tackle the growing obesity rates in order to reduce NCD incidence and severity. Here, we review the current understanding of the impact of obesity on NCD burden in general, as well as the epidemiological and mechanistic relationship between obesity and some of the most common classes of NCDs. By literature review, we found that over 70% of NCDs have a documented association with obesity, highlighting the importance of a better understanding of the pathophysiologies underlying obesity/overweight as well as the interaction between obesity and NCDs in order to reduce global disease burden.

A 68-year-old male presented to the Emergency Department with a one-month history of intermittent epigastrium pain. Laboratory tests revealed leukocytosis and elevated lipase (4129 UI/l), with normal liver function, so he was admitted for its first episode of acute pancreatitis. Abdominal ultrasound showed liver steatosis, without cholelithiasis or bile duct dilatation. A thoraco-abdominal computed tomography was performed, revealing a pedunculated gastric polyp in lesser curvature measuring 64x38mm with no evidence of metastatic disease. Gastroscopy was performed, showing a 7-cm pedunculated gastric polyp prolapsed through the pylorus into the duodenum. The polyp was moved into the stomach, and a fragmented resection of the polyp was carried out with a hot snare. Histopathologic evaluation was compatible with hyperplastic polyp with low-grade dysplasia. The patient had a favourable evolution with no complications after the procedure.

Macrophage infiltration and activation is a critical step during acute pancreatitis (AP). NLRP3 inflammasomes in macrophages plays a critical role in mediating pancreatic inflammatory responses. Qing-Yi Decoction(QYD)has been used for many years in clinical practice of Nankai Hospital combined with traditional Chinese and western medicine treatment of acute pancreatitis. Although QYD has a well-established clinical efficacy, little is known about its bioactive ingredients, how they interact with different therapeutic targets and the pathways to produce anti-inflammatory effects. Here, we elucidate the therapeutic effects of QYD against acute pancreatitis and reveal its mechanism of action.

The main components of QYD were identified using UHPLC-Q-Orbitrap MS. Network pharmacology was employed to predict potential therapeutic targets and their mechanisms of action. C57BL/6 mice were randomly divided into control group, model group, low, medium and high dose (6, 12, 24 g/kg) QYD groups, with 10 mice in each group. The therapeutic effect of QYD on cerulein-induced acute pancreatitis. (CER-AP) was evaluated by histopathological score, immunohistochemistry, serum amylase and cytokines detection by ELISA. The protein expressions of MyD88/NF-κB/NLRP3 signaling pathway were detected by Western blotting. Along with molecular docking of key bioactive compounds and targets, RAW264.7 cells stimulated with 1μg/ml LPS is used to screen components with more potent effects on target proteins. AR42 J cells were stimulated with 100 nM dexamethasone (dexa) combined with 10 nM cerulein (CN) as s a cell-culture model of acute pancreatitis. Inhibitory effects of the main chemical composition Wogonoside on NLRP3 inflammasomes were analyzed by qRT-PCR and Western blots.

Using UHPLC-Q-Orbitrap MS, 217 compounds were identified from QYD, including Wogonoside, Catechins, Rhein, etc. A visualization network of QYD-compounds-key targets-pathways-AP show that QYD may modulate PI3K-Akt signaling pathway, NOD-like receptor signaling pathway, MAPK signaling pathway, Ras signaling pathway and Apoptosis signaling pathway by targeting TNF, IL1β, AKT1, TP53 and STAT3 exerting a therapeutic effect on AP. QYD administration effectively mitigated CER-induced cytokine storm, pancreas edema and serum amylase. QYD (12 mg/kg) showed better effect. The protein expression levels of MyD88, NF-κB, NLRP3, Caspase-1 and GSDMD in pancreatic tissue were significantly decreased. Through molecular docking and LPS-RAW264.7 inflammation model, the selected Wogonoside significantly decreased IL-1β mRNA. The expression levels of NLRP3/Caspase-1/GSDMD pathway-related proteins were also decreased on AR42J-AP.

The results of network pharmacology indicate that QYD can inhibit AP through multiple pathways and targets. This finding was validated through in vivo tests, which demonstrated that QYD can reduce AP by inhibiting NLRP3 inflammasomes, additionally, it should be noted that 12mg/kg was a relatively superior dose. One of the main chemical compositions Wogonoside regulated NLRP3 inflammasome activation to protect against AP. This study is the first to verify the intrinsic molecular mechanism of QYD in treating AP by combining network pharmacology and animal experiments. The findings can provide evidence for subsequent clinical research and drug development.

Acute pancreatitis (AP) is a common disease of acute abdominal pain, the incidence of which is increasing annually, but its pathogenesis remains incompletely understood.

Gene expression profiles of AP were obtained from the Gene Expression Omnibus (GEO) database. R software was used to identify differentially expressed genes (DEGs) and perform functional analysis. The diagnostic value of HLA-DR-related genes was assessed by receiver operating characteristic (ROC) curves. Monocyte infiltration abundance in AP and normal groups was analyzed by Cibersort method, and the correlation between HLA-DR-related genes and monocyte abundance was analyzed. The modules highly correlated with HLA-DR-related genes were clarified by WGCNA modeling, and the core genes regulating HLA-DR were obtained by using LASSO regression. Finally, potential drugs targeting the above genes were analyzed by Enrichr database.

A Total of 3 HLA-DR-related genes (HLA-DRA, HLA-DRB1, and HLA-DRB5) were identified, which were negatively correlated with the severity of AP and had excellent disease diagnostic value (AUC = 0.761, 0.761, and 0.718), were were positively correlated with monocyte abundance. We identified 110 genes that positively regulate HLA-DR and 130 genes that negatively regulate HLA-DR. LASSO regression identified UCP2, GK, and SAMHD1 as the core nodes of the regulated genes. Compared with the normal group, UCP2 and SAMHD1 were reduced in AP, and the opposite was true for GK, and SAMHD1 had better sensitivity and specificity in diagnosing AP. Drug sensitivity analysis predicted 12 drugs acting on HLA-DRA, HLA-DRB1, and HLA-DRB5 and 8 drugs acting on UCP2, GK, and SAMHD1.

We identified 3 HLA-DR-related genes (HLA-DRA, HLA-DRB1, and HLA-DRB5) and 3 coregulatory nodes (UCP2, GK, and SAMHD1), which were associated with AP severity and monocyte abundance. Based on these genes, we predicted 20 potential therapeutic agents for AP.

There is a well-established link between the severity of hypertriglyceridaemia and acute pancreatitis and long-term triglyceride-lowering therapies known to prevent episodes of acute pancreatitis. Therefore, it has been assumed, without firm evidence, that rapid lowering of plasma triglycerides would be an effective strategy for reducing the clinical severity of acute pancreatitis and improving health outcomes. Therapies, such as intravenous heparin, intravenous insulin in normoglycaemic individuals (with glucose to prevent hypoglycaemia), and plasmapheresis, continue to be widely used as therapeutic interventions to rapidly reduce serum triglyceride concentration. These therapies are all associated with a risk of adverse reactions, require increased resources, and increase health-care costs. Randomised controlled clinical trials of these therapies have generally shown more rapid reductions in plasma triglycerides than conventional supportive care with the patient made nil by mouth. However, these three therapies alone or in combination, have failed to show effectiveness in improving substantial health benefit outcome measures. While we recognise the theoretical basis for rapidly reducing plasma triglycerides in hypertriglyceridaemia-induced pancreatitis-based on our review of studies using heparin, insulin, plasmapheresis, or a combination of these-these strategies overall do not reduce complications associated with acute pancreatitis or the rapidity of disease resolution. Therefore, we do not advocate the use of triglyceride-lowering therapies at this time, pending more convincing evidence.

Pancreatitis is a prominent and severe type of inflammatory disorder that has grabbed a lot of scientific and clinical interest to prevent its onset. It should be detected early to avoid the development of serious complications, which occur due to long-term damage to the pancreas. The accurate measurement of biomarkers that are released from the pancreas during inflammation is essential for the detection and early treatment of patients with severe acute and chronic pancreatitis, but this is sub-optimally performed in clinically relevant practices, mainly due to the complexity of the procedure and the cost of the treatment. Clinically available tests for the early detection of pancreatitis are often time-consuming. The early detection of pancreatitis also relates to disorders of the exocrine pancreas, such as cystic fibrosis in the hereditary form and cystic fibrosis-like syndrome in the acquired form of pancreatitis, which are genetic disorders with symptoms that can be correlated with the overexpression of specific markers such as creatinine in biological fluids like urine. In this review, we studied how to develop a minimally invasive system using hydrogel-based biosensors, which are highly absorbent and biocompatible polymers that can respond to specific stimuli such as enzymes, pH, temperature, or the presence of biomarkers. These biosensors are helpful for real-time health monitoring and medical diagnostics since they translate biological reactions into quantifiable data. This paper also sheds light on the possible use of Ayurvedic formulations along with hydrogels as a treatment strategy. These analytical devices can be used to enhance the early detection of severe pancreatitis in real time.

The severity of acute pancreatitis ranges from mild discomfort to severe illness with significant complications. While most cases resolve with supportive care, severe acute pancreatitis may lead to rare but serious issues such as spontaneous splenic rupture. A 46-year-old female with a history of alcohol use, hypertension, depression, and anxiety presented with persistent abdominal pain, nausea, and vomiting. Initial imaging revealed acute pancreatitis with peripancreatic fluid collections. Despite conservative management, her symptoms persisted. She experienced sudden worsening of abdominal pain and a significant drop in hemoglobin levels. Imaging confirmed a spontaneous splenic rupture with a large subcapsular hematoma and hemoperitoneum. She underwent splenic artery embolization to control the bleeding and received blood transfusions for anemia. Her condition improved with supportive care, and she was discharged with plans for outpatient follow-up. Spontaneous splenic rupture is a rare complication of acute pancreatitis resulting from the close anatomical relationship between the pancreas and spleen. Mechanisms behind it include direct enzymatic damage, pseudocyst extension, vascular injury, and increased pressure from splenic vein thrombosis. Early recognition is crucial for timely intervention. Clinicians should consider splenic complications when patients with pancreatitis exhibit sudden clinical deterioration or unexplained anemia. Prompt imaging and appropriate management can improve outcomes. Understanding the potential complications of severe pancreatitis is essential for effective patient care.

Although often overlooked, drug-induced pancreatitis is a frequent cause of pancreatitis. Pancreatic drug toxicity is defined according to the classification by Mallory et al. and Trivedi et al. Isotretinoin is only classified as possibly toxic to the pancreas (class 3). We report the first case of recurrence of pancreatitis after rechallenge, which argues for a modification of the classification of drug-induced pancreatitis.

We present here the case of a 20-year-old Belgian man who suffered several episodes of acute pancreatitis for which no etiology could be identified despite an exhaustive assessment. Eventually, as a precaution, isotretinoin was discontinued and there was no recurrence until it was reintroduced.

This is the 25th case described in the literature, but the first with a positive rechallenge on two occasions. This case therefore implies that isotretinoin should definitely be considered a class 1 toxic drug for the pancreas and should be incriminated in acute pancreatitis in patients treated with this drug.

Endoscopic retrograde cholangiopancreatography (ERCP) has evolved from a diagnostic to a therapeutic tool in acute pancreatitis management, largely due to the availability of less invasive diagnostic modalities such as endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP).

This review explores the therapeutic applications of ERCP across various acute pancreatitis etiologies and its role in managing complications such as bile duct obstructions, pancreatic duct disruptions, and infected necrosis. The discussion highlights the procedure's expanding indications and its critical role in addressing complex cases.

ERCP remains central to the management of acute pancreatitis complications. As endoscopic techniques and devices continue to advance, its therapeutic scope is likely to grow. Performing ERCP for appropriate indications and optimizing its use is essential for minimizing risks and improving outcomes.

Our study examined the composition of the intestinal microflora in a hospitalized patient with AP symptoms treated several months earlier for diverticulitis. The therapeutic intervention necessitated Hartmann's procedure, culminating in colostomy creation.

Employing a thorough microbiological analysis we attempted to demonstrate whether the microflora isolated from the peripancreatic fluid exhibited a stronger correlation with the contents of the stoma or with the rectal swab. Additionally, we sought to determine the association between later onset of AP and diverticulitis.

Following clinical materials from the patient in the initial phase of AP were collected: rectal swab, colostomy bag contents (in the publication referred to as stoma content/stool) and peripancreatic fluid. Microbiological analysis was performed, including classic culture methodology, NGS techniques, and genotyping methodologies. Furthermore, the effect of bile on the shift in the population of selected bacterial species was examined.

The NGS technique confirmed greater consistency in bacteria percentage (phyla/family) between stoma content and peripancreatic fluid. In both samples, a clear dominance of the Proteobacteria phyla (over 75%) and the Enterobacteriaceae family was demonstrated. Moreover, NGS verified the presence of the Fusobacteriota phylum and Fusobacteriaceae family only in rectal swabs, which may indicate a link between this type of bacteria and the etiology of diverticulitis. We observed that Escherichia coli 33 isolated from stool exhibited active gaseous metabolite production (mainly hydrogen).

The abundant production of hydrogen may substantially impact enzymatic processes, inducing specific alterations in disulfide bonds and trypsin inactivation. Our investigation alludes to the conceivable active involvement of bile in effecting qualitative and quantitative modifications in the peripancreatic microbiota composition, establishing a correlation between released bile and bacterial generation of gaseous metabolites.

Acute pancreatitis (AP) increases the risk of diabetes mellitus (DM). Our aim was to identify clinical, laboratory and imaging predictors of preDM/DM in youth post index AP.

This was a prospective cohort study of patients ≤21 years-old with an index admission for AP and follow up at 3 and/or 12 months. Clinical laboratory values, imaging findings, admission course, and plasma chemokine and cytokine measures collected at index admission were tested for association with preDM/DM development. A multivariable regression model was used to predict preDM/DM.

Among 187 enrolled participants, 137 (73 %) and 144 (77 %) underwent DM screening at 3 and 12 months respectively, and 137 (73 %) had imaging available. PreDM/DM occurred in 22/137 (16 %; preDM n = 21, DM n = 1) at 3 months and 23/144 (16 %; preDM n = 18, DM n = 5) participants at 12 months. Univariate associations with preDM/DM at 12 months included: severe AP (SAP) (52 % preDM/DM vs. 17 % no DM; p = 0.0008), median [IQR] IL-6 (910 pg/ml [618-3438] vs. 196 pg/ml [71-480], p < 0.05) and CRP (4.16 mg/L [1.67-10.7] vs. 1.55 mg/L [0.4-3.68], p = 0.1) at time of AP attack. The optimal multivariable model to predict preDM/DM included with clinical variables was severe acute pancreatitis (SAP), c reactive protein (CRP), interleukin-6 (IL-6), and age [AUC = 0.80; (0.70, 0.88)]. Including imaging markers, the ideal model included SAP, CRP, IL-6, subcutaneous fat area, age and presence of autoimmune disease with an AUC [0.82 (0.71, 0.90)].

Development of preDM/DM following an index AP episode can be predicted by baseline AP severity, baseline CRP, IL-6 levels, and subcutaneous fat area.

Acute pancreatitis (AP) is a major health threat, with a high mortality rate in severe forms. Though alcohol and bile-induced factors are the most common causes, increasing evidence suggests that viral infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human immunodeficiency virus (HIV) may also trigger AP development. Our study aims to explore this association in greater detail.

After the PROSPERO registration, we systematically searched PubMed, Embase, Cochrane Library, China Science and Technology Journal Database, China National Knowledge Infrastructure, and Wanfang Data Knowledge Service Platform in February 2023. We included studies with the following PECO framework: Population: AP patients, Exposure/Comparison: with/without virus infection, Outcome: mortality, severity, and complications of AP. Pooled odds ratios (OR) were calculated with 95 % confidence intervals (CIs).

Altogether, 29 cohorts with 2,295,172 patients were identified for the meta-analysis and 858 cases for the qualitative synthesis. Patients with concurrent SARS-CoV-2 infection and AP exhibited heightened odds of in-hospital mortality (OR: 3.15, CI: 2.08-4.76), and necrosis (OR: 1.83, CI: 1.13-2.97). Mild AP was less prevalent in the SARS-CoV-2 group (OR: 0.37, CI: 0.14-0.97) compared to moderately severe and severe AP together. Contrarily, no evidence was found that concomitant HIV infection elevated in-hospital mortality (OR: 1.12, CI: 0.92-1.37) or sepsis occurrence (OR:1.21, CI: 0.41-3.59).

Patients co-diagnosed with AP and SARS-CoV-2 infection require heightened attention due to an increased risk of mortality and complications. No evidence was found that HIV infection elevated the risk of a more severe outcome.

Severe acute pancreatitis (SAP) is a severe clinical condition associated with high rates of morbidity and mortality. Multiple organ dysfunction syndrome that follows systemic inflammatory response syndrome is the leading cause of SAP‑related death. Since the inflammatory mechanism of SAP remains unclear, there is currently a lack of effective drugs available for its treatment. Therefore, it is important to study effective therapeutic drugs and their molecular mechanisms based on studying the inflammatory mechanism of SAP. In the present study, in vivo, a mouse model of AP induced by cerulein (CR) combined with lipopolysaccharide (LPS) was established to clarify the therapeutic effect of artesunate (AS) in AP mice by observing the gross morphological changes of the pancreas and surrounding tissues, calculating the pancreatic coefficient, and observing the histopathology of the pancreas. The serum amylase activity in AP mice was detected by iodine colorimetry and the superoxide dismutase activity in the pancreas was detected by WST‑1 assay. The levels of proinflammatory cytokines in the serum, the supernatant of pancreatic tissue homogenates and the peritoneal lavage fluid were detected by ELISA assay. The total number of peritoneal macrophages was assessed using the cellular automatic counter, and the expression of proteins related to autophagy, and the TLR4 pathway was detected by immunohistochemistry and western blotting. In vitro, the effect of trypsin (TP) combined with LPS was observed by detecting the release of proinflammatory cytokine levels from macrophages by ELISA assay, and detecting the expression of proteins related to autophagy and the TLR4 pathway by immunofluorescence and western blotting. The present study revealed that AS reduced pancreatic histopathological damage, decreased pancreatic TP and serum amylase activities, increased superoxide dismutase activity, and inhibited pro‑inflammatory cytokine levels in a mouse model of AP induced by cerulein combined with lipopolysaccharide. In vitro, TP combined with LPS was found to synergistically induce pro‑inflammatory cytokine release from mouse macrophages and RAW264.7 cells, while AS could inhibit cytokine release. Furthermore, CR combined with LPS synergistically increased amylase activity in acinar cells, whereas AS decreased amylase activity. Autophagy serves an important role in the release of pro‑inflammatory cytokines. In the present study, it was revealed that the autophagy inhibitor LY294002 suppressed the release of pro‑inflammatory cytokines from macrophages treated with TP combined with LPS, and pro‑inflammatory cytokine release was not further reduced by AS combined with LY294002. Furthermore, AS not only inhibited the expression of important molecules in the Toll‑like receptor 4 (TLR4) signaling pathway, but also inhibited autophagy proteins and reduced the number of autolysosomes in mice with AP and in macrophages. In conclusion, these results suggested that AS may protect against AP in mice via inhibition of TLR4‑dependent autophagy; therefore, AS may be considered a potential therapeutic agent against SAP.

Acute pancreatitis (AP) presents a significant clinical challenge with limited therapeutic options. The complex etiology and pathophysiology of AP emphasize the need for innovative treatments. This study explores mRNA-based therapies delivering fibroblast growth factor 21 (FGF21) and apolipoprotein A1 (APOA1), alone and in combination, for treating experimental AP.

Liver-targeted lipid nanoparticles (LNP)-mRNA formulations encoding FGF21, APOA1, and a chimeric APOA1-FGF21, were first tested for protein expression and bioavailability in vitro and in mice fed a high-fat diet. Efficacy studies were performed in the caerulein-induced AP (Cer-AP) model, and a new AP model combining ethanol feeding with ethanol binge plus palmitoleic acid administration, the EtOH/POA-AP model. A single dose of the APOA1, FGF21, and APOA1-FGF21 LNP-mRNAs formulations was administered in both models. Serum levels of pancreatic lipase (LIPC), amylase (AMYL), and aspartate aminotransferase (AST), along with pancreatic tissue analyses using two histopathological scores were performed to evaluate treatment effects.

In vitro studies demonstrated the translation and secretion of APOA1, FGF21, and APOA1-FGF21 proteins encoded by the LNP-mRNAs. In vivo, LNP-mRNA administration increased serum levels of the respective proteins in metabolically impaired (i.e. high fat diet-fed) mice. In the Cer-AP model, serum markers of pancreatic injury were similarly reduced when mice were treated with APOA1, FGF21, and APOA1-FGF21 LNP-mRNA, and this effect was also observed in the histopathological analyses. The EtOH/POA-AP model was more aggressive than the Cer-AP model. FGF21 and APOA1-FGF21 LNP-mRNAs were protective according to LIPC and AMYL serum levels, while APOA1 LNP-mRNA had little effect. On the other hand, histological improvements were more evident in mice receiving APOA1 LNP-mRNA. In the EtOH/POA-AP model, FGF21 and APOA1-FGF21 LNP-mRNAs reduced serum AST levels, indicating hepatoprotective activity.

This proof-of-concept study demonstrates the potential of mRNA-based therapies delivering FGF21 and APOA1 in experimental AP. While individual treatments effectively reduced pancreatic injury, the APOA1-FGF21 fusion molecule did not exhibit superior activity. Liver-targeted LNP-mRNA administration may offer a promising approach for treating AP, leveraging endogenous production pathways for therapeutic proteins. Further research is warranted to elucidate the mechanisms underlying their therapeutic efficacy and optimize treatment regimens for clinical translation.

To examine the effects of obstructive jaundice on the outcomes of patients with acute biliary pancreatitis.

A retrospective chart review was conducted on 332 cases of acute biliary pancreatitis admitted to Rambam Health Care Campus, Israel, from January 1st, 2018, to December 31st, 2021. Patients were categorized based on the presence or absence of obstructive jaundice. Various clinical, laboratory, and radiological parameters were analyzed, including severity prediction scores, length of stay, interventions, and complications.

Obstructive jaundice was observed in 136 patients, while 196 patients had no jaundice. Initial predictive scores (Ranson and Glasgow-Imrie) indicated higher severity in the jaundiced group, but this difference did not translate into significant variations in the final outcomes. Endoscopic procedures and sonography were more frequently performed in jaundiced patients, affecting the diagnosis and management. Cholecystectomy was performed sooner in the jaundiced group, leading to fewer recurrent admissions.

The outcomes of jaundiced and non-jaundiced patients with acute biliary pancreatitis were found to be similar, despite initial predictions of worse outcomes in the jaundiced population. A lower threshold for initiation of rigorous treatment, including more frequent endoscopic procedures, administration of antibiotics and early surgical intervention may facilitate these results. Further studies with a larger sample size and long-term follow-up are warranted to validate these findings.

Bleeding is a rare but serious complication of pancreatitis, significantly increasing morbidity and mortality. It can arise from various sources, including erosion of blood vessels by inflammatory processes, formation of pseudoaneurysms, and gastrointestinal bleeding. Early diagnosis and timely intervention are crucial for patient survival. Imaging modalities such as computed tomography and angiography are essential for identifying the bleeding source, where endoscopy may help in detecting and treating intraluminal hemorrhage. Management strategies for patients with extraluminal bleeding may involve angioembolization or surgical intervention, depending on the severity and location of the bleeding. While advances in diagnostic and therapeutic techniques have improved outcomes, bleeding in pancreatitis remains a challenging clinical problem requiring a multidisciplinary approach. This review aims to focus its attention specifically on the bleeding complications of pancreatitis.

This study aims to evaluate the clinical efficacy of pancreatic duct stenting in the treatment of SAP, providing reference for clinical diagnosis and treatment.

A retrospective analysis was conducted on clinical data from patients with SAP admitted to the General Hospital of Ningxia Medical University from June 1, 2019 to December 31, 2022. A total of 51 patients were included (33 males, 18 females). Patients were divided into two groups based on treatment: the control group (n = 28) receiving conventional treatment and the stent group (n = 23) undergoing pancreatic duct stenting in addition to conventional treatment. Data collected and analyzed include demographic information, rates of late local complications, late surgical interventions, new-onset OF, infected pancreatic necrosis and new-onset systemic complications. Specific outcomes measured were incidences of new-onset respiratory, renal and circulatory failure, single and multiple OF, sepsis, ACS, abdominal hypertension, and pancreatogenic encephalopathy, as well as use of ≥ 3 types of antibiotics, time of antibiotic use, time of analgesic administration, oral refeeding, length of hospital stay, ICU care, and length of ICU stay. These indicators were used to assess the therapeutic efficacy of pancreatic duct stenting.

All 23 patients in the stent group successfully underwent stenting. The incidence of new-onset OF and new-onset systemic complications was significantly lower in the stent group compared to the control group (χ2 = 4.96, 6.65, P < 0.05). However, no significant differences were observed between the groups regarding late local complications, infected pancreatic necrosis, and late surgical intervention (χ2 = 0.22, 0.002, 0.024, P > 0.05). Notably, two patients in the control group required additional procedures due to inadequate drainage, with one undergoing endoscopic debridement and the other, laparotomy. Mortality rates were 3 (10.7%) in the control group and 4 (17.4%) in the stent group, with no statistically significant difference (P > 0.05). Furthermore, significant differences were noted in new-onset respiratory failure, single OF, sepsis, abdominal hypertension, time of analgesic administration, oral refeeding, length of enzyme inhibitor use, and hospitalization expenses (χ2 = 3.94, 4.37, 5.79, 4.79; Z = - 2.008, - 4.176, - 4.165, - 2.309; P < 0.05). No significant differences were found in new-onset renal, circulatory, multiple OF, ACS, pancreatogenic encephalopathy, use of ≥ 3 types of antibiotics, time of antibiotic use, length of hospital stay, ICU care, and length of ICU stay (P > 0.05).

Pancreatic duct stenting effectively reduces the incidence of new-onset systemic complications and OF in SAP, preventing further deterioration. Pancreatic duct stenting can alleviate symptoms, shorten oral refeeding, and promote patient recovery.

This study was recorded as a single-center, retrospective case-control study (ChiCTR1900025833).

Acute pancreatitis (AP) is an acute-onset gastrointestinal disease characterized by a significant inflammation of the pancreas. Most of the time, AP does not leave substantial changes in the pancreas after the resolution of the symptoms but the severe forms are associated with local or systemic complications. The pathogenesis of AP has long been investigated and, lately, the importance of intracellular mechanisms and the immune system has been described. The initial modifications in AP take place in the acinar cell. There are multiple mechanisms by which cellular homeostasis is impaired, one of the most important being calcium overload. Necrotic pancreatic cells initiate the inflammatory response by secreting inflammatory mediators and attracting immune cells. From this point on, the inflammation is sustained by the involvement of innate and adaptive immune systems. Multiple studies have demonstrated the importance of the first 48 h for identifying patients at risk for developing severe forms. For this reason, there is a need to find new, easy-to-use and reliable markers for accurate predictions of these forms. This review provides an overview of the main pathogenetic mechanisms involved in AP development and the most promising biomarkers for severity stratification.

Benign lesions, inflammation, cysts and pseudocysts, as well as neoplasms of the exocrine and endocrine parts of the pancreas can be easily identified using cytological methods. The sensitivity and specificity can be increased with the help of additional examination methods. The sensitivity of intraoperative rapid cytology reaches about 99%. In the literature, the sensitivity reaches an average of about 85% for biopsies. The method is easy to use, has very low complication rates (1%-2%) and is safe for the patient.

1290 cytological samples from pancreatic lesions were processed in the institute of pathology at Hannover Medical School (MHH), as cytological smears and stained with Giemsa and PAS stains as conventional methods. They were compared with the histological specimens that were processed at the same institute. Immunocytochemistry and molecularpathology have been processed only in selected cases. In general, it is routine in the university that the patients give their written consent to participate in clinical studies. The local ethics committee has stated that there is no need for approval due to the retrospective nature of the study.

In this work, we detected 20.077% malignant lesions, 63.333% benign findings and inflammation, 7.441% pseudocysts and cysts. About 9.147% samples were unrepresentative due to insufficient number of cells.

This work will highlight the importance of fine aspiration cytology (FNAC) of suspicious pancreatic lesions, its possibilities and limitations in routine diagnostics with discussing the differential diagnoses, pointing to its great value and safety for patients. FNAC is the gold standard, its power is strongly associated with high specificity and sensitivity in the diagnosis of pancreatic lesions, and is very useful in the differential diagnosis between malignant and inflammatory lesions in pancreas.

Acute pancreatitis (AP) is an inflammatory disease with multiple etiologies, and the emergence of complications. Between 0.1-5% of cases are attributed to drugs. The absence of specific characteristics complicates the diagnosis and treatment of drug-induced AP. Reviewing patients admitted with the diagnosis of drug-induced AP can provide information and improve its management.

This is a descriptive, observational, and retrospective study. All patients admitted to the Hospital Universitari de Bellvitge between June 2007 and March 2023 with suspected drug-induced AP were included. The data were obtained from the hospital pharmacovigilance program database.

Thirty-eight patients with suspected drug-induced AP were identified, representing 0.62% of all adverse drug reactions (n=6.085). Of these, 65.8% (n=25) had a single suspected drug. The median latency period for the onset of adverse drug reactions was 160.5 days (IQR: 18-582 days), and the median hospital stay was 5 days (IQR: 3-7 days). Fifty-nine suspected drugs were identified, involving 26 active principles. Azathioprine and atorvastatin were the most frequent, with 9 cases each (15.2%), followed by enalapril with 8 cases (13.6%). Drug etiology was assessed in 23 cases (60.5%), and the suspected drug was discontinued in all cases. There was one fatal case documented (2.63%).

This study can contribute to better understanding of drug-induced pancreatitis episodes. We propose a diagnostic algorithm that includes the assessment of the drug as a possible cause.

Acute pancreatitis (AP) is a common acute gastrointestinal disorder affecting approximately 20% of patients with systemic inflammatory responses that may cause pancreatic and peripancreatic fat necrosis. This condition often progresses to multiple organ failure, significantly increasing morbidity and mortality. Oxidative stress, characterized by an imbalance between the body's reactive oxygen species (ROS) and antioxidants, activates the inflammatory signaling pathways. Although the pathogenesis of AP is not fully understood, ROS are increasingly recognized as critical in the disease's progression and development. Modulating the oxidative stress pathway has shown efficacy in mitigating the progression of AP. Despite numerous basic studies examining this pathway, comprehensive reviews of recent research remain sparse. This systematic review offers an in-depth examination of the critical role of oxidative stress in the pathogenesis and progression of AP and evaluates the therapeutic potential of antioxidant interventions in its management.

Heavy alcohol intake is one of the most common causes of acute pancreatitis (AP). We have previously shown that ethanol (EtOH) decreases the expression and activity of the cystic fibrosis transmembrane conductance regulator (CFTR), which plays a key role in alcohol-induced AP development. The prescription drug, Orkambi (a combination of ivacaftor and lumacaftor) can correct impaired CFTR function and expression in cystic fibrosis (CF) patients. Thus, the present study aimed to investigate whether Orkambi can mitigate alcohol-induced AP. Intact guinea-pig pancreatic ducts were pre-treated with different concentrations of ethanol (EtOH; 30, 50 and 100 mm) for 12 h alone or in combination with ivacaftor (VX770) and/or lumacaftor (VX-809), and CFTR expression and activity were evaluated by immunostaining and by the patch clamp technique, respectively. Alcoholic AP was induced in Orkambi-treated guinea-pigs, and standard laboratory and histological parameters were measured. Ivacaftor and lumacaftor alone or in combination dose-dependently restored the apical expression and activity of CFTR after EtOH treatment in vitro. Oral administration of Orkambi reduced the severity of alcohol-induced AP and restored impaired CFTR activity and expression. Orkambi is able to restore the CFTR defect caused by EtOH and decreases the severity of alcohol-induced pancreatitis. This is the first in vivo pre-clinical evidence of Orkambi efficacy in the treatment of alcohol-induced AP. KEY POINTS: Acute pancreatitis is one of the leading causes of hospital admission among gastrointestinal diseases in which the lack of a specific drug therapy plays a crucial role. The cystic fibrosis transmembrane conductance regulator (CFTR) plays an essential role in pancreatic ductal HCO3 - secretion; inappropriate CFTR function, as seen in heavy alcohol consumption, increases the risk of pancreatitis development. CFTR modulators are able to prevent the inhibitory effect of ethanol and reduce pancreatic ductal injury and the severity of alcohol-induced pancreatitis. CFTR modulators present a novel option in the pharmacotherapy of alcohol-induced pancreatitis by enhancing pancreatic functions or preventing recurrence.

Sphingosine-1-phosphate (S1P) is a sphingolipid metabolic product produced via the phosphorylation of sphingosine by sphingosine kinases (SPHKs), serving as a powerful modulator of various cellular processes through its interaction with S1P receptors (S1PRs). Currently, this incompletely understood mechanism in pancreatic diseases including pancreatitis and pancreatic cancer, largely limits therapeutic options for these disorders. Recent evidence indicates that S1P significantly contributes to pancreatic diseases by modulating inflammation, promoting pyroptosis in pancreatic acinar cells, regulating the activation of pancreatic stellate cells, and affecting organelle functions in pancreatic cancer cells. Nevertheless, no review has encapsulated these advancements. Thus, this review compiles information about the involvement of S1P signaling in exocrine pancreatic disorders, including acute pancreatitis, chronic pancreatitis, and pancreatic cancer, as well as prospective treatment strategies to target S1P signaling for these conditions. The insights presented here possess the potential to offer valuable guidance for the implementation of therapies targeting S1P signaling in various pancreatic diseases.

Acute pancreatitis (AP) is increasingly recognized as a risk factor for diabetes mellitus (DM). We aimed to study the association of pancreatitis genes with pancreatic endocrine insufficiency (pre-DM and DM) development post-AP in children.

This was an observational cohort study that enrolled subjects ≤21 years with their first episode of AP and followed them for 12 months for the development of pancreatic endocrine insufficiency. Pancreatitis risk genes (CASR, CEL, CFTR, CLDN2, CPA1, CTRC, PRSS1, SBDS, SPINK1, and UBR1) were sequenced. A genetic risk score was derived from all genes with univariable P < .15.

A total 120 subjects with AP were genotyped. Sixty-three subjects (52.5%) had at least 1 reportable variant identified. For modeling the development of pancreatic endocrine insufficiency at 1 year, 6 were excluded (2 with DM at baseline, 3 with total pancreatectomy, and 1 death). From this group of 114, 95 remained normoglycemic and 19 (17%) developed endocrine insufficiency (4 DM, 15 pre-DM). Severe AP (58% vs 20%; P = .001) and at least 1 gene affected (79% vs 47%; P = .01) were enriched among the endocrine-insufficient group. Those with versus without endocrine insufficiency were similar in age, sex, race, ethnicity, body mass index, and AP recurrence. A model for pre-DM/DM development included AP severity (odds ratio, 5.17 [1.66-16.15]; P = .005) and genetic risk score (odds ratio, 4.89 [1.83-13.08]; P = .002) and had an area under the curve of 0.74.

In this cohort of children with AP, pancreatitis risk genes and AP disease severity were associated with pre-DM or DM development post-AP.

Introduction: Acute necrotizing pancreatitis (ANP) is the acute inflammation of pancreatic parenchyma, most commonly due to alcohol abuse or cholelithiasis. The treatment can be either conservative or invasive, including a variety of techniques; however, it has not yet been established if the intervention should be early or if it should be delayed. The aim of this review is to investigate the optimal time for intervention in ANP. Methods: A literature search was conducted in PubMed and Scopus from inception until September 2024 for studies reporting the comparison between early and late intervention. Results: Early intervention, within 4 weeks of symptom onset, often involves drainage via percutaneous, endoscopic, or combined methods. Delayed intervention occurs after 4 weeks of symptom onset. This can be conducted either surgically or via minimally invasive means. The results of this review reveal that the time of intervention for ANP plays an important role in the prognosis and the course of the disease. In particular, early intervention is associated with higher mortality, which is also the primary clinical outcome. Delayed intervention is also superior regarding secondary clinical outcomes, specifically the complications associated with the intervention. Thus, it is accompanied by fewer episodes of new-onset organ failure, bleeding, gastrointestinal fistula, pancreatic fistula, wound infection, endocrine pancreatic insufficiency, and other complications. Finally, delayed intervention results in shorter stays, both in hospitals and the ICU. Conclusions: Delayed intervention is clearly more effective than early intervention and should be preferred. However, early intervention appears to be both safe and effective, and it is feasible.

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.

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.

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%).

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.

In the United States, acute pancreatitis is one of the most common gastrointestinal conditions that results in hospital admission. Necrotizing pancreatitis is a form of acute pancreatitis that can lead to various local and systemic complications. It is also associated with a high risk of mortality and morbidity without prompt intervention. In this case report, we discuss the case of a 33-year-old female with a history of alcoholism hospitalized with necrotizing pancreatitis due to hypertriglyceridemia. Our goal was to promptly identify the case by evaluating the signs and symptoms and intervening to prevent the associated complications. Our other objective was to change the diet and lifestyle of the patient to prevent the recurrence of necrotizing pancreatitis and readmission for the same reason.

Acute pancreatitis (AP) has a high incidence of hospitalizations, morbidity, and mortality worldwide. A growing number of studies on AP pathogenesis are based on cerulein-induced experimental model, which simulates human AP in vivo. It has been demonstrated that both pancreatic acinar cells and peritoneal macrophages are involved in pancreatic inflammation and damage. However, their connection has not been well understood.

A cerulein-induced AP model was established on the pancreatic acinar cell line AR42J. Rat macrophages were isolated from the peritoneal cavity. The effects of cerulein-induced pancreatic exosomes on the peritoneal macrophage and pancreas in vivo and in vitro were examined. The underlying molecular mechanism was investigated by exploring the regulatory role of downstream molecules.

We found that exosomes derived from cerulein-treated AR42J cells induced rat peritoneal macrophage M1 polarization and pyroptosis. miR-24-3p was upregulated in cerulein-stimulated exosomes, whereas the miR-24-3p inhibitor counteracted the effect of pancreatic exosomes on peritoneal macrophage M1 polarization and pyroptosis. Furthermore, miR-24-3p inhibited March3 expression, whereas MARCH3 mediated NLRP3 ubiquitination in rat peritoneal macrophages, which, in turn, contributed to the apoptosis, reactive oxygen species production, and inflammation in AR42J cells.

Exosomes derived from cerulein-stimulated pancreatic acinar cells mediate peritoneal macrophage M1 polarization and pyroptosis via an miR-24-3p/MARCH3/NLRP3 axis in AP.

Helicobacter pylori (H. pylori) infection is a bacterial disease of the stomach that has been associated with an increased incidence of cholelithiasis. While the updated German guideline emphasizes the relevance of H. pylori as a pathogen and recommends eradication therapy, systematic data on the association between H. pylori infection, its eradication, and the subsequent diagnosis of cholelithiasis in Germany are missing.

A total of 25 416 patients with and 25 416 propensity score-matched individuals without H. pylori infection were identified from the Disease Analyzer database (IQVIA) between 2005 and 2021. A subsequent diagnosis of cholelithiasis was analyzed as a function of H. pylori infection as well as its eradication using Cox regression models.

After 10 years of follow-up, 8.0% versus 5.8% of patients with and without H. pylori infection were diagnosed with cholelithiasis (P < 0.001). Regression analysis revealed a significant association between H. pylori infection and cholelithiasis (hazard ratio [HR]: 1.45; 95% confidence interval [CI]: 1.33-1.58), which was stronger in men (HR: 1.63; 95% CI: 1.41-1.90) than in women (HR: 1.36; 95% CI: 1.22-1.52). In terms of eradication therapy, both an eradicated H. pylori infection (HR: 1.48; 95% CI: 1.31-1.67) and a non-eradicated H. pylori infection (HR: 1.41; 95% CI: 1.25-1.60) were associated with a subsequent diagnosis of cholelithiasis.

The present study reveals a strong association between H. pylori infection and a subsequent diagnosis of cholelithiasis in a large real-world cohort from Germany. Eradication therapy was not associated with a reduced incidence of cholelithiasis in our cohort.

Previous research has shown that the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in macrophages can promote severe acute pancreatitis through the release of inflammatory factors. The role of this pathway in pancreatic acinar cells, however, has not been studied, and understanding its mechanism could be crucial. We analysed plasma from 50 acute pancreatitis (AP) patients and 10 healthy donors using digital PCR, which links mitochondrial DNA (mtDNA) levels to the severity of AP. Single-cell sequencing of the pancreas during AP revealed differentially expressed genes and pathways in acinar cells. Experimental studies using mouse and cell models, which included mtDNA staining and quantitative PCR, revealed mtDNA leakage and the activation of STING-related pathways, indicating potential inflammatory mechanisms in AP. In conclusion, our study revealed that the mtDNA-STING-nuclear factor κB(NF-κB) pathway in pancreatic acinar cells could be a novel pathogenic factor in AP.

Acute pancreatitis, a common exocrine inflammatory disease affecting the pancreas, is characterized by intense abdominal pain and multiple organ dysfunction. However, the alterations in retinal blood vessels among individuals with acute pancreatitis remain poorly understood. This study employed optical coherence tomography angiography (OCTA) to examine the superficial and deep retinal blood vessels in patients with pancreatitis. Sixteen patients diagnosed with pancreatitis (32 eyes) and 16 healthy controls (32 eyes) were recruited from the First Affiliated Hospital of Nanchang University for participation in the study. Various ophthalmic parameters, such as visual acuity, intraocular pressure, and OCTA image for retina consisting of the superficial retinal layer (SRL) and the deep retinal layer (DRL), were recorded for each eye. The study observed the superficial and deep retinal microvascular ring (MIR), macrovascular ring (MAR), and total microvessels (TMI) were observed. Changes in retinal vascular density in the macula through annular partitioning (C1-C6), hemispheric quadrant partitioning (SR, SL, IL, and IR), and early diabetic retinopathy treatment studies (ETDRS) partitioning methods (R, S, L, and I). Correlation analysis was employed to investigate the relationship between retinal capillary density and clinical indicators. Our study revealed that in the superficial retinal layer, the vascular density of TMI, MIR, MAR, SR, IR, S, C2, C3 regions were significantly decreased in patients group compared with the normal group. For the deep retinal layer, the vascular density of MIR, SR, S, C1, C2 regions also reduced in patient group. The ROC analysis demonstrated that OCTA possesses significant diagnostic performance for pancreatitis. In conclusion, patients with pancreatitis may have retinal microvascular dysfunction, and OCTA can be a valuable tool for detecting alterations in ocular microcirculation in pancreatitis patients in clinical practice.

Background/Objectives: Sickle cell disease (SCD) impacts about 100,000 people in the US. SCD increases the risk of cholelithiasis and microvascular ischemia, which could increase the risk of acute pancreatitis (AP). Abdominal pain is a common presenting symptom of AP and sickle cell vaso-occlusive crisis. The purpose of our systematic review is to estimate the prevalence and determine the severity of AP in individuals with SCD compared to the general population. Methods: Multiple electronic databases were searched. We included studies that included children and adults (population) and addressed the association of SCD (exposure) with AP (outcome) compared to the same population without SCD (control). Two authors screened titles and abstracts independently, and data were abstracted in duplication from included studies. We registered this protocol in PROSPERO-CRD42023422397. Results: Out of 296 studies screened from multiple electronic databases, we identified 33 studies. These studies included 17 case reports, one case series, and 15 retrospective cohort studies, and 18 studies included children. Eight of the AP case reports were in patients with HbSS genotype, two with sickle beta thalassemia, and one with HbSoArab, and in six case reports, a genotype was not specified. Complications were reported in 11 cases-respiratory complication (in at least four cases), splenic complications (three cases), pancreatic pseudocyst (two cases) and death from AP (one case). Of the four AP cases in the case series, three had HbSS genotype, and two cases had complications and severe pancreatitis. AP prevalence in SCD was estimated to be 2% and 7% in two retrospective studies, but they lacked a comparison group. In retrospective studies that evaluated the etiology of AP in children, biliary disease caused mostly by SCD was present in approximately 12% and 34%, respectively. Conclusions: Data on the prevalence of AP in individuals with SCD are limited. Prospectively designed studies aiming to proactively evaluate AP in individuals with SCD who present with abdominal pain are needed to improve timely diagnosis of AP in SCD and outcomes.

CMV is a ubiquitous DNA virus that establishes infection and results in 40-100% seropositivity. Viral replication occurs following an acquired primary infection (or reinfection) or by the reactivation of life-long latency. In immunocompetent patients, CMV infection is mostly asymptomatic or mild and self-limited. However, an extensive review of the literature published up to April 2024 reveals that despite immunocompetence, CMV can cause a very large variety of clinical syndromes in any part of the gastrointestinal tract (the most common pattern), the central or peripheral nervous system, and the eyes, as well as hematological, pulmonary, cardiac, and cutaneous disease. Not uncommonly, more than one system is involved, and though the disease is often self-limited, treatment with intravenous ganciclovir or oral valganciclovir may be required, and in isolated cases, fatalities may occur. Thus, a potential CMV infection should be considered in the differential of myriad syndromes in non-immunocompromised patients. Associated systemic symptoms (fever, sweats, and weight loss), lymphocytosis, and hepatitis are not uncommon and can be a useful clue. Some populations, such as critically ill patients in intensive care, pregnant women, elderly patients, and those with inflammatory bowel disease, may be more susceptible. Moreover, the potential of past, latent CMV infection (i.e., CMV seropositivity) to be associated with significant cardiovascular morbidity and all-cause mortality years later is intriguing and requires further study. All these data indicate the outstanding importance of developing a vaccine against CMV, which hopefully will become available in the foreseeable future. Meanwhile, a solid diagnosis of active CMV infection can be quickly established (or ruled out) by widely available serology tests and PCR amplification, and clinicians in all disciplines need to be more aware of the diverse guises of CMV infection and remember to consider it in any host, including an immunocompetent one.

Acute pancreatitis (AP) is a significant cause of morbidity, even in children, and is frequently associated with systemic manifestations. There are many cytokines involved in the inflammatory response characteristic of this disease. Interleukin 6 (IL-6) is one of the most important cytokines involved in AP, beginning from cellular injury and continuing to the systemic inflammatory response and distant organ involvement. IL-6 is a multifunctional cytokine that regulates acute-phase response and inflammation. It is produced by various cells and exerts its biological role on many cells through its high-affinity complex receptor. IL-6 has been investigated as a predicting maker for severe forms of AP. Many studies have validated the use of IL-6 serum levels in the first 48 h as a reliable marker for severe evolution and multisystemic involvement. Still, it has not been used in daily practice until now. This review discusses the main binding mechanisms by which IL-6 triggers cellular response and the AP pathogenetic mechanisms in which IL-6 is involved. We then emphasize the promising role of IL-6 as a prognostic marker, which could be added as a routine marker at admission in children with AP.

During acute pancreatitis, intestinal permeability increases due to intestinal motility dysfunction, microcirculatory disorders, and ischemia-reperfusion injury, and disturbances in the intestinal flora make bacterial translocation easier, which consequently leads to local or systemic complications such as pancreatic and peripancreatic necrotic infections, acute lung injury, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Therefore, adjusting intestinal ecosystem balance may be a promising approach to control local and systemic complications of acute pancreatitis. In this paper, we reviewed the causes and manifestations of intestinal flora disorders during acute pancreatitis and their complications, focused on the reduction of acute pancreatitis and its complications by adjusting the intestinal microbial balance, and innovatively proposed the treatment of acute pancreatitis and its complications by gut microbiota-derived extracellular vesicles.

Incretin therapies, comprised of the dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have been increasingly utilized for the treatment of type 2 diabetes (T2DM). Previous studies have conflicting results regarding risk of pancreatitis associated with these agents-some suggest an increased risk and others find no correlation. Adverse event reporting systems indicate that incretin therapies are some of the most common drugs associated with reports of pancreatitis.

This study aimed to compare the odds of developing pancreatitis in veterans with T2DM prescribed an incretin therapy versus thiazolidinediones (TZDs: pioglitazone and rosiglitazone) within the Veterans Health Administration (VHA).

This was a retrospective cohort study analyzing veterans with T2DM first prescribed an incretin therapy or a TZD between January 1, 2011, and December 31, 2021. A diagnosis of pancreatitis within 365 days of being prescribed either therapy was counted as a positive case. Data was collected and analyzed utilizing VA's Informatics and Computing Infrastructure (VINCI) and an adjusted odds ratio was calculated.

The TZD cohort consisted of 42 912 patients compared with the incretin cohort of 304 811 patients. The TZD cohort had a pancreatitis incidence rate of 1.94 cases per 1000 patients. The incretin cohort had a incidence rate of 2.06 cases per 1000 patients. An adjusted odds ratio found no statistical difference of pancreatitis cases between the TZD and incretin cohorts (adjusted odds ratio [AOR] = 0.94, 95% CI [0.75, 1.18]).

This retrospective cohort study of national VHA data found a relatively low incidence of pancreatitis in both cohorts, and an adjusted odds ratio found no statistical difference of pancreatitis in patients prescribed an incretin therapy compared with a control group. This data adds to growing evidence that incretin therapies do not seem to be associated with an increased risk of developing pancreatitis.