{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T02:02:43Z","timestamp":1789437763801,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. pediatr. gastroenterol. nutr."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators (HEMTs) have significantly improved outcomes in people with cystic fibrosis (CF). Their impact on established pancreatic disease remains uncertain. We aimed to evaluate the effects of HEMTs on exocrine pancreatic function in children with CF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective dual\u2010center observational study included children with CF treated with HEMTs for at least 12 months at the CF centers of Naples and Florence, Italy. Patients received elexacaftor\/tezacaftor\/ivacaftor (ETI) or ivacaftor (IVA). Fecal elastase\u20101 (FE\u20101), body mass index (BMI) z\u2010score, sweat chloride, ppFEV1, pancreatic enzyme replacement therapy (PERT) use and history of recurrent acute pancreatitis (RAP) were evaluated at baseline and during follow\u2010up. Patients with EPI were categorized as responders if FE\u20101 increased by \u2265100\u2009\u03bcg\/g.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 136 children (median age 11 years) were included. At baseline, 116\/136 (85.3%) had EPI. Median FE\u20101 increased from 7.5\u2009\u03bcg\/g (interquartile range [IQR] 7.5\u201311) at baseline to 11.9\u2009\u03bcg\/g (IQR 7.5\u201321) after 12 months (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). An increase in FE\u20101 was observed in 55\/116 patients (47.4%), while a clinically relevant increase (\u2265\u2009100\u2009\u03bcg\/g) occurred in 5 patients at 12 months and in 3 additional patients at 24 months. One patient reached repeated FE\u20101 values in the pancreatic\u2010sufficient range and discontinued PERT under clinical and nutritional monitoring. Significant improvements were observed in BMI z\u2010score, ppFEV1, and sweat chloride (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Among pancreatic\u2010sufficient patients, none with prior RAP experienced recurrence during follow\u2010up.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Clinically meaningful FE\u20101 improvement in established EPI appears limited, although a subset of younger patients may show meaningful improvement. HEMTs may also reduce pancreatitis recurrence in pancreatic\u2010sufficient individuals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jpn3.70555","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:05:14Z","timestamp":1789041914000},"source":"Crossref","is-referenced-by-count":0,"title":["Exocrine pancreatic function and highly effective modulators: A dual center retrospective study"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2239-5776","authenticated-orcid":false,"given":"Raffaele","family":"Cerchione","sequence":"first","affiliation":[{"name":"Department of Translational Medical Sciences, Paediatric Unit, Cystic Fibrosis Regional Reference Center University of Naples Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0470-6839","authenticated-orcid":false,"given":"Antonella","family":"Tosco","sequence":"additional","affiliation":[{"name":"Department of Maternal and Child health Paediatric Unit, Cystic Fibrosis Regional Reference Center, A.O.U. Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3078-4662","authenticated-orcid":false,"given":"Chiara","family":"Cimbalo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Medicine Cystic Fibrosis Regional Reference Center, Meyer Children's Hospital IRCCS Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3407-2875","authenticated-orcid":false,"given":"Francesca","family":"Capasso","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Paediatric Unit, Cystic Fibrosis Regional Reference Center University of Naples Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Salvadori","sequence":"additional","affiliation":[{"name":"Department of Maternal and Child health Paediatric Unit, Cystic Fibrosis Regional Reference Center, A.O.U. Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5252-2941","authenticated-orcid":false,"given":"Gabriele","family":"Simonetti","sequence":"additional","affiliation":[{"name":"Department of Pediatric Medicine Cystic Fibrosis Regional Reference Center, Meyer Children's Hospital IRCCS Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3642-8928","authenticated-orcid":false,"given":"Cristina","family":"Fevola","sequence":"additional","affiliation":[{"name":"Department of Pediatric Medicine Cystic Fibrosis Regional Reference Center, Meyer Children's Hospital IRCCS Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8317-9928","authenticated-orcid":false,"given":"Daniela","family":"Dolce","sequence":"additional","affiliation":[{"name":"Department of Pediatric Medicine Cystic Fibrosis Regional Reference Center, Meyer Children's Hospital IRCCS Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8446-0861","authenticated-orcid":false,"given":"Alice","family":"Castaldo","sequence":"additional","affiliation":[{"name":"SC of Pneumology and UTSIR, AORN Santobono\u2010Pausilipon Naples Italy"},{"name":"Dipartimento di Sanit\u00e0 Pubblica University of Naples Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1106-4424","authenticated-orcid":false,"given":"Vito","family":"Terlizzi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Medicine Cystic Fibrosis Regional Reference Center, Meyer Children's Hospital IRCCS Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Sepe","sequence":"additional","affiliation":[{"name":"Department of Maternal and Child health Paediatric Unit, Cystic Fibrosis Regional Reference Center, A.O.U. Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2216474"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2017.06.011"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2006.01.005"},{"issue":"2","key":"e_1_2_8_5_1","first-page":"1","article-title":"Registro Italiano Fibrosi Cistica (RIFC). Rapporto 2021\u20102022 [Italian Cystic Fibrosis Registry (ICFR). Report 2021\u20102022]","volume":"48","author":"Campagna G","year":"2024","journal-title":"Epidemiol Prev"},{"issue":"1","key":"e_1_2_8_6_1","first-page":"S53","article-title":"Pancreatitis in cystic fibrosis: Presentation, medical and surgical management, and the impact of modulator therapies","volume":"59","author":"Milano RV","year":"2024","journal-title":"Pediatr Pulmonol"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2014.01.007"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2004.04.049"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004310000536"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2009.09.001"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anpedi.2025.503857"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2019.09.014"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(16)30032-7"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.24353"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.24454"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.24952"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.25065"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41395-018-0123-7"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2021.08.032"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/PG9.0000000000000096"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2018.05.018"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.71156"},{"issue":"26","key":"e_1_2_8_23_1","first-page":"S1569","article-title":"Consensus\u2010based guidance for the nutritional management of children with cystic fibrosis on ELEXACAFTOR\/TEZACAFTOR\/IVACAFTOR","volume":"1","author":"Katz T","year":"2026","journal-title":"J Cyst Fibros"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2025.09.004"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2025.07.015"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.914790"},{"key":"e_1_2_8_27_1","unstructured":"European Medicines Agency (EMA). Kaftrio (elexacaftor\/tezacaftor\/ivacaftor) Summary of Product Characteristics (Product Information EN).2026."},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2022.10.003"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2023.09.005"},{"key":"e_1_2_8_30_1","unstructured":"Clinical and Laboratory Standard Institute (CLSI). Sweat Testing: Sample Collection and Quantitative Analysis; Approved Guideline \u2010 Third Edition. CLSI document C34\u2010A2 (ISBN 1\u201356238\u2013713\u20108). 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