Disrupted identities, invisibility and precarious support: a mixed methods study of LGBTQI adolescents and young adults with cancer.

BACKGROUND: Lesbian, gay, bisexual, transgender, queer and intersex (LGBTQI) adolescents and young adults (AYAs) with cancer report higher levels of depression and anxiety and lower health related quality of life than non-LGBTQI AYAs with cancer, and LGBTQI adults with cancer. This mixed methods study examined LGBTQI AYAs' experiences of cancer and cancer care, to understand these health disparities. METHODS: Online surveys were completed by 95 LGBTQI AYAs with cancer (age 16-39 years); 19 AYAs took part in a one-to-one semi structured interview. Reflexive thematic analysis of interviews and open-ended survey responses facilitated in-depth examination of subjective experiences; descriptive statistics performed on individual closed-ended survey items identified the percentage of AYAs reporting experiences identified in the qualitative analysis. RESULTS: 63% of AYAs reported high or very high distress on the K10. Three themes were identified in the qualitative analysis: 1) "Identities in flux", included subthemes "Cancer disrupts developing identities, and involvement with LGBTQI communities"; "Internalized prejudice impacts identities"; and "Cancer facilitates identities and embodiment". 2) "Invisibility in cancer care", included subthemes "Navigating disclosure amongst cis-heteronormative assumptions", "Discrimination and paternalistic cancer care" and " Cis-heteronormativity within cancer information". 3) "Precarious social support for LGBTQI AYAs with cancer", included subthemes " Social support during cancer is helpful for LGBTQI AYAs", "LGBTQI AYAs navigate limited support", and" Finding cancer peer support networks is difficult for LGBTQI AYAs". CONCLUSIONS: LGBTQI AYAs with cancer experience psychosocial vulnerabilities related to identity development, experiences of care, and social support networks. These factors likely contribute to their previously evidenced elevated risk of distress, relative to both non-LGBTQI AYAs and LGBTQI older adults. AYAs affected by cancer may require additional, tailored supportive care, including targeted information resources, LGBTQI AYA specific cancer support groups, or partnerships and referrals to LGBTQI community organisations. Additionally, it is evident that health care professionals and cancer services have much work to do in ensuring LGBTQI AYAs receive affirming and appropriate care across paediatric and adult clinical settings. They must move beyond assuming all patients are cisgender, heterosexual and do not have intersex variations unless otherwise stated; work to signal inclusivity and facilitate disclosure; and be able to respond appropriately with tailored information and care, which is inclusive of LGBTQI partners, chosen family, and support systems.

Almost invisible: A review of inclusion of LGBTQI people with cancer in online patient information resources.

OBJECTIVE: This review assessed the inclusion of lesbian, gay, bisexual, trans, queer and/or intersex (LGBTQI) people in online cancer information. METHODS: The websites of Australian cancer organizations were reviewed to identify if they included LGBTQI people and the extent and nature of this inclusion. Websites that did not include LGBTQI people were then reviewed to identify if information was implicitly LGBTQI inclusive. International LGBTQI cancer information resources were reviewed to identify key content. RESULTS: Of sixty-one Australian cancer organization websites reviewed, eight (13%) mentioned LGBTQI people, including 13 information resources targeted to LGBTQI people and 19 general cancer information resources that mentioned LGBTQI people. For Australian cancer websites that did not mention LGBTQI people, 88% used gender neutral language to refer to partners, 69% included a range of sexual behaviours, 13% used gender neutral language when referring to hormones or reproductive anatomy but none acknowledged diverse relationship types. Internationally, 38 LGBTQI-specific cancer information resources were identified. CONCLUSIONS: Cancer patient information resources need to be LGBTQI inclusive. LGBTQI-targeted resources are required to address this population's unique needs and improve cultural safety and cancer outcomes. PRACTICE IMPLICATIONS: Recommendations are provided for LGBTQI inclusive cancer patient information resources.

Informed self-assessment during the transition to medical school: a longitudinal narrative study.

OBJECTIVES: To explore how medical students' narratives of informed self-assessment (ISA) change during their first 18 months of study. DESIGN: This longitudinal study used student narratives drawn from qualitative interviews and written reflections during the transition to medical school, to examine changes in ISA. Our analysis was informed by Situated Cognition Theory which recognises the impact and interplay of personal and environmental factors in cognition. SETTING: To study medicine, first year students need to adapt their self-regulated learning in the context of a new peer group, study demands and educational culture. During this adaptation, students need to seek and interpret available cues to inform their self-assessment. PARTICIPANTS: Longitudinal data were collected at five time points over 18 months from a diverse sample of seven first year medical students in an undergraduate medical programme, including 13.5 hours of interviews and 12 written reflections. RESULTS: Before and after starting medical school, the participants' self-assessments were informed by environmental influences (exam results and comparison with peers), and personal influences (fear of failure and anxiety about not belonging). Early uncertainty meant self-assessments were overestimated and underestimated.By the end of first year, an enhanced sense of belonging coincided with less fear of failure, less emphasis on exam performance and reduced competition with peers. Self-assessments became increasingly informed by evidence of clinical skills and knowledge gained related to future professional competence. CONCLUSION: Influences on medical students' ISAs change during the transition to studying medicine. A greater sense of belonging, and evidence of progress towards clinical competence became more important to self-assessment than comparison with peers and exam performance. Our findings reinforce the importance of formative assessments, opportunities to study and socialise with peers and early clinical experiences during first year. These experiences enhance ISA skills during the transition to medical school.

Protocol for a Delphi consensus study to select indicators of high-quality general practice to achieve Quality Equity and Systems Transformation in Primary Health Care (QUEST-PHC) in Australia.

BACKGROUND: High-quality general practice has been demonstrated to provide cost-effective, equitable health care and improve health outcomes. Yet there is currently not a set of agreed comprehensive indicators in Australia. We have developed 79 evidence-based indicators and their corresponding 129 measures of high-quality general practice. This study aims to achieve consensus on relevant and feasible indicators and measures for the Australian context. METHODS: This Delphi consensus study, approved by WSU Human Research Ethics Committee, consists of three rounds of online survey with general practice experts including general practitioners, practice nurses and primary health network staff. The identified indicators and measures are grouped under an attribute framework aligned with the Quadruple Aim, and further grouped under structures, processes and outcomes according to the Donabedian framework. Participants will rate each indicator and measure for relevance and feasibility, and provide comments and recommendations of additional indicators or measures. In the last round, participants will also be asked their views on the implementation of a quality indicator tool. Each indicator and measure will require ≥70% agreement in both relevance and feasibility to achieve consensus. Aggregated ratings will be statistically analysed for response rates, level of agreement, medians, interquartile ranges and group rankings. Qualitative responses will be analysed thematically using a mixed inductive and deductive approach. DISCUSSION: This protocol will add to the current knowledge of the translation of performance guidelines into quality practice across complex clinical settings and in a variety of different contexts in Australian general practice. The Delphi technique is appropriate to develop consensus between the diverse experts because of its ability to offer anonymity to other participants and minimise bias. Findings will contribute to the design of an assessment tool of high-quality general practice that would enable future primary health care reforms in Australia.

Phase 0 Study of Vandetanib-Eluting Radiopaque Embolics as a Preoperative Embolization Treatment in Patients with Resectable Liver Malignancies.

PURPOSE: To assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies. MATERIALS AND METHODS: The VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC). Patients received 1 mL of BTG-002814 transarterially (containing 100 mg of vandetanib) 7-21 days prior to surgery. The primary objectives were to establish the safety and tolerability of BTG-002814 and determine the concentrations of vandetanib and the N-desmethyl vandetanib metabolite in the plasma and resected liver after treatment. Biomarker studies included circulating proangiogenic factors, perfusion computed tomography, and dynamic contrast-enhanced magnetic resonance imaging. RESULTS: Eight patients were enrolled: 2 with HCC and 6 with mCRC. There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days after treatment, with a mean maximum concentration of 24.3 ng/mL (standard deviation ± 13.94 ng/mL), and in resected liver tissue up to 32 days after treatment (441-404,000 ng/g). The median percentage of tumor necrosis was 92.5% (range, 5%-100%). There were no significant changes in perfusion imaging parameters after TACE. CONCLUSIONS: BTG-002814 has an acceptable safety profile in patients before surgery. The presence of vandetanib in the tumor specimens up to 32 days after treatment suggests sustained anticancer activity, while the low vandetanib levels in the plasma suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies.

A qualitative study of COVID-19 vaccine intentions and mistrust in Black Americans: Recommendations for vaccine dissemination and uptake.

BACKGROUND: COVID-19 vaccination rates among Black Americans have been lower than White Americans and are disproportionate to their population size and COVID-19 impact. This study examined reasons for low vaccination intentions and preferred strategies to promote COVID-19 vaccination. METHODS: Between November 2020 and March 2021, we conducted semi-structured interviews with 24 participants who expressed low vaccination intentions in a RAND American Life Panel survey; we also interviewed five stakeholders who represent organizations or subgroups in Black communities that have been highly affected by COVID-19. RESULTS: Many interviewees discussed the "wait-and-see" approach, citing that more time and evidence for vaccine side effects and efficacy are needed. Perceived barriers to COVID-19 vaccination included structural barriers to access (e.g., transportation, technology) and medical mistrust (e.g., towards the vaccines themselves, the government, healthcare providers and healthcare systems, and pharmaceutical companies) stemming from historical and contemporary systematic racism against Black communities. Interviewees also discussed strategies to promote COVID-19 vaccines, including acknowledging systemic racism as the root cause for mistrust, preferred messaging content (e.g., transparent messages about side effects), modes, and access points (e.g., a variety of medical and non-medical sites), and trusted information sources (e.g., trusted leaders, Black doctors and researchers). CONCLUSIONS: These insights can inform ways to improve initial and booster vaccination uptake as the COVID-19 pandemic progresses.

Physician Identification Badges: A Multispecialty Quality Improvement Study to Address Professional Misidentification and Bias.

OBJECTIVE: To evaluate whether providing resident physicians with "DOCTOR" role identification badges would impact perceptions of bias in the workforce and alter misidentification rates. PARTICIPANTS AND METHODS: Between October 2019 and December 2019, we surveyed 341 resident physicians in the anesthesiology, dermatology, internal medicine, neurologic surgery, otorhinolaryngology, and urology departments at Mayo Clinic in Rochester, Minnesota, before and after an 8-week intervention of providing "DOCTOR" role identification badges. Differences between paired preintervention and postintervention survey answers were measured, with a focus on the frequency of experiencing perceived bias and role misidentification (significance level, α=.01). Free-text comments were also compared. RESULTS: Of the 159 residents who returned both the before and after surveys (survey response rate, 46.6% [159 of 341]), 128 (80.5%) wore the "DOCTOR" badge. After the intervention, residents who wore the badges were statistically significantly less likely to report role misidentification at least once a week from patients, nonphysician team members, and other physicians (50.8% [65] preintervention vs 10.2% [13] postintervention; 35.9% [46] vs 8.6% [11]; 18.0% [23] vs 3.9% [5], respectively; all P<.001). The 66 female residents reported statistically significantly fewer episodes of gender bias (65.2% [43] vs 31.8% [21]; P<.001). The 13 residents who identified as underrepresented in medicine reported statistically significantly less misidentification from patients (84.6% [11] vs 23.1% [3]; P=.008); although not a statistically significant difference, the 13 residents identifying as underrepresented in medicine also reported less misidentification with nonphysician team members (46.2% [6] vs 15.4% [2]; P=.13). CONCLUSION: Residents reported decreased role misidentification after use of a role identification badge, most prominently improved among women. Decreasing workplace bias is essential in efforts to improve both diversity and inclusion efforts in training programs.

COVID-19 Vaccine Intentions and Mistrust in a National Sample of Black Americans.

BACKGROUND: National data indicate low intentions for COVID-19 vaccination among a substantial minority of Black Americans, and disproportionately lower vaccination rates among Black Americans than White Americans. METHODS: A total of 207 of the 318 Black participants (65%) in the RAND American Life Panel, a nationally representative internet panel, were surveyed about COVID-19 vaccine intentions in November-December 2020. Participants' census tracts were geocoded using the Centers for Disease Control and Prevention's Social Vulnerability Index. RESULTS: Overall, 35% agreed or strongly agreed that they would not get a COVID-19 vaccine, 40% agreed or strongly agreed that they would get vaccinated, and 25% reported "don't know." Significant multivariable predictors of not wanting to get vaccinated included high mistrust of the vaccine itself (e.g., concerns about harm and side effects), OR (95% CI) = 2.2 (1.2-3.9), p = .007, and weak subjective norms for vaccination in one's close social network, OR (95% CI) = 0.6 (0.4-0.7), p < .001. Residence in an area of higher socioeconomic vulnerability was a marginally significant predictor, OR (95% CI) = 3.1 (0.9-11.0), p = .08. CONCLUSIONS: High mistrust around COVID-19 vaccines may lower vaccine confidence. Social network members' attitudes can be influential in encouraging vaccination. Public health communications could use transparent and clear messaging on safety and efficacy, and acknowledge historical and ongoing discrimination and racism as understandable reasons for low confidence in COVID-19 vaccines. Future research is needed to consider vaccine access challenges in tandem with mistrust as contributing to low vaccination rates across health conditions.

Trans Women's Responses to Sexual Violence: Vigilance, Resilience, and Need for Support.

Despite experiencing high rates of sexual violence, there is limited research that explores coping and support needs among trans women of color and those from migrant backgrounds. This article examines the impact of sexual violence, as well as responses and support needs in relation to sexual violence, among 31 trans women of color, aged between 18-54 years, living in Australia. Women were recruited using purposive and snowball sampling, local LGBTQI + networks, and social media. Study advertisements invited participation from people 18 years and older, who identified as a "trans woman of color" or "trans woman from a non-English speaking background," to take part in a study about their lives as trans women of color and experiences of sexual violence. In-depth interviews and photovoice took place between September 2018 and September 2019. Findings were analyzed through thematic analysis, drawing on intersectionality theory. Sexual violence was reported to be associated with fear, anxiety, and depression, and, for a minority of women, self-blame. While women reported hypervigilance and avoiding going out in public as measures to anticipate and protect themselves from sexual violence, they also demonstrated agency and resilience. This included putting time and effort into appearing as a cisgender woman, naming violence, seeking support, rejecting self-blame, and engaging in self-care practices to facilitate healing. Trans women highlighted the need for multi-faceted sexual violence prevention activities to encourage education, empowerment and cultural change across the general population and support services, in order to promote respect for gender, sexuality and cultural diversity.

Managing the premenstrual body: a body mapping study of women's negotiation of premenstrual food cravings and exercise.

BACKGROUND: Women's eating behaviours and exercise patterns have been found to fluctuate across the menstrual cycle, manifested by premenstrual food cravings and reduced exercise. However, the meaning and consequences of premenstrual changes in eating and exercise behaviours remains underexplored. The aim of this qualitative study was to explore how women who feel negatively about their premenstrual bodies construct and experience premenstrual changes to eating and exercise practices, which disrupt their usual patterns of body management. METHODS: Four hundred and sixty women aged 18-45 completed an online survey in response to a Facebook advertisement targeted at women who feel negatively about their bodies during the premenstrual phase of the cycle. Participants reported moderate premenstrual distress, high body shame and high risk of disordered eating attitudes using standardised measures. Sixteen women reporting rich accounts of premenstrual body dissatisfaction were invited to participate in body-mapping, involving visually illustrating experiences on a life-sized outline of the body, followed by a telephone interview. Thematic analysis was used to explore qualitative survey, interview, and body-mapping data. RESULTS AND DISCUSSION: Results found that outside of the premenstrual phase these women engaged in restrictive eating and intensive exercise behaviours, which were disrupted by premenstrual cravings, hunger, fatigue, pain and feeling physically uncomfortable. For a minority of the women, this facilitated self-care in reducing the strict management of their bodies during the premenstrual phase. Others experienced feelings of guilt, shame, self-disgust and pushed their bodies physically through increased exercise. CONCLUSIONS: These findings emphasise the need to acknowledge changes in body management across the menstrual cycle, with implications for women's mental health and feelings about the self. Internalisation of pressures placed on women to manage their bodies through restrictive eating behaviours and rigorous exercise plays a role in women's premenstrual body dissatisfaction and distress. The current study aimed to explore how women who feel negatively about their premenstrual bodies construct and experience premenstrual changes to eating and exercise practices. Outside of the premenstrual phase these women engaged in restrictive eating and intensive exercise behaviours which were disrupted by premenstrual cravings, hunger, fatigue, pain and feeling physically uncomfortable. Some women allowed themselves to take a premenstrual break from their usual strict eating and exercise behaviours, whereas others felt guilt, shame, self-disgust and physically pushed their bodies through increased exercise. These findings emphasise that changes to eating and exercise behaviours across the menstrual cycle and pressures placed on women to manage their eating and exercise behaviours have implications for women's premenstrual distress and body dissatisfaction.

HIV Disclosure-Professional Body Guidelines, the Law and the Boundaries of Medical Advice.

This article examines the current BHIVA/BASHH guidelines on the disclosure of HIV+ status in the context of sexual activity. It assesses whether the guidance provided on how to avoid criminal prosecution accurately reflects the prevailing position in law. Given that aspects of the guidance related to non-disclosure of HIV infection in the context of low or negligible risk are as yet untested in UK law, it is argued that there is some uncertainty as to whether the professional body guidelines and the law can be reconciled with each other. The article also considers whether the BHIVA/BASHH guidelines stray beyond the boundaries of medical advice as normally understood (focused on the protection of health and the prevention of onward transmission), by posing both as legal advice on how to avoid prosecution and offering what could be viewed as a moral judgement as to when disclosure is required. While a bio-medical assessment of risk naturally shapes clinical guidelines and may also inform views as to appropriate sexual behaviour and risk-taking, it is unclear whether scientific assessment of risk should be the sole guide when it comes to determining the nature of any disclosure obligation or the medical advice to be given on this matter.

The Discourse of Dignity in the Charlie Gard, Alfie Evans and Isaiah Haastrup Cases.

There are competing accounts of dignity and no agreement about how to adjudicate between them, but this does not prevent dignity from playing an important role in the law. In fact, this very multiplicity enables dignity to perform a range of functions, both explicit and implicit, intended and unintended. Its 'open character' allows dignity to serve as a locus of agreement, but it can also silence debate and limit speaker control of how their statements are received and interpreted. This paper considers dignity's roles in recent English court judgments relating to withdrawal of ventilation and associated care from three unresponsive, paralysed infants: Charlie Gard, Alfie Evans, and Isaiah Haastrup. It presents a critical discourse analysis focusing on the judgments of first instance in relation to these infants. It argues that a range of conceptions of dignity are operationalised, serving four functions: to express esteem; to establish a hierarchy of credibility; to justify a best interests judgment, and to socialise that judgment. The overall effect is that dignity serves to compel acceptance of, rather than providing reasons to support, a best interests judgment. While recognising the value of unspecified invocations of dignity, we voice a warning about its potential to stifle debate and legitimise and enforce existing power relations.

Radiopaque beads loaded with doxorubicin in the treatment of patients with hepatocellular carcinoma: A retrospective, multi-center study.

BACKGROUND AND AIMS: Radiopaque drug-eluting beads are an emerging treatment option for patients with hepatocellular carcinoma (HCC). The primary objective of this study was to evaluate overall disease and target tumor response of non-resectable HCC after TACE with a doxorubicin-loaded radiopaque microsphere. METHODS: Data were abstracted from records of patients with unresectable HCC who received TACE with doxorubicin-loaded radiopaque LC Bead LUMITM microspheres at one of five United States centers between February 2016 - November 2017. Response was measured using modified response criteria in solid tumors. Primary efficacy endpoints included objective response rate (ORR) and disease control rate (DCR) at first assessment post-treatment, both overall and for targeted tumors. ORR was the sum of complete and partial response. DCR was ORR plus stable disease. Toxicity was calculated using common terminology criteria for adverse events. RESULTS: Eighty-two patients were included. Overall ORR and DCR were 47.6% (39/82) and 76.8% (63/82), respectively. ORR and DCR of target tumors were 56% and 98%, respectively. Five patients experienced adverse events (5/82, 6.1%). No grade 4-5 toxicities occurred. CONCLUSIONS: TACE with drug-loaded radiopaque beads is a promising treatment for unresectable HCC. Prospective studies should evaluate whether radiopaque beads reduce off-target distribution of microspheres.

VEROnA Protocol: A Pilot, Open-Label, Single-Arm, Phase 0, Window-of-Opportunity Study of Vandetanib-Eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies.

BACKGROUND: Transarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) and is also a treatment option for patients with liver metastases from colorectal cancer. However, TACE is not a curative treatment, and tumor progression occurs in more than half of the patients treated. Despite advances and technical refinements of TACE, including the introduction of drug-eluting beads-TACE, the clinical efficacy of TACE has not been optimized, and improved arterial therapies are required. OBJECTIVE: The primary objectives of the VEROnA study are to evaluate the safety and tolerability of vandetanib-eluting radiopaque embolic beads (BTG-002814) in patients with resectable liver malignancies and to determine concentrations of vandetanib and the N-desmethyl metabolite in plasma and resected liver following treatment with BTG-002814. METHODS: The VEROnA study is a first-in-human, open-label, single-arm, phase 0, window-of-opportunity study of BTG-002814 (containing 100 mg vandetanib) delivered transarterially, 7 to 21 days before surgery in patients with resectable liver malignancies. Eligible patients have a diagnosis of colorectal liver metastases, or HCC (Childs Pugh A), diagnosed histologically or radiologically, and are candidates for liver surgery. All patients are followed up for 28 days following surgery. Secondary objectives of this study are to evaluate the anatomical distribution of BTG-002814 on noncontrast-enhanced imaging, to evaluate histopathological features in the surgical specimen, and to assess changes in blood flow on dynamic contrast-enhanced magnetic resonance imaging following treatment with BTG-002814. Exploratory objectives of this study are to study blood biomarkers with the potential to identify patients likely to respond to treatment and to correlate the distribution of BTG-002814 on imaging with pathology by 3-dimensional modeling. RESULTS: Enrollment for the study was completed in February 2019. Results of a planned interim analysis were reviewed by a safety committee after the first 3 patients completed follow-up. The recommendation of the committee was to continue the study without any changes to the dose or trial design, as there were no significant unexpected toxicities related to BTG-002814. CONCLUSIONS: The VEROnA study is studying the feasibility of administering BTG-002814 to optimize the use of this novel technology as liver-directed therapy for patients with primary and secondary liver cancer. TRIAL REGISTRATION: ClinicalTrial.gov NCT03291379; https://clinicaltrials.gov/ct2/show/NCT03291379. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13696.

Vandetanib-eluting Radiopaque Beads: Pharmacokinetics, Safety, and Efficacy in a Rabbit Model of Liver Cancer.

Background Transarterial chemoembolization with cytotoxic drugs is standard treatment for unresectable intermediate-stage hepatocellular carcinoma but achieves suboptimal outcomes because of hypoxic stress and the production of detrimental proangiogenic factors. An alternative approach using radiopaque embolization beads loaded with the antiangiogenic drug vandetanib may provide improved anticancer efficacy. Purpose To evaluate the pharmacokinetics, safety, and efficacy of vandetanib-eluting radiopaque bead (VERB) chemoembolization of rabbit liver tumors. Materials and Methods Between April 2015 and March 2016, 60 New Zealand white rabbits with VX2 liver tumors were randomly treated with VERBs at different doses, with nonloaded radiopaque beads (ROBs), or with intra-arterial vandetanib suspension (VS) or were not treated. Vandetanib plasma concentration and tumor growth at US were evaluated. Animals were euthanized after 3 days or 3 weeks. Assessment included bead distribution at x-ray imaging and histologic examination, tumor viability at histologic examination, and vandetanib tissue concentration. Group comparison analysis (Mann-Whitney, Kruskal-Wallis, and χ2 tests) and predictive factor analysis for tumor growth and viability were performed. Results Vandetanib plasma concentration was lower with VERBs than with VS (P < .01), while concentration in tumor was higher for VERBs (than for VS) at 3 days (median, 29.2 vs 2.74 ng/mg; P = .48). Tumor growth was lower with VERBs than with ROBs and with VS at both time points, with median values of +114%, +192%, and +466% at 3 weeks, respectively. Tumor viability was lower at 3 days for VERBs than for ROBs and for VS (3%, 18%, and 38%, respectively) but was not significantly different at 3 weeks. The volume of bead in tumor was a significant predictive factor for lower tumor growth in multivariable analysis at 3 days (P = .03). Drug tumor concentration was a significant predictive factor for lower tumor growth at 3 weeks (P = .04). Conclusion Vandetanib-eluting radiopaque bead chemoembolization showed a pharmacokinetic advantage over intra-arterial drug administration in a preclinical model of liver cancer. High deposition of beads and high vandetanib concentration in tumor led to stronger antitumor effects. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Kim and Van den Abbeele in this issue.

The Efficacy of Crotalidae Polyvalent Immune Fab (Ovine) Antivenom Versus Placebo Plus Optional Rescue Therapy on Recovery From Copperhead Snake Envenomation: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial.

STUDY OBJECTIVE: Copperhead snake (Agkistrodon contortrix) envenomation causes limb injury resulting in pain and disability. It is not known whether antivenom administration improves limb function. We determine whether administration of antivenom improves recovery from limb injury in patients envenomated by copperhead snakes. METHODS: From August 2013 through November 2015, we performed a multicenter, randomized, double-blind, placebo-controlled, clinical trial to evaluate the effect of ovine Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) antivenom therapy on recovery of limb function in patients with copperhead snake envenomation at 14 days postenvenomation. The study setting was 18 emergency departments in regions of the United States where copperhead snakes are endemic. Consecutive patients aged 12 years or older with mild- to moderate-severity envenomation received either FabAV or placebo. The primary outcome was limb function 14 days after envenomation, measured by the Patient-Specific Functional Scale. Additional outcomes included the Patient-Specific Functional Scale at other points; the Disorders of the Arm, Shoulder, and Hand, Lower Extremity Functional Scale, and Patient's Global Impression of Change instruments; grip strength; walking speed; quality of life (Patient-Reported Outcomes Measurement Information System Physical Fucntion-10); pain; and analgesic use. RESULTS: Seventy-four patients received study drug (45 FabAV, 29 placebo). Mean age was 43 years (range 12 to 86 years). Fifty-three percent were men, 62% had lower extremity envenomation, and 88% had mild initial severity. The primary outcome, the least square mean Patient-Specific Functional Scale score at 14 days postenvenomation, was 8.6 for FabAV-treated subjects and 7.4 for placebo recipients (difference 1.2; 95% confidence interval 0.1 to 2.3; P=.04). Additional outcome assessments generally favored FabAV. More FabAV-treated subjects experienced treatment-emergent adverse events (56% versus 28%), but few were serious (1 in each group). CONCLUSION: Treatment with FabAV reduces limb disability measured by the Patient-Specific Functional Scale 14 days after copperhead envenomation.

Transcatheter chemoembolization in the treatment of HCC in patients not eligible for curative treatments: midterm results of doxorubicin-loaded DC bead.

PURPOSE: To examine the results of segmental transcatheter arterial chemoembolization with doxorubicin-loaded DC Bead in the treatment of hepatocellular carcinoma (HCC) in non-surgical candidates. MATERIAL AND METHODS: Seventy-one patients (60% men; 11% women; mean age 63; range 46-71 years) with documented HCC of 3-10 cm in diameter (mean 6.2) were enrolled prospectively in the study. All patients had cirrhosis-related HCC that was developed on an underlying controlled hepatitis infection. Only patients with compensated cirrhosis--Child A or B--were included in this study. RESULTS: Overall complete response (CR) according to EASL on an intention to treat basis was seen in 11 patients who developed complete necrosis (15.5%). Objective response (OR) ranged from 66.2% to 85.5% across the four treatments. Survival at 12 months was 97.05%. Sustained CR was observed in 11 (16.1%), and OR in 49 (72%). Sustained partial response was seen in 49 patients (72.05%). Survival at 18 months was 94.1%. At 24 months follow-up survival was 91.1%. Sustained OR was seen in 45 patients (66.2%) while sustained CR was 16.1% (11/68). At 30 months survival was 88.2%. One patient with CR developed multifocal HCC in areas that most likely were not embolized during the previous embolization sessions. In this patient recurrence-free survival was 28 months. Alpha Fetroprotein levels decreased significantly in measurements 1 month post each procedure (p < 0.001). Bilirubin, gamma-GT, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase (ALP) showed only transient increases observed during the study period. Severe procedure-related complications were seen in 4.2% (cholecystitis: n = 1; liver abscess: n = 1; pleural effusion: n = 1). Post Embolization Syndrome (PES) was observed in all patients. CONCLUSION: Transcatheter arterial chemoembolization with DC Bead is an effective and safe procedure in the treatment of HCC patients not eligible for curative treatments with high rates of response and high rates of mid term survival.

In vivo evidence from an Agrostis stolonifera selection genotype that chloroplast small heat-shock proteins can protect photosystem II during heat stress.

Previous in vitro experiments indicated that chloroplast small heat-shock proteins (sHsp) could associate with thylakoids and protect PSII during heat and other stresses, possibly by stabilizing the O2-evolving complex (OEC). However, in vivo evidence of sHsp protection of PSII is equivocal at present. Using previously characterized selection genotypes of Agrostis stolonifera Huds. that differ in thermotolerance and production of chloroplast sHsps, we show that both genotypes contain thylakoid-associating sHsps, but the heat-tolerant genotype, which produces an additional sHsp isoform not made by the sensitive genotype, produces a greater quantity of chloroplast and thylakoid sHsp. Following a pre-heat stress to induce sHsps, in vivo PSII function decreased less at high temperatures in the tolerant genotype. Differences in PSII thermotolerance in vivo were associated with increased thermotolerance of the OEC proteins and O2-evolving function of PSII, and not with other PSII proteins or functions examined. In vivo cross-linking experiments indicated that a greater amount of sHsp associated with PSII proteins during heat stress in the tolerant genotype. PSII was the most thermosensitive component of photosynthetic electron transport, and no differences between genotypes in the thermotolerance of other electron transport components were observed. These results indicate that in vivo chloroplast sHsps can protect O2 evolution and the OEC proteins of PSII during heat stress.