GGT1 is a SNP eQTL gene involved in STAT3 activation and associated with the development of Post-ERCP pancreatitis.

Post-ERCP pancreatitis (PEP) is an acute pancreatitis caused by endoscopic-retrograde-cholangiopancreatography (ERCP). About 10% of patients develop PEP after ERCP. Here we show that gamma-glutamyltransferase 1 (GGT1)-SNP rs5751901 is an eQTL in pancreatic cells associated with PEP and a positive regulator of the IL-6 amplifier. More PEP patients had the GGT1 SNP rs5751901 risk allele (C) than that of non-PEP patients at Hokkaido University Hospital. Additionally, GGT1 expression and IL-6 amplifier activation were increased in PEP pancreas samples with the risk allele. A mechanistic analysis showed that IL-6-mediated STAT3 nuclear translocation and STAT3 phosphorylation were suppressed in GGT1-deficient cells. Furthermore, GGT1 directly associated with gp130, the signal-transducer of IL-6. Importantly, GGT1-deficiency suppressed inflammation development in a STAT3/NF-κB-dependent disease model. Thus, the risk allele of GGT1-SNP rs5751901 is involved in the pathogenesis of PEP via IL-6 amplifier activation. Therefore, the GGT1-STAT3 axis in pancreas may be a prognosis marker and therapeutic target for PEP.

Endoscopic Retrograde Cholangiopancreatography for the Management of Pancreatic Duct Leaks and Fistulas.

Pancreatic duct (PD) leaks are a common complication of acute and chronic pancreatitis, trauma to the pancreas, and pancreatic surgery. Diagnosis of PD leaks and fistulas is often made with contrast-enhanced pancreatic protocol computed tomography or magnetic resonance imaging with MRCP. Endoscopic retrograde pancreatography with pancreatic duct stenting in appropriately selected patients is often an effective treatment, helps to avoid surgery, and is considered first-line therapy in cases that fail conservative management.

Endoscopic Drainage of Pancreatic Fluid Collections.

Pancreatic fluid collections (PFCs) are commonly encountered complications of acute and chronic pancreatitis. With the advancement of endoscopic ultrasound (EUS) techniques and devices, EUS-directed transmural drainage of symptomatic or infected PFCs has become the standard of care. Traditionally, plastic stents have been used for drainage, although lumen-apposing metal stents (LAMSs) are now favored by most endoscopists due to ease of use and reduced procedure time. While safety has been repeatedly demonstrated, follow-up care for these patients is critical as delayed adverse events of indwelling drains are known to occur.

[Severe acute pancreatitis secondary to hypertriglyceridemia as the onset of Type 1 Diabetes Mellitus in the pediatric age]. / Pancreatitis aguda grave secundaria a hipertrigliceridemia como debut de Diabetes Mellitus Tipo 1 en edad pediátrica.

Hypertriglyceridemia (HTG)-induced acute pancreatitis (AP) secondary to insulin deficiency following the onset of type 1 diabetes mellitus (T1DM) is a rare but serious complication in children. OBJECTIVE: To describe the diagnosis and treatment of severe HTG and to emphasize the need for timely diagnosis of T1DM. CLINICAL CASE: A 15-year-old female adolescent with a history of overweight presented with a two-weeks history of fever, anorexia, and diffuse abdominal pain. Laboratory tests revealed triglycerides of 17,580 mg/dL, lipase of 723 U/L, and blood glucose of 200 mg/dL. An abdominal CT scan showed an enlarged and edematous pancreas. She was hospitalized with a diagnosis of AP and severe HTG, which progressed to acute necro-hemorrhagic pancreatitis. Treatment included continuous intravenous insulin infusion until triglyceride levels decreased. Upon discontinuation of insulin, fasting hyperglycemia (206 mg/dL) and metabolic acidosis recurred, therefore DM was suspected. Upon targeted questioning, a history of polydipsia, polyuria, and weight loss during the last 3 months stood out. Glycated hemoglobin was markedly elevated (14.7%). Insulin therapy was optimized, achieving stabilization of laboratory parameters after 15 days of treatment and complete anatomical resolution of pancreatic involvement at one year of follow-up. CONCLUSIONS: The presence of severe HTG in pediatrics compels us to consider its secondary causes, such as the onset of T1DM. It is crucial to improve the ability to diagnose T1DM early, as it may present with infrequent and high-risk presentations for the patient.

Prediction for post-ERCP pancreatitis in non-elderly patients with common bile duct stones: a cross-sectional study at a major Chinese tertiary hospital (2015-2023).

BACKGROUND: Post-ERCP pancreatitis is one of the most common adverse events in ERCP-related procedures. The purpose of this study is to construct an online model to predict the risk of post-ERCP pancreatitis in non-elderly patients with common bile duct stones through screening of relevant clinical parameters. METHODS: A total of 919 cases were selected from 7154 cases from a major Chinese tertiary hospital. Multivariable logistic regression model was fitted using the variables selected by the LASSO regression from 28 potential predictor variables. The internal and external validation was assessed by evaluating the receiver operating characteristic curve and the area under curve. Restricted cubic spline modelling was used to explore non-linear associations. The interactive Web application developed for risk prediction was built using the R "shiny" package. RESULTS: The incidence of post-ERCP pancreatitis was 5.22% (48/919) and significantly higher in non-elderly patients with female, high blood pressure, the history of pancreatitis, difficult intubation, endoscopic sphincterotomy, lower alkaline phosphatase and smaller diameter of common bile duct. The predictive performance in the test and external validation set was 0.915 (95% CI, 0.858-0.972) and 0.838 (95% CI, 0.689-0.986), respectively. The multivariate restricted cubic spline results showed that the incidence of pancreatitis was increased at 33-50 years old, neutrophil percentage > 58.90%, hemoglobin > 131 g/L, platelet < 203.04 or > 241.40 × 109/L, total bilirubin > 18.39 umol / L, aspartate amino transferase < 36.56 IU / L, alkaline phosphatase < 124.92 IU / L, Albumin < 42.21 g / L and common bile duct diameter between 7.25 and 10.02 mm. In addition, a web server was developed that supports query for immediate PEP risk. CONCLUSION: The visualized networked version of the above model is able to most accurately predict the risk of PEP in non-elderly patients with choledocholithiasis and allows clinicians to assess the risk of PEP in real time and provide preventive treatment measures as early as possible.

Case report: GLP1RA for the treatment of diabetes in liver transplanted people. Do they increase the risk of pancreatitis?

The incidence of acute pancreatitis (AP) in liver transplanted people is reported to be 1.5-8%. On the other hand, the evidence for a causal relationship between glucagon-like peptide 1 receptor agonists (GLP1RAs) and pancreatitis in people with type 2 diabetes is still weak. In addition, there are currently no data on a possible increased risk of AP in liver-transplanted individuals with diabetes treated with GLP1RAs. In a population of liver-transplanted individuals with diabetes receiving GLP1RA-based therapy, we reported an incidence of AP of 3.0% (two subjects). No cases were reported in liver-transplanted individuals with diabetes receiving SGLT2 inhibitors, insulin or metformin, neither in kidney or lung-transplanted patients treated with GLP1RAs. In both patients with AP, the only additional risk factor for its development was a history of re-transplantation (liver or combined kidney/liver). For this reason, we suggest particular caution when considering GLP1RAs-based therapies in liver transplanted patients with multiple risk factors for AP, such as a history of repeated and complex abdominal surgery.

Gastrointestinal Conditions: Pancreatitis.

Acute pancreatitis is among the most common gastrointestinal disorders requiring hospitalization. The main causes are gallstones and alcohol use. Patients typically present with upper abdominal pain radiating to the back, worse with eating, plus nausea and vomiting. Diagnosis requires meeting two of three criteria: upper abdominal pain, an elevated serum lipase or amylase level greater than 3 times the normal limit, and imaging findings consistent with pancreatitis. After pancreatitis is diagnosed, the Atlanta classification and identification of the systemic inflammatory response syndrome can identify patients at high risk of complications. Management includes fluid resuscitation and hydration maintenance, pain control that may require opioids, and early feeding. Feeding recommendations have changed and "nothing by mouth" is no longer recommended. Rather, oral feeding should be initiated, as tolerated, within the first 24 hours. If it is not tolerated, enteral feeding via nasogastric or nasojejunal tubes should be initiated. Antibiotics are indicated only with radiologically confirmed infection or systemic infection symptoms. Surgical or endoscopic interventions are needed for biliary pancreatitis or obstructive pancreatitis with cholangitis. One in five patients will have recurrent episodes of pancreatitis; alcohol and smoking are major risk factors. Some develop chronic pancreatitis, associated with chronic pain plus pancreatic dysfunction, including endocrine failure (insulin insufficiency) and/or exocrine failure that requires long-term vitamin supplementation.

Acute pancreatitis: A narrative review.

Acute pancreatitis is a common cause of acute abdominal pain and can range from mild oedema to severe necrosis of the pancreas. It has a significant impact on morbidity, mortality and financial burden. The global prevalence of pancreatitis is substantial, with the highest rates observed in central and eastern Europe. Diagnosing acute pancreatitis involves considering clinical symptoms, elevated serum amylase and/or lipase levels, and characteristic imaging findings. The causes of acute pancreatitis include obstructive disorders, such as gallstones and biliary sludge, alcohol consumption, smoking, drug-induced pancreatitis, metabolic disorders, trauma, medical procedures, infections, vascular diseases and autoimmune pancreatitis. Appropriate management of acute pancreatitis involves determining the severity of the condition, providing supportive care, addressing the underlying cause, and preventing complications. Advances in classifying the severity of acute pancreatitis and implementing goal-directed therapy have contributed to a decrease in mortality rates. Understanding its prevalence, aetiology and management principles is crucial for clinicians to appropriately diagnose and manage patients with acute pancreatitis.

Effectiveness of the pharmacological therapy to prevent post ERCP acute pancreatitis: a network meta-analysis.

OBJECTIVE: To determine the effectiveness of the different pharmacological agents in preventing post-ERCP acute pancreatitis. METHODS: We included clinical trials of pharmacological interventions for prophylaxis of acute post-ERCP pancreatitis. The event evaluated was acute pancreatitis. We conducted a search strategy in MEDLINE (OVID), EMBASE, and Cochrane Central Register of Controlled Trials from inception to nowadays. We reported the information in terms of relative risks (RR) with a 95% confidence interval. We assessed the heterogeneity using the I2 test. RESULTS: We included 84 studies for analysis (30,463 patients). The mean age was 59.3 years (SD ± 7.01). Heterogeneity between studies was low (I2 = 34.4%) with no inconsistencies (p = 0.2567). Post ERCP pancreatitis was less in prophylaxis with NSAIDs (RR 0.65 95% CI [0.52 to 0.80]), aggressive hydration with Lactate Ringer (RR 0.32 95% CI [0.12-0.86]), NSAIDs + isosorbide dinitrate (RR 0.28 95% CI [0.11-0.71]) and somatostatin and analogues (RR 0.54 [0.43 to 0.68]) compared with placebo. CONCLUSIONS: NSAIDs, the Combination of NSAIDs + isosorbide dinitrate, somatostatin and analogues, and aggressive hydration with lactate ringer are pharmacological strategies that can prevent post-ERCP pancreatitis when compared to placebo. More clinical trials are required to determine the effectiveness of these drugs.

Management of ERCP complications.

Managing complications of ERCP poses a significant clinical challenge to endoscopists. ERCP complications can occur even after all preventive measures, which can lead to significant morbidity and even mortality. Major complications include pancreatitis, bleeding, perforation, cholangitis, and sedation-related adverse events. Early recognition of post-ERCP pancreatitis (PEP) is feasible by monitoring clinical parameters and specific cutoffs of serum amylase and lipase at 2-6 h post-ERCP. Pancreatic stenting for PEP is not recommended and can increase the incidence of infected necrosis in addition to being technically challenging. Post-sphincterotomy bleeds can be treated by diluted epinephrine with or without thermal therapy, or mechanical therapy (clips or fully covered metallic stents) failing which angiographic embolization and rarely open surgical vessel ligation may be warranted. Post-ERCP perforations can lead to significant morbidity and are usually treated with endoscopic closure of the defect, diverting bile flow, draining collections, and reducing fluid load at the site of perforation failing which surgery may be warranted. Broad-spectrum antibiotics with endoscopic or radiologic drainage of undrained segments help treat post-ERCP cholangitis. Hypoxia and hypertension are the most common sedation-related adverse events without long-term consequences except aspiration pneumonia (<0.5%). Awareness with a high index of suspicion is crucial for timely diagnosis and management of uncommon post-ERCP complications.

Prevention of post-ERCP complications.

Endoscopic retrograde cholangiopancreatography (ERCP) is a common endoscopic procedure which plays a key role in the management of diseases of the bile ducts and the pancreas. Despite ERCP being performed routinely since more than 4 decades, it is still related to a considerable rate of complications with post-ERCP pancreatitis being the most frequent one. Lately, endoscopic techniques have evolved, and numerous modalities have been developed to prevent or manage ERCP-related complications, especially PEP, such as the use of intra-rectal non-steroidal anti-inflammatory drugs (NSAIDs), insertion of prophylactic stents in the pancreatic duct (PD) or intravenous hyperhydration. Knowledge of the various risk factors and applying validated preventive methods are keys in providing a safe procedure and optimizing overall patient care.

Assessment of triglyceride clearance of haemoperfusion from three cases of hypertriglyceridaemia-induced acute pancreatitis: a case series.

Rapid reduction of plasma triglycerides (TG) is believed to improve the outcome of pancreatitis in the context of hypertriglyceridaemia (HTG)-induced acute pancreatitis (HTG-AP). Previous studies have suggested that haemoperfusion (HP) with the Jafron cartridge series could be effective for reducing TG concentrations in patients with HTG-AP. However, the clearance capacity (CC) for TG removal has not been reported. This case series reports on data from three patients with HTG-AP who underwent HP with HA230 or HA330 cartridges. Blood samples were collected from both before and after the cartridge circuit every 30 min and the CC was calculated. Twelve pairs of blood samples were collected for each type of HP cartridge. The mean ± SD CC of the HA230 cartridge for TG removal in this case series was 0.009781 ± 1.117235 ml/min (95% confidence interval [CI], -0.7000762, 0.7196384 ml). The mean ± SD CC of the HA330 cartridge for TG removal in this case series was 0.344914 ± 1.412183 ml/min (95% CI, -0.5523448, 1.2421721 ml). Based on the findings of this small case series, special caution is advised when considering the use of the HA230 and HA330 cartridges for reducing blood TG concentration pending further conclusive evidence from larger studies.

Penoscrotal Edema as a Rare Complication of Acute Pancreatitis: A Case Report.

Background and Objectives: Scrotal swelling or hydrocele is a rare complication of acute pancreatitis described in the literature. We present a case of penoscrotal swelling caused by the first attack of acute interstitial edematous alcohol-induced pancreatitis in a young male patient. Case report: A 22-year-old man was admitted to the emergency unit due to diarrhea and vomiting since morning which was followed by severe abdominal pain. Urgent abdominal multislice CT scan showed steatosis, pancreatic swelling and acute peripancreatic fluid collection (interstitial edematous pancreatitis). Also, scan showed fluid between small bowel loops and along the anterior renal fascia, while there was minimal amount of fluid in the Douglas space. There was no sign of penoscrotal swelling. On the second day of admission, the patient developed left scrotal swelling and mild pain without erythema. On the fourth day, a control CT scan showed progression to moderately severe pancreatitis (CT severity index 4). Dilated scrotal veins of the pampiniform venous plexus with an increased caliber of the testicular veins were present on both sides, from the scrotum to the level of the inguinal canal. Penoscrotal swelling was significantly reduced on discharge. Conclusions: Penoscrotal swelling is a rare complication or manifestation of acute inflammation of the pancreas. It is important to identify scrotal swelling caused by pancreatitis because in severe cases it can be related to possible infertility in the future.

Acute peripartum pancreatitis complicating seronegative antiphospholipid antibody syndrome in pregnancy.

Antiphospholipid antibody syndrome is an autoimmune condition with clinical manifestations of vascular thrombosis and adverse pregnancy outcomes including recurrent miscarriage, fetal loss, growth restriction and pre-eclampsia with persistent antiphospholipid antibodies on laboratory examination. Treatment is targeted at preventing recurrent thrombosis and improving pregnancy outcomes. Commonly, treatment includes aspirin and anticoagulation, however, newer immunomodulatory treatments may also improve outcomes. The case describes a patient with a history of multiple miscarriages and pregnancy losses, fetal growth restriction and pre-eclampsia, and pulmonary embolism. Because of her significant adverse pregnancy outcomes, she was treated with certolizumab with a successful delivery at 33 weeks and 6 days. She also developed acute pancreatitis in the postpartum period. This is a rare condition, affecting 1-14/10 000 births. The pancreatitis resolved with conservative management, and she had an uncomplicated interval cholecystectomy.

An Unusual Case of Treatment-naive HIV Patient Presenting with Acute Pancreatitis in Sepsis with Infective Endocarditis and Bilateral Pulmonary Thromboembolism.

Acute pancreatitis is seen in patients with human immunodeficiency virus (HIV) as a result of antiretroviral drug therapy and hypertriglyceridemia. Thrombotic complications are known in patients of HIV as a result of endothelial dysfunction, and right-sided infective endocarditis (IE) is seen in HIV patients mostly due to intravenous (IV) drug abuse. However, the occurrence of acute pancreatitis with sepsis, IE, and bilateral thromboembolism in the same patient is rare. Here, we report this case of a treatment-naive nondrug abuser HIV patient with acute pancreatitis in sepsis, IE, and bilateral pulmonary thromboembolism who recovered completely with treatment.

Aetiology, presentation and outcomes of patients presenting with acute pancreatitis in a tertiary care hospital.

Acute pancreatitis (AP) is a multi-causal disease with a high rate of hospita lisation. Only a few cl inical stud ies have i nvestig ated the aetiologic al backgroun d, sever it y, and outcome of AP in Pakistan. Hence, this study was carried out to determine the aforementioned factors and correlate them w ith outcomes in a tert iary care set ting. This was a cros s -sec tional, retrospective study conducted at the Department of Gast roe nterolo gy, Aga Khan University Hospita l, Karachi, from Januar y 1, 2022, to December 31, 2022. Data was analysed using statis tical s oftware SPSS version 25. Vomiting was th e predominant presenting complaint and was seen in 139 (78.5%) patients. Gallstones were the predominant cause in 68 (37%) patients, followed by idiop athic panc reatitis in 22 (12%) p atients. Thirteen (7.1 % ) pat ients expire d. Patients with syst emi c complications were lik ely to suffer fro m severe disease (p=0.0 2), whereas those with lo cal complications were at an increa sed ris k of mor tal it y (p=0.04). Due to lac k of diagnostic facilities, the aetiology of a large number of AP cases remains unknown.