Oncologists’ Perceptions of Tumor Genomic Profiling and the Communication of Test Results and Risks

Tumor genomic profiling (TGP) identifies genetic targets for precision cancer treatments. The complexity of TGP can expose gaps in oncologists’ skills, complicating test interpretation and patient communication. Research on oncologists’ use and perceptions of TGP could inform practice patterns and training needs. To study this, a sample of oncologists was surveyed to assess TGP use, perceptions, and perceived skills in TGP interpretation/communication, especially in communication of hereditary risks. Genomic self-efficacy and TGP knowledge were also assessed. The goal sample (<i>n</i> = 50) was accrued from 12/2019 to 1/2020. Respondents were primarily medical oncologists (78%) with &#x3e;10 (mean 17.7) years of practice experience. TGP use was moderate/high (median 50 [range 2–398]) tests/year. Most oncologists reported informal/no training in interpretation (72%) or communication (86%) of TGP results and risks. Genomic self-efficacy was high and was associated with higher use of TGP (<i>p</i> = 0.047). Perceptions of the benefits and limitations of TGP were mixed: heterogeneity was seen by years of experience, TGP use, and knowledge. Most participants agreed that additional training in TGP communication was needed, especially in communication of hereditary risks, and that an online training tool would be useful (86%). We conclude that oncologists are frequently using TGP despite having mixed views about its utility and not feeling prepared to communicate risks to patients. Oncologists receive little education in interpreting TGP or communicating its results and risks, and would value training in this area.

Exposure to cisplatin in the operating room during hyperthermic intrathoracic chemotherapy

Purpose Hyperthermic intrathoracic chemotherapy (HITOC) is an additive, intraoperative treatment for selected malignant pleural tumors. To improve local tumor control, the thoracic cavity is perfused with a cisplatin-containing solution after surgical cytoreduction. Since cisplatin is probably carcinogenic to humans, potential contamination of surfaces and pathways of exposure should be systematically investigated to enable risk assessments for medical staff and thus derive specific recommendations for occupational safety. Methods Wipe sampling was performed at pre-selected locations during and after ten HITOC procedures, including on the surgeon's gloves, for the quantitation of surface contaminations with cisplatin. After extraction of the samples with hydrochloric acid, platinum was determined as a marker for cisplatin by voltammetry. Results High median concentrations of cytostatic drugs were detected on the surgeons’ (1.73 pg Cis-Pt/cm2, IQR: 9.36 pg Cis-Pt/cm2) and perfusionists’ (0.69 pg Cis-Pt/cm2, IQR: 1.73 pg Cis-Pt/cm2) gloves. The display of the perfusion device showed partially elevated levels of cisplatin up to 4.92 pg Cis-Pt/cm2 and thus could represent an origin of cross-contamination. In contrast, cisplatin levels on the floor surfaces in the area of the surgeon and the perfusion device or in the endobronchial tube were relatively low. Conclusion With a correct use of personal protective equipment and careful handling, intraoperative HITOC appears to be safe to perform with a low risk of occupational exposure to cisplatin.

OP0078 HIGH MEDIAN NERVE LESION SECONDARY TO SEVERE GIANT CELL ARTERITIS (GCA)

Background:Giant cell arteritis (GCA) is a systemic vasculitis affecting large to medium-sized vessels. Cranial nerve lesions are frequently documented secondary to GCA, however peripheral nerves are rarely involved.Objectives:We present an unusual case of a GCA-associated isolated high median nerve palsy.Methods:Case report.Results:A 76 year old white British female presented in Spain with three weeks of frontotemporal headaches, mandibular claudication, photopsia and constitutional symptoms, followed by acute-onset right hand paresis and dysaesthesia. Acute-phase reactants were elevated. COVID-19 PCR was negative. Shortly after admission she developed acute bilateral anterior ischaemic optic neuropathy and tongue necrosis with autoamputation. Temporal artery ultrasound and biopsy confirmed GCA. PET-CT showed no evidence of a diffuse large-vessel vasculitis. She was repatriated to the UK for ongoing inpatient care. Upper limb neurophysiology two months later demonstrated an isolated right high median nerve lesion, with reduced median motor responses and absent sensory responses with denervation in extensor carpi radialis. Imaging excluded a central lesion. The timing of her symptoms suggested the lesion was secondary to GCA. Treatment was with tocilizumab, methotrexate and tapering corticosteroids, alongside PEG feeding and careful multi-disciplinary rehabilitation.Conclusion:We suggest there are two important learning points from this complex case. Firstly, peripheral nerve lesions can occur in GCA, although they are rare. A literature search identified a modest number of case reports of brachial plexus or lower cervical nerve lesions1,2. Neurologic manifestations in GCA are attributed to vasculitis of the vasa nervorum, or extension of inflammation from arteries to contiguous nerves1,2. The restriction of clinical involvement to the median nerve alone would appear to favour the former mechanism. Functional recovery of neurological deficits is typically partial at best.Secondly, this case highlights the difficulty faced by clinicians in recognising GCA and the importance of urgent treatment with glucocorticoids. The patient developed GCA during the ongoing COVID-19 pandemic when Spain was the second-worst affected European country (5% seroprevalence; 95% CI 4.7-5.4)3. The partial overlap in symptoms between GCA and COVID-19 (e.g. headache, pyrexia, malaise, elevated acute-phase reactants) can cause diagnostic confusion and treatment delay4. GCA should be considered in the differential diagnosis of older patients with suspected COVID-19, or the non-specifically unwell elderly patient.References:[1]Blaise S, et al. Horton’s disease revealed by brachial C5 plexopathy [French]. Rev Med Interne. 2005;26(7):578-82.[2]Merianos P, et al. Giant cell arteritis of the median nerve simulating carpal tunnel syndrome. Hand. 1983;15(3): 249-251.[3]Pollán M, et al. Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. Lancet. 2020; 396(10250): 535-544.[4]Monti S, Delvino P, et al. Impact of delayed diagnoses at the time of COVID-19: increased rate of preventable bilateral blindness in giant cell arteritis. Ann Rheum Dis. 2020;79:1658-1659.Table 1.Area/movementResultAbductor pollicis brevisGrade 2 weaknessOpponens pollicisGrade 4 weaknessPronator teres/quadratusGrade 4 weaknessFlexor pollicis longusGrade 1-2 weaknessFlexor digitorum profundus (digit 2 and 3)Grade 1-2 weaknessFinger abductionPreservedFinger extensionPreservedOther commentsDysaesthesia in distribution of median nerveDisclosure of Interests:Kundan Iqbal: None declared, James Miller Speakers bureau: Dr Miller has participated in pharmaceutical-sponsored symposiums previously but not in last five years., Consultant of: Dr Miller has participated in pharmaceutical-sponsored consultancy previously but not in last five years., Ming Lai: None declared, Mia Charnley: None declared, Muhammad Meraj: None declared, Ben Thompson Speakers bureau: Dr Thompson has participated in educational talks for Roche, Novartis, Lilly and UCB., Consultant of: Dr Thompson has participated in advisory boards for Roche, Novartis, Lilly, Gilead, Abbvie and UCB.

Pulmonary Lobe Segmentation in CT Images Based on Lung Anatomy Knowledge

In computed tomography (CT) images, pulmonary lobe segmentation is an arduous task due to its complex structures. To remedy the problem, we introduce a new framework based on lung anatomy knowledge for lung lobe segmentation. Firstly, the priori knowledge of lung anatomy is used to identify the fissure region of interest. Then, an oriented derivative of stick filter is applied to isolate plate-like structures from clutters for lobar fissure verification. Finally, a surface fitting model is employed to complete the incomplete fissure surface for lung lobe segmentation. Compared with manually segmented fissure references, the designed approach obtained a high median F1-score of 0.8865 in the left lung and obtained a high median F1-score of 0.9200 in the right lung. The average percentages of the segmented lung lobes in the lung lobe ground truth are 0.960, 0.989, 0.973, 0.920, and 0.985 for the left upper, left lower, right upper, right middle, and right lower lobes, respectively. The perfect performance of the proposed scheme is tested by visual inspection and quantitative evaluation.

The pandemic politics of existential anxiety: Between steadfast resistance and flexible resilience

We all know we will die, but not when and how. Can private death awareness become public, and what happens when it does? This mixed-method research on the Covid-19 crisis reveals how pandemic politics cultivates and uses mass existential anxiety. Analyzing global discourse across vast corpora, we reveal an exceptional rise in global ‘mortality salience’ (awareness of death), and trace the socio-political dynamics feeding it. Comparing governmental pandemic policies worldwide, we introduce a novel model discerning ‘mortality mitigation’ (coping mechanisms) on a scale from steadfast resistance (‘oak’) to flexible resilience (‘reed’). We find that political trust, high median age, and social anxiety predict a reedy approach; and that the oak, typically pushing for stricter measures, better mitigates mortality. Stringency itself, however, hardly affects Covid-related cases/deaths. We enrich our model with brief illustrations from five countries: China and Israel (both oaks), Sweden and Germany (reeds) and the USA (an oak–reed hybrid).

Higher CD1a Levels Correlate with PD-L1 Expression and Predict Worse Overall Survival in Triple-Negative Breast Carcinoma

Objective: The aim of this study was to measure the expression of PD-L1, CD1a (a marker for immature dendritic cells), and CD83 (a marker for mature dendritic cells) and further examine the associations of PD-L1, CD83, and CD1a with overall survival (OS) in triple-negative breast carcinoma patients. Methods: PD-L1, CD1a, and CD83 expression in breast carcinoma tissues and CD83 expression in lymph node tissues were examined by immunohistochemistry and tissue microarray in 159 patients. Patients were classified into the low, medium, and high PD-L1, CD1a, and CD83 levels. Pearson χ2 test was used to analyze the correlations between PD-L1, CD1a, and CD83. The Kaplan-Meier method was used to calculate the OS. Multivariate analysis was used to identify determinants of 3- and 5-year OS. Results: 25.1, 25.8, and 49.1% of the patients had low, medium, and high PD-L1 levels, respectively. PD-L1 levels significantly correlated with CD1a (r = 0.30409, p < 0.001) and CD83 levels (r = 0.6146, p < 0.001) in breast carcinoma tissue, as well as CD83 levels (r = 0.17508, p = 0.027) in lymph node. The median OS was 83 months (range 12–106), and the 3- and 5-year OS rates were 94.97% (95% CI 91.57–98.37) and 86.79% (95% CI 81.53–92.06), respectively. Moreover, patients with high median CD1a levels had a significantly lower 5-year OS rate (75.6%) than those with low median CD1a levels (93.5%, p = 0.038). Conclusion: PD-L1, CD1a, and CD83 are variably expressed in triple-negative breast carcinoma tissues, and PD-L1 expression correlates with CD1a and CD83. Higher CD1a levels correlate with PD-L1 expression and predict worse OS in triple-negative breast carcinoma.

Burden and social support in informal caregivers of people undergoing kidney dialysis: a mixed study

ABSTRACT Objectives: to analyze the burden and the social support of the informal caregivers of people undergoing kidney dialysis. Methods: mixed study, based on the Theory of Stress and Overload, using instruments of sociodemographic characterization, the Social Support Survey from the Medical Outcomes Study, Zarit’s Burden Scale, and guiding questions. Analysis of data used statistical and thematic inferences. Results: 55 caregivers were evaluated, most were women, from 31 to 50 years old, married, and having worked in care for more than three years. A high level of affective and material support was observed, with a light overload on the caregiver. The central theme of the discourses was: “Experiences of the caregiver: between the burden of responsibility and the search for meaning”. Conclusions: a small overload was found in the participants, with a high median in the dimensions of affective and emotional support, in the relations between positive social interactions and the burden of the caregivers, in addition to the duality or responsibility and the meaning of care.

Neutrophil subpopulations and their activation potential in patients with antiphospholipid syndrome and healthy individuals

Objectives Patients with APS are at increased risk of thromboembolism. Neutrophils have been shown to play a role in inducing thrombosis. We aimed to investigate differences in neutrophil subpopulations, their potential of activation and neutrophil extracellular trap (NET) formation comparing high and low-density neutrophils (HDNs/LDNs) as well as subpopulations in patients with APS and controls to gain deeper insight into their potential role in thrombotic manifestations in patients with APS. Methods HDNs and LDNs of 20 patients with APS and 20 healthy donors were isolated by density gradient centrifugation and stimulated. Neutrophil subpopulations, their activation and NET release were assessed by flow cytometry. Results LDNs of both groups showed higher baseline activation, lower response to stimulation (regulation of activation markers CD11b/CD66b), but higher NET formation compared with HDNs. In patients with APS, the absolute number of LDNs was higher compared with controls. HDNs of APS patients showed higher spontaneous activation [%CD11b high: median (interquartile range): 2.78% (0.58–10.24) vs 0.56% (0.19–1.37)] and response to stimulation with ionomycin compared with HDNs of healthy donors [%CD11b high: 98.20 (61.08–99.13) vs 35.50% (13.50–93.85)], whereas no difference was found in LDNs. NET formation was increased in patients’ HDNs upon stimulation. Conclusion HDNs and LDNs act differently, unstimulated and upon various stimulations in both healthy controls and APS patients. Differences in HDNs and LDNs between patients with APS and healthy controls indicate that neutrophils may enhance the risk of thrombosis in these patients and could thus be a target for prevention of thrombosis in APS.