tbuckley/cabot-search huggingface dataset:
High levels of butyrate and propionate in early life are associated with protection against atopy
Authors: Caroline Roduit, Remo Frei, Ruth Ferstl, Susanne Loeliger, Patrick Westermann, Claudio Rhyner, Elisa Schiavi, Weronika Barcik, Noelia Rodriguez‐Perez, Marcin Wawrzyniak, Christophe Chassard, Christophe Lacroix, Elisabeth Schmausser‐Hechfellner, Martin Depner, Erika von Mutius, Charlotte Braun‐Fahrländer, Anne M. Karvonen, Pirkka V. Kirjavainen, Juha Pekkanen, Jean‐Charles Dalphin, Josef Riedler, Cezmi Akdis, Roger Lauener, Liam O'Mahony
Journal: Allergy (2018)

Dietary changes are suggested to play a role in the increasing prevalence of allergic diseases and asthma. Short-chain fatty acids (SCFAs) are metabolites present in certain foods and are produced by microbes in the gut following fermentation of fibers. SCFAs have been shown to have anti-inflammatory properties in animal models. Our objective was to investigate the potential role of SCFAs in the prevention of allergy and asthma.We analyzed SCFA levels by high-performance liquid chromatography (HPLC) in fecal samples from 301 one-year-old children from a birth cohort and examined their association with early life exposures, especially diet, and allergy and asthma later in life. Data on exposures and allergic diseases were collected by questionnaires. In addition, we treated mice with SCFAs to examine their effect on allergic airway inflammation.Significant associations between the levels of SCFAs and the infant's diet were identified. Children with the highest levels of butyrate and propionate (≥95th percentile) in feces at the age of one year had significantly less atopic sensitization and were less likely to have asthma between 3 and 6 years. Children with the highest levels of butyrate were also less likely to have a reported diagnosis of food allergy or allergic rhinitis. Oral administration of SCFAs to mice significantly reduced the severity of allergic airway inflammation.Our results suggest that strategies to increase SCFA levels could be a new dietary preventive option for allergic diseases in children.
Abdominal Pain in Pregnancy
Authors: Julie Vaynshtein, Ohad Guetta, Ilya Replyansky
Journal: JAMA Surgery (2018)

A healthy 29-year- old pregnant woman, with 34 weeks’ gestational age, presented to the ER emergency room with diffused acute abdominal pain and vomiting. The pain was located in the periumbilical region and intensified within a few hours. What is your diagnosis?
Inhibition of epidermal growth factor receptor (EGFR) signaling enhances TRAIL-induced apoptosis in breast cancer cells by a PI3-kinase dependant but Akt independent mechanism
Authors: Monzur Rahman, Jing Bao, Marion M. Nau, Dao M. Nguyen, Stan Lipkowitz
Journal: Cancer Research (2006)

745   The EGFR is frequently expressed in breast cancer cells and its expression has been associated with poor prognosis, increased risk of recurrence, and poor response to endocrine therapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of cancer cell lines. However, we have shown previously that the majority of breast cancer cell lines are resistant to TRAIL-mediated apoptosis. We investigated if inhibition of EGFR signaling could enhance TRAIL-induced apoptosis in breast cancer cells. We found that AG 1478, a specific tyrosine kinase inhibitor of the EGFR, enhanced TRAIL-induced apoptosis in both TRAIL-sensitive and TRAIL-resistant breast cancer cell lines which expressed EGFR ( i.e. , MB231 and MB468). In contrast, AG 1478 did not increase the TRAIL sensitivity in the EGFR expressing, non-transformed MCF10A cell line. The combination of AG 1478 and TRAIL resulted in the dramatically enhanced activation of caspases-8/10, -9, and -3 and the cleavage of the caspase substrate, PARP, compared to TRAIL or AG 1478 alone. Apoptosis induced by the combination of AG 1478 and TRAIL and by TRAIL alone was inhibited by the pan-caspase inhibitor ZVAD-FMK. Investigation of downstream signaling pathways in cell lines in which TRAIL-induced apoptosis was enhanced by AG 1478 revealed inhibition of Akt activity. However, direct inhibition of Akt by infecting breast cancer cells with an adenovirus containing dominant negative Akt did not increase TRAIL sensitivity. Also transfecting those same cell lines with constitutively active Akt did not affect TRAIL sensitivity. These results demonstrate that inhibition of Akt is not responsible for the increase in TRAIL-mediated apoptosis induced by EGFR inhibition. Inhibition of PI3-kinase activity with LY-294002 enhanced TRAIL-mediated apoptosis in the breast cancer cell lines similar to that induced by the inhibition of EGFR. Transfection of cells with a constitutively active catalytic subunit of PI3-kinase reduced the effect of EGFR inhibition. Together these data suggest that EGFR inhibition enhances TRAIL-mediated apoptosis by a PI3-kinase dependent but Akt independent mechanism.
Antibiotic and acid-suppression medications during early childhood are associated with obesity
Authors: Christopher M Stark, Apryl Susi, Jill Emerick, Cade M Nylund
Journal: Gut (2018)

Gut microbiota alterations are associated with obesity. Early exposure to medications, including acid suppressants and antibiotics, can alter gut biota and may increase the likelihood of developing obesity. We investigated the association of antibiotic, histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) prescriptions during early childhood with a diagnosis of obesity.We performed a cohort study of US Department of Defense TRICARE beneficiaries born from October 2006 to September 2013. Exposures were defined as having any dispensed prescription for antibiotic, H2RA or PPI medications in the first 2 years of life. A single event analysis of obesity was performed using Cox proportional hazards regression.333 353 children met inclusion criteria, with 241 502 (72.4%) children prescribed an antibiotic, 39 488 (11.8%) an H2RA and 11 089 (3.3%) a PPI. Antibiotic prescriptions were associated with obesity (HR 1.26; 95% CI 1.23 to 1.28). This association persisted regardless of antibiotic class and strengthened with each additional class of antibiotic prescribed. H2RA and PPI prescriptions were also associated with obesity, with a stronger association for each 30-day supply prescribed. The HR increased commensurately with exposure to each additional medication group prescribed.Antibiotics, acid suppressants and the combination of multiple medications in the first 2 years of life are associated with a diagnosis of childhood obesity. Microbiota-altering medications administered in early childhood may influence weight gain.
Balancing the Risks and Desires for Pregnancy in Older Mothers
Authors: Stephanie B. Teal, Jeanelle Sheeder
Journal: JAMA Internal Medicine (2018)

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Equitably improving outcomes for cancer survivors and supporting caregivers: A blueprint for care delivery, research, education, and policy
Authors: Catherine M. Alfano, Corinne R. Leach, Tenbroeck G. Smith, Kim D. Miller, Kassandra I. Alcaraz, Rachel S. Cannady, Richard C. Wender, Otis W. Brawley
Journal: CA A Cancer Journal for Clinicians (2018)

Cancer care delivery is being shaped by growing numbers of cancer survivors coupled with provider shortages, rising costs of primary treatment and follow-up care, significant survivorship health disparities, increased reliance on informal caregivers, and the transition to value-based care. These factors create a compelling need to provide coordinated, comprehensive, personalized care for cancer survivors in ways that meet survivors' and caregivers' unique needs while minimizing the impact of provider shortages and controlling costs for health care systems, survivors, and families. The authors reviewed research identifying and addressing the needs of cancer survivors and caregivers and used this synthesis to create a set of critical priorities for care delivery, research, education, and policy to equitably improve survivor outcomes and support caregivers. Efforts are needed in 3 priority areas: 1) implementing routine assessment of survivors' needs and functioning and caregivers' needs; 2) facilitating personalized, tailored, information and referrals from diagnosis onward for both survivors and caregivers, shifting services from point of care to point of need wherever possible; and 3) disseminating and supporting the implementation of new care methods and interventions.
Photopolymerizable Platelet Lysate Hydrogels for Customizable 3D Cell Culture Platforms
Authors: Sara C. Santos, Catarina A. Custódio, João F. Mano
Journal: Advanced Healthcare Materials (2018)

Abstract 3D cell culture platforms have emerged as a setting that resembles in vivo environments replacing the traditional 2D platforms. Over the recent years, an extensive effort has been made on the development of more physiologically relevant 3D cell culture platforms. Extracellular matrix–based materials have been reported as a bioactive and biocompatible support for cell culture. For example, human plasma derivatives have been extensively used in cell culture. Despite all the promising results, in most cases these types of materials have poor mechanical properties and poor stability in vitro. Here plasma‐based hydrogels with increased stability are proposed. Platelet lysates are modified by addition of methacryloyl groups (PLMA) that polymerize in controlled geometries upon UV light exposure. The hydrogels could also generate porous scaffolds after lyophilization. The results show that PLMA materials have increased mechanical properties that can be easily adjusted by changing PLMA concentration or modification degree. Cells readily adhere, proliferate, and migrate, exhibiting high viability when encapsulated in PLMA hydrogels. The innovation potential of PLMA materials is based on the fact that it is a complete xeno‐free solution for human cell culture, thus an effective alternative to the current gold standards for 3D cell culture based on animal products.
Carfilzomib-Lenalidomide-Dexamethasone Versus Bortezomib-Lenalidomide-Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma: Results from the Prospective, Longitudinal, Observational Commpass Study
Authors: Ola Landgren, David S Siegel, Daniel Auclair, Ajai Chari, Michael Boedigheimer, Tim Welliver, Khalid Mezzi, Karim Iskander, Andrzej Jakubowiak
Journal: Blood (2018)
FRI0235 Effect of serum uric acid (SUA) on gout flares (GF) and tophi resolution in gout patients. pooled post hoc analysis of clear 1 &amp; clear 2 trials
Authors: F. Perez-Ruiz, P. Richette, R.G. Karra, I. Wild, H. Hagedorn, P. Kandaswamy, T. Bardin
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Gout is caused by crystal deposition due to persistent hyperuricemia. EULAR<sup>1</sup> and other guidelines recommend a target sUA of &lt;5–6 mg/dL (0.30 to 0.36 mmol/L) depending on severity. Despite physiological plausibility and abundant literature evidence there is an absence of consensus among physicians on the targets and necessity of long term urate lowering therapy (ULT)<sup>2</sup>. <h3>Objectives</h3> To investigate the effects of sUA and target sUA &lt;5–6 mg/dl with respect to the occurrence of GF, flares requiring treatment (GFRT) and the percent change in the area of tophi (TR) from baseline irrespective of treatment arms. <h3>Methods</h3> Data of 1213 patients (PT) was pooled from CLEAR trials<sup>3&amp;4</sup>, two randomised, double-blind, placebo-controlled Phase 3 studies that evaluated Lesinurad 200/400 mg daily in combination with allopurinol vs allopurinol. Prophylaxis for flares was given from baseline to month (M) 5. PT who met the sUA target of &lt;5–6 mg/dl at M 6 and 12 were compared against those not on target with respect to the TR from baseline using a Wilcoxon test. In addition, the mean sUA measurements for PT with or without GFs and GFRT was compared at M 6 and 12 using a t-test. <h3>Results</h3> PT with sUA on target &lt;5–6 mg/dl showed a larger decrease (increase in percent reduction) in area of tophi with a difference of 27.9%, and 17.3% at M 12 only compared to the PT not on target (table 1). The mean sUA levels were 0.227 mg/dL lower for PT with GF and 0.389 mg/dL lower for PT with GFRT compared to PT without GF and GFRT at M 6 (table 2), but not at M 12. <h3>Conclusions</h3> These results confirm that sUA on target &lt;5–6 mg/dl is essential for TR, and longer the control better the TR. The lower mean sUA levels for PT with GF and GFRT was observed at M6 and not at M 12, maybe owing to the fact that flares are common during the first months of ULT initiation and then taper off and urate deposits were more fragile and not completely dissolved. Also M 6 and 12 may not be optimal to observe statistically significant differences between treatments with respect to TR, GF and GFRT. <h3>References</h3> [1] Richette P, et al. Ann Rheum Dis 2017;76:29−42. [2] Qaseem A, et al. Ann Intern Med2017;166(1):58–68. [3] Saag KG, et al. Arthritis Rheumatol2017;69:203–12. [4] Bardin T, et al. Ann Rheum Dis2017;76:811–20. <h3>Disclosure of Interest</h3> F. Perez-Ruiz Consultant for: Grünenthal, Menarini, Speakers bureau: Grünenthal, Menarini, P. Richette Consultant for: Grünenthal, Speakers bureau: Grünenthal, R. Karra Employee of: Grünenthal, I. Wild Employee of: Grünenthal, H. Hagedorn Employee of: Grünenthal, P. Kandaswamy Employee of: Grünenthal, T. Bardin Consultant for: Grünenthal
Results on sports-related injuries in children from NHS emergency care dataset Oxfordshire pilot: an ecological study
Authors: Graham Kirkwood, Thomas C Hughes, Allyson M Pollock
Journal: Journal of the Royal Society of Medicine (2018)

To analyse and report on sports-related injuries using enhanced injury data collected by the testbed for the NHS emergency care injury data set and admissions data collected from inpatients.Ecological study design.Two Oxfordshire NHS England hospitals.Emergency department attendees and inpatients aged 0-19 years with sports injuries.Data were analysed from 1 January 2012 to 30 March 2014 by age, gender sport, injury location, injury mechanism and diagnosis including concussion/post-concussion, bone fractures and ligament damage. Admissions data were analysed from 1 January 2012 to 24 January 2015.Children and adolescents aged 0-19 years accounted for almost half (47.4%) of sports injury-related emergency department attendances and almost one-quarter (23.5%) of sports injury-related admissions for all ages. The highest rates of attendance occurred at 14 years for boys (68.22 per 1000 person-years) and 12 years for girls (33.72 per 1000 person-years). For male 0-19-year-olds the three main sports were (in order) football (soccer), rugby union and rugby league and for females, trampoline, netball and horse-riding. The largest gender differences were in netball where injuries were predominantly in females and in wheeled motorsports where injuries were predominantly in males. Almost one-quarter of emergency department sports-related injuries recorded were fractures, the highest percentage to the upper limbs.Public health departments in local authorities and schools should consider target sports injury prevention at children in the first four years of secondary school. For younger age groups, trampolines in the home warrant improved safety. Rugby and horse-riding should also be a focus for interventions.
Surgical Resection Versus Transarterial Chemoembolization for Intermediate Stage Hepatocellular Carcinoma (BCLC‐B): An Unsolved Question
Authors: Ismail Labgaa, Nicolas Demartines, Emmanuel Melloul
Journal: Hepatology (2018)

Potential conflict of interest: Nothing to report. TO THE EDITOR: We have read the article of Hyun et al. with great interest.1 We commend the authors for this study that tackles a crucial point in the treatment of hepatocellular carcinoma (HCC). There is a critical need to refine and eventually to expand the selection criteria of HCC patients who may benefit from curative therapies such as surgical resection (SR). There is accumulating evidence on improved survival after SR as opposed to transarterial chemoembolization (TACE) in patients with intermediate stage HCC (Barcelona Clinic Liver Cancer Stage B; BCLC‐B), although American (American Association for the Study of Liver Diseases) and European (European Association for the Study of the Liver; EASL) consensus guidelines recommend TACE in this setting.2 To investigate the advantage of SR in HCC patients with intermediate‐ (BCLC‐B) and advanced‐stage (BCLC‐C) HCC, the authors performed a systematic review and meta‐analysis of studies comparing SR and TACE; their results showed increased 5‐year survival rates in patients undergoing SR, in both stages. The main debate is on whether a subset of HCC patients with BCLC‐B should undergo SR rather than TACE. We would like to address two shortcomings of this meta‐analysis: (1) one study (by Luo et al.) included patients with sequential treatments (SR and TACE)4; it is therefore difficult to collect accurate survival data from this article, and, more important, (2) 4 of 9 analyzed studies included patients with single large HCC. As stipulated by the recent EASL guidelines for HCC, the current intermediate HCC definition includes a wide range of patients, in particular large solitary HCC beyond 5 cm with an expansive growth. This large definition triggers controversies and refinement is needed. If technically feasible, those patients may benefit from surgical resection and should be classified as BCLC‐A.3 As a consequence, the meta‐analysis of Hyun et al. included a substantial number of patients who were rather at BCLC‐A stage. For these reasons, the question of SR versus TACE for HCC patients at intermediate stage remains unsolved and other meta‐analyzes or randomized controlled trials, strictly including BCLC‐B HCC, are needed.
Mouse Models of Nonalcoholic Steatohepatitis: Toward Optimization of Their Relevance to Human Nonalcoholic Steatohepatitis
Authors: Geoff Farrell, Jörn M. Schattenberg, Isabelle Leclercq, Matthew M. Yeh, Robert Goldin, Narci Teoh, Detlef Schuppan
Journal: Hepatology (2018)

Nonalcoholic steatohepatitis (NASH) arises from a variable interplay between environmental factors and genetic determinants that cannot be completely replicated in animals. Notwithstanding, preclinical models are needed to understand NASH pathophysiology and test mechanism‐based therapies. Among several mouse models of NASH, some exhibit the key pathophysiologic as well as histopathologic criteria for human NASH, whereas others may be useful to address specific questions. Models based on overnutrition with adipose restriction/inflammation and metabolic complications, particularly insulin resistance, may be most useful to investigate critical etiopathogenic factors. In‐depth pathologic description is required for all models. Some models demonstrate hepatocyte ballooning, which can be confused with microvesicular steatosis, whereas demonstration of an inflammatory infiltrate and pattern of liver fibrosis compatible with human NASH is desirable in models used for pharmacologic testing. When mice with specific genetic strains or mutations that cause overeating consume a diet enriched with fat, modest amounts of cholesterol, and/or simple sugars ("Western diet"), they readily develop obesity with liver disease similar to human NASH, including significant fibrosis. Purely dietary models, such as high‐fat/high‐cholesterol, Western diet, and choline‐deficient, amino acid–defined, are similarly promising. We share concern about using models without weight gain, adipose pathology, or insulin resistance/hyperinsulinemia and with inadequate documentation of liver pathology. NASH‐related fibrosis is a key endpoint in trials of possible therapies. When studied for this purpose, NASH models should be reproducible and show steatohepatitis (ideally with ballooning) and at least focal bridging fibrosis, while metabolic factors/disordered lipid partitioning should contribute to etiopathogenesis. Because murine models are increasingly used to explore pharmacologic therapies for NASH, we propose a minimum set of requirements that investigators, drug companies, and journals should consider to optimize their translational value.
US drug prices should be tied to foreign prices to tackle “global freeloading,” says Trump
Authors: Owen Dyer
Journal: BMJ (2018)

The Trump administration has proposed indexing the prices that Medicare pays for drugs to those paid by health systems in other developed countries, to help bring down the relatively high prices paid by US patients.

The prices the US government pays through Medicare for 27 leading drugs are, on average, 80% higher than those that buyers pay in other developed countries, said a report from the US Department of Health timed to coincide with President Trump’s press conference announcing an “international pricing index.”1

Under the five year proposal the US government would, in an unspecified “50% of the country,” pay steadily lower reimbursements under Medicare part B, the prescription drug coverage programme, until it was paying just 26% more than the “international” price. This, the …
Association between human herpes virus seropositivity and frailty in the elderly: A systematic review and meta-analysis
Authors: Aline Carla Araújo Carvalho, Mário Luis Tavares Mendes, Victor Santana Santos, Diego Moura Tanajura, Marco Antônio Prado Nunes, Paulo Ricardo Saquete Martins-Filho
Journal: Ageing Research Reviews (2018)
Animal protein intake and hepatic steatosis in the elderly
Authors: George Yizhou Tang, Jake Peter Mann
Journal: Gut (2018)

We read with interest the work by Alferink et al ,1 which reports that intake of animal protein, but not that of monosaccharides and disaccharides, was found to be independently associated with non-alcoholic fatty liver disease (NAFLD). This is a surprising finding from a well-conducted cohort study that facilitated adjustment for metabolic covariates, in addition to sociodemographics and other lifestyle factors. However, we have reservations about the generalisability of these findings to patients with NAFLD or non-alcoholic steatohepatitis (NASH).

The studied population had an average age of 70 years, which is unusual for …
Moderate-intensity endurance-exercise training in patients with sickle-cell disease without severe chronic complications (EXDRE): an open-label randomised controlled trial
Authors: Barnabas Gellen, Laurent A Messonnier, Frédéric Galactéros, Etienne Audureau, Angèle N Merlet, Thomas Rupp, Sandrine Peyrot, Cyril Martin, Léonard Féasson, Pablo Bartolucci, Anoosha Habibi, Emma Guillet, Justine Gellen-Dautremer, Jean-Antoine Ribeil, Jean-Benoit Arlet, Sarah Mattioni, Jugurtha Berkenou, Noemie Delrieux, François Lionnet, Jean-François Grenot, Jose Mira, Arthur Peyrard, Roxane Lacroix, Arnauld Garcin, Gaetana Di Liberto, Christophe Hourdé
Journal: The Lancet Haematology (2018)