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Background: Non-suicidal self-injury (NSSI) is common among adolescents receiving inpatient psychiatric treatment and the months post-discharge is a high-risk period for self-injurious behavior. Thus, identifying predictors that shape the course of post-discharge NSSI may provide insights into ways to improve clinical outcomes. Accordingly, we used machine learning to identify the strongest predictors of NSSI trajectories drawn from a comprehensive clinical assessment., Methods: The study included adolescents (N = 612; females n = 435; 71.1%) aged 13-19-years-old (M = 15.6, SD = 1.4) undergoing inpatient treatment. Youth were administered clinical interviews and symptom questionnaires at intake (baseline) and before termination. NSSI frequency was assessed at 1-, 3-, and 6-month follow-ups. Latent class growth analyses were used to group adolescents based on their pattern of NSSI across follow-ups., Results: Three classes were identified: Low Stable (n = 83), Moderate Fluctuating (n = 260), and High Persistent (n = 269). Important predictors of the High Persistent class in our regularized regression models (LASSO) included baseline psychiatric symptoms and comorbidity, past-week suicidal ideation (SI) severity, lifetime average and worst-point SI intensity, and NSSI in the past 30 days (bs = 0.75-2.33). Only worst-point lifetime suicide ideation intensity was identified as a predictor of the Low Stable class (b = -8.82); no predictors of the Moderate Fluctuating class emerged., Conclusions: This study found a set of intake clinical variables that indicate which adolescents may experience persistent NSSI post-discharge. Accordingly, this may help identify youth that may benefit from additional monitoring and support post-hospitalization., (© 2024 Association for Child and Adolescent Mental Health.)

Background: Patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA alterations have poor outcomes. MAGNITUDE found patients with homologous recombination repair gene alterations (HRR+), particularly BRCA1/2, benefit from first-line therapy with niraparib plus abiraterone acetate and prednisone (AAP). Here we report longer follow-up from the second prespecified interim analysis (IA2)., Patients and Methods: Patients with mCRPC were prospectively identified as HRR+ with/without BRCA1/2 alterations and randomized 1 : 1 to niraparib (200 mg orally) plus AAP (1000 mg/10 mg orally) or placebo plus AAP. At IA2, secondary endpoints [time to symptomatic progression, time to initiation of cytotoxic chemotherapy, overall survival (OS)] were assessed., Results: Overall, 212 HRR+ patients received niraparib plus AAP (BRCA1/2 subgroup, n = 113). At IA2 with 24.8 months of median follow-up in the BRCA1/2 subgroup, niraparib plus AAP significantly prolonged radiographic progression-free survival {rPFS; blinded independent central review; median rPFS 19.5 versus 10.9 months; hazard ratio (HR) = 0.55 [95% confidence interval (CI) 0.39-0.78]; nominal P = 0.0007} consistent with the first prespecified interim analysis. rPFS was also prolonged in the total HRR+ population [HR = 0.76 (95% CI 0.60-0.97); nominal P = 0.0280; median follow-up 26.8 months]. Improvements in time to symptomatic progression and time to initiation of cytotoxic chemotherapy were observed with niraparib plus AAP. In the BRCA1/2 subgroup, the analysis of OS with niraparib plus AAP demonstrated an HR of 0.88 (95% CI 0.58-1.34; nominal P = 0.5505); the prespecified inverse probability censoring weighting analysis of OS, accounting for imbalances in subsequent use of poly adenosine diphosphate-ribose polymerase inhibitors and other life-prolonging therapies, demonstrated an HR of 0.54 (95% CI 0.33-0.90; nominal P = 0.0181). No new safety signals were observed., Conclusions: MAGNITUDE, enrolling the largest BRCA1/2 cohort in first-line mCRPC to date, demonstrated improved rPFS and other clinically relevant outcomes with niraparib plus AAP in patients with BRCA1/2-altered mCRPC, emphasizing the importance of identifying this molecular subset of patients., Competing Interests: Disclosure KNC received consulting fees from Amgen, Astellas, AstraZeneca, Bayer, Janssen, Merck, Pfizer, POINT Biopharma, and Roche; and grants (to institution) from Amgen, AstraZeneca, Bayer, ESSA, Janssen, Merck, POINT Biopharma, and Roche. SS received honoraria from AstraZeneca, Bristol Myers Squibb, Janssen, Merck, and Novartis (DSM Committee Chair); and grants from AstraZeneca, Genentech, Merck, Novartis, and Pfizer. MRS received consulting or advisory fees from Amgen, Astellas, Bayer, Janssen, Eli Lilly, Novartis, and Pfizer; research funding from Bayer, ESSA, Janssen, Eli Lilly, and ORIC Pharmaceuticals; and travel, accommodations, and expense reimbursements from Amgen, Bayer, Janssen, and Eli Lilly. GA received honoraria from Astellas and Janssen; consulting or advisory fees from Abbott Laboratories, Astellas, AstraZeneca, Bayer, ESSA, Ferring, Janssen, Medivation, Millennium Pharmaceuticals, Novartis, Pfizer, Ventana Medical Systems, and Veridex; speakers’ bureau fees from Astellas, AstraZeneca, Ferring, Ipsen, Janssen, Sanofi, Takeda, and Ventana Medical Systems; research funding from Arno Therapeutics, Innocrin Pharma, and Janssen; has patents or other intellectual property or received royalties for abiraterone acetate; received travel, accommodations, or expense reimbursements from Abbott Laboratories, Astellas, Bayer, ESSA, Ferring, Janssen, Medivation, Pfizer, and Ventana Medical Systems; and is affiliated with the Institute of Cancer Research. MS received honoraria and consulting or advisory role fees from AstraZeneca, Astellas, Amgen, Ipsen, Johnson & Johnson, Merck, and Pfizer; grants (to institution) from Johnson & Johnson and Merck; and travel, accommodations, and expense reimbursements from Cipla, Ipsen, and Pfizer. DO received honoraria from Astellas, Bayer, and Janssen; consulting or advisory role fees from AstraZeneca, Bayer, Clovis Oncology, Daiichi Sankyo, Janssen, and Merck; research funding from Astellas, AstraZeneca, Bayer, Genentech/Roche, Janssen, Medivation, Merck, and Pfizer; and travel, accommodations, or expense reimbursements from Astellas, AstraZeneca, Bayer, Ipsen, Janssen, and Roche. EC received honoraria from Astellas, AstraZeneca, Bayer, Janssen, Merck, Pfizer, and Telix Pharmaceuticals; consulting or advisory fees from Astellas, AstraZeneca, Bayer, Daiichi Sankyo, Janssen, Merck, and Pfizer; grants (to institution) from AstraZeneca, Bayer, and Janssen; and travel, accommodations, or expense reimbursements from AstraZeneca, Bayer, Janssen, and Pfizer. GR received consulting or advisory role fees from Astellas, AstraZeneca (to institution), Bayer, Gilead (to institution), Janssen, Ipsen, and Pfizer; research funding from Bayer (to institution); honoraria for lectures/speakers’ bureau fees from AstraZeneca (to institution), Bayer, and Janssen; and travel, accommodations, or expense reimbursements from AstraZeneca, Bayer, and Janssen. AJPdSG received honoraria for lectures/speakers’ bureau fees from Adium Pharma, Astellas, AstraZeneca, Bayer, and Janssen; and travel, accommodations, and expense reimbursements from Astellas and Janssen. EJS has stock or other ownership of Fortis and Teon Therapeutics; received honoraria from Janssen and Johnson & Johnson; and received consulting or advisory role fees from Fortis and Janssen. DER received grants (to institution) from AstraZeneca, Bayer, Bristol Myers Squibb/Celgene, Promontory Therapeutics, and Taiho Pharma; consulting or advisory fees from AstraZeneca, Bayer, Bristol Myers Squibb/Celgene, Genentech, Myovant, and Promontory Therapeutics; and medical writing assistance from Genentech and Janssen. HG received consulting or advisory fees from Astellas, AstraZeneca, Ipsen, Janssen, Merck, Merck-Serono, and Pfizer; honoraria for lectures/speakers’ bureau fees from Ipsen and Merck; and received travel, accommodations, and expense reimbursements from AstraZeneca. EE received consulting or advisory fees, speakers’ bureau fees, and research funding from Astellas, AstraZeneca, Merck, Myovant Sciences, Novartis, Pfizer, and Sanofi. GEM, SD, DW, BD, KU, AdC, PF, and WK are employed by Janssen Research & Development, LLC. WJ has declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

BACKGROUND: Niraparib is a highly selective poly (adenosine diphosphateribose) polymerase-1 and poly (adenosine diphosphate-ribose) polymerase-2 inhibitor indicated for select patients with ovarian, fallopian tube, and primary peritoneal cancer. The phase 2 GALAHAD trial (NCT02854436) demonstrated that niraparib monotherapy is tolerable and efficacious in patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations, particularly those with breast cancer gene ( BRCA ) alterations who had progressed on prior androgen signaling inhibitor therapy and taxane-based chemotherapy. OBJECTIVE: To report the prespecified patient-reported outcomes analysis from GALAHAD. METHODS: Eligible patients with alterations to BRCA1 and/or BRCA2 ( BRCA cohort) and with pathogenic alterations in other HRR genes (other HRR cohort) were enrolled and received niraparib 300 mg once daily. Patient-reported outcome instruments included the Functional Assessment of Cancer Therapy-Prostate and the Brief Pain Inventory-Short Form. Changes from baseline were compared using a mixed-effect model for repeated measures. RESULTS: On average, health-related quality of life ( HRQoL) improved in the BRCA cohort by cycle 3 (mean change = 6.03; 95% CI = 2.76-9.29) and was maintained above baseline until cycle 10 (mean change = 2.84; 95% CI = -1.95 to 7.63), whereas the other HRR cohort showed no early change in HRQoL from baseline (mean change = -0.07; 95% CI = -4.69 to 4.55) and declined by cycle 10 (mean change = -5.10; 95% CI = -15.3 to 5.06). Median time to deterioration in pain intensity and pain interference could not be estimated in either cohort. CONCLUSIONS: Patients with advanced mCRPC and BRCA alterations treated with niraparib experienced more meaningful improvement in overall HRQoL, pain intensity, and pain interference compared with those with other HRR alterations. In this population of castrate, heavily pretreated patients with mCRPC and HRR alterations, stabilization, and improvement in HRQoL may be relevant to consider when making treatment decisions. DISCLOSURES: This work was supported by Janssen Research & Development, LLC (no grant number). Dr Smith has received grants and personal fees from Bayer, Amgen, Janssen, and Lilly; and has received personal fees from Astellas Pharma, Novartis, and Pfizer. Dr Sandhu has received grants from Amgen, Endocyte, and Genentech; has received grants and personal fees from AstraZeneca and Merck; and has received personal fees from Bristol Myers Squibb and Merck Serono. Dr George has received personal fees from the American Association for Cancer Research, Axess Oncology, Capio Biosciences, Constellation Pharma, EMD Serono, Flatiron, Ipsen, Merck Sharp & Dohme, Michael J. Hennessey Association, Millennium Medical Publishing, Modra Pharma, Myovant Sciences, Inc., NCI Genitourinary, Nektar Therapeutics, Physician Education Resource, Propella TX, RevHealth, LLC, and UroGPO; has received grants and personal fees from Astellas Pharma, AstraZeneca, Bristol Myers Squibb, and Pfizer; has received personal fees and nonfinancial support from Bayer and UroToday; has received grants from Calithera and Novartis; and has received grants, personal fees, and nonfinancial support from Exelixis, Inc., Sanofi, and Janssen Pharma. Dr Chi has received grants from Janssen during the conduct of the study; has received grants and personal fees from AstraZeneca, Bayer, Astellas Pharma, Novartis, Pfizer, POINT Biopharma, Roche, and Sanofi; and has received personal fees from Daiichi Sankyo, Merck, and Bristol Myers Squibb. Dr Saad has received grants, personal fees, and nonfinancial support from Janssen during the conduct of the study; and has received grants, personal fees, and nonfinancial support from AstraZeneca, Astellas Pharma, Pfizer, Bayer, Myovant, Sanofi, and Novartis. Dr Thiery-Vuillemin has received grants, personal fees, and nonfinancial support from Pfizer; has received personal fees and nonfinancial support from AstraZeneca, Janssen, Ipsen, Roche/Genentech, Merck Sharp & Dohme, and Astellas Pharma; and has received personal fees from Sanofi, Novartis, and Bristol Myers Squibb. Dr Olmos has received grants, personal fees, and nonfinancial support from AstraZeneca, Bayer, Janssen, and Pfizer; has received personal fees from Clovis, Daiichi Sankyo, and Merck Sharp & Dohme; and has received nonfinancial support from Astellas Pharma, F. Hoffman-LaRoche, Genentech, and Ipsen. Dr Danila has received research support from the US Department of Defense, the American Society of Clinical Oncology, the Prostate Cancer Foundation, Stand Up to Cancer, Janssen Research & Development, Astellas Pharma, Medivation, Agensys, Genentech, and CreaTV. Dr Gafanov has received grants from Janssen during the conduct of the study. Dr Castro has received grants from Janssen during the conduct of the study; has received grants and personal fees from Janssen, Bayer, AstraZeneca, and Pfizer; and has received personal fees from Astellas Pharma, Merck Sharp & Dohme, Roche, and Clovis. Dr Moon has received research funding from SeaGen, HuyaBio, Janssen, BMS, Aveo, Xencor, and has received personal fees from Axess Oncology, MJH, EMD Serono, and Pfizer. Dr Joshua has received nonfinancial support from Janssen; consulted or served in an advisory role for Neoleukin, Janssen Oncology, Ipsen, AstraZeneca, Sanofi, Noxopharm, IQvia, Pfizer, Novartis, Bristol Myers Squibb, Merck Serono, and Eisai; and received research funding from Bristol Myers Squibb, Janssen Oncology, Merck Sharp & Dohme, Mayne Pharma, Roche/Genentech, Bayer, MacroGenics, Lilly, Pfizer, AstraZeneca, and Corvus Pharmaceuticals. Drs Mason, Liu, Bevans, Lopez-Gitlitz, and Francis and Mr Espina are employees of Janssen Research & Development. Dr Mason owns stocks with Janssen. Dr Fizazi has participated in advisory boards and talks for Amgen, Astellas, AstraZeneca, Bayer, Clovis, Daiichi Sankyo, Janssen, MSD, Novartis/AAA, Pfizer, and Sanofi, with honoraria to his institution (Institut Gustave Roussy); has participated in advisory boards for, with personal honoraria from, Arvinas, CureVac, MacroGenics, and Orion. Study registration number: NCT02854436.

Purpose: Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including BRCA1/2 alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naïve mCRPC when combined with androgen receptor signaling inhibition., Methods: MAGNITUDE (ClinicalTrials.gov identifier: NCT03748641) is a phase III, randomized, double-blinded study that evaluates niraparib and abiraterone acetate plus prednisone (niraparib + AAP) in patients with (HRR+, n = 423) or without (HRR-, n = 247) HRR-associated gene alterations, as prospectively determined by tissue/plasma-based assays. Patients were assigned 1:1 to receive niraparib + AAP or placebo + AAP. The primary end point, radiographic progression-free survival (rPFS) assessed by central review, was evaluated first in the BRCA1/2 subgroup and then in the full HRR+ cohort, with secondary end points analyzed for the full HRR+ cohort if rPFS was statistically significant. A futility analysis was preplanned in the HRR- cohort., Results: Median rPFS in the BRCA1/2 subgroup was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.6 v 10.9 months; hazard ratio [HR], 0.53; 95% CI, 0.36 to 0.79; P = .001). In the overall HRR+ cohort, rPFS was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.5 v 13.7 months; HR, 0.73; 95% CI, 0.56 to 0.96; P = .022). These findings were supported by improvement in the secondary end points of time to symptomatic progression and time to initiation of cytotoxic chemotherapy. In the HRR- cohort, futility was declared per the prespecified criteria. Treatment with niraparib + AAP was tolerable, with anemia and hypertension as the most reported grade ≥ 3 adverse events., Conclusion: Combination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP., [Media: see text].

Niraparib (NIRA) is a highly selective inhibitor of poly (adenosine diphosphate-ribose) polymerase, PARP1 and PARP2, which play a role in DNA repair. The phase II QUEST study evaluated NIRA combinations in patients with metastatic castration-resistant prostate cancer who were positive for homologous recombination repair gene alterations and had progressed on 1 prior line of novel androgen receptor-targeted therapy. Results from the combination of NIRA with abiraterone acetate plus prednisone, which disrupts androgen axis signaling through inhibition of CYP17, showed promising efficacy and a manageable safety profile in this patient population., (© The Author(s) 2023. Published by Oxford University Press.)

The association between adolescents' involvement in sexual intercourse and their experiences with adolescent dating violence (ADV) is an understudied topic. This study examined this relationship for 178 Jamaican adolescents in Grades 9-11. The expectation that adolescents who reported having had sexual intercourse would report greater victimization and greater perpetration than adolescents who had not had intercourse was consistent only for sexual abuse. Analyses also showed that sexually experienced males perpetrated and experienced more psychological abuse compared to males who were not so experienced. These results suggest different experiences based on adolescents' sex and so support others' calls for ADV research to do more examinations by sex. Also, it endorses the importance of doing research on both victims and perpetrators of intimate abuse. Implications of these findings for sexual and relationship education of adolescents are discussed., (© Copyright 2022 Springer Publishing Company, LLC.)

Background: Metastatic castration-resistant prostate cancers are enriched for DNA repair gene defects (DRDs) that can be susceptible to synthetic lethality through inhibition of PARP proteins. We evaluated the anti-tumour activity and safety of the PARP inhibitor niraparib in patients with metastatic castration-resistant prostate cancers and DRDs who progressed on previous treatment with an androgen signalling inhibitor and a taxane., Methods: In this multicentre, open-label, single-arm, phase 2 study, patients aged at least 18 years with histologically confirmed metastatic castration-resistant prostate cancer (mixed histology accepted, with the exception of the small cell pure phenotype) and DRDs (assessed in blood, tumour tissue, or saliva), with progression on a previous next-generation androgen signalling inhibitor and a taxane per Response Evaluation Criteria in Solid Tumors 1.1 or Prostate Cancer Working Group 3 criteria and an Eastern Cooperative Oncology Group performance status of 0-2, were eligible. Enrolled patients received niraparib 300 mg orally once daily until treatment discontinuation, death, or study termination. For the final study analysis, all patients who received at least one dose of study drug were included in the safety analysis population; patients with germline pathogenic or somatic biallelic pathogenic alterations in BRCA1 or BRCA2 (BRCA cohort) or biallelic alterations in other prespecified DRDs (non-BRCA cohort) were included in the efficacy analysis population. The primary endpoint was objective response rate in patients with BRCA alterations and measurable disease (measurable BRCA cohort). This study is registered with ClinicalTrials.gov, NCT02854436., Findings: Between Sept 28, 2016, and June 26, 2020, 289 patients were enrolled, of whom 182 (63%) had received three or more systemic therapies for prostate cancer. 223 (77%) of 289 patients were included in the overall efficacy analysis population, which included BRCA (n=142) and non-BRCA (n=81) cohorts. At final analysis, with a median follow-up of 10·0 months (IQR 6·6-13·3), the objective response rate in the measurable BRCA cohort (n=76) was 34·2% (95% CI 23·7-46·0). In the safety analysis population, the most common treatment-emergent adverse events of any grade were nausea (169 [58%] of 289), anaemia (156 [54%]), and vomiting (111 [38%]); the most common grade 3 or worse events were haematological (anaemia in 95 [33%] of 289; thrombocytopenia in 47 [16%]; and neutropenia in 28 [10%]). Of 134 (46%) of 289 patients with at least one serious treatment-emergent adverse event, the most common were also haematological (thrombocytopenia in 17 [6%] and anaemia in 13 [4%]). Two adverse events with fatal outcome (one patient with urosepsis in the BRCA cohort and one patient with sepsis in the non-BRCA cohort) were deemed possibly related to niraparib treatment., Interpretation: Niraparib is tolerable and shows anti-tumour activity in heavily pretreated patients with metastatic castration-resistant prostate cancer and DRDs, particularly in those with BRCA alterations., Funding: Janssen Research & Development., Competing Interests: Declaration of interests MRS has received grants or contracts to their institution from Bayer, Janssen, Pfizer, AstraZeneca, and Lilly; has received consulting fees from Astellas Pharma, Novartis, Janssen, AstraZeneca, Bayer, Lilly, and Pfizer; and has participated on data safety monitoring boards, advisory boards, or both for Janssen, Pfizer, and AstraZeneca. HIS has a leadership role in Asterias Biotherapeutics; holds stock and other ownership interests in Asterias Biotherapeutics; received grants or contracts to their institution from Epic Sciences, Illumina, Menarini Silicon Biosystems, ThermoFisher, and AIQ Pharma; provided consulting to Ambry Genetics Corporation/Konica Minolta, Amgen (uncompensated), Bayer, ESSA Pharma (uncompensated), Menarini Silicon Biosystems (uncompensated), Pfizer, Sun Pharmaceuticals, and WCG Oncology; has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Sidney Kimmel Cancer Center—Jefferson Health; has received support for attending meetings or travel from Amgen, Bayer, ESSA Pharma, Menarini Silicon Biosystems, Epic Sciences, Pfizer, WCG Oncology, and Phosplatin; has patents planned, issued, or pending via their institution with BioNTech, Elucida Oncology, MabVax Therapeutics, and Y-mAbs Therapeutics; and has other financial or non-financial interests in Elsevier, Prostate Cancer Foundation (via institution), National Cancer Institute (via institution), Department of Defense (via institution), MabVax Therapeutics, and BioNTech. SS has received grants from Amgen, Advanced Accelerator Applications (a Novartis company), Merck Sharp & Dohme, AstraZeneca, and Genentech; has received grants and personal fees from AstraZeneca, Bristol Myers Squibb, and Merck Sharp & Dohme; and participated on a data safety monitoring board for Advanced Accelerator Applications (a Novartis company). EE has received grants or contracts, consulting fees, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Sanofi, Astellas, Pfizer, Myovant, Merck Sharp & Dohme, AstraZeneca, and Novartis, and has participated on data safety monitoring boards, advisory boards, or both for Sanofi, Astellas, Pfizer, Myovant, Merck Sharp & Dohme, AstraZeneca, and Novartis. PNL Jr has received grants or contracts from Janssen to their institution. EYY has received grants or contracts from Bayer, Dendreon, Merck Sharp & Dohme, Seagen, Taiho, Blue Earth, and Lantheus; and has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bayer, Clovis, Janssen, Merck Sharp & Dohme, Seagen, Sanofi, AbbVie, Advanced Accelerator Applications (a Novartis company), and Exelixis. DJG has received grants or contracts to their institution from Astellas, Bristol Myers Squibb, Calithera, Exelixis, Janssen, Novartis, Pfizer, and Sanofi; has received consulting fees from Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Constellation, Exelixis, Flatiron, IdeoOncology, Janssen, Merck, Myovant Sciences, Physician Education Resource, Pfizer, PlatformQ, Propella, RevHealth, Sanofi, Seattle Genetics, WebMD, and Xcures; has received payment or honoraria for lectures, presentation, speakers bureaus, manuscript writing, or educational events from Bayer, EMD Serono, Exelixis, Ipsen, Michael J Hennessey, Pfizer, Sanofi, UroGPO, and UroToday; has received payment for expert testimony from Wilmer Hale Attorneys; has received support for attending meetings or travel from Bayer, Exelixis, Sanofi, and UroToday; has participated on data safety monitoring boards, advisory boards, or both for Astellas, AstraZeneca, Janssen, and Modra; and holds a leadership or fiduciary role in the American Association for Cancer Research (senior editor), AstraZeneca (CAPI-281 study coordinator), Bristol Myers Squibb (study coordinator), Capio Biosciences (scientific advisory board), Millennium Medical Publishing (co-editor-in-chief, Clinical Advances in Hematology & Oncology), NCI Genitourinary (study coordinator), Nektar Therapeutics (study coordinator), and Pfizer (study coordinator). KNC has received grants or contracts to their institution from Janssen, AstraZeneca, Merck, Novartis, and Point Biopharma; has received consulting fees from Astellas, AstraZeneca, Janssen, Merck Sharp & Dohme, Novartis, Point Biopharma, and Roche; and has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Astellas, Janssen, Merck Sharp & Dohme, AstraZeneca, and Novartis. FS has received grants or contracts, consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events, and has received equipment, materials, drugs, medical writing, gifts, or other services from Janssen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Myovant, Sanofi, Novartis, and Pfizer; and has participated on data safety monitoring boards, advisory boards, or both for Janssen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Myovant, Sanofi, Novartis, and Pfizer. DO has received grants or contracts from AstraZeneca, Bayer, and Janssen; has received consulting fees from Clovis, Daiichi Sankyo, AstraZeneca, Bayer, Roche, Merck Sharp & Dohme, and Janssen; has received support for attending meetings or travel from AstraZeneca, Janssen, and Roche; and has participated on data safety monitoring boards, advisory boards, or both for Janssen, AstraZeneca, and Bayer. DCD has received consulting fees from Angle, Axiom, Janssen, Astellas, Medivation, Pfizer, Genzyme, and Agensys; and has other financial or non-financial interests (research support) in the US Department of Defense, the American Society of Clinical Oncology, the Prostate Cancer Foundation, Stand Up to Cancer, Janssen, Astellas, Medivation, Agensys, Genentech, and CreaTV. GEM, BME, KAU, PF, and AL-G are employees of Janssen Research & Development. GEM and PF own stocks with Janssen. XZ was an employee of Janssen at the time of this study. KAU has been listed as an inventor on a patent as an employee of Janssen Research & Development. KF has received consulting fees from AAA, Astellas, AstraZeneca, Bayer, Novartis, Janssen, Amgen, Pfizer, Orion, Curevac, and Sanofi; has received payment or honoraria from lectures, presentations, speakers bureaus, manuscript writing, or educational events from Astellas, AstraZeneca, Bayer, Janssen, Novartis, Merck Sharp & Dohme, Bristol Myers Squibb, and Orion; and has participated on data safety monitoring boards, advisory boards, or both for Astellas, AstraZeneca, Bayer, Novartis, Janssen, Amgen, Pfizer, Sanofi, Orion, and Curevac. OS declares no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The safety and immunogenicity of JNJ-64041809 (JNJ-809), a live-attenuated, double-deleted Listeria monocytogenes (LADD Lm)-based immunotherapy targeting 4 relevant prostate cancer antigens, was evaluated in a phase 1 study in patients with metastatic castration-resistant prostate cancer (mCRPC)., Methods: Men with progressive mCRPC who had received ≥2 prior approved therapies were enrolled. Primary study objectives were to determine the recommended phase 2 dose (RP2D) and to evaluate the safety and immunogenicity of JNJ-809., Results: A total of 26 patients received JNJ-809 (1 × 10 8 CFU (n = 6); 1 × 10 9 CFU (n = 20)). No dose-limiting toxicities were reported, and 1 × 10 9 CFU was selected as the RP2D. The most common adverse events (AEs) reported were chills (92%), pyrexia (81%), and fatigue (62%). The most frequent grade ≥3 AEs were lymphopenia (27%) and hypertension (23%). Serious AEs were reported in 27% of patients including 1 patient with grade 3 intestinal obstruction. JNJ-809 transiently induced peripheral cytokines, including interferon-γ, interleukin-10, and tumor necrosis factor-α. Of the 7 patients evaluable for T cell responses at the 1 × 10 9 CFU dose, evidence of post-treatment antigenic responses were observed in 6 to the Listeria antigen listeriolysin O and in 5 to ≥1 of the 4 encoded tumor antigens. Best overall response was stable disease in 13/25 response-evaluable patients. The study was terminated early as data collected were considered sufficient to evaluate safety and immunogenicity., Conclusions: JNJ-809 has manageable safety consistent with other LADD Lm-based therapies. Limited antigen-specific immune responses were observed, which did not translate into objective clinical responses., (© 2021. The Author(s).)

Introduction: JNJ-64041757 (JNJ-757) is a live, attenuated, double-deleted Listeria monocytogenes -based immunotherapy expressing human mesothelin. JNJ-757 was evaluated in patients with advanced NSCLC as monotherapy (phase 1) and in combination with nivolumab (phase 1b/2)., Methods: Patients with stage IIIB/IV NSCLC who had received previous therapy were treated with JNJ-757 (1 × 10 8 or 1 × 10 9 colony-forming units [CFUs]) alone (NCT02592967) or JNJ-757 (1 × 10 9 CFU) plus intravenous nivolumab 240 mg (NCT03371381). Study objectives included the assessment of immunogenicity, safety, and efficacy., Results: In the monotherapy study, 18 patients (median age 63.5 y; women 61%) were treated with JNJ-757 (1 × 10 8 or 1 × 10 9 CFU) with a median duration of 1.4 months (range: 0-29). The most common adverse events (AEs) were pyrexia (72%) and chills (61%), which were usually mild and resolved within 48 hours. Peripheral proinflammatory cytokines and lymphocyte activation were induced posttreatment with transient mesothelin-specific T-cell responses in 10 of 13 biomarker-evaluable patients. With monotherapy, four of 18 response-evaluable patients had stable disease of 16 or more weeks, including one patient with a reduction in target lesions. In the combination study, 12 patients were enrolled (median age 63.5 y; women 33%). The most common AEs with combination therapy were pyrexia (67%) and chills (58%); six patients had grade 3 AEs or greater, including two cases of treatment-related fatal pneumonitis. The best overall response for the combination was stable disease in four of nine response-evaluable patients., Conclusions: As monotherapy, JNJ-757 was immunogenic and tolerable, with mild infusion-related fever and chills. The limited efficacy of JNJ-757, alone or with nivolumab, did not warrant further investigation of the combination., (© 2020 The Authors.)

Postcontrast 3-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequences have reduced vascular and flow-related artifacts and high sensitivity to low gadolinium concentrations. We compared the performance of postcontrast spoiled gradient echo images to 3D-FLAIR in the detection of leptomeningeal metastases in 47 pediatric patients with brain tumors. We found 10 cases with more leptomeningeal signal abnormalities on 3D-FLAIR. Overall there were significantly more lesions on 3D-FLAIR than spoiled gradient echo sequences. We believe the increased detection of leptomeningeal signal abnormality is due to increased sensitivity for low concentrations of gadolinium in regions of early blood brain barrier breakdown. Our study was limited by the lack of leptomeningeal metastases in cerebrospinal fluid sampling. We plan to conduct future studies which will determine whether the time-based concentration of gadolinium affects the performance and results. Future studies will also require more cases of pathology-proven leptomeningeal disease.

Nivolumab is an immune checkpoint inhibitor (ICI) currently undergoing Phase III clinical trials for the treatment of glioblastoma. The authors present the case of a 10-year-old girl with glioblastoma treated with nivolumab under compassionate-use guidelines. After the first dose of nivolumab the patient developed hemiparesis, cerebral edema, and significant midline shift due to severe tumor necrosis. She was managed using intravenous dexamethasone and discharged on a dexamethasone taper. The patient's condition rapidly deteriorated after the second dose of nivolumab, demonstrating hemiplegia, seizures, and eventually unresponsiveness with a fixed and dilated left pupil. Computed tomography of her brain revealed malignant cerebral edema requiring emergency decompressive hemicraniectomy. Repeat imaging demonstrated increased size of the lesion, reflecting immune-mediated inflammation and tumor necrosis. The patient remained densely hemiplegic, but became progressively more interactive and was ultimately extubated. She resumed nivolumab several weeks later, but again her condition deteriorated with headache, vomiting, swelling at the craniectomy site, and limited right-sided facial movement following the sixth dose. MRI demonstrated severe midline shift and uncal herniation despite her craniectomy. Her condition gradually declined, and she died several days later under "do not resuscitate/do not intubate" orders. To the authors' knowledge, this represents the first case of malignant cerebral edema requiring operative intervention following nivolumab treatment for glioblastoma in a pediatric patient.

There is no curative treatment for patients with diffuse intrinsic pontine glioma (DIPG). However, with the recent availability of biopsy and autopsy tissue, new data regarding the biologic behavior of this tumor have emerged, allowing greater molecular characterization and leading to investigations which may result in improved therapeutic options. Treatment strategies must address both primary disease sites as well as any metastatic deposits, which may be variably sensitive to a particular approach.In this case report, we present a patient with DIPG treated with irradiation and serial investigational agents. The clinical, pathological and molecular phenotypes of both the progressive primary tumor as well as concomitant metastatic deposits obtained at autopsy are discussed. While some mRNA differences were demonstrated, all analyzed sites of disease shared similar mutational arrangements, suggesting that targeting the mutations of the primary tumor may be effective for all sites of disease., Competing Interests: All authors have no conflicts of interest to disclose.

Among brain tumors, the BRAF (V600E) mutation is frequently associated with pleomorphic xanthoastrocytomas (PXAs) and gangliogliomas (GGs). This oncogenic mutation is also detected in ~5 % of other pediatric low-grade gliomas (LGGs) including pilocytic astrocytomas (PAs) and diffuse astrocytomas. In the current multi-institutional study of 56 non-PXA/non-GG diencephalic pediatric LGGs, the BRAF (V600) mutation rate is 36 %. V600-mutant tumors demonstrate a predilection for infants and young children (

Purpose: Although functional differences have been described between patients with lower extremity bone sarcoma with amputation and limb-preservation surgery, differences have not clearly been shown between the two groups related to quality of life. The purpose of the study was to determine if there is a difference in overall quality of life in lower extremity bone sarcoma survivors related to whether they had an amputation or a limb-preservation procedure while identifying psychological differences for further evaluation. The main hypothesis was that sparing a person's limb, as opposed to amputating it, would result in a better quality of life., Patients and Methods: Eighty-two long-term survivors of lower extremity bone sarcoma were studied to make a comparison of the overall quality of life, pain assessment, and psychological evaluations in limb preservation and amputation patients. Forty-eight patients with limb preservation and thirty-four patients with amputations were enrolled in the study. Validated psychometric measures including the Quality of Life Questionnaire (QLQ), the Minnesota Multiphasic Personality Inventory, and visual analog scales were utilized., Results: The overall quality of life of patients with limb preservation was significantly higher than patients with amputation (p-value < 0.01). Significant differences were noted in the categories of material well-being, job satisfiers, and occupational relations., Conclusion: The overall quality of life of patients with limb-preservation appears to be better than for those patients with amputation based on the QLQ in patients surviving lower extremity bone sarcoma. Further analysis needs to verify the results and focus on the categories that significantly affect the overall quality of life.

The goal of this exploratory study was to examine correlates of sexual assault disclosure and social reactions in female victims with and without drinking problems. An ethnically diverse sample of sexual assault survivors was recruited from college, community, and mental health agencies. Ethnic minority women were less likely to disclose assault, and women with a greater number of traumatic life events disclosed assault more often. Although there were no differences in disclosure likelihood by drinking status; of those disclosing, problem drinkers told more support sources and received more negative and positive social reactions than nonproblem drinkers. Correlates of receiving negative social reactions were similar for normal and problem drinkers; however, negative social reactions to assault disclosure were related to more problem drinking for women with less frequent social interaction. Implications for future research and possible support interventions with problem-drinking victims are provided.

This prospective study used 3 years of longitudinal data to explore relationships among intimate partner violence (IPV), perceived emotional and material social support, employment stability, and job turnover among current and former female welfare recipients in the immediate post-welfare reform era. Higher levels of current IPV and lower levels of current social support predicted less stable future employment; however, current employment stability did not predict either future IPV or future social support. Current social support did not predict future IPV, and perceived social support did not mediate the relationship between IPV and employment stability during a 3-year period.

This study examined differences in male-perpetrated adult sexual assault experiences among women of various sexual orientations using a large urban convenience sample (N = 1,022). Results showed many similarities in disclosure to others, perceived helpfulness, and attributions of blame, but there were also differences by sexual orientation. Heterosexual women were more likely to experience completed sexual assault than lesbian or bisexual women. Lesbians were more likely to be assaulted by relatives than bisexual or heterosexual women. Finally, bisexual women disclosed the assault to the greatest number of formal support sources, were most likely to tell a romantic partner about the assault, received the fewest positive social reactions overall, and had higher posttraumatic stress disorder (PTSD) symptomatology.

Two factors potentially affect observers'attributions of responsibility to a rape survivor: how closely they identify with the survivor and how much they adhere to rape myths. To assess the impact of these factors, 157 female college students categorized by their sexual assault history and by their acceptance of rape myths, evaluated a sexual assault scenario. It was hypothesized that previously victimized participants would attribute less blame, and that those participants who self-identify as rape survivors would view the assault as rape more often than other participants. Neither hypothesis was supported. As expected, those who scored higher on the Rape Myths Acceptance Scale(RMAS) blamed the victim more and were less likely to believe rape had occurred. Only one subscale of the RMAS, Adversarial Sexual Beliefs, was consistently associated with participants'evaluation of the scenario, suggesting that this dimension may be especially important to understanding an observer's assessment of rape.

This article presents the descriptive results of a statewide evaluation of hotline, advocacy, and counseling services provided to sexual assault victims in Illinois. Collaborative efforts of a multidisciplinary research team and sexual assault service providers resulted in victim-sensitive evaluation measures and data that reflect, for the first time, the collective impact of services on rape victims across the state of Illinois. Results of the evaluation suggest that, overall, services provided to rape victims provided support, increased information and knowledge, and helped victims to understand options and make decisions. The evaluation approach is notable for its collaborative nature and its sensitivity to rape victims during help-seeking and delivery; however, due to the high levels of distress common among rape survivors, some evaluation methods may not be appropriate for crisis intervention services such as hotline or advocacy. Implications for future evaluation research and policy are noted.

The lungs and gastrointestinal tracts from 18 hunter-killed bighorn rams (Ovis canadensis californiana) were examined in total or in part for helminth parasites during a two-year study of three separate herds in Eastern Oregon. Prevalence was 100% with the lungworm Protostrongylus stilesi. The gastrointestinal fauna from 11 rams comprised Cooperia oncophora, Marshallagia marshalli, Nematodirus oiratianus, Oesophagostomum spp., Ostertagia occidentalis, O. ostertagi, Skrjabinema ovis, Trichostrongylus axei and Trichuris spp. Adult Wyominia tetoni and cysticerci of Taenia hydatigena were recovered from two of six livers examined. Additionally, searches for potential molluscan intermediate hosts for P. stilesi were conducted on one bighorn range. Snails identified as belonging to the genera Euconulus, Pupilla and Vallonia were found on both the summer and winter ranges.