Andrew James Giustini

Background: Although direct oral anticoagulants (DOACs) have been used in the adult population for over a decade, DOACs use has begun to rise in pediatric populations since FDA approval of rivaroxaban and dabigatran, DOACs offer several advantages for pediatric patients, to other anticoagulants, including a similar safety profile, minimal lab monitoring, and ease of administration. The rise in DOAC use has led to an increasing number of pediatric patients managed on DOACs presenting for elective and urgent procedures. Perioperative management of anticoagulation is often challenging for providers due to the lack of expert consensus guidelines and the difficulty in balancing a patient's thrombotic risk with bleeding risk for a given procedure. Aims: Using the most up to date literature, we provide a focused review on the perioperative management of DOACs in pediatric patients. Conclusions: This work presents a focused review for pediatric anesthesiologists on clinically available DOACs, perioperative monitoring and management of DOACs, as well as options and indications for reversal. While consensus expert practice guidelines are still needed, we hope this work will familiarize perioperative physicians with these agents, recommended uses, and potential perioperative management.

Background: Recent consternation over the number of unfilled Pediatric Anesthesiology fellowship positions in the United States compelled us to assess the change in the ratio of Pediatric Anesthesiology fellows to the number of graduating anesthesiology residents over the 14‐year period between 2008 and 2022. We also sought to report the total ratio of anesthesiology fellows to graduating residents and trends in the annual number of fellowship applicants relative to the number of Accreditation Council for Graduate Medical Education (ACGME)‐accredited anesthesiology fellowship positions by specialty.Methods: We used publicly available resources, including ACGME Data Resource Books, National Resident Matching Program (NRMP) data, San Francisco (SF) Match data, and American Board of Medical Specialties (ABMS) data, to determine the ratio of anesthesiology fellows to graduating anesthesiology residents and to compare the number of fellowship applicants to fellowship positions for Adult Cardiothoracic Anesthesiology, Critical Care Anesthesiology, Obstetric Anesthesiology, Pain Medicine and Pediatric Anesthesiology.Results: Since 2008, the ratio of ACGME‐accredited anesthesiology fellows to graduating residents increased from 0.36 in 2008 (2007 residency graduates) to 0.59 in 2022 (2021 residency graduates) and the ratio of Pediatric Anesthesiology fellows to graduating residents remained relatively stable from 0.10 to 0.11. The number of unmatched positions in Pediatric Anesthesiology increased from 17 in 2017 to 86 in 2023, and all ACGME‐accredited fellowships had more positions available than applicants in 2023.Conclusion: In the USA, while the ratio of Pediatric Anesthesiology fellowship graduates to anesthesiology residency graduates remained relatively constant from 2008 to 2022, this is likely a lagging indicator that has not yet accounted for the recent decrease in fellowship applicants. These findings refute prior estimates for a surplus in Pediatric Anesthesia supply in the USA and have significant implications for the future.

Summary: Phaeochromocytomas and paragangliomas are rare neuroendocrine tumours that often secrete catecholamines, which can cause dramatic swings in blood pressure and end‐organ damage. During surgical resection of these tumours, antihypertensive drug infusions are often required, but after resection patients may become vasoplegic, in part due to cessation of catecholamine secretion by the tumour in the context of pre‐operative α₁ adrenoceptor antagonism. Numerous medications have been used to treat vasoplegia in this setting, including noradrenaline, vasopressin and, more recently, angiotensin II. We report the case of a patient who experienced vasoplegia after phaeochromocytoma resection which was refractory to vasopressin and angiotensin II infusions but was successfully treated with high dose hydroxocobalamin.

Moyamoya disease is a rare, progressive cerebral vasculopathy which most commonly presents in the first and fourth decades of life. The mainstay of treatment is surgical revascularization; without treatment, most patients experience ischemic or hemorrhagic strokes. This report reviews moyamoya disease, its associated conditions, surgical treatment techniques, and anesthetic management of patients with moyamoya disease.

Citations are used to assess the impact of scientific authors, articles, and journals but may not fully reflect how they affect journal readership or the public. Newer metrics include article views and the Altmetric attention score (AAS),¹ which uses an algorithm to weight mentions of an article in social platforms such as Twitter and Facebook and in the news media. Prior investigations have shown only a modest association between these newer metrics and article citations, but none have assessed the pediatric literature, which may have a different readership.^1-4 The primary objective of this study was to examine the association between traditional metrics (citations), the AAS, and views of pediatric articles from 4 high-impact journals. Strong correlation would imply that citations-based metrics indicate popular engagement in scientific articles.

USP18 (ubiquitin-specific protease 18) removes ubiquitin-like modifier interferon stimulated gene 15 (ISG15) from conjugated proteins. USP18 null mice in a FVB/N background develop tumors as early as 2 months of age. These tumors are leiomyosarcomas and thus represent a new murine model for this disease. Heterozygous USP18 +/− FVB/N mice were bred to generate wild-type, heterozygous and homozygous cohorts. Tumors were characterized immunohistochemically and two cell lines were derived from independent tumors. Cell lines were karyotyped and their responses to restoration of USP18 activity assessed. Drug testing and tumorigenic assays were also performed. USP18 immunohistochemical staining in a large series of human leiomyosacomas was examined. USP18 −/− FVB/N mice spontaneously develop tumors predominantly on the back of the neck with most tumors evident between 6–12 months (80 % penetrance). Immunohistochemical characterization of the tumors confirmed they were leiomyosarcomas, which originate from smooth muscle. Restoration of USP18 activity in sarcoma-derived cell lines did not reduce anchorage dependent or independent growth or xenograft tumor formation demonstrating that these cells no longer require USP18 suppression for tumorigenesis. Karyotyping revealed that both tumor-derived cell lines were aneuploid with extra copies of chromosomes 3 and 15. Chromosome 15 contains the Myc locus and MYC is also amplified in human leiomyosarcomas. MYC protein levels were elevated in both murine leiomyosarcoma cell lines. Stabilized P53 protein was detected in a subset of these murine tumors, another feature of human leiomyosarcomas. Immunohistochemical analyses of USP18 in human leiomyosarcomas revealed a range of staining intensities with the highest USP18 expression in normal vascular smooth muscle. USP18 tissue array analysis of primary leiomyosarcomas from 89 patients with a clinical database revealed cases with reduced USP18 levels had a significantly decreased time to metastasis (P = 0.0441). USP18 null mice develop leiomyosarcoma recapitulating key features of clinical leiomyosarcomas and patients with reduced-USP18 tumor levels have an unfavorable outcome. USP18 null mice and the derived cell lines represent clinically-relevant models of leiomyosarcoma and can provide insights into both leiomyosarcoma biology and therapy.