tbuckley/cabot-search huggingface dataset:
Prevalence and Geographic Distribution of Obstetrician-Gynecologists Who Treat Medicaid Enrollees and Are Trained to Prescribe Buprenorphine
Authors: Max Jordan Nguemeni Tiako, Jennifer Culhane, Eugenia South, Sindhu K. Srinivas, Zachary F. Meisel
Journal: JAMA Network Open (2020)

The incidence of opioid use during pregnancy is increasing, and drug overdoses are a leading cause of postpartum mortality. Most women who are pregnant do not receive medications for treatment of opioid use disorder, despite the mortality benefit that these agents confer. Furthermore, buprenorphine is associated with milder symptoms of neonatal abstinence syndrome (NAS) compared with methadone.To describe the prevalence and geographic distribution across the US of obstetrician-gynecologists who can prescribe buprenorphine (henceforth described as X-waivered) in 2019.A cross-sectional, nationwide study linking physician-specific data to county- and state-level data was conducted from September 1, 2019, to March 31, 2020. Data were obtained on 31 211 obstetrician-gynecologists who accept Medicaid insurance through the Centers for Medicare & Medicaid Services Physician Compare data set and linked to the Drug Addiction Treatment Act buprenorphine-waived clinician list.State-level NAS incidence and county-level uninsured rates and rurality.Prevalence and geographic distribution of obstetrician-gynecologists who are trained to prescribe buprenorphine.Among the 31 211 identified obstetrician-gynecologists, 18 710 (59.9%) were women. Most had hospital privileges (23 236 [74.4%]) and worked in metropolitan counties (28 613 [91.7%]). Only 560 of the identified obstetrician-gynecologists (1.8%) were X-waivered. Obstetrician-gynecologists in counties with fewer than 5% uninsured residents had nearly twice the odds of being X-waivered (adjusted odds ratio [aOR], 1.59; 95% CI, 1.04-2.44; P = .04) compared with those in counties with greater than 15% uninsured residents. Compared with those located in metropolitan counties, obstetrician-gynecologists in suburban counties (eg, urban population of ≥20 000 and adjacent to a metropolitan area) were more likely to be X-waivered (aOR, 1.85; 95% CI, 1.26-2.71; P = .002). Compared with states with an NAS rate of 5 per 1000 births or less, obstetrician-gynecologists in states with an NAS rate of 15 per 1000 births or greater had nearly 5 times the odds of being X-waivered (aOR, 4.94; 95% CI, 3.60-6.77; P < .001). Obstetrician-gynecologists without hospital privileges were more likely to be X-waivered (aOR, 1.32; 95% CI, 1.08-1.61; P = .007).Fewer than 2% of obstetrician-gynecologists who accept Medicaid are able to prescribe buprenorphine, and their geographic distribution appears to be skewed in favor of suburban counties. This finding suggests that there is an opportunity for health systems and professional societies to incentivize X-waiver trainings among obstetrician-gynecologists to increase patients' access to buprenorphine, especially during pregnancy.
RONC-13. RADIATION INDUCED BRAIN STEM GLIOMA AFTER RADIATION THERAPY FOR MIXED GERM CELL TUMOR
Authors: Natsumi Yamamura, Masahiro Nonaka, Akio Asai
Journal: Neuro-Oncology (2020)

Abstract We report a case of radiation-induced glioma in the pons after radiation therapy for germ cell tumor. A 17-year-old man was diagnosed as HCG and AFP secreting germ cell tumor at the age of 9. The tumor was located in the suprasellar region, which filled up most part of the third ventricle. Five courses of chemotherapy with cisplatin, etoposide, and cyclophosphamide, and whole ventricle plus local radiation therapy (total 51.2 Gy / 32Fr) were performed. After the treatment, most part of the tumor was regressed, and only small enhanced lesion remained. Six years after the treatment, he started to be ataxic, and worsened. An MRI revealed an enhanced lesion in the pons. Lesion biopsy was performed via the right cerebellar peduncle. Histopathological diagnosis confirmed the lesion was high grade glioma. He underwent extended local radiation therapy (50.4 Gy / 28 Fr) and administered temozolomide. Later, bevacizumab was added, and 3 months after treatment started, the size of the tumor was reduced and his symptoms were improving. There is no established treatment for radiation induced glioma. However, additional radiation therapy, temozolomide and bevacizumab appears to be useful to reduce tumor size and resolve the symptoms, even if it is transient.
Pre-Transplant Clonal Mosaicism Is Associated with Increased Relapse and Lower Survival in Acute Lymphoblastic Leukemia Patients Undergoing Allogeneic Hematopoietic Cell Transplant
Authors: Yiwen Wang, Weiyin Zhou, Junke Wang, Ezgi Karaesmen, Hancong Tang, Philip L. McCarthy, Marcelo C. Pasquini, Youjin Wang, Lisa J. McReynolds, Hormuzd Katki, Mitchell Machiela, Meredith Yeager, Loreall Pooler, Xin Sheng, Christopher Haiman, David Van Den Berg, Stephen R. Spellman, Tao Wang, Michelle Kuxhausen, Stephen J. Chanock, Stephanie J. Lee, Alyssa I. Clay-Gilmour, Theresa E. Hahn, Shahinaz M Gadalla, Lara E. Sucheston-Campbell
Journal: Blood (2020)
История гастроэнтерологии в зеркале нумизматики
Authors: O.V. Syniachenko, V.M. Iermolaeva, S.M. Verzilov, K.V. Liventsova, S.F. Verzilova
Journal: GASTROENTEROLOGY (2020)

Целью работы был анализ истории гастроэнтерологии по нумизматическим материалам. Отрасль исторической науки нумизматика (от лат. numisma — «монета») зародилась в XIX столетии и стала тесно связанной с экономикой, политикой, культурой и правом, включает в себя тематическое изучение монет, медалей и плакет. Лучше всего историю гастроэнтерологии иллюстрируют разные формы медальерного изобразительного искусства (экзонумия, или паранумизматика), а медаль стала прообразом памятной (мемориальной) монеты. В данной работе представлен каталог 110 нумизматических материалов (в том числе некоторых уникальных, впервые приведенных), отражены этапы развития изучения использования лечебных факторов, имеются ссылки на значимые исторические события, упоминаются краткие биографии медиков, внесших неоценимый вклад в формирование этой научной дисциплины, представлены научные форумы гастроэнтерологов на медалях и плакетах.
MBCL-43. RECURRENT MEDULLOBLASTOMA – LONG-TERM SURVIVAL WITH A “MEMMAT” BASED ANTIANGIOGENIC APPROACH
Authors: Irene Slavc, Andreas Peyrl, Johannes Gojo, Stefan Holm, Klas Blomgren, Astrid M Sehested, Pierre Leblond, Thomas Czech
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Patients with recurrent medulloblastoma have a poor prognosis with only around 8% of patients surviving at 5 years irrespective of salvage therapy used. We report on 29 patients from four institutions treated with a “MEMMAT” based antiangiogenic combination therapy. PATIENTS AND METHODS From 11/2006 to 06/2016, 29 patients were diagnosed with a recurrent medulloblastoma (19 first, 10 multiple recurrences). Median age at start of antiangiogenic therapy was 10 years (range 1–27). Subgroup of medulloblastoma was available in 18 patients and was group 3 or 4 in all except two (one WNT, one SHH-infant). For their current relapse patients received an antiangiogenic combination therapy consisting of bevacizumab, thalidomide, celecoxib, fenofibrate, and etoposide, alternating with cyclophosphamide and augmented with intraventricular therapy (etoposide and liposomal cytarabine). RESULTS As of 01/2020, 8/29 patients are alive at a median of 44 months after recurrence. 6/8 surviving patients are currently in CCR between 66 and 134 months after recurrence that prompted MEMMAT therapy. Two patients are again in remission after intercurrent relapses 105 and 102 months after first starting MEMMAT therapy. Five patients died of another cause (accident, leukemia, septicemia). OS (median 44 months) was 44±10% at 5 years and 39±10% at 10 years, PFS was 33±10% at 5 years and 28 ±9% at 10 years. Therapy was well tolerated and toxicities were manageable. CONCLUSION Our results suggest that antiangiogenic metronomic chemotherapy has clinical activity in recurrent medulloblastoma. Further investigation with an international phase II study is ongoing (MEMMAT; ClinicalTrials.gov Identifier: NCT01356290).
Treatment of HF in an Era of Multiple Therapies
Authors: Ankeet S. Bhatt, William T. Abraham, JoAnn Lindenfeld, Michael Bristow, Peter E. Carson, G. Michael Felker, Gregg C. Fonarow, Stephen J. Greene, Mitchell A. Psotka, Scott D. Solomon, Norman Stockbridge, John R. Teerlink, Muthiah Vaduganathan, Janet Wittes, Mona Fiuzat, Christopher M. O’Connor, Javed Butler
Journal: JACC Heart Failure (2020)

The treatment of heart failure with reduced ejection fraction (HFrEF) has changed considerably over time, particularly with the sequential development of therapies aimed at antagonism of maladaptive biologic pathways, including inhibition of the sympathetic nervous system and the renin-angiotensin aldosterone system. The sequential nature of earlier HFrEF trials allowed the integration of new therapies tested against the background therapy of the time. More recently, multiple heart failure therapies are being evaluated simultaneously, and the number of therapeutic choices for treating HFrEF has grown considerably. In addition, implementation science has lagged behind discovery science in heart failure. Furthermore, given there are currently >200 ongoing clinical trials in heart failure, further complexities are anticipated. In an effort to provide a decision-making framework in the current era of expanding therapeutic options in HFrEF, the Heart Failure Collaboratory convened a multi-stakeholder group, including patients, clinicians, clinical investigators, the U.S. Food and Drug Administration, industry, and payers who met at the U.S. Food and Drug Administration campus on March 6, 2020. This paper summarizes the discussions and expert consensus recommendations.
Lymphoma 101: The Plot Thickens
Authors: Leo I. Gordon
Journal: Journal of the National Comprehensive Cancer Network (2020)

Staging in lymphoma has changed significantly over time, from the Ann Arbor criteria (1971) to the Cotswolds criteria (1989) to the Lugano Classification (2011). The evolution of imaging technology has played a major role in these changes, and PET/CT is now standard for certain lymphomas, whereas chest radiographs are no longer routine. More recently, response criteria have been refined to account for possible flare reactions of immunomodulatory therapy with a provisional term called “indeterminate response.” The latest RECIL criteria use single-dimension measurements to assess response to therapy in patients with lymphoma. Finally, clinical data can be represented graphically in many ways, including the Kaplan-Meir plot, forest plot, waterfall plot, and swimmers plot. Each representation has its own strengths and limitations.
52P Discontinuation of immune checkpoint inhibitor (ICI) above 18 months of treatment in real-life patients with non small-cell lung carcinoma (NSCLC): INTEPI, a multicentric retrospective study
Authors: G. Bilger, N. Girard, H. Doubre, M. Giaj Levra, E. Giroux Leprieur, F. Giraud, C. Decroisette, A. Livartowski, M-A. Massiani
Journal: Annals of Oncology (2020)
成人T細胞白血病/リンパ腫(ATL)治療のための非血縁臍帯血(RI-UCBT)からの骨髄非破壊的前処置法による幹細胞移植(RIST):6人の患者の可能性調査
Authors: Yuji K, Miyakoshi S, Kato D, Kusumi E, Ueyama J, Morinaga S, Muto Y, Taniguchi S
Journal: Blood (2003)
GCT-02. THE LONG-TERM OUTCOMES AND SEQUELAE ANALYSIS OF INTRACRANIAL GERMINOMA FROM 187 PATIENTS IN THE SINGLE INSTITUTE: NECESSITY FOR THE ADAPTATION OF RADIOTHERAPY DOSE AND VOLUME
Authors: Joo Ho Lee, Il Han Kim, Keun-Yong Eom, Seung Ki Kim, Kyu-Chang Wang, Tae Min Kim, Dae Seog Heo, Hyoung Jin Kang, Hee Young Shin
Journal: Neuro-Oncology (2020)

Abstract PURPOSE We aimed to refine the radiotherapy (RT) volume and dose determinant for disease failures and long-term sequelae in the intracranial germinoma. METHODS The main treatment for intracranial germinoma was craniospinal RT only (n=51) during 1981–1992 and RT with upfront chemotherapy (CRT) (n=152) during 1992–2015 in Seoul National University Hospital. All 187 cases were confirmed histologically. RT fields included craniospinal, whole-ventricle (WV), whole-brain (WB), and focal radiotherapy. RT dose was dependent on the M status and combination of chemotherapy. The median follow-up duration was 115 months (range, 3–358). RESULTS The 10-year overall and recurrence-free survival was 94.5% and 91.4%. The complete response rate after chemotherapy was 62.6%. For the patients with complete response, WV RT 16–20 Gy, and focal boost of 25–36 Gy after upfront chemotherapy showed no in-field recurrence. The causes of death were progression (n=3), 2nd malignancy (n=6), treatment-related complications (n=7), and others (n=8). For non-sellar tumors, the rate of hormonal replacement treatment was significantly related to WB RT and WB/WV RT dose ≥ 30 Gy (p=.030, and .026). After a latency of the median 20 years, ten patients (5.3%) developed 2nd malignancy. WB RT and WB/WV dose ≥ 30 Gy were significantly correlated with the 2nd malignancy (p=.024, and .004). The rate of severe neurocognitive dysfunction was significantly associated with WB/WV dose ≥ 30 Gy (p=.027). CONCLUSION: CONCLUSION RT with or without upfront chemotherapy exhibits the excellent control rate of disease. However, the intensity and volume of RT are critical for managing treatment toxicities. Adaptation and further de-intensification of RT should be followed.
DIPG-82. CLINICAL EXPERIENCE OF CONVECTION ENHANCED DELIVERY (CED) OF CARBOPLATIN AND SODIUM VALPROATE INTO THE PONS FOR THE TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) IN CHILDREN AND YOUNG ADULTS AFTER RADIOTHERAPY
Authors: Elwira Szychot, David Walker, Peter Collins, Harpreet Hyare, Ananth Shankar, Alison Bienemann, Milo Hollingworth, Steven Gill
Journal: Neuro-Oncology (2020)

Abstract PURPOSE Effective treatment of diffuse intrinsic pontine glioma (DIPG) remains a formidable challenge due to inadequate penetration of the blood-brain barrier (BBB) by systemically administered chemotherapies. The BBB can be overcome by directly infusing drugs into pons using method of convection-enhanced delivery (CED). We describe our clinical experience and what we have learned about the safety and feasibility of treating DIPG with intermittent CED of carboplatin and sodium valproate to the pons through the Renishaw Drug Delivery System (RDDS). METHODS Retrospective review (2017–2020) of children with DIPG, who following radiotherapy, received compassionate treatment commencing 3.3–10 months post diagnosis (median 4.9 months). They received up to 7 cycles of 3–6 weekly pontine infusions of carboplatin (0.12-0.18mg/ml) and sodium valproate (14.4- 28.8mg/ml). RESULTS 13 children 3–19 years (mean 6.9 years) were treated. There were no surgical complications. With the exception of infusion channels blocking in one device there were no adverse device effects. Two patients developed persistent 6th nerve palsies, which led to drug concentration reduction in the combination therapy. Subsequently infusion/ drug related toxicities were transient. Tumour was controlled in pons in 11/13 patients. Median progression free survival (PFS) was 13.0 months, while median overall survival (OS) was 15.3 months. CONCLUSIONS Use of the RDDS was safe and well tolerated in all 13 patients. Treatment improved control of pontine disease resulting in longer PFS and OS than reported for conventional therapy and merits further evaluation in a clinical trial.
EXTH-23. MULTIVALENT TARGETED CYTOLYTIC AGENTS FOR GLIOBLASTOMA TREATMENT
Authors: Puja Sharma, Denise Herpai, Callie Roberts, Izabela Fokt, Waldemar Priebe, Stephen Tatter, John Rossmeisl, Waldemar Debinski
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma (GBM) complexity and heterogeneity requires treatment that addresses those pathobiological features. We have been developing selective cytotoxic agents able to target at the same time several GBM-associated factors. The chosen targets are responsible for the disease progression and/or recurrence as well as for resistance to the existing therapies. As a proof of concept, a Phase I clinical trial of a cytotoxic cocktail targeting IL-13RA2 and EphA2 receptors demonstrated dramatic anti-tumor responses in dogs with spontaneous gliomas that represent the closest translational model to human disease. To this end, we have developed multivalent agents that target four receptors specific to GBM: IL-13RA2, EphA2, EphA3, and EphB2, the combined expression of which covers virtually the whole tumor microenvironment. We have designed a multivalent protein termed QUAD 3.0 that contains an IgG1 scaffold, ephrinA5, which is a ligand for the EphA2, EphA3, and EphB2 receptors, and IL-13.E13K, a mutated version of interleukin 13 (IL-13), which binds preferentially to IL-13RA2. In QUAD 3.0, there is a cysteine at the C-terminal end of the protein to allow site-specific conjugation to cytotoxic cargo. QUAD 3.0 bound effectively to the four receptors in vitro and in vivo. QUAD 3.0 was conjugated to a modified form of Pseudomonas Exotoxin A (PE38QQR) and highly potent DNA binding agents based on modified doxorubicin (WP936, WP1737 and WP1244). All conjugates were highly cytotoxic to established and primary GBM cells with IC50s &amp;lt; 50 nM. We also treated the first dogs with QUAD 3.0-PE38QQR and QUAD 3.0-WP936 at a dose of 1.6 mg/ml using real-time monitored convection-enhanced delivery and observed up to 60% of tumor shrinkage and long-term survival. Thus, multivalent targeted agents demonstrate highly promising anti-tumor activity as single pharmaceutical, off-the-shelf agents. We also expect that our targeted drug candidates produce immune responses against tumors amplifying their cytolytic anti-tumor effect
Dual-mode endogenous and exogenous sensitization of tumor radiotherapy through antifouling dendrimer-entrapped gold nanoparticles
Authors: Chao Yang, Yue Gao, Yu Fan, Liu Cao, Jin Li, Yulong Ge, Wenzhi Tu, Yong Liu, Xueyan Cao, Xiangyang Shi
Journal: Theranostics (2020)

Development of a powerful sensitization system to alleviate radioresistance for enhanced tumor radiotherapy (RT) remains to be explored. Herein, we present a unique dual-mode endogenous and exogenous nanosensitizer based on dendrimer-entrapped gold nanoparticles (Au DENPs) to realize enhanced tumor RT. Methods: Generation 5 poly(amidoamine) dendrimers partially modified with 1,3-propanesultone were used for templated synthesis of Au NPs, and the created zwitterionic Au DENPs were adopted for serum-enhanced delivery of siRNA to lead to the knockdown of hypoxia-inducible factor-1α (HIF-1α) protein and downstream genes to relieve tumor invasion. The Au DENPs/siRNA polyplexes were also used for dual-mode endogenous and exogenous sensitization of tumor RT in vivo. Results: Due to the dual-mode endogenous sensitization through HIF-1α gene silencing and the exogenous sensitization through the existing Au component, enhanced RT of cancer cells in vitro and a tumor model in vivo can be realized, which was confirmed by enhanced cytotoxic reactive oxygen species (ROS) generation in vitro and double-strand DNA damage verified from the γ-H2AX protein expression in tumor cells in vivo. By integrating the advantages of HIF-1α gene silencing-induced downregulation of downstream genes and the dual-mode sensitization-enhanced RT, simultaneous inhibition of primary tumors and metastasis can be readily realized. Conclusions: The developed zwitterionic Au DENPs may be used as a promising platform for dual-mode endogenously and exogenously sensitized RT of other tumor types.
PATH-31. THE IMPACT OF MOLECULAR PROFILING OF PEDIATRIC CNS TUMORS ON TUMOR DIAGNOSIS AND MANAGEMENT - A SINGLE CENTER EXPERIENCE
Authors: Kazuhiro Sabet, Marike Zwienenberg, Mirna Lechpammer, Lee-Way Jin, David Solomon, Cassie Kline, Reuben Antony
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Next generation sequencing (NGS) plays a role in neuro-oncology research and in clinical diagnosis and management. Here, we describe how NGS for pediatric CNS tumors impacted clinical diagnosis and therapy at a single institution. METHODS NGS was performed using the UCSF 500 Gene Panel (targeted sequencing platform covering about 500 cancer associated genes). Patients were selected for NGS based on tumor pathology /need to identify therapeutic targets. We collected data on patient demographics, tumor histology/pathway alterations/therapeutic targets/therapy and used descriptive statistics for data analysis. RESULTS Between January 2016 and July 2019, about one-third of patients with CNS tumors seen at our institution (N=29) were interrogated. NGS revealed pathway alterations in 20/29 patients. Treatment recommendations/modifications based on pathway alterations/therapeutic targets impacted the therapy of 18 patients. Patient groups: Medulloblastoma (N=6), alterations in WNT, SHH, and TP53 pathways (Vismodegib recommended for SHH pathway alteration but not used). High-grade glioma (N=4), alterations (with treatment changes) included, NF1(Trametinib, Everolimus); MSH2/MLH1(Nivolumab); CDKN2A/CDKN2B/CDKN2C(Abemaciclib); EGFR (Osimertinib, Afatinib); H3K27M (Panobinostat/ONC201); BRAFV600 (Dabrafenib, Trametinib); ATRT (N=1) SMARCB1; Low Grade Glioma (N=10), BRAFV600(Vemurafenib) /BRAFKIAA1549 fusion (Trametinib)/ PIK3CA; DIPG (N=5), H3K27M/BCOR/ P53/ACVR/PIK3CA (LY3023414, Everolimus)/PDGFR(Dasatinib); Ependymoma (N=3), PFA/PFB/RELA Fusion. Seven patients were treated with targeted therapy + conventional therapy. In 8 patients targeted therapy remains an option but not yet needed. CONCLUSIONS NGS of pediatric brain tumors is widely available and contributes to the diagnosis/therapy of pediatric CNS tumors. Optimal chemotherapy/targeted therapy combinations are areas of study.
Severe COVID-19 patients exhibit an ILC2 NKG2D+ population in their impaired ILC compartment
Authors: Alejandra Gomez-Cadena, Laurie Spehner, Marie Kroemer, Myriam Ben Khelil, Kevin Bouiller, Grégory Verdeil, Sara Trabanelli, Christophe Borg, Romain Loyon, Camilla Jandus
Journal: Cellular and Molecular Immunology (2020)
Abstract 13314: Effect of Eicosapentaenoic Acid and Docosahexaenoic Acid on Epicardial Fat Volume; Results From a Randomized Controlled Trial
Authors: Abdul Aziz Asbeutah, Maral Amangurbanova, Smaha Waseem, Hasan Mirza, Francine K Welty
Journal: Circulation (2020)

Introduction: Epicardial adipose tissue is an ectopic fat depot that may be associated with coronary artery atherosclerosis. Reduction in weight has been associated with a reduction in epicardial fat volume in several studies. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are known to lower triglyceride level. Whether the reduction in triglyceride level is associated with a reduction in epicardial fat volume is unknown. Hypothesis: We hypothesize that EPA and DHA reduce triglyceride levels and possibly can cause regression of epicardial fat volume after 30 months of therapy. Methods: A total of 139 patients with stable coronary artery disease on statins were randomized to EPA and DHA versus none for 30 months. Epicardial fat volume was measured with coronary computed tomographic angiography at baseline and 30 months. Change in epicardial fat volume was calculated. Results: No difference in baseline characteristics was observed (Table). At 30-month follow-up, those on EPA and DHA had a significant 6.7% reduction in triglyceride level compared to a 12.6% increase in controls (p=0.02). However, there was no difference in percent change in epicardial fat volume between control and EPA/DHA groups at 30 months (-3.1% [-16.7, 4.9] vs. -5.0% [-13.1,7.3], p-value=0.80, respectively). There was no significant change in body mass index in either group at 30-month follow-up. Conclusions: EPA and DHA led to a significant reduction of triglyceride level; however, there was no corresponding significant reduction in epicardial fat volume. This finding suggests that lowering triglyceride level does not affect epicardial fat volume.