Oncologic Safety of Close Margins in Patients With Low- to Intermediate-Grade Major Salivary Gland Carcinoma.

Importance: Postoperative radiation therapy for close surgical margins in low- to intermediate-grade salivary carcinomas lacks multi-institutional supportive evidence. Objective: To evaluate the oncologic outcomes for low- and intermediate-grade salivary carcinomas with close and positive margins. Design, Setting, and Participants: The American Head and Neck Society Salivary Gland Section conducted a retrospective cohort study from 2010 to 2019 at 41 centers. Margins were classified as R0 (negative), R1 (microscopically positive), or R2 (macroscopically positive). R0 margins were subclassified into clear (>1 mm) or close (≤1 mm). Data analysis was performed from June to October 2023. Main Outcomes and Measures: Main outcomes were risk factors for local recurrence. Results: A total of 865 patients (median [IQR] age at surgery, 56 [43-66] years; 553 female individuals [64%] and 312 male individuals [36%]) were included. Of these, 801 (93%) had parotid carcinoma and 64 (7%) had submandibular gland carcinoma, and 748 (86%) had low-grade tumors and 117 (14%) had intermediate-grade tumors, with the following surgical margins: R0 in 673 (78%), R1 in 168 (19%), and R2 in 24 (3%). Close margins were found in 395 of 499 patients with R0 margins (79%), for whom margin distances were measured. A total of 305 patients (35%) underwent postoperative radiation therapy. Of all 865 patients, 35 (4%) had local recurrence with a median (IQR) follow-up of 35.3 (13.9-59.1) months. In patients with close margins as the sole risk factor for recurrence, the local recurrence rates were similar between those who underwent postoperative radiation therapy (0 of 46) or observation (4 of 165 [2%]). Patients with clear margins (n = 104) had no recurrences. The local recurrence rate in patients with R1 or R2 margins was better in those irradiated (2 of 128 [2%]) compared to observed (13 of 64 [20%]) (hazard ratio [HR], 0.05; 95% CI, 0.01-0.24). Multivariable analysis for local recurrence found the following independent factors: age at diagnosis (HR for a 10-year increase in age, 1.33; 95% CI, 1.06-1.67), R1 vs R0 (HR, 5.21; 95% CI, 2.58-10.54), lymphovascular invasion (HR, 4.47; 95% CI, 1.43-13.99), and postoperative radiation therapy (HR, 0.10; 95% CI, 0.04-0.29). The 3-year local recurrence-free survivals for the study population were 96% vs 97% in the close margin group. Conclusions and Relevance: In this cohort study of patients with low- and intermediate-grade major salivary gland carcinoma, postoperative radiation therapy for positive margins was associated with decreased risk of local recurrence. In isolation from other risk factors for local recurrence, select patients with close surgical margins (≤1 mm) may safely be considered for observation.

Do Triarchic Psychopathy Components of New Zealand High-Risk Parolees Predict Probation Officer Relationship Quality, Quality of Life on Parole, and Recidivism?

The Triarchic Psychopathy Measure (TriPM) is a self-report scale based on the Triarchic Model that has been little used in research in the criminal justice system. We sought to examine associations between pre-release TriPM components, probation officer relationships, and parolee quality of life, both measured after 2 months in the community, and reconviction 12 months after release. Using data from 234 New Zealand male high-risk prisoners, we tested four multivariate models each across three timepoints. Pre-release, we found Boldness was not predictive, but Meanness predicted poorer relationship quality after 2 months, both from probation officer and parolee perspectives, with the former in turn predicting reconviction within 12 months. Disinhibition predicted 12-month recidivism regardless of relationship quality or external life circumstances. This relationship to recidivism was partially explained in the final model which linked Disinhibition and poorer subjective wellbeing, with the latter in turn predicting recidivism.

Sequentially inducible mouse models reveal that Npm1 mutation causes malignant transformation of Dnmt3a-mutant clonal hematopoiesis.

Clonal hematopoiesis (CH) is a common aging-associated condition with increased risk of hematologic malignancy. Knowledge of the mechanisms driving evolution from CH to overt malignancy has been hampered by a lack of in vivo models that orthogonally activate mutant alleles. Here, we develop independently regulatable mutations in DNA methyltransferase 3A (Dnmt3a) and nucleophosmin 1 (Npm1), observed in human CH and AML, respectively. We find Dnmt3a mutation expands hematopoietic stem and multipotent progenitor cells (HSC/MPPs), modeling CH. Induction of mutant Npm1 after development of Dnmt3a-mutant CH causes progression to myeloproliferative disorder (MPD), and more aggressive MPD is observed with longer latency between mutations. MPDs uniformly progress to acute myeloid leukemia (AML) following transplant, accompanied by a decrease in HSC/MPPs and an increase in myeloid-restricted progenitors, the latter of which propagate AML in tertiary recipient mice. At a molecular level, progression of CH to MPD is accompanied by selection for mutations activating Ras/Raf/MAPK signaling. Progression to AML is characterized by additional oncogenic signaling mutations (Ptpn11, Pik3r1, Flt3) and/or mutations in epigenetic regulators (Hdac1, Idh1, Arid1a). Together, our study demonstrates that Npm1 mutation drives evolution of Dnmt3a-mutant CH to AML and rate of disease progression is accelerated with longer latency of CH.

Do High-risk Prisoners Entering Treatment Have Clinically Impaired Cognitive Impulse Control?

Moffitt's (1993) developmental theory suggests that offenders on the life-course persistent (LCP) trajectory inherit or acquire neuropsychological deficits that compromise impulse control, and ultimately contribute to criminality. Empirical tests of this notion with adult LCP offenders are rare; the expected degree of impairment and which mechanisms are unclear. This research adopted a neurocognitive framework that proposes three cognitive mechanisms of impulse control: decision-making, perceptual control, and motor impulse control. Participants were 77 adult males, predominantly LCP prisoners completed five assessment tasks during pre-treatment assessment. Overall, proportions of impairment were unexpectedly low within and across cognitive impulse control domains. The highest proportions of impairment were observed on tasks requiring cognitive flexibility and sustained attention, and only cognitive flexibility uniquely predicted estimated pre-treatment violence risk. Results suggest the need to disaggregate cognitive from personality and behavioural variants of impulsivity and to further investigate how impaired cognitive flexibility affects progress during and following treatment.