tbuckley/cabot-search huggingface dataset:
GCT-55. INTRACRANIAL GERMINOMA ORIGINATING FROM ATYPICAL LOCATION WITH SUBCLINICAL ADH INSUFFICIENCY
Authors: Yuki Kuranari, Tomoru Miwa, Maya Kono, Tokunori Kanazawa, Kazunari Yoshida
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Intracranial germinomas are rare tumors which usually develop in the midline structures and affect in 90% of cases the pineal gland and suprasellar regions. Sometimes they involve basal ganglia, septum pellucidum, and other regions. We report a very unusual presentation of an intracranial germinoma originating from the lateral ventricle. METHODS A 10-year-old boy presented with a 1-year history of polydipsia and polyuria. During the hypertonic saline test, a low ADH was detected and established the diagnosis of subclinical ADH insufficiency. MRI showed a heterogeneously enhancing periventricular lesion in the lateral ventricle, but no other abnormal findings, including hypophyseal stalk. Initially, the correlation of imaging findings and clinical symptoms were not clear. With suspected subependymoma, tumor removal was performed by small craniotomy. Since the intra-operative pathological diagnosis was germinoma, we performed only partial removal of the tumor. After establishing the histological diagnosis of germinoma, the patient received chemotherapy using carboplatin and etoposide, followed by radiation therapy. MRI showed no recurrence for five years after treatment. RESULTS/ CONCLUSION Our case presents two atypical features. First, intracranial germinoma originating from the lateral ventricle is quite rare. Though the cases with intracranial germinoma originating from septum pellucidum and corpus callosum have been reported, this case is even different. Second, imaging findings did not match clinical symptoms. The cause of subclinical ADH deficiency may be the occult hypophyseal germinoma. In conclusion, we report a 10-year-old case with a very unusual presentation of an intracranial germinoma originating from the lateral ventricle.
SURG-38. SEIZURE OUTCOME AFTER EPILEPSY SURGERY IN CHILDREN WITH BRAIN TUMORS
Authors: Ayat Siddiqui, Amy L McGregor, James W Wheless, Stephen P Fulton, Sarah E Weatherspoon, Paul Kilmo, Frederick A Boop, Raja B Khan
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Epilepsy is a common chronic neurological complication of childhood brain tumors and seizures are refractory to medical therapy in up to 10% of patients. Referral for a diagnostic evaluation is recommended in patients with seizures refractory to ≥2 anti-epileptic drugs (AED). Utility of epilepsy surgery is not established in children with brain tumors. OBJECTIVE Primary aim of this study was to determine seizure outcome after epilepsy surgery in children with childhood brain tumors. METHODS Institutional Review Board’s approval was obtained for this retrospective study. A diagnosis of childhood brain tumor and a referral to the epilepsy monitoring unit (EMU) were required to be included in this study. Seizure outcome was defined according to International League Against Epilepsy (ILAE) outcome scale. Pre and post-operative MRIs were reviewed. RESULTS Forty-two children were referred to the EMU from May 2004 to July 2019. Of the 10 patients that underwent epilepsy surgery, 7 (70%) had pre-surgery frequency of &amp;gt;10 seizures/month and 3(30%) of these had multiple daily seizures; the rest had 3-4 seizures/month. All were taking ≥3 AEDs. Median time from first seizure to surgery was 83.7 months (range 24.3-151.6). At a median follow-up of 67.5 months (range 4.9-133.5) after epilepsy surgery, 60% reported no seizures in the 6-months before the last follow-up. Three (30%) had ILAE class-1 outcome, 4 (40%) class-3, and 3 (30%) were class-4. One child was off AEDs and the others were on a single AED at last follow-up. No post-operative neurological or cognitive deficits were recognized. Focal cortical atrophy was present in 40% of children before and in 30% after surgery. CONCLUSION Epilepsy surgery improved seizure outcome in all children that had epilepsy surgery and reduced the number of AEDs needed to treat seizures. Children with brain tumors and intractable seizures should be referred for epilepsy surgery evaluation.
Psoriasis: an example of the complexity of decision making
Authors: C. Bergqvist, R.S. Stern, O. Chosidow
Journal: British Journal of Dermatology (2020)

Until the early 2000s, treatment options for moderate-to-severe psoriasis were limited to a few systemic therapies, PUVA, and Narrowband-UVB. Since then, insights about the pathogenesis of psoriasis have led to the development of cytokine-based therapies which have revolutionized psoriasis management. However, with more than a dozen targeted therapies approved for psoriasis, keeping pace with the fast-growing repertoire of therapies and synthesizing the literature has become a more complex task.
Optimizing Autologous Stem Cell Transplant for High-Risk Patients with Plasma Cell Dyscrasias
Authors: Naveed Ali, Brenda W. Cooper, Merle Kolk, Richard Creger, Gina Hoffman, Hillard M Lazarus, Ben K. Tomlinson, Paolo Caimi, Leland Metheny, Marcos de Lima, Ehsan Malek
Journal: Blood (2017)
Combined PD-1/VEGFR Blockade: A New Era of Treatment for Hepatocellular Cancer
Authors: David J. Pinato, Petros Fessas, Alessio Cortellini, Lorenza Rimassa
Journal: Clinical Cancer Research (2021)

Combination immunotherapy is an expanding therapeutic modality in hepatocellular carcinoma (HCC), a disease where single-agent immunotherapy has failed to lead to survival benefit. The RESCUE trial adds camrelizumab and apatinib to the therapeutic armamentarium of advanced HCC, raising questions around the optimal positioning of various combination regimens in liver cancer.See related article by Xu et al., p. 1003.
Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a network meta-analysis of randomized trials (vol 44, pg 1, 2018)
Authors: Waleed Alhazzani, Fayez Alshamsi, Emilie Belley-Cote, Diane Heels-Ansdell, Romina Brignardello-Petersen, Mustafa Alquraini, Anders Perner, Morten Hylander Moller, Mette Krag, Saleh Almenawer, Bram Rochwerg, Joanna Dionne, Roman Jaeschke, Mohammed Alshahrani, Adam Deane, Dan Perri, Lehana Thebane, Awad Al-Omari, Simon Finfer, Deborah Cook, Gordon Guyatt
Journal: Intensive Care Medicine (2018)
LGG-54. DETECTION OF THE KIAA1549-BRAF FUSION GENE IN CELLS FORMING MICROVASCULAR PROLIFERATIONS IN PILOCYTIC ASTROCYTOMA
Authors: Shinji Yamashita, Hideo Takeshima, Kiyotaka Saito, Takashi Watanabe, Hajime Ohta, Kiyotaka Yokogami
Journal: Neuro-Oncology (2020)

Abstract Microvascular proliferation (MVP), an aberrant vascular structure is a histopathological hallmark of glioblastoma multiforme (GBM). Although MVP tends to be associated with high-grade glioma, it has also been detected in WHO grade I pilocytic astrocytoma (PA). However, little is known about the mechanism underlying its formation. Using TP53 point mutations as a marker for tumor-derived cells, we earlier reported that MVP was partially converted from tumor cells via mesenchymal transition. In the current study we used the KIAA1549-BRAF fusion gene as a marker to assess whether MVPs in PA contained tumor-derived cells and/or phenotypically distinct tumor cells expressing vascular markers. Samples from three PA patients harbored the KIAA1549 exon 15, BRAF exon 9 fusion gene. In two patient samples with abundant MVP, RT-PCR assay detected strong bands arising from the KIAA1549-BRAF fusion gene in both tumor cells and cellular components of MVP. Digital PCR showed that vis-à-vis tumor tissue, its relative expression in cellular components of MVP was 42% in one- and 76% in another sample. FISH revealed amplified signals in both tumor cells and cellular components of MVP indicative of tandem duplication. Our findings suggest that in patients with PA, some cellular components of MVP contained tumor derived cell and/or phenotypically distinct tumor cells expressing vascular markers.
NCOG-29. O6-METHYLGUANINE DNA METHYLTRANSFERASE (MGMT) PROMOTER METHYLATION STATUS AND THE INCIDENCE OF TEMOZOLOMIDE-INDUCED HEMATOLOGIC TOXICITY: AN ASSOCIATION STUDY
Authors: Alyssa Strohbusch, Heather Pound, Patrick Regis, Robert Cavaliere
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Despite the growing body of evidence demonstrating an increased clinical benefit of alkylating agents in glioblastoma patients with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, little is known regarding the effect of MGMT status on toxicity. The purpose of this investigation is to provide insight into the potential association between MGMT promoter methylation and the development of Grade 3/4 hematologic toxicities in patients receiving temozolomide. METHODS A total of 63 patients with documented glioblastoma or anaplastic astrocytoma diagnoses were evaluated retrospectively. A chi-square test of independence was utilized to evaluate the incidence of hematologic toxicities and patient overall survival was determined by univariate analysis estimated through use of Kaplan-Meier curves. Relative frequencies of treatment discontinuation secondary to myelosuppression were also compared. RESULTS At the time of study completion, 71.4% of patients with MGMT promoter hypermethylation had survived compared with 50% of patients with hypomethylation (HR 0.86; 95% CI 0.71 to 1.05; P&amp;gt;0.05). The percentage of patients who experienced Grade 3/4 hematologic toxicities during concurrent treatment was 20% and 5.1% within the hypermethylated and hypomethylated groups, respectively, and 26.7% and 17.9% throughout standard therapy. While a statistical difference was not found between the cumulative incidences of Grade 3/4 hematologic toxicity events throughout both phases of treatment, a statistical difference was noted in the incidence of Grade 4 occurrences with ten events occurring in the hypermethylated group and zero in those with hypomethylated promoter regions (P&amp;lt; 0.01). Furthermore, use of temozolomide in hypermethylated patients resulted in fewer completed cycles of standard therapy and higher rates of treatment delays and drug discontinuation. CONCLUSIONS This study showed marked differences in the frequency of temozolomide-induced hematologic toxicities and treatment discontinuation based on tumor MGMT promoter methylation status. Further research is warranted in larger patient populations to both validate and determine the clinical significance of these findings.
In cancer-related VTE, DOACs reduce recurrent VTE compared with LMWH; groups do not differ for major bleeding
Authors: Anjlee Mahajan, Richard H. White
Journal: Annals of Internal Medicine (2020)

Haykal T, Zayed Y, Deliwala S, et al. Direct oral anticoagulant versus low-molecular-weight heparin for treatment of venous thromboembolism in cancer patients: an updated meta-analysis of randomized controlled trials. Thromb Res. 2020;194:57-65. 32788122.
ETMR-11. A CASE OF PRIMARY DIFFUSE LEPTOMENINGEAL PRIMITIVE NEUROECTODERMAL TUMOR
Authors: Masahiro Sugawa, Keita Terashima, Yukihiro Matsukawa, Takanori Mizuno, Kyohei Isshiki, Shinichi Tsujimoto, Meri Uchiyama, Kenichi Sakamoto, Yoshihiro Gocho, Tomoo Osumi, Yoko Shioda, Chikako Kiyotani, Motohiro Kato, Daisuke Tomizawa, Kenichi Usami, Hideki Ogiwara, Yoshiaki Tsutsumi, Masayuki Nakano, Takako Yoshioka, Kimikazu Matsumoto
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Primary diffuse leptomeningeal primitive neuroectodermal tumor (PDL PNET) is a rare embryonal brain tumor which arises primarily in the meninges without an intraparenchymal mass. Few previous reports of this condition exist, and the clinical outcomes are poor. We herein report a case of a child with PDL PNET and present a cursory review of the literature. CASE: A 3-year-old female patient was seen at a local clinic due to vomiting, headaches, and seizures. As a head MRI revealed hydrocephalus but no mass, acute encephalopathy was initially diagnosed. She received steroid pulse therapy, but the symptoms progressed to hallucination and lethargy. Another MRI at the 1-month follow-up revealed diffuse leptomeningeal enhancement. Thereafter she was transferred to our hospital. A spine MRI revealed spinal dissemination. She underwent a dura mater biopsy, and the pathological analysis led to the diagnosis of PDL PNET. She received chemotherapy consisting of vincristine, cyclophosphamide, etoposide, cisplatin, and intrathecal methotrexate injections two months after the initial presentation. The progressive hydrocephalus was managed with external ventricular drainage. Two weeks after the first cycle of chemotherapy the hydrocephalus resolved, and the external ventricular drainage was removed. A follow-up MRI showed that the leptomeningeal enhancement decreased during the four cycles of chemotherapy without radiotherapy. The patient is scheduled to receive high-dose chemotherapy as consolidation therapy. CONCLUSION PDL PNET is extremely rare, and its diagnosis is often delayed. Treatment of PDL PNET is very difficult due to its aggressive course, and surgical resection is impossible. Early diagnosis may help improve outcomes.
Non-canonical glutamate signaling in a genetic model of migraine with aura
Authors: Patrick D. Parker, Pratyush Suryavanshi, Marcello Melone, Punam A. Sawant-Pokam, Katelyn M. Reinhart, Dan Kaufmann, Jeremy J. Theriot, Arianna Pugliese, Fiorenzo Conti, C. William Shuttleworth, Daniela Pietrobon, K.C. Brennan
Journal: Neuron (2020)

Migraine with aura is a common but poorly understood sensory circuit disorder. Monogenic models allow an opportunity to investigate its mechanisms, including spreading depolarization (SD), the phenomenon underlying migraine aura. Using fluorescent glutamate imaging, we show that awake mice carrying a familial hemiplegic migraine type 2 (FHM2) mutation have slower clearance during sensory processing, as well as previously undescribed spontaneous "plumes" of glutamate. Glutamatergic plumes overlapped anatomically with a reduced density of GLT-1a-positive astrocyte processes and were mimicked in wild-type animals by inhibiting glutamate clearance. Plume pharmacology and plume-like neural Ca2+ events were consistent with action-potential-independent spontaneous glutamate release, suggesting plumes are a consequence of inefficient clearance following synaptic release. Importantly, a rise in basal glutamate and plume frequency predicted the onset of SD in both FHM2 and wild-type mice, providing a novel mechanism in migraine with aura and, by extension, the other neurological disorders where SD occurs.
The Impact of Cytomegalovirus (CMV) Reactivation on Clinical Course and Immunomodulatory Effect in Children with Immune-Thrombocytopenia (ITP)
Authors: Mohsen Saleh Elalfy, Iman Ragab, Marwa Reda, Mohamed Sallam, Hoda Ezz El-Arab, Omneya Shafei, Alaa Mousa
Journal: Blood (2017)
Stay alive! What are living systematic reviews and what are their advantages and challenges?
Authors: Marinus Winters, Robert-Jan de Vos, Marienke van Middelkoop, Michael Skovdal Rathleff, Adam Weir
Journal: British Journal of Sports Medicine (2020)

Living systematic reviews (LSRs) are ‘high-quality, up-to-date online summaries of health research that are updated as new research becomes available’.1 You may not yet be familiar with living reviews as the first ones in sports medicine were only published this year.2 3 These are ‘living’ documents where essential aspects like the search, risk of bias assessment and drawing conclusions are updated regularly. This increases their life expectancy. Our editorial discusses what LSRs are, along with the advantages and challenges.

SRs have changed medicine for the better and allow us to make better informed decisions with our patients. While essential, the time and resources required to perform and publish SRs are major drawbacks. By the time a review is published, the search is often at least a year old. It takes from 2.5 to 6.5 years once a randomised controlled trial (RCT) is published for it to be included in a new review.1 This is likely to apply for other areas too, such as diagnosis, prognosis and aetiology.

Having taken a long time to create, SRs then have a limited life span: new studies are …
CBIO-04. MUTATION-SPECIFIC NON-CANONICAL PATHWAY OF PTEN AS A DISTINCT THERAPEUTIC TARGET FOR GLIOBLASTOMA
Authors: Seung Won Choi, Yeri Lee, Kayoung Shin, Donggeon Kim, Se Jeong Lee, Hyunho Kim, Seok Chung, Jihye Shin, Cheolju Lee, Do-Hyun Nam
Journal: Neuro-Oncology (2020)

Abstract The dominant-negative effect of PTEN mutation has been described previously, suggesting that aberrant gain of function attributed to mutation might be more disastrous than deletion in respect to malignant potential. In present study, we explored the functional implications of hot spot mutations of PTEN in GBM tumors. Subcellular location of PTEN is important for its distinct function and spatial distribution within the cytoplasm is known to be associated with cellular locomotion. We evaluated the subcellular compartmentalization of different PTEN mutants and found that some PTEN mutants located at cellular edges of chemotaxing cells. Moreover, these PTEN mutations exhibited invasive phenotype, which was not disrupted by PI3K inhibitor, but microtubule inhibitors. This finding suggests that cytoskeletal assembly as a novel non-canonical pathway of PTEN, thus unraveling a novel therapeutic vulnerability of PTEN. Mutation-specific therapeutic options should be considered in treating GBM patients with PTEN mutations.
Long-acting Cabotegravir Shot Prevents HIV Among Women
Authors: Jennifer Abbasi
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
LINC-12. COMBINED ADULT AND PAEDIATRIC NEURO-ONCOLOGY LONG-TERM SURVIVOR CLINIC EXPERIENCE FROM A TERTIARY CANCER CENTRE IN A LOW-MIDDLE-INCOME COUNTRY
Authors: Rahul Krishnatry, Maya Prasad, Girish Chinnaswamy, Abhisheik Chaterjee, Jayant Goda, Epari Sridhar, Aliasgar Moiyadi, Prakash Shetty, Arushi Saha, Vikas Singh, Nayana Golambade, Tejpal Gupta
Journal: Neuro-Oncology (2020)

Abstract NeuroOncology survivor clinics (NOS) is uncommon in low-middle-income countries. We started combined (paediatric and adult) NOS clinic in our tertiary a cancer centre (Jan-2017) and review here the demographic, clinical-pathological and treatment spectrum for our paediatric (0-18years) and adult (&amp;gt;18years) survivors (&amp;gt;5years since their initial diagnosis) till date. Of total 312 patients registered, 198 (63.5%) were adults while 114 (36.5%) were paediatric at-diagnosis with median age (IQR) at presentation: 34 (23–41) and 9(6 – 13) years respectively. In both groups, only 33% were females. The median (IQR) time since diagnosis was 9 (9–14) and 8 (6–12) years respectively with 60% of paediatric turning into adult survivors. The commonest paediatric tumours were glioma (52, 45.6%), embryonal (34, 29.8%), and ependymoma (12, 10.5%) versus gliomas (114, 57.6%) and benign tumours (42, 21.2%) in adults. The low-grade-glioma comprised 90.4% of all pediatric gliomas and intermediate-grade (90%) in adults. The primary treatment consisted of radiotherapy and chemotherapy in 95% and 43% versus 99% and 36% in adults versus paediatric patients respectively. Temozolomide and multi-drug combinations were the commonest chemotherapy used in adults and paediatrics respectively. Relapse and retreatments were seen in 16.6 and 14% of adults and paediatric patients. There were two deaths each in each group since registration (median 12 months). Although the baseline diagnosis/treatment characteristics are different, survivors of both group had a similar number of retreatments and deaths. Combined survivor clinics may present an interesting and unique opportunity to learn and provide challenging service in this part of the world.
HGG-51. PAIRED EPITHELIOID GLIOBLASTOMA PATIENT DERIVED XENOGRAFT MODELS WITH/WITHOUT MOLECULAR TARGET THERAPY
Authors: Jo Sasame, Kensuke Tateishi, Naoki Ikegaya, Yohei Miyake, Shigeta Miyake, Taishi Nakamura, Tetsuya Yamamoto
Journal: Neuro-Oncology (2020)

Abstract Epithelioid glioblastoma (E-GBM) predominantly arises at younger age and promotes dismal prognosis. Because of its rare etiology, pathological and genetical characterization of E-GBM remains elusive. Herein, we report 2 patient-derived E-GBM xenograft (PDX) models from young adult patients (YMG62 and YMG89) with BRAFV600E and TERT promoter mutation. The YMG62 patient received dabrafenib with trametinib, while YMG89 patient received dabrafenib monotherapy after recurrence with Stupp regimen. These molecular target therapies were initially responded, but gradually became resistant (YMG62R and YMG89R) and resulted in lethal. Treatment resistant cells were collected from CSF. These primary cells were propagated at multiple passage in vitro. Paired PDX models were established from initial and recurrent cells. All PDX tumors were preferentially disseminated and negative expression of GFAP, which were recapitulated to the patient characteristics. BRAF and MEK inhibitor moderately suppressed cell viability of YMG62 and YMG89 in vitro. However, BRAF and MEK inhibitor became resistant at recurrence in vitro. Western blotting indicated retained phospho-MEK expression after BRAF/MEK inhibitor treatment in recurrent cells, which implies crucial role of MEK activation for tumor maintenance in BRAFV600E mutant E-GBM. Together, paired E-GBM PDX models with/without molecular target therapy recapitulate patient characteristics, which may contribute to elucidate tumor biology and establish novel therapeutic target in E-GBM.