Medical Management of Chronic Pancreatitis in Children: A Position Paper by the NASPGHAN Pancreas Committee
This position paper summarizes the current understanding of the medical management of chronic pancreatitis (CP) in children in light of the existing medical literature, incorporating recent advances in understanding of nutritional, pain, lifestyle considerations and sequelae of CP. This article complements and is intended to integrate with parallel position papers on endoscopic and surgical aspects of CP in children. Concepts and controversies related to pancreatic enzyme replacement therapy (PERT), the use of antioxidants and other CP medical therapies are also reviewed. Highlights include inclusion of tools for medical decision making for PERT, CP-related diabetes, and multimodal pain management (including an analgesia ladder). Gaps in our understanding of CP in children and avenues for further investigations are also reviewed.
Anti-tumor Necrosis Factor-alpha Exposure Impacts Vedolizumab Mucosal Healing Rates in Pediatric Inflammatory Bowel Disease
BACKGROUND:Vedolizumab (VDZ) is effective for treating both adult and pediatric onset inflammatory bowel disease (IBD). Clinical outcomes, however, have been reported to be superior in patients naÃ¯ve to anti-tumor necrosis factor (TNF). With the growing interest in endoscopic endpoints, we aimed to describe rates of mucosal healing in pediatric patients being treated with VDZ and examine the influence of anti-TNF on outcomes. METHODS:We conducted a retrospective review of all IBD patients â‰¤21 years of age who initiated VDZ and underwent endoscopy. Primary outcome was mucosal healing (composite of endoscopic [SES-CD] and Mayo score UC) and histological remission [Nancy index-UC and Crohn disease (CD) histologic activity]. Descriptive statistics summarized the data. Comparisons were made for endpoints based on anti-TNF exposure using univariate testing. RESULTS:Sixty-eight patients were included in the final analysis; 35 with UC and 33 with CD. Thirty-two patients (22 UC and 10 CD) were anti-TNF-naÃ¯ve and 36 patients (13 UC and 23 CD) were anti-TNF-exposed. The median duration on VDZ before endoscopic assessment was 49 (IQR 32-73) weeks. A total of 38% (25/66) of patients met the primary outcome of mucosal healing and did not differ between anti-TNF-naÃ¯ve or anti-TNF-exposed. Endoscopic remission was achieved by 51% with significantly more anti-TNF naÃ¯ve patients reaching this endpoint (66% vs 40%, Pâ€Š=â€Š0.03). Histologic remission was achieved by 42% of patients with a nonsignificant trend towards improved histologic remission rates in anti-TNF-naÃ¯ve patients (52% vs 33%, Pâ€Š=â€Š0.13). CONCLUSIONS:VDZ is associated with mucosal healing in pediatric IBD. Anti-TNF exposure significantly impacted endoscopic remission, but not histologic remission in children on VDZ.
Conserved cysteine residues within the attachment G glycoprotein of respiratory syncytial virus play a critical role in the enhancement of cytotoxic T-lymphocyte responses
The cytotoxic T-lymphocyte (CTL) response plays an important role in the control of respiratory syncytial virus (RSV) replication and the establishment of a Th1-CD4+ T cell response against the virus. Despite lacking Major Histocompatibility Complex I (MHC I)-restricted epitopes, the attachment G glycoprotein of RSV enhances CTL activity toward other RSV antigens, and this effect depends on its conserved central region. Here, we report that RSV-G can also improve CTL activity toward antigens from unrelated pathogens such as influenza, and that a mutant form of RSV-G lacking four conserved cysteine residues at positions 173, 176, 182, and 186 fails to enhance CTL responses. Our results indicate that these conserved residues are essential for the wide-spectrum pro-CTL activity displayed by the protein.