No abstract

Abstract Background Thiopurine methyltransferase (TPMT) activity influences azathioprine conversion into active metabolite 6-thioguanine nucleotide (6-TGN). Low TPMT activity correlates with high 6-TGN and risk for myelosuppression. Conversely normal-to-high TPMT activity may be associated with low 6-TGN and drug resistance, so called hyper-metabolizers. Our aim was to identify the effect of normal-to-high TPMT activity on 6-TGN concentrations in an IBD population. Methods A retrospective chart review of patients aged ≥ 18 with IBD, on azathioprine, with documented TPMT activity and 6-TGN concentration was performed. Correlations were evaluated via Spearman’s Rho correlation coefficient. Linear regression was used to determine the effect of TPMT activity on 6-TGN accounting for confounders. Relationships between TPMT activity, drug dose and 6-TGN levels were defined via Average Causal Mediation Effects (ACME). Results One hundred patients were included. No correlation was observed between TPMT activity, azathioprine dosing, and metabolite concentrations. Overall, 39% of the cohort had a therapeutic 6-TGN level of >230 pmol/8x108 red blood cells (RBCs). No patient under 1mg/kg achieved a therapeutic 6-TGN level, whereas 42% of patients taking 2.5mg/kg did. The median 6-TGN concentration was higher for those in remission (254 pmol/8x108 RBCs, interquartile range (IQR): 174, 309) versus those not in remission (177 pmol/8x108 RBCs, IQR: 94.3, 287.8), though not significantly (p = 0.08). Smoking was the only clinical factor associated with 6-TGN level. On multivariate linear regression, only age, azathioprine dose, and obese BMI were predictive of metabolite concentration. Conclusions Variations within the normal range of TPMT activity do not impact 6-TGN concentration.

No abstract

Introduction: Inflammatory dysregulation of the coagulation cascade and vascular stasis in hospitalized necrotizing pancreatitis (NP) patients serve as a milieu for venous thromboembolism which is often underrecognized. We aimed to identify the incidence and independent risk factors for deep vein thrombosis (DVT) and pulmonary embolism (PE) in our NP cohort. Methods: All adult NP patients hospitalized at our center between 2009 and 2022 were identified from a prospective database and categorized into two groups based on development of DVT or PE (cases) or not (controls), within 6 months after NP hospitalization. Baseline data included demographics, ASA score, SIRS and organ failure on admission and at 48 hours, interventions (endoscopic, percutaneous or surgical), length of stay, transfer status, need for ICU, clinical and imaging characteristics and anticoagulation during admission. Univariable and multivariable analysis identified independent predictors for DVT and PE. P , 0.05 was considered significant. Results: Among 641 NP patients, 510 patients [males 349 (68%), median age 52 years (IQR 38-64)] were eligible for inclusion. DVT/PE developed in 62 (12%) patients; 26 DVT (5%), 22 PE (4%) and 14 with both (3%) after a median 17 (IQR 7-34) days from NP. Demographics were similar between groups though cases were older with more comorbidities (higher ASA) including a personal history of cancer. Nearly all patients [n 5 506, (99%)] including all cases were on DVT prophylaxis (pharmacologic or mechanical) during hospitalization. Significant clinical and imaging predictors for DVT/PE on multivariable analysis were age (.50 years) [OR 2.1 (1.05-4.13)], personal history of cancer ], peripancreatic extent )], infected necrosis ] and increased length of stay (LOS) ]. Conclusion: Incidence of DVT/PE in our NP cohort was 12% (comparable to incidence rates in cancer and IBD), usually diagnosed within one month of NP hospitalization. Age .50, peripancreatic necrosis extent, personal history of cancer, infected necrosis, and prolonged hospitalization were independent risk factors. This high-risk group of patients may benefit from intensified DVT prophylaxis during hospitalization and closer follow up after discharge (Table 1).

results were negative for viral hepatitis panel, antinuclear antibodies, anti-mitochondrial antibodies, alpha-1 antitrypsin levels, and normal ceruloplasmin levels. Colonoscopy was unrevealing except for a diminutive tubular adenoma. EGD later revealed blunted villi with flat mucosa in the first and second portion of the duodenum. Biopsy results later confirmed pathology results compatible with celiac disease. During this course of workup, the patient developed nephrolithiasis and with incidental findings of pancreatic atrophy and pancreatic head calcifications detected on CT urogram. Chronic pancreatitis was later confirmed on endoscopic ultrasound with evidence of multiple intraductal stones. Patient did not have a history of alcohol use or pancreatic problems in the family. After being diagnosed with Celiac disease and secondary chronic pancreatitis with exocrine pancreatic insufficiency, he was started on a gluten-free diet and pancrelipase. Patient was noted to have 9-pound weight gain during a 4 month follow-up appointment. Discussion: Chronic pancreatitis is a rare extraintestinal manifestation of celiac disease, reported to have a threefold increased risk but only with a reported incidence of 0.52% at least 30 days after diagnosis of celiac disease compared to 0.13% in non-celiac disease patients.