tbuckley/cabot-search huggingface dataset:
I Am Worried About Gonorrhea
Authors: Neil Keshvani, Arjun Gupta, Michael A. Incze
Journal: JAMA Internal Medicine (2018)

I Am Worried About Gonorrhea What Do I Need to Know?What Is Gonorrhea and How Is It Spread?Gonorrhea is a sexually transmitted infection that can affect both men and women.The bacteria that cause gonorrhea spread from person to person through unprotected oral, vaginal, or anal sex.They are not spread by casual touching such as hugging or kissing.Gonorrhea can also spread from a pregnant woman to her baby.You can reduce your risk of infection by avoiding intercourse, using condoms, limiting sexual partners, and getting tested if symptoms develop.
RARE-35. LONG-TERM RESULTS OF HIGH-DOSE METHOTREXATE TREATMENT FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA. A MULTI-INSTITUTIONAL EXPERIENCE
Authors: Wan-Soo Yoon, Jae-Sung Park, Young-il Kim, Seung-Ho Yang, Dong-Sup Chung, Sin-Soo Jeun, Yong-Kil Hong
Journal: Neuro-Oncology (2018)

In spite of multi-modality treatments, primary central nervous system lymphoma (PCNSL) has been a challenging tumor. For a long time, high-dose methotrexate (HD-MTX) is used as a first option for the treatment. Here, we present the experience of HD-MTX for PCNSL with one protocol in 3 institutions and suggest the prognostic factors. METHOD: From 2001 to 2016, 68 patients with PCNSL was treated with HD-MTX in 3 hospitals in Republic of Korea. The protocol of HD-MTX was composed with the 3 cycles of induction chemotherapy and 6 cycles of maintenance chemotherapy. Data was collected retrospectively and Kaplan-Meier method was used to analyze the survival. The scheduled 3 cycles of induction chemotherapy with HD-MTX was performed in 53 patients and maintenance chemotherapy was performed in only 26 patients. Good radiologic response was shown in 39 patients (57.4%) after induction chemotherapy, and overall radiologic responses after the completion of HD-MTX chemotherapy were complete remission in 24 (35.3%), partial response in 3 (4.4%), stable disease in 2 (2.9%), progressive disease in 24 (35.3%), and unknown in 15 patients (22.1%). The recurrence was evented in 16 patients among the good response patients, and median recurrence free period was 24.6 months (95%CI; 22.4–26.8 months). The median overall survival of our patients treated was 51.8 months (95%CI: 39.7–63.9). The patients with age less than 70 years old, the good radiologic response after induction HD-MTX chemotherapy, or the over 3 cycles of induction chemotherapy showed the long overall survival time significantly (p Although this study was performed retrospectively, the response of HD-MTX was significantly related to age and the response and number of cycles of induction chemotherapy. We suggest that the HD-MTX is still the ponderable treatment as the first therapy for PCNSL.
RARE-36. MALIGNANT PHEOCHROMOCYTOMA METASTATIC TO THORACIC VERTEBRA: PALLIATIVE NEUROSURGICAL MANAGEMENT
Authors: Esteban Ramirez Ferrer, Juan Munoz Montoya, Nicolás Gil Guevara, Camilo Zubieta, Pedro Penagos
Journal: Neuro-Oncology (2018)

Describe a rare case of metastatic pheochromocytoma to thoracic vertebra and the neurosurgical management with palliative objective in the context of malignant pheochromocytoma. Up to 10% of pheochromocytomas can be malignant. Bone metastases are an usual site of dissemination with some reports of rates up to 71%. However, the involvement of vertebra its very rare, Liu et al reported that in November 2017 only exist 17 reported cases of vertebral metastases of malignant pheochromocytoma. Also, within the thorax the most common places for paragangliomas are the mediastinum and, in second place, the heart. For this kind of pheochromocytoma, the survival rate to five years is close to 40% to malignant, and there is no curative treatment, and do not exist reliable data about the improvement of survival rates given by surgical management of metastatic lesions, that is the reason why the surgical treatment is focus in prevent local complications given by the metastatic disease. This case is about a 40 year old male with previous diagnosis of pheochromocytima treated surgically in the past, who presented now with precordial pain. In diagnosis studies was ruled out cardiac disease, and confirmed progression of disease to sternum, and incidentally findings in T4 vertebra. The patient doesn’t present neurological symptoms. The case were presented in the weekly meeting for neurooncology decision making, in which was decided to perform a palliative surgery consisten in medullar decompression and arthrodesis two levels above and below the lesion. Surgical pathology revealed paraganglioma with chromaffin cells. Malignant pheochromocytoma is a rare entity, with common metastases to bone. Once the metastases is stablished, there is no curative treatment for the disease and the treatment should be focus to ameloriate the quality of life and prevent local complications, in this case, medullary compression.
NIMG-65. VOLUMETRIC ASSESSMENT OF PERITUMORAL EDEMA: EXCELLENT TOOL FOR DIFFERENTIAL DIAGNOSIS OF CEREBRAL GLIOMAS AND SOLITARY METASTASES
Authors: Sae Min Kwon, Jeong Hoon Kim, Joonho Byun
Journal: Neuro-Oncology (2018)

Differentiating cerebral gliomas from metastatic brain tumors is essential since their management and prognosis is widely different. However it is still challenging to differentiate them without pathologic confirm. In this study, we evaluated the value of tumor volume and peritumoral edema as a tool for differentiating cerebral gliomas and solitary metastases. METHOD: We retrospectively reviewed conventional MR images of 91 patients with supratentorial solitary intra-axial tumor which were pathologically confirmed by surgical procedures. Patients were classified as cerebral glioma (n=57) and metastatic tumor group (n=34). Glioma group was also subdivided as glioblastoma multiform (GBM) and non-GBM subgroups. Tumor volume, peritumoral edema volume and edema index (peritumoral edema volume/tumor volume) were analyzed by using a semi-automated 3D slicer, and compared between groups. RESULT: Cerebral glioma group showed significantly small edema volume (median 48.90ml, interquartile range[IQR] 62.12 versus 94.02ml, IQR 81.85; p<0.001) and edema index (2.01, IQR 3.15 versus 5.35, IQR 7.99; p<0.001) compared to metastatic tumor group. GBM subgroup also presented large tumor volume (median 31.45ml, IQR 40.29 versus 17.37ml, IQR 21.80; p=0.007), small edema volume (52.43ml, IQR 55.06; p=0.004) and edema index (2.03, IQR 2.16; p<0.001) than metastatic tumor group. There were no difference between non-GBM and GBM subgroups. Tumor volume, peritumoral edema volume and edema index can contribute differentiating cerebral gliomas from metastases. In particular, measuring edema index can be an excellent tool for differential diagnosis in addition to other radiologic features.
SURG-03. A COMPARISON OF SURVIVAL OUTCOMES AFTER BIOPSY VERSUS RESECTION IN PRIMARY CNS LYMPHOMA: A SINGLE INSTITUTION EXPERIENCE
Authors: Christopher Hong, Frank Barbiero, Veronica Chiang, Jennifer Moliterno, Joseph Piepmeier, Zachary Corbin, Joachim Baehring
Journal: Neuro-Oncology (2018)

Primary CNS lymphoma (PCNSL) is an aggressive, often multifocal neoplasm sensitive to chemoradiation. Surgery has conventionally been diagnostic biopsy rather than resection. Recently, studies have challenged this paradigm, suggesting resection is safe and possibly more efficacious. We addressed this via analysis of our institutions experience. A retrospective review was conducted in patients treated with surgery and chemotherapy with or without radiation for PCNSL between March 2002 and February 2018. Indications for surgery were predominantly for tissue diagnosis. Statistical analyses included Kaplan-Meier, log-rank, and Pearsons chi-squared analyses. There were 138 patients (mean age, 61.2-years; range, 14.9–89.7). 5 had GTR, 13 had STR, and 120 had biopsy. Biopsied patients (45/75, 37.5%) harbored more multifocal lesions than GTR (0/5, 0%) and STR (2/11, 15.4%) (p=0.03). Complete remission rates at 6-months were similar in biopsy (67/120, 55.8%) vs GTR (2/5, 40%) or STR (7/13, 53.8%) (p=0.78), even when GTR and STR were combined (p=0.64). There were no differences in PFS between GTR and STR: 8.5-months [95%-CI: 0.2–16.9] vs 21.3-months [4.6–38.0], respectively (p=0.22) or OS: 37.8-months [0–100.1] vs 28.3-months [10.7–45.8], respectively (p=0.96). For biopsy, PFS: 26.5-months [19.9–33.1] and OS: 39-months [30.8–47.2] did not differ from GTR (PFS: p=0.14, OS: p=0.87) or STR (PFS: p=0.83, OS: p=0.30) (Fig. 1). Likewise, when data from GTR and STR were combined (PFS: 17.7-months [0–38.1)], OS: 30.9-months [10.6–51.3]), there remained no significant differences compared to biopsy (PFS: p=0.43) (OS: p=0.50). 7/11 resected patients (6 STR, 1 GTR) had improvement in preoperative deficits after resection, including one with rapid relief of life-threatening mass effect. Our experience supports the current surgical paradigm towards PCNSL, demonstrating resection does not improve survival outcomes over biopsy. Resection, regardless of GTR or STR, may have a role in rapid relief of preoperative symptoms, but further studies are needed to answer this question.
TMOD-29. MOLECULAR CHARACTERIZATION OF GLIOMA PATIENT-DERIVED ORTHOTOPIC XENOGRAFTS: FROM BASIC RESEARCH TO PRECLINICAL STUDIES
Authors: Ann-Christin Hau, Anna Golebiewska, Anais Oudin, Linsey Houben, Daniel Stieber, Francisco Azuaje, Tony Kaoma, Arnaud Muller, Frank Hertel, Michel Mittelbronn, Rolf Bjerkvig, Simone Niclou
Journal: Neuro-Oncology (2018)

It is well recognized that long term cell cultures are poor models to study human cancer, largely because of loss of clonal heterogeneity, accumulation or loss of genomic alterations and adaptation to a highly artificial environment. Patient-derived orthotopic xenografts (PDOX) based on organotypic three-dimensional tumor spheroids from human glioma samples are proposed to represent a reliable and clinically-relevant animal model. We have generated a living biobank of PDOX models from 34 glioma patients (grade III and IV), including longitudinal patient samples with matched recurrent tumors. Using an efficient orthotopic xenografting procedure we obtain an overall tumor take-rate of close to 80%. We show that our glioma PDOX retain the genetic and epigenetic profiles of primary patient biopsies throughout several generations of xenotransplantation. In particular they not only faithfully recapitulate gene amplification and expression of EGFR and EGFRvIII variant in a reproducible manner, also amplification and expression of rarer patient-specific EGFR variants is maintained. Overall genome-wide transcriptomic profiles of PDOX remain very similar to patient biopsies and correlate better with the GBM cohort of TCGA (538 GBM samples) than conventional cell lines. Observed differences at the transcriptomic level are largely based on the replacement of human to mouse stromal cells, which impacts on the molecular sub-classification of GBM. We conclude that glioma PDOX models closely reflect patient heterogeneity and treatment response, and thus represent appropriate avatars for reproducible pre-clinical trials. Furthermore, by combining profiling of the somatic mutational landscape with large-scale drug screening, PDOX-derived tumor organoids can elucidate druggable targets and tumor response profiles in a personalized patient-specific manner.
Abstract 297: Efficacy of Ventilation with the Laryngeal Tube During Out-of-Hospital Cardiopulmonary Resuscitation
Authors: Peter Stratil, Christoph Testori, Christian Wallmüller, Andreas Schober, Thomas Uray, Fritz Sterz
Journal: Circulation (2014)

BACKGROUND: Airway management in cardiac arrest victims is a challenging ambition. The preclinical use of a supraglottic airway device, the laryngeal tube, also known as King LT, is currently on th...
CD72 is associated with kidney cancer.
Authors: Bing Yang, Sunita Borse, Katherine Y. Sun
Journal: Cancer Research (2005)

122  CD72 is a membrane protein that involves in the negative regulation of B cells. CD72 is also expressed in many other cell types and its function is still unknown. In the analysis of cDNAs from tumor tissues, we have found that mutations exist in cDNA clones from several forms of tumor including thyroid follicular carcinoma, leukemia, chondrosarcoma and endometrial adenocarcinoma. Human CD72 gene has nine exons and contains variable numbers of tandem repeat in Intron 8. When normal human population was investigated, one or two tandem repeats were found. In another region of Intron 8, allele with a deletion of four nucleotides was found (CACT- allele). We investigated if the alleles of CD72 are associated with kidney cancer. 45 kidney tumor samples, 66 tissue samples of normal individuals were analyzed by polymerase chain reaction to determine the alleles. The tandem repeat of Intron 8 is not associated with kidney cancer. However, 2 out of 33 (6%) tumor tissues were found to have microsatellite instability in the tandem repeat region. We also investigated the association of CACT alleles with kidney cancer. CACT+ is negatively associated with kidney cancer (3 out of 45 vs 23 out of 66 normal samples, 2-tailered Fisher’s exact test, P
IMMU-13. EFFECT OF COMBINED ANTI-PD-1 AND TEMOZOLOMIDE THERAPY IN GLIOBLASTOMA
Authors: Junseong Park, Chang Gon Kim, Jae Eun Lee, Jin-Kyoung Shim, Eui Hyun Kim, Jong Hee Chang, Eui-Cheol Shin, Seok-Gu Kang
Journal: Neuro-Oncology (2018)

Although programmed death-1 (PD-1) blockade is effective in treating several types of cancer, the efficacy of this agent in glioblastoma (GBM) is largely unknown. We evaluated therapeutic effects of anti-PD-1, temozolomide (TMZ), and their combination in an orthotopic murine GBM model. The phenotype, number, and composition of lymphocytes were evaluated using flow cytometry. Transcriptional profiles of tumor tissues were analyzed using microarrays. Generation of antitumor immunological memory was investigated upon rechallenge. Combined treatment with anti-PD-1 and TMZ yielded synergistic antitumor efficacy in the presence of donor-originated PD-1+CD8+ T cells in vitro, necessitating in vivo validation. Whereas TMZ did not rescue GBM-implanted mice, anti-PD-1 completely eradicated GBM in 44.4% of mice, and combination of anti-PD-1 and TMZ in all mice. Anti-PD-1 significantly increased the number of tumor-infiltrating lymhpocytes (TILs), and reduced frequencies of exhausted T cells and regulatory T cells. However, combining TMZ with anti-PD-1 significantly decreased the number of TILs, which was also observed with TMZ treatment alone. A transcriptome analysis of tumor tissues revealed that anti-PD-1 monotherapy perturbed immune-related genes, distinctly with combined therapy. Upon rechallenge, tumor growth was not observed in mice cured by anti-PD-1 monotherapy, whereas tumors regrew in the combination group. Furthermore, an analysis of peripheral blood revealed that antitumor memory T cells were generated in mice cured by anti-PD-1 monotherapy, not in the combination group. PD-1 blockade induces long-term therapeutic response, and combination with TMZ further enhances antitumor efficacy. However, immunological memory is provoked by anti-PD-1 monotherapy, not by combined therapy.
NIMG-02. STRAIN ELASTOGRAPHY: INTRA-OPERATIVE BRAIN TUMOUR CARACHTERIZATION
Authors: Francesco Prada, Massimiliano DelBene, Luca Maria Sconfienza, Francesco DiMeco
Journal: Neuro-Oncology (2018)

Sonoelastography is an ultrasound imaging technique able to assess mechanical properties of tissues. Strain elastography (SE) is qualitative sonoelastographic modality with a wide range of clinical applications, but its use in brain tumor surgery is very limited. We describe the first large-scale implementation of SE in oncological neurosurgery for lesions discrimination and characterization. We analyzed retrospective data from 64 patients aiming at (i) evaluating the stiffness of the lesion and of the surrounding brain, (ii) assessing the correspondence between B- mode and SE, and (iii) performing subgroup analysis for gliomas characterization i) In all cases we visualized the lesion and the surrounding brain with SE, permitting a qualitative stiffness assessment. ii) In 90% of cases, lesion representations in B-mode and SE were superimposable with identical morphology and margins. In 64% of cases lesion margins were sharper in SE than in B-mode. iii) In 76% of cases, glioma margins were sharper in SE than in B-mode. Lesions morphology/dimensions in SE and in B-mode were superimposable in 89%. Low grade (LGG) and high grade (HGG) gliomas were significantly different in terms of lesion stiffness, stiffness of the surrounding brain, and stiffness contrast between tumours and brain, LGG appearing stiffer while HGG softer than brain (all p SE allows to understand mechanical properties of the brain and lesions in exam and permits a better discrimination between different tissues compared to B-mode. Additionally, SE can differentiate between LGG and HGG.
Abstract 19644: Dietary Sodium, Potassium Levels and Sodium Potassium Ratios in India Using 24-hour Urinary Excretion Assessment
Authors: Sailesh Mohan, Roopa Shivashankar, Shweta Khandelwal, Shuchi Anand, Dimple Kondal, Anand Krishnan, Ritvik Amarchand, Neil Poulter, K.Srinath Reddy, Dorairaj Prabhakaran
Journal: Circulation (2015)

Introduction: Hypertension is a major public health burden in India and most hypertensives are inadequately treated and controlled. Thus, population based sodium reduction strategies are essential for hypertension control. However, contemporary data on sodium consumption, which are essential to implement effective sodium reduction strategies are lacking. Objective: To assess the dietary sodium, potassium intakes and sodium potassium ratios using 24 hour urinary samples among a representative sample of adults aged ≥ 20years in urban and rural India. Methods: We conducted a population based cross sectional survey among 1397 adults aged ≥ 20 years residing in urban Delhi and rural Haryana, India. Subjects were selected using a systematic random sampling technique (multi stage cluster random sampling in urban area and simple random sampling in rural area). Data were obtained using an interviewer administered questionnaire, anthropometry and a 24-hour urine collection. Results: In the urban area, the mean age of the participants was 45 years (SD=14.4) and half of them were women while in the rural area it was 46 years (SD=15.3) and 60% were women. Mean sodium intake as assessed by 24 hour urinary sodium excretion was higher in rural [3798 mg/day (SD=2106)] compared to the urban area [2421 mg/day (SD=1743)]. Mean potassium intake was low in both rural [1607 mg/day (SD=826)] and urban areas [1144 (SD=755)], and the overall sodium potassium ratio was high (2.4).Men had higher sodium intake and sodium potassium ratio. Conclusion: Sodium intake in this sample is high and exceeds the current World Health Organization (WHO) recommended levels while potassium intake is low. Sodium reduction efforts combined with policies to increase potassium intake should be initiated in India to prevent and control hypertension as well as to contribute to the proposed United Nations WHO targets for reducing chronic non-communicable diseases by 2025.
DDIS-10. ENGINEERED EXOSOMES FOR GLIOMA THERAPY
Authors: Anwar Hossain, Irtiza Hasan, Satoshi Adachi, Joy Gumin, Brittany Kerrigan, Frederick Lang
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM) is the most common among all malignant brain tumors, with 17,000 diagnoses every year in the United States. Despite receiving surgery, radiotherapy, and chemotherapy, the median survival of GBM patients is only 14.6 months, and less than 10% of GBM patients survive more than 5 years. There is an urgent need for the development of more effective therapies. To this end, we have developed a novel method to deliver therapeutic antiglioma genes by exploiting exosomes derived from engineered HEK293 cells that can package plasmid DNA (pDNA), messenger RNA (mRNA) or microRNA (miRNA). These exosomes are modified using ligand display technologies to allow delivery of cargo to cell types of choice. For proof of concept we used the glioma cell line U87 containing a “floxed” dsR cassette upstream of a green fluorescent protein (eGFP) transgene; in the absence of the cre these cells express red fluorescent protein. Transfer of either cre expressing pDNA or mRNA using engineered exosomes induced cre recombinse-mediated excision of the floxed tdTomato cassette, and subsequent expression of eGFP in vitro as well as in in vivo glioma models. In addition to using engineered exosomes to deliver cre, we also successfully delivered both luciferase and cytosine deaminase-uracil phosphoribosyl transferase. This model provides a unique functional readout demonstrating that engineered exosomes can be used to deliver any functional genetic cargoes to the cell of choice. This technology allows the delivery of pDNA/mRNA/miRNA to treat GBMs, and has powerful implications for a broad range of biotherapeutics: cancer therapy, cancer vaccines or immunotherapeutics, and DNA editing (CRISPR/Cas9).
CRISPR/Cas9 offers a new tool for studying the role of chromatin architecture in disease pathogenesis
Authors: Xiang Guo, Ann Dean
Journal: Genome biology (2018)

A recent study used CRISPR/Cas9 to reveal long-range looping between disease-related genes and their regulatory elements that is mediated by the CCCTC-binding factor (CTCF) in prostate cancer.
Abstract 17306: The Most Expensive Patients in the Hospital
Authors: Karen E Joynt, Maggie Makar, Atul Gawande, David Cutler, Ziad Obermeyer
Journal: Circulation (2014)

Introduction: In the Medicare population, 1% of the patients is responsible for 15% of spending. There are two patterns typical of highest-cost patients: those who cycle in and out of the hospital with preventable conditions, and those who have a single catastrophic event. While a great deal of focus has been placed on the former, much less is known about the latter. We do know that a large proportion of these most-expensive patients receive prolonged mechanical ventilation (PMV). Methods/Results: We used national Medicare data to explore diagnoses, procedures, and costs associated with these most-expensive patients. There were 91,054 hospitalizations for Medicare patients with a DRG containing PMV in 2010. The majority of PMV patients were admitted emergently (71.9%); an additional 16.7% were admitted urgently. Elective admissions represented 9.5%, and trauma accounted for 1.8%. Median length of stay was 16 days, and the median stay in the intensive care unit was 11 days. Procedures were performed in the majority of these patients, and clinical outcomes were exceedingly poor (table). The financial costs associated with this group of patients were high. The average total hospitalization charge was $227,917; the maximum charge was over $9 million. The mean Medicare payment for PMV patients in 2010 was $61,995, with a maximum of $1.3 million. This was largely through the set DRG price (mean $59,491), though outlier payments (mean $5,957, maximum $1.2 million) and patient-paid coinsurance (mean $835, maximum $88,644) played a significant role as well. Conclusions: A small group of Medicare beneficiaries undergoing PMV have extremely high costs and poor outcomes. This shared clinical pathway suggests that there is room for improvement, both in terms of identifying these patients early during hospitalization to prevent progression to PMV, as well as in terms of clinical innovation to improve care within the intensive care unit for those who are already ventilated.
A TCR mechanotransduction signaling loop induces negative selection in the thymus
Authors: Jinsung Hong, Chenghao Ge, Prithiviraj Jothikumar, Zhou Yuan, Baoyu Liu, Ke Bai, Kaitao Li, William Rittase, Miho Shinzawa, Yun Zhang, Amy Palin, Paul Love, Xinhua Yu, Khalid Salaita, Brian D. Evavold, Alfred Singer, Cheng Zhu
Journal: Nature Immunology (2018)