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Introduction. Colon cancer impacts the lives of Kansans and those across the United State.(1, 2) Epidermal growth factor receptor (EGFR) inhibitors, such as panitumumab and cetuximab, have gained popularity as first-line treatment for stage 4 colon cancer despite their toxicities.(3-5) EGFR inhibitors are an efficacious first-line treatment for stage 4 colon cancer, but no study has investigated outcomes comparing EGFR inhibitors as first-line treatment to it used as second- or third-line treatment. This study investigates EGFR inhibitor therapy estimated survival when used as first-, second-, and third-line. Methods. A retrospective review was done for patients with stage 4 colon cancer who underwent EGFR inhibitor treatment at a large academic center from November 2007 to August 2021. The patients were stratified into five groups by the line in which they received the EGFR inhibitor treatment. A log-rank test was used to analyze the groups, and the median survival for each group was determined. Results. A total of 68 patients were reviewed; 18 received first-line, 23 received second-line, 18 received third-line, 6 received fourth-line, and 3 received sixth-line treatment with an EGFR inhibitor. Fourth- and sixth-line therapies were excluded due to the small patient size. There was no significant difference in estimated survival time between any of the lines. Median survival of the therapies was found. Conclusions. There is no statistical difference in survival when EGFR inhibitors are used as first-, second-, or third-line for stage 4 colon cancer which should be considered when prescribing chemotherapy second- or third-line for this cancer.

Introduction Implementing a health system-based hypertension programme may lower blood pressure (BP). Methods We performed a randomized, controlled pilot study to assess feasibility, acceptability, and safety of a home-based virtual hypertension programme integrating evidence-based strategies to overcome current barriers to BP control. Trained clinical pharmacists staffed the virtual collaborative care clinic (vCCC) to remotely manage hypertension using a BP dashboard and phone “visits” to monitor BP, adherence, side effects of medications, and prescribe anti-hypertensives. Patients with uncontrolled hypertension were identified via electronic health records. Enrolled patients were randomized to either vCCC or usual care for 3 months. We assessed patients’ home BP monitoring behaviour, and patients’, physicians’, and pharmacists’ perspectives on feasibility and acceptability of individual programme components. Results Thirty-one patients (vCCC = 17, usual care = 14) from six physician clinics completed the pilot study. After 3 months, average BP decreased in the vCCC arm (P = 0.01), but not in the control arm (P = 0.45). The vCCC participants measured BP more (9.9 vs. 1.2 per week, P < 0.001). There were no intervention-related adverse events. Participating physicians (n = 6), pharmacists (n = 5), and patients (n = 31) rated all programme components with average scores of >4.0, a pre-specified benchmark. Nine adaptations in vCCC design and delivery were made based on potential barriers to implementing the programme and suggestions. Conclusion A home-based virtual hypertension programme using team-based care, technology, and a logical integration of evidence-based strategies is safe, acceptable, and feasible to intended users. These pilot data support studies to assess the effectiveness of this programme at a larger scale.

Objectives:To determine base rates of invalid performance on the Test of Memory Malingering (TOMM) in patients with traumatic brain injury (TBI) undertaking rehabilitation who were referred for clinical assessment, and the factors contributing to TOMM failure.Methods:Retrospective file review of consecutive TBI referrals for neuropsychological assessment over seven years. TOMM failure was conventionally defined as performance Results:Four hundred and ninety one TBI cases (Median age = 40 years [IQR = 26–52], 79% male, 82% severe TBI) were identified. Overall, 48 cases (9.78%) failed the TOMM. Logistic regression analyses revealed that use of an interpreter during the assessment (adjusted odds ratio [aOR] = 8.25, 95%CI = 3.96–17.18), outpatient setting (aOR = 4.80, 95%CI = 1.87–12.31) and post-injury psychological distress (aOR = 2.77, 95%CI = 1.35–5.70) were significant multivariate predictors of TOMM failure. The TOMM failure rate for interpreter cases was 49% (21/43) in the outpatient setting vs. 7% (2/30) in the inpatient setting. By comparison, 9% (21/230) of non-interpreter outpatient cases failed the TOMM vs. 2% (4/188) of inpatient cases.Conclusions:TOMM failure very rarely occurs in clinical assessment of TBI patients in the inpatient rehabilitation setting. It is more common in the outpatient setting, particularly in non-English-speaking people requiring an interpreter. The findings reinforce the importance of routinely administering stand-alone performance validity tests in assessments of clinical TBI populations, particularly in outpatient settings, to ensure that neuropsychological test results can be interpreted with a high degree of confidence.

Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma.Significance:Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA.

Supplementary figure 1: Cohort overview. Number of samples sequenced with whole exome, panel or whole RNA sequencing. Supplementary figure 2: Phylogeny and WGD events in CRUKP1047. Supplementary figure 3: Ploidy and SCNA burden. Supplementary figure 4: Overview of each case. Supplementary figure 5: MEDICC2 copy number sample trees. Supplementary figure 6: MEDICC tree of all exome samples demonstrating that samples cluster together by patient, and not by melanoma subtype. Supplementary figure 7: SCNA frequency of cutaneous (a), acral (b) and melanoma of unknown primary (MUP, c). Supplementary figure 8: Correlation between liver copy number distance to other sites and time of emergence after stage IV diagnosis. Supplementary figure 9: Examination of tumour heterogeneity of alterations to antigen-presentation machinery genes, with site and patient annotation. Supplementary figure 10: Boxplots indicating the proportion of losses in the cohort for each segment. Supplementary figure 11: Balance of expression between nonsynonymous mutations that were not predicted to be neoantigens and clonal predicted neoantigens. Supplementary figure 12: Barplot of TIL infiltration score frequencies, determined by pathologist assessment of histology, across all samples. Supplementary figure 13: Number of samples per patient that are classified as either none-low in terms of TILs or moderate-heavy. Supplementary figure 14: Histogram of purity for samples with RNA-seq data. Supplementary figure 15: TME deconvolution. Supplementary figure 16: The effect of metastatic site on transcriptional profiles. Supplementary figure 17: Association of PHF3 copy number with expression. Supplementary figure 18: Overview of gene fusions identified in RNA-seq data. Supplementary figure 19: Comparison of ploidy estimates from panel sequencing data, exome data and FISH. Supplementary figure 20: Comparison of ploidy estimates in panel, exome, FISH and single cell data. Supplementary figure 21: FACs sort plot for CRUKP2567 diaphragmatic metastasis. Supplementary figure 22: Ploidy and wGII values from single cell sequencing of FACS-sorted tumour cells. Supplementary figure 23: Copy number profiles on chromosome 5 for bulk samples from primary and DI_2_R2, a diaphragmatic metastasis. Supplementary figure 24: Histogram of purity of samples for which RNA-seq was performed faceted by patient. Supplementary figure 25: Histogram of purity of samples for which RNA-seq was performed faceted by tissue site.

S. Table 1: List of PEACE Consortium members. S. Table 2: Sample database used for the study for Panel, Exome and RNASeq samples. S. Table 3: Overview of lines of treatment given to each patient. S. Table 4: Lesions and patients included in the lesion-level response to ICI analysis. S. Table 5: Hallmark genesets significantly upregulated in normal tissue vs tumor tissue. Table shows p-values for tissue type, purity; T value for tissue type, purity; q-value for tissue type, purity (FDR corrected). S. Table 6: Hallmark genesets significantly upregulated in tumor tissue vs normal tissue. Table shows p-values for tissue type, purity; T value for tissue type, purity; q-value for tissue type, purity (FDR corrected). S. Table 7: Genes included in the target panel. S. Table 8: Tree topology comparisons between manually constructed trees and pairtree-constructed trees.

Aims We systematically studied the presence of hyperglycaemia during treatment with Immune Checkpoint Inhibitors (ICPI) for cancer, in those with and without diabetes at baseline, and determined the cause of new-onset hyperglycaemia, Methods Retrospective review of electronic records of those receiving an ICPI for melanoma, lung or renal cancer. Results Overall, 959 participants were included. In this study, 103 had diabetes at baseline (10.7%). Those with lung cancer had the highest frequency of diabetes; 131 people had hyperglycaemia (defined as at least one glucose ≥11.1 mmol/L) in the year after starting an ICPI. The incidence was 55% in those with diabetes at baseline, and 8.6% in those without baseline diabetes. Among 74 with new-onset hyperglycaemia (without pre-existing diabetes) 76% was attributable to steroid induced diabetes, with 9.5% due to ICPI Induced diabetes resembling type 1 diabetes. Conclusions Hyperglycaemia is common in persons receiving an ICPI for cancer, including 8.6% of those without known diabetes. While much of this is due to glucocorticoid use, care is needed to avoid missing those with ICPI-induced diabetes who are at risk of diabetic ketoacidosis, which is a medical emergency.

Background Brain tumours are the most common and fatal of all solid tumours for children and adolescents. The effects of the tumour and treatment (chemotherapy, radiation, and/or surgery) results in significant disruptions to childhood development and large amounts of missed schooling. Among other challenges for families, this produces obstacles for children and adolescents to achieve and maintain academic performance and experience positive schooling encounters. Aims We thus aimed to systematically identify and synthesize qualitative evidence on how families experience paediatric brain tumour from diagnosis and beyond with regards to their schooling and education to identify gaps in service delivery, research, and policy. Methods A protocol for this review was registered with PROSPERO (ID: CRD42020177165). Searches were conducted in Medline, CINAHL, PsycInfo, Embase, and Web of Science, and yielded 22 eligible papers (representing 17 studies). Data were extracted into NVivo12 and analysed by qualitative description. Results We formed the following domain summaries: academic (perceived failure to keep up with peers and finding success where one could, the importance of encouragement for diagnosed children), social (the importance of friendships and the harm of bullying), and support (the defining factor in overall return-to-school experience, often not enough received from educational professionals and clinicians). Our review highlights the need for more comprehensive, individualized, and integrated support for diagnosed children to return to educational institutions, and for the need to address their social experiences, particularly with regards to bullying, potentially through a school-wide social and emotional learning approach. Conclusion Funding support, evidence-based guidelines, staff skill development, and clear communication structures across families, health care facilities, schools, and educational departments are essential to achieving this.

OBJECTIVE Incidental rib hyperostosis is defined as asymmetric cortical thickening and sclerosis of the medial posterior ribs and is important because it may lead to unnecessary laboratory testing, additional imaging and occasionally biopsy. The purpose of this study is to identify the incidence of rib hyperostosis within different patient groups known to have an increased propensity towards osteophyte formation and ankylosis. METHODS This study was a retrospective cohort study reviewing chest CT examinations in a control group of patients over 50 years old and three different patient populations: psoriatic arthritis, ankylosing spondylitis, and diffuse idiopathic skeletal hyperostosis (DISH). Each CT was evaluated by an attending musculoskeletal and cardiothoracic radiologist to identify rib hyperostosis, osteophyte formation, ankylosis, and spinal curvature. Two senior radiology residents also performed consensus reads and inter-reader reliability was calculated between the two groups. RESULTS Two hundred eighty-two individuals were included in the study of which 38 (13.5%) had at least one hyperostotic rib. The ankylosing spondylitis population and the DISH population had the highest incidence of rib hyperostosis with a relative risk of 5.6 (p = 0.012) and 5.3 (p =

Excretion of cytoplasmic protein (ECP) is a commonly observed phenomenon in bacteria, and this partial extracellular localisation of the intracellular proteome has been implicated in a variety of stress response mechanisms. In response to hypoosmotic shock and ribosome stalling inEscherichia coli, ECP is dependent upon the presence of the large-conductance mechanosensitive channel and the alternative ribosome–rescue factor A gene products. However, it is not known if a mechanistic link exists between the corresponding genes and the respective stress response pathways. Here, we report that the correspondingmscLandarfAgenes are commonly co-located on the genomes of Gammaproteobacteria and display overlap in their respective 3′ UTR and 3′ CDS. We show this unusual genomic arrangement permits an antisense RNA–mediated regulatory control betweenmscLandarfA, and this modulates MscL excretory activity inE. coli. These findings highlight a mechanistic link between osmotic, translational stress responses and ECP inE. coli, further elucidating the previously unknown regulatory function ofarfAsRNA.

Objectives Brain tumors are the most common and fatal of all solid tumors for children and adolescents; those who survive live with long-term physical and emotional consequences, as do their families. We aimed to synthesize relevant qualitative evidence on families' experiences and psychosocial service needs across the lifespan to identify gaps in care delivery and research. Methods Searches were conducted in Medline, CINAHL, PsycInfo, Embase, and Web of Science. Identified papers were assessed with the Joanna Briggs Institute Critical Appraisal Tool. Data were extracted into NVivo12 and analyzed by qualitative description and, where appropriate, thematic analysis. Results The search yielded 628 papers, of which 40 (33 studies) were eligible (6%). Although the methodological quality of the papers was low, we identified concerns that were consistently reported over time and from different perspectives. Individual family members had varying psychosocial needs to be addressed within healthcare, schooling, and public policy. These include for survivor's mental health (particularly for body image), and to the disproportionate biopsychosocial burden faced by mother-caregivers. Conclusions Addressing the biological aspects of brain tumor cannot be our only focus. We have an obligation to provide services that meet the needs of families across diagnosis, treatment, survivorship, palliative care, and bereavement.

Patients with cancer are currently prioritized in coronavirus disease 2019 (COVID-19) vaccination programs globally, which includes administration of mRNA vaccines. Cytokine release syndrome (CRS) has not been reported with mRNA vaccines and is an extremely rare immune-related adverse event of immune checkpoint inhibitors. We present a case of CRS that occurred 5 d after vaccination with BTN162b2 (tozinameran)—the Pfizer-BioNTech mRNA COVID-19 vaccine—in a patient with colorectal cancer on long-standing anti-PD-1 monotherapy. The CRS was evidenced by raised inflammatory markers, thrombocytopenia, elevated cytokine levels (IFN-γ/IL-2R/IL-18/IL-16/IL-10) and steroid responsiveness. The close temporal association of vaccination and diagnosis of CRS in this case suggests that CRS was a vaccine-related adverse event; with anti-PD1 blockade as a potential contributor. Overall, further prospective pharmacovigillence data are needed in patients with cancer, but the benefit–risk profile remains strongly in favor of COVID-19 vaccination in this population., A rare case of cytokine release syndrome in a patient on anti-PD-1 blockade that was likely related to BNT162b2 vaccination supports prospective monitoring of patients with cancer after COVID-19 vaccine administration.

Transplant centers hesitate to transplant patients with cognitive impairment. It is unclear if pre-kidney transplant (KT) cognitive screening can predict post-KT cognitive function.We evaluated pre- to post-KT cognitive function with the Montreal Cognitive Assessment (MoCA) in a cohort of 108 patients. We used an adjusted logistic regression model to assess pre- to post-KT changes in cognitive status (continuous variable) and a linear mixed model to assess changes in MoCA scores (categorical variable) pre- to post- KT.The average pre- and post-KT MoCA scores were 25.3 ± 3.0 and 26.4 ± 2.8, respectively. Final pre-KT score did not predict post-KT cognitive status (OR = 1.08; 95% CI: .92-1.26; P = .35). 32% of the patients with a final pre-KT score ≥26 had at least one post-KT score 26. Conversely, 61% of the patients with a final pre-KT score 26 had at least one post KT score ≥26. In the linear mixed model analysis, the final pre-KT score was associated with a small, clinically insignificant (β = .34; 95% CI: .19-.49; P .001) effect on the post-KT score.A low pre-KT MoCA score is not a strong independent predictor of post-KT cognitive function and should not preclude patients from receiving a KT.

Background and Objective Omadacycline is an aminomethylcycline antibiotic approved in the USA as once-daily intravenous/oral monotherapy for adults with community-acquired bacterial pneumonia (CABP). Omadacycline demonstrated noninferiority to the fluoroquinolone moxifloxacin in a phase III CABP trial; adverse-event rates were similar between treatment groups except for Clostridioides difficile infection (CDI), which occurred in 2% of moxifloxacin-treated patients and 0% of patients on omadacycline. Conceptual healthcare-decision analytic models were developed to better understand the economic implications of antibiotic selection and CDI risk in acute-care facilities. Methods A conceptual healthcare-decision analytic model was created to estimate incremental costs associated with treating 100 hospitalized CABP patients with an initial 5-day inpatient regimen of omadacycline instead of moxifloxacin. The underlying model assumption was that treatment with omadacycline has the potential to reduce CDI events relative to moxifloxacin. The model included excess costs associated with each treatment group from admission through discharge. Attributable CDI cost per case in the moxifloxacin group varied from $15,000 to $45,000 (US$). Omadacycline acquisition cost was $300–600/day for 5 days. Results At a CDI attributable cost per case of $30,000 (base-case analyses), the incremental treatment cost (US$) per 100 patients ranged from $300,000 to $− 120,000 (cost savings). The excess CDI incidence in moxifloxacin-treated patients would need to be 5–10% for omadacycline to be cost-saving, assuming the attributable CDI cost is approximately $30,000. Conclusion Targeted omadacycline use may reduce economic burden associated with hospitalized CABP patients treated with moxifloxacin if it can reduce excess cases of moxifloxacin-associated CDI.

Individuals on the autism spectrum experience high rates of mental health issues. Meta-analyses indicate promising effects of psychological therapies, but challenges remain in ensuring and supporting access. This systematic review identified 12 studies that report on the barriers and facilitators to accessing psychological treatments for mental health or emotional/behavioural challenges for individuals on the autism spectrum. The most commonly reported barrier was a lack of therapist knowledge or expertise in autism or an inability or unwillingness on the part of the therapist to tailor approaches to support the needs of those on the autism spectrum. Fewer studies identified facilitators to accessing services. The findings highlight avenues for improving access to mental health services for individuals on the autism spectrum.

Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886), we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralizing antibody titers (NAbTs) using a live virus microneutralization assay against wild-type (WT), Delta, and Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titers and T cell responses after the fourth vaccine dose increased compared with that after the third vaccine dose. Patients who received B cell-depleting therapies within the 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination.

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer.

ABSTRACT INTRODUCTIONScreening tools assist primary care clinicians to identify mental health, addiction and family violence problems. Electronic tools have many advantages, but there are none yet available in the perinatal context. AIMTo assess the acceptability and feasibility of the Maternity Case-finding Help Assessment Tool (MatCHAT), a tool designed to provide e-screening and clinical decision support for depression, anxiety, cigarette smoking, use of alcohol or illicit substances, and family violence among pre- and post-partum women under the care of midwives. METHODSA co-design approach and an extensive consultation process was used to tailor a pre-existing electronic case-finding help assessment tool (eCHAT) to a maternity context. Quantitative MatCHAT data and qualitative data from interviews with midwives were analysed following implementation. RESULTSFive midwives participated in the study. They reported that MatCHAT was useful and acceptable and among the 20 mothers screened, eight reported substance use, one depression and five anxiety. Interviews highlighted extensive contextual barriers of importance to the implementation of maternity-specific screening. DISCUSSIONMatCHAT has potential to optimise e-screening and decision support in maternity settings, but in this study, use was impeded by multiple contextual barriers. The information from this study is relevant to policymakers and future researchers when considering how to improve early identification of common mental health, substance use and family violence problems.

Not all patients with cancer, in particular those with hematogic malignancies, develop functional immunity against SARS-CoV-2 variants of concern (VOC) following COVID-19 vaccines. Durability of vaccine-induced immunity after two doses and the impact of a third dose were evaluated in CAPTURE (NCT03226886), a longitudinal prospective cohort study of vaccine responses in patients with cancer. In evaluating 316 patients, at a median of 111 days following two doses of either BNT16b2 or ChadOX, we observed a time-dependant decline in neutralising antibody titres (NAbT) in a proportion of patients, where NAbTs became undetectable against Delta and Beta in 17% and 15% of patients, respectively. Vaccine-induced T cell responses declined in 44% of patients. Patients with breakthrough infections following two vaccines doses were characterised by absent/low NAbT to Delta prior to infection. Administration of the third vaccine dose boosted NAb responses against VOC in the majority of patients with cancer, especially those with solid cancer. In patients with hematologic malignancies who had undetectable NAbT against Delta after two vaccine doses, 54% did not develop NAb against both Beta and Delta following the third dose. Third vaccine dose boosted T cell responses were boosted in patients with both solid and hematologic malignancies. These results provide critical information on vaccine responses in patients with cancer, especially against VOCs and support widespread access to a third COVID-19 vaccination in this patient group.

FOLFIRINOX, a combination of chemotherapy drugs (Fluorouracil, Oxaliplatin, Irinotecan -FOI), provides the best clinical benefit in pancreatic ductal adenocarcinoma (PDAC) patients. In this study we explore the role of miRNAs (MIR) as modulators of chemosensitivity to identify potential biomarkers of response. We find that 41 and 84 microRNA inhibitors enhance the sensitivity of Capan1 and MiaPaCa2 PDAC cells respectively. These include a MIR1307-inhibitor that we validate in further PDAC cell lines. Chemotherapy-induced apoptosis and DNA damage accumulation are higher in MIR1307 knock-out (MIR1307KO) versus control PDAC cells, while re-expression of MIR1307 in MIR1307KO cells rescues these effects. We identify binding of MIR1307 to CLIC5 mRNA through covalent ligation of endogenous Argonaute-bound RNAs cross-linking immunoprecipitation assay. We validate these findings in an in vivo model with MIR1307 disruption. In a pilot cohort of PDAC patients undergoing FOLFIRONX chemotherapy, circulating MIR1307 correlates with clinical outcome., Understanding which patients will respond to FOLFIRINOX therapy is important for clinical outcome. Here, the authors show that the MIR1307 is increased pancreatic cancer cell lines and inhibition of the microRNA sensitises cells to treatment.’ stratifying patients to achieve the best clinical outcome. Here, the authors show that the MIR1307 is increased in a subgroup of human pancreatic cancers and inhibition of the microRNA in in vitro and in vivo models of pancreatic cancer sensitises cells to treatment.

Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic.

Anxiety in autism is commonly reported by parents, but teacher reports of anxiety in their students with autism have received little attention. This paper presents the results from the first systematic review on anxiety in children with autism at school. Six intervention studies (five of which were based upon cognitive–behavioural therapy) and 26 descriptive/non-experimental studies met inclusion criteria. Sample populations from included studies were frequently drawn from psychiatric clinics, with females and children attending special schools underrepresented, making generalisability of results difficult. Few studies used anxiety-specific measures, with most reporting anxiety-related subscale means from broader emotional/behavioural questionnaires. While 19 studies included multiple informants, which is recommended practice, only seven studies combined parent, teacher and child reports of anxiety. Comparison between informants proved difficult, with varying sample sizes and few studies using the same measure across participant groups. To further our understanding of the presentation of anxiety in children with autism attending school, studies need to include multiple informants and, where possible, extend beyond reporting average scores from broad anxiety subscales to provide descriptions of presentation and symptomatology.

Endometriosis is currently poorly understood by the medical sciences; contemporary healthcare has been evidenced as failing to meet the diverse needs of the women who live with the condition. This study examined women’s experiences of navigating knowledge and power within medical encounters for endometriosis. In-depth interviews were conducted with 26 women who have been diagnosed with endometriosis about their experiences of the condition and associated healthcare. Women valued both their own knowledge and their doctor’s clinical expertise; as to which they privileged was situational, but it was essential the woman dictated which it would be. Women were wary of the social status and power of doctors to reduce their wellbeing through medical labels they did not identify with or by inhibiting their access to care. They identified the need for doctors to listen to and believe them as being essential to the provision of healthcare that meets women’s needs and addresses the complexities of endometriosis. Our findings suggest that medical education needs to equip doctors with the skills to acknowledge and incorporate women’s knowledge of their bodies within the medical encounter, and to understand how their practice affects women’s social and economic participation.

This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR002) of the Conference Proceedings. Citation Format: Alexander Coulton, Irene Lobon, Lavinia Spain, Andrew Rowan, Desiree Shnidrig, Scott Shepherd, Ben Shum, Fiona Byrne, Lewis Au, Kim Edmonds, Ellie Carlyle, Alexandra Renn, Christina Messiou, Charlotte Spencer, Andreas M. Schmidt, Zayd Tippu, Aljosja Rogiers, Max Emmerich, Camille Gerard, Husayn Pallikonda, Cristina Naceur-Lombardelli, Floris Foijer, Hilda van den Bos, René Wardenaar, Diana Spierings, Kate Young, Lisa Pickering, Andrew Furness, Elaine Borg, Miriam Mitchison, David Moore, Mary Falzon, Ian Proctor, Ruby Stewart, Ula Mahadeva, Anna Green, James Larkin, Charles Swanton, Mariam Jamal-Hanjani, Kevin Litchfield, Samra Turajlic. Advanced melanoma exhibits a diversity of evolutionary routes to lethality [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A012.