tbuckley/cabot-search huggingface dataset:
P14.106 One-year survival of radiotherapy vs conservative therapy in patients with metastatic brain disease in Cipto Mangunkusumo General Hospital 2014–2016
Authors: T Aninditha, P Y Pratama, D Imran, R A Aman, R A Werdhani, H R Sofyan, J Odilo, T A S Ranakusuma
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND There are several palliative treatment choices in patients with brain metastasis. Radiotherapy is one of palliative treatment modality in brain metastasis. The role of radiotherapy in metastatic brain disease has already been established. Patients with metastatic brain disease also treated conservatively. Sole conservative treatment were also done in regarding qualification of patient. This study aimed to compare radiotherapy and conservative treatment in one-year survival on brain metastasis patients. MATERIAL AND METHODS This study was a retrospective cohort study. The data acquired from Dept. of Neurology Cipto Mangunkusumo General Hospital between 2014–2016. Subjects with metastatic brain disease underwent radiotherapy and conservative treatment were included in this study. Sex, age, marital status, survival time, were retrieved from the subjects. The follow-up period were 1 year. Univariate analysis were done using t-test and chi-square test. Multivariate analysis were done using Log-rank test and Cox regression. RESULTS There were 41 subjects included in the study. Of 41 subjects, 21 (51.2%) underwent radiotherapy. The mean age of subjects underwent radiotherapy were 53.3 (SD ±12.6) vs 43.1 (SD ±14.7) in subjects with conservative management (P = 0.022). Women accounted for 27 out of 41 (65.9%) subjects. Married subjects accounted for 32 out of 41 (78%) subjects. There were no significance difference of treatment choices between married and unmarried subjects (P = 0.130). At the end of follow-up period, only 4 (19%) subjects from conservative treatment and 2 (10%) subjects from radiotherapy treatment survived (P = 0.854). Median survival of radiotherapy treatment were 5 month and 4 month in conservative treatment. Palliative treatment didn’t raise risk of death compared to conservative treatment [Hazard Ratio (HR) 0.94, 95% Confidence Interval (CI): 0.48–1.85, P = 0.867). CONCLUSION Radiotherapy treatment didn’t increase one-year survival in patients with metastatic brain disease. Other confounding factors that influenced survival should be included in further study to understand factors that interact with palliative treatment in brain metastases.
Trial of SAGE-217 in Patients with Major Depressive Disorder
Authors: Handan Gunduz-Bruce, Christopher Silber, Inder Kaul, Anthony J. Rothschild, Robert Riesenberg, Abdul J. Sankoh, Haihong Li, Robert Lasser, Charles F. Zorumski, David R. Rubinow, Steven M. Paul, Jeffrey Jonas, James J. Doherty, Stephen J. Kanes
Journal: New England Journal of Medicine (2019)

Altered neurotransmission of γ-aminobutyric acid (GABA) has been implicated in the pathogenesis of depression. Whether SAGE-217, an oral, positive allosteric modulator of GABA type A receptors, is effective and safe for the treatment of major depressive disorder is unknown.In this double-blind, phase 2 trial, we enrolled patients with major depression and randomly assigned them in a 1:1 ratio to receive 30 mg of SAGE-217 or placebo once daily. The primary end point was the change from baseline to day 15 in the score on the 17-item Hamilton Depression Rating Scale (HAM-D; scores range from 0 to 52, with higher scores indicating more severe depression). Secondary efficacy end points, which were assessed on days 2 through 8 and on days 15, 21, 28, 35, and 42, included changes from baseline in scores on additional depression and anxiety scales, a reduction from baseline of more than 50% in the HAM-D score, a HAM-D score of 7 or lower, and a Clinical Global Impression of Improvement score of 1 (very much improved) or 2 (much improved) (on a scale of 1 to 7, with a score of 7 indicating that symptoms are very much worse).A total of 89 patients underwent randomization: 45 patients were assigned to the SAGE-217 group, and 44 to the placebo group. The mean baseline HAM-D score was 25.2 in the SAGE-217 group and 25.7 in the placebo group. The least-squares mean (±SE) change in the HAM-D score from baseline to day 15 was -17.4±1.3 points in the SAGE-217 group and -10.3±1.3 points in the placebo group (least-squares mean difference in change, -7.0 points; 95% confidence interval, -10.2 to -3.9; P<0.001). The differences in secondary end points were generally in the same direction as those of the primary end point. There were no serious adverse events. The most common adverse events in the SAGE-217 group were headache, dizziness, nausea, and somnolence.Administration of SAGE-217 daily for 14 days resulted in a reduction in depressive symptoms at day 15. Adverse events were more common in the SAGE-217 group than in the placebo group. Further trials are needed to determine the durability and safety of SAGE-217 in major depressive disorder and to compare SAGE-217 with available treatments. (Funded by Sage Therapeutics; ClinicalTrials.gov number, NCT03000530.).
P11.42 Magnetic targeting of the granzyme B functionalized nanoparticles for therapy of glioblastoma
Authors: M Shevtsov, S Stangl, Y Marchenko, L Yakovleva, V Ryzhov, B Nikolaev, O Galibin, E Pitkin, G Multhoff
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Magnetic drug targeting by employing external magnetic fields represents a promising approach for treatment of glioblastoma. To increase the anti-tumor therapeutic effect magnetic nanocarriers could be functionalized with tumor-targeting bioligands such as granzyme B (GrB). The serine protease GrB that is produced as an effector molecule by activated NK and T cells can induce specific tumor cell apoptosis. MATERIAL AND METHODS The targeting potential of the dextran-coated superparamagnetic iron oxide nanoparticles conjugated with GrB (GrB-SPIONs) was assessed in glioblastoma cells (U87, C6, GL261) by flow cytometry, confocal and electron microscopies. Magnetic field strength (320 mT) in the models of U87 glioblastoma in NMRI nu/nu mice and C6 glioma in Wistar rats was achieved by employing NdFeB cylindrical ferromagnet. The irradiation of the implanted tumors was performed using the CT-image guided Small Animal Radiation Research Platform (SARRP). Accumulation of the nanoparticles was assessed in paraffine-embedded specimens employing Prussian blues staining. Sections were additionally analyzed by IHC for apoptosis (caspase 3). RESULTS Synthesized GrB-SPIONs incorporated into the cytoplasm of tumor cells via the endolysosomal pathway and induced apoptosis in a dose-dependent manner. Intravenous injection of GrB-SPIONs resulted in the glioma-specific retention of the nanoparticles as was shown by high-field (11 T) magnetic resonance imaging and biodistribution studies (NLR-M2 measurements). Magnetic targeting of the nanoparticles in vivo drastically enhanced the accumulation of nanoparticles to the location of the magnet. Thus the local retention of nanoparticles was 12.3-fold higher as compared to application of GrB-SPIONs without external magnetic field. The presence of granzyme B on SPIONs has been shown to promote tumor cells death (IHC staining for caspase 3) and significantly increased overall survival. A combination of nanoparticle treatment with a single radiation dose (10 Gy) significantly prolonged the survival of rats as compared to animals treated only with magnetic targeting of GrB-SPIONs or radiotherapy alone (P&lt;0.001). CONCLUSION Single-agent therapy with GrB-SPIONs demonstrated an impressive increase in overall survival of tumor-bearing animals. Combinatorial regimen employing magnetic targeting and stereotactic radiotherapy further enhanced the therapeutic potential of magnetic conjugates.
Judge rules that doctors can perform caesarean section if woman loses mental capacity
Authors: Clare Dyer
Journal: BMJ (2019)

A High Court judge has given doctors permission to perform a caesarean section on a 30 year old woman with bipolar disorder in the event that she loses the capacity to make decisions about her treatment during labour.

The case follows a similar decision in June authorising doctors to manage the labour of a 27 year old woman with paranoid schizophrenia should she become agitated during labour and lose the capacity to take decisions herself.

The cases are highly unusual because both women had the mental capacity to decide for themselves at the time …
Evaluation of Reproducible Research Practices in Oncology Systematic Reviews With Meta-analyses Referenced by National Comprehensive Cancer Network Guidelines
Authors: Cole Wayant, Matthew J. Page, Matt Vassar
Journal: JAMA Oncology (2019)

Reproducible research practices are essential to biomedical research because these practices promote trustworthy evidence. In systematic reviews and meta-analyses, reproducible research practices ensure that summary effects used to guide patient care are stable and trustworthy.To evaluate the reproducibility in theory of meta-analyses in oncology systematic reviews cited by the 49 National Comprehensive Cancer Network (NCCN) guidelines for the treatment of cancer by site and evaluate whether Cochrane reviews or systematic reviews that report adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines use more reproducible research practices.A cross-sectional investigation of all systematic reviews with at least 1 meta-analysis and at least 1 included randomized clinical trial (RCT) that are cited by NCCN guidelines for treatment of cancer by site. We scanned the reference list of all NCCN guidelines (n = 49) for potential systematic reviews and meta-analyses. All retrieved studies were screened, and data were extracted, independently and in duplicate. The analysis was carried out between May 6, 2018, and January 28, 2019.The frequency of reproducible research practices, defined as (1) effect estimate and measure of precision (eg, hazard ratio with 95% confidence interval); (2) clear list of studies included for each analysis; and (3) for subgroup and sensitivity analyses, it must be clear which studies were included in each group or level.We identified 1124 potential systematic reviews, and 154 meta-analyses comprising 3696 meta-analytic effect size estimates were included. Only 2375 of the 3696 meta-analytic estimates (64.3%), including subgroup and sensitivity analyses, were reproducible in theory. Forest plots appear to improve the reproducibility of meta-analyses. All meta-analytic estimates were reproducible in theory in 100 systematic reviews (64.9%), and in 15 systematic reviews (9.7%), no meta-analytic estimates could potentially be reproduced. Data were said to be imputed in 29 meta-analyses, but none specified which data. Only 1 meta-analysis included a link to an online data set.More reproducible research practices are needed in oncology meta-analyses, as suggested by those that are cited by the NCCN. Reporting meta-analyses in forest plots and requirements for full data sharing are recommended.
Xenografting of human umbilical mesenchymal stem cells from Wharton’s jelly ameliorates mouse spinocerebellar ataxia type 1
Authors: Pei-Jiun Tsai, Chang-Ching Yeh, Wan-Jhen Huang, Ming-Yuan Min, Tzu-Hao Huang, Tsui-Ling Ko, Pei-Yu Huang, Tien-Hua Chen, Sanford P. C. Hsu, Bing-Wen Soong, Yu-Show Fu
Journal: Translational Neurodegeneration (2019)

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by the expansion of CAG repeats in ATXN1 gene resulting in an expansion of polyglutamine repeats in the ATXN1 protein. Unfortunately, there has yet been any effective treatment so far for SCA1. This study investigated the feasibility of transplanting human umbilical mesenchymal stem cells (HUMSCs) into transgenic SCA1 mice containing an expanded uninterrupted allele with 82 repeats in the ATXN1-coding region. 106 human umbilical mesenchymal stem cells were transplanted into the cerebella at 1 month of age. HUMSCs displayed significant ameliorating effects in SCA1 mice in terms of motor behaviors in balance beam test and open field test as compared with the untransplanted SCA1 mice. HUMSCs transplantation effectively reduced the cerebellar atrophy, salvaged Purkinje cell death, and alleviated molecular layer shrinkage. Electrophysiological studies showed higher amplitudes of compound motor action potentials as indicated by increasing neuronal-muscular response strength to stimuli after stem cell transplantation. At 5 months after transplantation, HUMSCs scattering in the mice cerebella remained viable and secreted cytokines without differentiating into neuronal or glia cells. Our findings provide hope for a new therapeutic direction for the treatment of SCA1.
P08.05 Cognitive impairment in patients with newly-diagnosed high-grade gliomas
Authors: M Ribeiro, T Durand, J Jacob, D Psimaras, G Noel, L Feuvret, K Hoang-Xuan, M Roussel, O Godefroy, M Bernier, D Ricard
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Cognitive dysfunction is frequent in patients with primary brain tumor, impairing attention, memory and executive function. It compromises functional independence, decision making capacity and psycho-social well-being. Cognitive functioning is highly correlated to disease progression and quality of survival, thus cognitive follow-up is essential in the management of the disease. Cognitive screening tools are often used, since a comprehensive battery may be time consuming and challenging for patients. The objective of this study was to identify a pattern of cognitive dysfunction in patients with newly-diagnosed high-grade gliomas and evaluate the sensitivity and specificity of the MoCA (Montreal Cognitive Assessment) as a cognitive screening tool in the clinical practice. MATERIAL AND METHODS We compared performances in tests of memory, action speed, visuospatial ability and executive function of 156 patients with newly-diagnosed WHO Grade III and IV gliomas, after surgery and prior to radiochemotherapy, to those of a group of healthy controls (n=1003). Relatives assessed behavior through a questionnaire of behavioral dysexecutive syndrome. A stepwise logistic regression was performed to select cognitive domains better discriminating patients from healthy controls and we tested the sensitivity and specificity of the MOCA using ROC curve analysis. RESULTS The stepwise logistic regression analysis identified the 3 following factors better discriminating patients from controls: TMT-B completion time (OR: 0.673; 95% CI: 0.511–0.886; p=0.0005), a verbal memory index (OR:0.507; 95% CI: 0.358–0.718; p=0.0001) and a behavioral dysexecutive score (OR:0.616; 95% CI: 0.468–0.812, p=0.001). Prevalence of cognitive-behavioral impairment was of 35.94%; 95% CI: 28.3 - 43.5. The ROC curve analysis for the assessment of the MoCA sensitivity and specificity in detecting impairment yielded 0.795 (95%CI: 0.714–0.875) for the MoCA raw score, and 0.804 (95%CI: 0.727 - 0.881) for the adjusted z score. The optimal discrimination was obtained for a raw score ≤ 25 (sensitivity of 0.526; specificity of 0.832). For the adjusted score, optimal discrimination value was observed with a -0.603 z score (sensitivity of 0.716; specificity of 0.768). CONCLUSION Cognitive impairment and behavioral dysexecutive syndrome is frequent in patients with newly-diagnosed high-grade glioma. The MoCA lacks sensitivity in screening cognitive impairment to discriminate patients from healthy controls in this setting, and a comprehensive neuropsychological assessment is still recommended.
P03.14 New features of modern 3D conformal external radiotherapy (RT) of benign head tumors in children
Authors: F Antonenko, E Slobina, E Abbasova, A Smyslov, A Dykina, N Sidibe, S Abdullaeva, V Vasilyev
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND demonstrate the possibilities of radiation therapy (LT) in children with benign head tumors using IMRT, VMAT, IGRT techniques - high-precision modern 3D conformal radiation therapy MATERIAL AND METHODS From 1990 to 2007 for the first time in Russia, 88 children with juvenile angiofibromas were treated in Russian Scientific Center of Roentgenoradiology. The studies were carried out on the gamma-therapeutic apparatus “AGAT-P1” and on the linear accelerator “Phillips SL75” Total dose was 35–45 Gy. In 2014–2018 we treated 29 patients aged 3–17 years with benign tumors of the skull base and brain (angiofibromas, craniopharyngiomas, hemangiomas) using high-precision techniques (IMRT, VMAT, IGRT). 15 of 29 patients were repeatedly operated in various domestic and foreign clinics and were admitted to RT with the threat of bleeding, with recurrent growth of tumors, including after multiple selective angioembolization. RESULTS Up to 80% of patients had a 5-year stable remission, and the optimal total dose for radiation therapy of benign head tumors in children was scientifically substantiated. It was found that there is a high risk of continued growth after RT in children under 8 years of age, complications in 10% of patients in the coming years after RT and in 100% of those reirradiated. In all 29 cases of RT in children, we observed a positive clinical effect - stopping bleeding from the nasopharynx after 1–3 sessions of 3D conformal RT (Dose per fraction 1.8 Gy, total dose 45–54 Gy), positive clinical symptoms under the supervision of an Head and Neck surgeon. The effect of hardening and stopping the growth of tumors according to MRI data were followed up after 3 months, 6 months, 1 year. CONCLUSION The development of navigational, endosurgical and fibro-endoscopic minimally invasive technologies in the last 30 years has allowed to expand the indications for surgical methods of treatment for benign head tumors in children, which has reduced their flow to RT. However, after modern surgical interventions, 6–10% of these patients experience recurrences and bleeding, the number of which can be reduced with timely RT. New technologies in LT provide minimal impact on surrounding healthy tissues and allow wider use of RT in recurrent and difficult-to-reach benign skull base tumors in children
Long‐term safety and efficacy of rituximab in 248 adults with immune thrombocytopenia: Results at 5 years from the French prospective registry ITP‐ritux
Authors: Samuel Deshayes, Mehdi Khellaf, Anissa Zarour, Richard Layese, Olivier Fain, Louis Terriou, Jean‐François Viallard, Stéphane Cheze, Julie Graveleau, Borhane Slama, Sylvain Audia, Manuel Cliquennois, Mikael Ebbo, Guillaume Le Guenno, Gilles Salles, Caroline Bonmati, France Teillet, Lionel Galicier, Olivier Lambotte, Arnaud Hot, François Lefrère, Matthieu Mahévas, Florence Canoui‐Poitrine, Marc Michel, Bertrand Godeau
Journal: American Journal of Hematology (2019)

Rituximab is a second-line option in adults with immune thrombocytopenia (ITP), but the estimated 5-year response rate, only based on pooled retrospective data, is about 20%, and no studies have focused on long-term safety. We conducted a prospective multicenter registry of 248 adults with ITP treated with rituximab with 5 years of follow-up to assess its long-term safety and efficacy. The median follow-up was 68.4 [53.7-78.5] months. The incidence of severe infections was only 2/100 patient-years. Profound hypogammaglobulinemia (<5 g/L) developed in five patients at 15 to 31 months after the last rituximab infusion. In total, 25 patients died at a median age of 80 [69.5-83.9] years, corresponding to a mortality rate of 2.3/100 patient-years. Only three deaths related to infection that occurred 12 to 14 months after rituximab infusions could be due in part to rituximab. At 60 months of follow-up, 73 (29.4%) patients had a sustained response. On univariate and multivariate analysis, the only factor significantly associated with sustained response was a previous transient response to corticosteroids (P = .022). Overall, 24 patients with an initial response and then relapse received retreatment with rituximab, which gave a response in 92%, with a higher duration of response in 54%. As a result of its safety profile and its sustained response rate, rituximab remains an important option in the current therapeutic armamentarium for adult ITP. Retreatment could be an effective and safe option.
P03.10 Analyzing the role of reoperation in high grade gliomas: a retrospective study
Authors: V González, J Ibáñez, J Fuster, M Brell
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Primary treatment of high grade glioma consists in a standard therapeutic regimen that involves maximal surgical safe resection followed by chemoradiotherapy. Unfortunately, due to its aggressive behavior, relapse is the rule in all patients. When this situation arises, treatment strategy is less clear and reintervention in selected cases is controversial and still a reason for debate. MATERIAL AND METHODS We retrospectively analysed (n=393) patients affected with high grade glioma in our institution during a period of 14 years (from January 2005 to March 2019). Treatment modality at diagnosis and recurrence, overall and progression-free survival were reviewed. RESULTS There were 320 grade IV and 73 grade III gliomas. Regarding to the modality of treatment, more procedures with radical intention (n=227) than biopsies (n=166) were performed. At progression, glioblastoma patients were treated in (n=118) cases. We decided to reoperate (n=30) cases who also received second-line chemotherapies.The other group (n=88) received only systemic treatment. Median overall survival assessed from initial diagnosis was 23 months(95% CI 17–28.9) versus 17 months (95% CI 15.7–18.2) in patients with surgery at recurrence comparing to those who did not undergo second surgery, (p&lt; 0.05). In addition, clinical condition of most patients did not worsen after the second surgery. CONCLUSION Second surgery for recurrent glioblastoma was associated with a survival advantage. Reoperation should be considered in patients with tumours located in low eloquence areas and good clinical condition.
Helen Salisbury: (I can’t get no) patient satisfaction
Authors: Helen Salisbury
Journal: BMJ (2019)

The National Patient Satisfaction survey results were published in July: patients gave their opinions on reception teams, clinicians, and their overall experience of using their GP surgery.We've been judged, sorted, and ranked accordingly.That our surgery was rated highly suggests that we're managing to fulfil our patients' needs, but our own sense of satisfaction shouldn't distract from pointing out the problems inherent in this process.
Patient Characteristics and Adenoma Detection Rates
Authors: Tomoyuki Kawada
Journal: JAMA Surgery (2019)

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