Peer support for people living with hepatitis B virus-A foundation for treatment expansion.

Chronic hepatitis B infection (CHB) affects 300 million people worldwide and is being targeted by the United Nations 2030 Sustainable Development Goals (SDGs) and the World Health Organisation (WHO), working towards elimination of hepatitis B virus (HBV) as a public health threat. In this piece, we explore the evidence and potential impact of peer support to enhance and promote interventions for people living with CHB. Peer support workers (PSWs) are those with lived experience of an infection, condition or situation who work to provide support for others, aiming to improve education, prevention, treatment and other clinical interventions and to reduce the physical, psychological and social impacts of disease. Peer support has been shown to be a valuable tool for improving health outcomes for people living with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), but to date has not been widely available for communities affected by HBV. HBV disproportionately affects vulnerable and marginalised populations, who could benefit from PSWs to help them navigate complicated systems and provide advocacy, tackle stigma, improve education and representation, and optimise access to treatment and continuity of care. The scale up of peer support must provide structured and supportive career pathways for PSWs, account for social and cultural needs of different communities, adapt to differing healthcare systems and provide flexibility in approaches to care. Investment in peer support for people living with CHB could increase diagnosis, improve retention in care, and support design and roll out of interventions that can contribute to global elimination goals.

Opt-out testing for hepatitis B and C infections in adults attending the emergency department of a large London teaching hospital.

BACKGROUND: The National Health Service (NHS) in England commissioned opt-out testing in London Emergency Departments (ED) in April 2022 to allow early identification and management of hepatitis B (HBV) and hepatitis C virus (HCV) infection in patients unaware of their infection status. METHODS: All adults over the age of 16 undergoing blood tests in the ED at the Royal Free Hospital were tested for HBV surface antigen and anti-HCV IgG unless they opted out. Data was collected between the 12th of April and 22nd of August 2022. OUTCOME: Of 11,215 patients tested for HCV, 164 patients were found to be anti-HCV IgG positive, giving a seroprevalence rate of 1.46 %. 52 of the anti-HCV IgG positive patients did not have any previous HCV serology result. 23 of the anti-HCV IgG positive patients were also HCV RNA positive giving an RNA seroprevalence of 0.21 %, and 17 of those were new diagnoses of HCV viraemia. For HBV testing, 82 (0.73 %) out of 11,192 patients tested were found to be HBsAg positive, including one patient who presented acutely with a positive HBV core IgM. 39 of the HBsAg positive patients were previously unknown to us; of these, 9 had an HBV viral load of more than 2000 IU/mL, including 3 patients with positive HBV e antigen and one patient with hepatitis D virus co-infection. CONCLUSION: Opt-out screening of HBV and HCV in ED is effective at identifying patients with previously undiagnosed viral hepatitis infection and providing an opportunity to engage them in specialist care.

Identification and Optimization of RNA-Splicing Modulators as Huntingtin Protein-Lowering Agents for the Treatment of Huntington's Disease.

Huntington's disease (HD) is caused by an expanded CAG trinucleotide repeat in exon 1 of the huntingtin (HTT) gene. We report the design of a series of HTT pre-mRNA splicing modulators that lower huntingtin (HTT) protein, including the toxic mutant huntingtin (mHTT), by promoting insertion of a pseudoexon containing a premature termination codon at the exon 49-50 junction. The resulting transcript undergoes nonsense-mediated decay, leading to a reduction of HTT mRNA transcripts and protein levels. The starting benzamide core was modified to pyrazine amide and further optimized to give a potent, CNS-penetrant, and orally bioavailable HTT-splicing modulator 27. This compound reduced canonical splicing of the HTT RNA exon 49-50 and demonstrated significant HTT-lowering in both human HD stem cells and mouse BACHD models. Compound 27 is a structurally diverse HTT-splicing modulator that may help understand the mechanism of adverse effects such as peripheral neuropathy associated with branaplam.

Mortality rates among patients successfully treated for hepatitis C in the era of interferon-free antivirals: population based cohort study.

OBJECTIVES: To quantify mortality rates for patients successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals and compare these rates with those of the general population. DESIGN: Population based cohort study. SETTING: British Columbia, Scotland, and England (England cohort consists of patients with cirrhosis only). PARTICIPANTS: 21 790 people who were successfully treated for hepatitis C in the era of interferon-free antivirals (2014-19). Participants were divided into three liver disease severity groups: people without cirrhosis (pre-cirrhosis), those with compensated cirrhosis, and those with end stage liver disease. Follow-up started 12 weeks after antiviral treatment completion and ended on date of death or 31 December 2019. MAIN OUTCOME MEASURES: Crude and age-sex standardised mortality rates, and standardised mortality ratio comparing the number of deaths with that of the general population, adjusting for age, sex, and year. Poisson regression was used to identify factors associated with all cause mortality rates. RESULTS: 1572 (7%) participants died during follow-up. The leading causes of death were drug related mortality (n=383, 24%), liver failure (n=286, 18%), and liver cancer (n=250, 16%). Crude all cause mortality rates (deaths per 1000 person years) were 31.4 (95% confidence interval 29.3 to 33.7), 22.7 (20.7 to 25.0), and 39.6 (35.4 to 44.3) for cohorts from British Columbia, Scotland, and England, respectively. All cause mortality was considerably higher than the rate for the general population across all disease severity groups and settings; for example, all cause mortality was three times higher among people without cirrhosis in British Columbia (standardised mortality ratio 2.96, 95% confidence interval 2.71 to 3.23; P<0.001) and more than 10 times higher for patients with end stage liver disease in British Columbia (13.61, 11.94 to 15.49; P<0.001). In regression analyses, older age, recent substance misuse, alcohol misuse, and comorbidities were associated with higher mortality rates. CONCLUSION: Mortality rates among people successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals are high compared with the general population. Drug and liver related causes of death were the main drivers of excess mortality. These findings highlight the need for continued support and follow-up after successful treatment for hepatitis C to maximise the impact of direct acting antivirals.

Delivery of biannual ultrasound surveillance for individuals with cirrhosis and cured hepatitis C in the UK.

BACKGROUND: Previous studies show the uptake of biannual ultrasound (US) surveillance in patients with cirrhosis is suboptimal. Here, our goal was to understand in broader terms how surveillance is being delivered to cirrhosis patients with cured hepatitis C in the UK. METHODS: Hepatitis C cirrhosis patients achieving a sustained viral response (SVR) to antiviral therapies were identified from the national Hepatitis-C-Research-UK resource. Data on (i) liver/abdominal US examinations, (ii) HCC diagnoses, and (iii) HCC curative treatment were obtained through record-linkage to national health registries. The rate of US uptake was calculated by dividing the number of US episodes by follow-up time. RESULTS: A total of 1908 cirrhosis patients from 31 liver centres were followed for 3.8 (IQR: 3.4-4.9) years. Overall, 10 396 liver/abdominal USs were identified. The proportion with biannual US was 19% in the first 3 years after SVR and 9% for all follow-up years. Higher uptake of biannual US was associated with attending a liver transplant centre; older age and cirrhosis decompensation. Funnel plot analysis indicated significant inter-centre variability in biannual US uptake, with 6/29 centres outside control limits. Incident HCC occurred in 133 patients, of which 49/133 (37%) were treated with curative intent. The number of US episodes in the two years prior to HCC diagnosis was significantly associated with higher odds of curative-intent treatment (aOR: 1.53; 95% CI: 1.12-2,09; p = .007). CONCLUSIONS: This study provides novel data on the cascade of care for HCC in the UK. Our findings suggest biannual US is poorly targeted, inefficient and is not being delivered equitably to all patients.

Falling treatment uptake in the hepatitis C care cascade is a growing threat to achieving elimination.

Most high-income countries are not on track to achieve the World Health Organization hepatitis C elimination targets. As elimination programmes assess growing proportions of patients in community-based pathways, rates of treatment uptake may fall. We aimed to identify factors associated with DAA treatment uptake and measure changes in their prevalence over time. We performed a time-to-treatment analysis on 2728 patients approved for hepatitis C Direct-Acting Antiviral treatment in the North Central London region between January 2016 and October 2019. We investigated the association between treatment uptake and factors including assessment/treatment setting (hospital, drug service or prison), patient age, gender, injection drug use, harmful alcohol use, cirrhosis status and previous treatment. The likelihood of treatment uptake was reduced by three independent risk factors. These included assessment setting: prison-based or drug-service pathways (aHR 0.29 or 0.81 vs. hospital outpatient pathway, 95% CI 0.21-0.40 and 0.70-0.94 respectively, p < .001); being UK-born (aHR 0.89 vs. non-UK born, 0.82-0.98, p = .01); and history of harmful alcohol use (aHR 0.84 vs. no history, 0.72-0.99, p = .04). The average number of these risk factors for not starting treatment per patient increased over time (R2  = 0.66 p < .001). Independent of these, there was an additional 5% reduction in rate of treatment initiation in each successive year of the programme (aHR 0.95, 0.91-0.99, p = .02). In conclusion, disengagement from care before treatment uptake was found to be a growing threat to elimination. Despite provision of community-based test-to-cure pathways, there are persistent barriers to treatment uptake and these are increasing over time.

Fugitive methane emissions from two agricultural biogas plants.

This study quantified fugitive methane (CH4) losses from multiple sources (open digestate storages, digesters and flare) at two biogas facilities over one year, providing a much needed dataset integrating all major loss pathways and changes over time. Losses of CH4 from Facility A were primarily from digestate storage (5.8% of biogas CH4), followed by leakage/venting (5.5%) and flaring (0.2%). At Facility B, losses from digestate storage were higher (10.7%) due to shorter hydraulic retention time and lack of a screwpress. Fugitive emissions from leakage were initially 3.8% but were reduced to 0.6% after the dome membrane was repaired at Facility B. For biogas to have a positive impact on greenhouse gas emissions and provide a low-carbon fuel, it is important to minimize fugitive losses from digestate storage and avoid leakage during abnormal operation (leakage, roof failure).

Quantifying Huntingtin Protein in Human Cerebrospinal Fluid Using a Novel Polyglutamine Length-Independent Assay.

BACKGROUND: The use of biomarkers has become a major component of clinical trial design. In Huntington's disease (HD), quantifying the amount of huntingtin protein (HTT) in patient cerebrospinal fluid (CSF) has served as a pharmacodynamic readout for HTT-lowering therapeutic approaches and is a potential disease progression biomarker. To date, an ultrasensitive immunoassay to quantify mutant HTT protein (mHTT) has been used, but additional assays are needed to measure other forms of HTT protein. OBJECTIVE: We aimed to develop an ultrasensitive immunoassay to quantify HTT protein in a polyglutamine length-independent manner (mHTT and non-expanded wild type HTT combined) in control and HD participant CSF samples. METHODS: An ultrasensitive, bead-based, single molecule counting (SMC) immunoassay platform was used for the detection of HTT protein in human CSF samples. RESULTS: A novel ultrasensitive SMC immunoassay was developed to quantify HTT protein in a polyglutamine length-independent manner and shown to measure HTT in both control and HD participant CSF samples. We validate the selectivity and specificity of the readout using biochemical and molecular biology tools, and we undertook a preliminary analytical qualification of this assay to enable its clinical use. We also used this novel assay, along with the previously described mHTT assay, to analyze CSF from control and HD participants. The results of this preliminary set suggests that correlation is present between mHTT and the polyglutamine length-independent HTT levels in human CSF. CONCLUSION: We have developed a novel ultrasensitive immunoassay that is able to quantify HTT protein in a polyglutamine length-independent manner in control and HD participant CSF.

Development of mAb-based polyglutamine-dependent and polyglutamine length-independent huntingtin quantification assays with cross-site validation.

Huntington's disease (HD) is caused by an expansion of the CAG trinucleotide repeat domain in the huntingtin gene that results in expression of a mutant huntingtin protein (mHTT) containing an expanded polyglutamine tract in the amino terminus. A number of therapeutic approaches that aim to reduce mHTT expression either locally in the CNS or systemically are in clinical development. We have previously described sensitive and selective assays that measure human HTT proteins either in a polyglutamine-independent (detecting both mutant expanded and non-expanded proteins) or in a polyglutamine length-dependent manner (detecting the disease-causing polyglutamine repeats) on the electrochemiluminescence Meso Scale Discovery detection platform. These original assays relied upon polyclonal antibodies. To ensure an accessible and sustainable resource for the HD field, we developed similar assays employing monoclonal antibodies. We demonstrate that these assays have equivalent sensitivity compared to our previous assays through the evaluation of cellular and animal model systems, as well as HD patient biosamples. We also demonstrate cross-site validation of these assays, allowing direct comparison of studies performed in geographically distinct laboratories.

The fate of indeterminate liver lesions: What proportion are precursors of hepatocellular carcinoma?

BACKGROUND: The natural history and incidence of hepatocellular carcinoma (HCC) arising from indeterminate liver lesions are not well described. We aimed to define the incidence of HCC in a cohort of patients undergoing surveillance by magnetic resonance imaging (MRI) and estimate any associations with incident HCC. METHODS: We performed a retrospective follow-up study, identifying MRI scans in which indeterminate lesions had been reported between January 2006 and January 2017. Subsequent MRI scan reports were reviewed for incident HCC arising from indeterminate lesions, data were extracted from electronic patient records and survival analysis performed to estimate associations with baseline factors. RESULTS: One hundred and nine patients with indeterminate lesions on MRI were identified. HCC developed in 19 (17%) patients over mean follow up of 4.6 years. Univariate Cox proportional hazards analysis found incident HCC to be significantly associated with baseline low platelet count (hazard ratio (HR) = 7.3 (95% confidence intervals (CI) 2.1-24.9), high serum alpha-fetoprotein level (HR = 2.7 (95% CI 1.0-7.1)) and alcohol consumption above fourteen units weekly (HR = 3.1 (95% CI 1.1-8.7)). Multivariate analysis, however, found that only low platelet count was independently associated with HCC (HR = 5.5 (95% CI 0.6-5.1)). CONCLUSIONS: HCC arises in approximately one fifth of indeterminate liver lesions over 4.6 years and is associated with a low platelet count at the time of first diagnosis of an indeterminate lesion. Incidence of HCC was more common in people with viral hepatitis and in those consuming > 14 units of alcohol per week. Our data may be used to support a strategy of enhanced surveillance in patients with indeterminate lesions.

Generation of T-cell-redirecting bispecific antibodies with differentiated profiles of cytokine release and biodistribution by CD3 affinity tuning.

T-cell-redirecting bispecific antibodies have emerged as a new class of therapeutic agents designed to simultaneously bind to T cells via CD3 and to tumor cells via tumor-cell-specific antigens (TSA), inducing T-cell-mediated killing of tumor cells. The promising preclinical and clinical efficacy of TSAxCD3 antibodies is often accompanied by toxicities such as cytokine release syndrome due to T-cell activation. How the efficacy and toxicity profile of the TSAxCD3 bispecific antibodies depends on the binding affinity to CD3 remains unclear. Here, we evaluate bispecific antibodies that were engineered to have a range of CD3 affinities, while retaining the same binding affinity for the selected tumor antigen. These agents were tested for their ability to kill tumor cells in vitro, and their biodistribution, serum half-life, and anti-tumor activity in vivo. Remarkably, by altering the binding affinity for CD3 alone, we can generate bispecific antibodies that maintain potent killing of TSA + tumor cells but display differential patterns of cytokine release, pharmacokinetics, and biodistribution. Therefore, tuning CD3 affinity is a promising method to improve the therapeutic index of T-cell-engaging bispecific antibodies.

The Immediate Physiological Effects of E-Cigarette Use and Exposure to Secondhand E-Cigarette Vapor.

BACKGROUND: Vaping continues to grow as an alternative to smoking and as a recreational activity for people of all ages, including minors. The billion-dollar industry offers users a plethora of flavors, nicotine concentrations, e-juice combinations, and devices. While some studies suggest vaping is beneficial for certain ailments and as a smoking cessation tool, many studies report concerning health outcomes associated with vape use. Recent FDA regulations have banned certain vaping products following an increase of vaping-related lung injuries reported in 2019. Health care providers need to better understand the physiological effects of vaping-specific products and the impact of secondhand vapor. The specific aims of the present study were to understand the immediate effects on heart rate, breathing frequency, blood pressure, blood sugar, [Formula: see text], pulmonary function, and oral temperature following e-cigarette use and secondhand vapor exposure. METHODS: A total of 149 volunteers participated in this study; 76 subjects vaped mint-flavored e-cigarettes with 5% nicotine for 20 min while seated next to 73 nonvaping subjects who agreed to be exposed to the vapor. Health variables including heart rate, blood pressure, breathing frequency, blood glucose, FVC, [Formula: see text], and oral temperature were obtained prior to vaping or exposure to vapor and again after 20 min. RESULTS: Subjects who vaped had significantly higher heart rate, breathing frequency, and oral temperature, and significantly lower blood oxygenation levels (ie, [Formula: see text]) after vaping for 20 min. Nonvaping subjects exposed to vapor had significantly higher oral temperature after 20 min of exposure. Blood sugar and FVC were not significantly affected by vaping or exposure to vapor. CONCLUSIONS: Vaping with mint-flavored e-cigarettes with 5% nicotine for 20 min resulted in significant immediate physiological changes. Exposure to e-cigarette vapor significantly increased oral temperature within the same amount of time.

Identifying facial expressions in dogs: A replication and extension study.

This study replicated and extended previous research (Bloom & Friedman, 2013) indicating that humans can correctly identify emotional expressions in photographs of dog faces when tested with one breed (i.e., a Malinois). It examined the effect of dog facial morphology on accuracy of emotion identification by using images of a Malinois, as well as two-different breeds (Doberman and Rhodesian Ridgeback) expressing six-discrete emotions (happiness, sadness, anger, fear, disgust, surprise). Using a sample of 105-undergraduate students, participants were shown slides presenting four different expressive images of the same breed and asked to identify the image that best depicted one of the six emotions. Analyses indicated that participants were able to correctly identify all emotions across all dog breeds significantly better than chance, replicating the previous study for the Malinois, and extending its findings to additional breeds. Accuracy of emotion identification was predicted to be lower for the Doberman due to its darker coloration, possibly interfering with recognition of subtle emotional cues, but was found to be highest for the Malinois, followed by the Doberman, and then the Rhodesian Ridgeback.

Analysis of mutant and total huntingtin expression in Huntington's disease murine models.

Huntington's disease (HD) is a monogenetic neurodegenerative disorder that is caused by the expansion of a polyglutamine region within the huntingtin (HTT) protein, but there is still an incomplete understanding of the molecular mechanisms that drive pathology. Expression of the mutant form of HTT is a key aspect of diseased tissues, and the most promising therapeutic approaches aim to lower expanded HTT levels. Consequently, the investigation of HTT expression in time and in multiple tissues, with assays that accurately quantify expanded and non-expanded HTT, are required to delineate HTT homeostasis and to best design and interpret pharmacodynamic readouts for HTT lowering therapeutics. Here we evaluate mutant polyglutamine-expanded (mHTT) and polyglutamine-independent HTT specific immunoassays for validation in human HD and control fibroblasts and use to elucidate the CSF/brain and peripheral tissue expression of HTT in preclinical HD models.

A Mixed Methods Pilot Study on the Short-Term Physiological Effects of Vaping and Attitudes Regarding Its Use and Health Effects in Samples of Young Adults.

Vaping is a fairly new and legal way young people are inhaling substances into their lungs. Very little is currently known about the immediate physiological impact or the psychosocial reasons surrounding vape use. This study used a mixed methods approach to (a) understand the short-term physiological implications of vape use compared with people who do not vape and (b) investigate the reasons people choose to vape compared with those who choose not to vape. Twenty-four people participated in the study: 12 self-identified as nonvapers, and 12 self-identified as people who vape. All participants were between 18 and 24 years old. Qualitative analysis suggested people vape because they think it is cool, think it is less risky than smoking, and enjoy the social aspects of vaping. People who choose not to vape are concerned about the unknown health implications, think it is a waste of resources, and are apathetic toward it. Quantitative results revealed statistically significant increases in heart rate and decreases in the percentage of blood oxygenation after 20 minutes of vape use. Blood pressure, respiratory rate, and blood sugar scores did not significantly change after 20 minutes of vape use. Differences in the frequencies of men and women across the two groups were found. Significant differences found for systolic blood pressure, respiratory rate, and pulmonary function test became nonsignificant after controlling for gender. Both long- and short-term effects of vaping need to be further evaluated. The psychosocial reasons why certain people vape whereas others in the same peer group do not also need to be better understood.

Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy.

Monoclonal antibodies that block the programmed cell death 1 (PD-1) checkpoint have revolutionized cancer immunotherapy. However, many major tumor types remain unresponsive to anti-PD-1 therapy, and even among responsive tumor types, most of the patients do not develop durable antitumor immunity. It has been shown that bispecific antibodies activate T cells by cross-linking the TCR/CD3 complex with a tumor-specific antigen (TSA). The class of TSAxCD3 bispecific antibodies have generated exciting results in early clinical trials. We have recently described another class of "costimulatory bispecifics" that cross-link a TSA to CD28 (TSAxCD28) and cooperate with TSAxCD3 bispecifics. Here, we demonstrate that these TSAxCD28 bispecifics (one specific for prostate cancer and the other for epithelial tumors) can also synergize with the broader anti-PD-1 approach and endow responsiveness-as well as long-term immune memory-against tumors that otherwise do not respond to anti-PD-1 alone. Unlike CD28 superagonists, which broadly activate T cells and induce cytokine storm, TSAxCD28 bispecifics display little or no toxicity when used alone or in combination with a PD-1 blocker in genetically humanized immunocompetent mouse models or in primates and thus may provide a well-tolerated and "off the shelf" combination approach with PD-1 immunotherapy that can markedly enhance antitumor efficacy.

Detection, stratification and treatment of hepatitis C-positive prisoners in the United Kingdom prison estate: Development of a pathway of care to facilitate the elimination of hepatitis C in a London prison.

The United Kingdom is committed to eliminating hepatitis C virus (HCV) infection by 2025. The prison estate provides an opportunity to identify and treat HCV-positive individuals in a high-prevalence environment. We designed and implemented a pathway of care within a London prison to diagnose, stratify and link HCV-positive prisoners into care. This study was a two-phase case study of a HCV care pathway. New arrivals to the prison were offered blood-borne virus screening with dried blood spot testing at their secondary health check. Those with active infection completed disease stratification tests and were reviewed at a weekly hospital-based multidisciplinary team meeting to determine management. In Phase-2, the pathway was redesigned to improve testing and the referral of HCV-positive prisoners into treatment. Over the 30-month evaluation period, 12,946 people were received in the prison. During Phase-1, 19.6% of new arrivals completed blood-borne virus testing, with 7.3% identified as HCV-positive. Just 8.3% of HCV-positive individuals were treated or referred for treatment in Phase-1. During Phase-2, 30% of new receptions completed BBV testing and 3.9% were identified as HCV-positive. Linkage into care was improved, with 38.9% treated or referred during the second phase. Poor access to testing and referral to treatment limit the effectiveness of care provision for prisoners with HCV. Elimination of HCV in prisons requires local service configuration to ensure high uptake of testing, with all HCV-positive cases then offered treatment during custody or referral on to treatment after release.

A class of costimulatory CD28-bispecific antibodies that enhance the antitumor activity of CD3-bispecific antibodies.

T cell activation is initiated upon binding of the T cell receptor (TCR)/CD3 complex to peptide-major histocompatibility complexes ("signal 1"); activation is enhanced by engagement of a second "costimulatory" receptor, such as the CD28 receptor on T cells binding to its cognate ligand(s) on the target cell ("signal 2"). CD3-based bispecific antibodies act by replacing conventional signal 1, linking T cells to tumor cells by binding a tumor-specific antigen (TSA) with one arm of the bispecific and bridging to TCR/CD3 with the other. Although some of these so-called TSAxCD3 bispecifics have demonstrated promising antitumor efficacy in patients with cancer, their activity remains to be optimized. Here, we introduce a class of bispecific antibodies that mimic signal 2 by bridging TSA to the costimulatory CD28 receptor on T cells. We term these TSAxCD28 bispecifics and describe two such bispecific antibodies: one specific for ovarian and the other for prostate cancer antigens. Unlike CD28 superagonists, which broadly activate T cells and resulted in profound toxicity in early clinical trials, these TSAxCD28 bispecifics show limited activity and no toxicity when used alone in genetically humanized immunocompetent mouse models or in primates. However, when combined with TSAxCD3 bispecifics, they enhance the artificial synapse between a T cell and its target cell, potentiate T cell activation, and markedly improve antitumor activity of CD3 bispecifics in a variety of xenogeneic and syngeneic tumor models. Combining this class of CD28-costimulatory bispecific antibodies with the emerging class of TSAxCD3 bispecifics may provide well-tolerated, off-the-shelf antibody therapies with robust antitumor efficacy.

Effects on vital signs after twenty minutes of vaping compared to people exposed to second-hand vapor.

INTRODUCTION: Very little is known about the immediate physiological implications of vaping or inhaling second-hand vapor. This study used a quantitative approach to understand the short-term physiological implications of vape use and exposure to sec-ond-hand vapor for people who do not vape. MATERIAL AND METHODS: One hundred and forty-eight people participated in the study, 75 self-identified as non-vapers and 73 self-identified as people who vape. All participants were over the age of 18. Participants used or were exposed to non-flavored e-juice without nicotine in Sorin® vape devices. Heart rate, blood pressure, respiratory rate, blood oxygenation, blood glucose and pulmonary function tests were assessed. Physiological parameters were assessed prior to vape use or exposure to vapor and again after 20 minutes of vaping. RESULTS: Findings indicated there were no significant changes in most health parameters except blood pressure which was reduced in both groups. Heart rate was also significantly reduced for vaping participants. CONCLUSION: Vaping without flavorings or nicotine do not appear to have an immediate negative health impact on vital signs. The physiological effects of long-term exposure and/or vape use requires additional investigation. Information was established regarding the physiological effects of non-flavored, non-nicotine vaping so future studies can compare the effects of vaping with assorted flavors and nicotine concentrations to the effects of vaping only the base ingredients (vegetable glycerin and propylene glycol). New knowledge was gleaned relating to exposure to vapor, a phenomenon not previously examined but common espe-cially among non-vaping people who attend social events where people are vaping.