tbuckley/cabot-search huggingface dataset:
Abstract 15941: The Effects of Training and Detraining on T Wave Inversion in Athletes
Authors: Aneil Malhotra, Sneha Varkey, Harshil Dhutia, Mike Walker, Rajay Narain, Ahmed Merghani, Lynne Millar, Michael Papadakis, Sanjay Sharma
Journal: Circulation (2015)

Introduction: T wave inversion (TWI) is the electrical hallmark of primary cardiomyopathies which are substrates for sudden death in young athletes. Such repolarization anomalies can feature on the ECG of an apparently healthy athlete and pose major diagnostic dilemmas in sports cardiology. Athletes are reluctant to detrain during the season. Hypothesis: This study hypothesized that detraining would affect TWI in athletes. Methods: Between 2013-2014, 36 professional footballers demonstrated TWI at mid-season ECG screenings (trained period). They were followed up during the "off-season" after a period of detraining (6-8 weeks). TWI was defined as –0.1 mV or greater 2 or more contiguous leads: anterior leads-V2-V3/4; inferior-II,III,aVF; or lateral-beyond V4 +/-aVL. Comparisons were drawn by 2 independent cardiologists, between trained and detrained ECGs. All players were also investigated for an underlying cardiomyopathy. Results: *Athletes were male, aged 24.5+/-2.7 years. *27 (75%) were Afro-Caribbean and 25% Caucasian (p=0.0141). *TWI was most common in the anterior leads (n=20, 55%), followed by inferior (n=10, 28%) and lateral (n=6, 17%) as in the bar chart. *No Caucasian player had TWI laterally. *After detraining, 16 players demonstrated resolution of anterior TWI (80%, p=0.0293), 8 in inferior leads (80%, p=0.2353) and 4 in the lateral leads (67%, p=0.638) (Figures 1a &amp; b). *All players with abnormal TWI according to consensus guidelines were evaluated with no cardiomyopathy identified. Conclusions: In athletes who detrained during the 'off-season', we observed resolution of TWI in the majority of athletes (both Afro-Caribbean and Caucasian) after a relatively brief period of detraining which may be a physiological phenomenon. This was statistically significant in the anterior leads. However, TWI in the inferior and/or lateral leads should always raise the suspicion of an underlying cardiomyopathy, especially if persistent after detraining.
Prognostic value of neo-adjuvant treatment in localized rectal cancer about 78 cases
Authors: K. Darif, Z. Benbrahim, M. Benhami, I. Ahalli, R. Boujarnija, H. Erraichi, R. Elhazzaz, H. Ouahbi, L. Amaadour, K. Oualla, F. El M'rabet, S. Arifi, N. Mellas
Journal: Annals of Oncology (2018)

Introduction: The frequency of colorectal adenocarcinoma continues to increase, which is the leading cause of cancer deaths in developed countries. Unlike colon cancer, there is currently no compelling evidence for the value of adjuvant chemotherapy in rectal cancer. Preoperative chemoradiotherapy has become the standard for middle and low rectum tumors, improving local control without improving survival without metastatic relapse and overall survival. Methods: It's a retrospective study based on 78 patients with non metastatic rectal adenocarcinoma who received adjuvant chemotherapy, collected at the Medical Oncology Department of Hassan II University Hospital for a period of 4 years between January 2014 and June 2017. The aim of the study is to determine the place of neoadjuvant treatment as a prognostic factor using a univariate study (Kaplan-Meier survival analysis). Results: The average age of patients was 56 +/- 14, 42% men and 75% women. The tumor was located in the middle rectum in 28%; 34% in the lower rectum and 37% in the upper rectum. Histologically, the biopsy showed that the lieberkuhnian adenocarcinoma was well differentiated in 53%, moderately differentiated in 45% and in 2% poorly differentiated. Most patients (86%) received neo-adjuvant therapy: radiochemotherapy (RCC) was performed in 63% and short cycle radiotherapy alone for 23%. Histological examination classified the patients according to the TNM classification with 30% at stage II, 61% at stage III and 9% at stage IV. The mean overall survival was 31 months (95% CI). 32% of patients had a recurrence within an average of 12 months. The analysis of neo-adjuvant treatment did not show a significant improvement in overall survival, and the mean non-relapse-free survival was 12 months in the group that received the neo-adjuvant treatment versus 7 months (group not received neoadjuvant treatment), but the difference was statistically insignificant. Conclusion: Despite the progress made in diagnostics and therapeutics, particularly with adjuvant treatments and resection of metastases, five-year survival does not exceed 25%.
Trim33 mediates the proinflammatory function of Th17 cells
Authors: Shinya Tanaka, Yu Jiang, Gustavo J. Martinez, Kentaro Tanaka, Xiaowei Yan, Tomohiro Kurosaki, Vesa Kaartinen, Xin-Hua Feng, Qiang Tian, Xiaohu Wang, Chen Dong
Journal: The Journal of Experimental Medicine (2018)

Transforming growth factor–β (TGF-β) regulates reciprocal regulatory T cell (T reg) and T helper 17 (Th17) differentiation, the underlying mechanism of which is still not understood. Here, we report that tripartite motif-containing 33 (Trim33), a modulator of TGF-β signaling that associates with Smad2, regulates the proinflammatory function of Th17 cells. Trim33 deficiency in T cells ameliorated an autoimmune disease in vivo. Trim33 was required for induction in vitro of Th17, but not T reg cells. Moreover, Smad4 and Trim33 play contrasting roles in the regulation of IL-10 expression; loss of Trim33 enhanced IL-10 production. Furthermore, Trim33 was recruited to the Il17a and Il10 gene loci, dependent on Smad2, and mediated their chromatin remodeling during Th17 differentiation. Trim33 thus promotes the proinflammatory function of Th17 cells by inducing IL-17 and suppressing IL-10 expression.
QOL-13. ESTABLISHMENT OF A REHABILITATION CLINICAL SPECIALIST IN ONCOLOGY SIGNIFICANTLY IMPROVED REHABILITATION ACCESS FOR PEDIATRIC NEUROONCOLOGY PATIENTS: A SINGLE INSTITUTION EXPERIENCE
Authors: Lynn Tanner, Anne Bendel
Journal: Neuro-Oncology (2018)

Pediatric survivors of central nervous system (CNS) tumors face decreased physical, cognitive, and social function, resulting in poorer quality of life. Impairments, including weakness, ataxia, visual-perception disturbance, lower cognition, aphasia, dysphagia, and dysarthria, may be addressed by rehabilitation; however, services can be challenging to provide in the environment of surgery, radiation, and chemotherapy. Children’s Minnesota developed the rehabilitation clinical specialist in oncology (RCSO) role, which targeted improving rehabilitation through increasing interdisciplinary collaboration, defining a specialized rehabilitation team, providing outpatient (OP) services within the cancer clinic, improving OP scheduling, and designing inpatient (IP) clinical pathways and order sets. We compared IP and OP physical therapy (PT), occupational therapy (OT), and speech language pathology (SLP) visits for all children with CNS tumors from diagnosis to 3 years post-diagnosis in a historical cohort (2001-2006) pre-RCSO and current cohort (2009-2014) post-RCSO. Patient totals included 155 historical and 221 current patients. Rehabilitation referral percentages grew in IP and OP settings (IP 28.04% and OP 154.70%). Average rehabilitation visits per patient grew in IP by 26.33%, and in OP by 131.82%. The largest areas of growth were OP OT (3.21 to 12.61 visits) and OP PT (7.14 to 21.41 visits). The growth in OP rehabilitation in the neurooncology population surpassed the overall growth of rehab in all populations at Children’s. Implementation of the RSCO role and access systems improved rehabilitation services for neurooncology patients. Further investigation is needed regarding the impact of improved rehabilitation access and service on function and quality of life.
Effectiveness of TAS-102 in patients with metastatic colorectal cancer in a single comprehensive cancer center
Authors: C. Sales, I. Julião, A. Rosinha, D. Marques, F. Carneiro, C. Faustino, M. Machado, P. Ferreira, M. Fragoso, N. Sousa
Journal: Annals of Oncology (2018)

Introduction: Trifluridine/tipiracil (TAS-102) prolongs progression free survival (PFS) and overall survival (OS) of patients with metastatic colorectal cancer (mCRC) whose disease progressed after at least two standard therapies. TAS-102 is available in Portugal since 2016. The authors evaluate the effectiveness of TAS-102 in patients with mCRC in routine clinical practice. Methods: Consecutive case series of mCRC patients treated with TAS-102, between November 2016 and March 2018. Clinical and pathologic characteristics are described. Tolerance to treatment is evaluated by cumulative incidence of adverse events and therapeutic efficacy by response rate, PFS and OS. Patient follow-up was complete by March 2018. Results: Twenty-seven patients were included, with a median age of 61 years (min. 40; max. 72) of which, 20 (74%) were male. Twenty-two patients (81%) had left-sided colon cancer and 17 patients (63%) had metastatic disease in two or more organs (70% with liver metastasis and 67% with lung metastasis). RAS complex mutation was present in 14 patients (52%). Median duration of treatment was 3 months with 21 patients (78%) presenting at least 1 adverse event. Nineteen patients (70%) presented haematological toxicity of any grade (48% neutropenia and 22% anemia). Grade ≥3 haematological toxicity was seen in 7 patients (26%). Sixteen patients (59%) had non-haematological toxicity (41% nausea, 30% anorexia, 22% asthenia, 15% diarrhea and 11% vomiting), all grade 1 or 2. Only one patient discontinued treatment due to an adverse event. Eleven patients (41%) required hospitalization during treatment with TAS-102 (22% due to cancer-related symptoms, 11% due to infectious intercurrences and 7% due to grade 3 haematological toxicity). At the time of data censorship, median follow up for patients alive was 5,8 months with 7 patients (26%) still undergoing treatment. Best response to treatment was stable disease (22%), with no partial or complete responses. Median PFS was 3,5 months (95% CI 2.3-4.7) and median OS was 6,6 months (95% CI 5.8-7.3). Conclusion: TAS-102 has been adopted to current clinical practice with a toxicity profile that is similar from what was observed on its pivotal trial, and no new treatment adverse reactions were noted. Efficacy of TAS-102 in our center is similar to that which was described in the RECOURSE trial.
Pre-treatment peripheral neutrophil-lymphocyte ratio as a prognostic factor in gastric cancer
Authors: A. Gaballah, T. Hussein, A. Ezzat, M. Magdy
Journal: Annals of Oncology (2018)

Introduction: Gastric cancer is the fifth common cancer worldwide. Systemic inflammatory response increases metastasis through apoptosis inhibition and angiogenesis augmentation. The neutrophil-lymphocyte ratio (NLR) which is a balance between pro-cancer inflammatory response and anti-cancer immune response was proved as prognostic marker in malignancies. Peripheral NLR is a good reflection of tumor microenvironment. Methods: We retrospectively collected data of gastric and gastro-esophageal cancer (GC) patients treated at our department from January 2013 till December 2016. Sixty-one patients were included. Pre-treatment absolute neutrophils-lymphocytes counts were collected and the NLR was calculated. We extracted the different clinic-epidemiological and pathological data of the patients and tumors. Event-free and overall survivals were plotted using Kaplan-Meier curves. Results: Median age was 55. Male to female ratio was 1:1. Forty-seven patients (77%) were smokers. Most of the patients (93.4%) had good performance status (ECOG 0-2). Forty-six patients had gastric and 15 patients had gastro-esophageal cancer. According to Lauren's classification; 50.8% were diffuse type. Grade 3 represented 49.2% and grade 2 46%. Twelve patients (19.7%) had ascites at diagnosis. Staging at presentation was; 1.6% stage 1, 4.9% stage 2, 27.9% stage 3, 50.8% stage 4 and 14.8% unknown. The median NLR was 2.4. The patients divided into high NLR (>2.4) (30 patients) and low NLR (≤ 2.4) (31 patients). The NLR showed no significant correlation with different clinic-epidemiologic and pathological variables except for presence of ascites; where ascites was associated with high NLR with p = 0.046. Median event-free survival (EFS) and overall survival (OS) were 6 and 8 months respectively. High NLR was significantly correlated with worse EFS; 5 months compared to 8 months in low NLR group (95% CI, p = 0.001). Also high NLR was associated with worse OS; 6 months compared to 9 months (95% CI, p = 0.013). Conclusion: Gastric cancer is aggressive disease with short survival. Most of our patients presented with advanced stage. Pre-treatment NLR is an independent prognostic factor in GC; irrespective stage or any other prognostic factor.
A phase III, double-blind, randomized study of pamiparib versus placebo as maintenance therapy in patients with inoperable, locally advanced, or metastatic gastric cancer that responded to platinum-based first-line chemotherapy
Authors: F. Ciardiello, Y.-J. Bang, J. Bendell, A. Cervantes, R. Brachmann, K. Zhang, M. Raponi, H. Farin, L. Shen
Journal: Annals of Oncology (2018)
NURS-07. PROGRAMMABLE VP SHUNTS: INDICATIONS, SAFETY AND WARNINGS
Authors: Maria Donzelli
Journal: Neuro-Oncology (2018)

Tumor-associated hydrocephalus is common in pediatric patients with brain tumors, often necessitating placement of a permanent ventriculoperitoneal (VP) shunt. The programmable VP shunt has a magnetic externally adjustable valve that provides the option of changing the opening pressure (valve setting) to regulate the outflow of cerebrospinal fluid (CSF). Maximal resistance adjustments can be used for the administration of chemotherapy or radioimmunotherapy. Integrated reservoirs also provide an easy source of diagnostic CSF sampling. Strong magnetic field interference may cause an unintended change in valve setting. Newer models have a mechanism that provides security against inadvertent readjustment caused by MRI 3 Tesla or less. At MSKCC, 52 pediatric patients with various programmable VP shunt models have been treated. Intrathecal radioimmunotherapy or chemotherapy was given to 17 (33%), all without complication. CSF sampling from the VP shunt was well tolerated without any known iatrogenic infections. The ease of shunt reprogramming varied among the different models;1 patient (2%) presented with an unintentional valve setting change. Nurse practitioners and nurses play a vital role in the successful management of patients with a programmable VP shunt. Knowledge about the indications and management of programmable shunts, associated complications, magnetic field safety, MRI safety, shunt reprogramming technique, and nursing considerations is critical.
HECTD3 mediates TRAF3 polyubiquitination and type I interferon induction during bacterial infection
Authors: Fubing Li, Yang Li, Huichun Liang, Tao Xu, Yanjie Kong, Maobo Huang, Ji Xiao, Xi Chen, Houjun Xia, Yingying Wu, Zhongmei Zhou, Xiaomin Guo, Chunmiao Hu, Chuanyu Yang, Xu Cheng, Ceshi Chen, Xiaopeng Qi
Journal: Journal of Clinical Investigation (2018)

Lysine-63–linked (K63-linked) polyubiquitination of TRAF3 coordinates the engagement of pattern-recognition receptors with recruited adaptor proteins and downstream activator TBK1 in pathways that induce type I IFN. Whether autoubiquitination or other E3 ligases mediate K63-linked TRAF3 polyubiquitination remains unclear. We demonstrated that mice deficient in the E3 ligase gene Hectd3 remarkably increased host defense against infection by intracellular bacteria Francisella novicida, Mycobacterium, and Listeria by limiting bacterial dissemination. In the absence of HECTD3, type I IFN response was impaired during bacterial infection both in vivo and in vitro. HECTD3 regulated type I IFN production by mediating K63-linked polyubiquitination of TRAF3 at residue K138. The catalytic domain of HECTD3 regulated TRAF3 K63 polyubiquitination, which enabled TRAF3-TBK1 complex formation. Our study offers insights into mechanisms of TRAF3 modulation and provides potential therapeutic targets against infections by intracellular bacteria and inflammatory diseases.
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) induced by immune checkpoint inhibitors
Authors: Anissa Roger, Matthieu Groh, Gwenael Lorillon, Claire Le Pendu, Jeremy Maillet, Dimitri Arangalage, Abdellatif Tazi, Celeste Lebbe, Barouyr Baroudjian, Julie Delyon
Journal: Annals of the Rheumatic Diseases (2018)

Figure 1 Timeline showing the relationship between serum eosinophil count and treatment with immune checkpoint inhibitors (double arrow: nivolumab 1 mg/kg and ipilimumab 3 mg/kg infusions; single arrow: nivolumab 3 mg/kg infusion).on July 15,
MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study
Authors: Philip Ambery, Victoria E Parker, Michael Stumvoll, Maximilian G Posch, Tim Heise, Leona Plum-Moerschel, Lan-Feng Tsai, Darren Robertson, Meena Jain, Marcella Petrone, Cristina Rondinone, Boaz Hirshberg, Lutz Jermutus
Journal: The Lancet (2018)
Utility of Drinking Water in Hepatobiliary Scintigraphy When Possible Acute Cholecystitis Was Considered
Authors: Xia Bai, Xuemei Wang
Journal: Clinical Nuclear Medicine (2018)

A 15-year-old boy underwent hepatobiliary scintigraphy for suspected acute cholecystitis. The initial images revealed an activity in the neighborhood of normal gallbladder fossa, suggestive of possible activity in the gallbladder, which would be inconsistent with a diagnosis of acute cholecystitis. However, after drinking 6 oz of water, the activity was no longer seen. Acute cholecystitis was confirmed pathologically after cholecystectomy.
MBRS-10. RISK STRATIFICATION OF MEDULLOBLASTOMA ON THE BASIS OF MOLECULAR SUBGROUPING; AN EXPERIENCE FROM A SINGLE TERTIARY CARE CENTER FROM A DEVELOPING COUNTRY
Authors: Naureen Mushtaq, Quratulain Riaz, Cynthia Hawkins, Vijay Ramaswamy, Khurram Minhas, Eric Bouffet
Journal: Neuro-Oncology (2018)

Medulloblastoma is the most common malignant child hood brain tumor. It has been risk stratified on the basis of clinical and histological types and recently as 4 molecular subgroups which includes (WNT, SHH, Group 3 and group 4). There is very scarce data available on the molecular subgrouping of medulloblastoma from developing countries. This is the only data from Pakistan on the molecular subgrouping in children with medulloblastoma. All children (0 – 16 years) with Medulloblastoma from April 2014 till December 2016 at Aga Khan University Hospital were reviewed retrospectively for clinical data, histology, molecular sub grouping, risk stratification, management and outcome. Biopsy samples of patients were sent for molecular sub grouping to Hospital for Sick Children, Toronto as a part of twinning program with Aga Khan University Hospital. 19 children were included in the study. Molecular subgrouping was done for 14 patients and showed Group 4 in 5, SHH in 4, WNT in1 patient. There were no patients with Group 3 and the subgrouping was inconclusive in 4 patients. Risk stratification based on extent of resection, metastasis and molecular subgrouping showed that there was only one low risk patient. There were 6 patients who were standard risk, 11 patients in high risk and 1 patient in very high risk group. There were 14 patients who were treated with chemo radiation followed by maintenance chemotherapy. This is the only study from Pakistan. Twinning programs can significantly help in proper diagnosis and management of pediatric brain tumors in LMIC.
The clinical effectiveness and safety of re-induction oxaliplatin, irinotecan and fluorouracil (FOLFOXIRI regimen) for the treatment of metastatic colorectal cancer after two lines of chemotherapy (oxaliplatin- and irinotecan-based regimens)
Authors: E. Ledin, A. Mochalova, Y. Zaitseva
Journal: Annals of Oncology (2018)

Introduction: The choice of antitumor agents used in the treatment of metastatic colorectal cancer (mCRC) is limited, which reduces the therapeutic possibilities. The improvement in survival for mCRC patient led to there is a significant number of patients progressing beyond the second or third line of treatment still suitable for further therapy when enrollment into clinical trial is not possible. In this situation, any rechallenge therapy plays an important role. We evaluated the efficacy and safety of the re-induction of oxaliplatin, irinotecan and fluorouracil (FOLFOXIRI regimen) in the third line of chemotherapy mCRC. Methods: A total of 22 patients (median age = 62) with mCRC, all of whom had developed progressive disease within at least 3 months of discontinuing two sequential chemotherapy lines (oxaliplatin- and irinotecan-containing regimens), were accrued in this study. The majority (85%) had FOLFOX as first-line chemotherapy and FOLFIRI as second-line chemotherapy. Bevacizumab was added to chemotherapy in 45% (n = 10) of patients. Only one patient was with wild-type KRAS genotype, therefore in the third-line all of other patients couldn't receive cetuximab. Treatment regimen third line was FOLFOXIRI (irinotecan 165 mg/m2 on day 1, oxaliplatin 85 mg/m2 on day 1, leucovorin 400 mg/m2 on day 1, 5-fluorouracil 2400 mg/m2 46-hours infusion every 14 days). The response evaluation of antitumor treatment was carried out every 2 months on the basis of RECIST 1.1 criteria. The primary end point was progression free survival (PFS), the secondary end point was overall survival (OS), objective response rate (ORR) and safety. Results: The median number of chemotherapy cycles was seven. The objective response rate (ORR) by intent-to-treat analysis was 23,8% (n = 5), and 61,9% (n = 13) had stable disease. The disease progression at the first follow-up examination was registered in 13,6% of cases (n = 3). The disease control rate was 86,4%. The median progression-free survival and overall survival were 5,2 months (range: 2-17 months) and 7,21 months (range: 4-35 months), respectively. The main hematological toxicity was grade III/IV neutropenia, which occurred in 27,2% of patients (n = 6), including febrile neutropenia in 3,1% (n = 5), while anemia and thrombocytopenia were uncommon. Grade III/IV non-hematological toxicities were asthenia nausea (9%); vomiting (9%), sensory neuropathy (4,5%) and diarrhea (13,6%). No toxic death was observed, one patient with grade IV vomiting after the eighth cycle refused chemotherapy. Conclusion: The re-induction of oxaliplatin, irinotecan and fluorouracil (FOLFOXIRI) in the third line of mCRC treatment provided a significant antitumor effect. This approach significantly expands the therapeutic possibilities in mCRC and promotes an increase in the life expectancy of patients.