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Cytokines x PRC1	1

Author: Downs, Elissa M ; Liu, Quin Y ; Lindblad, Doug ; Uc, Aliye ; Morinville, Veronique D ; Fishman, Douglas S ; Cress, Gretchen A ; Noel, Robert A. ; Grover, Amit S ; Mark, Jacob A ; Chugh, Ankur ; Fishman, Douglas S. ; Morinville, Veronique D. ; Downs, Elissa M. ; Sellers, Zachary M ; Schwarzenberg, Sarah Jane ; Ruan, Wenly ; Noel, Robert A ; Grover, Amit S. ; Mark, Jacob A. ; Giefer, Matthew J ; Gariepy, Cheryl E ; Freeman, A Jay ; Gariepy, Cheryl E. ; Perito, Emily R. ; Cress, Gretchen A. ; Yuan, Ying ; Wilschanski, Michael ; Lowe, Mark E ; Ng, Kenneth ; Giefer, Matthew J. ; Abu-El-Haija, Maisam A ; McFerron, Brian A. ; Mehta, Megha S. ; Troendle, David M ; Maqbool, Asim ; Lowe, Mark E. ; Phadke, Madhura Y. ; Sellers, Zachary M. ; Liu, Quin Y. ; Phadke, Madhura Y ; Cohen, Reuven Z ; Ooi, Chee Y. ; Troendle, David M. ; Gonska, Tanja Y. ; Cohen, Reuven Z. ; Abu-El-Haija, Maisam A. ; Ooi, Chee Y ; Freeman, A. Jay ; Gonska, Tanja Y ; McFerron, Brian A ; Mehta, Megha S ; Perito, Emily R ; Wang, Fuchenchu ; Zheng, Yuhua

OBJECTIVETo determine if mild-moderate hypertriglyceridemia (HTG) is associated with increased development of chronic pancreatitis (CP) or pancreatitis-associated complications in children with acute recurrent or CP.STUDY DESIGNLongitudinal data from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2) cohort of children with acute recurrent or CP (n = 559) were analyzed. Subjects were divided into normal triglycerides (<150 mg/dL; 1.7 mmol/L), any HTG (≥150 mg/dL; ≥1.7 mmol/L), mild-moderate HTG (150-499 mg/dL; 1.7-5.6 mmol/L), moderate HTG (500-999 mg/dL; 5.6-11.3 mmol/L), and severe HTG groups (≥1000 mg/dL; ≥11.3 mmol/L), based on highest serum triglyceride value. Laboratory, imaging, pancreatitis and hospital events, complications, and quality of life data were analyzed.RESULTSIn children with acute recurrent or CP and HTG, there was no increase in the number of pancreatitis attacks per person-years, nor an increase in CP prevalence. However, HTG severity was associated with increased pancreatic inflammation, pancreatic cysts, pain, hospital days, number of hospitalizations, intensive care, and missed school days.CONCLUSIONSMild-moderate HTG in children with acute recurrent or CP was not associated with increased pancreatitis frequency, nor increased development of CP, but was associated with increased pancreatitis complications and disease burden. As a treatable condition, treatment of mild-moderate HTG may be considered to reduce pancreatitis-associated complications and medical burden in children with acute recurrent or CP.

01 Oct 2024·American Journal of Gastroenterology

Pancreatic Enzyme Use Reduces Pancreatitis Frequency in Children With Acute Recurrent or Chronic Pancreatitis: A Report From INSPPIRE

Article

Author: Uc, Aliye ; Andersen, Dana K. ; Lindblad, Douglas ; Schwarzenberg, Sarah Jane ; Chugh, Ankur ; McFerron, Brian A. ; Goday, Praveen ; Yuan, Ying ; Morinville, Veronique D. ; Freeman, Alvin Jay ; Zheng, Yuhua ; Cress, Gretchen A. ; Gonska, Tanja Y. ; Ooi, Chee Y. ; Lowe, Mark E. ; Sellers, Zachary M. ; Grover, Amit S. ; Liu, Quin Y. ; Mark, Jacob A. ; Giefer, Matthew J. ; Ng, Kenneth ; Fishman, Douglas S. ; Noel, Robert A. ; Wilschanski, Michael ; Perito, Emily R. ; Mehta, Megha S. ; Abu-El-Haija, Maisam A. ; Maqbool, Asim ; Gariepy, Cheryl E. ; Wang, Fuchenchu

INTRODUCTION:Among children who suffer from acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP), acute pancreatitis (AP) episodes are painful, often require hospitalization, and contribute to disease complications and progression. Despite this recognition, there are currently no interventions to prevent AP episodes. In this retrospective cohort study, we assessed the impact of pancreatic enzyme therapy (PERT) use on clinical outcomes among children with pancreatic-sufficient ARP or CP.METHODS:Children with pancreatic-sufficient ARP or CP in the INSPPIRE-2 cohort were included. Clinical outcomes were compared for those receiving vs not receiving PERT, as well as frequency of AP before and after PERT. Logistic regression was used to study the association between development of AP episodes after starting PERT and response predictors.RESULTS:Among 356 pancreatic-sufficient participants, 270 (76%) had ARP, and 60 (17%) received PERT. Among those on PERT, 42% did not have a subsequent AP episode, during a mean 2.1 years of follow-up. Children with a SPINK1 mutation (P = 0.005) and those with ARP (compared with CP, P = 0.008) were less likely to have an AP episode after starting PERT. After initiation of PERT, the mean AP annual incidence rate decreased from 3.14 down to 0.71 (P < 0.001).DISCUSSION:In a retrospective analysis, use of PERT was associated with a reduction in the incidence rate of AP among children with pancreatic-sufficient ARP or CP. These results support the need for a clinical trial to evaluate the efficacy of PERT to improve clinical outcomes among children with ARP or CP.

01 Jul 2024·Cell Reports Medicine

Intergenic risk variant rs56258221 skews the fate of naive CD4+ T cells via miR4464-BACH2 interplay in primary sclerosing cholangitis

Article

Author: Schwinge, Dorothee ; Evangelakos, Ioannis ; Lohse, Ansgar W ; Iuso, Nicola ; Poch, Tobias ; Schramm, Christoph ; Schäfer, Anne-Marie ; Sebode, Marcial ; Laschtowitz, Alena ; Franke, Andre ; Huber, Samuel ; Liebig, Laura A ; Hubner, Norbert ; Gilladi, Hilla ; Schlein, Christian ; Gagliani, Nicola ; Casar, Christian ; Krause, Jenny ; Folseraas, Trine ; Kunzmann, Lilly K ; Bahn, Jonas ; Galun, Eithan ; Engesæter, Lise K ; Steinmann, Silja ; Karlsen, Tom H

Primary sclerosing cholangitis (PSC) is an immune-mediated liver disease of unknown pathogenesis, with a high risk to develop cirrhosis and malignancies. Functional dysregulation of T cells and association with genetic polymorphisms in T cell-related genes were previously reported for PSC. Here, we genotyped a representative PSC cohort for several disease-associated risk loci and identified rs56258221 (BACH2/MIR4464) to correlate with not only the peripheral blood T cell immunophenotype but also the functional capacities of naive CD4⁺ T (CD4⁺ T_N) cells in people with PSC. Mechanistically, rs56258221 leads to an increased expression of miR4464, in turn causing attenuated translation of BACH2, a major gatekeeper of T cell quiescence. Thereby, the fate of CD4⁺ T_N is skewed toward polarization into pro-inflammatory subsets. Clinically, people with PSC carrying rs56258221 show signs of accelerated disease progression. The data presented here highlight the importance of assigning functional outcomes to disease-associated genetic polymorphisms as potential drivers of diseases.

100 Deals associated with Hadassah-Hebrew University Hospital

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100 Translational Medicine associated with Hadassah-Hebrew University Hospital

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Pipeline

Pipeline Snapshot as of 20 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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