History Of Pancreatitis Research Articles

A case report of hemosuccus pancreaticus: the cause of upper gastrointestinal bleeding demystified after 9 months of episodic bleeding

Hemosuccus pancreaticus is a rare but potentially fatal cause of upper gastrointestinal (GI) bleeding. It is defined as bleeding from the pancreatic duct with blood draining into the duodenum through the ampulla of Vater. In patients with pancreatitis, peri-pancreatic blood vessels may be inflamed by pancreatic enzymes and form a pseudoaneurysm which can rupture and bleed into the pancreatic duct. We report a case of a 43-year-old man who presented with episodic upper GI bleeding of unclear etiology over 9 months without a clear documented history of pancreatitis. The etiology remained elusive even after multiple upper and lower endoscopies. Computed tomography angiography of the abdomen and pelvis during an acute episode detected a pseudoaneurysm of the gastroduodenal artery (GDA) with contrast extravasation into the dilated pancreatic duct. The pseudoaneurysm was treated with coil embolization, resulting in a persisting resolution of the patient’s symptoms. Clinicians should consider abdominal angiography when diagnosing obscure GI bleeding.

Abstract 4122620: Triglyceride Levels Associate With Cardiovascular Risk Across the Full Range but Not Among Individuals With Mild-to-Moderate Hypertriglyceridemia

Background: Guidelines focus on individuals with triglyceride levels of 200 to 499 mg/dL (2.3 and 5.6 mmol/L), a group for whom triglyceride-lowering therapy does not convincingly decrease risk. Hypotheses and goals: We re-assessed the hypotheses that triglyceride levels across the full biological range and within this constrained range strongly associate with cardiovascular risk. Methods: We calculated multivariable adjusted hazard ratios for major cardiovascular events and death according to baseline triglyceride levels among 119,573 individuals with triglycerides across the full biological range from the Copenhagen General Population Study, among 27,757 individuals with baseline triglycerides between 200 and 499 mg/dL (2.3 and 5.6 mmol/L) from the Copenhagen General Population Study and the Women’s Health Study, and among 31,372 individuals with mild-to-moderate hypertriglyceridemia participating in the PROMINENT, REDUCE-IT, and STRENGTH randomized trials. Results: Increasing triglyceride levels across the full range were associated with increasing risk of major cardiovascular events (N=12,241) (Figure 1). In individuals with mild-to-moderate hypertriglyceridemia from the two cohorts, combined hazard ratios (95% confidence interval) for major cardiovascular events (N=3,928) from lowest to highest triglyceride quartile were 1.0 (referent), 0.95 (0.87-1.04), 1.04 (0.95-1.13), and 1.13 (1.04-1.23). In the contemporary trials of patients selected for mild-to-moderate hypertriglyceridemia, the corresponding hazard ratios for major cardiovascular events (N=4,265) from lowest to highest triglyceride quartile were 1.0 (referent), 1.01 (0.93-1.10), 1.05 (0.96-1.14), and 1.10 (1.01-1.19). In neither prospective cohorts nor trials were triglyceride levels strongly associated with risk of cardiovascular or all-cause death within the constrained range. Conclusions: Contrary to expectations, individuals with mild-to-moderate hypertriglyceridemia may not express the same magnitude of cardiovascular risk as that observed across the full range of plasma triglycerides. Future trials of triglyceride-lowering therapy may want to consider enrollment across a wider range of triglyceride levels if there is no prior history of pancreatitis.

Transition of patients with familial chylomicronaemia syndrome from volanesorsen to olezarsen: safety and pharmacokinetic results

Abstract Background Familial chylomicronaemia syndrome (FCS) is a rare genetic disorder of lipoprotein lipase deficiency resulting in severe hypertriglyceridaemia and pancreatitis risk. Volanesorsen is a weekly-injected antisense oligonucleotide (ASO) designed to degrade APOC3 mRNA that is approved as an adjunct to diet to treat FCS in the EU, UK, and Brazil. Olezarsen is an investigational monthly-injected ASO-GalNAC3 conjugate also designed to degrade APOC3 mRNA, but directed to hepatocytes, resulting in more potency and less systemic exposure and making it a potential alternative to volanesorsen for FCS. Purpose This interim analysis of an open-label phase 3 trial evaluated olezarsen safety and pharmacokinetics in patients (pts) with FCS previously treated with volanesorsen. Methods Adults with FCS with prior volanesorsen treatment, or actively participating in an expanded access programme (US and Canada), started olezarsen 80 mg by subcutaneous injection every 4 weeks after a minimum washout of 6 weeks. Historical volanesorsen laboratory and safety data were unavailable. The primary objective was to assess safety from changes vs baseline in platelet count, liver enzymes, and renal function; bleeding events; and adverse events. Pharmacokinetic measurements included plasma volanesorsen and olezarsen concentrations. Immunogenicity was assessed by measuring anti-drug antibodies (Abs). Results Of 24 pts enrolled, the majority were female (n=13; 54.2%) and White (n=21; 87.5%), with mean age of 49.1 years; 20 (83.3%) had genetically and 4 (16.7%) clinically validated FCS, all had history of acute pancreatitis (or symptoms suggestive of pancreatitis requiring hospitalisation or emergency room/urgent care visit; mean, 3.4 episodes within 5 years) and 5 (20.8%) of thrombocytopaenia. Time since last volanesorsen dose was 42—1118 days. Baseline fasting triglyceride (median [interquartile range (IQR)], 18.6 [9.6,34.0] mmol/L [1648 (852,3007) mg/dL]; mean [standard deviation (SD)], 25.5 [20.5] mmol/L [2256 (1812) mg/dL]) and apolipoprotein C-III (median [IQR], 0.2 [0.1,0.4] g/L [16.1 (12.4,39.0) mg/dL]; mean [SD], 0.3 [0.2] g/L [25.9 (19.5) mg/dL]) levels were elevated. During a mean (SD) of 329 (95) days of olezarsen 80 mg treatment, no pts experienced hepatic failure, renal impairment, major bleeding events, or platelet count below the prespecified threshold of 50,000 mm³ (Table 1). Olezarsen levels at trough were elevated during the first 3 months, mainly due to residual volanesorsen levels in pts with washout <90 days (Figure 1). Eleven (45.8%) pts had treatment-emergent anti-olezarsen Abs, of whom 5 (20.8%) had anti-volanesorsen Abs, with no impact on safety or efficacy; pts with vs without anti-drug Abs had higher olezarsen trough levels (mean, 4.4–7.8 ng/mL vs 1.1 ng/mL). Conclusions In this interim analysis, olezarsen was safe and well tolerated in pts with FCS previously treated with volanesorsen after a minimum washout of 6 weeks.

Gamma-glutamyl transferase: A potential biomarker for pancreas steatosis in patients with concurrent obesity, insulin resistance and metabolic dysfunction-associated steatotic liver disease.

To evaluate the relationship between serum gamma-glutamyl transferase (GGT) levels and fatty pancreas in subjects with concurrent obesity, insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD) without a history of pancreatitis. From March 2019 to September 2021, 31 adult subjects with concurrent obesity and MASLD were recruited as part of the study investigating the biological impact of bariatric surgery and lifestyle modification on obesity. Chemical shift encoded MRI of the abdomen, LiverMultiScan, anthropometric, clinical and blood biochemistry analyses were performed prior to any intervention at baseline. GGT (p <.001) was significantly different between those 'with fatty pancreas' and 'without fatty pancreas' groups. GGT (p <.001) was significantly different between those 'with both metabolic syndrome and fatty pancreas' and those 'with metabolic syndrome but without fatty pancreas.' GGT (p <.001) was also significantly different between those 'with both diabetes and fatty pancreas' and those 'with diabetes but without fatty pancreas'. Logistic regression analysis showed that abnormal GGT levels (p = .010) and Hypertension (p = .045) were significant independent predictors of fatty pancreas. GGT was associated with fatty pancreas by an odds ratio 7.333 (95% [CI]: 1.467-36.664), while the AUROC of GGT in determining fatty pancreas was 0.849. Elevation in serum GGT might be a potential marker to identify fatty pancreas.

8443 Incretin-Mimetic Therapy In Hypertriglyceridemia-Induced Pancreatitis - A Case Report

Abstract Disclosure: A. Iqbal: None. U. Alwahab: None. Introduction The use of incretin-mimetic therapy (IMT), which includes human glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) agonists, in patients with a history of pancreatitis is controversial. While clinical trials have demonstrated a slightly increased incidence of acute pancreatitis (AP) in patients on IMT, it is unclear if patients with hypertriglyceridemia (HTG)-induced pancreatitis areat similar risk. In patients with type 2 diabetes (T2D) and HTG, control of diabetes and improvement of metabolic profile using IMT could decrease the risk of HTG-induced pancreatitis. Case Description We report a case of a patient with diabetes and a history of HTG-induced pancreatitis where IMT was successfully used without precipitation of AP. Patient A is a 44-year-old male with obesity (BMI 38.25 kg/m2 ), T2D, and severe HTG associated with recurrent episodes of AP. His triglyceride (TG) level has ranged from 983 to &amp;gt;4,000 mg/dL. He is on fenofibrate, icosapent ethyl, and rosuvastatin. His last hospitalization for acute pancreatitis was 3months prior. His most recent hemoglobin A1c is 7.4%, TG is 302mg/dL, and he is being treated with glipizide, metformin, empagliflozin, and multiple daily injections of insulin. For management of his obesity and T2D, he is then started on tirzepatide, in conjunction with diet and lifestyle modification, which is slowly up-titrated to 7.5 mg weekly. After 12 months of tirzepatide treatment, he has lost 10 lbs, his A1C is now 5.9%, triglycerides have improved to 172 mg/dL, and he has had no precipitation of AP. Discussion While a history of pancreatitis is a relative contraindication to the use of IMT, attention should be paid to the cause of pancreatitis. Obesity and uncontrolled diabetes are frequent triggers of AP. IMT helps improve metabolic profile in patients with obesity, uncontrolled diabetes, and hypertriglyceridemia, thus decreasing triglyceride levels and preventing further episodes of AP as seen in our patient. The use of IMT in patients with a history of AP should be done on an individualized basis. Controlling the trigger for the AP (such as hypertriglyceridemia) should be prioritized and shared medical decision-making with the patient should be done regarding the benefits and risks of IMT. Presentation: 6/3/2024

6531 Assessing the Risk of Recurrence in Acute Pancreatitis Among Patients with Type 2 Diabetes Initiating GLP-1 Receptor Agonists Therapy

Abstract Disclosure: M. Nassar: None. H. Abosheaishaa: None. P. Dandona: None. H. Ghanim: None. A. Chaudhuri: None. Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recognized therapeutic agents for patients with type 2 diabetes mellitus and obesity. However, due to concerns about pancreatitis, clinicians do not recommend these agents for patients with a history of pancreatitis. Existing research presents conflicting evidence about this association. Our primary aim was to evaluate the risk of recurrence of acute pancreatitis (AP) associated with initiating GLP-1 RAs in patients with a history of AP. Methods: Our retrospective cohort study deployed the TriNetX platform, leveraging a large dataset from 106 healthcare organizations and approximately 127 million patients across 15 countries. We obtained data specific to our research on September 21, 2023. Using the ICD-10-CM code, we identified groups of adults with AP. We investigated the effect of GLP-1 RA vs. SGLT2i, DPP4i, and no medication (GLP-1 RA, SGLT2i, and DPP4i) on the recurrence of AP within 5 years of starting treatment. We ensured comparability between cohorts by employing propensity score matching, which focused on critical variables such as age, gender, body mass index (BMI), cholelithiasis, tobacco use, serum triglyceride, and HbA1c levels. Results: We matched the GLP-1 and SGLT2i cohorts, which initially had 4,680 and 7,212 patients, respectively, down to 3,926 in each group. Similarly, the GLP-1 vs. DPP4i comparison matched both cohorts to 3,324 patients from initial counts of 4,680 and 5,723 patients. In the matched cohorts, the GLP-1 group showed a lower AP recurrence risk (15.2%) than the SGLT2i group (24%). This difference was significant (-8.9%, 95% CI: -0.106, -0.071), with a notable risk ratio of 0.630 and an odds ratio of 0.564. For the GLP-1 vs. DPP4i comparison, the GLP-1 group's AP recurrence risk was 14.4%, lower than the 23.3% in the DPP4i group. This difference (-8.9%, 95% CI: -0.108 to -0.071) was also significant, with a risk ratio of 0.616 and an odds ratio of 0.552. For the GLP-1 vs. no medication (GLP-1RA, DPP4i, and SGLT2i) comparison, the GLP-1 group's AP recurrence risk was 14.5%, lower than the 51.6% in the comparison group. This difference (-37.1%, 95% CI: -0.388 to -0.353) was also significant, with a risk ratio of 0.282 and an odds ratio of 0.16. Conclusion: Our research showed that starting GLP-1 RA therapy in people who have had a history of AP does not increase and may potentially lower the risk of recurrence of AP than starting SGLT2i or DPP4i therapy and no medication group. These findings highlight the potential of GLP-1 RA therapy as a safer therapeutic option in this patient population, which requires further investigation. Presentation: 6/1/2024

9232 Assessing the Risk of Recurrence in Acute Pancreatitis Among Patients with Type 2 Diabetes Initiating GLP-1 Receptor Agonists Therapy

Abstract Disclosure: M. Nassar: None. H. Abosheaishaa: None. P. Dandona: None. H. Ghanim: None. A. Chaudhuri: None. Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recognized therapeutic agents for patients with type 2 diabetes mellitus and obesity. However, due to concerns about pancreatitis, clinicians do not recommend these agents for patients with a history of pancreatitis. Existing research presents conflicting evidence about this association. Our primary aim was to evaluate the risk of recurrence of acute pancreatitis (AP) associated with initiating GLP-1 RAs in patients with a history of AP. Methods: Our retrospective cohort study deployed the TriNetX platform, leveraging a large dataset from 106 healthcare organizations and approximately 127 million patients across 15 countries. We obtained data specific to our research on September 21, 2023. Using the ICD-10-CM code, we identified groups of adults with AP. We investigated the effect of GLP-1 RA vs. SGLT2i, DPP4i, and no medication (GLP-1 RA, SGLT2i, and DPP4i) on the recurrence of AP within 5 years of starting treatment. We ensured comparability between cohorts by employing propensity score matching, which focused on critical variables such as age, gender, body mass index (BMI), cholelithiasis, tobacco use, serum triglyceride, and HbA1c levels. Results: We matched the GLP-1 and SGLT2i cohorts, which initially had 4,680 and 7,212 patients, respectively, down to 3,926 in each group. Similarly, the GLP-1 vs. DPP4i comparison matched both cohorts to 3,324 patients from initial counts of 4,680 and 5,723 patients. In the matched cohorts, the GLP-1 group showed a lower AP recurrence risk (15.2%) than the SGLT2i group (24%). This difference was significant (-8.9%, 95% CI: -0.106, -0.071), with a notable risk ratio of 0.630 and an odds ratio of 0.564. For the GLP-1 vs. DPP4i comparison, the GLP-1 group's AP recurrence risk was 14.4%, lower than the 23.3% in the DPP4i group. This difference (-8.9%, 95% CI: -0.108 to -0.071) was also significant, with a risk ratio of 0.616 and an odds ratio of 0.552. For the GLP-1 vs. no medication (GLP-1RA, DPP4i, and SGLT2i) comparison, the GLP-1 group's AP recurrence risk was 14.5%, lower than the 51.6% in the comparison group. This difference (-37.1%, 95% CI: -0.388 to -0.353) was also significant, with a risk ratio of 0.282 and an odds ratio of 0.16. Conclusion: Our research showed that starting GLP-1 RA therapy in people who have had a history of AP does not increase and may potentially lower the risk of recurrence of AP than starting SGLT2i or DPP4i therapy and no medication group. These findings highlight the potential of GLP-1 RA therapy as a safer therapeutic option in this patient population, which requires further investigation. Presentation: 6/1/2024

12618 A Rare Case Of Diabetic Ketoacidosis Leading To Severe Hypertriglyceridemia-induced Necrotizing Pancreatitis

Abstract Disclosure: E.R. Perez Roman: None. D.A. Lopez Rodriguez: None. K. Ramirez Gorbea: None. M. Sanchez Cordero: None. Y. Garcia Cruz: None. Acute pancreatitis is an acute inflammatory process of the pancreas that if left untreated can become complicated resulting in multiple organ damage and a fatal outcome in approximately 10%-40% of patients. There are well-known causes that can lead to pancreatitis such as alcohol, hereditary disorders, cholelithiasis, prior pancreatitis, and medications. Less frequently, it can be related to poorly controlled diabetes mellitus and diabetic ketoacidosis (DKA), given that in a state of low or deprived insulin, there is a breakdown of triglycerides into toxic fatty acids by pancreatic lipases; this lipotoxicity can result in the development of acute pancreatitis. We present a case of a 50-year-old woman with a past medical history of untreated hyperlipidemia and previous pancreatitis who was transferred to our institution with acute epigastric pain radiating to the back, nausea, and persistent vomiting. Upon arrival, blood glucose was 299 mg/dL, HbgA1c of 11.4%, lactic acid of 3.6 mmol/L, hypocalcemia of 6.0 mg/dl, hypoalbuminemia, and elevated pancreatic enzymes, amylase 869 U/L and lipase 2,493 U/L. The lipid panel was remarkable for total cholesterol of 1,085 mg/dL and triglycerides of 4,369mg/dL. Abdominopelvic CT scan confirmed acute pancreatitis with extensive peripancreatic and regional mesenteric edema. This patient was treated with aggressive IV fluid resuscitation and treated for DKA as per protocol. Despite prompt treatment, the patient rapidly deteriorated, developing pulmonary effusions and impending respiratory failure requiring mechanical ventilation. Her hyperglycemia was challenging to control and in the setting of severe hypertriglyceridemia, insulin requirements were higher, as intravenous insulin is useful in patients with concomitant findings, in the absence of plasmapheresis availability. Despite the marked reduction of triglyceride to 978 mg/dL and a decrease in pancreatic enzymes, multiorgan failure developed. Unfortunately, the patient died. Repeated abdominopelvic CT imaging revealed the progression of the disease to necrotizing pancreatitis involving the pancreatic head, uncinate process, and neck of the pancreas with evidence of a small hypodense lesion at the level of the tail of the pancreas. This case emphasizes the importance of prompt recognition of acute pancreatitis secondary to uncontrolled hyperglycemia with concomitant severe hypertriglyceridemia since it can lead to a worse clinical outcome as seen in our patient who developed rapid progression to necrotizing pancreatitis. It is paramount not to delay treatment with aggressive fluid resuscitation, continuous insulin infusion, and if available, plasmapheresis; as these treatment strategies in conjunction can be life-saving. Presentation: 6/3/2024

12615 Extremely High-dose Insulin Requirement In A Child With Covid-19 Infection

Abstract Disclosure: R. Pratibha: None. T.R. Langner: None. Background: COVID-19 infection has been associated with new diagnosis of diabetes, worsening of hyperglycemia, and increased frequency and severity of diabetic ketoacidosis (DKA) in type 1 diabetes (DM) patients. Stress- related and steroid induced hyperglycemia are also well described during COVID infection with poor glycemic control being linked to more severe SARS-CoV-2 infection outcomes. While insulin needs increase during infection, extremely high insulin requirement is uncommon and not described in the pediatric population. We present here a case of mild COVID infection with transient markedly high insulin requirements. Clinical Case A 16-year-old-African-American- female with history of fairly well controlled type 2 diabetes mellitus on closed loop system insulin pump (Omnipod) with continuous glucose monitor (CGM), was admitted with COVID-19, aspiration pneumonia and hyperglycemia. She had been diagnosed 10 months prior with Hemoglobin A1c (HbA1c) of 11.4% and mild diabetic ketoacidosis (DKA). Diabetes antibodies were negative. Four months prior to admission her HbA1c was 7.8%. Upon this hospitalization she had no hypoxemia or respiratory failure and did not need steroids. Procalcitonin level 0.09 ng/mL was normal. Developmental delay, non-ambulatory and non-verbal status, an underlying mitochondrial neurological disease with G tube and ventilator dependence added to the medical complexity. HbA1c (8.1%) and Fructosamine 316 (n 200-285 mcmol/L) were not indicative of poor control. While her pneumonia resolved promptly, blood sugar (BG) elevation prolonged her hospitalization. She was not in DKA. Despite increasing her basal rate by 50% and an additional 20% higher temporary basal rate via her insulin pump there was little response. She was switched to Insulin drip by the 7th day. Her Insulin rate had increased to 26 units per hour (at 0.64 Units/Kg/hour) by day 8. This high insulin-dose need lasted for around 36 hours, before gradually reducing over a week. She has a history of recurrent pancreatitis. Lipase 335 U/L was elevated initially but started reducing within 2 days and had normalized by day 13. She was transitioned back to her pump although at higher basal rate than the previous home regimen, by 14th day. Conclusion While a constellation of factors such as stress, steroids, underlying poor glycemic control may cause hyperglycemia in COVID-19, these do not explain the high insulin demand in our patient. COVID infection with impaired insulin secretion, mild pancreatitis may have contributed to the brief remarkably high-dose insulin requirement, but it appears to be increased insulin resistance which could possibly explain the transient derangement. To our knowledge this has previously not been described in a pediatric diabetic patient. Presentation: 6/3/2024

7654 Unusual Case of Lipodystrophy: A Novel Disease Phenotype?

Abstract Disclosure: M. Celik Guler: None. E.D. Frontera: None. K. Hoose: None. M.C. Foss de Freitas: Advisory Board Member; Self; PTC Therapeutics. Speaker; Self; Amryt. L. Douyon: None. E.A. Oral: Advisory Board Member; Self; Amryt, Regeneron Pharmaceuticals. Consulting Fee; Self; Regeneron Pharmaceuticals, Amryt, Third Rock Ventures. Grant Recipient; Self; Regeneron Pharmaceuticals, Amryt. Research Investigator; Self; Novo Nordisk, Ionis Pharmaceuticals Inc., Fractyl, GI Dynamics, Rhythm Pharmaceuticals. Other; Self; Amryt. Background: Lipodystrophy syndromes (LD) are rare disorders characterized by varying degrees of adipose tissue deficiency that can predispose individuals to severe metabolic complications. Although these syndromes are traditionally subclassified based on inheritance patterns and the degree of adipose tissue loss, patients may exhibit highly heterogeneous clinical presentations. In this context, we report a unique case of partial lipodystrophy with an unusual distribution of adipose tissue that likely represents a novel syndrome and challenges conventional phenotypes. Clinical Case: A 60-year-old Puerto Rican female patient with medical history of type 1 diabetes mellitus (DM), obesity, hyperlipidemia, irritable bowel syndrome, asthma, and coronary artery disease was referred to us for unexplained asymmetric distribution of adipose tissue. She had chronic left posterolateral hip pain and lipoatrophy in her left lower extremity. Her medical history showed that she was born approximately 7 lbs., with no evidence of trauma during delivery. Her mother was given an unknown medication for improving circulation to the placenta. She had a morphea like rash on the arms and chest wall more prominent on the left upper body at birth. In addition, a dimple on her hip was noticed by her mother during the early stages of infancy. Despite the normal progression of neurological development (walking/climbing stairs), she always had a very mild limp. Also, her right arm was always 2 inches larger than her left arm. When she gained weight, she also put on more asymmetric weight on the left side of the abdomen and left lower torso. She had been treated with insulin injections since she was diagnosed with diabetes at the age of 11. She never demonstrated any islet cell specific antibodies. She had a normal weight until pregnancy at the age of 27, during which she gained 20 lbs. Her weight continued to increase over time, and the maximum was 212 lbs. Her examination reveals a BMI of 41.46 kg/m² with excess fat in the right arm, mid-section, left thigh, and left mons pubis. Conversely, only the left leg appears to demonstrate specific fat atrophy, with a near-total loss of adipose tissue starting from the mid-gluteal region. The hip MRI result reported moderate osteoarthritis of the left hip. EMG revealed signs of length-dependent sensorimotor axonal polyneuropathy and long duration/large amplitude motor unit potentials isolated only in the left medial gastrocnemius muscle. Triglyceride level was 73 mg/dL, HbA1c level was 6.8%, with an average total insulin dosage of around 43 IU/day. There was no history of pancreatitis due to hypertriglyceridemia. Conclusion: Our case highlights the heterogeneity of the lipodystrophy spectrum with a novel presentation of lipodystrophy. In addition, there may be homeostatic control of deposition of fat to seek symmetry between upper versus lower and right versus left sided depots. Presentation: 6/1/2024

Decreased risk of recurrent acute pancreatitis with semaglutide and tirzepatide in people with type 2 diabetes or obesity with a history of acute pancreatitis: A propensity matched global federated TriNetX database-based retrospective cohort study

BackgroundAcute pancreatitis (AP) is a significant health concern with potential for recurrent episodes and serious complications. The risk of recurrence in type 2 diabetes (T2D) or obesity can be influenced by various factors and treatments, including GLP-1 receptor agonists (GLP-1RAs). This study evaluates the risk of recurrent AP among patients with a history of the condition, focusing on the effects of different GLP-1RA treatments. ObjectivesOur objective is to compare the recurrence risks of AP between patients treated with different GLP-1RAs. MethodsWe conducted a retrospective cohort study using the TriNetX platform, encompassing 258,238 individuals with T2D or obesity who have a history of AP. We assessed the recurrence of AP over a five-year period, analyzing data on treatment regimens, with a focus on the use of Semaglutide, Tirzepatide, and other GLP-1RAs. ResultsGLP-1RA users experienced significantly lower recurrence rates of AP, with those without risk factors showing GLP-1RA users had a recurrence rate of 13.8 % compared to 40.9 % for non-users. Semaglutide and Tirzepatide showed the most favorable outcomes; Semaglutide users had lower recurrence rates than Exenatide (10.1 % vs. 27 %) and slightly lower than Dulaglutide (13.6 % vs. 15.4 %), though not statistically significant with Dulaglutide. Tirzepatide users displayed the lowest recurrence risk at 6.2 %, significantly lower than those on Semaglutide (11.7 %). ConclusionsGLP-1RAs, particularly Semaglutide and Tirzepatide, are associated with a reduced risk of recurrent AP in people with T2D or obesity. The differential risk profile between these drugs highlights the need for further studies and personalized treatment plans.

Groove pancreatitis – an unusual case of pancreatitis, case report

Groove pancreatitis is a rare form of chronic pancreatitis affecting the pancreaticoduodenal groove, leading to ductal stenosis and symptoms like abdominal pain, vomiting, and jaundice. It often coexists with cystic dystrophy of the duodenal wall (CDDW), marked by duodenal wall thickening and cyst formation. We report a case of a 36-year-old male with persistent abdominal pain and a history of acute pancreatitis, diagnosed with CDDW via MRI. Despite multiple endoscopic interventions, ductal access was challenging due to inflammation and conservative management with proton pump inhibitors and pancreatic enzymes provided symptom relief. Diagnostic tools include MRI, endoscopy, and EUS were administered. Management of groove pancreatitis still remains a challenge consisting of treatment ranging from conservative methods to surgical intervention for refractory cases, emphasizing a cautious, stepwise approach and lifestyle changes.

Incidence of Post-ERCP Pancreatitis in Patients Receiving Rectal Indomethacin vs. Compounded Rectal Diclofenac Prophylaxis.

Endoscopic retrograde cholangiopancreatography (ERCP) carries a 3-15% risk of post-ERCP pancreatitis (PEP). Rectal indomethacin reduces the risk of PEP, but its cost has increased more than 20-fold over the past decade. Rectal diclofenac is also used to prevent PEP but is not commercially available in the United States. The aim of this study is to compare the incidence of PEP after administration of commercially available rectal indomethacin versus compounded rectal diclofenac and assess financial implications. ERCP cases at our institution with administration of 100mg rectal indomethacin or 100mg compounded rectal diclofenac between May 2018 and January 2022 were retrospectively reviewed. The incidence and severity of PEP was compared between the indomethacin (n = 728) and diclofenac (n = 304) groups. Risk factors (young age, female sex, history of pancreatitis or PEP, sphincterotomy during procedure, pancreatic indication, trainee involvement) and protective factors (prior sphincterotomy, pancreatic duct stenting) for PEP were compared between groups. 60 patients (8.2%) in the rectal indomethacin group and 25 patients (8.2%) in the compounded rectal diclofenac group developed PEP, resulting in moderate or severe PEP in 9 (15.0%) and 2 (8.0%) patients, respectively. The compounded rectal diclofenac group had more trainee involvement (46.1% vs. 32.8%, p = 0.0001) and more prior sphincterotomy cases (15.8% vs. 10.6%, p = 0.0193) compared to the rectal indomethacin group; no statistically significant differences were observed in all other risk and protective factors. Following switch to compounded rectal diclofenac, institutional annual cost savings amounted to $441,460.62 and patient charge decreased 45-fold. This retrospective single-center real-world analysis showed similar efficacy of rectal indomethacin and compounded rectal diclofenac in preventing PEP but demonstrates substantial cost savings after switching to compounded rectal diclofenac.

The incidence of acute pancreatitis with GLP-1 receptor agonist therapy in individuals with a known history of pancreatitis

Glucagon-like peptide-1 receptor agonists (GLP-1RA) have been reported to increase the risk of acute pancreatitis (AP). This real-world study did not observe a higher frequency of AP with GLP-1RA exposure in adults with T2D and a prior history of AP regardless of etiology.

Pancreatic cancer risk in diabetic patients using the Japanese Regional Insurance Claims

Pancreatic cancer presents a critical health issue characterized by low survival rates. Identifying risk factors in specific populations, such as those with diabetes, is crucial for early detection and improved outcomes. This study aimed to identify risk factors for pancreatic cancer in diabetic patients using a longitudinal cohort from the Shizuoka Kokuho database, spanning April 2012 to September 2021. Diabetic patients were identified and monitored for the onset of pancreatic cancer. Factors analyzed included age, sex, the Elixhauser comorbidity index, and specific comorbidities. Statistical analyses involved univariate and multivariate Cox proportional hazards regression. The study identified 212,775 as diabetic patients and 1755 developed pancreatic cancer during the period. The annual incidence rate of pancreatic cancer in this group was 166.7 cases per 100,000 person-years. The study identified older age, male sex, a history of liver disease, chronic pancreatitis, and pancreatic cystic lesions as significant risk factors for pancreatic cancer in diabetic patients. The study also highlighted the absence of a significant association between diabetes type or diabetic complications and the onset of pancreatic cancer. These findings may aid in the early diagnosis of pancreatic cancer in diabetic patients and may inform revisions in screening practices in diabetic patients.

Incretin mimetics and acute pancreatitis: enemy or innocent bystander?

The incretin enhancers and mimetics, including dipeptidyl peptidase-4 (DPP-4) inhibitors, GLP-1 receptor agonists (GLP-1RA) and GLP-1/GIP co-agonists, have become mainstays in the treatment of type 2 diabetes (T2D). Recently, the approval of certain GLP-1RA and GLP-1/GIP co-agonists for the treatment of obesity has broadened their popularity and use. In this review, we summarize the evidence for an association of these drugs with acute pancreatitis and other adverse events of special interest to gastroenterologists. In addition to pancreatic islets, GLP-1 receptors are expressed in the exocrine cells of the pancreas. There is inconsistent evidence for an association of DPP-4 inhibitors, GLP-1RA and co-agonists with risk for acute pancreatitis in individual trials. Meta-analyses of long-term randomized controlled trials indicate a small risk of acute pancreatitis associated with DPP-4 inhibitors but not GLP-1RA or co-agonists. Cholecystitis and cholelithiasis may be more common among those treated with GLP-1RA and GLP-1/GIP co-agonists. There is no evidence that any of these drugs are associated with an increased risk of pancreatic cancer. While drugs that leverage the incretin system are increasingly being used for patients with T2D and obesity, caution in warranted in those with a history of pancreatitis and gallbladder disease.

Effect of endoscopic sphincterotomy and endoscopic papillary balloon dilation endoscopic retrograde cholangiopancreatographies on the sphincter of Oddi.

Endoscopic retrograde cholangiopancreatography (ERCP), with its clinical ad-vantages of less trauma and faster recovery, has become the primary treatment for choledocholithiasis. To investigate the effects of different ERCP procedures on the sphincter of Oddi. The clinical data of 91 patients who underwent ERCP at Yixing Hospital of Traditional Chinese Medicine between February 2018 and February 2021 were analyzed retrospectively. The patients were divided into endoscopic sphincterotomy (EST, n = 24) and endoscopic papillary balloon dilation (EPBD, n = 67) groups. The duration of operation, pancreatic development, pancreatic sphincterotomy, intubation difficulties, stone recurrence, and incidence of reflux cholangitis and cholecystitis were statistically analyzed in patients with a history of choledocholithiasis, pancreatitis, and Oddi sphincter dysfunction in the EST and EPBD groups. Differences in hypertension, diabetes, increased bilirubin, small diameter of the common bile duct, or ampullary diverticulum between the two groups were not significant. Statistically significant differences were observed between the two groups concerning sex and age (< 60 years). Patients with a history of choledocholithiasis, pancreatitis, and Oddi sphincter dysfunction were higher in the EST group than in the EPBD group. The number of cases of pancreatic development, pancreatic duct sphincterotomy, and difficult intubation were higher in the EST group than in the EPBD group. The number of Oddi's sphincter manometries, ERCP surgical outcomes, and guidewires entering the pancreatic duct several times in EST group were lower than those in the EPBD group. The numbers of stone recurrences, reflux cholangitis, and cholecystitis were higher in the EST group than in the EPBD group. In summary, common bile duct stones, pancreatitis history, and multiple guided wire introductions into the pancreatic duct are independent risk factors for EST and EPBD. Based on this evidence, this study can provide actionable insights for clinicians and researchers.

Diagnostic accuracy of endoscopic ultrasonographic shear wave elastography for assessing early chronic pancreatitis using the Japanese diagnostic criteria 2019.

Endoscopic ultrasound shear wave elastography (EUS-SWE) can facilitate an objective evaluation of pancreatic fibrosis. Although it is primarily applied in evaluating chronic pancreatitis, its efficacy in assessing early chronic pancreatitis (ECP) remains underinvestigated. This study evaluated the diagnostic accuracy of EUS-SWE for assessing ECP diagnosed using the Japanese diagnostic criteria 2019. In total, 657 patients underwent EUS-SWE. Propensity score matching was used, and the participants were classified into the ECP and normal groups. ECP was diagnosed using the Japanese diagnostic criteria 2019. Pancreatic stiffness was assessed based on velocity (Vs) on EUS-SWE, and the optimal Vs cutoff value for ECP diagnosis was determined. A practical shear wave Vs value of ≥50% was considered significant. Each group included 22 patients. The ECP group had higher pancreatic stiffness than the normal group (2.31 ± 0.67 m/s vs. 1.59 ± 0.40 m/s, p < 0.001). The Vs cutoff value for the diagnostic accuracy of ECP, as determined using the receiver operating characteristic curve, was 2.24m/s, with an area under the curve of 0.82 (95% confidence interval: 0.69-0.94). A high Vs was strongly correlated with the number of EUS findings (rs = 0.626, p < 0.001). Multiple regression analysis revealed that a history of acute pancreatitis and ≥2 EUS findings were independent predictors of a high Vs. There is a strong correlation between EUS-SWE findings and the Japanese diagnostic criteria 2019 for ECP. Hence, EUS-SWE can be an objective and invaluable diagnostic tool for ECP diagnosis.

Association of Smoking with progression from low-risk to high-risk intraductal papillary mucinous neoplasms and pancreatic cancer

BackgroundFactors associated with the risk of pancreatic adenocarcinoma (PDAC) may play a role in the development and progression of Intraductal Papillary Mucinous Neoplasms (IPMNs). However, data are limited. AimTo compare exposome factors in three groups of patients with “high or low-risk” IPMNs, as assessed at diagnosis and during a 24-months follow-up, and with PDAC. MethodsPatients were matched (same sex, age ±5) 1:1. Exposure variables were compared across groups using Kruskal-Wallis, ANOVA, or Chi-square tests with Bonferroni correction. ResultsA total of 151 patients were enrolled in each of the three groups (453 overall). The proportion of current smokers was progressively higher in “low-risk”, “high-risk” IPMNs and PDAC patients (8.1 %, 11.2 %, 23.3 %; p = 0.0002). The three groups did not differ in terms of ever or heavy smoking, BMI, history of diabetes, cancer, cholecystectomy or chronic pancreatitis, use of statins or aspirin, and family history of cancer. A history of peptic ulcer was more common in PDAC (7.2 %) than in either “low-risk” (2.0 %) or “high-risk” (2.6%) IPMNs (p = 0.02, not significant after Bonferroni correction). ConclusionActive smoking seems associated with the progression of IPMNs to malignancy, and cessation of active smoking might be advised in patients with IPMN.

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)

BackgroundPost-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.MethodsA 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.ResultsThe 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.ConclusionThe 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.