Visual hallucinations after resection of cerebral metastases: two patients with complex phantom images.

PURPOSE: Complex visual hallucinations are rarely seen in neurooncology. They are commonly observed alongside psychotic symptoms in schizophrenia or dementia, in Parkinson's or Lewy-body disease, after opioid medications or anesthesia, and, in particular, they appear with visual impairments. METHODS: Here we report two normal-sighted and mentally healthy patients with unusual visual hallucinations after the resection and irradiation of brain metastases, the main features of which were persistent colorful and meaningful images with hallucinatory perseveration. RESULTS: These cases demonstrate the occurrence of complex visual hallucinations after resection of visual cortices as an effect of deafferentation, so-called visual release hallucinations or phantom images, similar to phantom pain after amputation of a limb. CONCLUSION: This case serves to heighten awareness in the radiooncology practitioner of the occurrence of visual release hallucinations (Charles Bonnet syndrome) related to multidisciplinary treatment of brain metastases.

Induction of cancer neoantigens facilitates development of clinically relevant models for the study of pancreatic cancer immunobiology.

Neoantigen burden and CD8 T cell infiltrate are associated with clinical outcome in pancreatic ductal adenocarcinoma (PDAC). A shortcoming of many genetic models of PDAC is the lack of neoantigen burden and limited T cell infiltrate. The goal of the present study was to develop clinically relevant models of PDAC by inducing cancer neoantigens in KP2, a cell line derived from the KPC model of PDAC. KP2 was treated with oxaliplatin and olaparib (OXPARPi), and a resistant cell line was subsequently cloned to generate multiple genetically distinct cell lines (KP2-OXPARPi clones). Clones A and E are sensitive to immune checkpoint inhibition (ICI), exhibit relatively high T cell infiltration, and have significant upregulation of genes involved in antigen presentation, T cell differentiation, and chemokine signaling pathways. Clone B is resistant to ICI and is similar to the parental KP2 cell line in terms of relatively low T cell infiltration and no upregulation of genes involved in the pathways noted above. Tumor/normal exome sequencing and in silico neoantigen prediction confirms successful generation of cancer neoantigens in the KP2-OXPARPi clones and the relative lack of cancer neoantigens in the parental KP2 cell line. Neoantigen vaccine experiments demonstrate that a subset of candidate neoantigens are immunogenic and neoantigen synthetic long peptide vaccines can restrain Clone E tumor growth. Compared to existing models, the KP2-OXPARPi clones better capture the diverse immunobiology of human PDAC and may serve as models for future investigations in cancer immunotherapies and strategies targeting cancer neoantigens in PDAC.

Feasibility and Accuracy of Measuring Carotid Plaque Volume (Burden) With Contrast-Enhanced Tomographic 3D Ultrasound and Ultrasound Image Fusion.

BACKGROUND: Stenosis severity has been the indication for carotid endarterectomy (CEA) for 4 decades, but the annual stroke risk in asymptomatic carotid stenosis >70% is under 2%. Atherosclerotic volume has emerged as a risk factor for future stroke, but needs to be measured noninvasively. Tomographic ultrasound (tUS) is a novel technology that assembles 3D images in seconds. We evaluated accuracy of measuring Carotid Plaque Volume (CPV) with tUS in patients undergoing CEA. METHOD: Consecutive patients were imaged immediately before CEA by tUS and contrast-enhanced tUS (CEtUS). CPV was measured using tUS, CEtUS, and a fused images incorporating both tUS and CEtUS by trained vascular scientists. Precise volume of the endarterectomy specimen was measured using Archimedes technique. RESULTS: Mean ± sd (range) CPV in 129 endarterectomy specimens was 0.75 ± 0.43 cm3 (0.10-2.47 cm3). Mean ± sd CPV measured by tUS (n = 114) was 0.87 ± 0.51 cm3, CEtUS (n = 104) was 0.75 ± 0.45 cm3 and with fusion (n = 95) was 0.83 ± 0.49 cm3. Differences between specimen volume and CPV measured by tUS (0.13 ± 0.24 cm3), CEtUS (-0.01 ± 0.21 cm3) or fusion (-0.08 ± 0.20) were clinically insignificant. Intra-/interobserver differences were minimal. CONCLUSIONS: tUS accurately measures CPV with excellent intra-/interobserver agreement. CEtUS improves accuracy if precise CPV measurement is needed for research but tUS alone would be sufficient for population screening.

Stereotactic radiosurgery and radiotherapy for resected brain metastases: current pattern of care in the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Association for Radiation Oncology (DEGRO).

PURPOSE: Preoperative stereotactic radiosurgery (SRS) of brain metastases may achieve similar local control and better leptomeningeal control rates than postoperative fractionated stereotactic radiotherapy (FSRT) in patients treated with elective metastasectomy. To plan a multicentre trial of preoperative SRS compared with postoperative FSRT, a survey of experts was conducted to determine current practice. METHODS: A survey with 15 questions was distributed to the DEGRO Radiosurgery and Stereotactic Radiotherapy Working Group. Participants were asked under what circumstances they offered SRS, FSRT, partial and/or whole brain radiotherapy before or after resection of a brain metastasis, as well as the feasibility of preoperative stereotactic radiosurgery and neurosurgical resection within 6 days. RESULTS: Of 25 participants from 24 centres, 22 completed 100% of the questions. 24 respondents were radiation oncologists and 1 was a neurosurgeon. All 24 centres have one or more dedicated radiosurgery platform and all offer postoperative FSRT. Preoperative SRS is offered by 4/24 (16.7%) centres, and 9/24 (37.5%) sometimes recommend single-fraction postoperative SRS. Partial brain irradiation is offered by 8/24 (33.3%) centres and 12/24 (50%) occasionally recommend whole-brain irradiation. Two centres are participating in clinical trials of preoperative SRS. SRS techniques and fractionation varied between centres. CONCLUSION: All responding centres currently offer postoperative FSRT after brain metastasectomy. Approximately one third offer single-fraction postoperative SRS and four already perform preoperative SRS. With regard to potential co-investigators, 18 were identified for the PREOP­2 multicentre trial, which will randomise between preoperative SRS and postoperative FSRT.

I22: SAXS/WAXS beamline at Diamond Light Source - an overview of 10 years operation.

Beamline I22 at Diamond Light Source is dedicated to the study of soft-matter systems from both biological and materials science. The beamline can operate in the range 3.7 keV to 22 keV for transmission SAXS and 14 keV to 20 keV for microfocus SAXS with beam sizes of 240 µm × 60 µm [full width half-maximum (FWHM) horizontal (H) × vertical (V)] at the sample for the main beamline, and approximately 10 µm × 10 µm for the dedicated microfocusing platform. There is a versatile sample platform for accommodating a range of facilities and user-developed sample environments. The high brilliance of the insertion device source on I22 allows structural investigation of materials under extreme environments (for example, fluid flow at high pressures and temperatures). I22 provides reliable access to millisecond data acquisition timescales, essential to understanding kinetic processes such as protein folding or structural evolution in polymers and colloids.

Jumping in lantern bugs (Hemiptera, Fulgoridae).

Lantern bugs are amongst the largest of the jumping hemipteran bugs, with body lengths reaching 44 mm and masses reaching 0.7 g. They are up to 600 times heavier than smaller hemipterans that jump powerfully using catapult mechanisms to store energy. Does a similar mechanism also propel jumping in these much larger insects? The jumping performance of two species of lantern bugs (Hemiptera, Auchenorrhyncha, family Fulgoridae) from India and Malaysia was therefore analysed from high-speed videos. The kinematics showed that jumps were propelled by rapid and synchronous movements of both hind legs, with their trochantera moving first. The hind legs were 20-40% longer than the front legs, which was attributable to longer tibiae. It took 5-6 ms to accelerate to take-off velocities reaching 4.65 m s-1 in the best jumps by female Kalidasa lanata. During these jumps, adults experienced an acceleration of 77 g, required an energy expenditure of 4800 µJ and a power output of 900 mW, and exerted a force of 400 mN. The required power output of the thoracic jumping muscles was 21,000 W kg-1, 40 times greater than the maximum active contractile limit of muscle. Such a jumping performance therefore required a power amplification mechanism with energy storage in advance of the movement, as in their smaller relatives. These large lantern bugs are near isometrically scaled-up versions of their smaller relatives, still achieve comparable, if not higher, take-off velocities, and outperform other large jumping insects such as grasshoppers.

Five fraction stereotactic radiotherapy after brain metastasectomy: a single-institution experience and literature review.

PURPOSE: The outcomes of five fraction stereotactic radiotherapy (hfSRT) following brain metastasectomy were evaluated and compared with published series. METHODS: 30 Gy in 5 fractions HfSRT prescribed to the surgical cavity was reduced to 25 Gy if the volume of 'brain-GTV' receiving 20 Gy exceeded 20 cm3. Endpoints were local recurrence, nodular leptomeningeal recurrence, new brain metastases and radionecrosis. The literature was searched for reports of clinical and dosimetric outcomes following postoperative hfSRT in 3-5 fractions. RESULTS: 39 patients with 40 surgical cavities were analyzed. Cavity local control rate at 1 year was 33/40 (82.5%). 3 local failures followed 30 Gy/5 fractions and 4 with 25 Gy/5 fractions. The incidence of leptomeningeal disease (LMD) was 7/40 (17.5%). No grade 3-4 toxicities, particularly no radionecrosis, were reported. The incidence of distant brain metastases was 15/40 (37.5%). The median overall survival was 15 months. Across 13 published series, the weighted mean local control was 83.1% (adjusted for sample size), the mean incidence of LMD was 14.9% (7-34%) and the mean rate of radionecrosis was 10.3% (0-20.6%). CONCLUSION: Postoperative hfSRT can be delivered with 25-30 Gy in 5 fractions with efficacy in excess of 82% and no significant toxicity when the dose to 'brain-GTV' does not exceed 20 cm3.

Imaging digital arteries in systemic sclerosis by tomographic 3-dimensional ultrasound.

Objective methods are needed to quantify digital artery disease in systemic sclerosis (SSc) for clinical trials of vascular therapies. Our primary aim was to examine feasibility of a novel tomographic three-dimensional-(3-D) ultrasound (tUS) with high-frequency ultrasound (HFUS) or ultra-high-frequency ultrasound (UHFUS) to assess the digital arteries in patients with SSc compared to healthy controls. A secondary objective was to compare the total wall volume (TWV) as a measure of intimal/medial thickness. Eighteen patients with a confirmed diagnosis of SSc were studied by tUS HFUS (17.5 MHz, n = 10) or tUS UHFUS (48 and 70 MHz, n = 8) with equal numbers of healthy controls of similar age and gender. The majority of patients had limited cutaneous SSc and were representative of a spectrum of digital vasculopathy, with over half (n = 6 HFUS and n = 5 UHFUS) having previous digital ulceration. Over half were receiving oral vasodilatory therapy. TWV was measured in both digital arteries of the middle finger bilaterally. At least, two digital arteries could be identified at 17.5 MHz in all patients and healthy controls. Whereas, at least two digital arteries could be identified in relatively fewer patients compared to healthy controls using 48 MHz (n = 6 and 10) and especially 70 MHz (n = 4 and 10) UHFUS. The median difference in TWV between patients and healthy controls was -6.49 mm3 using 17.5 MHz, 1.9 mm3 at 48 MHz, and -0.4 mm3 at 70 MHz. tUS using UHFUS is a feasible method to measure TWV of digital arteries in SSc. Transducer frequency plays an important factor in successful digital artery measurement, with 48 MHz being the optimal frequency.

The After Diagnosis Head and Neck cancer-specific Patient Concerns Inventory (HaNC-AD) as a pre-treatment preparation aid during the COVID-19 pandemic.

The coronavirus disease 2019 pandemic has resulted in new challenges for clinicians, head and neck cancer (HNC) patients and carers. There is evidence that the current crisis is affecting the management of HNC patients. Most healthcare systems have introduced remote consultations to decrease the risk of coronavirus infection to patients, carers and clinicians. At present, HNC patients may be anxious and due to logistical issues, may not be adequately prepared for their treatment. To ensure that patients have a thorough understanding of their treatment and expected outcome during the current COVID-19 crisis there may be merit in the use of the HaNC-AD PCI.

Quality of life, cognitive, physical and emotional function at diagnosis predicts head and neck cancer survival: analysis of cases from the Head and Neck 5000 study.

PURPOSE: The aim of this paper is to determine whether health-related quality of life (HRQOL) at diagnosis of head and neck cancer (HNC) is associated with overall survival following treatment with curative intent after adjusting for other factors. METHODS: Data were collected from 5511 participants of the Head and Neck 5000 study (HN5000). HRQOL was measured using the EORTC QLQ-C30. Questionnaire and covariate data were available from 2171 participants diagnosed as follows: oral cavity (655), oropharynx HPV+ (723) and HPV- (277), and larynx (516). On average, participants were followed up 3.2 years (SD 1.2) after diagnosis. Data were adjusted for age, gender, co-morbidity, intended treatment, education level, income from benefits, smoking status and alcohol consumption. RESULTS: There was a clinically meaningful difference between Global HRQOL scores at diagnosis and survival in an unadjusted and adjusted model: [HR = 0.86, CI 0.82-0.89, p < 0.001 (unadjusted) and HR = 0.90, CI 0.86-0.94, p < 0.001 (adjusted)]. In analyses stratified by tumour site and HPV status, this association was similarly noted before adjustment and persisted after. There were some tumour sub-site variations: improved survival for people with laryngeal cancer reporting higher levels of physical role or social functioning and people with oral cancer reporting higher levels of role or social functioning. CONCLUSION: As survival is the main priority for most people diagnosed with cancer, pre-treatment HRQOL is an additional factor to be included in risk stratification and case-mix adjustments. There is merit in incorporating HRQOL into routine clinical care as this is a useful facet in patient-clinician decision making, prognostication and recovery.

"I Don't Feel Like I Have a Problem Because I Can Still Go To Work and Function": Problem Recognition Among Persons With Substance Use Disorders.

Background: Persons with substance use disorders (SUDs) who do not recognize their substance use as problematic are less likely to perceive needing treatment and less motivated to seek help. Factors that contribute to problem recognition among persons with SUDs are poorly understood. Objective: To explore in-depth factors that may explain why those who meet diagnostic criteria for SUDs do not perceive having a substance abuse problem. Methods: We recruited 54 participants with recent (i.e., past-5-year) SUD for qualitative interviews. Participants were recruited via online ads and screened for eligibility through an online survey. Interview questions focused on participants' alcohol and drug use behaviors, adverse consequences stemming from their substance use, past treatment use experiences, and barriers/reasons for not using specialty treatment. Interviews were thematically coded to identify prominent themes that may explain low problem recognition. Results: We identified two prominent themes that contributed to problem recognition: modifying substance use behaviors to avoid adverse consequences and stigma (i.e., "othering"). Participants who (1) reported adjusting their alcohol and drug use in ways that would not interfere with important life responsibilities, especially work-responsibilities; (2) described those with alcohol and drug problems negatively; and (3) associated treatment with personal defeat were less likely to perceive having a SUD. Conclusions/Importance: These findings can be used to inform intervention strategies aimed at increasing problem recognition among persons with SUDs. Such strategies may facilitate motivation (i.e., desire for help and treatment readiness) to use and complete treatment, thereby reducing the unmet treatment gap among persons with SUDs.

Carotid plaque volume in patients undergoing carotid endarterectomy.

BACKGROUND: The main indication for carotid endarterectomy (CEA) is severity of carotid artery stenosis, even though most strokes in carotid disease are embolic. The relationship between carotid plaque volume (CPV) and symptoms of cerebral ischaemia, and the measurement of CPV by minimally invasive tomographic ultrasound imaging, were investigated. METHODS: The volume of the endarterectomy specimen was measured using a validated saline suspension technique in patients undergoing CEA. Time from last symptom and severity of stenosis measured by duplex ultrasonography were recorded. Middle cerebral artery emboli were counted using transcranial Doppler imaging (TCD) in a subset of patients. RESULTS: Some 339 patients were included, 270 with symptomatic and 69 with asymptomatic carotid stenosis. Mean(s.d.) CPV was higher in symptomatic than in asymptomatic patients (0·97(0·43) versus 0.74(0·41) cm3 ; P < 0·001). CPV did not correlate with severity of carotid stenosis (P = 0·770). Mean CPV was highest at 1·03(0·46) cm3 in the 4 weeks following cerebral symptoms, declining to 0·78(0·36) cm3 beyond 8 weeks. Among 33 patients who had TCD, mean CPV was 1·00(0·48) cm3 in the 27 patients with ipsilateral cerebral emboli compared with 0·67(0·16) cm3 in those without (P = 0·142). There was excellent correlation between CPV measured by tomographic ultrasound imaging and the endarterectomy specimen in 34 patients (r = 0·93, P < 0·001). CONCLUSION: CPV correlated with symptoms of cerebral ischaemia, but not carotid stenosis. It could be a potential indicator for CEA.

A review of question prompt lists used in the oncology setting with comparison to the Patient Concerns Inventory.

A question prompt list (QPL) is a simple and inexpensive communication tool used to facilitate patient participation in medical consultations. The QPL is composed of a structured list of questions and has been shown to be an effective way of helping ensure patients' individual information needs are appropriately met. This intervention has been investigated in a variety of settings but not specifically head and neck cancer (HNC). The aim of this paper was to perform a narrative review of literature reporting the use of a QPL for oncology patients and to draw comparison to the Patient Concerns Inventory (PCI-HN). The databases Scopus, PubMed and MEDLINE were searched using the key terms 'question prompt list', 'question prompt sheet', 'cancer' and 'oncology'. Of 98 articles hand searched, 30 of which were found to meet all inclusion criteria, and described in a tabulated summary. The studies concluded that the QPL was an effective intervention, enabling active patient participation in medical consultations. The PCI-HN is specific for HNC and differs from many QPLs, which are more general cancer tools. The QPL approach should prove to be a useful intervention for HNC sufferers, however further research into the clinical utility is required.

Fear of cancer recurrence in oral and oropharyngeal cancer patients: An investigation of the clinical encounter.

Fear of cancer recurrence (FCR) is common among individuals treated for cancer. Explorations of how this fear is expressed within an oncology setting and responded to are currently lacking. The aim was to investigate how head and neck cancer survivors in follow-up consultations express FCR, investigate how a healthcare professional addresses recurrence fears, and examine how survivors experience this interaction. We recorded the follow-up consultations of those participants who have reported FCR as a concern on the Patient Concerns Inventory. We also conducted a follow-up phone interview with the participants. We analysed the transcripts using thematic analysis. Five men and six women were recruited, aged 55-87 (mean age = 64). Follow-up consultation analyses revealed that the consultant used "normalising FCR," "reassurance," and "offer of referral to a counsellor." Interviews revealed themes around how they coped with FCR, relevance of personal history on FCR, and the impact of feeling gratitude towards the consultant on expression of FCR. Analyses indicate that patients may feel reluctant to raise their FCR with their clinician for fear of appearing "ungrateful" or of damaging a relationship that is held in high esteem. Findings indicate the initiation of FCR with patients can be beneficial for patient support.

Time to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study.

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. SUBJECTS AND METHODS: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. RESULTS: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate. CONCLUSIONS: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.

Exploring Jordan's rule in Pacific three-spined stickleback Gasterosteus aculeatus.

Coastal marine Gasterosteus aculeatus were captured from seven locations along the Pacific coast of North America, ranging across 21·8° latitude to test Jordan's rule, i.e. that vertebral number should increase with increasing latitude for related populations of fish. Vertebral number significantly increased with increasing latitude for both total and caudal vertebral number. Increasing length with latitude (sensu Bergmann's rule) was also supported, but the predictions for Jordan's rule held when controlling for standard length. Pleomerism was weakly evidenced. Gasterosteus aculeatus exhibited sexual dimorphism for Jordan's rule, with both sexes having more vertebrae at higher latitudes, but only males showing a positive association between latitude and the ratio of caudal to abdominal vertebrae. The number of dorsal- and anal-fin rays and basals increased with increasing latitude, while pectoral-fin ray number decreased. This study reinforces the association between phenotypic variation and environmental variation in marine populations of G. aculeatus.

Cortisol metabolism, postnatal depression and weight changes in the first 12 months postpartum.

BACKGROUND & OBJECTIVES: Postnatal depression correlates with postpartum weight retention, and dysregulated cortisol metabolism is evident in depressed individuals. Cortisol metabolism, BMI and metabolic phenotype are robustly associated, but the role of cortisol metabolism in postnatal mental health and weight loss has never been examined. DESIGN: A longitudinal observation. PATIENTS: Forty nine healthy women with uncomplicated pregnancy. MEASUREMENTS: BMI and urinary steroid metabolites at 1 week and 1, 3, 6 and 12 months postpartum. Validated urinary steroid metabolite ratios were measured to determine the activities of 11ß-hydroxysteroid dehydrogenases (11ß-HSD) that interconvert inactive cortisone and active cortisol and the 5α-reductases that clear cortisol to its inactive metabolites. Postnatal depression symptoms were measured at 1, 6 and 12 months. RESULTS: Low 5α-reductase activity was associated with greater weight loss across the first year, independent of demographics, breastfeeding and depression. Postpartum BMI change was unrelated to postnatal depression at any time. Symptoms of postnatal depression were related to higher cortisol metabolite production at 12 months, independent of demographics and breastfeeding. CONCLUSIONS: Greatest weight loss in the postpartum year was associated with lower conversion of cortisone to cortisol and lower conversion of cortisol to its metabolites, supporting previous work that demonstrates the facilitative role of lower 5α-reductase and 11ß-HSD-1 in weight loss. Greater depression symptoms were associated with higher cortisol metabolite production rates. Whilst weight and mental health are both associated with dysregulation of the HPA axis, there may be different pathways towards depressed and obese phenotypes in healthy postpartum samples.

Multilayering of Calcium Aerosol-OT at the Mica/Water Interface Studied with Neutron Reflection: Formation of a Condensed Lamellar Phase at the CMC.

Using specular neutron reflection, the adsorption of sodium and calcium salts of the surfactant bis(2-ethylhexyl) sulfosuccinate (Aerosol-OT or AOT) has been studied at the mica/water interface at concentrations between 0.1 and 2 CMC. The pH dependence of the adsorption was also probed. No evidence of the adsorption of Na(AOT) was found even at the critical micelle concentration (CMC) while the calcium salt was found to adsorb significantly at concentrations of 0.5 CMC and above. This interesting and somewhat unexpected finding demonstrates that counterion identity may be used to tune the adsorption of anionic surfactants on anionic surfaces. At the CMC, three condensed bilayers of Ca(AOT)2 were adsorbed at pH 7 and 9 and four bilayers adsorbed at pH 4. Multilayering at the CMC of Ca(AOT)2 on the mica surface is an unusual feature of this surfactant/surface combination. Only single bilayer adsorption has been observed at other surfaces at the CMC. We suggest this arises from the high charge density of mica which must provide an excellent template for the surfactant.