Background Genomic studies of high-grade/progressive meningiomas have reported a heterogeneous mutation spectrum, identifying few recurrently mutated genes. Most studies have been underpowered to detect genomic subclasses of aggressive meningiomas due to relatively small number of available samples. Here, we present a genomic survey of one of the largest multi-institutional cohorts of high-grade/progressive meningiomas to date. Methods 850 high-grade/progressive meningiomas, including 441 WHO grade 2 and 176 WHO grade 3 meningiomas and 220 progressive WHO grade 1 meningiomas, were tested as part of a clinical testing program by hybridization capture of 406 cancer-related genes to detect base substitutions, indels, amplifications, deletions, and rearrangements. Information from pathology reports, histopathology review, and patient clinical data was assessed. Results Genomic analyses converged to identify at least three distinct patterns of biologically-aggressive meningiomas. The first and most common contained NF2-mutant tumors (n = 426, 50%), was associated with male sex (64.4% %, p = 0.0001) and often harbored additional mutations in CDKN2A/B (24%), and the chromatin regulators ARID1A (9%), and KDM6A (6%). A second group (NF2-agnostic) featured TERT promoter (TERTp; n = 56) or TP53 mutations (n = 25) and were either NF2-mutant or wild-type, and displayed no association with either sex (p = 0.39). The remaining group generally lacked NF2 mutations, and accounted for 40% of the cases—with three subgroups. One consistent primarily of grade 3 lesions harboring alterations in chromatin regulators BAP1 (n = 22) or PBRM1 (n = 16). A second subgroup contained AKT1 (n = 26), PIK3CA (n = 14) and SMO (n = 7) mutant skull-based meningiomas, and a third mixed subgroup included 237 meningiomas with a heterogeneous spectrum of low frequency and non-recurrent alterations. Conclusions Our findings indicate that the patterns of genomic alterations in high-grade/progressive meningiomas commonly group into three different categories. The most common NF2-associated canonical group frequently harbored CDKN2A/B alterations, which is potentially amenable to targeted therapies. An NF2-agnostic group harbored frequent TERTp and TP53 mutations. The final subclass, distinct from the canonical NF2 mutant associated pathway, was partly characterized by BAP1/PBRM1 alterations (rhabdoid/papillary histology) or skull-base disease. Overall, these data increase our understanding of the pathobiology of high-grade/progressive meningiomas and can guide the design of clinical trials. IRB approval status Reviewed and approved by Western IRB; Protocol No. 20152817.
Little is known about how integrating peers into frontline staff might improve the quality of inpatient psychiatric care. In the current study, we interviewed 18 former adult patients of inpatient psychiatric facilities using semi-structured interviews. We first asked about positive and negative past experiences with traditional staff. We then asked participants to share their opinions on the potential benefits of peers as part of frontline staff. We identified themes through a joint inductive and deductive approach. Participants reported past positive experiences with traditional staff as being (a) personable and caring, (b) validating feelings and experiences, (c) de-escalating, and (d) providing agency. Past negative experiences included (a) not sharing information, (b) being inattentive, (c) not providing agency, (d) being dehumanizing/disrespectful, (e) incompetency, (f) escalating situations, and (g) being apathetic. Participants believed that peers as part of frontline staff could champion emotional needs in humanizing and nonjudgmental ways, help navigate the system, and disrupt power imbalances between staff and patients. Further research is needed to understand financial, organizational, and cultural barriers to integrating peers into frontline staff. [ Journal of Psychosocial Nursing and Mental Health Services, 60 (3), 15–22.]
Study Design: Retrospective cohort study. Objective: To identify disparities in surgical decision making for lumbar disc pathologies based on patient demographics, hospital characteristics, and temporal characteristics of admission. Methods: A retrospective analysis of patients admitted for surgical intervention of disc herniation or degeneration was performed to observe the effect of demographic, hospital, and admission-related factors on the decision to perform an isolated decompression or decompression with single level fusion using the National Inpatient Sample. Results: Of 84 953 patients with lumbar disc pathologies, 69 975 patients were treated electively, and 14 978 patients were treated nonelectively. Hispanic and Asian/Pacific Islander patients were less likely to receive a fusion for elective cases compared with White patients (odds ratio [OR] 0.88, P = .004; OR 0.70, P < .001, respectively). In elective cases, privately insured and self-paying patients were less likely to receive a fusion compared with Medicare patients (OR 0.83, P < .001; OR 0.66, P < .001, respectively), while this effect was limited to self-pay patients in nonelective cases (OR 0.44, P < .001). Urban teaching and nonteaching hospitals were less likely to perform fusions compared with rural hospitals in nonelective cases (OR 0.47, P < .001; OR 0.58, P < .001, respectively). Private for-profit hospitals were associated with higher rates of fusion in both elective and nonelective cases (OR 1.16, P = .003; OR 1.94, P < .001). Conclusion: This study illustrates disparities in the modality of surgical intervention for lumbar disc pathologies in terms of demographics, hospital characteristics, and temporal characteristics of admission. The development of more evidence-based guidelines is warranted to reduce variability seen in treatment regimens for these conditions.
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