Mitigating the Youth Vaping Epidemic through Increasing Screening Rates for Youth Vaping/E-Cigarette Use in Pediatrics.

INTRODUCTION: E-cigarette/vaping use in adolescents has increased 77.8% among high schoolers and 48.5% among middle schoolers in 2017-2018. As such, there is need for an effective workflow for screening for vaping. We aimed to increase screening rates of e-cigarette/vaping users from less than 1% to at least 50% in 6 months. METHODS: Screening for vaping in youth was implemented in a pediatric clinic in Northern California beginning in the summer of 2019 for 6 months. Depending on comorbidity, severity, and readiness to quit, patients were referred to treatment. Outcomes included screening rates, process measure included positive screening rates, and balancing measure was provider time. RESULTS: The clinic completed 1414 physicals with an average screening rate of 76% and a positive rate of 7.9%. The average age of patients was 15 (standard deviation = 1.3), 48% were female and 29% were Asian/Pacific Islander, 23% Hispanic, and 23% White. After 6 months, we met our goal in all but 1 plan-do-study-act (PDSA) cycle. DISCUSSION: We created a standardized workflow that identified teens who vaped. When compared to other studies, the positive rate for this study was low which is likely due to misinterpretation by staff of screening questions as well as the fact that data were collected during a clinic visit. CONCLUSIONS: It is important to find ways in which providers can mitigate this epidemic given the alarming increase in e-cigarette/vaping use among adolescents. This study furthers the effort to develop a screening method that is simple and brief, allowing physicians to intervene if necessary.

Phase I study of intraventricular administration of rituximab in patients with recurrent CNS and intraocular lymphoma.

PURPOSE: We previously determined that intravenous administration of rituximab results in limited penetration of this agent into the leptomeningeal space. Systemic rituximab does not reduce the risk of CNS relapse or dissemination in patients with large cell lymphoma. We therefore conducted a phase I dose-escalation study of intrathecal rituximab monotherapy in patients with recurrent CNS non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: The protocol planned nine injections of rituximab (10 mg, 25 mg, or 50 mg dose levels) through an Ommaya reservoir over 5 weeks. The safety profile of intraventricular rituximab was defined in 10 patients. RESULTS: The maximum tolerated dose was determined to be 25 mg and rapid craniospinal axis distribution was demonstrated. Cytologic responses were detected in six patients; four patients exhibited complete response. Two patients experienced improvement in intraocular NHL and one exhibited resolution of parenchymal NHL. High RNA levels of Pim-2 and FoxP1 in meningeal lymphoma cells were associated with disease refractory to rituximab monotherapy. CONCLUSION: These results suggest that intrathecal rituximab (10 to 25 mg) is feasible and effective in NHL involving the CNS.

Gene expression and angiotropism in primary CNS lymphoma.

Primary CNS lymphoma is an aggressive form of non-Hodgkin lymphoma whose growth is restricted to the central nervous system. We used cDNA microarray analysis to compare the gene expression signature of primary CNS lymphomas with nodal large B-cell lymphomas. Here, we show that while individual cases of primary CNS lymphomas may be classified as germinal center B-cell, activated B-cell, or type 3 large B-cell lymphoma, brain lymphomas are distinguished from nodal large B-cell lymphomas by high expression of regulators of the unfolded protein response (UPR) signaling pathway, by the oncogenes c-Myc and Pim-1, and by distinct regulators of apoptosis. We demonstrate that interleukin-4 (IL-4) is expressed by tumor vasculature as well as by tumor cells in CNS lymphomas. We also identify high expression in CNS lymphomas of several IL-4-induced genes, including X-box binding protein 1 (XBP-1), a regulator of the UPR. In addition, we demonstrate expression of the activated form of STAT6, a mediator of IL-4 signaling, by tumor cells and tumor endothelia in CNS lymphomas. High expression of activated STAT6 in tumors was associated with short survival in an independent set of patients with primary CNS lymphoma who were treated with high-dose intravenous methotrexate therapy.

The signature of seeds in resurrection plants: a molecular and physiological comparison of desiccation tolerance in seeds and vegetative tissues.

Desiccation-tolerance in vegetative tissues of angiosperms has a polyphyletic origin and could be due to 1) appropriation of the seed-specific program of gene expression that protects orthodox seeds against desiccation, and/or 2) a sustainable version of the abiotic stress response. We tested these hypotheses by comparing molecular and physiological data from the development of orthodox seeds, the response of desiccation-sensitive plants to abiotic stress, and the response of desiccation-tolerant plants to extreme water loss. Analysis of publicly-available gene expression data of 35 LEA proteins and 68 anti-oxidant enzymes in the desiccation-sensitive Arabidopsis thaliana identified 13 LEAs and 4 anti-oxidants exclusively expressed in seeds. Two (a LEA6 and 1-cys-peroxiredoxin) are not expressed in vegetative tissues in A. thaliana, but have orthologues that are specifically activated in desiccating leaves of Xerophyta humilis. A comparison of antioxidant enzyme activity in two desiccation-sensitive species of Eragrostis with the desiccation-tolerant E. nindensis showed equivalent responses upon initial dehydration, but activity was retained at low water content in E. nindensis only. We propose that these antioxidants are housekeeping enzymes and that they are protected from damage in the desiccation-tolerant species. Sucrose is considered an important protectant against desiccation in orthodox seeds, and we show that sucrose accumulates in drying leaves of E. nindensis, but not in the desiccation-sensitive Eragrostis species. The activation of "seed-specific" desiccation protection mechanisms (sucrose accumulation and expression of LEA6 and 1-cys-peroxiredoxin genes) in the vegetative tissues of desiccation-tolerant plants points towards acquisition of desiccation tolerance from seeds.

Comparative genome analysis of Vibrio vulnificus, a marine pathogen.

The halophile Vibrio vulnificus is an etiologic agent of human mortality from seafood-borne infections. We applied whole-genome sequencing and comparative analysis to investigate the evolution of this pathogen. The genome of biotype 1 strain, V. vulnificus YJ016, was sequenced and includes two chromosomes of estimated 3377 kbp and 1857 kbp in size, and a plasmid of 48,508 bp. A super-integron (SI) was identified, and the SI region spans 139 kbp and contains 188 gene cassettes. In contrast to non-SI sequences, the captured gene cassettes are unique for any given Vibrio species and are highly variable among V. vulnificus strains. Multiple rearrangements were found when comparing the 5.3-Mbp V. vulnificus YJ016 genome and the 4.0-Mbp V. cholerae El Tor N16961 genome. The organization of gene clusters of capsular polysaccharide, iron metabolism, and RTX toxin showed distinct genetic features of V. vulnificus and V. cholerae. The content of the V. vulnificus genome contained gene duplications and evidence of horizontal transfer, allowing for genetic diversity and function in the marine environment. The genomic information obtained in this study can be applied to monitoring vibrio infections and identifying virulence genes in V. vulnificus.

Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment.

Most lymphomas that involve the central nervous system are B-cell neoplasms that express the cell surface molecule CD20. After intravenous administration, rituximab can be reproducibly measured in the cerebrospinal fluid (CSF) in patients with primary central nervous system lymphoma; however, the CSF levels of rituximab are approximately 0.1% of serum levels associated with therapeutic activity in patients with systemic non-Hodgkin lymphoma. Because lymphomatous meningitis is a frequent complication of non-Hodgkin lymphoma, we have conducted an analysis of the safety and pharmacokinetics of direct intrathecal administration of rituximab using cynomolgus monkeys. No significant acute or delayed toxicity, neurologic or otherwise, was detected. Pharmacokinetic analysis suggests that drug clearance from the CSF is biphasic, with a terminal half-life of 4.96 hours. A phase 1 study to investigate the safety and pharmacokinetics of intrathecal rituximab in patients with recurrent lymphomatous meningitis will be implemented based on these findings.