Taking a BiTE out of Lymphoma: Bispecific Antibodies in B-Cell Non-Hodgkin Lymphoma.

B-cell non-Hodgkin's lymphoma (NHL) refers to a heterogenous group of diseases, all of which have a wide range of treatment strategies and patient outcomes. There have been multiple novel, immune-based therapies approved in NHL in the last decade, including bispecific antibodies (BsAbs) and chimeric antigen receptor therapy (CAR-T). With a host of new therapies, an important next step will be determining how these therapies should be sequenced in contemporary management strategies. This review seeks to offer a framework for the ways in which BsABs can be incorporated into the current management paradigm for NHL, with special attention paid to diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL).

Triple Combination Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% for Acne: Efficacy and Safety from a Pooled Phase 3 Analysis.

INTRODUCTION: A three-pronged approach to acne treatment combining an antibiotic, antimicrobial, and retinoid may be more efficacious than single/double treatments while potentially reducing antibiotic resistance. This study evaluated the efficacy and safety of the first fixed-dose, triple-combination topical acne product, clindamycin 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) using pooled phase 3 data. METHODS: In two identical phase 3 (N = 183; N = 180), double-blind, 12-week studies, participants aged ≥ 9 years with moderate-to-severe acne were randomized 2:1 to receive once-daily CAB or vehicle gel. Endpoints included ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in acne lesion counts. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were evaluated. RESULTS: At week 12, 50.0% of participants achieved treatment success with CAB versus 22.6% with vehicle gel (P < 0.001). CAB resulted in > 70% reductions in inflammatory and noninflammatory lesions at week 12 (77.9% and 73.0%, respectively), which were significantly greater than vehicle (57.9% and 48.2%; P < 0.001, both). Most TEAEs were of mild-moderate severity, and < 3% of CAB-treated participants discontinued study/treatment because of AEs. Transient increases from baseline in scaling, erythema, itching, burning, and stinging were observed with CAB, but resolved back to or near baseline values by week 12. CONCLUSIONS: The innovative fixed-dose, triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel was efficacious and well tolerated in children, adolescents, and adults with moderate-to-severe acne. Half of participants achieved clear/almost clear skin by 12 weeks, rates not previously seen in clinical studies of other topical acne products. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04214639 and NCT04214652.

Secukinumab in adult patients with lichen planus: Efficacy and safety results from the randomised, placebo-controlled, proof-of-concept PRELUDE study.

BACKGROUND: Patients with lichen planus (LP) refractory to available therapies often experience a high disease burden; representing a population with a clear unmet need for new treatments. OBJECTIVES: To evaluate the efficacy and safety of secukinumab 300 mg over 32 weeks in adult patients with biopsy-proven cutaneous LP (CLP), mucosal LP (MLP) or lichen planopilaris (LPP), inadequately controlled by topical corticosteroids. METHODS: PRELUDE was a, randomised, double-blind, placebo-controlled, Phase 2 proof-of-concept study that enrolled patients with CLP, MLP or LPP. Eligible patients were randomised to eithersecukinumab 300 mg every 4 weeks for 32 weeks (SECQ4W), or placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (SECQ2W) for 16 weeks. The primary endpoint was achievement of the newly designed Investigator's Global Assessment (IGA) score ≤2 at Week 16. RESULTS: Overall, 111 patients were randomised (n=37 each) to CLP, MLP and LPP cohorts. As the proof-of-concept criteria were not met for any of the 3 cohorts, the primary objective was not met. A numerically higher proportion of patients achieved IGA ≤2 response at Week 16 with SECQ4W vs. placebo in the MLP (37.5% [95% credibility interval (Crl): 20.3-57.2] vs. 23.1% [95% Crl: 6.5-49.2]) and LPP cohorts (37.5% [95% Crl: 20.2-57.3] vs. 30.8% [95% Crl: 10.8-57.6]). In the LPP cohort, a sustained response for IGA ≤2 from Week 16 to Week 32 was achieved with SECQ4W (Week 16: 37.5%; Week 32: 45.8%), and a substantial improvement was observed in IGA ≤2 response in patients of this cohort switching from placebo (Week 16: 30.8%) to SECQ2W after Week 16 (Week 32: 63.6%). The safety profile was consistent with the known profile of secukinumab and showed no new or unexpected signals. CONCLUSIONS: PRELUDE is the first randomised controlled basket trial evaluating interleukin-17A inhibition with secukinumab across 3 subtypes of LP. Secukinumab was well-tolerated and safe, showing different response rates across the 3 subtypes, with numerical IGA improvements in MLP and LPP, and no response in CLP. The study raises the question of a differential role of interleukin-17A across LP subtypes. The novel IGA score showed significant correlation with patient as well as physician reported outcome measurements. TRIAL REGISTRATION NUMBER: NCT04300296.

Rosacea Core Domain Set for Clinical Trials and Practice: A Consensus Statement.

Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.

Barriers and Facilitators Affecting Long-Term Antibiotic Prescriptions for Acne Treatment.

Importance: Dermatologists prescribe more oral antibiotics per clinician than clinicians in any other specialty. Despite clinical guidelines that recommend limitation of long-term oral antibiotic treatments for acne to less than 3 months, there is little evidence to guide the design and implementation of an antibiotic stewardship program in clinical practice. Objective: To identify salient barriers and facilitators to long-term antibiotic prescriptions for acne treatment. Design, Setting, and Participants: This qualitative study assessed data collected from stakeholders (including dermatologists, infectious disease physicians, dermatology resident physicians, and nonphysician clinicians) via an online survey and semistructured video interviews between March and August 2021. Data analyses were performed from August 12, 2021, to January 20, 2024. Main Outcomes and Measures: Online survey and qualitative video interviews developed with the Theoretical Domains Framework. Thematic analyses were used to identify salient themes on barriers and facilitators to long-term antibiotic prescriptions for acne treatment. Results: Among 30 participants (14 [47%] males and 16 [53%] females) who completed the study requirements and were included in the analysis, knowledge of antibiotic guideline recommendations was high and antibiotic stewardship was believed to be a professional responsibility. Five salient themes were to be affecting long-term antibiotic prescriptions: perceived lack of evidence to justify change in dermatologic practice, difficulty navigating patient demands and satisfaction, discomfort with discussing contraception, iPLEDGE-related barriers, and the absence of an effective system to measure progress on antibiotic stewardship. Conclusions and Relevance: The findings of this qualitative study indicate that multiple salient factors affect long-term antibiotic prescribing practices for acne treatment. These factors should be considered in the design and implementation of any future outpatient antibiotic stewardship program for clinical dermatology.

The feasibility of an adapted virtual mindfulness intervention for Special Olympics athletes and their caregivers.

BACKGROUND: Virtual mindfulness may be helpful for individuals with intellectual disabilities in the context of COVID-related disruptions of in-person programming, such as Special Olympics (SO). This study examined the feasibility of a virtual mindfulness intervention for SO athletes and their caregivers. METHOD: SO athletes (n = 44) and their caregivers (n = 29) participated in a 6-week adapted virtual mindfulness intervention. Athletes completed mindfulness and well-being questionnaires prior to, immediately following, and 3-months post-intervention. Caregivers completed questionnaires assessing their own stress, mindfulness, and well-being, as well as athlete mental health. Exit interviews were conducted immediately following the intervention. RESULTS: The intervention was feasible in terms of demand, implementation, acceptability, and limited testing efficacy. There were significant improvements in athlete well-being and mental health, and caregiver stress and mindfulness post-intervention. CONCLUSIONS: Adapted virtual mindfulness groups may be an effective intervention in improving the well-being of adults with intellectual disabilities and their caregivers.

Acalabrutinib, venetoclax and obinutuzumab in relapsed CLL: Final efficacy and ctDNA analysis of the CLL2-BAAG trial.

The phase 2 CLL2-BAAG trial tested the measurable residual disease (MRD)-guided triple combination of acalabrutinib, venetoclax and obinutuzumab after an optional bendamustine debulking in 45 patients with relapsed/refractory CLL (one patient was excluded from the analysis due to a violation of exclusion criteria). MRD was measured by flow cytometry (FCM, undetectable MRD <10-4) in peripheral blood (PB) and circulating tumor DNA (ctDNA) by digital droplet PCR (ddPCR) of variable-diversity-joining (VDJ) rearrangements and CLL-related mutations in plasma. MRD recurrence was defined as detectable ctDNA and/or MRD ≥10-4 after achieving both uMRD/undetectable ctDNA. The median number of previous treatments was 1 (range 1-4), 18 patients (40%) had received a BTK inhibitor (BTKi) and/or venetoclax prior to inclusion, 14/44 (31.8%) had TP53 aberrations, 34 (75.6%) had unmutated IGHV. With a median observation time of 36.3 months and all patients off treatment for a median of 21.9 months, uMRD <10-4 in PB was achieved in 42/45 patients (93.3%) at any time point, including 17/18 (94.4%) previously exposed to venetoclax/BTKi and 13/14 (92.9%) with TP53 aberrations. The estimated three-year progression-free and overall survival rates were 85.0% and 93.8%. Overall 585 paired FCM/ctDNA samples were analyzed and 18 MRD recurrences (5 with and 13 without clinical progression) occurred after the end of treatment. Twelve were first detected by ctDNA, three by FCM and three synchronously. Patients with earlier detection by ctDNA appeared to have genetically higher risk disease. In conclusion, time-limited MRD-guided acalabrutinib, venetoclax and obinutuzumab achieved deep remissions in almost all patients with relapsed/refractory CLL. The addition of ctDNA-based analyses to FCM MRD assessment seems to improve early detection of relapses. ClinicalTrials.gov Identifier: NCT03787264.

Lessons learned in measuring patient engagement in a Canada-wide childhood disability network.

BACKGROUND: The CHILD-BRIGHT Network, a pan-Canadian childhood disability research Network, is dedicated to patient-oriented research, where numerous stakeholders, including patient-partners, researchers, and clinicians are involved at different levels. The Network is committed to continuously improving the level of engagement and partnerships' impact. Measuring patient engagement is therefore important in reflecting on our practices and enhancing our approaches. We aimed to measure patient engagement longitudinally and explore in greater depth the perceived benefits, barriers and facilitators, and overall satisfaction with patient engagement, from the perspectives of the different stakeholders. METHODS: Patient engagement was measured using online surveys. In a longitudinal study design over a 3-years period (2018-2020) the Community-Based Participatory Research (CBPR) questionnaire was used. To enrich our understanding of patient engagement in Year 3, we employed the Public and Patient Engagement Evaluation Tool (PPEET) in a cross-sectional, convergent parallel mixed-method study design. Descriptive statistics and a thematic-based approach were used for data analysis. RESULTS: The CBPR questionnaire was completed by n = 167 (61.4% response rate), n = 92 (30.2% response rate), and n = 62 (14.2% response rate) Network members in Years 1, 2, and 3, respectively. Ninety-five (n = 95, 21.8% response rate) members completed the PPEET in Year 3. CBPR findings demonstrate a stable and high satisfaction level with patient engagement over time, where 94%, 86%, and 94% of stakeholders indicated that the project is a "true partnership" in Years 1, 2, and 3, respectively. In Years 2 and 3, we noted an improvement in patient-partners' comfort level in sharing their views and perspectives (92% and 91% vs. 74%). An increase in critical reflective trust (i.e., allowing for discussing and resolving mistakes) from Year 1 to 3 was found, both from the perspectives of patient-partners (51-65%) and researchers (48-75%). Using the PPEET, patient engagement factors (i.e., communications and supports for participation, ability to share views and perspectives) and impact were highly rated by most (80-100%) respondents. PPEET's qualitative responses revealed several patient engagement advantages (e.g., increased projects' relevance, enhanced knowledge translation), barriers (e.g., group homogeneity), facilitators (e.g., optimal communication strategies), and solutions to further improve patient engagement (e.g., provide clarity on goals). CONCLUSION: Our 3-years patient engagement evaluation journey demonstrated a consistent and high level of satisfaction with patient engagement within the Network and identified advantages, barriers, facilitators, and potential solutions. Improvements were observed in members' comfort in sharing their views and perspectives, along with an increase in critical reflective trust. These findings underscore the Network's commitment to enhancing patient engagement and provide valuable insights for continued improvement and optimization of collaborative efforts.

The CHILD-BRIGHT Network, a Canadian childhood disability research Network, is dedicated to patient-oriented research. It engages more than 300 diverse stakeholders, including patient-partners, researchers, and healthcare professionals. We conducted a 3-years study aimed to measure patient engagement over time and delve into the perceived benefits, barriers, and facilitators from the perspectives of the different members. We administered the Community-Based Participatory Research (CBPR) questionnaire in Years 1­3 (completed by 167, 92, and 62 members, respectively) and the Public and Patient Engagement Evaluation Tool (PPEET) in Year 3 (completed by 95 members). Through the CBPR, we identified in which research processes were Network members involved (e.g., defining the research question, results dissemination), appraised the partnership between researchers and other stakeholders such as patient-partners, and determined the type of trust in this partnership. The use of the PPEET allowed us to explore patient engagement impact and what factors facilitate and limit patient engagement (e.g., communication and supports). CBPR results showed a consistently high satisfaction level with patient engagement, with increased comfort among patient-partners in expressing their views over time, showcasing positive collaborative dynamics. Most stakeholders reported a "true partnership" in their engagement, indicating widespread belief in equitable relationships. Additionally, critical reflective trust, allowing for discussing and resolving mistakes in collaborative working activities, increased over the years, with the highest endorsement in Year 3, demonstrating growing trust among stakeholders. The PPEET findings showed positive ratings for communication, support, and impact of patient engagement. Its qualitative responses identified advantages (e.g., increased project relevance), barriers (e.g., lack of diversity in members' demographic characteristics), facilitators (e.g., effective communication), and suggested improvements (e.g., ensuring goal clarity). In conclusion, our project showed that the partnership between researchers and patient-partners was beneficial, satisfactory and evolved positively over time. The findings are encouraging provided the breadth of the Network, where hundreds of members are primarily connected virtually. We learned that: (1) It is possible to measure patient engagement in a large Network, both at one point in time and over time, and multiple tools can be used together to get a better picture. (2) Regular evaluations are important to optimize the partnership and its impact. (3) The partnership can be improved and strengthened with time through ongoing collaboration, open communication, and a commitment to address the evolving needs and dynamics of all stakeholders involved.

Noninvasive minimal residual disease assessment in relapsed/refractory large B-cell lymphoma using digital droplet PCR.

Although several promising approaches for the treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL) have been approved recently, it remains unclear which patients will ultimately achieve long-term responses. Circulating tumor (ct)DNA sequencing has emerged as a valuable tool to assess minimal residual disease (MRD). Correlations between MRD and outcomes have been shown in previously untreated DLBCL, but data on the repeated assessment of MRD in the dynamic course of rrDLBCL is limited. Here, we present an approach leveraging cost- and time-sensitivity of digital droplet (dd)PCR to repeatedly assess MRD in rrDLBCL and present proof-of-principle for its ability to predict outcomes.

Guidelines of care for the management of acne vulgaris.

BACKGROUND: Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older. OBJECTIVE: The objective of this study was to provide evidence-based recommendations for the management of acne. METHODS: A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements. LIMITATIONS: Analysis is based on the best available evidence at the time of the systematic review. CONCLUSIONS: These guidelines provide evidence-based recommendations for the management of acne vulgaris.

Consensus recommendations on the management of toxicity associated with CD3×CD20 bispecific antibody therapy.

ABSTRACT: Bispecific antibodies (BsAb) that target CD3 and CD20 represent a new milestone in the treatment of patients with B-cell non-Hodgkin lymphoma. These drugs have demonstrated remarkable single-agent activity in patients with heavily pretreated disease, and 3 drugs have so far received regulatory approvals in various countries. However, BsAbs can potentially lead to severe toxicity associated with T-cell activation, particularly cytokine release syndrome (CRS). The anticipated widespread use of these off-the-shelf products poses challenges for implementation and highlights the need for guidance in anticipating, mitigating, and managing adverse events. In clinical trials, guidance for the evaluation and treatment of CRS and neurotoxicity associated with BsAb therapy has been modeled after algorithms originally created for chimeric antigen receptor (CAR) T-cell therapies and other immune effector therapies, yet notable differences in timing, quality, and severity exist between the toxicities of BsAbs and CAR T-cell therapies. We therefore convened an international panel of academic and community practice physicians, advanced practitioners, registered nurses, and pharmacists with experience using CD3×CD20 BsAbs in clinical trial and off-trial settings to provide comprehensive, consensus-based recommendations specific to the assessment and management of CD3×CD20 BsAb-related toxicities.

Coherence of Parental Representations Following Therapy for Autistic Children.

Autistic children experience high rates of mental health challenges, and links have been found between child mental health and the parent-child relationship. As parents of autistic children are often actively involved in their child's treatment, it is important to consider aspects of the parent-child relationship within this context. The present study investigated changes in a component of the parent-child relationship, the coherence of parental representations, following participation in a 10-week cognitive behavioural therapy intervention designed to address autistic children's mental health challenges. Relationships were examined between coherence and child characteristics (i.e., autism symptoms, mental health), and associations with child treatment outcomes (i.e., mental health). Participants included 81 children (89% boys) aged 8 to 13 years and their parents (85% mothers) aged 35 to 54 years. Baseline levels of coherence were related to children's mental health symptoms but not autism symptoms. Although there were no significant changes in overall coherence across therapy, subscale-level improvements (i.e., concern, acceptance) emerged. Changes in coherence across therapy were linked with children's post-intervention behavioural symptoms and were approaching significance for internalizing problems, but were not associated with externalizing problems. It is critical to investigate factors that shape the coherence of parents' representations of their children, as this may provide insight into potential targets for intervention. Ascertaining whether participation in therapy improves parental coherence, and consequently child treatment outcomes, can advocate for parent-involved therapy, which will ultimately benefit the well-being of autistic children.

A Review of the Diagnostic and Therapeutic Gaps in Rosacea Management: Consensus Opinion.

Rosacea is a common, chronic inflammatory disease characterized by both fluctuating and fixed heterogeneous signs such as facial erythema, papules/pustules, telangiectasia, acute vasodilation (flushing), and phymatous changes, and symptoms such as cutaneous stinging and burning. The shift to a phenotype-based approach to rosacea management has improved the consistency of recommendations across recent published guidelines. Consistent and thorough guidance for the classification, diagnosis, and management of the disease is difficult, as the mechanisms underlying the development of rosacea are still not completely understood nor universally accepted. Here, we provide a critical review of current published guidance, and gaps in the knowledge and management of rosacea. We present the recently approved microencapsulated benzoyl peroxide as an effective topical treatment option for papulopustular rosacea. Benzoyl peroxide (BPO) has been used in acne management for many years; however, many clinicians perceive treatment of rosacea with any BPO formulation to be counterintuitive because of concerns of potential skin irritation, while the lack of an accepted mechanism of action on rosacea pathophysiology means that others may be hesitant to use BPO as a treatment. Minocycline foam 1.5% is also an option for the treatment of inflammatory lesions in rosacea, with a decreased risk of systemic adverse events compared with oral minocycline.

Parent, child, and family outcomes following Acceptance And Commitment Therapy for parents of autistic children: A randomized controlled trial.

LAY ABSTRACT: Parents of autistic children commonly experience difficulties with their own mental health. This study looked at the effects of a brief group-based Acceptance and Commitment Therapy program, developed for parents of autistic children, youth, and adults. ACT focuses on increasing psychological flexibility, which is the ability to be mindful and accepting of difficult thoughts and experiences, shown to be important for mental wellness. Participants included 54 parents of autistic people, ages 3-34. Parents were randomly divided into two groups: a Treatment group that received the intervention right away, and a Waitlist group that completed the program after the Treatment group completed the trial. All parents filled out questionnaires right before the program began, and at 3, 7, and 17 weeks after randomization. Compared to the group that was waiting to participate in the program, parents in the Treatment group reported greater improvements in depression and family distress, and these improvements were still present 4 months later. Parents in the Treatment group also reported short-term improvements in their positive feelings and personal goals, compared to those waiting. Results showed that ACT may help improve some aspects of mental health for parents of autistic children, but further research is recommended.

Best practices in the treatment of melasma with a focus on patients with skin of color.

BACKGROUND: Melasma is a chronic hypermelanosis of the skin that affects approximately 1% of the global population, predominantly affects women, and is more prevalent in skin of color. Melasma is a common driver for patients with skin of color to seek out a dermatologist for treatment, and ensuring the right approach for these patients is important because some treatments may be associated with adverse side effects. Because of the chronicity of the disease and established psychosocial and emotional impacts, there is a large need to ensure care follows the best available evidence on the treatment of patients with melasma. OBJECTIVE: Here, we summarized current available topical treatments for melasma with considerations dermatologists should have for their patients with skin of color. METHODS: Steering committee consensus on clinical best practices. RESULTS: We describe a flexible and focused treatment algorithm that reflects both treatment and maintenance periods that is a consensus of our extensive clinical experience. LIMITATIONS: Use of real-world evidence and potential for individual practice bias. CONCLUSION: Melasma can be challenging to treat, particularly in patients with skin of color, and our recommendations for best practices for patients in the United States are an important step toward standardizing care.

Entirely noninvasive outcome prediction in central nervous system lymphomas using circulating tumor DNA.

ABSTRACT: State-of-the-art response assessment of central nervous system lymphoma (CNSL) by magnetic resonance imaging is challenging and an insufficient predictor of treatment outcomes. Accordingly, the development of novel risk stratification strategies in CNSL is a high unmet medical need. We applied ultrasensitive circulating tumor DNA (ctDNA) sequencing to 146 plasma and cerebrospinal fluid (CSF) samples from 67 patients, aiming to develop an entirely noninvasive dynamic risk model considering clinical and molecular features of CNSL. Our ultrasensitive method allowed for the detection of CNSL-derived mutations in plasma ctDNA with high concordance to CSF and tumor tissue. Undetectable plasma ctDNA at baseline was associated with favorable outcomes. We tracked tumor-specific mutations in plasma-derived ctDNA over time and developed a novel CNSL biomarker based on this information: peripheral residual disease (PRD). Persistence of PRD after treatment was highly predictive of relapse. Integrating established baseline clinical risk factors with assessment of radiographic response and PRD during treatment resulted in the development and independent validation of a novel tool for risk stratification: molecular prognostic index for CNSL (MOP-C). MOP-C proved to be highly predictive of outcomes in patients with CNSL (failure-free survival hazard ratio per risk group of 6.60; 95% confidence interval, 3.12-13.97; P < .0001) and is publicly available at www.mop-c.com. Our results highlight the role of ctDNA sequencing in CNSL. MOP-C has the potential to improve the current standard of clinical risk stratification and radiographic response assessment in patients with CNSL, ultimately paving the way toward individualized treatment.

The role of thriving in mental health among people with intellectual and developmental disabilities during the COVID-19 pandemic in Canada.

BACKGROUND: The COVID-19 pandemic has had a negative impact on the mental health of people with intellectual and developmental disabilities. Numerous pandemic-related stressors experienced by people with intellectual and developmental disabilities may have impacted their ability to thrive, which has been linked to mental health outcomes. The current study examined the associations among COVID-19 stressors, thriving, and mental health problems among youth and adults with intellectual and developmental disabilities. METHOD: Caregivers of 159 people with intellectual and developmental disabilities between 12 and 35 years of age from Canada completed an online questionnaire. RESULTS: A mediation analysis revealed that COVID-19 stressors were positively associated with mental health problems, and that thriving partially mediated this association. CONCLUSION: Our findings suggest that experiences of thriving may be an important target for mental health support for people with intellectual and developmental disabilities.

Specific Polo-Like Kinase 1 Expression in Nodular Lymphocyte-Predominant Hodgkin Lymphoma Suggests an Intact Immune Surveillance Program.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare and relatively indolent B-cell lymphoma. Characteristically, the [lymphocyte-predominant (LP)] tumor cells are embedded in a microenvironment enriched in lymphocytes. More aggressive variants of mature B-cell and peripheral T-cell lymphomas exhibit nuclear expression of the polo-like kinase 1 (PLK1) protein, stabilizing MYC (alias c-myc) and associated with worse clinical outcomes. This study demonstrated expression of PLK1 in the LP cells in 100% of NLPHL cases (n = 76). In contrast, <5% of classic Hodgkin lymphoma cases (n = 70) showed PLK1 expression within the tumor cells. Loss-of-function approaches demonstrated that the expression of PLK1 promoted cell proliferation and increased MYC stability in NLPHL cell lines. Correlation with clinical parameters revealed that the increased expression of PLK1 was associated with advanced-stage disease in patients with NLPHL. A multiplex immunofluorescence panel coupled with artificial intelligence algorithms was used to correlate the composition of the tumor microenvironment with the proliferative stage of LP cells. The results showed that LP cells with PLK1 (high) expression were associated with increased numbers of cytotoxic and T-regulatory T cells. Overall, the findings demonstrate that PLK1 signaling increases NLPHL proliferation and constitutes a potential vulnerability that can be targeted with PLK1 inhibitors. An active immune surveillance program in NLPHL may be a critical mechanism limiting PLK1-dependent tumor growth.

Participation of Children With Autism During COVID-19: The Role of Maternal Participation.

BACKGROUND: Little is known about participation during adverse times. OBJECTIVES: This study described participation of children with autism aged 6 to 13 during COVID-19 pandemic and examined the extent to which child factors, mother's own participation, and environmental barriers/supports explain child participation in home and community. METHOD: A total of 130 mothers completed the Participation and Environment Measure for Children and Youth, the Health Promoting Activities Scale, functional issues checklist, and sociodemographic questionnaire. RESULTS: Children's participation frequency and involvement were significantly higher at home than in the community. In both settings, mothers desired change in 71% of activities. Multiple regression models indicated that child's age and mother's participation frequency significantly explained child's home involvement (R2 = 21%), where mother's participation (frequency) had a unique contribution (ΔR2 = 10.4%) at home but not in the community. CONCLUSION: Findings imply the importance of maternal participation to child's participation at home and suggest redirecting attention for enhancing family participation as a whole.

Facilitators and barriers in psychotherapy from the perspective of autistic adults: an enhanced critical incident study.

PURPOSE: A significant portion of autistic adults experience mental health challenges. Currently, the literature is incomplete when it comes to understanding the needs and preferences of autistic adults who receive therapy. This study elicited the perspectives of autistic adults, focusing on the facilitators, barriers and ways to enhance psychotherapy based on receiving this care for mental health problems. METHODS: Using the qualitative, exploratory approach of the Enhanced Critical Incident Technique, eight autistic adults took part in interviews. RESULTS: A total of 147 critical incidents were extracted from participant interviews and categories salient to therapeutic practice. The study identified key factors influencing therapy, such as trust and respect, practical approaches, client factors, structure of sessions, knowledge about autism, support for individualized needs, access to mental health services, and involvement of family/advocate. These factors were categorized into eight main areas relevant to therapeutic practice. CONCLUSIONS: Findings from this research reveal that psychotherapy with autistic adults is analogous to performing this work with non-autistic adults, in the sense that this work too entails elements of individually tailored treatment and the reliance on common therapeutic factors. There are also differences in this work that necessitate providers having foundational knowledge about autism. Learning directly from autistic adults' insights may help to improve upon the delivery of mental health care for autistic adults.