Impact of Ethno-racial Factors on Clinical Outcomes and Health Care Utilization in Chronic Pancreatitis.

BACKGROUND: Healthcare disparities adversely affect clinical outcomes in racial and ethnic minorities. Chronic pancreatitis (CP) is a complex disorder, and pressures for time and cost-containment may amplify the disparity for minorities in this condition. This study aimed to assess ethno-racial differences in the clinical outcomes of CP patients cared for at our institution. METHODS: This is a study of CP patients with available ethno-racial information followed at our pancreas center. We reviewed their demographics, comorbidities, clinical outcomes, and resource utilization: pain, frequent flares (≥ 2/year), local complications, psychosocial variables, exocrine, and endocrine insufficiency, imaging, endoscopic procedures, and surgeries. The outcomes underwent logistic regression to ascertain association(s) with covariates and were expressed as odds ratio (95% confidence intervals). RESULTS: Of the 445 CP patients, there were 23 Hispanics, 330 Non-Hispanic Whites, 47 Non-Hispanic Blacks, 16 Asian Americans, and 29 patients from Other/mixed races. Over a median follow-up of 7 years, no significant differences in the pain profile (p = 0.36), neuromodulator use (p = 0.94), and opioid use for intermittent (p = 0.34) and daily pain (p = 0.80) were observed. Frequent flares were associated with Hispanic ethnicity [2.98(1.20-7.36); p = 0.02], despite adjustment for smoking [2.21(1.11-4.41); p = 0.02)] and alcohol [1.88(1.06-3.35); p = 0.03]. Local complications (pseudocysts, mesenteric thrombosis, and biliary obstruction), exocrine and endocrine dysfunction, and healthcare resource utilization (cross-sectional imaging, endoscopic procedures, celiac blocks, or surgeries) were comparable across all ethno-racial groups. CONCLUSIONS: Although no significant differences in clinical outcomes, and health resource utilization were noted across ethno-racial groups, Hispanic ethnicity had significant association with CP flares. This study calls for further investigation of an understudied minority population with CP.

Impact of Geospatial Food Access on Acute Pancreatitis Outcomes.

BACKGROUND AND AIM: Food access is an important social determinant of health and refers to geographical and infrastructural aspects of food availability. Using publicly available data on food access from the United States Department of Agriculture (USDA), geospatial analyses can identify regions with variable food access, which may impact acute pancreatitis (AP), an acute inflammatory condition characterized by unpredictable outcomes and substantial mortality. This study aimed to investigate the association of clinical outcomes in patients with AP with geospatial food access. METHODS: We examined AP-related hospitalizations at a tertiary center from January 2008 to December 2018. The physical addresses were geocoded through ArcGIS Pro2.7.0 (ESRI, Redlands, CA). USDA Food Access Research Atlas defined low food access as urban areas with 33% or more of the population residing over one mile from the nearest food source. Regression analyses enabled assessment of the association between AP outcomes and food access. RESULTS: The study included 772 unique patients with AP residing in Massachusetts with 931 AP-related hospitalizations. One hundred and ninety-eight (25.6%) patients resided in census tracts with normal urban food access and 574 (74.4%) patients resided in tracts with low food access. AP severity per revised Atlanta classification [OR 1.88 (95%CI 1.21-2.92); p = 0.005], and 30-day AP-related readmission [OR 1.78(95%CI 1.11-2.86); p = 0.02] had significant association with food access, despite adjustment for demographics, healthcare behaviors, and comorbidities (Charlson Comorbidity Index). However, food access lacked significant association with AP-related mortality (p = 0.40) and length of stay (LOS: p = 0.99). CONCLUSION: Low food access had a significant association with 30-day AP-related readmissions and AP severity. However, mortality and LOS lacked significant association with food access. The association between nutrition, lifestyle, and AP outcomes warrants further prospective investigation.

Long-Term Follow-up of Disabled Patients With Chronic Pancreatitis: Evaluation of Clinical Characteristics, Outcomes, and Predictors.

BACKGROUND/AIMS: Patients with chronic pancreatitis (CP) often report a poor quality of life and may be disabled. Our study identifies clinical characteristics, predictors and outcomes in CP patients with disability. METHODS: A review of established CP patients followed in our Pancreas Center between January 1, 2016 and April 30, 2021. Patients were divided into 2 groups based on disability. Univariate analysis was performed to identify differences in demographics, risk factors, comorbidities, complications, controlled medications, and resource utilization. Multivariate analysis was conducted to identify predictors for disability. RESULTS: Out of 404 CP patients, 18% were disabled. These patients were younger (53.8 vs. 58.8, P =0.001), had alcoholic CP (54.1% vs. 30%; P <0.001), more recurrent pancreatitis (83.6% vs. 61.1%; P =0.001), chronic abdominal pain (96.7% vs. 78.2%; P =0.001), exocrine pancreatic insufficiency (83.6% vs. 55.5%; P <0.001), concurrent alcohol (39.3% vs. 23.3%; P =0.001) and tobacco abuse (42.6% vs. 26%; P =0.02), anxiety (23% vs. 18.2%; P <0.001), and depression (57.5% vs. 28.5%; P <0.001). A higher proportion was on opiates (68.9% vs. 43.6%; P <0.001), nonopiate controlled medications (47.5% vs. 23.9%; P <0.001), neuromodulators (73.3% vs. 44%; P <0.001), and recreational drugs (27.9% vs. 15.8%; P =0.036). Predictors of disability were chronic pain (OR 8.71, CI 2.61 to 12.9, P < 0.001), celiac block (OR 4.66, 2.49 to 8.41; P <0.001), neuromodulator use (OR 3.78, CI 2.09 to 6.66; P <0.001), opioid use (OR3.57, CI 2.06 to 6.31; P < 0.001), exocrine pancreatic insufficiency (OR3.56, CI 1.89 to 6.82; P <0.001), non-opioid controlled medications (OR 3.45, CI 2.01 to 5.99; P <0.001), history of recurrent acute pancreatitis (OR 2.49, CI 1.25 to 4.77; P <0.001), depression (OR 2.26, CI 1.79 to 3.01; P <0.001), and active smoking (OR1.8, CI 1.25 to 2.29; P <0.001). CONCLUSION: CP patients with disability have unique characteristics and predictors, which can be targeted to reduce disease burden and health care expenditure in this population.

Prospective Evaluation of Sexual Dysfunction in Men With Chronic Pancreatitis: A Pilot Study.

OBJECTIVE: Our study aimed to determine the prevalence of sexual dysfunction (SD) and its association with quality of life (QOL) in men with chronic pancreatitis (CP). MATERIALS AND METHODS: Male patients with CP were prospectively enrolled in our pancreas center and completed the following 4 validated questionnaires: International Index of Erectile Function 5, Erectile Hardness Score, Pancreatitis Quality of Life Instrument, and Short Form Survey. Patients were classified as having mild, moderate, or severe SD based on review of questionnaires. RESULTS: Thirty patients were enrolled in the study, of which 18 patients had SD (mild in 9, moderate in 1, and severe in 8 patients). No significant differences were seen demographic or clinical characteristics in patients with and without SD. Patients with SD had more abdominal pain compared with those without SD (94.4% vs 83.3%, P = 0.001). No significant differences were noted in QOL metrics between the 2 groups. CONCLUSIONS: This pilot study shows that SD is present in 60% males with CP. No difference was noted in the QOL of patients with and without SD, albeit limited by our small sample size. Physicians caring for CP patients should routinely inquire for symptoms of SD and offer a urology referral if indicated.

GlycA: Evaluation of a New Biomarker of Acute Pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a leading cause of gastrointestinal hospital admissions, with up to 40% mortality in patients with moderate-severe AP. Glycoprotein acetylation (GlycA) is measured as a nuclear magnetic resonance signal (NMR) of the post-translational modification of glycosylated acute-phase proteins released during inflammation. We aimed to investigate the role of GlycA as an inflammatory biomarker of AP. METHODS: We prospectively enrolled 20 AP patients and 22 healthy controls and collected EDTA plasma samples at admission and discharge. NMR spectra were acquired from these samples using a 400 MHz Vantera® Clinical Analyzer, and GlycA concentrations were calculated (normal = 400 µmol/L). The GlycA NMR signal, at 2.00 ± 0.01 ppm in the NMR spectrum, is derived from the N-acetyl methyl group protons within the carbohydrate side chains of circulating glycoproteins such as α1-acid glycoprotein, haptoglobin, α1-antitrypsin, α1-antichymotrypsin, and transferrin. GlycA levels were then compared between AP patients and controls, as well as within the AP group, based on etiology and severity. RESULTS: Demographic comparisons were similar, except for a higher BMI in AP patients compared to healthy controls (29.9 vs. 24.8 kg/m2; p < 0.001). AP was mild in 10 patients, moderate in 7, and severe in 3. GlycA levels were higher in AP patients than healthy controls on admission (578 vs. 376 µmol/L, p < 0.001) and at discharge (655 vs. 376 µmol/L, p < 0.001). GlycA levels were significantly higher in patients with moderate-severe AP than in those with mild AP at discharge (533 vs. 757 µmol/L, p = 0.023) but not at admission. After adjusting for BMI, multivariable regression indicated that patients with GlycA levels > 400 µmol/L had significantly higher odds of having AP of any severity (OR = 6.88; 95% CI, 2.07-32.2; p = 0.004) and mild AP (OR = 6.12; 95% CI, 1.48-42.0; p = 0.025) than controls. CONCLUSION: Our pilot study highlights the use of GlycA as a novel diagnostic biomarker of inflammation in patients with AP. Our study shows that GlycA levels were significantly higher in hospitalized AP patients compared to healthy controls. Patients with moderate-to-severe AP had higher GlycA levels compared to patients with mild AP at the time of their hospital discharge, suggesting persistent inflammation in patients with severe disease.

Natural history, clinical characteristics, outcomes, and long-term follow-up of pain-free chronic pancreatitis.

Background: Chronic pancreatitis (CP) is characterized by chronic abdominal pain and functional insufficiency. However, a small subset of patients with prior acute pancreatitis (AP) and/or underlying risk factors for developing CP may be pain-free at diagnosis and may have a different clinical course. We aimed to compare the clinical characteristics, outcomes, and healthcare utilization between CP patients with and without pain. Methods: Reviewed patients with established CP were followed in our Pancreas Center between January 2016 and April 2021. Patients without risk factors for developing CP and/or without AP prior to their diagnosis and only with incidental radiologic features of CP were excluded, so as to minimize confounding factors of pancreatopathy unrelated to CP. Patients were divided into painful and pain-free groups to analyze differences in demographics, outcomes, and healthcare utilization. Results: Of 368 CP patients, 49 (13.3%) were pain-free at diagnosis and had remained so for >9 years. There were no significant differences in body mass index, race, sex, or co-morbidities between the two groups. Pain-free patients were older at diagnosis (53.9 vs 45.7, P = 0.004) and had less recurrent AP (RAP) (43.8% vs 72.5%, P < 0.001) and less exocrine pancreatic insufficiency (EPI) (34.7% vs 65.7%, P < 0.001). Pain-free patients had less disability (2.2% vs 22.0%, P = 0.003), mental illness (20.4% vs 61.0%, P < 0.001), surgery (0.0% vs 15.0%, P = 0.059), and therapeutic interventions (0.0% vs 16.4%, P = 0.005) for pain. Conclusions: We described a unique subset of patients with underlying risk factors for CP and/or prior AP who were pain-free at diagnosis. They were older at diagnosis, had less EPI and RAP, and overall favorable outcomes with minimal resource utilization.

Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis.

INTRODUCTION: The coefficient of fat absorption (CFA) quantifies fat that remains in stool after digestion and is not a direct measure of lipolysis. CFA has been used to assess treatment of pancreatic insufficiency but does not correlate with pancreatic enzyme replacement therapy dose. We explored use of an omega-3 substrate absorption challenge test as a sensitive test of lipolysis and absorption. METHODS: We studied a novel microbially-derived lipase (SNSP003) employing an established surgical model commonly used to study the uptake of macronutrients, the exocrine pancreatic insufficient pig. Pigs were fed a high-fat diet and given a standardized omega-3 substrate challenge to test the effect of lipolysis on its absorption. Blood was drawn at 0, 1, 2, 4, 6, 8, 12, and 24 hours following the substrate challenge and was analyzed for omega-3 and total fat levels (c14:c24). SNSP003 was also compard to porcine pancrelipase. RESULTS: The absorption of omega-3 fats was significantly increased following administration of 40, 80 and 120 mg SNSP003 lipase by 51% (p = 0.02), 89%, (p = 0.001) and 64% (p = 0.01), respectively, compared to that observed when no lipase was administered to the pigs, with Tmax at 4 hours. The two highest SNSP003 doses were compared to porcine pancrelipase and no significant differences were observed. Both doses increased plasma total fatty acids (141% for the 80 mg dose (p = 0.001) and 133% for the 120 mg dose (p = 0.006), compared to no lipase) and no significant differences were observed between the SNSP003 lipase doses and porcine pancrelipase. CONCLUSION: The omega-3 substrate absorption challenge test differentiates among different doses of a novel microbially-derived lipase and correlates with global fat lipolysis and absorption in exocrine pancreatic insufficient pigs. No significant differences were observed between the two highest novel lipase doses and porcine pancrelipase. Studies in humans should be designed to support the evidence presented here that suggests the omega-3 substrate absorption challenge test has advantages over the coefficient of fat absorption test to study lipase activity.

Fat digestion using RELiZORB in children with short bowel syndrome who are dependent on parenteral nutrition: Protocol for a 90-day, phase 3, open labeled study.

BACKGROUND: Short bowel syndrome (SBS) is a leading cause of intestinal failure resulting in parenteral nutrition (PN) dependence and nutritional deficiencies. Long-term PN use is associated with the development of sepsis and intestinal failure-associated liver disease. Achieving enteral autonomy is the optimal way to prevent these complications. In SBS, the decreased intestinal length, bile acid deficiency, and rapid transit time contribute to fat malabsorption and continued PN dependence. We propose the use of an immobilized lipase cartridge (ILC; RELiZORB) that connects in-line with enteral feed tubing sets and is designed to breakdown the majority of fats provided in enteral nutrition (EN). Preclinical studies have demonstrated both improved fat and fat-soluble vitamin absorption with ILC use in a porcine model of SBS. To evaluate the clinical applicability of these findings, we designed a phase 3, open labeled, single center, clinical trial to determine the safety, tolerability, and efficacy of the RELiZORB enzyme cartridge when used daily with EN for 90 days. METHODS: The patient population will include PN dependent children with SBS, aged 2-18 years. The primary outcome is the change in PN calories from baseline, assessed weekly throughout the study. Changes in growth Z-scores, 72-hour fecal fat and coefficient of fat absorption, plasma fatty acids and fat-soluble vitamins will also be evaluated. Assessment of change in continuous outcomes will be made using the area under the curve, expressed as a percent change relative to baseline, calculated over study day 7 to 90 (AUC7-90). The incidence of adverse events will be monitored and summarized by system organ class. DISCUSSION: If successful, RELiZORB may offer a safe alternative to reducing PN dependence and achieving enteral autonomy in pediatric intestinal failure. These results would be clinically significant given the clear association between long-term PN use and complications in SBS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03530852; registered on May 21st, 2018, last update posted on September 14th, 2022.

Prospective evaluation of an emergency department protocol to prevent hospitalization in mild acute pancreatitis: Outcomes and predictors of discharge.

BACKGROUND: While acute pancreatitis (AP) contributes significantly to hospitalizations and costs, most cases are mild with minimal complications. In 2016, we piloted an observation pathway in the emergency department (ED) for mild AP and showed reduced admissions and length of stay (LOS) without increased readmissions or mortality. After 5 years of implementation, we evaluated outcomes of the ED pathway and identified predictors of successful discharge. METHODS: We reviewed a prospectively enrolled cohort of patients with mild AP presenting to a tertiary care center ED between 10/2016 and 9/2021, evaluating LOS, charges, imaging, and 30-day readmission, and assessed predictors of successful ED discharge. Patients were divided into two main groups: successfully discharged via the ED pathway ("ED cohort") and admitted to the hospital ("admission cohort"), with subgroups to compare outcomes, and multivariate analysis to determine predictors of discharge. RESULTS: Of 619 AP patients, 419 had mild AP (109 ED cohort, 310 admission cohort). The ED cohort was younger (age 49.3 vs 56.3,p < 0.001), had lower Charlson Comorbidity Index (CCI) (1.30 vs 2.43, p < 0.001), shorter LOS (12.3 h vs 116 h, p < 0.001), lower charges (mean $6768 vs $19886, p < 0.001) and less imaging, without differences in 30-day readmissions. Increasing age (OR: 0.97; p < 0.001), increasing CCI (OR: 0.75; p < 0.001) and biliary AP (OR: 0.10; p < 0.001) were associated with decreased ED discharge, while idiopathic AP had increased ED discharge (OR: 7.8; p < 0.001). CONCLUSIONS: After appropriate triage, patients with mild AP (age <50, CCI <2, idiopathic AP) can safely discharge from the ED with improved outcomes and cost savings.

A Large-Scale Proteomics Resource of Circulating Extracellular Vesicles for Biomarker Discovery in Pancreatic Cancer.

Pancreatic cancer has the worst prognosis of all common tumors. Earlier cancer diagnosis could increase survival rates and better assessment of metastatic disease could improve patient care. As such, there is an urgent need to develop biomarkers to diagnose this deadly malignancy earlier. Analyzing circulating extracellular vesicles (cEVs) using 'liquid biopsies' offers an attractive approach to diagnose and monitor disease status. However, it is important to differentiate EV-associated proteins enriched in patients with pancreatic ductal adenocarcinoma (PDAC) from those with benign pancreatic diseases such as chronic pancreatitis and intraductal papillary mucinous neoplasm (IPMN). To meet this need, we combined the novel EVtrap method for highly efficient isolation of EVs from plasma and conducted proteomics analysis of samples from 124 individuals, including patients with PDAC, benign pancreatic diseases and controls. On average, 912 EV proteins were identified per 100µL of plasma. EVs containing high levels of PDCD6IP, SERPINA12 and RUVBL2 were associated with PDAC compared to the benign diseases in both discovery and validation cohorts. EVs with PSMB4, RUVBL2 and ANKAR were associated with metastasis, and those with CRP, RALB and CD55 correlated with poor clinical prognosis. Finally, we validated a 7-EV protein PDAC signature against a background of benign pancreatic diseases that yielded an 89% prediction accuracy for the diagnosis of PDAC. To our knowledge, our study represents the largest proteomics profiling of circulating EVs ever conducted in pancreatic cancer and provides a valuable open-source atlas to the scientific community with a comprehensive catalogue of novel cEVs that may assist in the development of biomarkers and improve the outcomes of patients with PDAC.

Burden of bone disease in chronic pancreatitis: A systematic review and meta-analysis.

BACKGROUND: Bone disease is an under-recognized cause of morbidity in chronic pancreatitis (CP). Over the past decade, publications of original studies on bone disease in CP has warranted synthesis of the evidence to ascertain the true burden of the problem. AIM: To quantify the prevalence of osteopenia, osteoporosis, and fragility fractures in CP patients and investigate the associated clinical features and outcomes. METHODS: A systematic search identified studies investigating bone disease in CP patients from Cochrane Library, Embase, Google Scholar, Ovid Medline, PubMed, Scopus, and Web of Science, from inception until October 2022. The outcomes included prevalence of osteopenia, osteoporosis, and fragility fractures, which were meta-analyzed using a random-effects model and underwent metaregression to delineate association with baseline clinical features. RESULTS: Twenty-one studies were included for systematic review and 18 studies were included for meta-analysis. The pooled prevalence of osteopenia and osteoporosis in CP patients was 41.2% (95%CI: 35.2%-47.3%) and 20.9% (95%CI: 14.9%-27.6%), respectively. The pooled prevalence of fragility fractures described among CP was 5.9% (95%CI: 3.9%-8.4%). Meta-regression revealed significant association of pancreatic enzyme replacement therapy (PERT) use with prevalence of osteoporosis [coefficient: 1.7 (95%CI: 0.6-2.8); P < 0.0001]. We observed no associations with mean age, sex distribution, body mass index, alcohol or smoking exposure, diabetes with prevalence of osteopenia, osteoporosis or fragility fractures. Paucity of data on systemic inflammation, CP severity, and bone mineralization parameters precluded a formal meta-analysis. CONCLUSION: This meta-analysis confirms significant bone disease in patients with CP. Other than PERT use, we observed no patient or study-specific factor to be significantly associated with CP-related bone disease. Further studies are needed to identify confounders, at-risk population, and to understand the mechanisms of CP-related bone disease and the implications of treatment response.

Unexplained Acute Distal Pancreatitis: Association With Subsequent Diagnosis of Pancreatic Cancer.

BACKGROUND. Distal pancreatitis is an atypical imaging subtype of acute pancreatitis involving only the pancreatic body and tail, the head being spared. If no cause is identified, suspicion of a small imaging-occult cancer may be warranted. OBJECTIVE. The purpose of this study was to determine the frequency of subsequently diagnosed pancreatic cancer in patients with unexplained acute distal pancreatitis and to compare this frequency to that found in patients with unexplained nondistal pancreatitis. METHODS. This retrospective study included patients who underwent contrast-enhanced CT between January 1, 2019, and December 31, 2020, that showed acute pancreatitis without identifiable explanation. Studies were classified as showing distal or nondistal acute pancreatitis on the basis of consensus. The Fisher exact test was used to compare the frequency of subsequent histologic diagnosis of pancreatic cancer between groups. Negative classification required 6 or more months of imaging follow-up and/or 12 or more months of clinical follow-up. Interreader agreement among seven readers of varying experience was assessed by Fleiss kappa. RESULTS. Among 215 patients with acute pancreatitis, 116 (54%) had no identifiable explanation and formed the study sample. A total of 100 of 116 (86%) patients (59 men, 41 women; mean age, 57 ± 18 [SD] years) had nondistal acute pancreatitis; 16 of 116 (14%) patients (10 men, six women; mean age, 66 ± 14 years) had distal acute pancreatitis. Among patients with nondistal pancreatitis, none were subsequently diagnosed with pancreatic cancer; 62 had sufficient follow-up (median, 2.5 years) to be classified as having negative follow-up for pancreatic cancer. Among patients with distal pancreatitis, nine were subsequently diagnosed with pancreatic cancer (median interval to suspected cancer on subsequent CT, 174 days); five had sufficient follow-up (median, 3.1 years) to be classified as having negative follow-up for pancreatic cancer. The frequency of pancreatic cancer was higher (p < .001) in patients with distal pancreatitis (9/14 [64%; 95% CI, 35-87%]) than in with those with nondistal pancreatitis (0/62 [0%; 95% CI, 0-6%]). Interreader agreement on classification of distal versus nondistal pancreatitis was almost perfect (κ = 0.81). CONCLUSION. Distal pancreatitis without identifiable cause on CT is an uncommon but unique imaging subtype of acute pancreatitis that is associated with a high frequency of pancreatic cancer. CLINICAL IMPACT. In patients with acute distal pancreatitis without identifiable cause, endoscopic ultrasound-guided biopsy should be considered to evaluate for an underlying small cancer.

Smoking Is Associated with Worse Clinical Outcomes in Chronic Pancreatitis.

BACKGROUND: Tobacco smoking is a known risk factor for progression of chronic pancreatitis (CP). AIM: We compare clinical outcomes of CP patients with current or former smoking with those who have never smoked. METHODS: We reviewed all patients with followed at our Pancreas Center from 2016 to 2021, comparing the demographics, clinical features, comorbidities, outcomes, and resource utilization between smokers and non-smokers. RESULTS: Of 439 CP patients, 283 were smokers (125 current, 158 former). Significantly more smokers were men (58.3% vs 40.4%), with alcoholic CP (45.5% vs 12.1%), chronic abdominal pain (77.7% vs 65.4%), anxiety and depression (22.6% vs 14.1% and 38.9% vs 23.1%), and with more local pancreatic complications [splanchnic vein thrombosis (15.7% vs 5.13%), pseudocyst (42.7% vs 23.7%), biliary obstruction (20.5% vs 5.88%)], exocrine pancreatic insufficiency (65.8% vs 46.2%), hospitalizations (2.59 vs 1.75 visits), and emergency department visits (8.96% vs 3.25%). Opioid and neuromodulator use were significantly higher (59.2% vs 30.3% and 58.4% vs 31.2%). Current smokers had worse outcomes than former smokers. Multivariate analysis controlling for multiple factors identified smoking as an independent predictor of chronic abdominal pain (OR 2.49, CI 1.23-5.04, p = 0.011), opioid (OR 2.36, CI 1.35-4.12, p = 0.002), neuromodulators (OR 2.55, CI 1.46-4.46, p = 0.001), and non-opioid-controlled medications (OR 2.28, CI 1.22-4.30, p = 0.01) use, as well as splanchnic vein thromboses (OR 2.65, CI 1.02-6.91, p = 0.045) and biliary obstruction (OR 4.12, CI 1.60-10.61, p = 0.003). CONCLUSION: CP patients who smoke or formerly smoked have greater morbidity and worse outcomes than non-smokers.

Comparison of Opioid-Based Patient-Controlled Analgesia with Physician-Directed Analgesia in Acute Pancreatitis: A Retrospective Cohort Study.

BACKGROUND: Patient-controlled analgesia (PCA) is commonly used for acute postoperative pain management. Clinicians may also use PCA in the management of acute pancreatitis (AP); however, there is limited data on its impact on patient outcomes. We aimed to characterize a cohort of patients receiving PCA therapy for pain management in AP compared to those patients receiving standard physician-directed delivery of analgesia. METHODS: We conducted a retrospective cohort study of adult patients admitted with AP at a tertiary care center from 2008 to 2018. Exclusion criteria included patients with chronic opioid use, chronic pancreatitis and pancreatic cancer. Primary outcomes include length of stay (LOS) and time to enteral nutrition. Secondary outcomes include proportion of patients discharged with opioid and complications. Multivariate regression analysis and t-test were used for analysis. RESULTS: Among 656 AP patients who met the criteria, patients receiving PCA (n = 62) and standard delivery (n = 594) were similar in admission pain score, Charlson Comorbidity Index, and pancreatitis severity. There were significantly greater proportion of women, Caucasians and nonalcoholics who received PCA therapy (p < 0.01) than standard delivery. Multivariate regression analysis revealed that patients in the PCA group have a longer LOS (7.17 vs. 5.43 days, p < 0.007, OR 1.03; 95% CI 1.01-1.07), longer time to enteral nutrition (3.84 days vs. 2.56 days, p = 0.012, OR 1.11; 95% CI 1.02-1.20), and higher likelihood of being discharged with opioids (OR 1.94; 95% CI 1.07-3.63, p = 0.03). CONCLUSION: The use of PCA in AP may be associated with poorer outcomes including longer LOS, time to enteral intake and a higher likelihood of being discharged with opioids.

Pre-existing, Concurrent/Early-Onset, and Late-Onset Diabetes in Chronic Pancreatitis: Do Outcomes Differ?

BACKGROUND/AIMS: Diabetes secondary to endocrine insufficiency in chronic pancreatitis (CP) may develop at any time during the disease course. We sought to evaluate the differences in clinical characteristics and outcomes in CP patients with pre-existing, early-onset, and late-onset diabetes. METHODS: We reviewed CP patients seen at our Pancreas Center during 2016-2021. We divided them into four groups: those without diabetes, with pre-existing diabetes, with early-onset diabetes, and with late-onset diabetes. We then compared clinical characteristics and outcomes. RESULTS: We identified 450 patients with CP: 271 without diabetes, 99 with pre-existing diabetes, 51 with early-onset diabetes, and 29 with late-onset diabetes. Early-onset diabetics were younger (54.1 vs 57.3 vs 62.5 vs 61.9 years), had more alcohol-related CP (45.1% vs 31.7% vs 32.3% vs 31%), had higher HbA1C levels (8.02% vs 5.11% vs 7.71% vs 7.66%), were more likely to be on insulin (78.4% vs 0% vs 48.4% vs 65.5%), and used more opioids (64.7% vs 43.9% vs 55.1% vs 44.8%) and gabapentinoids (66.7% vs 43.5% vs 48% vs 60.7%) compared to other groups (p < 0.05). Patients who developed diabetes after CP diagnosis had more exocrine insufficiency (72.4% vs 70.6% vs 65.7% vs 53.1%), anatomical complications, and interventions for pain control (p < 0.05). There was no difference in pancreatic cancer in the four groups. CONCLUSION: CP patients who are younger and use alcohol are at higher risk of having early-onset diabetes and have poorer glucose control compared other CP patients. Patients who develop diabetes after CP diagnosis have worse outcomes and use more resources.

Need to study simplification of gastrointestinal medication regimen in cystic fibrosis in the era of highly effective modulators.

INTRODUCTION: The success of highly effective modulator therapy (HEMT) has led to consideration of simpler regimens for people with CF (PwCF) with opportunities to modify burdensome regimens. Despite the intuitive appeal of discontinuing chronic therapies no longer necessary, this process should be pursued systematically to ensure safety, adherence, and validate patient-centered preferences. We designed a questionnaire to determine the state of use of acid-suppressive medications (ASM) and pancreatic enzyme therapy (PERT), current self-withdrawal and provider-directed withdrawal practices, and interest in a standardized withdrawal study. METHODS: In collaboration with CF Foundation (CFF), a questionnaire was developed and distributed to members of Community Voice (CV, comprised of PwCF and their loved ones), and CF providers regarding the need to study simplifying the gastrointestinal (GI) regimen for PwCF on HEMT. RESULTS: Approximately 20-40% of CV or CF providers have decreased or stopped ASM for those on HEMT. For PERT, CV and CF providers have decreased dose (34%-48% and approximately 25%, respectively) more often than having stopped it altogether (13%-24% and 3%-12%, respectively). Cumulatively, there is interest in pursuing research in this area (86% CV and 89% CF providers) and willingness to enroll in such a study (80% CV and 89% CF providers). CONCLUSION: Systematically studying the withdrawal of common GI medications, ASM and PERT, is important to CV and CF providers. Decreases in dosing and withdrawal are already taking place without evidence to support this practice. This questionnaire is the first step in designing a GI medication simplification study in PwCF on HEMT.

Elexacaftor/tezacaftor/ivacaftor and gastrointestinal outcomes in cystic fibrosis: Report of promise-GI.

BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI) improves pulmonary disease in people with cystic fibrosis (PwCF), but its effect on gastrointestinal symptoms, which also affect quality of life, is not clear. METHODS: PROMISE is a 56-center prospective, observational study of ETI in PwCF >12 years and at least one F508del allele. Gastrointestinal symptoms, evaluated by validated questionnaires: Patient Assessment of Upper Gastrointestinal Disorders-Symptom (PAGI-SYM), Patient Assessment of Constipation-Symptom (PAC-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL)), fecal calprotectin, steatocrit and elastase-1 were measured before and 6 months after ETI initiation. Mean difference and 95% confidence intervals were obtained from linear regression with adjustment for age and sex. RESULTS: 438 participants fully completed at least 1 questionnaire. Mean (SD) for baseline PAGI-SYM, PAC-SYM, and PAC-QOL total scores were 0.56 (0.59), 0.47 (0.45), and 0.69 (0.53) out of maximum 5, 4, and 5, respectively (higher score indicates greater severity). Corresponding age- and sex-adjusted 6 months mean changes (95% CI) in total scores were -0.15 (-0.21, -0.09) for PAGI-SYM, -0.14 (-0.19, -0.09) for PAC-SYM, and -0.15 (-0.21, -0.10) for PAC-QOL. While statistically significant, changes were small and unlikely to be of clinical importance. Fecal calprotectin showed a change (95% CI) from baseline of -66.2 µg/g (-86.1, -46.2) at 6 months, while fecal elastase and steatocrit did not meaningfully change. CONCLUSIONS: After 6 months of ETI, fecal markers of inflammation decreased. Gastrointestinal symptoms improved, but the effect size was small. Pancreatic insufficiency did not improve.

Multicenter prospective study showing a high gastrointestinal symptom burden in cystic fibrosis.

BACKGROUND AND AIMS: People with cystic fibrosis (PwCF) suffer from gastrointestinal (GI) symptoms affecting their quality of life (QOL). Despite the relevance of GI symptoms to the overall health of PwCF, a paucity of studies only have comprehensively assessed the prevalence, severity and QOL of GI symptoms in both children and adults with Cystic Fibrosis (CF). METHODS: Eligible participants ≥2 years of age across 26 US CF centers were followed for 4 weeks. Three validated GI electronic patient-reported outcome measures (ePROMs) with a recall period of 2 weeks and a stool-specific questionnaire were administered weekly over four weeks. Total and domain scores of ePROMs were evaluated overall and in subgroups using linear mixed-effect models. RESULTS: Of 402 enrolled, 58% were ≥ 18 years of age (52% male). The mean (SD) of the total score for PAC-SYM was 0.52 (0.55), for PAGI-SYM was 0.63 (0.67), and for PAC-QOL was 0.67 (0.55). For specific ePROM questions, prevalence of moderate to very severe symptoms were as follows: straining (20.3%), fullness (18.3%), incomplete bowel movements (17.1%), bloating (16.4%), distension (16.4%), abdominal pain (upper-5.1%, lower-7.5%). Comparing participants ≥18 versus <18, a higher prevalence of bloating (63.7% versus 27.3%), lower abdominal pain (39.8% vs 26.2%), stomach fullness (75.6% versus 56.2%), and abdominal distension (60.2% versus 34.9%) was found. Both age groups reported high treatment dissatisfaction as measured with PAC-QOL, mean 1.39 (95% CI: 1.30, 1.47). CONCLUSION: GI symptoms were reported in all age ranges irrespective of gender, with higher prevalence observed amongst older and female subgroups. Dissatisfaction with GI targeted treatments were reported in a large proportion of participants despite therapy, highlighting an unmet need for clinical interventions. CLINICALTRIALS: GOV: NCT03801993.

Update in Advancing the Gastrointestinal Frontier in Cystic Fibrosis.

Clinical complications of cystic fibrosis (CF) include a variety of gastrointestinal (GI) and hepatobiliary manifestations. Recent years have witnessed several advances in the understanding and management of these complications, in addition to opportunities for therapeutic innovations. Herein we review the current understanding of these disorders and also discuss the management of the GI and hepatobiliary complications experienced by persons with CF.