{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:42:16Z","timestamp":1790109736675,"version":"4.0.1"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T00:00:00Z","timestamp":1699228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and objectives<\/jats:title><jats:p>Initially developed as immunosuppressive agents, mammalian target of rapamycin (mTOR) inhibitors are currently used widely in the management of vascular malformations and tumors. The incidence of infectious complications in the vascular anomalies (VA) population is not well defined. The goal of this systematic review was to better define the types and severity of reported infectious complications in patients with VAs treated with mTOR inhibition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a systematic review conducted following PRISMA guidelines evaluating all research articles focused on infectious complications in patients with VAs treated with sirolimus or everolimus. Thirty articles including 1182 total patients and 316 infections (in 291 unique patients) were ultimately included.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The majority of infections were viral upper respiratory (<jats:italic>n<\/jats:italic>\u00a0=\u00a0137, 54%), followed by pneumonia (<jats:italic>n<\/jats:italic>\u00a0=\u00a053, 20%), and cutaneous infections (<jats:italic>n<\/jats:italic>\u00a0=\u00a020, 8%). There were six total infection\u2010related fatalities, which all occurred in patients younger than 2\u00a0years. Two cases of <jats:italic>Pneumocystis jirovecii<\/jats:italic> pneumonia (PJP) were reported. These were infants with kaposiform hemangioendothelioma (KHE) who were also treated with steroids and did not receive PJP prophylaxis. Almost one\u2010third (<jats:italic>n<\/jats:italic>\u00a0=\u00a096, 32%) of infectious complications were graded 3\u20134 according to Common Terminology Criteria for Adverse Events (CTCAE) criteria. Details of patient age, subtype of VA, and timing of infection were lacking from many reports.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Most infectious complications reported in patients with VA on mTOR inhibitors were viral respiratory infections and non\u2010severe. Bacteremia, infectious fatalities, and PJP are exceedingly rare. Future studies are needed to clarify the spectrum of infectious risks in VA patients and to provide guidance for infection prevention.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.30758","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T07:34:46Z","timestamp":1699342486000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Infectious complications of vascular anomalies treated with sirolimus: A systematic review"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2336-5764","authenticated-orcid":false,"given":"Rachel","family":"Kalbfell","sequence":"first","affiliation":[{"name":"Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Cohen\u2010Cutler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Pediatric Oncology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Grisham","sequence":"additional","affiliation":[{"name":"St. Louis Children's Hospital  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Bereitschaft","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Hematology\/Oncology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7316-8643","authenticated-orcid":false,"given":"Alexandra J.","family":"Borst","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Pediatric Oncology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abby M.","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Hematology\/Oncology Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Department of Pediatrics Division of Infectious Diseases Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel N.","family":"Willis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Hematology\/Oncology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Yaeger","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7658-8096","authenticated-orcid":false,"given":"Julie","family":"Blatt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Hematology\/Oncology University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2456-2476","authenticated-orcid":false,"given":"Bryan A.","family":"Sisk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Hematology\/Oncology Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Department of Medicine Bioethics Research Center Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-49980-8_31"},{"key":"e_1_2_9_3_1","unstructured":"ISSVA.ISSVA classification of vascular anomalies.ISSVA;2018. 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