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.

Evaluating the accuracy of American Society for Gastrointestinal Endoscopy guidelines in patients with acute gallstone pancreatitis with choledocholithiasis.

BACKGROUND: Acute gallstone pancreatitis (AGP) is the most common cause of acute pancreatitis (AP) in the United States. Patients with AGP may also present with choledocholithiasis. In 2010, the American Society for Gastrointestinal Endoscopy (ASGE) suggested a management algorithm based on probability for choledocholithiasis, recommending additional imaging for patients at intermediate risk and endoscopic retrograde cholangiopancreatography (ERCP) for patients at high risk of choledocholithiasis. In 2019, the ASGE guidelines were updated using more specific criteria to categorize individuals at high risk for choledocholithiasis. Neither ASGE guideline has been studied in AGP to determine the probability of having choledocholithiasis. AIM: To determine compliance with ASGE guidelines, assess outcomes, and compare 2019 vs 2010 ASGE criteria for suspected choledocholithiasis in AGP. METHODS: We conducted a retrospective cohort study of 882 patients admitted with AP to a single tertiary care center from 2008-2018. AP was diagnosed using revised Atlanta criteria and AGP was defined as the presence of gallstones on imaging or with cholestatic pattern of liver injury in the absence of another cause. Patients with chronic pancreatitis and pancreatic malignancy were excluded as were those who went directly to cholecystectomy prior to assessment for choledocholithiasis. Patients were assigned low, intermediate or high risk based on ASGE guidelines. Our primary outcomes of interest were the proportion of patients in the intermediate risk group undergoing magnetic resonance cholangiopancreatography (MRCP) first and the proportion of patients in the high risk group undergoing ERCP directly without preceding imaging. Secondary outcomes of interest included outcome differences based on if guidelines were not adhered to. We then evaluated the diagnostic accuracy of 2019 in comparison to the 2010 ASGE criteria for patients with suspected choledocholithiasis. We performed the t test or Wilcoxon rank sum test, as appropriate, to analyze if there were outcome differences based on if guidelines were not adhered to. Kappa coefficients were calculated to measure the degree of agreement between pairs of variables. RESULTS: In this cohort, we identified 235 patients with AGP of which 79 patients were excluded as they went directly to surgery for cholecystectomy without prior MRCP or ERCP. Of the remaining 156 patients, 79 patients were categorized as intermediate risk and 77 patients were high risk for choledocholithiasis according to the 2010 ASGE guidelines. Among 79 intermediate risk patients, 54 (68%) underwent MRCP first whereas 25 patients (32%) went directly to ERCP. For the 54 patients with intermediate risk who had MRCP first, 36 patients had no choledocholithiasis while 18 patients had evidence of choledocholithiasis prompting ERCP. Of these patients, ERCP confirmed stone disease in 11 patients. Of the 25 intermediate risk patients who directly underwent ERCP, 18 patients had stone disease. One patient with a normal ERCP developed post ERCP pancreatitis. Patients undergoing MRCP in this group had a significantly longer length of stay (5.0 vs 4.0 d, P = 0.02). In the high risk group, 64 patients (83%) had ERCP without preceding imaging, of which, 53 patients had findings consistent with choledocholithiasis, of which 13 patients (17%) underwent MRCP before ERCP, all of which showed evidence of stone disease. Furthermore, all of these patients ultimately had an ERCP, of which 8 patients had evidence of stones and 5 had normal examination.Our cohort also demonstrated that 58% of all 156 patients with AGP had confirmed choledocholithiasis (79% of the high risk group and 37% of the intermediate group when risk was assigned based on the 2010 ASGE guidelines). When the updated 2019 ASGE guidelines were applied instead of the original 2010 guidelines, there was moderate agreement between the 2010 and 2019 guidelines (kappa = 0.46, 95%CI: 0.34-0.58). Forty-two of 77 patients were still deemed to be high risk and 35 patients were downgraded to intermediate risk. Thirty-five patients who were originally assigned high risk were reclassified as intermediate risk. For these 35 patients, 26 patients had ERCP findings consistent with choledocholithiasis and 9 patients had a normal examination. Based on the 2019 criteria, 9/35 patients who were downgraded to intermediate risk had an unnecessary ERCP with normal findings (without a preceding MRCP). CONCLUSION: Two-thirds in intermediate risk and 83% in high risk group followed ASGE guidelines for choledocholithiasis. One intermediate-group patient with normal ERCP had post-ERCP AP, highlighting the risk of unnecessary procedures.

Extrapancreatic Complications in Hospitalized Patients With Mild Acute Pancreatitis Are Associated With Poorer Outcomes: Results From a Single-Center Study.

OBJECTIVE: Patients with acute pancreatitis (AP) are at risk for extrapancreatic complications (EPCs) when admitted to the intensive care unit (ICU). We assessed the prevalence of EPCs in non-ICU AP patients and their outcomes. METHODS: We retrospectively studied EPCs in non-ICU AP patients between 2008 and 2018. Outcomes such as length of stay (LOS), inpatient mortality, and 30-day readmission rates were compared between those with and without EPC. RESULTS: Of the 830 AP patients, 151 (18.1%) had at least 1 EPC. These included urinary tract infection (15.9%), Clostridium difficile infection (17.2%), pneumonia (7.3%), bacteremia (17.2%), acute kidney injury requiring dialysis (3.3%), gastrointestinal bleeding (12.5%), alcohol withdrawal (24.5%), delirium (14.5%), and falls (1.32%). Patients with EPC had increased mean LOS (6.98 vs 4.42 days; P < 0.001) and 30-day readmissions (32.5% vs 19%; P < 0.001). On multivariate regression, EPCs were independently associated with higher LOS (odds ratio, 1.45 [95% confidence interval, 1.36-1.56]; P < 0.001) and 30-day readmissions (odds ratio, 1.94 [95% confidence interval 1.28-2.95]; P < 0.001). CONCLUSIONS: The EPCs are common among noncritical AP patients and contribute to poor outcomes like increased LOS and 30-day readmissions.

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 the Clinical Characteristics and Outcomes of Idiopathic Acute Pancreatitis: Comparison With Nonidiopathic Acute Pancreatitis Over a 10-Year Period.

OBJECTIVE: Up to 30% of acute pancreatitis (AP) cases do not have an established etiology (idiopathic AP [IAP]). We evaluated the characteristics and outcomes of hospitalized IAP patients compared with those with established AP cause (non-IAP). METHODS: A retrospective study of AP patients admitted to a single center from 2008 to 2018 was performed. Patients were divided into IAP and non-IAP groups. Outcomes included mortality, 30-day and 1-year readmission, length of stay (LOS), intensive care unit admissions, and complications. RESULTS: Of 878 AP patients, 338 had IAP and 540 non-IAP (234 gallstone, 178 alcohol). Groups had similar demographics, Charlson Comorbidity Index, and pancreatitis severity. The IAP patients had more 1-year readmissions (0.64 vs 0.55, P = 0.006) but similar 30-day readmissions and mortality. Patients with IAP had shorter LOS (4.98 vs 5.99 days, P = 0.01), and fewer intensive care unit admissions (3.25% vs 6.85%, P = 0.03) and extrapancreatic complications (15.4% vs 25.2%, P = 0.001). There was no difference in pain level between groups. CONCLUSIONS: The IAP patients tend to have more readmissions in 1 year, but less severe presentations, shorter LOS, and fewer complications. Readmission rates may be related to lack of defined etiology and treatment to prevent recurrence.

The Impact of an Inpatient Pancreatitis Service and Educational Intervention Program on the Outcome of Acute Pancreatitis.

BACKGROUND: We introduced an inpatient pancreatitis consultative service aimed to 1) provide guideline-based recommendations to acute pancreatitis inpatients and 2) educate inpatient teams on best practices for acute pancreatitis management. We assessed the impact of pancreatitis service on acute pancreatitis outcomes. METHODS: Inpatients with acute pancreatitis (2008-2018) were included in this cohort study. Primary outcomes included length of stay and refeeding time. The educational intervention was a guideline-based decision support tool, reinforced at hospital-wide educational forums. In Part A (n = 965), we compared outcomes pre-service (2008-2010) to post-service (2012-2018), excluding 2011, when the pancreatitis service was introduced. In Part B (n = 720, 2012-2018), we divided patients into 2 groups based on if co-managed with the pancreatitis service, and compared outcomes, including subgroup analysis based on severity, focusing on mild acute pancreatitis. RESULTS: In Part A, for mild acute pancreatitis, length of stay (111 vs 88.4 h, P = .001), refeeding time (61.8 vs 47.4 h, P = .002), and infections (10.0% vs 1.87%, P < .001) were significantly improved after the pancreatitis service was introduced, with multivariable analysis showing reduced length of stay (odds ratio 0.83; 95% confidence interval, 0.82-0.84; P < .001) and refeeding time (odds ratio 0.75; 95% confidence interval, 0.74-0.77; P < .001). In Part B, for mild acute pancreatitis, refeeding time (44.2 vs 50.3 h, P = .123) and infections (5.58% vs 4.70%, P = .80) were similar in patients cared for without and with the service. Length of stay was higher in the pancreatitis service group (93.3 vs 81.2 h, P = .05), as they saw more gallstone acute pancreatitis patients who had greater length of stay and magnetic resonance cholangiopancreatography. In the post-service period, a majority of patients with moderate/severe acute pancreatitis and nearly all intensive care unit admits received care from the pancreatitis service. CONCLUSIONS: Implementation of an inpatient pancreatitis service was associated with improved outcomes in mild acute pancreatitis. Guideline-based educational interventions have a beneficial impact on management of mild acute pancreatitis by admitting teams even without pancreatitis consultation.

Tissue sodium stores in peritoneal dialysis and hemodialysis patients determined by 23-sodium magnetic resonance imaging.

BACKGROUND: Tissue sodium content in patients on maintenance hemodialysis (MHD) and peritoneal dialysis (PD) were previously explored using 23Sodium magnetic resonance imaging (23NaMRI). Larger studies would provide a better understanding of sodium stores in patients on dialysis as well as the factors influencing this sodium accumulation. METHODS: In this cross-sectional study, we quantified the calf muscle and skin sodium content in 162 subjects (10 PD, 33 MHD patients, and 119 controls) using 23NaMRI. Plasma levels of interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) were measured to assess systemic inflammation. Sixty-four subjects had repeat 23NaMRI scans that were analyzed to assess the repeatability of the 23NaMRI measurements. RESULTS: Patients on MHD and PD exhibited significantly higher muscle and skin sodium accumulation compared to controls. African American patients on dialysis exhibited greater muscle and skin sodium content compared to non-African Americans. Multivariable analysis showed that older age was associated with both higher muscle and skin sodium. Male sex was also associated with increased skin sodium deposition. Greater ultrafiltration was associated with lower skin sodium in patients on PD (Spearman's rho=-0.68, P = 0.035). Higher plasma IL-6 and hsCRP levels correlated with increased muscle and skin sodium content in the overall study population. Patients with higher baseline tissue sodium content exhibited greater variability in tissue sodium stores on repeat measurements. CONCLUSIONS: Our findings highlight greater muscle and skin sodium content in dialysis patients compared to controls without kidney disease. Tissue sodium deposition and systemic inflammation seen in dialysis patients might influence one another bidirectionally.

LIN28 Regulates Stem Cell Metabolism and Conversion to Primed Pluripotency.

The RNA-binding proteins LIN28A and LIN28B play critical roles in embryonic development, tumorigenesis, and pluripotency, but their exact functions are poorly understood. Here, we show that, like LIN28A, LIN28B can function effectively with NANOG, OCT4, and SOX2 in reprogramming to pluripotency and that reactivation of both endogenous LIN28A and LIN28B loci are required for maximal reprogramming efficiency. In human fibroblasts, LIN28B is activated early during reprogramming, while LIN28A is activated later during the transition to bona fide induced pluripotent stem cells (iPSCs). In murine cells, LIN28A and LIN28B facilitate conversion from naive to primed pluripotency. Proteomic and metabolomic analysis highlighted roles for LIN28 in maintaining the low mitochondrial function associated with primed pluripotency and in regulating one-carbon metabolism, nucleotide metabolism, and histone methylation. LIN28 binds to mRNAs of proteins important for oxidative phosphorylation and modulates protein abundance. Thus, LIN28A and LIN28B play cooperative roles in regulating reprogramming, naive/primed pluripotency, and stem cell metabolism.