Neuropsychology consultation to identify learning disorders in children and adolescents: a proposal based on lessons learned during the COVID-19 pandemic.

Learning disorders are common neurodevelopmental conditions, occurring both idiopathically and in the context of other medical conditions. They are frequently comorbid with other neurodevelopmental and psychiatric conditions. Delayed identification and treatment have been associated with significant negative psychosocial consequences. The need for pediatric neuropsychologists to efficiently screen for learning disorders is likely to increase in the months and years following the COVID-19 pandemic, which has severely disrupted access to educational services, especially for children who also face racial and economic disparities. In this paper, we describe a consultation model that can be used to screen for learning disorders and can be completed using both in-person and telemedicine visits. Implementation may result in earlier intervention for struggling children, increase access to neuropsychological services without increasing wait times for comprehensive evaluations, and provide opportunities for collaborations with other health professionals (e.g., pediatricians, therapists, psychiatrists, and neurologists).

Pembrolizumab for advanced prostate adenocarcinoma: findings of the KEYNOTE-028 study.

Background: Patients with castration-resistant prostate cancer derive only modest clinical benefit from available therapies. Blockade of the inhibitory programmed death 1 (PD-1) receptor by monoclonal antibodies has been effective in several malignancies. Results from the prostate adenocarcinoma cohort of the nonrandomized phase Ib KEYNOTE-028 trial of pembrolizumab in advanced solid tumors are presented. Materials and methods: Key eligibility criteria included advanced prostate adenocarcinoma, unsuccessful standard therapy, measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), and PD-1 ligand (PD-L1) expression in ≥1% of tumor or stromal cells. Patients received pembrolizumab 10 mg/kg every 2 weeks until disease progression or intolerable toxicity for up to 24 months. Primary end point was objective response rate (ORR) per RECIST v1.1 by investigator review. Results: Median patient age in this cohort (n = 23) was 65 years; 73.9% of patients received at least two prior therapies for metastatic disease. There were four confirmed partial responses, for an ORR of 17.4% [95% confidence interval (CI) 5.0%-38.8%]; 8 of 23 (34.8%) patients had stable disease. Median duration of response was 13.5 months. Median progression-free survival (PFS) and overall survival (OS) were 3.5 and 7.9 months, respectively; 6-month PFS and OS rates were 34.8% and 73.4%, respectively. One patient remained on treatment at data cutoff. After a median follow-up of 7.9 months, 14 (60.9%) patients experienced treatment-related adverse events (TRAEs), most commonly nausea (n = 3, 13.0%). Four (17.3%) experienced grade 3/4 TRAEs: grade 3 peripheral neuropathy, grade 3 asthenia, grade 3 fatigue, and grade 4 lipase increase. No pembrolizumab-related deaths or discontinuations occurred. Conclusion: Pembrolizumab resulted in durable objective response in a subset of patients with heavily pretreated, advanced PD-L1-positive prostate cancer, and its side effect profile was favorable. ClinicalTrials.gov Identifier: NCT02054806.

Efficacy of the nanoparticle-drug conjugate CRLX101 in combination with bevacizumab in metastatic renal cell carcinoma: results of an investigator-initiated phase I-IIa clinical trial.

BACKGROUND: Anti-angiogenic therapies are effective in metastatic renal cell carcinoma (mRCC), but resistance is inevitable. A dual-inhibition strategy focused on hypoxia-inducible factor (HIF) is hypothesized to be active in this refractory setting. CRLX101 is an investigational camptothecin-containing nanoparticle-drug conjugate (NDC), which durably inhibits HIF1α and HIF2α in preclinical models and in gastric cancer patients. Synergy was observed in the preclinical setting when combining this NDC and anti-angiogenic agents, including bevacizumab. PATIENTS AND METHODS: Patients with refractory mRCC were treated every 2 weeks with bevacizumab (10 mg/kg) and escalating doses of CRLX101 (12, 15 mg/m(2)) in a 3 + 3 phase I design. An expansion cohort of 10 patients was treated at the recommended phase II dose (RP2D). Patients were treated until progressive disease or prohibitive toxicity. Adverse events (AEs) were assessed using CTCAE v4.0 and clinical outcome using RECIST v1.1. RESULTS: Twenty-two patients were response-evaluable in an investigator-initiated trial at two academic medical centers. RCC histologies included clear cell (n = 12), papillary (n = 5), chromophobe (n = 2), and unclassified (n = 3). Patients received a median of two prior therapies, with at least one prior vascular endothelial tyrosine kinase inhibitor therapy (VEGF-TKI). No dose-limiting toxicities were observed. Grade ≥3 AEs related to CRLX101 included non-infectious cystitis (5 events), fatigue (3 events), anemia (2 events), diarrhea (2 events), dizziness (2 events), and 7 other individual events. Five of 22 patients (23%) achieved partial responses, including 3 of 12 patients with clear cell histology and 2 of 10 patients (20%) with non-clear cell histology. Twelve of 22 patients (55%) achieved progression-free survival (PFS) of >4 months. CONCLUSIONS: CRLX101 combined with bevacizumab is safe in mRCC. This combination fulfilled the protocol's predefined threshold for further examination with responses and prolonged PFS in a heavily pretreated population. A randomized phase II clinical trial in mRCC of this combination is ongoing.

Stability and predictive value of self-report personality traits pre- and post-electroconvulsive therapy: a preliminary study.

The accuracy and value of personality assessment for depressed patients receiving electroconvulsive therapy (ECT) is an underexplored and controversial area. However, there are data suggesting that personality traits and personality disorders affect the ultimate outcome of depressed patients receiving a variety of somatic treatments including ECT. Despite these data, controversy continues regarding the advisability of evaluating personality functioning in patients with severe depression. This study sought to explore the stability and predictive value of self-reported personality traits in depressed patients undergoing ECT. Sixteen subjects completed a self-report test of personality functioning and the Beck Depression Inventory (BDI) before and after ECT treatment. The results showed that the majority of self-report personality traits were stable pre- and post-ECT treatment. However, major depressive disorder did significantly affect the report of avoidant, histrionic, aggressive-sadistic, and schizotypal personality traits. Treatment did not change the overall personality profile of these subjects. Furthermore, regression analysis controlling for pretreatment depression showed pretreatment borderline personality traits to be significantly related to the posttreatment depression scores (response to treatment). These findings suggest that routine administration of a standard self-report measure of personality may aid in the evaluation of and treatment planning for patients receiving ECT.

Protein-binding polyhedral boranes.

A series of polyhedral borane derivatives containing protein-binding functional groups has been synthesized. Problems encountered in earlier studies (low incorporation levels, gross precipitation of conjugates) have been overcome by including a water-solubilizing gluconamide group in the structure. This modification has allowed high levels of boron to be covalently bound to HGG, forming a completely water-soluble conjugate.