tbuckley/cabot-search huggingface dataset:
Хирургическая тактика при лечении больных с грыжами пищеводного отверстия диафрагмы
Authors: N.V. Prolom, B.F. Shevchenko, A.M. Babii, S.A. Tarabarov, A.A. Galinsky
Journal: GASTROENTEROLOGY (2020)

Цель исследования: разработать показания к хирургическому лечению больных с грыжами пищеводного отверстия диафрагмы (ГПОД) и оценить его результаты. Материалы и методы. В отделении хирургии органов пищеварения ГУ «Институт гастроэнтерологии НАМН Украины» за период 2017–2019 гг. обследовано и прооперировано 45 пациентов с грыжами пищеводного отверстия диафрагмы. Отдаленные результаты лечения изучены в сроки от 6 мес. до 2 лет у 19 (42,2 %) больных. Результаты. В наших исследованиях среди 45 оперированных пациентов у 27 (60,0 %) диагностирована аксиальная ГПОД (тип I), у 9 (20,0 %) — параэзофагеальная ГПОД (тип II), у 8 (17,8 %) — смешанная ГПОД (тип III), у 1 (2,2 %) — укорочение пищевода (тип IV). Гигантские ГПОД, требующие аллопластики, наблюдались у 8 (17,8 %) больных, укорочение пищевода на фоне больших ГПОД с формирующейся стриктурой нижней трети пищевода диагностировано у 1 (2,2 %) пациента. Крурорафия выполнена всем больным: задняя — в 24 (53,3 %) случаях, передняя и задняя — в 13 (28,9 %), аллопластика — в 8 (17,8 %). Проведены лапароскопические фундопликации: по Ниссену — у 36 (80,0 %) пациентов, по Тупе — у 6 (13,3 %), по Дору — у 3 (6,7 %). Летальных исходов не было. Средняя продолжительность вмешательства составила (135 ± 24) мин, среднее время фиксации трансплантата — (24 ± 12) мин. Выводы. Лапароскопические антирефлюксные операции являются высокоэффективными в лечении ГПОД, хорошо переносятся и характеризуются небольшой частотой осложнений (6 (13,3 %) случаев), быстрым восстановлением больных в послеоперационном периоде, что позволяет признать их операциями выбора в лечении данной патологии. Выбор метода хирургического вмешательства при ГПОД определяется особенностями анатомических взаимоотношений и задачами восстановления пищеводно-желудочного перехода и диафрагмы.
Management of immune checkpoint therapy for patients with cancer in the face of COVID-19
Authors: Chen Shen, Qianru Li, Yongchang Wei, Yuting Li, Jun Li, Juan Tao
Journal: Journal for ImmunoTherapy of Cancer (2020)

The COVID-19 outbreak caused by SARS-CoV-2 challenges the medical system by interfering with routine therapies for many patients with chronic diseases. In patients with cancer receiving immune checkpoint inhibitors (ICIs), difficulties also arise from the incomplete understanding of the intricate interplay between their routine treatment and pathogenesis of the novel virus. By referring to previous ICI-based investigations, we speculate that ICIs themselves are not linked to high-infection risks of respiratory diseases or inflammation-related adverse effects in patients with cancer. Moreover, ICI treatment may even enhance coronavirus clearance in some patients with malignant tumor by boosting antiviral T-cell responsiveness. However, the ‘explosive’ inflammation during COVID-19 in some ICI-treated patients with cancer was illustrated as exuberant immunopathological damage or even death. In case of the COVID-19 immunopathogenesis fueled by ICIs, we propose a regular monitor of pathogenic T-cell subsets and their exhaustion marker expression (eg, Th17 and interleukin (IL)-6-producing Th1 subsets with surface programmed death 1 expression) to guide the usage of ICI. Here we aimed to address these considerations, based on available literature and experience from our practice, that may assist with the decision-making of ICI administration during the pandemic.
SURG-17. EFFICACY AND SAFETY OF LASER INTERSTITIAL THERMAL ABLATION IN ELDERLY BRAIN TUMOR PATIENTS
Authors: Jacob Pawloski, Sameah Haider, Hassan Fadel, Hesham Zakaria, Thomas Noh, Michael Bazydlo, Ian Lee
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Open craniotomy for tumor carries notable perioperative risks as well as associated prolonged ICU stays. Risks of surgery are increased in elderly patients. In addition, many tumors are not amenable to resection due to their deep or eloquent location. Magnetic resonance-guided laser interstitial thermal ablation (LITT) offers an alternative, minimal-access procedure. OBJECTIVE To examine the safety and efficacy of LITT procedures in elderly brain tumor patients. METHODS Data was gathered on patients over the age of 65 who underwent MRI-guided LITT for ablation of tumor at our institution between 2014-2019. These cases were analyzed retrospectively and data was collected on patient demographics, tumor characteristics, procedural details, and post-operative complications and outcomes. RESULTS 19 patients over the age of 65 underwent LITT during the study time period and were included in the analysis. The average age was 70 years (range 65-81), with a median follow up of 7 months. Patients had an average of 3.5 pre-existing medical comorbidities with a mean pre-operative Karnofsky Performance Score (KPS) of 87 (SD = 10.4). 13 patients underwent LITT for primary CNS tumor and 6 for metastatic lesions. The average lesion volume was 3.44 cm3 with approximately one-third in eloquent areas. An average extent of ablation of 98% was achieved (90-100%). 5/19 patients experience at least one post-op complication including 2 venous thromboembolic events and 1 stroke within 30 days. The average length of stay was 2.3 days, and 13/19 patients were discharged home. No patients experienced new permanent neurological deficits and the average post-operative KPS was 83 (SD = 12.4). 9 patients experienced progression of disease after an average of 155 days, and 11 patients were deceased (average survival = 504 days). CONCLUSION LITT is well tolerated in appropriately selected elderly patients with short post-operative length of stay and minimal surgical morbidity.
MBCL-52. ENDOCRINE PROFILE AFTER MEDULLOBLASTOMA TREATMENT
Authors: Miriam Pavon-Mengual, Helen Curry, Vrinda Saraff, Zainaba Mohamed, Helen Benghiat, Daniel Ford, Andrew Peet, Jenny Adamski, Martin English
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Treatment of medulloblastoma has evolved substantially with more chemotherapy, risk-adapted dosing of radiotherapy (RT) and new RT techniques. We present the endocrine profile for our patients treated over a 20-year period. METHODS The charts of patients treated for medulloblastoma between 1/1/00 and 31/12/19 were reviewed. 105 were available. Group 1 received chemotherapy alone, Group 2 received 23.4 Gy whole CNS RT with a posterior fossa (PF) boost to 54 Gy, Group 3 received &amp;gt; 35 Gy whole CNS RT with PF boost to 54–59 Gy, Group 4 received PF RT to 54 Gy. All received chemotherapy according to national guidelines or clinical trials relevant at the time. RESULTS Group 1 (M:F 11:6, 7 survivors mean age 2 years range 1–7) had no endocrinopathies. At 5 years from diagnosis Group 2 (M:F 15:13) and Group 3 (M:F 35:14) had the following % RESULTS Survival 77:61; Growth Hormone deficiency 92:100; Thyroid deficiency 75:81; ACTH deficiency 42:33. Girls were more likely to need sex hormone replacement than boys. Group 4 (M:F 7:5 mean age 2) were all treated in the first decade. 3 survivors, one GH deficiency, one thyroxine deficiency, one both. CONCLUSIONS There is a trend to earlier endocrinopathies in the group 3 vs group 2 patients, but it does not reach statistical significance. Girls are more likely to need sex hormone replacement than boys. This investigation provides a contemporary profile of endocrinopathy after treatment for medulloblastoma that can be used for future comparisons.
EPCO-13. GENOME-WIDE ASSOCIATION STUDY IN INDIVIDUALS OF ASHKENAZI JEWISH ANCESTRY IDENTIFIES NOVEL RISK LOCI FOR GLIOMA
Authors: Quinn Ostrom, Jinyoung Byun, Christopher Amos, Elizabeth Claus, Melissa Bondy
Journal: Neuro-Oncology (2020)

Abstract Population stratification, or systematic differences in allele frequencies between subpopulations, can distort the results from genome-wide association studies (GWAS). While GWAS are usually conducted within continental (e.g. European) ancestry groups, sub-groups may have specific population histories that result in enrichment for risk or protective alleles for complex disease. In this analysis, we examined genetic risk for glioma in a US population with predominantly Ashkenazi Jewish (AJ) ancestry. Genotyping data were obtained from three prior glioma case-control studies. Best-guess assignment to one of seven subcontinental European ancestry groups was performed using AIPS (https://github.com/biomedicaldatascience/AIPS). Out of a total of 6,416 cases and 7,441 controls across all three studies, 202 cases (3% of all cases, 63% GBM) and 403 controls (5% of all controls) were assigned to the AJ ancestry group. Unconditional logistic regression was performed for by study (adjusted for age and first two principal components) and then studies were combined using fixed effects meta-analysis. No associations reached genome-wide significance (p&amp;lt; 5x10-8), including those detected in prior pan-European GWAS. A nominally significant association was detected on chromosome 17 in ASPA (rs9904040, MAF=20%, p=2.61x10-6, Odds ratio=2.22 [95% confidence interval=1.59–3.09]) which is in linkage equilibrium (r2=0.0013) with the previously detected glioma risk SNP in TP53 (MAF=0.3% in this analysis, p=0.8801) in the European population. In our prior pan-European meta-analysis (Melin et al., 2017, this SNP was non-significant (p=0.0620). This study failed to replicate many previously identified glioma risk alleles, likely due to diminished power due to small sample size. We did identify a novel risk allele on chromosome 17 in ASPA, which encodes for aspartoacylase (which catalyzes deacylation of N-acetyl_L-aspartic acid). Larger sample sizes identified via targeted recruitment are necessary in order to fully characterize genetic risk for glioma in this population, including assessment of rare (MAF&amp;lt; 5%) risk allele associations.
Inflammatory Endotype–associated Airway Microbiome in Chronic Obstructive Pulmonary Disease Clinical Stability and Exacerbations: A Multicohort Longitudinal Analysis
Authors: Zhang Wang, Nicholas Locantore, Koirobi Haldar, Mohammadali Yavari Ramsheh, Augusta S. Beech, Wei Ma, James R. Brown, Ruth Tal-Singer, Michael R. Barer, Mona Bafadhel, Gavin C. Donaldson, Jadwiga A. Wedzicha, Dave Singh, Tom M. A. Wilkinson, Bruce E. Miller, Christopher E. Brightling
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Understanding the role of the airway microbiome in chronic obstructive pulmonary disease (COPD) inflammatory endotypes may help to develop microbiome-based diagnostic and therapeutic approaches.
EXTH-69. INCREASED CANCER CELL PERMEABILITY FOLLOWING TUMOR TREATING FIELDS (TTFIELDS) APPLICATION IN VITRO
Authors: Tali Voloshin, Yaara Porat, Noa Kaynan, Anat Klein-Goldberg, Rom Paz, Alexandra Volodin, Moshe Giladi, Uri Weinberg, Yoram Palti
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Tumor Treating Fields (TTFields), encompassing alternating electric fields within the intermediate frequency range, is an anticancer treatment delivered to the tumor region through transducer arrays placed non-invasively on the skin. This novel loco-regional treatment has demonstrated efficacy and safety and is FDA-approved in patients with glioblastoma (GBM) and malignant pleural mesothelioma. TTFields are currently being investigated in other solid tumors in ongoing trials. Recently, TTFields were reported to alter the cellular membrane structure of GBM cells, rendering them more permeable. The objective of this study was to characterize TTFields-induced cellular permeability in cancerous cell lines. METHODS TTFields were applied to uterine sarcoma, glioblastoma, and breast adenocarcinoma cell lines across a range of frequencies (50–500 kHz). Cellular permeability was assessed by quantifying the percentages of cells with accumulated 7-aminoactinomycin D (7-AAD) using flow cytometry and cytotoxicity was assessed based on cell counts. Kinetics were determined using different 7-AAD exposure times relative to TTFields treatment end. Changes in intracellular accumulation of anthracycline chemotherapeutics were evaluated in chemotherapy-sensitive and chemotherapy-resistant cells. RESULTS TTFields induced cellular permeability to 7-AAD in all 4 cancer cell lines tested. The optimal frequency for TTFields-induced cellular permeability was different from the optimal cytotoxic frequency. Kinetics measurements demonstrated that TTFields-induced permeability is transient and is effective only during application of TTFields. In combination experiments, TTFields improved intracellular accumulation of chemotherapeutic agents. Furthermore, combining chemotherapy with TTFields treatment facilitated accumulation of chemotherapeutics in chemotherapy-resistant cells to levels comparable with accumulation in chemotherapy-sensitive cancer cells. CONCLUSIONS This study demonstrates that TTFields can transiently increase cancer cell permeability in vitro with an optimal frequency that is variable from the frequency that is used to induce cancer cell cytotoxicity. Moreover, this effect is reversible and cellular permeability is restored to a normal state upon TTFields treatment cessation.
NCOG-10. ASSESSMENT OF SURVIVAL AND SAFETY FOLLOWING INTRATHECAL CHEMOTHERAPY VIA OMMAYA RESERVOIR FOR LEPTOMENINGEAL DISEASE
Authors: Shiv Shah, Richard Butterfield, Bernard Bendok, Mark Lyons, John Ariete, Eric Yancey, Maciej Mrugala
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Leptomeningeal disease (LMD) is an aggressive, late-stage complication of systemic cancers that maintains a poor prognosis with an average survival of 3-6 months. Ommaya reservoirs (OR) are an accessible alternative to serial lumbar punctures for the delivery of intrathecal chemotherapy in the treatment of LMD. However, widespread use of OR has been limited by reports of complications, limited physicians trained in their use, and the stigma of brain surgery. Here, we assess survival and complication rates for patients who received intrathecal chemotherapy through OR for LMD treatment. METHODS After IRB approval, chart review of patients who received at least one administration of intrathecal chemotherapy through OR for LMD treatment between 2017- 2020 at Mayo Clinic in Phoenix, Arizona was conducted. Charts were reviewed for demographics, treatment type, complications, and outcomes. RESULTS A total of 10 patients were included. The median overall survival from date of first OR injection was 110.5 days (95% CI: 64 – not estimable). The median time to progression from the first injection was 55.5 days (95% CI: 45 – 753). A total of 82 OR injections were conducted for an average of approximately 8 injections per patient. Two patients (20%) experienced mild adverse events – grade 2 or lower by Common Terminology Criteria for Adverse Events with a single injection. The majority of injections involved no adverse events with the overall risk of any complication at 2.4%. None of the patients experienced infection, a commonly reported complication of OR use. CONCLUSIONS Our results support the inclusion of intrathecal chemotherapy via OR into the treatment paradigm in patients with leptomeningeal malignancies. This approach is feasible, safe, and median survival is comparable with data reported in published series. The overall complication rate in patients receiving intrathecal chemotherapy through OR is very low including the risk of infection.
TAMI-42. H3K27M MUTANT GLIOMAS HIJACK A CONSERVED AND CRITICAL METABOLIC PATHWAY USED BY IDH1 MUTANT GLIOMAS TO MAINTAIN THEIR PREFERRED EPIGENETIC STATE
Authors: Chan Chung, Stefan Sweha, Drew Pratt, Benita Tamrazi, Pooja Panwalkar, Adam Banda, Jill Bayliss, Debra Hawes, Fusheng Yang, Ho-Joon Lee, Mengrou Shan, Marcin Cieslik, Tingting Qin, Christian Werner, Daniel Wahl, Costas Lyssiotis, Viveka Nand Yadav, Carl Koschmann, Arul Chinnaiyan, Stefan Blumul, Alexander Judkins, Sriram Venneti
Journal: Neuro-Oncology (2020)

Abstract H3K27M-midline gliomas are fatal tumors that mainly harbor H3.3K27M mutations resulting in global H3K27me3 reduction that impacts neuroglial-differentiation. However, the exact mechanisms by which H3.3K27M mutations promote cancer are poorly understood. Metabolic reprogramming is a hallmark of cancer and we hypothesized that H3.3K27M mutations can reprogram metabolism to support uncontrolled growth. We demonstrate that H3.3K27M-mutant cells show elevated levels of critical enzymes related to glycolysis and TCA cycle metabolism including hexokinase-2, isocitrate dehydrogenase (IDH)-1 and glutamate dehydrogenase. H3.3K27M cells also demonstrated enhanced glycolysis, glutamine and TCA-cycle metabolism accompanied by increased alpha-ketoglutarate (α-KG) production. Mutant IDH (mIDH)1/2 converts α-KG to D-2-hydroxyglutarate (D-2HG). D-2HG increases H3K27me3 by inhibiting α-KG’s function to drive H3K27-demethylases. We discovered that H3.3K27M cells use α-KG in an opposing manner to maintain low H3K27me3. Inhibiting enzymes related to α-KG generation including hexokinase-2, glutamate-dehydrogenase and wild type-IDH1 increased global H3K27me3, altered chromatin accessibility at neuroglial-differentiation factors and lowered tumor cell proliferation. In vivo inhibition of glutamine metabolism and/ or wild type-IDH1 using blood-brain barrier penetrant small molecule inhibitors increased overall survival in vivo in two independent H3.3K27M animal models (p&amp;lt; 0.0001). H3K27M and mIDH1 were mutually exclusive in patient tumor samples and D-2HG treatment or forced-mIDH1 expression in H3.3K27M cells increased global H3K27me3 and cell death. Finally H3.3K27M and mIDH1 were synthetic lethal in vitro. Our data suggest that H3.3K27M and mIDH1 hijack a critical and conserved metabolic pathway in opposing manners to regulate global H3K27me3. These results have implications for understanding the pathogenesis of fatal H3K27M-gliomas and for developing therapeutic strategies by disruption of an integrated metabolic/epigenetic-axis.
PATH-28. MOLECULAR DIAGNOSIS FOR CENTRAL DIAGNOSIS OF BRAIN TUMORS FROM 2016 TO 2019— A REPORT FROM THE JAPAN CHILDREN’S CANCER GROUP (JCCG)
Authors: Yoshiko Nakano, Junko Hirato, Takako Yoshioka, Sumihito Nobusawa, Tomoko Shoufuda, Mai Kitahara, Kohei Fukuoka, Kai Yamasaki, Hiroaki Sakamoto, Ryo Nishikawa, Junichi Hara, Yonehiro Kanemura, Koichi Ichimura
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Since 2016, the Japan Children’s Cancer Group (JCCG) has established a nationwide network that prospectively provides pathological review and molecular analysis. METHODS Patients who were diagnosed with brain tumors between ages 0 and 29 were eligible. The central office at National Center for Child Health and Development served as a hub for the hospitals involved and institutions conducting pathological and molecular analysis, and managed the patients’ clinical information and tumor samples. Histopathology of all cases were centrally reviewed. Routine non-NGS based analyses were conducted based on histological diagnosis and included pyrosequencing for glioma-associated hot spot mutations and PFA/PFB classification for ependymoma, RT-PCR for RELA fusion and BRAF fusion, and nanostring for subgrouping medulloblastoma. In selected cases, methylation analysis, RNA sequencing and exon sequencing of 93 genes were performed in selected cases. RESULTS In total, 985 cases were registered to this study in four years. Frozen samples were collected from approximately 80% of cases. The number increased from 152 in 2016 to 326 in 2019. They includes glioma (n=268), medulloblastoma (n=161), ependymoma (n=103), germ cell tumor (n=93), ATRT (n=29) and others. In 55 % of the glioma cases, at least one abnormality was detected by the routine analysis. The detailed analysis for atypical cases identified targetable alternations. DISCUSSION: This nationwide central diagnostic system has now been well established. Current issues and future prospective of the system will be discussed.
European first responder systems and differences in return of spontaneous circulation and survival after out-of-hospital cardiac arrest: A study of registry cohorts
Authors: Iris Oving, Corina de Graaf, Siobhan Masterson, Rudolph W. Koster, Aeilko H. Zwinderman, Remy Stieglis, Hajriz AliHodzic, Enrico Baldi, Susanne Betz, Diana Cimpoesu, Fredrik Folke, Dennis Rupp, Federico Semeraro, Anatolij Truhlar, Hanno L. Tan, Marieke T. Blom
Journal: The Lancet Regional Health - Europe (2021)

In Europe, survival-rates after out-of-hospital cardiac arrest (OHCA) vary widely between regions. Whether a system dispatching First Responders (FRs; main FR-types: firefighters, police officers, citizen-responders) is present or not may be associated with survival-rates. This study aimed to assess the association between having a dispatched FR-system and rates of return of spontaneous circulation (ROSC) and survival across Europe.Results of an inventory of dispatched FR-systems for OHCA in Europe were combined with aggregate ROSC and survival data from the EuReCa-TWO study and additionally collected data. Regression analysis (weighted on number of patients included per region) was performed to study the association between having a dispatched FR-system and ROSC and survival-rates to hospital discharge in the total population and in patients with shockable initial rhythm, witnessed OHCA and bystander cardiopulmonary resuscitation (CPR; Utstein comparator group). For regions without a dispatched FR-system, the theoretical survival-rate if a dispatched FR-system would have existed was estimated.We included 27 European regions. There were 15,859 OHCAs in the total group and 2,326 OHCAs in the Utstein comparator group. Aggregate ROSC and survival-rates were significantly higher in regions with an FR-system compared to regions without (ROSC: 36% [95%CI 35%-37%] vs. 24% [95%CI 23%-25%]; P<0.001; survival in total population [N=15.859]: 13% [95%CI 12%-15%] vs. 5% [95%CI 4%-6%]; P<0.001; survival in Utstein comparator group [N=2326]: 33% [95%CI 30%-36%] vs. 18% [95%CI 16%-20%]; P<0.001), and in regions with more than one FR-type compared to regions with only one FR-type. All main FR-types were associated with higher survival-rates (all P<0.050).European regions with dispatched FRs showed higher ROSC and survival-rates than regions without.This project/work has received funding from the European Union's Horizon 2020 research and innovation programme under acronym ESCAPE-NET, registered under grant agreement No 733381 (IO, HLT and MTB) and the European Union's COST programme under acronym PARQ, registered under grant agreement No CA19137 (IO, DC, HLT, MTB). HLT and MTB were supported by a grant from the Netherlands CardioVascular Research Initiative, Dutch Heart Foundation, Dutch Federation of University Medical Centres, Netherlands Organization for Health Research and Development, Royal Netherlands Academy of Sciences - CVON2017-15 RESCUED (HLT), and CVON2018-30 Predict2 (HLT and MTB).