tbuckley/cabot-search huggingface dataset:
Long term survival analysis of osimertinib in stage IV NSCLC patients harbored acquired EGFR T790M mutation: A real-word study in China
Authors: S. Wang, B. Han
Journal: Annals of Oncology (2019)

Background: Aura studies have demonstrated the efficacy of osimertinib in advanced NSCLC patients harbored acquired EGFR T790M mutation. However, the real word data remains rare in China. Methods: This retrospective study was conducted in Shanghai Chest Hospital. We collected data form stage IV NSCLC patients diagnosed with acquired EGFR T790M mutation. The whole median overall survival (OS) and OS from osimertinib, progression free survival (PFS) of osimertinib were observed. Results: A total of 584 patients were tested positive for EGFR T790M mutation either by tissue or blood from Jan 2012 to Dec 2017. Finally, 238 patients (60.1% female, 62.2% 19del, 19.7% smokers) received osimertinib and have enough data to analysis. The median whole OS and OS from osimertinib were 54.8 and 24.33 month, respectively. And PFS of osimertinib was 11.0 month. Patients with 19del have better PFS, OS and whole survival from osimertinb (12 vs 10month, P = 0.054; 24.4 vs 20.27month, P = 0.012; 42.7 vs 60.9month, P = 0.056). The therapy line and EGFR T790M mutation detection methods (tissue or blood) had no impacts on PFS and OS. Additionally, in 63 patients with brain metastases (BM), osimertinib plus local therapy could contribute to the OS (61.3 VS 47.8, p = 0.086). After osimertinib failure, 39 patients benefited from rebiopsy. Conclusions: This study gave us information that osimertinib could be a standard therapy in patients with EGFR T790M mutation, these patients have a better prognosis and an indolent progress. In addition, although osimertinib showed good control of BM, local therapy although show be taken into consideration for patients with BM. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Degree of STING activation is associated with disease outcomes
Authors: Qiongyuan Hu, Jie Wu, Yanhan Ren, Xiuwen Wu, Lin Gao, Gefei Wang, Guosheng Gu, Huajian Ren, Zhiwu Hong, Dominic A Slade, Jianan Ren
Journal: Gut (2019)

We read with interest the recent paper by Zhao et al ,1 which reported that stimulator of interferon genes (STING) signalling alleviated chronic pancreatitis (CP)-induced inflammation and fibrosis. There is increasing evidence that STING activation could lead to inflammatory response and fibrosis. In our opinion, this contention is associated with three major issues: the form of stimulators that activate STING, the degree of STING activation and the type of immune cell lineages activated STING signalling are able to affect its role in the process of disease.

Self-DNA released from various types of cells during infection or inflammation may stimulate cyclic guanosine monophosphate–adenosine monophosphate (GMP–AMP)  synthase (cGAS)–STING pathway to different degrees. Zhao et al 1 did not investigate how STING signalling was activated; however, the amount, manner and rate of DNA release under different ways of cell deaths all played important roles in activating downstream pathways. Additionally, recent reports indicated that the extent of DNA oxidation is a key factor in promoting an enhanced inflammatory …
Transvaginal mesh: FDA orders remaining products off US market
Authors: Owen Dyer
Journal: BMJ (2019)

The US Food and Drug Administration has told the two manufacturers of the remaining three transvaginal mesh products to present a plan within 10 days for withdrawing from the US market, after they failed to provide evidence to allay safety concerns.

More than 100 000 women have sued over transvaginal mesh devices, complaining of symptoms such as persistent vaginal bleeding or discharge, chronic pelvic pain, or pain during sex.

Boston Scientific, which makes two of the three devices, has been named in 48 000 lawsuits by women claiming injury. The maker of the other device is a Danish company, …
FRI-396-Hypoadiponectinemia as a predictor of cardiovascular events in liver transplant recipients
Authors: Mohammad Bilal Siddiqui, Samarth Patel, Fei-Pi Lin, Joseph Clinton, John Laurenzano, Anchalia Chandrakumaran, Trevor Reichman, Chandra Bhati, Mohammad Siddiqui
Journal: Journal of Hepatology (2019)
PS-158-Paneth cells drive microbial induced signals to promote angiogenesis and regulate portal hypertension
Authors: Mohsin Hassan, Sheida Moghadamrad, Marcel Sorribas, Sergi Muntet, Philipp Kellmann, Coralie Trentesaux, Marie Fraudeau, Paolo Nanni, Witold Wolski, Beatrice Romagnolo, Siegfried Hapfelmeier, Prof. Dr. Reiner Wiest, Andrea De Gottardi
Journal: Journal of Hepatology (2019)
SAT-250-Effects of sustained virological response on the endothelial dysfunction and the cardiovascular risk in hepatitis C after direct antiviral angets treatment: HEPCAR study
Authors: Rocio Munoz hernandez, javier ampuero, Raquel Millan, Sheila Gato, hada c macher, Angela Rojas, Antonio Gil-Gomez, Rocío Gallego-Durán, Rocío Montero-Vallejo, Douglas Maya-Miles, Yolanda Sánchez, Manuel Romero Gomez
Journal: Journal of Hepatology (2019)
Exercise-too much of a good thing?
Authors: Iain McNamara
Journal: BMJ (1999)

“The credit belongs to those actually in the arena, who strive valiantly; who know the great enthusiasms, the great devotions, the worthy cause they spend themselves in; who at the best know the triumph of high achievement; and who at the worst, if they fail, fail while daring greatly so that their place shall never be with those cold and timid souls who know neither victory or defeat.” Theodore Roosevelt

Watching the 1999 boat race (Oxford students versus Cambridge students) proved very difficult. For 10 months I had trained hard in the hope that I would be selected for one of the crews. I raced with Oxford University Boat Club at Henley in July and at the national rowing championship three weeks later in what was to be the final event before the summer break. Unfortunately, my brief rowing career came to a sudden halt.

I had been feeling very tired before travelling to the event. This was to be expected as we had been training six days a week, twice a day, for some months. The first session, usually in the morning, was either a weights session or, more often, 60 minutes on the rowing ergometer. In the afternoon we had 90 minutes' intensive rowing, often at race pace. As we travelled up to Scotland the tiredness bothered me, and, in addition, I felt as if I was developing a cold. I was determined to race, however, and felt fine when rowing, and the races went well.

Once back home I still felt tired and ill. After spending two days in bed I very reluctantly started training again. It was difficult, but I thought that it was because I had rested. I was also getting very irritable and having trouble sleeping even though I felt exhausted. Then literally overnight …
Maintenance Rituximab or Observation after Frontline Treatment with Bendamustine-Rituximab (BR) for Follicular Lymphoma: A Real World Analysis Across 13 US Cancer Centers
Authors: Brian T. Hill, Loretta Nastoupil, Allison M. Winter, Melody R Becnel, James R. Cerhan, Thomas M Habermann, Brian K Link, Matthew J Maurer, Bita Fakhri, Prathima Reddy, Stephen D. Smith, Dhruvika Mukhija, Deepa Jagadeesh, Amrita Desai, Juan Pablo Alderuccio, Izidore S Lossos, Pooja Mehra, Craig A. Portell, Max L. Goldman, Oscar Calzada, Jonathon B Cohen, Mohammad Junaid Hussain, Nilanjan Ghosh, Paolo Caimi, Timothy Tiutan, Peter Martin, Abhigna Kodali, Andrew M Evens, Brad S Kahl
Journal: Blood (2017)
FRI-077-Influence of drug categorization according to labelling information in the phenotypic presentation of drug-induced liver injury (DILI): An analysis in the Spanish DILI registry
Authors: Laura Sanz-Villanueva, Cecilio Parra-Martinez, I Medina-Caliz, J Sanabria-Cabrera, M Robles-Díaz, A Ortega-Alonso, J Gasca, Rocío Sanjuan-Jimenez, MR Cabello, Miren Garcia Cortes, Maria Isabel Lucena, A González-Jiménez, Raul J. Andrade
Journal: Journal of Hepatology (2019)
FRI-441-A novel heterozygous ABCB, RUNDC3B and ABCB1 deletion associated with severe cholestatic liver disease in adults
Authors: Benedetta Terziroli, Richard Thompson, Pierre Foskett, Andreas Cerny, Elisabetta Merlo, Diego Vergani, Anne-Laure Rougemont, Isabelle Moix, Giorgina Mieli-Vergani, Michael Morris
Journal: Journal of Hepatology (2019)
The prognostic significance of MIBG uptake in left supraclavicular lymph nodes in high risk neuroblastoma patients.
Authors: Shifra Ash, Isaac Yaniv, Adam Steinmetz, Zvi Bar-Sever
Journal: Journal of Clinical Oncology (2015)

10046 Background: Metastatic MIBG localization in the soft tissues of the left supraclavicular (LSC) region is occasionally seen in children with high risk (HR) neuroblastoma. The purpose of the study was to evaluate the prognostic significance of this uptake. Methods: We performed a retrospective analysis of MIBG studies and clinical data of 77 HR neuroblastoma patients treated at Schneider Children's Medical Center of Israel between 1998 – 2015. The median age was 2.8 years (0.1-7.6) and the median follow up was 39 months (1-202). HR was defined as patients diagnosed as stage 3 with MYCN amplification and stage 4. Treatment consisted of induction chemotherapy, surgery, autologous bone marrow transplantation, local radiation and retinoic acid with or without immunotherapy. MIBG studies included whole body surveys, SPECT or SPECT/CT with the supraclavicular regions in the field of view. Results: LSC uptake was identified in 13/77 children (17%). All children with LSC MIBG uptake had abdominal primary tumors. Patients with LSC uptake had a 5y relapse free survival (RFS) of only 16%±14 as opposed to 42%± 7 for patients with no uptake (p = 0 .021). Five year overall survival (OS) was 0% in children with LSC uptake and 57%±7 in those without (p = 0.001). Within the group of 46/77 patients without MYCN amplification, 5y OS was 0% in 8 children with LSC uptake and 51%± 9 in 38 without (p = 0.014). On multivariate analysis for survival, only LSC MIBG uptake was found to be a poor independent prognostic factor, with an increased risk of 3.69 fold (95% CI 1.6-8.3, p = 0.002). Conclusions: Avid metastases identified by MIBG in the LSC region can identify HR patients with worse prognosis. This phenomenon resembles metastatic spread to Virchow nodes from gastric cancer and can be used as a prognostic factor. Cross sectional imaging with MIBG (or other modalities) should always include the left supraclavicular region. The presence of left supraclavicular disease should be considered for therapy planning.
Intensified, sort duration chemotherapy of pediatric non-Hodgkin’s lymphoma
Authors: A. Mukhopadhyay, K. Saha, B. Kundu, B. Barman, R. Sarkar, S. Jana, P. R. Gupta
Journal: Journal of Clinical Oncology (2005)

8560 Background: The non-Hodgkin's Lymphomas (NHL) in childhood are of diffuse histology and are characterized by wide dissemination and rapid progression. Methods: We describe here the result of MCP 842 Protocol is a series of patient treated at the Netaji Subhash Chandra Bose Cancer treatment & Research Institute between June 1996 and November 2004. Patient less than 25 yrs of age with a diagnosis of NHL and no prior treatment were eligible for the study. All patients had complete haematological and biochemical assessment including renal and hepatic function test, chest x-ray, abdominal ultra sound, bone marrow, biopsy and cerebrospinal fluid examination. A computerized tomography scan of primary site was performed to determine the extent of local disease. Pleural and ascetic fluids, if present, were examined for the presence of malignant cells. Patients are clinically stage according to the St. Jude's (Murphy's) classification. Patients with > 25% blasts in the bone marrow were treated as leukemia and excluded from the patient study. Response was assessed at the completion of 2 cycles of chemotherapy (1 each of A and B). Results: Complete response (CR) was defined as the absence of demonstrable tumor of clinical examination, supplemented by radiological examination of the original sites of disease. Partial response (PR) was defined as a reduction greater than 50% (Products of the widest diameters) in the volume of all measurable disease. A total of 75 previously untreated patients were entered on study. The age range was 2 to 25yrs (median 11). 36 patients had Lymphoblastic Lymphoma (LL), 15 diffuse Large B Cell Lymphoma (DLCL) and 22 of undifferentiated lymphoma (UD). The abdomen was the most common site of involvement followed by the mediastinum. 71 (95%) patients achieved complete response after 2 cycles of therapy 5(7.5%) achieved partial response and two had no response, 4 were not evaluable. A total of 20 patients (12 LL, 2 DLCL and 6 UDP) have died. The causes of death were progressive disease in 13, infection in 4, hepatitis in 2, and unknown 1.55 patients are alive and in complete remission. Conclusions: The results of protocol NCP 842 are promising. No significant financial relationships to disclose.
Abstract P078: Childhood Social Determinants Explain Ethnic Disparities in Obesity Among Black American Women
Authors: Debbie Barrington
Journal: Circulation (2017)

Introduction: Black American women have the highest prevalence of obesity in the United States (US). Ethnic disparities in this risk factor for cardiovascular disease have been found; Afro-Caribbean women have lower rates of obesity compared with African American women. Contributing factors of the ethnic disparity in adult obesity have yet to be fully elucidated. However, the emergence of the ethnic disparity in adolescence suggests a potential role for childhood social determinants. Hypothesis: Childhood social determinants are hypothesized to explain the ethnic disparity in obesity between African American and Afro-Caribbean women in the United States. Methods: Multiple logistic regression models were used to examine childhood social factors and adult social, health and lifestyle risk factors that explain the ethnic disparity in obesity between African American (N = 2299) and Afro-Caribbean women (N = 978), 18 years and older, in the National Survey of American Life (2001-2003). Adult socioeconomic factors included marital status, education, occupation, home ownership and poverty status. Adult health and lifestyle risk covariates included hypertension, diabetes, menopausal status, smoking, alcohol use and physical activity. Childhood social factors included measures of parental education, receipt of public assistance prior to 18 years of age, and type of high school attended (private/parochial vs. public). Odds ratios (OR) of the association between ethnicity and adult obesity were estimated after adjusting age and adult socioeconomic measures, adult health and lifestyle measures and childhood social factors within the models. Results: The prevalence of obesity was 40.5% among African American women and 30.8% among Afro-Caribbean women. Afro-Caribbean women had 34% lower odds of obesity than African American women; age-adjusted OR = 0.66; 95%CI: (0.52, 0.82). Adjusting for age and adult socioeconomic factors slightly decreased the ethnic disparity; adjusted OR = 0.70; 95%CI: (0.53, 0.94). Adjusting for age and adult health and lifestyle factors decreased the disparity by 11%; adjusted OR = 0.73; 95%CI: (0.55, 0.97). Adjusting for age and childhood social factors eliminated the ethnic disparity; adjusted OR = 1.00; 95%CI: (0.82, 1.23). Conclusions: These findings suggest that childhood social factors are key contributors to the ethnic disparities in obesity between African American and Afro-Caribbean women in the US.
THU-046-Implementation of acute kidney injury criteria to patients with acute-on-chronic liver failure: Characteristics of effect on outcomes
Authors: Laura Napoleone, Cristina Solé, Elisa Pose, Marta Carol, Adrià Juanola, Patrícia Huelín, Glòria De Prada, Marta Cervera, Martín Bonacci, Núria Fabrellas, Isabel Graupera, Elsa Solà, Pere Ginès
Journal: Journal of Hepatology (2019)
Utilization and deferral of hospice in patients with hematologic malignancies: A single center experience.
Authors: Ted Yamamoto, Max Vergo
Journal: Journal of Clinical Oncology (2015)

e20554 Background: Early palliative care and hospice at the end of life has been shown to result in improved survival, reduced symptom burden, and reduced costs and yet studies demonstrate that these services are underutilized in patients with hematologic malignancies. Prior studies demonstrate a pattern of late admission to hospice. There is little known about the utilization and deferral of hospice in this population and therefore this study was performed to assess hospice utilization and reasons for deferral. Methods: This was a single center retrospective review of patients with a hematologic malignancy (limited to acute leukemia, multiple myeloma, and myelodysplastic syndrome) over a 5 year period (July 2009- June 2014). Six hundred and forty three patients met inclusion criteria. Patient charts were reviewed for demographic information, oncologic diagnosis, transfusion dependence, living status, hospitalization at death, admission and duration of hospice, and documented reasons for hospice deferral. Results: Of the 643 patients, 315 had acute leukemia, 214 had multiple myeloma, and 114 had myelodysplastic syndrome. Two-hundred and fifty patients were deceased (38.9%). Of the deceased patients, only 55 were admitted to hospice with a median LOS of 4 days (SD 14). Eighty-nine patients died in the hospital. Reasons for hospice deferral were usually not documented, but in cases of documentation, most cited transfusion dependence as the reason for deferral (13 of 16). Other reasons for deferral included patient refusal and palliative chemotherapy and radiation. Of the deceased patients, eight-three (33.2%) were dependent on regular blood product transfusions. Conclusions: Patients with hematologic malignancies are referred late to hospice and many die in the hospital. As many are dependent on blood product transfusions at the end of life, providers defer admission to hospice to continue with these supportive services. More research on palliative services at the end of life is needed to better determine whether expensive services such as transfusions should be included as part of hospice care.
Colitis-Induced Th17 Cells Increase the Risk for Severe Subsequent Clostridium difficile Infection
Authors: Mahmoud M. Saleh, Alyse L. Frisbee, Jhansi L. Leslie, Erica L. Buonomo, Carrie A. Cowardin, Jennie Z. Ma, Morgan E. Simpson, Kenneth W. Scully, Mayuresh M. Abhyankar, William A. Petri
Journal: Cell Host & Microbe (2019)
SAT-256-Influence of metabolic syndrome on fibrosis regression regulated by LOXL-2 after SVR
Authors: Angela Puente, Miguel Posadas, Jose Ignacio Fortea, Agustin Garcia, María Teresa Arias Loste, Joaquin Cabezas, Susana Llerena, Laura Rasines, Paula Iruzubieta, Emilio Fabrega, Javier Crespo
Journal: Journal of Hepatology (2019)
Two weeks versus four weeks of antibiotic therapy after surgical drainage for native joint bacterial arthritis: a prospective, randomised, non-inferiority trial
Authors: Ergys Gjika, Jean-Yves Beaulieu, Konstantinos Vakalopoulos, Morgan Gauthier, Cindy Bouvet, Amanda Gonzalez, Vanessa Morello, Christina Steiger, Stefanie Hirsiger, Benjamin Alan Lipsky, Ilker Uçkay
Journal: Annals of the Rheumatic Diseases (2019)

The optimal duration of postsurgical antibiotic therapy for adult native joint bacterial arthritis remains unknown.We conducted a prospective, unblinded, randomised, non-inferiority study comparing either 2 or 4 weeks of antibiotic therapy after surgical drainage of native joint bacterial arthritis in adults. Excluded were implant-related infections, episodes without surgical lavage and episodes with a follow-up of less than 2 months.We enrolled 154 cases: 77 in the 4-week arm and 77 in the 2-week arm. Median length of intravenous antibiotic treatment was 1 and 2 days, respectively. The median number of surgical lavages was 1 in both arms. Recurrence of infection was noted in three patients (2%): 1 in the 2-week arm (99% cure rate) and 2 in the 4-week arm (97% cure rate). There was no difference in the number of adverse events or sequelae between the study arms. Of the overall 154 arthritis cases, 99 concerned the hand and wrist, for which an additional subgroup analysis was performed. In this per-protocol subanalysis, we noted three recurrences: one in the 2-week arm (97 % cure); two in the 4-week arm (96 % cure) and witnessed sequelae in 50% in the 2-week arm versus 55% in the 4-week arm, of which five (13%) and six (13%) needed further interventions.After initial surgical lavage for septic arthritis, 2 weeks of targeted antibiotic therapy is not inferior to 4 weeks regarding cure rate, adverse events or sequelae and leads to a significantly shorter hospital stay, at least for hand and wrist arthritis.NCT03615781.
Abstract 12382: A Novel Angiogenic Adipokine Neuregulin-4 Preserves Metabolic Homeostasis by Regulating Adipose Tissue Angiogenesis
Authors: Dhite Bayu Nugroho, Koji Ikeda, Agian Jeffilano Barinda, Donytra Arby Wardhana, Ken-ichi Hirata, Noriaki Emoto
Journal: Circulation (2015)

Adipose tissue angiogenesis is a crucial factor for the maintenance of adipocyte functions, impairment of which causes systemic metabolic disorders. Adipocytes produce various angiogenic factors; however the interactive communications between endothelial cells (EC) and mature adipocytes in the regulation of adipose tissue homeostasis remains largely unexplored. We searched for genes that is highly expressed in adipose tissue, and the expression of which is regulated by EC. We found several genes with unknown functions; one of which encodes neuregulin-4 (Nrg4), a latest member of neuregulin family that are part of the EGF family proteins. Here, we show that Nrg4 is a paracrine-acting adipokine that regulates adipose tissue angiogenesis through a communication between EC and mature adipocytes. Nrg4 is highly and preferentially expressed in mature adipocytes, while its receptor is expressed in EC but not in adipocyte. Nrg4 activated endothelial angiogenic functions and enhanced angiogenesis both in vitro and in vivo. Of note, Nrg4 expression was substantially reduced in white adipose tissue during diet-induced obesity. Furthermore, targeted activation of Nrg4 in adipocytes (aP2-Nrg4-Tg) led to significantly improved glucose tolerance and better insulin sensitivity comparing to those in WT mice after a high fat-diet, while their body weight was similar. Adipose tissue angiogenesis was enhanced in aP2-Nrg4-Tg mice, resulting in ameliorated adipose tissue hypoxia and inflammation. Interestingly, expression of Nrg4 in adipocytes was negatively regulated by EC and/or blood vessels, constituting a negative-feedback loop for adipose Nrg4. These data unveiled a significant role of interactive communication between EC and mature adipocytes in the regulation of adipose tissue angiogenesis, and shed light on Nrg4 as a therapeutic target for the treatment of metabolic disorders associated with obesity.