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.

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.

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.

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.

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.

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.

Clinical Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor in People with Cystic Fibrosis: A Clinical Trial.

Rationale: The cystic fibrosis (CF) modulator drug, elexacaftor/tezacaftor/ivacaftor (ETI), proved highly effective in controlled clinical trials for individuals with at least one F508del allele, which occurs in at least 85% of people with CF. Objectives: PROMISE is a postapproval study to understand the broad effects of ETI through 30 months' clinical use in a more diverse U.S. patient population with planned analyses after 6 months. Methods: Prospective, observational study in 487 people with CF age 12 years or older with at least one F508del allele starting ETI for the first time. Assessments occurred before and 1, 3, and 6 months into ETI therapy. Outcomes included change in percent predicted FEV1 (ppFEV1), sweat chloride concentration, body mass index (BMI), and self-reported respiratory symptoms. Measurements and Main Results: Average age was 25.1 years, and 44.1% entered the study using tezacaftor/ivacaftor or lumacaftor/ivacaftor, whereas 6.7% were using ivacaftor, consistent with F508del homozygosity and G551D allele, respectively. At 6 months into ETI therapy, ppFEV1 improved 9.76 percentage points (95% confidence interval [CI], 8.76 to 10.76) from baseline, cystic fibrosis questionnaire-revised respiratory domain score improved 20.4 points (95% CI, 18.3 to 22.5), and sweat chloride decreased -41.7 mmol/L (95% CI, -43.8 to -39.6). BMI also significantly increased. Changes were larger in those naive to modulators but substantial in all groups, including those treated with ivacaftor at baseline. Conclusions: ETI by clinical prescription provided large improvements in lung function, respiratory symptoms, and BMI in a diverse population naive to modulator drug therapy, using existing two-drug combinations, or using ivacaftor alone. Each group also experienced significant reductions in sweat chloride concentration, which correlated with improved ppFEV1 in the overall study population. Clinical trial registered with www.clinicaltrials.gov (NCT NCT04038047).

Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome.

BACKGROUND: Familial chylomicronemia syndrome is a rare genetic disorder that is caused by loss of lipoprotein lipase activity and characterized by chylomicronemia and recurrent episodes of pancreatitis. There are no effective therapies. In an open-label study of three patients with this syndrome, antisense-mediated inhibition of hepatic APOC3 mRNA with volanesorsen led to decreased plasma apolipoprotein C-III and triglyceride levels. METHODS: We conducted a phase 3, double-blind, randomized 52-week trial to evaluate the safety and effectiveness of volanesorsen in 66 patients with familial chylomicronemia syndrome. Patients were randomly assigned, in a 1:1 ratio, to receive volanesorsen or placebo. The primary end point was the percentage change in fasting triglyceride levels from baseline to 3 months. RESULTS: Patients receiving volanesorsen had a decrease in mean plasma apolipoprotein C-III levels from baseline of 25.7 mg per deciliter, corresponding to an 84% decrease at 3 months, whereas patients receiving placebo had an increase in mean plasma apolipoprotein C-III levels from baseline of 1.9 mg per deciliter, corresponding to a 6.1% increase (P<0.001). Patients receiving volanesorsen had a 77% decrease in mean triglyceride levels, corresponding to a mean decrease of 1712 mg per deciliter (19.3 mmol per liter) (95% confidence interval [CI], 1330 to 2094 mg per deciliter [15.0 to 23.6 mmol per liter]), whereas patients receiving placebo had an 18% increase in mean triglyceride levels, corresponding to an increase of 92.0 mg per deciliter (1.0 mmol per liter) (95% CI, -301.0 to 486 mg per deciliter [-3.4 to 5.5 mmol per liter]) (P<0.001). At 3 months, 77% of the patients in the volanesorsen group, as compared with 10% of patients in the placebo group, had triglyceride levels of less than 750 mg per deciliter (8.5 mmol per liter). A total of 20 of 33 patients who received volanesorsen had injection-site reactions, whereas none of the patients who received placebo had such reactions. No patients in the placebo group had platelet counts below 100,000 per microliter, whereas 15 of 33 patients in the volanesorsen group had such levels, including 2 who had levels below 25,000 per microliter. No patient had platelet counts below 50,000 per microliter after enhanced platelet-monitoring began. CONCLUSIONS: Volanesorsen lowered triglyceride levels to less than 750 mg per deciliter in 77% of patients with familial chylomicronemia syndrome. Thrombocytopenia and injection-site reactions were common adverse events. (Funded by Ionis Pharmaceuticals and Akcea Therapeutics; APPROACH Clinical Trials.gov number, NCT02211209.).

Acetaminophen and Xenobiotic Metabolites in Human Milk and the Development of Bronchopulmonary Dysplasia and Retinopathy of Prematurity in a Cohort of Extremely Preterm Infants.

This retrospective cohort study sought to identify the association between certain xenobiotic metabolites in maternal breast milk and the diagnoses of bronchopulmonary dysplasia and retinopathy of prematurity in extremely preterm infants. Several acetaminophen metabolites were associated with a 3- to 6-fold increased odds of these disorders, and metabolites of certain food products, benzoate, and caffeine were associated with decreased odds.

Impact of recurrent acute pancreatitis on the natural history and progression to chronic pancreatitis.

BACKGROUND AND AIMS: It is believed that acute pancreatitis (AP), recurrent AP (RAP) and chronic pancreatitis (CP) represent stages of the same disease spectrum. We aimed to identify risk factors, clinical presentation and outcomes in patients with prior RAP who develop CP. METHODS: We retrospectively reviewed patients with CP who were seen at our Pancreas Center during 2016-2021. We divided them into two groups: with and without RAP (≥2 episodes of AP). We compared demographics, clinical presentation and resource utilization between the two groups. RESULTS: We identified 440 patients with CP, of which 283 (64%) patients had preceding RAP. These patients were younger (55.6 vs 63.1 years), active smokers (36% vs 20%) and had alcohol-related CP (49% vs 25%) compared to those without RAP and CP (p < 0.05). More patients with RAP had chronic abdominal pain (89% vs 67.9%), nausea (43.3% vs 27.1%) and exocrine pancreatic insufficiency (65.8% vs 46.5%) (p < 0.05). More patients with RAP used opioids (58.4% vs 32.3%) and gabapentinoids (56.6% vs 34.8%) (p < 0.05). They also had more ED visits resulting in an opioid prescription (9.68% vs 2%) and more CP flares requiring hospitalization (3.09 vs 0.87) (p < 0.05). CONCLUSION: Young age, smoking and alcohol use are seen in patients with RAP who progress to CP. These patients are highly symptomatic and use more healthcare resources, suggestive of an overall a more course compared to those patients who develop CP without preceding RAP. Early identification and counselling of these patients may slow down progression to CP.

Inpatient Alcohol Cessation Counseling Is Associated With a Lower 30-Day Hospital Readmission in Acute Alcoholic Pancreatitis.

BACKGROUND: Alcohol use is a common cause of recurrent acute pancreatitis. Thus, guidelines recommend providing alcohol prevention resources during hospitalization. There is limited data on the real-world implementation of this recommendation. We aimed to assess how often inpatients admitted with alcohol-induced acute pancreatitis (AAP) receive counseling and to determine the impact of counseling on readmissions for AAP. METHODS: We retrospectively studied patients admitted with AAP at a tertiary care center from 2008 to 2018. We compared demographics, clinical features, and outcomes in patients who did and did not receive counseling. Outcomes studied were the proportion of patients with AAP receiving counseling, and readmission rates for AAP at 30 days and 1 year. RESULTS: A total of 243 patients with AAP were identified, of which 115 had inpatient alcohol counseling (47%). Demographic data were comparable between the 2 groups. Fewer patients receiving alcohol counseling were readmitted at 30 days compared with patients not receiving counseling (19.3% vs. 31.2%, P =0.048). At 1 year, the 2 groups had similar readmission rates. On multivariate analysis, patients who received counseling were half as likely to be readmitted in 30 days compared with those who did not receive counseling [odds ratio=0.52 (0.27, 0.98), P =0.046]. CONCLUSIONS: We note that <50% of patients receive alcohol counseling. Patients receiving alcohol counseling were less likely to be readmitted at 30 days, inferring possible value in the intervention provided. Similar readmission rates at 1 year suggest that the single intervention may not have a durable effect on alcohol prevention.

Evaluating Outcomes and Misuse in Opioid-Dependent Chronic Pancreatitis Using a State-Mandated Monitoring System.

INTRODUCTION: Patients with chronic pancreatitis (CP) often require opioids for pain control. The goal of our study was to characterize opioid use in patients with CP in a real-life practice using a state-mandated online monitoring program and to assess outcomes compared to CP patients without opioid dependency. METHODS: CP patients seen in our Pancreas Center from 2016 to 2021 were divided into two groups-with and without chronic opioid use. Details of opioids and other controlled prescriptions were obtained by review of the Massachusetts Prescription Awareness Tool (MassPat). RESULTS: Of the 442 CP outpatients, 216 used chronic opioids. Patients with opioid use had significantly more recurrent acute pancreatitis (76.6% vs. 52.7%), concurrent alcohol use (11.2% vs. 5.8%), tobacco use (37.8% vs. 19.7%), anxiety (22.4% vs. 16.6%), depression (43.5% vs. 23.5%) and daily pain (59.8% vs. 24.8%) (p < 0.001). They also concurrently used more benzodiazepines (43.7% vs. 12.4%), gabapentinoids (66.4% vs. 31.1%) and medical marijuana (14.9% vs. 4.19%) (p < 0.001). They had more celiac plexus blocks (22.0% vs. 6.67%), surgery (18.3% vs. 8.89%) and more hospitalizations for CP flares (3.6 vs. 1.0 visits) (p < 0.001). Less than 13% patients received opioids by means of ED visits; 81.7% patients received their prescriptions from one facility and 75% received them at regular intervals. CONCLUSION: Opioid-dependent CP patients exhibit polypharmacy and have worse outcomes with higher resource utilization. The state-monitoring program ensures that the majority of patients receive opioids from a single facility, thereby minimizing misuse.

Prospective evaluation of sleep disturbances in chronic pancreatitis and its impact on quality of life: a pilot study.

BACKGROUND: Patients with chronic pancreatitis (CP) have poor quality of life (QOL). Sleep disorders affect QOL when associated with chronic pain and opioid use. Hence patients with CP may have unrecognized sleep disturbances. AIMS: The aim of the study was to evaluate sleep disturbances in CP and its impact on QOL. METHODS: Established CP patients were prospectively enrolled after exclusion of patients with co-morbidities known to negatively affect sleep and QOL. Three questionnaires were used to identify sleep disturbances, PROMISv1SF8, Insomnia Severity Index, and Epworth Sleepiness Scale, and one for restless leg syndrome (RLS). PANQOLI and SF12 questionnaires were used to evaluate QOL. Two blinded sleep pulmonologists evaluated the responses. QOL assessments were then analyzed in patients with and without sleep disturbances. RESULTS: Of 89 patients, 48 met exclusion criteria, 41 were eligible, and 28 completed the study. Twenty patients (71%) had sleep disturbances with significantly worse scores across all 3 sleep questionnaires and also had lower scores on both PANQOLI (50 vs 76, p = 0.002) and SF-12 (physical component 29.3 vs 53.9, p < 0.001; mental component 36.4 vs 46.1, p = 0.03). Eleven patients (39%) had RLS and sleep disturbances. CONCLUSION: In patients with established CP there was a high prevalence of sleep disturbances and RLS with worse QOL representing a potential therapeutic target to improve QOL.

Parenteral lipid emulsions induce unique ileal fatty acid and metabolomic profiles but do not increase the risk of necrotizing enterocolitis in preterm pigs.

Necrotizing enterocolitis (NEC) is a manifestation of maladaptive intestinal responses in preterm infants centrally medicated by unattenuated inflammation. Early in the postnatal period, preterm infants develop a deficit in arachidonic and docosahexaenoic acid, both potent regulators of inflammation. We hypothesized that the fatty acid composition of parenteral lipid emulsions uniquely induces blood and intestinal fatty acid profiles which, in turn, modifies the risk of NEC development. Forty-two preterm pigs were randomized to receive one of three lipid emulsions containing 100% soybean oil (SO), 15% fish oil (MO15), or 100% fish oil (FO100) with enteral feedings over an 8-day protocol. Blood and distal ileum tissue were collected for fatty acid analysis. The distal ileum underwent histologic, proteomic, and metabolomic analyses. Eight pigs [3/14 SO (21%), 3/14 MO15 (21%), and 2/14 FO100 (14%)] developed NEC. No differences in NEC risk were evident between groups despite differences in induced fatty acid profiles in blood and ileal tissue. Metabolomic analysis of NEC versus no NEC tissue revealed differences in tryptophan metabolism and arachidonic acid-containing glycerophospholipids. Proteomic analysis demonstrated no differences by lipid group; however, 15 proteins differentiated NEC versus no NEC in the domains of tissue injury, glucose uptake, and chemokine signaling. Exposure to parenteral lipid emulsions induces unique intestinal fatty acid and metabolomic profiles; however, these profiles are not linked to a difference in NEC development. Metabolomic and proteomic analyses of NEC versus no NEC intestinal tissue provide mechanistic insights into the pathogenesis of NEC in preterm infants.NEW & NOTEWORTHY Exposure to parenteral lipid emulsions induces unique intestinal fatty acid and metabolomic profiles; however, these profiles are not linked to a difference in NEC risk in preterm pigs. Metabolomic and proteomic analyses provide mechanistic insights into NEC pathogenesis. Compared with healthy ileal tissue, metabolites in tryptophan metabolism and arachidonic acid-containing glycerophospholipids are increased in NEC tissue. Proteomic analysis differentiates NEC versus no NEC in the domains of tissue injury, glucose uptake, and chemokine signaling.

Hyperlipasemia in absence of acute pancreatitis is associated with elevated D-dimer and adverse outcomes in COVID 19 disease.

BACKGROUND: Coronavirus SARS-CoV-2 affects multiple organs. Studies have reported mild elevations of lipase levels of unclear significance. Our study aims to determine the outcomes in patients with COVID-19 and hyperlipasemia, and whether correlation with D-dimer levels explains the effect on outcomes. METHODS: Case-control study from two large tertiary care health systems, of patients with COVID-19 disease admitted between March 1 and May 1, 2020 who had lipase levels recorded. Data analyzed to study primary outcomes of mortality, length of stay (LOS) and intensive care utilization in hyperlipasemia patients, and correlation with D-dimer and outcomes. RESULTS: 992 out of 5597 COVID-19 patients had lipase levels, of which 429 (43%) had hyperlipasemia. 152 (15%) patients had a lipase > 3x ULN, with clinical pancreatitis in 2 patients. Hyperlipasemia had a higher mortality than normal lipase patients (32% vs. 23%, OR = 1.6,95%CI = 1.2-2.1, P = 0.002). In subgroup analysis, hyperlipasemia patients had significantly worse LOS (11vs.15 days, P = 0.01), ICU admission rates (44% vs. 66%,OR = 2.5,95%CI = 1.3-5.0,P = 0.008), ICU LOS (12vs.19 days,P = 0.01), mechanical ventilation rates (34% vs. 55%,OR = 2.4,95%CI = 1.3-4.8,P = 0.01), and durations of mechanical ventilation (14 vs. 21 days, P = 0.008). Hyperlipasemia patients were more likely to have a D-dimer value in the highest two quartiles, and had increased mortality (59% vs. 15%,OR = 7.2,95%CI = 4.5-11,P < 0.001) and LOS (10vs.7 days,P < 0.001) compared to those with normal lipase and lower D-dimer levels. CONCLUSION: There is high prevalence of hyperlipasemia without clinical pancreatitis in COVID-19 disease. Hyperlipasemia was associated with higher mortality and ICU utilization, possibly explained by elevated D-dimer.

Reducing Hospitalization in Mild Acute Pancreatitis: Results of Long-term Follow-up.

GOALS AND BACKGROUND: Acute pancreatitis (AP) is a common emergency department (ED) diagnosis, amounting to enormous costs. Our previous pilot study demonstrated the feasibility of reducing hospitalization using an ED-based observation pathway. In this follow-up study, we hypothesize that the pathway is durable in clinical practice, outside of research supervision, and patients can safely be managed without hospitalization. STUDY: We reviewed patients prospectively enrolled in the observation pathway after the end of the pilot study. We compared outcomes to patients enrolled in our pilot study and with a historic cohort of patients admitted with mild AP. Our primary outcome was hospitalization rate during the enrollment period and secondary outcomes included length of stay, 30-day readmissions, mortality, and health care utilization. RESULTS: Over a 2-year period 165 patients met criteria for AP with 118 (71.5%) having mild AP. Fifty-four of 118 patients (45.8%) were enrolled in the observation pathway and of these, 45 patients were discharged from the ED, reducing hospitalization by 31.2%, compared with pilot study (22.2%) and historic cohort (0%) (P<0.05). Median length of stay was shorter [19.9 (observation) vs. 72.0 h (historic cohort), P<0.01]. There were fewer radiographic examinations in the observation cohorts (pilot and current study) than in the historic cohort (P<0.05), with similar 30-day readmissions, and no reported deaths. CONCLUSIONS: This follow-up study demonstrates the durability of an observation-based pathway to manage mild AP outside of a research protocol and maintain its ability to reduce hospitalizations without affecting readmission rates or mortality.

How Would You Treat This Patient With Gallstone Pancreatitis?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Acute pancreatitis, a common cause of hospitalization in the United States, is often the result of biliary tract disease. In 2016, the American Gastroenterological Association released a guideline that addresses the practical considerations in managing acute pancreatitis within the first 72 hours after the patient presents. The guideline specifically recommends goal-directed hydration therapy, early enteral feeding, judicious use of endoscopic retrograde cholangiopancreatography (ERCP), and gallbladder surgery during the index admission for patients with mild pancreatitis. The authors discuss their approach to these interventions in the context of a patient with recurrent acute pancreatitis who chooses to delay surgery until after hospital discharge. They address hydration and timing of surgery, as well as how they would manage the patient's preferences in the face of existing guidelines.

Developmental Accretion of Docosahexaenoic Acid Is Independent of Fatty Acid Transporter Expression in Brain and Lung Tissues of C57BL/6 and Fat1 Mice.

BACKGROUND: Developmental expression of fatty acid transporters and their role in polyunsaturated fatty acid concentrations in the postnatal period have not been evaluated. OBJECTIVE: We hypothesized that transporter expression is developmentally regulated, tissue-specific, and that expression can modulate fatty acid accretion independently of diet. METHODS: Brain and lung transporter expression were quantified in C57BL/6 wild-type (WT) and Fat1 mice. Pups were dam-fed until day 21. Dams were fed AIN-76A 10% corn oil to represent a typical North American/European diet. After weaning, mice were fed the same diet as dams. Gene expression of Fatp1, Fatp4, Fabp5, and Fat/cd36 was quantified by quantitative reverse transcriptase-polymerase chain reaction. Fatty acid concentrations were measured by GC-MS. RESULTS: Brain docosahexaenoic acid (DHA) concentrations increased from day 3 to day 28 in both genotypes, with higher concentrations at days 3 and 14 in Fat1 than in WT mice [median (IQR)]: 10.7 (10.6-11.2) mol% compared with 6.6 (6.4-7.2) mol% and 12.5 (12.4-12.9) mol% compared with 8.9 (8.7-9.1) mol%, respectively; P < 0.05). During DHA accrual, transporter expression decreased. Fold changes in brain Fatp4, Fabp5, and Fat/cd36 were inversely correlated with fold changes in brain DHA concentrations in Fat1 relative to WT mice (ρ = -0.85, -0.75, and -0.78, respectively; P ≤ 0.001). Lung DHA concentrations were unchanged across the 3 time points for both genotypes. Despite unchanging DHA concentrations, there was increased expression of Fatp1 at days 14 and 28 (5-fold), Fatp4 at day 14 (2.3-fold), and Fabp5 at day 14 (3.8-fold) relative to day 3 in Fat1 mice. In WT mice, Fatp1 increased almost 5-fold at day 28 relative to day 3. There was no correlation between lung transporters and DHA concentrations in Fat1 relative to WT mice. CONCLUSIONS: Development of fatty acid transporter expression in C57BL/6 WT and Fat1 mice is genotype and tissue specific. Further, postnatal accretion of brain DHA appears independent of transporter status, with tissue concentrations representing dietary contributions.