tbuckley/cabot-search huggingface dataset:
P19.02 Care Coordination: The experience of a Brain Cancer Care Coordinator in Australia
Authors: S. Nixon, J. Morison
Journal: Neuro-Oncology (2017)

The role of the Brain Cancer Care Coordinator (BCCC) aims to provide expert clinical consultancy to support high level care coordination for patients diagnosed with primary brain cancer. The role has a district-wide focus within the Hunter New England Area (HNE), based at John Hunter Hospital, Newcastle, Australia and is funded by the Mark Hughes Foundation. HNE is a region of 131, 785 square kilometres and includes a metropolitan area, regional communities and a portion of remote communities. HNE consists of a population of 873, 741 which is more than Zurich, Geneva, Basel and Bern's population's combined. The diagnosis of a brain tumour can be devastating, debilitating and stressful for not only the patient themselves but also for their entire social support. Within the space of one day, lives can be changed, crucial decisions of treatment need to be made, and exposure to a range of healthcare professionals, tests, reports, and opinions need to be considered. The healthcare system can be incredibly confusing and complex due to the multitude of appointments, range of specialists, debilitating deficits, difficulty accessing services, lack of information, adverse effects from treatment, reduced social support if from a rural area and independence is often taken away such as the ability to drive. Accessing a range of services is difficult and often a lack of information is provided to patients and their families. Caring for a loved one diagnosed with brain cancer is challenging, both emotionally and physically. Witnessing sudden or subtle changes in someone you love is frightening. The varying degrees of change in personality, physical wellbeing, and ultimate loss of lifestyle, can be a burden few can cope with. The BCCC supports the patient and their families from diagnosis through treatment, follow-up, discharge or end of life care. The aim of the BCCC is to provide patient-centred care, advocacy, clinical advice, education, and support, assess needs and make appropriate referrals and bridge the gap between the patient and their specialists to ensure that complex needs of patients and their families are effectively managed. The BCCC coordinates the transitioning of care for rural patients who require care in a metropolitan centre and supports research such as bio banking and clinical trials. The experience of the BCCC since it's commencement in January 2016 is improved over-all well-being of patients and their family's through their entire illness trajectory, efficiency of transitions through care, reduced patient distress, and increased compliance with care. There are few BCCC's in Australia and these positions are often funded by charities such as the Mark Hughes Foundation. The BCCC role should have greater representation within multidisciplinary teams throughout Australia and the world to ensure the highest quality of care is delivered to patients diagnosed with brain cancer.
P04.21 Bing-Neel syndrome - bilateral cavernous sinus lymphoma causing visual failure
Authors: C. Pham, J. Griffiths, A. Kam, M. Hunn
Journal: Neuro-Oncology (2017)

Introduction: Central nervous system involvement is extremely rare in Waldenstrom macroglobulinaemia. Known as Bing-Neel syndrome, there are currently no established diagnostic criteria. Delayed recognition is not unusual as long intervals can occur between secondary central nervous system recurrence and initial presentation with systemic disease. AIM: We present the unique radiological findings of a 68-year-old male with compressive optic neuropathy from relapse of lymphoplasmacytic lymphoma in both cavernous sinuses and review the diagnostic and neuroradiological features of Bing-Neel syndrome. DISCUSSION: Magnetic resonance imaging identified contrast-enhancing extra-axial mass lesions involving both cavernous sinuses, extending anteriorly on the right through the superior orbital fissure and compressing the right optic nerve. The mass showed contiguous extension to the right foramen rotundum, pterygomaxillary fissure and inferior orbital fissure. The presence of “dural tails” extending posteriorly along the tentorial edge was initially thought to be suggestive of meningioma. However, in view of the patient’s history, perineural extension, bilateral cavernous sinus involvement atypical for meningioma and predilection for leptomeningeal involvement in secondary central nervous system lymphoma, relapse of Waldenstrom macroglobulinaemia was considered. Bing-Neel syndrome can present with focal lesions or with more diffuse symptoms resulting from infiltrative leptomeningeal or periventricular white matter involvement. Diagnostic considerations include neuroimaging findings, cerebrospinal fluid analysis and tissue biopsy. Neurosurgical intervention may be indicated to obtain histopathology although the marked clinical and radiological improvement to targeted chemotherapy in this case highlights that radiological features coupled with positive peripheral lymph node and marrow sampling can suffice to allow for diagnosis and prompt initiation of therapy. Conclusions: This is the first documented case to our knowledge of Bing-Neel syndrome presenting simultaneously in both cavernous sinuses. As outcomes following treatment for Waldenstrom macroglobulinaemia improve, greater awareness of its less common manifestations becomes important.
OS09.8 Randomized placebo-controlled trial of autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma
Authors: Y. Muragaki, T. Maruyama, E. Ishikawa, M. Nitta, S. Ikuta, T. Yamamoto, K. Tsuboi, A. Matsumura, H. Nakamura, J. Kuroda, T. Abe, T. Abe
Journal: Neuro-Oncology (2017)

Introduction: There is a growing interest in development of novel therapeutic modalities based on tumor-specific immune reactions for management of glioblastoma multiforme (GBM). Autologous formalin-fixed tumor vaccine (AFTV) was designed by our group for in vivo induction of killer lymphocytes and activation of T-lymphocyte (Nat Med 1995, 1996). In first trial for recurrent GBM, 3 responding patients survived more than 20 months after AFTV administration (Cancer Sci, 2007). Efficacy of AFTV concomitant with fractionated radiotherapy (FRT) without chemotherapy with temozolomide (TMZ) in patients with newly-diagnosed GBM was evaluated in prospective phase I/IIa trial (C00002), which showed median overall survival (OS) of 19.8 months (J Neurosurg, 2011). Another prospective multicenter phase I/IIa trial (UMIN01426) for evaluation of the combined use of AFTV and standard chemoradiotherapy with TMZ (AFTV+RT/TMZ: (Stupp regimen) for newly-diagnosed GBM, showing median progression-free survival (PFS) and OS of 8.2 and 22.2 months, respectively (J Neurosurg, 2013). Currently, prospective multicenter placebo-controlled double-blind phase IIb/III trial (UMIN10602) directing on evaluation of AFTV+RT/TMZ for newly-diagnosed GBM is ongoing and recruiting of patients for its phase IIb part has been finished in January 2016. We here report preliminary results before a key opening. METHODS: The phase IIb/III study investigated the AFTV plus chemoradiotherapy with temozolomide (AFTV + RT/TMZ; Stupp protocol) versus placebo plus chemoradio- therapy (Pla + RT/TMZ) for newly diagnosed glioblastoma. After resection surgery, patients with glioblastoma were randomly assigned 1:1 to receive AFTV (2 courses; 3 times, once a week) + RT/TMZ or Pla + RT/TMZ until disease progression. The primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), objective response rate, QOL, and safety. RESULTS: Adult 63 patients with supratentrial glioblastoma were enrolled, although 3 patients withdraw the consents. Among 60 patients for full analysis set, baseline characteristics were balanced. The median age was 61 years old, men vs. women were 33 vs. 27, and the median resection rate was 95%. Mean follow-up period was 15.8 months. The median PFS was 14.2 months and 6-month PFS was 75% both for AFTV+RT/TMZ and Pla+RT/TMZ. The median PFS was 21.4 months and 1-year survival was 86% both for AFTV+RT/TMZ and Pla+RT/TMZ. No severe adverse events caused by AFTV or placebo were observed. CONCLUSION: The phase IIb part of the trial has been done safely and trial would be promising because the median PFS for both groups was more than a year. If AFTV+RT/TMZ would show longer survival time compared to Pla+RT/TMZ by the key open, a phase III would be warranted.
US Adult Illicit Cannabis Use, Cannabis Use Disorder, and Medical Marijuana Laws
Authors: Deborah S. Hasin, Aaron L. Sarvet, Magdalena Cerdá, Katherine M. Keyes, Malka Stohl, Sandro Galea, Melanie M. Wall
Journal: JAMA Psychiatry (2017)

Over the last 25 years, illicit cannabis use and cannabis use disorders have increased among US adults, and 28 states have passed medical marijuana laws (MML). Little is known about MML and adult illicit cannabis use or cannabis use disorders considered over time.
Medical student abuse
Authors: Ralph D. Caldroney
Journal: JAMA (1984)

<h3>To the Editor.—</h3> Drs Rosenberg and Silver<sup>1</sup>in their COMMENTARY on medical student abuse have brought to an open forum a problem that has long been an embarrassment to those of us ensconced in academia. It is difficult to take issue with any of their central points. The problem does exist and doubtless occurs in each and every medical school. While the hair on the backs of the neck of many an academician was undoubtedly raised while reading this article, a vituperative response offers no hope for a balanced reply. Therefore, as my mother taught me, I have counted to ten and my gastrin level has returned to baseline. I feel I can safely proceed and respond to this gauntlet tossed down. Two points disturb me about this article. The first is quite simple. What is the scope of the problem? Is this a rare occurrence, as I suspect, or
Abstract 076: Lapatinib Reduced Cardiac Hypertrophy Induced By Combined Use Of A Pi3k-mtor Dual Inhibitor And Doxorubicin
Authors: Xinhua Yan, Yongyao Yang, Juyong Lee, Jillian Onufrak, John Fuseler, Robert Price, Thomas K Borg, James Morgan, David Goukassian, Joseph Carrozza
Journal: Circulation Research (2013)

The HER2-PI3K-mTOR pathway is pivotal for regulating the physiological function of the heart. Currently, drugs targeting the HER2-PI3K-mTOR pathway are either approved or being tested in clinical trials for cancer therapy. It is, therefore, important to evaluate the cardiac effects of using these drugs. In addition, it is necessary to develop countermeasures to prevent the cardiac side effects if any. Methods: Three-month old female FVB/n mice were treated with lapatinib (an HER2 inhibitor) or BEZ235 (BEZ, a PI3K-mTOR dual inhibitor), alone or with doxorubicin (DOX). Cardiac function was monitored by echocardiography and hemodynamic measurements. Cardiac morphology was assessed by confocal microscopy and transmission electron microscopy. The activation of signaling molecules were measured by Western blot analysis. Results: BEZ alone induced cardiac hypertrophy and subsequent heart failure and lapatinib alone induced cardiac failure, in a course of 17 months, respectively. Combination of BEZ with DOX, either concurrently or sequentially, induced cardiac hypertrophy which was associated with higher mortality rate compared to DOX alone. Neuregulin1, a HER receptor ligand worsened, while Lapatinib alleviated, cardiac hypertrophy in these mice. Lapatinib increased the activation of AMPK in DOX+BEZ treated hearts. The cardiac effect of lapatinib was blocked by Compound C, an AMPK inhibitor. Metformin, an AMPK activator, alleviated DOX+BEZ induced cardiac hypertrophy. Conclusions: BEZ or lapatinib treatment alone induced irreversible cardiac dysfunction in mice. Combined use of BEZ and DOX induced cardiac hypertrophy and early mortality, which were prevented by lapatinib. The cardioprotective effects of lapatinib may rely on activating AMPK in the heart.
High-Frequency Oscillatory Ventilation Compared with Conventional Mechanical Ventilation in the Treatment of Respiratory Failure in Preterm Infants
Journal: New England Journal of Medicine (1989)

We conducted a multicenter randomized clinical trial to compare the efficacy and safety of high-frequency ventilation with that of conventional mechanical ventilation in the treatment of respiratory failure in preterm infants. Of 673 preterm infants weighing between 750 and 2000 g, 346 were assigned to receive conventional mechanical ventilation and 327 to receive high-frequency oscillatory ventilation. The incidence of bronchopulmonary dysplasia was similar in the two groups (high-frequency ventilation, 40 percent; conventional mechanical ventilation, 41 percent; P = 0.79). High-frequency ventilation did not reduce mortality (18 percent, vs. 17 percent with conventional ventilation; P = 0.73) or the level of ventilatory support during the first 28 days. The crossover rate from high-frequency ventilation to conventional mechanical ventilation was greater than the crossover rate from mechanical to high-frequency ventilation (26 vs. 17 percent; P = 0.01). High-frequency ventilation, as compared with conventional mechanical ventilation, was associated with an increased incidence of pneumoperitoneum of pulmonary origin (3 vs. 1 percent; P = 0.05), grades 3 and 4 intracranial hemorrhage (26 vs. 18 percent; P = 0.02), and periventricular leukomalacia (12 vs. 7 percent; P = 0.05). These results suggest that high-frequency oscillatory ventilation, as used in this trial, does not offer any advantage over conventional mechanical ventilation in the treatment of respiratory failure in preterm infants, and it may be associated with undesirable side effects.
Exploration of Survival Stratification of Patients with Multiple Myeloma after First Relapse Using Real World Data
Authors: Roman Hájek, Jiri Jarkovsky, Walter Bouwmeester, Maarten Treur, Lucy DeCosta, Marco Campioni, Michel Delforge, Marc S. Raab, Paul Schoen, Zsolt Szabo, Brozova Lucie, Sebastian Gonzalez-McQuire
Journal: Blood (2016)
Abstract 276: Shockwave Reduces Macrophage Foam Cell Formation Via Increased Expression of ATP Binding Cassette Transporters.
Authors: Wonkyoung Cho, Young Eun Yoon, Kihwan Kwon, Young Mi Park
Journal: Circulation Research (2013)

Background: Excessive lipid accumulation by macrophages plays a crucial role in atherosclerosis. Foam cells are generated by uncontrolled uptake of modified LDL, especially oxidized LDL (oxLDL), and/or impaired cholesterol efflux mediated by ATP-binding cassette (ABC) family transporters, ABCA-1 and ABCG-1. Shockwave, elicited by transient pressure disturbance, have been used for extracorporeal lithotripsy or for treating musculoskeletal disorders. Our current study suggests an evidence that shockwave may have anti-atherogenic effect by inhibiting foam cell formation. Methods/Results: Murine peritoneal macrophages were exposed to shockwaves at 0.04 mJ/mm 2 with 1000 impulses, lysed after 6, 18 and 24 hours, and tested for expression of ABCA-1 and ABCG-1. The western blot showed that shockwave induced 2.0-2.8 fold increase of ABCA-1 and ABCG-1 within 18-24 hours. mRNA levels of ABCA-1 and ABCG-1 were also increased by shockwave with 2.0 fold of peak increase in 18 hours. The increased expression of ABCA-1 and ABCG-1 was mediated by phosphorylation of ERK 1/2 (Tyr204). Western blot analysis revealed that shockwave induced phosphorylation of ERK 1/2 (Tyr204) in murine macrophages. Shockwave-induced increase of ABCA-1 and ABCG-1 was blocked by U0126 (40µM), a specific inhibitor for ERK. Oil-red O staining showed that macrophages exposed to shockwave had 25% less intracellular lipid droplets. Intracellular cholesterol measured by cholesterol oxidase and esterase revealed that macrophages exposed to shockwave had 23% less intracellular cholesterol when incubated with oxLDL (50µg/ml) for 16 hours. In vitro migration assays including modified Boyden chamber migration assay and scratch wound healing migration assay showed that macrophages exposed to shockwave had 1.2 fold more migration and had diminished migration-inhibitory effect of oxLDL. Conclusions: Shockwave reduces macrophage foam cell formation via ERK-mediated increase of ABCA-1 and ABCG-1 mediating lipid efflux and promotes macrophage migration which may induce macrophage egress from atherosclerotic lesion. Our study suggests anti-atherogenic effects of shockwave as a potential treatment modality for atherosclerosis.
Abstract P321: Oxidative Stress Induces DNA Double-Strand Breaks and Activates DNA Damage Responses in Vascular Smooth Muscle Cells: A Possible Mechanism for Atherosclerosis Progression
Authors: Takafumi Ishida, Mari Ishida, Satoshi Tashiro, Chiemi Sakai, Hitomi Uchida, Kiyoshi Miyagawa, Masao Yoshizumi, Yasuki Kihara
Journal: Circulation Research (2011)

Backgrounds: Oxidative stress is thought to be a pathogenic mediator of atherosclerosis. Oxidative stress induces DNA damage, and the unrepaired or improperly repaired DNA damage increases genomic instability, which cause cell death, senescence, or dysregulation of cellular functions. Pathogenesis of both Hutchinson-Gilford Progeria syndrome and Werner syndrome, which feature prominent atherosclerotic disease at young age, involves impaired DNA repair and the resultant genomic instability. The purpose of this study is to determine whether oxidative stress causes DNA damage in vascular smooth muscle cells (VSMC) and to elucidate the role of DNA damage responses in atherosclerosis and the fate of VSMC. Methods and Results: Immunoreactivity against gamma-H2AX, a sensitive marker for DNA double-strand breaks (DSBs), which is the most severe form of DNA damage, was increased in human atherosclerotic plaques, but not in the adjacent normal areas. gamma-H2AX staining was observed in almost same regions where 8-oxo-dG immunoreactivity, an oxidative modification of DNA, was observed. Apoptotic cells were abundant in atherosclerotic lesions, but not in normal areas. In cultured human aortic smooth muscle cells (HASM), 15 min incubation with H2O2 (100 microM) induced foci formation of gamma-H2AX in the nuclei. H2O2 activated various signaling molecules involved in DNA damage responses, including ATM, Chk2, DNA-PK and p53 in HASM. Some H2O2-induced DSBs persisted after 24 hours, at which point apoptosis was induced in 7.1 ± 1.3 % of HASM, as detected by TUNEL method. Knockdown experiments using siRNA revealed that ATM-, DNA-PK-, or Chk2-deficient VSMC were more resistant to H2O2-induced apoptosis. Conclusions: In summary, 1) DNA double-strand breaks were accumulated in human atherosclerotic plaques, 2) oxidative stress induced double-strand breaks and activation of DNA damage response in vascular smooth muscle cells, and 3) impairment of DNA damage responses modulated damage-induced cell fate such as apoptosis. Thus, DNA damage itself or alteration in DNA damage responses may be involved in the mechanisms for progression of atherosclerosis.
OS08.7 The somatic landscape of Schwannoma
Authors: S. Agnihotri, M. Wilson, S. Jalali, M. Li, S. Pagnotta, A. Iavarone, K. Aldape, G. Zadeh
Journal: Neuro-Oncology (2017)

To date, clinical trials for schwannomas, which are common cranial and spinal nerve tumors, have generated dismal results. This is largely due to a lack of fully understanding the somatic alterations that occur in schwannoma. To gain a comprehensive molecular understanding of Schwannoma, we performed an integrative multiplatform analysis to determine the genetic landscape of sporadic schwannomas. Exome sequence analysis with validation by targeted DNA-sequencing of 125 samples uncovered, in addition to expected NF2 disruption, recurrent mutations in ARID1A, ARID1B and DDR1. Genome wide methylation profiling revealed that schwannomas consists of two molecular subgroups with unique gene signatures and anatomical location. RNA sequencing revealed a recurrent in-frame gene fusion on chromosome 10q in 12/125 (10%) cases involving two gene partners, SH3PXD2A and HTRA1. Further genomic analysis identified the mechanism to be from a balanced 19Mb chromosomal inversion. The presence of the fusion was associated with male gender predominance, occurring in one out of every six men with schwannoma. Expression of the fusion in both schwannomas and normal schwann cells resulted in elevated phosphorylated-ERK, increased proliferation, increased invasion and resulted in the formation of in vivo xenografts. Furthermore, the fusion increased cell invasion and enhanced protease activity. Targeting of the MEK/ERK pathway was effective in fusion-positive Schwann cells, suggesting a possible therapeutic approach for this subset of tumors.
Addiction to exercise
Authors: Heather A Hausenblas, Katherine Schreiber, James M Smoliga
Journal: BMJ (2017)

#### What you need to know

#### Author’s story

By the time KS entered college, her world revolved around the gym. No sooner would she finish a lecture than she would dash to the campus fitness centre. She would feel anxious if she missed a workout and would go no matter how tired or busy she was. Travelling was very difficult because of her obsessiveness about her exercise routines. She lost many friendships and career opportunities because she was barely available outside her exercise schedule. By the time she was 26 years old, KS had weathered two herniated discs and a stress fracture and had persistent exhaustion.

Exercise has numerous health benefits and is generally viewed as a positive behaviour,1 so patients and clinicians may overlook the dangers of excessive exercise and addiction. This article explores how healthcare professionals can recognise and understand the risks of primary exercise addiction.

#### Details of literature search

We searched PubMed and PsychINFO using the terms “exercise addiction,” “exercise dependence,” and “excessive exercise” for systematic reviews and experimental, cross-sectional, and case studies. The overall quality of the evidence for this area is modest with a reliance on descriptive and observational studies. Few controlled trials and experimental designs exist.

People with exercise addiction experience loss of control such that exercise becomes an obligation and excessive.23 Although exercise addiction is not officially classified as a mental health disorder, it is characterised by similar negative effects on emotional and social health as other addictions. Primary exercise addiction differs from excessive exercise seen in people with eating disorders (also known …