bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oestradiol concentrations in trans women with HIV suppressed on unboosted integrase inhibitor regimens versus trans women without HIV taking oral oestradiol: a pilot study
Authors: Loutfy Mona , Lacombe-Duncan Ashley , Tseng Alice , Persad Yasmeen , Underhill Angela , Kennedy V Logan , Armstrong Ian , Fung Raymond , Bourns Amy , Nguyen Quang , Hranilovic Sue , Weisdorf Thea , Chan L Y L , Kia Hannah , Halpenny Roberta , Iyer Harshita , Jeyarajah Nirubini , Kovchazov George , McCully Jennifer , Scarsi Kimberly K 
Published: September 2023

Abstract

Background
Feminizing hormone therapy (FHT) is essential to many trans women. Concern about negative drug interactions between FHT and ART can be an ART adherence barrier among trans women with HIV.

Objectives
In this single-centre, parallel group, cross-sectional pilot study, we measured serum oestradiol concentrations in trans women with HIV taking FHT and unboosted integrase strand transfer inhibitor (INSTI)-based ART versus trans women without HIV taking FHT.

Methods
We included trans women with and without HIV, aged ≥18 years, taking ≥2 mg/day of oral oestradiol for at least 3 months plus an anti-androgen. Trans women with HIV were on suppressive ART ≥3 months. Serum oestradiol concentrations were measured prior to medication dosing and 2, 4, 6 and 8 h post-dose. Median oestradiol concentrations were compared between groups using Wilcoxon rank-sum tests.

Results
Participants (n = 8 with HIV, n = 7 without) had a median age of 32 (IQR: 28, 39) years. Among participants, the median oral oestradiol dose was 4 mg (range 2–6 mg). Participants had been taking FHT for a median of 4 years (IQR: 2, 8). Six trans women with HIV were taking bictegravir/emtricitabine/tenofovir alafenamide and two were taking dolutegravir/abacavir/lamivudine. All oestradiol concentrations were not significantly different between groups. Eleven (73%) participants had target oestradiol concentrations in the range 200–735 pmol/L at C4h (75% among women with HIV, 71% among those without HIV).

Conclusions
Oestradiol concentrations were not statistically different in trans women with HIV compared with those without HIV, suggesting a low probability of clinically relevant drug–drug interactions between FHT and unboosted INSTI-based ART.
When Positive is Negative: Health Literacy Barriers to Patient Access to Clinical Laboratory Test Results
Authors: Lazaro Gerardo 
Published: September 2023

AbstractBackgroundHealth literacy is a multidimensional set of skills (e.g., narrative, numeracy, digital, medication) that patients need to access and understand health information timely and accurately to make evidence-based informed decisions.ContentMultiple barriers prevent patients from effectively interacting with health information. The most salient barriers are poor overall health literacy skills and linguistic proficiency in English. As patients prefer direct access to laboratory test results, especially those of routine tests, contextualization and provider-directed interpretation of results are required to foster shared decision-making to address their healthcare issues and improve health outcomes.SummaryThe use of systematic approaches that account for poor health literacy skills and include culturally and linguistically appropriate planning and availability of resources is warranted at individual and population health levels (e.g., human-centered design of patient portals).
Reflections on the history of interoperability in hospitals
Authors: Simborg Donald W 
Published: September 2023

Abstract

Objective
To discuss the origins of HL7 and its subsequent impact on interoperability in hospitals.

Process
Reconstruction of historical events from review of personal notes, interviews with key participants and review of relevant publications.

Conclusions
The first versions of HL7 were based on the StatLAN protocol developed at the University of California, San Francisco and later commercialized by Simborg Systems Corporation. With the emergence of specialty clinical and departmental systems in the 1990s, a debate ensued between proponents of “open architecture” vs. “single vendor” systems. Although HL7 became the most widely used data-interchange protocol worldwide in healthcare, open architecture did not prevail in healthcare as it did in other industries. This is due to the unique market characteristics of the healthcare provider industry. The result today is the dominance of the healthcare IT marketplace by a small number of large vendors with relatively few options for in-depth specialty clinical systems.
What are the barriers to medical collaboration in community-based integrated care supporting cancer patients? A qualitative analysis of healthcare and long-term care providers’ perceptions
Authors: Mashiro Erina , Arao Harue , Aoki Miwa , Matsumoto Yoshihisa 
Published: September 2023

Abstract

Background
Patients required comprehensive cancer treatment in the community based on medical collaboration between designated cancer care hospitals and community medical and nursing care facilities to help them live life on their own terms. This study aims to describe the barriers to medical collaboration in community-based integrated care from the perspectives of healthcare providers (HCPs) and long-term care providers (LCPs) supporting cancer patients.

Methods
Semi-structured interviews were conducted with 88 HCPs and LCPs supporting cancer patients. We analyzed interview data to describe barriers to medical collaboration between designated cancer care hospitals and community medical and nursing care facilities using content analysis in MAXQDA.

Results
Participants were mostly HCPs, with physicians accounting for the largest proportion (27.3%). Totally, 299 codes were integrated into seven barriers to medical collaboration in community-based integrated care, including lack of information provision including life perspectives and a delay in sharing cancer patients’ values with HCPs to provide end-of-life care according to the patients’ wishes. Furthermore, insufficient coordination of cancer and non-cancer symptom management was identified as a barrier specific to older adults with cancer.

Conclusions
Barriers related to cancer treatment that integrate lifestyle perspectives, end-of-life care emphasizing patient values, and medical collaboration between cancer and non-cancer care are distinctive. They emphasize the importance of utilizing professionals to connect treatment and lifestyle information, establishing a central coordinating organization led by the DCCH, and developing a community palliative care network. Moreover, connecting cancer and non-cancer care through government and medical collaboration is crucial.
Ctrl-C: a cross-sectional study of the electronic health record usage patterns of US oncology clinicians
Authors: Sinha Sumi , Holmgren A Jay , Hong Julian C , Rotenstein Lisa S 
Published: September 2023

Abstract
Despite some positive impact, the use of electronic health records (EHRs) has been associated with negative effects, such as emotional exhaustion. We sought to compare EHR use patterns for oncology vs nononcology medical specialists. In this cross-sectional study, we employed EHR usage data for 349 ambulatory health-care systems nationwide collected from the vendor Epic from January to August 2019. We compared note composition, message volume, and time in the EHR system for oncology vs nononcology clinicians. Compared with nononcology medical specialists, oncologists had a statistically significantly greater percentage of notes derived from Copy and Paste functions but less SmartPhrase use. They received more total EHR messages per day than other medical specialists, with a higher proportion of results and system-generated messages. Our results point to priorities for enhancing EHR systems to meet the needs of oncology clinicians, particularly as related to facilitating the complex documentation, results, and therapy involved in oncology care.
KS01.7.A ADAPTOR FITC CAR T-CELLS AND OCTO-FLUO ELICIT PROMISING ANTITUMOR ACTIVITY IN MENINGIOMA VIA SSTR2
Authors: Chen J , Pellegrino C , Mastall M , Padevit L , Favalli N , Bassi G , Neidert M , Vasella F , Roth P , Neri D , Manz M , Weller M , Wirsching H 
Published: September 2023

Abstract

BACKGROUND
Effective treatment options for meningioma patients beyond surgical resection and radiotherapy are lacking. Somatostatin receptor (SSTR) 2 is expressed by most meningiomas. Here, we report pre-clinical and translational evidence for the activity of an SSTR2-targeted adaptor CAR T cell system in meningiomas.

MATERIAL AND METHODS
Tissue microarrays of meningioma (N=384) patient samples stained for SSTR2. Fluorescein-linked, octameric cyclic peptide SSTR2 antagonist OCTO-FLUO (kindly provided by Philogen, Otelfingen, Switzerland). Adaptor FITC CAR T-cells generated by lentiviral transduction of healthy donor T-cells. Flow cytometry-based killing assays in vitro in SSTR2-expressing meningioma (Ben-Men-1 IOMM-Lee) cells, and ex vivo utilizing freshly dissociated surgical meningioma specimens, by co-incubation with OCTO-FLUO and adaptor FITC CAR T-cells. Orthotopic growth and mouse survival following subdural implantation of IOMM-Lee cells, genetically engineered to express luciferase, i.v. treated with OCTO-FLUO and intratumoral injection of CAR T-cells.

RESULTS
SSTR2 expression was overall heterogeneous and was high or intermediate in most World Health Organization (WHO) grade 2 (87.8 %) or grade 3 (87.5 %) meningiomas. In vitro, 10 nM was determined as the optimal concentration of OCTO-FLUO, yielding tumor cell killing within 72 hours at effector-target cell (ET) ratios as low as 1:100 in Ben-Men-1 (CAR vs untransduced T-cells [UTT] 47.9 % vs 4.7 %, p &lt; 0.001) and IOMM-Lee (CAR vs UTT 40.2 % vs 4.9 %, p &lt; 0.001) cells. Tumor growth inhibition by the adaptor FITC CAR T-cell system in vivo was confined to SSTR2 expressing cells and was paralleled by prolonged survival compared to UTT in IOMM-Lee (hazard ratio [95% confidence interval], 0.3 [0.1 - 0.9], p=0.030). Preliminary ex vivo killing assays employing freshly dissociated patient samples yielded specific lysis-rates in the range of 15-20% (ET 1:1) at 12 hours. Updated ex vivo results employing optimized protocols will be presented at the conference.

CONCLUSION
Targeting SSTR2 positive meningioma cells with an adaptor FITC CAR T-cell system is feasible. Syngeneic murine models and the use of adaptor molecules directed against murine SSTR2 will be required to explore secondary immune reactions and off-tumor effects prior to proceeding to early phase clinical trials.
KS03.5.A COMPARING VOLUMETRIC GROWTH-RATE AND RANO CRITERIA IN DETERMINING THE RESPONSE OF MENINGIOMA TO BEVACIZUMAB THERAPY
Authors: Borenstein S , Amiel A , Siegal T , Gal O , Limon D , Eliahu R , Yust-Katz S 
Published: September 2023

Abstract

INTRODUCTION
Meningioma is the most prevalent primary tumor in the central nervous system (CNS). Although mostly benign, 15- 20% are aggressive and tend to recur and progress despite surgery and adjuvant radiation. Recent publications show that bevacizumab, a vascular endothelial growth factor inhibitor, effectively treats these refractory meningiomas. The standard method to monitor treatment’s effect on imaging is Response Assessment in Neuro-Oncology criteria (RANO). Recently, an alternative tool called 3D volumetric growth rate (3DVGR) has emerged as a result of significant advancements in the accuracy of volumetric measurement techniques. Our aim is to compare the effectiveness of conventional RANO criteria and the emerging 3DVGR measure in evaluating the response to bevacizumab treatment in patients with refractory meningiomas. We will also assess their correlation with clinical outcomes over a period of up to 9 months.

METHODS
68 MRI scans of 20 patients with aggressive meningiomas that progressed after radiation therapy and then received Bevacizumab were evaluated. Scans were obtained from two tertiary cancer centers. For each tumor both RANO and 3DVGR were conducted in two subsequent head MRI studies acquired prior to the initiation of bevacizumab treatment and then in at least one exam within 6 months post-treatment. Measurements were obtained using PACS and BRAIN LAB software by two radiologists.

RESULTS
A total of 43 lesions derived from 13 males and 7 females were included in the final analysis. The mean age was 65.5; mean number of pre-radiation treatments was 2.66; mean number of pre-surgical treatments was 2.7 and mean number of bevacizumab cycles was 22.7. All lesions showed a decrease or stabilization in growth rate compared to baseline. More specifically, 34 out of 43 lesions (79%) showed a negative growth rate value indicating decrease in tumor size. Comparison of treatment response using RANO criteria was not always in concordance with the 3DVGR measurement and showed inaccurate correlation with clinical outcome.

CONCLUSIONS
Although widely accepted for treatment response evaluation, RANO criteria are not an accurate technique for irregularly shaped lesions. As shown in our study, for atypical meningiomas, the 3DVGR measure seems to be more precise compared to RANO criteria. Furthermore, our results show great promise for treatment of refractory meningiomas with bevacizumab.
JS03.7.A INTERPLAY BETWEEN SELF-REPORTED AND PERFORMANCE-BASED SYMPTOMS IN PATIENTS WITH GLIOMA AND MENINGIOMA - A NETWORK ANALYSIS AND COMPARISON BETWEEN DIAGNOSES
Authors: Butterbrod E , van de Glind M , Rutten G , Sitskoorn M , Gehring K 
Published: September 2023

Abstract

BACKGROUND
Patients with brain tumors show complex symptomatology often involving self-reported complaints, e.g., concerning self-perceived cognitive function (SCF), fatigue or mood, as well as deficits in cognitive performance. Understanding the interplay between symptoms across diagnoses is crucial for intervention, but remains challenging. This study used network analysis to 1) uncover unique relationships between various multidimensional self-reported symptoms and cognitive performances in patients with meningioma and glioma, and 2) investigate differences in symptom networks between diagnoses.

MATERIAL AND METHODS
We used pre-surgical data from patients with meningioma (n=240) and glioma (n=208). Two Gaussian graphical models were constructed to explore conditional relationships among symptoms in the two samples. Included as symptoms in the networks were ten patient-reported measures: SCF (3 nodes), Anxiety, Depression, and Fatigue (5 nodes), and 5 cognitive performance measures: Inhibition, Cognitive flexibility, Verbal memory, Processing speed and Psychomotor speed. We evaluated the importance of the symptoms with three centrality indices; node strength, betweenness and closeness. We compared features of the networks between the diagnoses with a Network Comparison Test.

RESULTS
In both samples, particularly strong connections existed between Anxiety and Depression, Forgetfulness and False Triggering (SCF nodes), and General Fatigue and Physical Fatigue. These positive relationships were significantly stronger than most of the other relationships. The most central symptoms, based on the strength of their connections with other symptoms, were Forgetfulness, General Fatigue and Inhibition in glioma patients, and Forgetfulness, Physical Fatigue and Depression in meningioma patients. Activity-related fatigue appeared as the least central symptom in the glioma network, but it was in the top 5 in the meningioma network. The difference in the number of relationships found (meningioma: 49 vs. glioma: 41), was not significant. Visual inspection of the networks suggested additional connections between multiple fatigue and cognition nodes in meningioma that were absent in glioma. Significant differences were found between the networks regarding strength of the relationships General Fatigue-Physical Fatigue (stronger in glioma), and Physical Fatigue-Activity-related Fatigue (stronger in meningioma), p’s &lt; .01.

CONCLUSION
While symptom networks of patients with glioma and meningioma show similarities, they appear to differ with regard to which symptoms play a more central role and how strongly some symptoms are related. Particularly fatigue subtypes may carry different importance. Information that multidimensional symptom networks provide about how symptoms interact can guide treatment decisions for patients with different diagnoses.
JS04.5.A HEMIZYGOUSCDKN2A DELETION CONFERS WORSE SURVIVAL OUTCOMES IN IDH-MUTANT GLIOMAS
Authors: Kocakavuk E , Johnson K C , Sabedot T S , Reinhardt H C , Noushmehr H , Verhaak R G W 
Published: September 2023

Abstract

BACKGROUND
The tumor suppressor gene CDKN2A is frequently deactivated in cancer. Homozygous CDKN2A deletion is a Grade 4 defining criterion for IDH-mutant gliomas. However, the prognostic value of hemizygous CDKN2A deletions is unclear. We assessed CNV profiles of 1238 initial and 479 recurrent IDHmut gliomas to evaluate the association of CDKN2A hemizygous deletions with overall survival (OS) outcomes.

MATERIAL AND METHODS
The GLASS primary/recurrent glioma dataset was used to infer CDKN2A status with DNAseq (n=210) and DNA methylation array (n=100) data. Validation was conducted using DFCI, MSKCC, TCGA and DKFZ cohorts.

RESULTS
Longitudinal analyses of IDH-mutant gliomas without 1p-/19q-codeletion showed significant increases in CDKN2A homozygous deletion from n=6 to n=23 (5% to 20%, P=0.0001, Fisher’s-exact test) and hemizygous deletion from n=19 to n=34 (17% to 30%, P=0.002) at recurrence. CDKN2A hemizygous deletions were significantly associated with poor OS at initial diagnosis (P&lt;0.0001, log-rank test) and recurrence (P&lt;0.0001), remaining significant in multivariable cox regression model that accounted for age, treatment with radiotherapy and/or alkylating agents, and 1p/19q-codeletion status: HR 2.40 (95%-CI: 1.31-4.37, P=0.004). Validation in independent datasets confirmed increased frequencies of CDKN2A hemizygous deletions in recurrent cases as well as the association between CDKN2A hemizygous deletion and worse OS in IDHmut gliomas. Using the DKFZ DNA methylation profiling dataset we further confirmed that CDKN2A status can be accurately assessed through DNAseq and DNA methylation array profiling.

CONCLUSION
CDKN2A hemizygous deletion is associated with significantly worse OS in initial and recurrent IDHmut gliomas. Similar to CDKN2A homozygous deletion, CDKN2A hemizygous deletion is enriched in post-treatment, recurrent IDHmut gliomas, confirming the value of CDKN2A status (re-)assessment in recurrences. Our results highlight the importance of incorporating CDKN2A status in diagnostic workup to inform prognosis and treatment strategies, revealing the previously unrecognized prognostic value of hemizygous CDKN2A deletions.
JS05.5.A INTRAOPERATIVE MRI-GUIDED RESECTION IS NOT SUPERIOR TO 5-ALA-GUIDANCE IN NEWLY DIAGNOSED GLIOBLASTOMA: A PROSPECTIVE CONTROLLED MULTICENTER CLINICAL TRIAL
Authors: Roder C , Stummer W , Coburger J , Scherer M , Haas P , von der Brelie C , Kamp M , Löhr M , Hamisch C , Skardelly M , Scholz T , Schipmann S , Rathert J , Brand C , Pala A , Ernemann U , Stockhammer F , Gerlach R , Kremer P , Goldbrunner R , Ernestus R , Sabel M , Rohde V , Tabatabai G , Martus P , Bisdas S , Ganslandt O , Unterberg A , Wirtz C , Tatagiba M 
Published: September 2023

Abstract

BACKGROUND
Prospective data suggested a superiority of intraoperative MRI (iMRI) over 5-aminolevulinic acid (5-ALA) for achieving complete resections of contrast enhancement in glioblastoma surgery. We investigated this hypothesis in a prospective clinical trial and correlated residual disease volumes with clinical outcome in newly diagnosed glioblastoma.

MATERIAL AND METHODS
This is a prospective controlled multicenter parallel-group trial with two center-specific treatment arms (5-ALA and iMRI) and blinded evaluation. The primary endpoint was complete resection of contrast enhancement on early postoperative MRI. We assessed resectability and extent of resection by an independent blinded centralized review of pre- and post-operative MRI with 1mm slices. Secondary endpoints included progression-free (PFS) and overall survival (OS), patient-reported quality of life and clinical parameters.

RESULTS
We recruited 314 patients with newly diagnosed glioblastomas at eleven German centers. 127 patients in the 5-ALA and 150 in the iMRI arm were analyzed in the as treated analysis. Complete resections, defined as a residual tumor ≤0.175 cm³, were achieved in 90 patients (78%) in the 5-ALA and 115 (81%) in the iMRI arm (p=0.79). Incision-suture times (p&lt;0.001) were significantly longer in the iMRI arm (316 vs. 215 [5-ALA] minutes). Median PFS and OS were comparable in both arms. The lack of any residual contrast enhancing tumor (0cm³) was a significant favorable prognostic factor for PFS (p&lt;0.001) and OS (p=0.048), especially in MGMT unmethylated tumors (p=0.006).

CONCLUSION
We could not confirm superiority of iMRI over 5-ALA for achieving complete resections. Neurosurgical interventions in newly diagnosed glioblastoma shall aim for safe complete resections with 0 cm³ contrast-enhancing residual disease, as any other residual tumor volume is a negative predictor for PFS and OS.
JS05.7.A SURGICAL RE-RESECTION FOR RECURRENT GLIOBLASTOMA: PROGNOSTIC EVALUATION USING THE NOVEL RANO CLASSIFICATION FOR EXTENT OF RESECTION FROM THE RANORESECT GROUP
Authors: Karschnia P , Dono A , Young J S , Juenger S T , Teske N , Häni L , Sciortino T , Mau C Y , Bruno F , Nunez L , Morshed R A , Haddad A F , Weller M , van den Bent M , Beck J , Hervey-Jumper S , Molinaro A M , Tandon N , Rudà R , Vogelbaum M A , Bello L , Schnell O , Grau S J , Chang S M , Berger M S , Esquenazi Y , Tonn J 
Published: September 2023

Abstract

BACKGROUND
The value of re-resection in recurrent glioblastoma remains controversial as a randomized trial that specifies intentional incomplete resection cannot be justified ethically. Here, we aimed to (I) explore the prognostic role of extent of re-resection using the previously proposed RANO classification (based upon residual contrast-enhancing (CE) and non-CE tumor), and to (II) define factors consolidating the surgical effects on outcome.

MATERIAL AND METHODS
The RANO resect group retrospectively compiled a global, eight-center cohort of patients with first recurrence from previously resected glioblastomas. The combined associations of re-resection and other clinical factors with outcome were analyzed. Kaplan-Meier survival analysis and log-rank test were applied to calculate survival, and Cox’s proportional hazard regression models to adjust for multiple variables (significance level: p ≤ 0.05). Propensity score-matched analyses were constructed to mimic randomized clinical trials comparing the different RANO classes.

RESULTS
We studied 681 with first recurrence of IDH-wildtype glioblastomas, including 310 patients who underwent re-resection. Re-resection was associated with prolonged survival even when stratifying for clinical and molecular confounders on multivariate analysis (HR for re-resection: 0.65, CI: 0.5-0.8; p = 0.001); and ≤1 cm3 residual CE tumor was associated with longer survival than non-surgical management. Accordingly, ‘maximal CE resection’ (class 2) had superior survival compared to ‘submaximal CE resection’ (class 3) (median OS after recurrence: 12 vs. 9 months; p = 0.003). Administration of (radio-)chemotherapy further augmented the survival associations of smaller residual CE tumor. The prognostic role of residual CE tumor was confirmed in propensity score analyses. Conversely, ‘supramaximal CE resection’ targeting also non-CE tumor (class 1) was not associated with prolonged survival but frequently accompanied by post-operative deficits, hampering further adjuvant treatment.

CONCLUSION
The RANO resect classification serves to stratify patients with re-resection of glioblastoma. Complete CE resection according to RANO resect class 1 and 2 is prognostic of outcome. The beneficial effects of re-resection might be consolidated by (radio-)chemotherapy, and avoidance of post-operative deficits hampering such treatment is of critical importance.