tbuckley/cabot-search huggingface dataset:
Response to Comment on Cheng et al. Trends and Disparities in Cardiovascular Mortality Among U.S. Adults With and Without Self-Reported Diabetes, 1988–2015. Diabetes Care 2018;41:2306–2315
Authors: Yiling J. Cheng, Giuseppina Imperatore, Ann L. Albright, Edward W. Gregg
Journal: Diabetes Care (2019)

We thank Manicardi et al. (1) for their insightful discussion of potential factors affecting our study of cardiovascular disease (CVD) mortality trends in the population with diabetes (2). Changes in diagnostic criteria and early detection of diabetes could indeed have affected the risk level and changes in rates of CVD differentially over time. We further agree that the population today is likely much different from that in the 1980s, perhaps due to the significant …
YIA19-007: Patient-Derived Tumor Organoids for Drug Discovery of High-Risk Hepatoblastoma
Authors: Liqin Zhu, Liyuan Li, Laura Hamel, Dolores Lopez-Terrada
Journal: Journal of the National Comprehensive Cancer Network (2019)

Hepatoblastoma (HB), the most common liver cancer in children, has become the fastest growing pediatric cancer in the United States. The extent of tumor resection remains the most significant prognostic factor for HB, leaving children with unresectable HB limited treatment options and a largely stagnant survival rate below 40%. Due to the rareness and heterogeneity of this pediatric solid tumor, clinically-relevant, patient-derived models are in urgent need in order to develop more effective therapy for individual patients. Recent studies on many adult cancers have proven patient-derived organoids (PDOs) are faithful in vitro models mimicking disease biology and patient drug response. Via the support from a 2017 NCCN Young Investigator Award, our lab tested HB organoid culture using a large cohort of patient-derived xenografts (PDXs). To date, we have grown HB PDOs from PDXs derived from primary, metastatic, and recurrent tumors at 82% (11/14), 100% (7/7), and 100% (2/2) successful rate, respectively. These HB PDOs displayed histopathology consistent with that of their parental tumors. When we tested the first group of 6 PDO lines to the 10 drugs included in recently opened COG AHEP1531 clinical trial for pediatric liver cancer, we found 2 lines whose parental tumors did not respond to HB standard-of-care cisplatin. They showed the same resistance to cisplatin as well as 2 other platinum-based drugs, carboplatin and oxaliplatin. PDOs derived from 2 matched primary and metastatic tumors showed most similar overall response. These results provided encouraging evidence supporting the notion that HB PDOs mimic patient drug response. Intriguingly, in a subset of cisplatin-resistant HB PDOs, vincristine and gemcitabine showed strong antitumor activities, which we will further validate in vivo using a novel neonatal liver xenograft model developed in our lab. To accurately model the unique early developmental tumor microenvironment (TME) of HB, we have successfully engrafted HB cells into the liver of postnatal day 5–7 mice. We found TME of the neonatal liver, indeed, has a strong and unique metastasis-promoting effect compared to that of the adult liver. With this first PDO effort on pediatric HB and our exciting preliminary data, we are confident that we are approaching our long-term goal of building an integrated “HB PDO Clinic” to enable accurate evaluation of disease risk and therapeutic response to facilitate personalized HB patient care.
Characterization of gut microbiota composition and functions in patients with chronic alcohol overconsumption
Authors: Steinar Traae Bjørkhaug, Håvard Aanes, Sudan Prasad Neupane, Jørgen G. Bramness, Stine Malvik, Christine Henriksen, Viggo Skar, Asle W. Medhus, Jørgen Valeur
Journal: Gut Microbes (2019)

Excessive alcohol intake can alter the gut microbiota, which may underlie the pathophysiology of alcohol-related diseases. We examined gut microbiota composition and functions in patients with alcohol overconsumption for >10 years, compared to a control group of patients with a history of no or low alcohol intake. Faecal microbiota composition was assessed by 16S rRNA sequencing. Gut microbiota functions were evaluated by quantification of short-chain fatty acids (SCFAs) and predictive metagenome profiling (PICRUSt). Twenty-four patients, mean age 64.8 years (19 males), with alcohol overconsumption, and 18 control patients, mean age 58.2 years (14 males) were included. The two groups were comparable regarding basic clinical variables. Nutritional assessment revealed lower total score on the screening tool Mini Nutritional Assessment, lower muscle mass as assessed by handgrip strength, and lower plasma vitamin C levels in the alcohol overconsumption group. Bacteria from phylum Proteobacteria were found in higher relative abundance, while bacteria from genus Faecalibacterium were found in lower relative abundance in the group of alcohol overconsumers. The group also had higher levels of the genera Sutterella, Holdemania and Clostridium, and lower concentration and percentage of butyric acid. When applying PICRUSt to predict the metagenomic composition, we found that genes related to invasion of epithelial cells were more common in the group of alcohol overconsumers. We conclude that gut microbiota composition and functions in patients with alcohol overconsumption differ from patients with low consumption of alcohol, and seem to be skewed into a putative pro-inflammatory direction.
Thymic Carcinoma With Thyroid Transcription Factor-1 Expression: An Insidious Pitfall
Authors: Nicola Monaci, Giovanni Maria Comacchio, Enrico Verderi, Giuseppe Marulli, Marco Schiavon, Francesco Fortarezza, Federica Pezzuto, Fiorella Calabrese, Federico Rea
Journal: Journal of Thoracic Oncology (2019)
Membrane Radiolabelling of Exosomes for Comparative Biodistribution Analysis in Immunocompetent and Immunodeficient Mice - A Novel and Universal Approach
Authors: Farid N. Faruqu, Julie Tzu-Wen Wang, Lizhou Xu, Luke McNickle, Eden Ming-Yiu Chong, Adam Walters, Mark Gurney, Aled Clayton, Lesley A. Smyth, Robert Hider, Jane Sosabowski, Khuloud T. Al-Jamal
Journal: Theranostics (2019)

fo r c o m p a r a tiv e bio di s t ri b u tio n a n aly sis in i
Oleogels: Gels without Vapor Pressure: Soft, Nonaqueous, and Solvent‐Free Supramolecular Biomaterials for Prospective Parenteral Drug Delivery Applications (Adv. Healthcare Mater. 6/2019)
Authors: Anthony Tabet, Chun Wang
Journal: Advanced Healthcare Materials (2019)

In article number 1800908, Anthony Tabet and Chun Wang review strategies to design supramolecular solvent-free gels that lack appreciable vapor pressure. These networks may consist of nanoparticles with tailored surfaces bridged by hydrophobic or amphiphilic polymer chains in the melt. Such oleogel-like solvent-free materials are distinctly different - both in structure and property - than hydrogels and organogels and have much potential in the local delivery of hydrophobic drugs and combination drug therapies.
Response to: ‘MYCYC, unravelling the long road ahead in ANCA-associated vasculitis’ by Jain et al
Authors: Lorraine Harper, Rachel B Jones
Journal: Annals of the Rheumatic Diseases (2019)

In their letter to the editor, Jain et al raised some issues regarding our recent paper. We appreciate their interest in our study and their positive comments.1 

Jain et al highlight the fact that the presenting glomerular filtration rate (GFR) did not improve considerably during the study and were concerned that this raised the suspicion that there was a component of chronicity associated with the underlying disease. This is unlikely; at study entry it was an inclusion criteria that all patients had newly diagnosed disease, not relapsing disease and had not received either rituximab therapy or more than one intravenous pulse of cyclophosphamide or more than 2 weeks daily oral cyclophosphamide. Renal vasculitis can present in a number of different ways; from microscopic haematuria with a normal renal function to the syndrome of rapidly progressive glomerulonephritis necessitating dialysis. The stability of GFR over the course of the study reflects the facts that GFR at entry was relatively high (51 mL/min), that patients with a clinical syndrome of rapidly progressive glomerulonephritis were excluded (defined as a 20% fall in GFR over a 2 weeks), that patients with a GFR <30 mL/min were excluded and that active renal vasculitis was not a requirement for entry. Eighty-one per cent of patients had active renal …
miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis
Authors: Jiangyi Wu, Liang Kuang, Cheng Chen, Junjun Yang, Wei-Nan Zeng, Tao Li, Hao Chen, Shu Huang, Zhenlan Fu, Jiamiao Li, Renfeng Liu, Zhenhong Ni, Lin Chen, Liu Yang
Journal: Biomaterials (2019)
Zika warnings eased around the world as growing immunity brings lower risk
Authors: Owen Dyer
Journal: BMJ (2019)

The World Health Organization has said that it will relax its Zika travel recommendations in the coming weeks, days after the US Centers for Disease Control (CDC) eased warnings which at various times have advised pregnant women or those seeking to become pregnant to avoid 88 countries.1

The changes are similar to those announced in February by Public Health England and the National Travel Health Network and Centre.2

In all three cases, agencies …
Potential Consequences of Patient Complications for Surgeon Well-being
Authors: Sanket Srinivasa, Jason Gurney, Jonathan Koea
Journal: JAMA Surgery (2019)

Patient complications occur in all areas of surgery, and managing them is an important part of surgical practice. Several investigations have examined whether surgeon health affects patient outcomes; however, to date, whether adverse patient outcomes affect surgeon well-being has not been comprehensively examined.To examine how surgical complications in their patients affect the health of surgeons, in particular emotional outcomes, coping strategies, and support mechanisms.A systematic literature review was conducted to identify studies evaluating how patient complications affect surgeons with the aim of determining emotional outcomes, coping strategies, and support mechanisms. Studies pertaining to burnout alone or not conducted in surgeons were excluded. The databases searched included MEDLINE, Embase, PubMed, Web of Science, and Google Scholar, with all literature available on these data sets until the search date of May 1, 2018; collected data were analyzed between May 2 and June 1, 2018. The reference lists of all included studies, as well as related review articles, were manually searched to identify further relevant studies. An inductive approach was used to identify common themes.Nine case series or cross-sectional studies from the United Kingdom or North America were found (8518 unique participants), with 1 study in surgical trainees. Across all studies, surgeons were affected emotionally after complications, with adverse consequences in their professional and personal lives. Four themes were identified within the literature: the adverse emotional influence of complications (anxiety, guilt, sadness, shame, interference with professional and leisure activities) after intraoperative adverse events; coping mechanisms used by surgeons and trainees (limited discussion with colleagues, exercise, artistic or creative outlets, alcohol and substance abuse); institutional support mechanisms and barriers to support (clinical conferences, discussion with mentors, a perception that emotional distress would be perceived as a constitutional weakness); and the consequences of complications in future clinical practice (changes in practice, introduction of protocols, education of staff members, and participating in root-cause analysis).This study's findings suggest that complications affect surgeons adversely across multiple domains. Further efforts are required at a personal, departmental, institutional, and organizational level to provide effective support. This review highlights that the psychological consequences of patient complications seem to be an important occupational health issue for surgeons.
HSR19-109: The Healthy Days Measure in a Metastatic Castration-Resistant Prostate Cancer Population Treated With Novel Oral Therapies
Authors: Neil M. Schultz, Eleanor O. Caplan, Sam Wilson, Richard Sheer, Brandon T. Suehs
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Health-related quality of life (HRQoL) is an important patient-reported outcome to assess in patients with prostate cancer (PC). A variety of general and disease-specific measures have been developed, but there is a lack of evidence on performance of the Centers for Disease Control and Prevention (CDC) Healthy Days (HDs) measure in a population with metastatic disease relative to other validated scales. Objective: To report and understand general HRQoL using the HDs instrument in patients with metastatic PC taking novel oral therapies and compare results to validated scales. Methods: Patients currently enrolled in a Medicare Advantage or Prescription Drug plan treated with enzalutamide or abiraterone acetate were eligible for inclusion. Patients undertook a telephone-based survey including 2 HRQoL questionnaires (Short-Form 36, version 2 [SF-36] survey and the CDC HDs measures), the Service Satisfaction with Cancer Care (SCA) instrument, and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). Higher scores indicated higher HRQoL on all surveys, except the HDs scale, where higher numbers indicated lower HRQoL (ie, unhealthy days). Pearson correlations with SF-36 and HDs measures and SCA and FACIT-Fatigue were assessed. Results: 1,745 patients were eligible to participate; 269 completed the survey and were included in the analysis. The mean (standard deviation) age was 74.4 (±7.3) years and 82% were Caucasian. Patients had lower physical HRQoL and a higher number of physically unhealthy days, compared to mental health impacts on both scales. The mean Physical Component Summary (PCS) and Mental Component Summary (MCS) norm-based scores for the SF-36 were 39.9 (±10.6) and 53.4 (±10.4). The mean number of physically and mentally unhealthy days reported in a 30-day period were 9.2 (±11.3) and 3.9 (±7.7), respectively. The unadjusted correlations between scores were all statistically significant ( P &lt;.05). Conclusions: The SF-36 and HDs measures both indicated physical health was impacted more than mental health in these patients. The correlations with both HRQoL measures and the other scales were similar in terms of magnitude and significance. This indicates that the HDs instrument may be a useful measure for assessment of general HRQoL in patients with metastatic PC and provides an understanding of general HRQoL in this population that can be utilized to identify opportunities for enhancing patient-centered care.
Life expectancy gap between rich and poor in England widens
Authors: Gareth Iacobucci
Journal: BMJ (2019)

England has seen “significant widening” in life expectancy between rich and poor people, largely because of a fall in how long women in the most deprived parts of the country live, the latest figures show.1

The Office for National Statistics data show that life expectancy at birth of males living in England’s most deprived areas was 74.0 years in the years 2015 to 2017, whereas it was 83.3 years in the least deprived, a gap of 9.3 years. Women in the least deprived areas of England were expected to live 78.7 years in 2015-17, while those in the most affluent were expected to live 86.2 years, a gap of 7.5 …
Abstract 111: Analysis of Successful Resuscitation for an Emergency in School Demonstrates Contribution of Teachers and Proposes Issue for Location of Automated External Defibrillator
Authors: Akiko Komori, Mamoru Ayusawa, Masataka Kato, Ami Chou, Hirofumi Watanabe, Yuriko Abe, Shino Jinbo, Hiroshi Kamiyama, Naokata Sumitomo, Shori Takahashi
Journal: Circulation (2014)

BACKGROUND: Considerable numbers of cardiac emergencies have been resuscitated without neurological sequel by public action of resuscitation and defibrillation. Since resuscitated cases are increasing also in Japanese schools, it is necessary to investigate factors for successful resuscitation. METHODS: Students resuscitated with AED were picked up from all issues in Mutual Aid Insurance System for Schools from 2005 to 2011. A total of 128 students were listed and classified to victims and survivors. Victims consisted of 62 cases that died or had brain sequel, and survivors consisted of 66 cases that recovered without sequel. Demography, causative disease, AED user, and the location of resuscitation in both groups were compared. RESULTS: Number of enrolled cases increased from 4 to 35 annually. School grade distribution is similar between two groups. Male to female ratio was 4.6 in victims and 2.1 in survivors (p=0.07). The most causative disease was cardiomyopathy (HCM) (22.6%) in victims, and ventricular fibrillation (VF) (28.8%) in survivors. They are the second in each other group. The third was congenital disease (8.1%) in victims, and long QT syndrome (LQT) in survivors (10.6%). In survivors, 6 cases were previously implanted ICD and 11 cases were implanted ICD after resuscitation and returned to school. Ambulance crew operated AED in 35.8% and 12.2% cases, and schoolteachers did in 64.2% and 87.8% of victims and survivors, respectively. Rate of successful resuscitation was significantly higher in cases operated by schoolteachers than that by ambulance crew (p&lt;0.01). Concerning location of resuscitation, 62.9% of victims and 71.2% of survivors were resuscitated at athletic field or gymnasium. Prevalence of resuscitation at swimming pool in victims was 2/62(3.2%) and was significantly less than that in survivors, which was 9/66(13.6%) (p&lt;0.05). Prevalence at classroom was 6/62(9.7%) in victims was significantly more than that in survivors, which was 1/66(1.5%) (p&lt;0.05). CONCLUSIONS: AED operation by teachers improve prognosis of cardiac emergencies in Japanese schools. AED should be placed near athletic field, gymnasium, pool, and ideally on the way to school for possible student.
Randomized Phase III Trial of Ibrutinib and Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Non–Germinal Center B-Cell Diffuse Large B-Cell Lymphoma
Authors: Anas Younes, Laurie H. Sehn, Peter Johnson, Pier Luigi Zinzani, Xiaonan Hong, Jun Zhu, Caterina Patti, David Belada, Olga Samoilova, Cheolwon Suh, Sirpa Leppä, Shinya Rai, Mehmet Turgut, Wojciech Jurczak, Matthew C. Cheung, Ronit Gurion, Su-Peng Yeh, Andres Lopez-Hernandez, Ulrich Dührsen, Catherine Thieblemont, Carlos Sergio Chiattone, Sriram Balasubramanian, Jodi Carey, Grace Liu, S. Martin Shreeve, Steven Sun, Sen Hong Zhuang, Jessica Vermeulen, Louis M. Staudt, Wyndham Wilson
Journal: Journal of Clinical Oncology (2019)

PURPOSE Ibrutinib has shown activity in non–germinal center B-cell diffuse large B-cell lymphoma (DLBCL). This double-blind phase III study evaluated ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in untreated non–germinal center B-cell DLBCL. PATIENTS AND METHODS Patients were randomly assigned at a one-to-one ratio to ibrutinib (560 mg per day orally) plus R-CHOP or placebo plus R-CHOP. The primary end point was event-free survival (EFS) in the intent-to-treat (ITT) population and the activated B-cell (ABC) DLBCL subgroup. Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. RESULTS A total of 838 patients were randomly assigned to ibrutinib plus R-CHOP (n = 419) or placebo plus R-CHOP (n = 419). Median age was 62.0 years; 75.9% of evaluable patients had ABC subtype disease, and baseline characteristics were balanced. Ibrutinib plus R-CHOP did not improve EFS in the ITT (hazard ratio [HR], 0.934) or ABC (HR, 0.949) population. A preplanned analysis showed a significant interaction between treatment and age. In patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS (HR, 0.579), PFS (HR, 0.556), and OS (HR, 0.330) and slightly increased serious adverse events (35.7% v 28.6%), but the proportion of patients receiving at least six cycles of R-CHOP was similar between treatment arms (92.9% v 93.0%). In patients age 60 years or older, ibrutinib plus R-CHOP worsened EFS, PFS, and OS, increased serious adverse events (63.4% v 38.2%), and decreased the proportion of patients receiving at least six cycles of R-CHOP (73.7% v 88.8%). CONCLUSION The study did not meet its primary end point in the ITT or ABC population. However, in patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS, PFS, and OS with manageable safety. In patients age 60 years or older, ibrutinib plus R-CHOP was associated with increased toxicity, leading to compromised R-CHOP administration and worse outcomes. Further investigation is warranted.
HSR19-085: A Real World Observational Assessment of the Impact of Immunotherapy on the Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)
Authors: Belqis El Ferjani, Sheenu Chandwani, Meita Hirschmann, Seydeh Dibaj, Emily Roarty, Jianjun Zhang, Waree Rinsurnogkawong, Jeff Lewis, Jack Lee, Jack A. Roth, Stephen Swisher, John V. Heymach, Thomas Burke, George R. Simon
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: NSCLC is the leading cause of cancer-related mortality worldwide. Recently reported clinical trials have firmly established the role of PD-1 and PD-L1 inhibitors in the treatment of patients (pts) with metastatic NSCLC (mNSCLC). We have established the prospective, observational, real-world Advanced Non-Small Cell Lung Holistic Registry (ANCHoR) to understand how the advent of immunotherapy impacts treatment choices and clinical outcomes. Objectives: The aim of this analysis is to measure the impact of immunotherapy on the treatment choice for the first-line treatment of mNSCLC and to determine the link between PD-L1 expression and the treatment choices made in routine clinical practice at the MD Anderson Cancer Center (MDA). Methods: From May 1, 2017, to June 30, 2018, English-speaking pts with mNSCLC at MDA who provided written informed consent were enrolled in ANCHoR and longitudinally followed. The PD-L1 testing rates were captured and the treatment decisions made were also captured and tabulated. The time of data cutoff for this study is June 30, 2018. Results: Of the 296 pts enrolled in the registry at the time of data cutoff, there were 49.7% males, 82.1% white, 45.9% ≥65 years old, 69.3% smokers, 83.1% with an initial stage IV diagnosis, 87.2% with nonsquamous histology, 36.1% with bone metastasis, 29.4% with brain metastasis, 43.2% with 0–1 performance status, and 21.6% with a known EGFR or ALK mutation. A total of 233 pts had been tested for PD-L1 (78.7%). Predominant reasons for not testing (63 pts) include not having available tissue (26 pts) or the test was not requested by the physician (31 pts). As of June 30, 2018, 38.5% of patients received immunotherapy as first-line therapy either as a single agent (18.9%, 56 pts) or in combination with chemotherapy (19.6%, 58 pts). Only 35.8% of the patients received platinum doublet chemotherapy alone. Two pts received chemotherapy combined with an anti-angiogenesis agent (0.68%). Targeted therapy was utilized either as a single agent (20.6%) or in combination with immunotherapy (2.4%). Conclusion: Immunotherapy is now utilized as a single agent or in combination in more than one-third of patients with mNSCLC. These numbers are expected to increase as data from recently reported studies get incorporated into common clinical practice. Compared to historic experience, there has been a dramatic decline in the use of chemotherapy with an anti-angiogenesis agent.