Objectives-Acute pancreatitis is a necroinflammatory disease that leads to 210,000 hospitalizations in the United States annually. Recent reports suggest that there may be important differences in clinical features between infants/toddlers and older children. Thus, in this study we make a direct comparison between the pediatric age groups in presentation and management trends of acute pancreatitis. Patients and Methods-We examined all children (ages 0 to 20 years) admitted to Yale-New Haven Children's Hospital with pancreatitis between 1994 and 2007.Results-Two hundred seventy-one cases met inclusion criteria for acute pancreatitis. Infants and toddlers manifested fewer signs and symptoms of abdominal pain, epigastric tenderness, and nausea compared with older children (43% vs 93%; 57% vs 90%; and 29% vs 76%, respectively; P < 0.05 for all comparisons). They were more likely to be diagnosed by serum lipase than by amylase and to undergo radiographic evaluation (P < 0.05). They had a longer hospital stay (19.5 vs 4 days; P < 0.05) and were less likely to be directly transitioned to oral nutrition (14% vs 71%; P < 0.05).Conclusions-Infants and toddlers with acute pancreatitis present with fewer classical symptoms and are managed differently from older children. We believe these data will be helpful in evaluating and understanding treatment practices in this age group. Keywords acute pancreatitis; amylase; infants; lipase; toddlers Acute pancreatitis is a necroinflammatory disease of the pancreas that has many associated etiologies such as common bile duct stones, alcohol, trauma, medications, toxins, and ductal defects. Acute pancreatitis accounts for more than 210,000 annual hospital admissions (1) and, tallied with chronic pancreatitis, leads to 31,000 deaths per year (2). Although practice parameters for acute pancreatitis are currently evolving using primarily adult studies, information about children is lacking. Although in children there are several studies examining pancreatitis incidence and etiology (3-7), few have characterized their clinical presentation and management (8,9). We hypothesized that in our pediatric population of NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript acute pancreatitis in New Haven, Connecticut, there are also age-related differences in the management of acute pancreatitis. Indeed, we found that infants and toddlers differ from older children in clinical presentation, level of serum biomarker elevation, type of radiographic evaluation, length of hospitalization, and mode of nutrition. PATIENTS AND METHODS Study GroupA retrospective chart review was conducted at Yale-New Haven Children's Hospital, New Haven. Children (younger than 21 years) admitted between August 1994 and July 2007 were screened for International Classification of Diseases-9 codes pertaining to pancreatitis. The study was approved by the Yale University School of Medicine institutional review board. Details of the cohort, including referral trends for pancreatitis over time, eti...

Acute pancreatitis is a painful, inflammatory disorder for which adequate treatments are lacking. An early, critical step in its development is the aberrant signaling of Ca(2+) within the pancreatic acinar cell. This Ca(2+) release is modulated by the intracellular Ca(2+) channel the ryanodine receptor (RYR). We have previously shown that RYR inhibition reduces pathological intra-acinar protease activation, an early marker of pancreatitis. In this study, we examined whether pretreatment with the RYR inhibitor dantrolene attenuates the severity of caerulein-induced pancreatitis in mice. Immunofluorescent labeling for RYR from mouse pancreatic sections showed localization to the basolateral region of the acinar cell. After 1 h of caerulein hyperstimulation in vivo, dantrolene 1) reduced pancreatic trypsin activity by 59% (P < 0.05) and 2) mitigated early ultrastructural derangements within the acinar cell. Eight hours after pancreatitis induction, dantrolene reduced pancreatic trypsin activity and serum amylase by 61 and 32%, respectively (P < 0.05). At this later time point, overall histological severity of pancreatitis was reduced by 63% with dantrolene pretreatment (P < 0.05). TUNEL-positive cells were reduced by 58% (P < 0.05). These data suggest that the RYR plays an important role in mediating early acinar cell events during in vivo pancreatitis and contributes to disease severity. Blockade of Ca(2+) signals and particularly RYR-Ca(2+) may be useful as prophylactic treatment for this disease in high-risk settings for pancreatitis.

SZ. Pharmacological and genetic inhibition of calcineurin protects against carbachol-induced pathological zymogen activation and acinar cell injury.

Disqualifying patients with intellectual disabilities (ID) from transplantation has received growing attention from the media, state legislatures, the Office of Civil Rights, and recently the National Council on Disability, as well as internationally. Compared with evidence-based criteria used to determine transplant eligibility, the ID criterion remains controversial because of its potential to be discriminatory, subjective, and because its relationship to outcomes is uncertain. Use of ID in determining transplant candidacy may stem partly from perceived worse adherence and outcomes for patients with ID, fear of penalties to transplant centers for poor outcomes, and stigma surrounding the quality of life for people with ID. However, using ID as a contraindication to solid organ transplantation is not evidence-based and reduces equitable access to transplantation, disadvantaging an already vulnerable population. Variability and lack of transparency in referral and evaluation allows for gatekeeping, threatens patient autonomy, limits access to lifesaving treatment, and may be seen as unfair. We examine the benefits and harms of using ID as a transplant eligibility criterion, review current clinical evidence and ethical considerations, and make recommendations for transplant teams and regulatory agencies to ensure fair access to transplant for individuals with ID.