Feasibility of a virtual reality intervention targeting distress and anxiety symptoms in patients with primary brain tumors: Interim analysis of a phase 2 clinical trial.

PURPOSE: Cancer patients experience distress and anxiety when undergoing imaging studies to monitor disease status, yet these symptoms are not always appropriately identified or well-managed. This interim analysis of a phase 2 clinical trial explored feasibility and acceptability of a virtual reality relaxation (VR) intervention for primary brain tumor (PBT) patients at the time of clinical evaluation. METHODS: English speaking, adult PBT patients with previous reports of distress and upcoming neuroimaging were recruited between March of 2021 and March 2022. A brief VR session was done within 2 weeks prior to neuroimaging with patient-reported outcomes (PROs) collected before and immediately post-intervention. Self-directed VR use over the next 1 month was encouraged with additional PROs assessments at 1 and 4 weeks. Feasibility metrics included enrollment, eligibility, attrition, and device-related adverse effects with satisfaction measured with qualitative phone interviews. RESULTS: Fifty-five patients were approached via email, 40 (73%) responded and 20 (50%) enrolled (9 declines, 11 screen fails). 65% of participants were ≤ 50 years, 50% were male, 90% were White/non-Hispanic, 85% had good KPS (≥ 90), and most were on active treatment. All patients completed the VR intervention, PROs questionnaires, weekly check-ins, and qualitative interview. Most (90%) reported frequent VR use and high satisfaction and only 7 mild AEs were recorded (headache, dizziness, nausea, neck pain). CONCLUSION: This interim analysis supports feasibility and acceptability of a novel VR intervention to target psychological symptoms for PBT patients. Trial enrollment will continue to assess for intervention efficacy. TRIAL REGISTRATION: NCT04301089 registered on 3/9/2020.

NCI intramural program approach to rare tumors: Natural history study of rare solid tumors in children and adults: A longitudinal, comprehensive data and biospecimen collection protocol.

Rare tumors across the world are lacking adequate knowledge, resources, and community. Through partnership with patients, advocacy organizations, researchers, and clinicians, we have developed a comprehensive, longitudinal, prospective, and retrospective natural history protocol to collect, analyze, and share data on patients with rare tumors. A strong collaborative effort is vital to ensure success of enrollment, patient engagement, data collection, and analysis to ultimately develop clinical trials to improve outcomes for patients with rare cancers.

Coping competence and hopelessness moderate the influence of perceived burdensomeness on suicidal ideation in undergraduate college students.

According to the interpersonal theory of suicide, the perception of imposing a burden on loved ones increases the risk for suicidal ideation. Little research, however, has examined the interaction of burdensomeness with cognitive variables in predicting suicidal ideation in college students even though the relationship between burdensomeness and ideation may be contingent on levels of cognitive risk factors. The present study thus examined the relationships between burdensomeness, hopelessness, coping competence, and suicidal ideation. Questionnaires were administered to 279 undergraduate students from a university in the Midwest United States. After controlling for depression, hopelessness, and coping competence, burdensomeness significantly predicted ideation and accounted for variance above and beyond the control variables. Moreover, the relationship between burdensomeness and suicidal ideation was significantly moderated by coping competence and hopelessness. The findings suggest that perceived burdensomeness plays a critical role in the risk for suicide in college students. More specifically, the findings suggest that coping competence and hopelessness can be ideal targets for interventions as changes in these variables may attenuate the association between perceived burdensomeness and suicidal ideation.

Goldmann and error correcting tonometry prisms compared to intracameral pressure.

BACKGROUND: Compare Goldmann applanation tonometer (GAT) prism and correcting applanation tonometry surface (CATS) prism to intracameral intraocular pressure (IOP), in vivo and in vitro. METHODS: Pressure transducer intracameral IOP was measured on fifty-eight (58) eyes undergoing cataract surgery and the IOP was modulated manometrically to 10, 20, and 40 mmHg. Simultaneously, IOP was measured using a Perkins tonometer with a standard GAT prism and a CATS prism at each of the intracameral pressures. Statistical comparison was made between true intracameral pressures and the two prism measurements. Differences between the two prism measurements were correlated to central corneal thickness (CCT) and corneal resistance factor (CRF). Human cadaver eyes were used to assess measurement repeatability. RESULTS: The CATS tonometer prism measured closer to true intracameral IOP than the GAT prism by 1.7+/-2.7 mmHg across all pressures and corneal properties. The difference in CATS and GAT measurements was greater in thin CCT corneas (2.7+/-1.9 mmHg) and low resistance (CRF) corneas (2.8+/-2.1 mmHg). The difference in prisms was negligible at high CCT and CRF values. No difference was seen in measurement repeatability between the two prisms. CONCLUSION: A CATS prism in Goldmann tonometer armatures significantly improve the accuracy of IOP measurement compared to true intracameral pressure across a physiologic range of IOP values. The CATS prism is significantly more accurate compared to the GAT prism in thin and less rigid corneas. The in vivo intracameral study validates mathematical models and clinical findings in IOP measurement between the GAT and CATS prisms.

Goldmann applanation tonometry error relative to true intracameral intraocular pressure in vitro and in vivo.

BACKGROUND: Goldmann applanation tonometry (GAT) error relative to intracameral intraocular pressure (IOP) has not been examined comparatively in both human cadaver eyes and in live human eyes. Futhermore, correlations to biomechanical corneal properties and positional changes have not been examined directly to intracameral IOP and GAT IOP. METHODS: Intracameral IOP was measured via pressure transducer on fifty-eight (58) eyes undergoing cataract surgery and the IOP was modulated manometrically on each patient alternately to 10, 20, and 40 mmHg. IOP was measured using a Perkins tonometer in the supine position on 58 eyes and upright on a subset of 8 eyes. Twenty one (21) fresh human cadaver globes were Intracamerally IOP adjusted and measured via pressure transducer. Intracameral IOP ranged between 5 and 60 mmHg. IOP was measured in the upright position with a Goldmann Applanation Tonometer (GAT) and supine position with a Perkins tonometer. Central corneal thickness (CCT) was also measured. RESULTS: The Goldmann-type tonometer error measured on live human eyes was 5.2 +/-1.6 mmHg lower than intracameral IOP in the upright position and 7.9 +/- 2.3 mmHg lower in the supine position (p < .05). CCT also indicated a sloped correlation to error (correlation coeff. = 0.18). Cadaver eye IOP measurements were 3.1+/-2.5 mmHg lower than intracameral IOP in the upright position and 5.4+/- 3.1 mmHg in the supine position (p < .05). CONCLUSION: Goldmann IOP measures significantly lower than true intracameral IOP by approximately 3 mmHg in vitro and 5 mmHg in vivo. The Goldmann IOP error is increased an additional 2.8 mmHg lower in the supine position. CCT appears to significantly affect the error by up to 4 mmHg over the sample size.

Pseudophakic cystoid macular edema prevention and risk factors; prospective study with adjunctive once daily topical nepafenac 0.3% versus placebo.

BACKGROUND: Define the effectiveness of a topical non-steroidal anti-inflammatory drug (NSAID) added to topical steroid use after uncomplicated phacoemulsification for the prevention of pseudophakic cystoid macular edema (PCME) using a prospective, randomized, double-masked, placebo-controlled clinical study. METHODS: Eyes (1000) were randomized to placebo (497) or nepafenac 0.3% (503) used once daily, post-operatively for 5 weeks at two ophthalmology clinics. Diagnosis of PCME was made by clinical, ocular coherence tomography (OCT), and with fluorescein angiography confirmation. Correlation of PCME to NSAID use and the presence of pre-operative risk factors for PCME were assessed including, contralateral PCME, diabetic retinopathy, retinal vein occlusion, macular hole, epiretinal membrane, macular degeneration, retinal detachment repair, and prostaglandin use. RESULTS: PCME was the most common complication associated with routine cataract surgery (4.2% with PCME risk factors, 2.0% with risk factors excluded). Topical nepafenac 0.3% significantly reduces the incidence of PCME compared to placebo when used after routine cataract surgery (p = .0001). When patients with pre-operative risk factors are excluded, the incidence of PCME between treatment and placebo groups is equivalent (p = 0.31). PCME relative risk (RR) was most significant in contralateral PCME (RR 19.5), diabetic retinopathy (RR 13.1), retinal vein occlusion (RR 12.9), macular hole (RR 7.7), and epiretinal membrane (RR 5.7). Prostaglandin use and previous retinal detachment were not shown to increase risk. CONCLUSION: Pseudophakic cystoid macular edema is common after phacoemulsification cataract surgery. Topical nepafenac 0.3% reduces PCME in patients with pre-operative risk factors for PCME compared to placebo but shows no benefit in patients without pre-operative risk factors. TRIAL REGISTRATION: NIH ClincalTrials.gov retrospectively registered January 15, 2017, NCT03025945 .

ENABLE (Exportable Notation and Bookmark List Engine): an Interface to Manage Tumor Measurement Data from PACS to Cancer Databases.

Oncologists evaluate therapeutic response in cancer trials based on tumor quantification following selected "target" lesions over time. At our cancer center, a majority of oncologists use Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 quantifying tumor progression based on lesion measurements on imaging. Currently, our oncologists handwrite tumor measurements, followed by multiple manual data transfers; however, our Picture Archiving Communication System (PACS) (Carestream Health, Rochester, NY) has the ability to export tumor measurements, making it possible to manage tumor metadata digitally. We developed an interface, "Exportable Notation and Bookmark List Engine" (ENABLE), which produces prepopulated RECIST v1.1 worksheets and compiles cohort data and data models from PACS measurement data, thus eliminating handwriting and manual data transcription. We compared RECIST v1.1 data from eight patients (16 computed tomography exams) enrolled in an IRB-approved therapeutic trial with ENABLE outputs: 10 data fields with a total of 194 data points. All data in ENABLE's output matched with the existing data. Seven staff were taught how to use the interface with a 5-min explanatory instructional video. All were able to use ENABLE successfully without additional guidance. We additionally assessed 42 metastatic genitourinary cancer patients with available RECIST data within PACS to produce a best response waterfall plot. ENABLE manages tumor measurements and associated metadata exported from PACS, producing forms and data models compatible with cancer databases, obviating handwriting and the manual re-entry of data. Automation should reduce transcription errors and improve efficiency and the auditing process.

Innovative use of a guideliner catheter to assist in snare retrieval of an entrapped kinked guide catheter during transradial coronary intervention.

Rescue techniques that enable removal of severe intravascular catheter kinking are always worthwhile. We herein demonstrate the novel employment of a GuideLiner support catheter to assist in the removal of a kinked and entrapped guide catheter within the radial artery during coronary intervention. © 2016 Wiley Periodicals, Inc.

Randomized trial of technology-assisted self-monitoring of blood glucose by low-income seniors: improved glycemic control in type 2 diabetes mellitus.

Self-monitoring of blood glucose (SMBG) has been recommended for people with type 2 diabetes mellitus. This trial tested an automated self-management monitor (ASMM) that reminds patients to perform SMBG, provides feedback on results of SMBG, and action tips for improved self-management. This delayed-start trial randomized participants to using the ASMM immediately (IG), or following a delay of 6 months (DG). Glycated hemoglobin (HgbA1c) level and survey data was collected at home visits every 3 months. 44 diabetic men and women, mean age 70, completed the 12-month trial. Baseline HgbA1c was 8.1 % ± 1.0, dropping to 7.3 ± 1.0 by 9 months, with a 3-month lag in the DG (F = 3.56, p = 0.004). Decrease in HgbA1c was significantly correlated to increased frequency of SMBG, R = 0.588, p < 0.01. Providing older diabetics with objective immediate contingent feedback resulted in more frequent SMBG that correlated with better glycemic control. This type of technology may provide real-time feedback not only to patient users, but to the health care system, allowing better integration of provider recommendations with patient-centered action.

Validating a new computed tomography atlas for grading ankle osteoarthritis.

As the most common joint disease, osteoarthritis (OA) poses a significant source of pain and disability. It can be defined by classic radiographic findings, particular symptoms, or a combination of the 2. Although specific grading scales have been developed to evaluate OA in various joints, such as the shoulder, hip, and knee, no definitive classification system is available for grading OA in the ankle. The purpose of the present study was to create and validate a standardized atlas for grading (or staging) ankle osteoarthritis using computed tomography (CT) and "hallmark" findings noted on coronal, sagittal, and axial views extrapolated from the Kellgren-Lawrence radiographic scale. The CT scans of 226 patients at the Miami Veterans Affairs Medical Center were reviewed. An atlas was derived from a retrospective review of 30 remaining CT scans taken from July 2008 to November 2011. After this review, 3 orthogonal static CT images, obtained from 11 remaining patients, were chosen to represent the various stages on the OA scale and were used to test the validity of the atlas developed by 2 of us (M.M.C. and N.D.V.). A multispecialty panel of 9 examiners, excluding ourselves, independently rated the 11 CT scan subjects. The differences among examiners and specialties were calculated, including an intra-examiner agreement for 2 separate readings spaced 9 months apart. Although the small number of subspecialty examiners made the intraspecialty comparisons difficult to validate, the findings nevertheless indicated excellent agreement among all specialty groups, with good intra-investigational (intraclass correlation coefficient 0.962 and 1) inter-investigational (intraclass correlation coefficient 0.851) values. These results appeared to validate the CT ankle OA atlas, which we believe will be a valuable clinical and research tool, one that will likely be more beneficial than less relevant generalized OA grading scales in use today.

Long-term survivors of glioblastoma: Tumor molecular, clinical, and imaging findings.

Background: Glioblastoma (GBM) is the most aggressive primary brain malignancy with <45% living a year beyond diagnosis. Previously published investigations of long-term survivors (LTS) provided clinical data but rarely incorporated a comprehensive clinical and molecular analysis. Herein, we identify clinical, imaging, molecular, and outcome features for 23 GBM-LTS patients and compare them with a matched cohort of short-term survivors (STS). Methods: Molecularly confirmed Isocitrate Dehydrogenase (IDH) wildtype GBM patients living ≥3 years post-diagnosis (NLTS = 23) or <3 years (NSTS = 75) were identified from our Natural History study. Clinical and demographic characteristics were compared. Tumor tissue was analyzed with targeted next generation sequencing (NGS) (NLTS = 23; NSTS = 74) and methylation analysis (NLTS = 18; NSTS = 28). Pre-surgical MRI scans for a subset of LTS (N = 14) and STS control (N = 28) matched on sex, age, and extent of resection were analyzed. Results: LTS tended to be younger. Diagnostic MRIs showed more LTS with T1 tumor hypointensity. LTS tumors were enriched for MGMTp methylation and tumor protein 53 (TP53) mutation. Three patients with classic GBM histology were reclassified based on NGS and methylation testing. Additionally, there were LTS with typical poor prognostic molecular markers. Conclusions: Our findings emphasize that generalized predictions of prognosis are inaccurate for individual patients and underscore the need for complete clinical evaluation including molecular work-up to confirm the diagnosis. Continued accrual of patients to LTS registries that containcomprehensive clinical, imaging, tumor molecular data, and outcomes measures may pro\vide important insights about individual patient prognosis.

Evolution of practice gaps in gastrointestinal and endoscopic surgery: 2012 report from the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Continuing Education Committee.

BACKGROUND: In an effort to fulfill its charge to develop and maintain a comprehensive educational program to serve the members of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), the SAGES Continuing Education Committee (CEC) reports a summary of findings related to its evaluation of the 2012 SAGES annual meeting. METHODS: All attendees to the 2012 annual meeting had the opportunity to complete an immediate postmeeting questionnaire as part of their continuing medical education (CME) certification in which they identified up to two learning themes, answered questions related to potential practice change items that are based on those learning themes, and complete a needs assessment related to important learning topics for future meetings. In addition, participants in the postgraduate and hands-on courses were asked to complete questions about case volume and comfort levels related to procedures/topics in those courses. All respondents to this initial survey were sent a 3-month follow-up questionnaire in which they were asked how successfully they had implemented the intended practice changes and what, if any, barriers they encountered. Postgraduate and hands-on course participants completed case volume and comfort level questions. Descriptive statistical analysis of this deidentified data was undertaken. RESULTS: Response rates were 42% and 56% for CME-eligible attendees/respondents for the immediate postmeeting and 3-month follow-up questionnaires, respectively. Top learning themes for respondents were Bariatric, Hernia, Foregut, and Colorectal. Improving minimally invasive surgical (MIS) technique and managing complications related to MIS procedures were top intended practice changes. Partial implementation was common with top barriers including cost restrictions, lack of institutional support, and lack of time. CONCLUSIONS: The 2012 annual meeting analysis provides insight into educational needs among respondents and will help with planning content for future meetings.

Quadriceps strength and corticospinal excitability as predictors of disability after anterior cruciate ligament reconstruction.

BACKGROUND: Disability is common in a proportion of patients after anterior cruciate ligament reconstruction (ACL-R). Neuromuscular quadriceps deficits are a hallmark impairment after ACL-R, yet the link between muscle function and disability is not understood. PURPOSES: To evaluate the ability of quadriceps strength and cortical excitability to predict self-reported disability in patients with ACL-R. METHODS: Fifteen participants with a history of ACL-R (11 female, 4 male; 172 ± 9.8 cm, 70.4 ± 17.5 kg, 54.4 ± 40.9 mo postsurgery) were included in this study. Corticospinal excitability was assessed using active motor thresholds (AMT), while strength was assessed with maximal voluntary isometric contractions (MVIC). Both voluntary strength and corticospinal excitability were used to predict disability measured with the International Knee Documentation Committee Index (IKDC). RESULTS: The overall multiple-regression model significantly predicted 66% of the variance in self-reported disability as measured by the IKDC index (R2 = .66, P = .01). Initial imputation of MVIC into the model accounted for 61% (R2 = .61, P = .01) of the variance in IKDC. The subsequent addition of AMT into the model accounted for an insignificant increase of 5% (Δ R2 = .05, P = .19) in the prediction capability of the model. CONCLUSIONS: Quadriceps voluntary strength and cortical excitability predicted two-thirds of the variance in disability of patients with ACL-R, with strength accounting for virtually all of the predictive capability of the model.

Heterogeneous clinicopathological findings and patient-reported outcomes in adults with MN1-altered CNS tumors: A case report and systematic literature review.

The uncommon MN1-altered primary central nervous system (CNS) tumors were recently added to the World Health Organization 2021 classification under the name Astroblastoma, MN1-altered. Another term used to describe them, "High-grade neuroepithelial tumor with MN1 alteration" (HGNET-MN1), makes reference to their distinct epigenetic profile but is currently not a recommended name. Thought to occur most commonly in children and predominantly in females, MN1-altered CNS tumors are associated with typical but not pathognomonic histological patterns and are characterized by a distinct DNA methylation profile and recurrent fusions implicating the MN1 (meningioma 1) gene. Diagnosis based on histological features alone is challenging: most cases with morphological features of astroblastoma (but not all) show these molecular features, whereas not all tumors with MN1 fusions show astroblastoma morphology. There is large variability in reported outcomes and detailed clinical and therapeutic information is frequently missing. Some patients experience multiple recurrences despite multimodality treatment, whereas others experience no recurrence after surgical resection alone, suggesting large clinical and biological heterogeneity despite unifying epigenetic features and recurrent fusions. In this report, we present the demographics, tumor characteristics, treatment, and outcome (including patient-reported outcomes) of three adults with MN1-altered primary CNS tumors diagnosed via genome-wide DNA methylation and RNA sequencing. All three patients were females and two of them were diagnosed as young adults. By reporting our neuropathological and clinical findings and comparing them with previously published cases we provide insight into the clinical heterogeneity of this tumor. Additionally, we propose a model for prospective, comprehensive, and systematic collection of clinical data in addition to neuropathological data, including standardized patient-reported outcomes.

Association of Employment Status With Symptom Burden and Health-Related Quality of Life in People Living With Primary CNS Tumors.

BACKGROUND AND OBJECTIVES: Financial toxicity significantly affects many patients, especially cancer survivors. We evaluated the association of unemployment as a major contributor to financial toxicity with patient-reported outcomes (PROs) assessing multiple illness experience domains in a primary CNS tumor (PCNST) cohort. METHODS: Patient and disease characteristics and PROs measuring symptom burden, interference, psychologic distress, functional impairment, and health-related quality of life (HRQOL) from participants enrolled in an institutional review board-approved observational study at the US NIH's Neuro-Oncology Branch were collected between September 2016 and December 2019. Descriptive statistics, tests of association, and comparison of group mean values were used to describe and evaluate PROs. RESULTS: Of the 277 participants diagnosed with a PCNST, 57% were male and 43% were female. Participants reported their race as White, non-Hispanic (78%); White, Hispanic/Latino (9%); Asian (7%); Black (4%); Native Hawaiian/Pacific Islander (1%); and other (2%) with 8% missing. The median age of the overall cohort was 45 years (range 18-74). Hispanic participants in the overall sample were 2.3 times more likely, and in the brain tumor group 3.2 times more likely, to report unemployment (p = 0.043, odds ratio [OR] 2.3, 95% CI 1.0-5.4 and p = 0.008, OR 3.2, 95% CI 1.3-7.9, respectively). 77 (28%) individuals unemployed due to tumor reported more functional impairment with walking, washing, dressing, and performing usual activities and reduced HRQOL (p < 0.001). More unemployed participants in the total sample reported moderate-to-severe depressive symptoms (25%) than those employed (8%) (χ2(1) = 13.9, p < 0.001, OR 3.7, 95% CI 1.8-7.8) and more moderate-to-severe anxiety symptoms (30%) than those employed (15%) (χ2(1) = 7.8, p = 0.005, OR 2.4, 95% CI 1.3-4.5). Unemployed participants with brain tumor reported on average 3 more symptoms as moderate-to-severe compared with those employed (t(83) = -4.0, 95% CI [Formula: see text] difference -5 to -2, p < 0.001, Hedge g = 0.70). DISCUSSION: Being unemployed due to a PCNST strongly correlated with high symptom burden, functional impairment, psychological distress, and reduced HRQOL, which may be impediments to returning to work that warrant intervention. Lack of employer-based health insurance and reduced earnings are financial sequelae of unemployment superimposed on the physical, social, and cognitive effects of living with a PCNST. Innovations to screen for and address financial toxicity and its contributing factors are needed.

Relationship between RANO-PRO Working Group standardised priority constructs and disease progression among malignant glioma patients: A retrospective cohort study.

Background: Recognising the importance of clinical outcomes assessments (COAs), the Response Assessment in Neuro-Oncology-Patient Reported Outcome (RANO-PRO) Working Group recommended inclusion of core symptoms and functions in clinical care or research for malignant glioma patients. This study evaluated the association of the recommended symptoms (pain, perceived cognition, seizures, aphasia, symptomatic adverse events) and functions (weakness, walking, work, usual activities) with disease progression in these patients. Methods: In this retrospective cohort study, patients with malignant glioma were included from the US National Cancer Institute Neuro-Oncology Branch Natural History Study (NOB-NHS) which follows primary central nervous system tumour patients aged 18 years and older throughout their disease trajectory. The M.D. Anderson Symptom Inventory-Brain Tumor (MDASI-BT), EQ-5D-3L, Karnofsky Performance Status (KPS), and Neurologic Function scores (NFS) were evaluated in relation to disease progression by chi-square tests, independent- and paired-samples t-tests, adjusted for multiple comparisons at first assessment and over time to a second assessment. Radiographic disease progression was determined on the interpretation of the imaging study by a radiologist and neuro-oncologist using standard criteria as part of clinical trial participation or routine standard of care. The priority constructs were evaluated to provide initial evidence of their relevance, relationship to disease status over time, and sensitivity to change in a diverse group of patients with malignant glioma. Findings: Seven hundred and sixty-five patients had enrolled into the NOB-NHS between September 1, 2016 and January 31, 2020. Three hundred and thirty-six patients had a diagnosis of a malignant glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, glioblastoma, and gliosarcoma) and were included in the current study. The sample was 64% male (n = 215), 36% female (n = 121), median age of 52 years (IQR = 18.75), 82% White (n = 276), and 65% had tumour recurrence (n = 219). One hundred and fifty-four (46%) had radiographic disease progression. Difficulty remembering, fatigue, and weakness were worse in the group whose imaging was interpreted as radiographic disease progression versus stable disease, as well as the functions of walking, work, activity, and self-care (1.1 < difference < 1.8). Patients with disease progression were four times more likely to have a poor KPS (≤80) and worse NFS. Among patients with disease progression at a second assessment (n = 112), all symptoms, except seizures, worsened between first assessment and disease progression and up to 22% of patients (n = 25) reported worsening mobility, self-care, and usual activity; 46% (n = 51) and 35% (n = 30) had worsened KPS and NFS, respectively. On average, 4 symptoms or functions (SD = 3) were reported as moderate-to-severe and 30% (n = 33) and 23% (n = 26) had a change to moderate-to-severe fatigue and walking, respectively, at time of disease progression. Over 7% of patients with worsening (n = 7 of 100) reported every symptom and function as having changed the most severely including seizures with fatigue and activity reported as the top symptom and function, respectively. Interpretation: The identified core symptoms and functions worsened at the time of progression, supporting the relevance and sensitivity of the priority constructs identified by the RANO-PRO Working Group for clinical care and clinical trials for malignant glioma patients. Funding: The Natural History Study is supported by Intramural Project 1ZIABC011786-03.

Feasibility of a virtual reality intervention targeting distress and anxiety symptoms in patients with primary brain tumors: Interim analysis of a phase 2 clinical trial.

Purpose: Cancer patients experience distress and anxiety when undergoing imaging studies to monitor disease status, yet these symptoms are not always appropriately identified or well-managed. This interim analysis of a phase 2 clinical trial explored feasibility and acceptability of a virtual reality relaxation (VR) intervention for primary brain tumor (PBT) patients at the time of clinical evaluation. Methods: English speaking, adult PBT patients with previous reports of distress and upcoming neuroimaging were recruited between March of 2021 and March 2022. A brief VR session was done within 2 weeks prior to neuroimaging with patient-reported outcomes (PROs) collected before and immediately post-intervention. Self-directed VR use over the next 1 month was encouraged with additional PROs assessments at 1 and 4 weeks. Feasibility metrics included enrollment, eligibility, attrition, and device-related adverse effects with satisfaction measured with qualitative phone interviews. Results: 55 patients were approached via email, 40 (73%) responded and 20 (50%) enrolled (9 declines, 11 screen fails). 65% of participants were ≤ 50 years, 50% were male, 90% were White/non-Hispanic, 85% had good KPS (≥ 90), and most were on active treatment. All patients completed the VR intervention, PROs questionnaires, weekly check-ins, and qualitative interview. Most (90%) reported frequent VR use and high satisfaction and only 7 mild AEs were recorded (headache, dizziness, nausea, neck pain). Conclusion: This interim analysis confirmed feasibility and acceptability of a novel VR intervention to target psychological symptoms for PBT patients. Trial enrollment will continue to assess for intervention efficacy. Trial Registration: NCT04301089 registered on 3/9/2020.

The Childhood Cancer Data Initiative: Using the Power of Data to Learn From and Improve Outcomes for Every Child and Young Adult With Pediatric Cancer.

Data-driven basic, translational, and clinical research has resulted in improved outcomes for children, adolescents, and young adults (AYAs) with pediatric cancers. However, challenges in sharing data between institutions, particularly in research, prevent addressing substantial unmet needs in children and AYA patients diagnosed with certain pediatric cancers. Systematically collecting and sharing data from every child and AYA can enable greater understanding of pediatric cancers, improve survivorship, and accelerate development of new and more effective therapies. To accomplish this goal, the Childhood Cancer Data Initiative (CCDI) was launched in 2019 at the National Cancer Institute. CCDI is a collaborative community endeavor supported by a 10-year, $50-million (in US dollars) annual federal investment. CCDI aims to learn from every patient diagnosed with a pediatric cancer by designing and building a data ecosystem that facilitates data collection, sharing, and analysis for researchers, clinicians, and patients across the cancer community. For example, CCDI's Molecular Characterization Initiative provides comprehensive clinical molecular characterization for children and AYAs with newly diagnosed cancers. Through these efforts, the CCDI strives to provide clinical benefit to patients and improvements in diagnosis and care through data-focused research support and to build expandable, sustainable data resources and workflows to advance research well past the planned 10 years of the initiative. Importantly, if CCDI demonstrates the success of this model for pediatric cancers, similar approaches can be applied to adults, transforming both clinical research and treatment to improve outcomes for all patients with cancer.

Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9.

Leukaemias and other cancers possess a rare population of cells capable of the limitless self-renewal necessary for cancer initiation and maintenance. Eradication of these cancer stem cells is probably a critical part of any successful anti-cancer therapy, and may explain why conventional cancer therapies are often effective in reducing tumour burden, but are only rarely curative. Given that both normal and cancer stem cells are capable of self-renewal, the extent to which cancer stem cells resemble normal tissue stem cells is a critical issue if targeted therapies are to be developed. However, it remains unclear whether cancer stem cells must be phenotypically similar to normal tissue stem cells or whether they can retain the identity of committed progenitors. Here we show that leukaemia stem cells (LSC) can maintain the global identity of the progenitor from which they arose while activating a limited stem-cell- or self-renewal-associated programme. We isolated LSC from leukaemias initiated in committed granulocyte macrophage progenitors through introduction of the MLL-AF9 fusion protein encoded by the t(9;11)(p22;q23). The LSC were capable of transferring leukaemia to secondary recipient mice when only four cells were transferred, and possessed an immunophenotype and global gene expression profile very similar to that of normal granulocyte macrophage progenitors. However, a subset of genes highly expressed in normal haematopoietic stem cells was re-activated in LSC. LSC can thus be generated from committed progenitors without widespread reprogramming of gene expression, and a leukaemia self-renewal-associated signature is activated in the process. Our findings define progression from normal progenitor to cancer stem cell, and suggest that targeting a self-renewal programme expressed in an abnormal context may be possible.

Glenoid bone augmentation: a contemporary and comprehensive systematic review of open procedures.

Introduction: There is a trend towards arthroscopically treating shoulder instability with glenoid deficiency. Despite this, there remains the option for treatment through an open technique. Multiple bone augmentation options are available for recurrent anterior shoulder instability. Objective: To provide a systematic review of recent studies for recurrent anterior shoulder instability necessitating glenoid bone augmentation specifically through open procedures using coracoid bone or free bone blocks [iliac crest bone autograft/allograft or distal tibia allograft (DTA)]. Methods: PubMed, Cochrane, EMBASE, and Google Scholar were searched for studies reporting open glenoid bone augmentation procedures with iliac crest, tibia, or coracoid bones within 10 years. Extracted data included study/patient characteristics, techniques, prior surgeries, prior dislocations, radiographic findings, range of motion (ROM), recurrent instability, patient-reported outcomes, and complications. Results: 92 met inclusion criteria (5693 total patients). Six were studies of iliac crest bone, four of DTA, and 84 using the coracoid bone. 29 studies measured postoperative arthritis showing no development or mild arthritis. 26 studies reported postoperative graft position. 62 studies reported ROM noting decline in internal/external rotation. 87 studies measured postoperative instability with low rates. Rowe Scores with noted improvement across 31/59 (52.5%) studies were seen. Common post operative complications included infection, hematoma, graft fracture, nerve injury, pain, and screw-related irritation. Conclusion: Despite a trend towards arthroscopic management of recurrent anterior shoulder instability with glenoid deficiency, open procedures continue to provide satisfactory outcomes. Additionally, studies have demonstrated safe and efficacious use of free bone block graft options in the primary and revision setting.