Temporal Analysis of Inflammatory Bowel Disease and Pancreatitis Co-Occurrence in Children and Adults in the United States.

INTRODUCTION: Pancreatitis in inflammatory bowel disease has been attributed to peripancreatic intestinal disease and/or drug-induced pancreatic toxicity. We used large cohort analyses to define inflammatory bowel disease and pancreatitis temporal co-occurrence with a detailed descriptive analysis to gain greater insight into the pathophysiological relationship between these 2 diseases. METHODS: Truven Health MarketScan private insurance claims from 141,017,841 patients (younger than 65 years) and 7,457,709 patients from 4 academic hospitals were analyzed. We calculated the prevalence of Crohn's disease or ulcerative colitis (UC) with acute pancreatitis or chronic pancreatitis (CP) and performed temporal and descriptive analyses. RESULTS: Of 516,724 patients with inflammatory bowel disease, 12,109 individuals (2.3%) had pancreatitis. Acute pancreatitis (AP) was 2-6x more prevalent than CP. In adults, AP occurred equally among Crohn's disease and UC (1.8%-2.2% vs 1.6%-2.1%, respectively), whereas in children, AP was more frequent in UC (2.3%-3.4% vs 1.5%-1.8%, respectively). The highest proportion of pancreatitis (21.7%-44.7%) was at/near the time of inflammatory bowel disease diagnosis. Of them, 22.1%-39.3% were on steroids during pancreatitis. Individuals with CP or recurrent pancreatitis hospitalizations had increased risk of a future inflammatory bowel disease diagnosis (odds ratio = 1.52 or 1.72, respectively). DISCUSSION: Pancreatitis in inflammatory bowel disease may not simply be a drug adverse event but may also involve local and/or systemic processes that negatively affect the pancreas. Our analysis of pancreatitis before, during, and after inflammatory bowel disease diagnosis suggests a bidirectional pathophysiologic relationship between inflammatory bowel disease and pancreatitis, with potentially more complexity than previously appreciated.

MELD 3.0 for adolescent liver transplant candidates.

BACKGROUND AND AIMS: Adolescents constitute a unique waitlist cohort that is distinct from younger children. Model for End-stage Liver Disease (MELD) 3.0, which was developed in an adult population of liver transplant candidates, is planned to replace MELD-Sodium in the current liver allocation system for both adults and adolescents aged 12-17. We evaluated the predictive performance of MELD-Sodium, MELD 3.0, and Pediatric End-stage Liver Disease for 90-day waitlist mortality risk among adolescent liver transplant registrants. APPROACH AND RESULTS: New waitlist registrations for primary liver transplants among individuals aged 12-17 and 18-25 for comparison were identified using Organ Procurement and Transplantation Network (OPTN) data from November 17, 2004, to December 31, 2021. The predictive performance of the current and proposed MELD and Pediatric End-stage Liver Disease scores was assessed using Harrell's concordance ( c ) statistic. There were 1238 eligible listings for adolescents aged 12-17 and 1740 young adults aged 18-25. In the adolescent group, 90-day survival was 97.8%, compared with 95.9% in those aged 18-25 (log-rank p = 0.005), with no significant differences when stratified by sex or indication. Among adolescents, increasing MELD 3.0 was associated with an increased hazard of mortality (HR=1.27, 95% CI: 1.18-1.37), and the c -statistic for 90-day waitlist survival using MELD 3.0 was 0.893 compared with 0.871 using MELD-Sodium and 0.852 using Pediatric End-stage Liver Disease. CONCLUSIONS: The discriminative ability of MELD 3.0 to rank adolescents according to the risk of death within 90 days was robust. Although MELD 3.0 was initially developed and validated in adults, MELD 3.0 may also improve the prediction of waitlist mortality in adolescents and better represent their urgency for liver transplants.

Procalcitonin as a Predictive Marker for Bacteremia in Children With a Central Line and Fever.

OBJECTIVES: Unnecessary use of antibiotics is an increasing problem. In this study, we sought to determine the diagnostic accuracy of procalcitonin in predicting bacteremia in children with a central line and fever, and we sought to determine optimal cutoff values to maximize sensitivity and specificity. This is the largest study to date in which procalcitonin is examined as a predictive marker of bacteremia in pediatric patients with a central line and fever. METHODS: We conducted a retrospective cohort study of children aged 0 to 23 years with a central line and fever of 38°C who had procalcitonin and blood cultures drawn before initiation of antibiotics and had no other identified bacterial infection. Patients were also prospectively monitored via a custom-built electronic medical record dashboard for eligibility. RESULTS: There were 523 patients and >2500 procalcitonin values reviewed for eligibility. Of these, 169 (47%) patients and 335 blood cultures with procalcitonin were included. There were 94 (28%) positive bacterial blood cultures and 241 (72%) negative bacterial blood cultures. In bacteremic cultures, the mean procalcitonin level was 9.96 ± 15.96 ng/mL, and the median procalcitonin level was 4.85 ng/mL (interquartile range 18.5). In nonbacteremic cultures, the mean procalcitonin level was 1.23 ± 10.37 ng/mL, and the median procalcitonin level was 0.3 ng/mL (interquartile range 0.7). A receiver operating characteristic analysis indicated a procalcitonin level of ≥0.6 ng/mL as the best cutoff point that produced a sensitivity of 85.6% and a specificity of 65.7% (area under the curve 0.85). CONCLUSIONS: Procalcitonin is a sensitive biomarker in predicting bacteremia in children with a central line and fever.

Nationwide Trends in Acute and Chronic Pancreatitis Among Privately Insured Children and Non-Elderly Adults in the United States, 2007-2014.

BACKGROUND & AIMS: Epidemiologic analyses of acute pancreatitis (AP) and chronic pancreatitis (CP) provide insight into causes and strategies for prevention and affect allocation of resources to its study and treatment. We sought to determine current and accurate incidences of AP and CP, along with the prevalence of CP, in children and adults in the United States. METHODS: We collected data from the Truven MarketScan Research Databases of commercial inpatient and outpatient insurance claims in the United States from 2007 through 2014 (patients 0-64 years old). We calculated the incidences of AP and CP and prevalence of CP based on International Classification of Diseases, 9th Revision diagnosis codes. Children were defined as 18 years or younger and adults as 19 to 64 years old. RESULTS: The incidence of pediatric AP was stable from 2007 through 2014, remaining at 12.3/100,000 persons in 2014. Meanwhile, the incidence for adult AP decreased from 123.7/100,000 persons in 2007 to 111.2/100,000 persons in 2014. The incidence of CP decreased over time in children (2.2/100,000 persons in 2007 to 1.9/100,000 persons in 2014) and adults (31.7/100,000 persons in 2007 to 24.7/100,000 persons in 2014). The prevalences of pediatric and adult CP were 5.8/100,000 persons and 91.9/100,000 persons, respectively, in 2014. Incidences of AP and CP increased with age. We found little change in incidence during the first decade of life but linear increases starting in the second decade. CONCLUSIONS: We performed a comprehensive epidemiologic analysis of privately insured, non-elderly adults and children with AP and CP in the United States. Changes in gallstone formation, smoking, and alcohol consumption, along with advances in pancreatitis management, may be responsible for the stabilization and even decrease in the incidences of AP and CP.

The impact of crowding on time until abdominal CT interpretation in emergency department patients with acute abdominal pain.

OBJECTIVE: We assessed the relationship between emergency department (ED) crowding and delays in care in patients presenting with abdominal pain who receive abdominal computed tomography (CT). METHODS: Prospective cohort study of adults who presented over a 1-year period to 2 urban academic EDs with abdominal pain and received CT. Each subject had 3 validated crowding measures assigned at enrollment (ED census, waiting room number, number of admitted patients). These were normalized to quartiles to signify least to most crowded. The Cuzick test was used for trend and log-linear regression and tested the association between ED crowding and time from triage to CT read. The time interval was further decomposed into triage to room, room to CT order, and order to CT read times. The adjusted analysis controlled for age, sex, race, pain score, time of day, triage level, and site. RESULTS: 767 patients were enrolled (mean age, 44 +/- 17 years; 61% female; 60% black). Median time from triage to CT read was 375 minutes (interquartile range [IQR], 276-497). Individual time intervals included triage to room (46 minutes [IQR, 16-111]), room to CT order (83 minutes [IQR, 38-151]), and order to CT read (203 minutes [IQR, 138-375]). Across waiting room quartiles, triage to CT read was associated with progressively longer times (318 vs 364 vs 414 vs 445 minutes; P < 0.001 for trend). Similar trends were noted for waiting room number and admitted patients (P < 0.001). In multivariable analysis, the association between ED crowding and time from triage to CT read remained significant and consistent across all crowding measures (P < 0.001). When decomposed into time intervals, triage to room time showed the greatest difference (22 vs 38 vs 72 vs 92 minutes; P < 0.001). CONCLUSION: ED crowding is associated with an approximately 2-hour delay to CT interpretation availability. Attempts to reduce delays in abdominal CTs may include earlier provider evaluation and placement in the queue for scanning.

Dopamine D(1) receptor activation of adenylyl cyclase, not phospholipase C, in the nucleus accumbens promotes maternal behavior onset in rats.

A body of evidence supports the idea that the mesolimbic dopamine (DA) system modulates the natural increase in responsiveness female rats show toward offspring (biological or foster) at birth. In the absence of the full hormonal changes associated with pregnancy and birth, female rats do not show immediate responsiveness toward foster offspring. Activation of the mesolimbic DA system can produce an immediate onset of maternal behavior in these females. For example, female rats that are hysterectomized and ovariectomized on day 15 of pregnancy (15HO) and presented with pups 48 hours later normally show maternal behavior after 2-3 days of pup exposure, but will show maternal behavior on day 0 of testing after microinjection of the DA D(1) receptor agonist, SKF 38393, into the nucleus accumbens (NA) at the time of pup presentation. DA D(1) receptor stimulation is known to activate cAMP intracellular signaling cascades via its stimulation of adenylyl cyclase (AC). However, some DA D(1) receptors are also linked to phospholipase C (PLC) and are capable of activating phosphatidylinositol signaling cascades. SKF 38393 stimulates both types of D(1) receptors. Here we provide evidence that the facilitatory effects of DA D(1) receptor stimulation in the NA on maternal behavior are mediated by AC-linked DA D(1) receptors. By examining the effects of intra-NA application of SKF 83822, a drug which selectively binds DA D(1)-AC receptors, or SKF 83959, a drug which selectively activates D(1)-PLC-linked receptors, we find that only SKF 83822 facilitates maternal behavior onset.

A single injection of 17beta-estradiol at the time of pup presentation promotes the onset of maternal behavior in pregnancy-terminated rats.

Female rats that are hysterectomized and ovariectomized on day 15 of pregnancy (15HO) and presented with pups 48 h later show maternal behavior after 2 or 3 days of pup exposure. In contrast, if 15HO females are administered (sc) 20 microg/kg of estradiol benzoate (EB) on day 15 of pregnancy after HO, they show near immediate maternal behavior when pups are presented 48 h later. EB has typically been administered on day 15 because of the underlying assumption that EB exerts genomic effects which require a long duration before being expressed in changes in neuronal phenotype. In light of the more recent evidence that estradiol can generate rapid changes in cellular function, we examined whether injection of a water-soluble form of 17beta-estradiol (E(2)) can facilitate maternal behavior in pregnancy-terminated females when it is administered at the time of pup presentation rather than at the time of HO. Female rats treated with 100 microg/kg of E(2) showed a robust facilitation of maternal behavior, requiring a median of 1 day of pup exposure before showing maternal behavior, compared with 3 days in vehicle-treated rats.