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Checkpoint inhibitor (CPI) therapy with anti-PD-1 antibodies has been associated with mixed outcomes in small cohorts of aggressive B-cell lymphoma patients following CAR T-cell therapy failure. To more definitively define CPI therapy efficacy in this population, we retrospectively evaluated clinical outcomes in a large cohort of 96 patients with aggressive B-cell lymphomas receiving CPI therapy after CAR-T failure across 15 U.S. academic centers. Most patients (53%) had DLBCL, were treated with axicabtagene ciloleucel (53%), relapsed early (≤180 days) after CAR-T (83%), and received pembrolizumab (49%) or nivolumab (43%). CPI therapy was associated with an overall response rate of 19% and a complete response rate of 10%. Median duration of response was 221 days. Median progression-free survival (PFS) and overall survival (OS) were 54 and 159 days, respectively. Outcomes to CPI therapy were significantly improved in patients with primary mediastinal B-cell lymphoma. PFS (128 versus 51 days) and OS (387 versus 131 days) were significantly longer in patients with late (>180 days) versus early (≤180 days) relapse after CAR-T. Grade ≥3 adverse events occurred in 19% of CPI-treated patients. Most patients (83%) died, commonly due to progressive disease. Only 5% had durable responses to CPI therapy. In the largest cohort of aggressive B-cell lymphoma patients treated with CPI therapy after CAR-T relapse, our results reveal poor outcomes, particularly among those relapsing early after CAR-T. In conclusion, CPI therapy is not an effective salvage strategy for most patients after CAR-T, where alternative approaches are needed to improve post-CAR-T outcomes.

Background: Understanding prognosis is critical to anticipating future public health needs, and to providing clinical care to individuals with psychotic disorders. However, the long-term course of remission and recovery in psychotic disorders remains unclear. In this cohort of 628 individuals followed for 25 years since first admission for psychosis, we describe the most common trajectories of illness course among those with psychotic disorders. Methods: Participants are from the Suffolk County Mental Health Project, an epidemiological study of first-admission psychosis. Participants were recruited from all 12 inpatient facilities in Suffolk County, New York between 1989 and 1995. 628 participants met criteria for the baseline sample. Data for the present study reflects remission and recovery at the 6-month, 24-month, 48-month, 10-year, 20-year, and 25-year follow-ups. 321 individuals were assessed at the 25-year follow-up. Common patterns of remission and recovery were assessed in both the baseline sample of 628 individuals, as well as the subsample of those observed at the 25-year follow up.Results: Common patterns of remission and recovery were assessed. In the baseline sample and 25-year subsample, among those with schizophrenia, the most common trajectory was one of no remission and no recovery. Among those with other psychotic disorders, in both baseline sample and the 25-year subsample, the modal pattern was one of intermittent remission and recovery. Those with psychotic disorders other than schizophrenia were more likely to experience stable remission (10.9%) and stable recovery (23.6%), than those with schizophrenia, where these outcomes were rare (0% and 0.7%, respectively). Discussion: These patterns emphasize the importance of sustained, long-term case for individuals with schizophrenia spectrum disorder and other psychoses. Though people with other psychoses often have periods of remission and recovery, the model longitudinal pattern is one of multiple episodes. Engagement in a long-term health care plan may help individuals detect and respond to these changes. Sustained remission and recovery are rare among people with schizophrenia spectrum disorders, and efforts should be put towards ensuring continual access to care, especially as they enter old age.

These are not normal times. As an editorial team, we felt that there was an urgency to reflect on our global experiences of the COVID-19 pandemic with our international colleagues. Instead of our planned debate series, we therefore commissioned a series of reflections on the impact of the pandemic on child and adolescent mental health throughout the world. We hope that you will find these reflections informative, thought-provoking, and in some cases, inspirational.

Asphyxiated infants treated with therapeutic cooling can have persistent oral feeding difficulty because of involvement of neural pathways in the brainstem, cortex, and basal ganglia. The goal is to predict the composite adverse outcome of death or persistent oral feeding difficulty using precooling/cooling attributes, and the severity and distribution of hypoxic–ischemic lesions, especially brainstem lesions on post-cooling brain magnetic resonance imaging (MRI). Retrospective review of 86 asphyxiated infants cooled from January 2006 to August 2014. Persistent feeding difficulty was defined as needing feeding support (gastrostomy tube (g-tube) or home gavage feeds) after discharge. Clinical and laboratory risk factors, and the brain MRI abnormalities including the presence of brainstem lesions were compared between infants with and without adverse outcome using univariate analysis. Significant variables were then analyzed in a stepwise logistic regression (LR) model. Infants with adverse outcome (n = 31, 4 died pre-discharge) had longer hospital stay (26 days, interquartile range (IQR) 19–43 vs. 13 days, IQR 9–20; p

Acetolactate synthase (ALS) enzymes have been isolated from numerous organisms including soybeans (Glycine max; GM-ALS) and catalyze the first common step in biosynthesis of branched chain amino acids. Expression of an ALS protein (GM-HRA) with two amino acid changes relative to native GM-ALS protein in genetically modified soybeans confers tolerance to herbicidal active ingredients and can be used as a selectable transformation marker. The safety assessment of the GM-HRA protein is discussed. Bioinformatics comparison of the amino acid sequence did not identify similarities to known allergenic or toxic proteins. In vitro studies demonstrated rapid degradation in simulated gastric fluid (

The glyphosate acetyltransferase (gat) gene from Bacillus licheniformis was subjected to multiple rounds of gene shuffling to optimize kinetics of corresponding GAT proteins to acetylate the herbicide active ingredient glyphosate. Genetically modified soybeans expressing the gat4601 gene (356043 soybeans) are tolerant to the application of glyphosate. The current manuscript reports the outcome of the allergenicity and toxicity assessment for the GAT4601 protein. Bioinformatic comparison of the amino acid sequence of GAT4601 did not identify similarities to known allergenic or toxic proteins. In vitro studies conducted with heterologously produced GAT4601 protein demonstrated that it was rapidly degraded in simulated gastric fluid containing pepsin (< 30 s) and in simulated intestinal fluid containing pancreatin (< 2 min) and completely inactivated at temperatures above 56 degrees C. The GAT4601 protein expressed in planta is not glycosylated and similar protein profiles were observed in flour extracts from 356043 soybeans and nontransgenic near isoline comparator soybeans (Jack) using serum from soy allergic persons. No evidence of adverse effects was observed in mice following acute oral exposure to 2000 mg/kg of GAT4601 protein or in a repeated dose dietary exposure study at doses of 800-1000 mg/kg/day. This comprehensive assessment demonstrates that the GAT4601 protein does not present a risk for adverse effects in humans when used in the context of agricultural biotechnology.

A single dose of endotoxin (lipopolysaccharide) from a common laboratory cloning and expression strain ( Escherichia coli BL21[DE3]) was administered to groups of male and female CD-1 mice ( n = 5/group) at doses up to 1,000,000 endotoxin units (EU) per mouse by oral gavage. The mice were observed for mortality, body weight effects, and clinical signs for 14 days after which they were sacrificed for gross organ necropsy. All mice survived until the scheduled sacrifice, no clinical signs of toxicity were observed, no test substance-related body weight losses occurred and no gross lesions were present at necropsy. Under the conditions of this study, oral administration of E. coli BL21(DE3) endotoxin to mice at a dose of up to 1,000,000 EU/mouse produced no evidence of toxicity.