Objectives/Hypothesis: To report key characteristics of the landscape of malpractice litigation with associated court proceedings in otolaryngology over the previous decade. Study Design: Retrospective database review. Methods: The LexisNexis database was queried to identify otolaryngology-related malpractices cases that yielded court opinions, jury verdicts, and settlements from federal and state courts across the United States from 2010 to 2019. Cases settled outside of court were not identifiable. Provider subspecialty, procedures, error type, legal allegations, and case outcomes were recorded. Frequency of error type was compared between otolaryngology subspecialties using Fisher exact tests. Results: Ninety-four medical malpractice cases related to otolaryngology with evidence of court proceedings were identified for the period between 2010 and 2019. An otolaryngologist was named as the sole defendant in 39 cases (41%). Rhinology was the most frequently implicated subspecialty (28% of all cases), followed by head and neck surgery (17%) and facial plastics (7%). Improper surgical performance was cited in nearly half of the identified cases (49%), followed by failure to diagnose/refer/treat (32%). Outcome and liability data were available for 56 cases (60%). Of these 56 cases, 50 (89%) were ruled in favor of the defendant otolaryngologist. Of the cases ruled in favor of the plaintiff, the average indemnity was $4.24 M (range, $150,000 M-$10.25 M). Fisher exact tests demonstrated statistically significant differences in consent issues (P = .040), failure to diagnose/refer/treat (P = .024), and improper surgical performance (P = .026) between subspecialties. Conclusions: In a limited, database-derived sample of medical malpractice cases involving otolaryngologists, trends in error type by subspecialty may warrant further investigation to identify specialty-wide and subspecialty-specific areas of practice improvement and education.
High hyperdiploidy (HD) is the most common cytogenetic subtype of childhood acute lymphoblastic leukemia (ALL), and a higher incidence of HD has been reported in ALL patients with congenital cancer syndromes. We assessed the frequency of predisposing germline mutations in 57 HD‐ALL patients from the California Childhood Leukemia Study via targeted sequencing of cancer‐relevant genes. Three out of 57 patients (5.3%) harbored confirmed germline mutations that were likely causal, in NBN, ETV6, and FLT3, with an additional six patients (10.5%) harboring putative predisposing mutations that were rare in unselected individuals (<0.01% allele frequency in the Exome Aggregation Consortium, ExAC) and predicted functional (scaled CADD score ≥ 20) in known or potential ALL predisposition genes (SH2B3, CREBBP, PMS2, MLL, ABL1, and MYH9). Three additional patients carried rare and predicted damaging germline mutations in GAB2, a known activator of the ERK/MAPK and PI3K/AKT pathways and binding partner of PTPN11‐encoded SHP2. The frequency of rare and predicted functional germline GAB2 mutations was significantly higher in our patients (2.6%) than in ExAC (0.28%, P = 4.4 × 10−3), an observation that was replicated in ALL patients from the TARGET project (P = .034). We cloned patient GAB2 mutations and expressed mutant proteins in HEK293 cells and found that frameshift mutation P621fs led to reduced SHP2 binding and ERK1/2 phosphorylation but significantly increased AKT phosphorylation, suggesting possible RAS‐independent leukemogenic effects. Our results support a significant contribution of rare, high penetrance germline mutations to HD‐ALL etiology, and pinpoint GAB2 as a putative novel ALL predisposition gene.
Adult-onset hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease of immune hyperactivation. Unlike pediatric HLH, adult HLH is rarely driven by germline genetic variants. Though numerous precipitating etiologies have been identified, the reason that HLH only occurs in a subset of individuals and how other factors contribute to the disease remains unknown. We hypothesized that clonal hematopoiesis (CH), a state in which somatic mutations in blood cells cause an expanded population of mutant hematopoietic cells and drive an aberrant inflammatory state, could contribute to adult-onset HLH. In a highly annotated cohort of older adults with HLH we found that CH was more prevalent than in control cohorts. Using the adult-onset HLH mouse model in which repeated treatments of the TLR9 agonist, ODN1826, is delivered to the mouse, we observed that macrophages carrying mutations in Tet2, one of the most commonly mutated genes in CH, have an enhanced inflammatory response to TLR9 agonism. Finally, mice carrying Tet2 mutations in the hematopoietic compartment (a common model for CH) display an exaggerated response to TLR9 agonism including worse splenomegaly and anemia. Our data suggests that CH is more common in individuals with adult-onset HLH and can contribute to the pathophysiology of this disease.
Key Points Some germline variants are predicted to disrupt protein function in HLH-associated genes. Such variants are neither enriched in adult-onset HLH nor associated with specific clinical or laboratory features of HLH.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.