tbuckley/cabot-search huggingface dataset:
Brodalumab in psoriatic arthritis: results from the randomised phase III AMVISION-1 and AMVISION-2 trials
Authors: Philip J Mease, Philip S Helliwell, Kasper Fjellhaugen Hjuler, Kyle Raymond, Iain McInnes
Journal: Annals of the Rheumatic Diseases (2020)

Objective To compare the efficacy and safety of brodalumab, an interleukin-17 receptor subunit A inhibitor, with placebo, in patients with psoriatic arthritis (PsA). Methods Adult patients with active PsA and inadequate response to, or intolerance to, conventional treatment were enrolled into two phase III studies ( NCT02029495 and NCT02024646 ) and randomised 1:1:1 to receive subcutaneous brodalumab 140 mg or 210 mg or placebo at weeks 0, 1 and every 2 weeks up to 24 weeks. About 30% of patients had prior use of biologics. The primary endpoint for both studies was the American College of Rheumatology 20 (ACR20) response at week 16. Results 962 patients were randomised across the studies prior to early termination due to sponsor decision. The primary endpoint was met in both studies. Based on comparable design and eligibility criteria, data from both studies were pooled. Significantly more patients achieved ACR20 at week 16 in both brodalumab treatment groups (45.8% and 47.9% for 140 mg and 210 mg, respectively) versus placebo (20.9%) (p&lt;0.0001). Similar results were observed at week 24. Significantly higher proportions of patients receiving brodalumab achieved ACR50/70, Psoriasis Area and Severity Index 75/90/100 and resolution of dactylitis and enthesitis versus placebo (p&lt;0.01). Adverse event rates were similar across treatments at week 16 (54.4%, 51.6% and 54.5% for placebo, brodalumab 140 mg and 210 mg, respectively). No new safety signals were reported. Conclusion Brodalumab was associated with rapid and significant improvements in signs and symptoms of PsA versus placebo. Brodalumab was well tolerated, with a safety profile consistent with other interleukin-17 inhibitors.
TCT CONNECT-112 Intervention Management Strategies and Association With Long-Term Mortality in Patients With Concomitant Aortic Valve Stenosis and Coronary Artery Disease
Authors: Sameh Yousef, Makoto Mori, Roland Assi, Kim Smolderen, Ryan Kaple, John Forrest, Michael Cleman, Carlos Mena-Hurtado, Arnar Geirsson, Prashanth Vallabhajosyula
Journal: Journal of the American College of Cardiology (2020)
Improving silymarin oral bioavailability using silica-installed redox nanoparticle to suppress inflammatory bowel disease
Authors: Thu-Ha Thi Nguyen, Nhu-Thuy Trinh, Han Ngoc Tran, Hao Thi Tran, Phong Quoc Le, Dai-Nghiep Ngo, Hieu Tran-Van, Toi Van Vo, Long Binh Vong, Yukio Nagasaki
Journal: Journal of Controlled Release (2020)
<i>ANXA11</i> mutations in ALS cause dysregulation of calcium homeostasis and stress granule dynamics
Authors: Minyeop Nahm, Su Min Lim, Young-Eun Kim, Jinseok Park, Min-Young Noh, Sanggon Lee, Ju Eun Roh, Sung-Min Hwang, Chul-Kyu Park, Yong Ho Kim, GyuTae Lim, Jinhyuk Lee, Ki-Wook Oh, Chang-Seok Ki, Seung Hyun Kim
Journal: Science Translational Medicine (2020)

ANXA11 dysfunction induces alteration of intracellular Ca 2+ homeostasis and stress granule disassembly in ALS.
A rapidly enlarging neck swelling
Authors: Duncan Baily, Sally Renwick
Journal: BMJ (2020)

A man in his mid 50s with type 2 diabetes and hypertension presented with four days of fever and worsening neck pain and swelling, initially left sided but subsequently spreading to the right. The pain and swelling had rapidly increased over the preceding 12 hours, forcing him to remove his dentures, and causing restricted mouth opening and progressive difficulty swallowing. His only remaining native tooth was his lower left first molar (LL7), all others having been extracted several years earlier owing to advanced decay.

Examination showed firm, tender bilateral submental and submandibular swelling with skin induration, mouth opening reduced to less than two finger breadths, and elevation and rightward displacement of the tongue by a prominent, fluctuant swelling of the left side of …
Abstract 86: AED Allocation: Creating Rules for AED Placement Based on Urban Risk Maps
Authors: Benjamin W Chrisinger, Anne V Grossestreuer, Meredith L Curtis, Nancy Ting, Douglas Wiebe, Charles Branas, Raina M Merchant
Journal: Circulation (2013)

Background: Although the prompt use of automatic external defibrillators (AEDs) in out of hospital cardiac arrest (OHCA) can be lifesaving, policies to guide placement of publicly accessible AEDs are not clearly defined. Objectives: To use location-based risk, location density, and presence of a designated responder to create a risk-based mapping framework to guide urban AED placement. Methods: Literature reporting frequency of OHCA by location type in urban areas was used to create a list of candidate sites in downtown Philadelphia, PA. Location-based risk areas were plotted using ArcGIS with a kernel density surface that reflected walking time of approximately 1.5 minutes. Locations were identified through available public records and the Google search engine. Designated responder status was assigned by location type. Sites were weighted by risk of arrest and multiplied by density of designated responders to create a composite “opportunity” layer. Hypothetical sites for 20 new AEDs were then mapped by selecting the point with the highest opportunity score, “placing” an AED, and recalculating opportunity scores for the entire study area. This process was iterated until 20 hypothetical AEDs were sited. Results: Thirty types of locations with previously-studied frequency of OHCA were identified. Figure 1 identifies several high-risk areas for OHCAs with AED caretakers present to use devices in an emergency that could benefit from close proximity to an AED. Conclusions: A location-based risk map for OHCA identifies specific higher-risk locations to locate AEDs in an urban area. The metrics to build this theoretical framework for device allocation can be used by cities to guide more strategic AED placement based on their unique cardiac arrest data and current AED placement. Figure 1:
Commentary: Nonalcoholic or metabolic dysfunction-associated fatty liver disease? The epidemic of the 21st century in search of the most appropriate name
Authors: Stergios A. Polyzos, Eun Seok Kang, Emmanuel A. Tsochatzis, Stergios Kechagias, Mattias Ekstedt, Stavra Xanthakos, Amedeo Lonardo, Alessandro Mantovani, Herbert Tilg, Isabelle Côté, Aldo Grefhorst, Michael W. Greene, David Araujo-Vilar, Anna Alisi, Felipe Casanueva, Christos S. Mantzoros
Journal: Metabolism (2020)
A Global Perspective on White Rice Consumption and Risk of Type 2 Diabetes
Authors: Rob M. van Dam
Journal: Diabetes Care (2020)

Preventive policies to improve diet and physical activity are urgently needed to stem the rising global burden of type 2 diabetes (1). In randomized trials, both high-carbohydrate diets (low in saturated fat and high in fiber), combined with physical activity and caloric restriction, and moderate-fat Mediterranean diets reduced diabetes risk (2). These findings suggest that diets with variable carbohydrate intakes are compatible with diabetes-prevention lifestyles but do not identify the optimal amount and type of dietary carbohydrates. Furthermore, the impact of high carbohydrate intakes in other parts of the world beyond the range studied in Western populations remains unclear.

Rice provides ∼20% of the world's calorie intake (3). Of the 10 countries with the largest number of diabetes cases, 6 countries in Asia and South America have rice as the main staple food (4). Rice is predominantly consumed as white rice, a refined grain resulting from a milling process that removes the bran and germ and leaves the starchy endosperm. As a result, white rice is low in fiber, polyphenols, and micronutrients such as magnesium that may benefit glucose metabolism (5–7). White rice also has a high glycemic index (GI) and glycemic load (GL), reflecting high postprandial blood glucose levels (5). In several (8–10) but not all (9–11) prospective cohort studies in Asian countries, higher white rice consumption was associated with a higher risk of type 2 diabetes. Therefore, it is crucial to determine whether white rice consumption contributes to the development of type 2 diabetes, particularly in populations with high intake levels.

Bhavadharini et al. (12) evaluated the association between …
Hepatoma-derived growth factor is highly expressed in developing liver and promotes fetal hepatocyte proliferation
Authors: Hirayuki Enomoto, Kenya Yoshida, Yoshihiko Kishima, Taisei Kinoshita, Mitsunari Yamamoto, Allen D. Everett, Atsushi Miyajima, Hideji Nakamura
Journal: Hepatology (2002)

Hepatoma-derived growth factor (HDGF) is a heparin-binding protein, which has been purified from the conditioned media of HuH-7 hepatoma cells. Recent studies have suggested the involvement of HDGF in development of the kidney and cardiovascular systems. In the present study, we investigated the possibility that HDGF was also involved in liver development. Northern blot and immunostaining revealed unique expression patterns of HDGF in liver development. HDGF expression was strongly detected in the fetal liver of the midgestation stage and was markedly decreased near birth. Its expression was mainly detected in stromal cells, including immature hepatocytes. Expression in hepatocytes decreased with differentiation. Administration of recombinant HDGF enhanced the growth of primary cultured fetal hepatocytes significantly, although the effect was small. The effect of exogenous HDGF on the proliferation of neonatal hepatocytes was also small and significant only at one point, despite the lower expression of endogenous HDGF, suggesting that the differences exist between fetal and neonatal hepatocytes. However, adenoviral introduction of HDGF antisense cDNA into the fetal hepatocytes significantly suppressed their proliferation, and the inhibitory effect of HDGF antisense virus was reversed by exogenous HDGF. In conclusion, HDGF helps regulate the hepatocyte proliferation in liver development. (Hepatology2002;36:1519-1527).
Splenectomy before allogeneic hematopoietic cell transplantation for myelofibrosis: A French nationwide study
Authors: Jean‐Baptiste Bossard, Jean‐Baptiste Beuscart, Marie Robin, Mohamad Mohty, Fiorenza Barraco, Patrice Chevallier, Tony Marchand, Marie‐Thérèse Rubio, Amandine Charbonnier, Didier Blaise, Jacques‐Olivier Bay, Carmen Botella‐Garcia, Gandhi Damaj, Florence Beckerich, Patrice Ceballos, Thomas Cluzeau, Jérôme Cornillon, Mathieu Meunier, Corentin Orvain, Alain Duhamel, Federico Garnier, Jean‐Jacques Kiladjian, Ibrahim Yakoub‐Agha
Journal: American Journal of Hematology (2020)

The value of pretransplant splenectomy in patients with myelofibrosis (MF) is subject to debate, since the procedure may preclude subsequent allogeneic hematopoietic cell transplantation (allo-HCT). To determine the impact of pretransplant splenectomy on the incidence of allo-HCT, we conducted a comprehensive retrospective study of all patients with MF for whom an unrelated donor search had been initiated via the French bone marrow transplantation registry (RFGM) between 1 January 2008 and 1 January 2017. Additional data were collected from the patients' medical files and a database held by the French-Language Society for Bone Marrow Transplantation and Cell Therapy (SFGM-TC). We used a multistate model with four states ("RFGM registration"; "splenectomy"; "death before allo-HCT", and "allo-HCT") to evaluate the association between splenectomy and the incidence of allo-HCT. The study included 530 patients from 57 centers. With a median follow-up time of 6 years, we observed 81 splenectomies, 99 deaths before allo-HCT (90 without splenectomy and nine after), and 333 allo-HCTs (268 without splenectomy and 65 after). In a bivariable analysis, the hazard ratio [95% confidence interval (CI)] for the association of splenectomy with allo-HCT was 7.2 [5.1-10.3] in the first 4 months and 1.18 [0.69-2.03] thereafter. The hazard ratio [95% CI] for death associated with splenectomy was 1.58 [0.79-3.14]. These reassuring results suggest that splenectomy does not preclude allo-HCT in patients with MF.
Ventilation management and clinical outcomes in invasively ventilated patients with COVID-19 (PRoVENT-COVID): a national, multicentre, observational cohort study
Authors: Michela Botta, Anissa M Tsonas, Janesh Pillay, Leonoor S Boers, Anna Geke Algera, Lieuwe D J Bos, Dave A Dongelmans, Marcus W Hollmann, Janneke Horn, Alexander P J Vlaar, Marcus J Schultz, Ary Serpa Neto, Frederique Paulus, Jesse P. van Akkeren, Anna Geke Algera, Cheetel K. Algoe, Rombout B. van Amstel, Onno L. Baur, Pablo van de Berg, Alida E. van den Berg, Dennis C.J.J. Bergmans, Dido I. van den Bersselaar, Freke A. Bertens, Alexander J.G.H. Bindels, Milou M. de Boer, Sylvia den Boer, Leonoor S. Boers, Margriet Bogerd, Lieuwe D.J. Bos, Michela Botta, Jennifer S. Breel, Hendrik de Bruin, Sanne de Bruin, Caro L. Bruna, Laura A. Buiteman-Kruizinga, Olaf L. Cremer, Rogier M. Determann, Willem Dieperink, Dave A. Dongelmans, Hildegard S. Franke, Michal S. Galek-Aldridge, Mart J. de Graaff, Laura A. Hagens, Jasper J. Haringman, Sebastiaan T. van der Heide, Pim L.J. van der Heiden, Nanon F.L. Heijnen, Stephan J.P. Hiel, Lotte L. Hoeijmakers, Liselotte Hol, Markus W. Hollmann, Marga E. Hoogendoorn, Janneke Horn, Robrecht van der Horst, Evy L.K. Ie, Dimitri P. Ivanov, Nicole Juffermans, Eline Kho, Eline S. de Klerk, Ankie W.M.M. Koopman-van Gemert, Matty Koopmans, Songul Kucukcelebi, Michael A. Kuiper, Dylan W. de Lange, Niels van Mourik, Sunny G.L.H. Nijbroek, Marisa Onrust, Evelien A.N. Oostdijk, Frederique Paulus, Charlotte J. Pennartz, Janesh Pillay, Luigi Pisani, Ilse M. Purmer, Thijs C.D. Rettig, Jan-Paul Roozeman, Michiel T.U. Schuijt, Marcus J. Schultz, Ary Serpa Neto, Mengalvio E. Sleeswijk, Marry R. Smit, Peter E. Spronk, Willemke Stilma, Aart C. Strang, Anissa M. Tsonas, Pieter R. Tuinman, Christel M.A. Valk, Felicia L. Veen-Schra, Lars I. Veldhuis, Patricia van Velzen, Ward H. van der Ven, Alexander P.J. Vlaar, Peter van Vliet, Peter H.J. van der Voort, Louis van Welie, Henrico J.F.T. Wesselink, Hermien H. van der Wier-Lubbers, Bas van Wijk, Tineke Winters, Wing Yi Wong, Arthur R.H. van Zanten
Journal: The Lancet Respiratory Medicine (2020)
Treatment monitoring of colorectal cancer by integrated analysis of plasma concentration and sequencing of circulating tumor DNA
Authors: Yu-Min Yeh, Peng-Chan Lin, Chung-Ta Lee, Shang-Hung Chen, Bo-Wen Lin, Shao-Chieh Lin, Po-Chuan Chen, Ren-Hao Chan, Meng-Ru Shen
Journal: Molecular Cancer (2020)

Circulating cell-free DNA (cfDNA) analysis is an important tool for cancer monitoring. The patient-specific mutations identified in colorectal cancer (CRC) tissues are usually used to design the cfDNA analysis. Despite high specificity in predicting relapse, the sensitivity in most studies is around 40-50%. To improve this weakness, we designed a cfDNA panel according to the CRC genomic landscape and recurrent-specific mutations. The pathological variants in cfDNA samples from 60 CRC patients were studied by a next-generation sequencing (NGS) method incorporating the dual molecular barcode. Interestingly, patients in the disease positive group had a significantly higher cfDNA concentration than those in the disease negative group. Based on receiver operating characteristic analysis, the cfDNA concentration of 7 ng/mL was selected into the analytical workflow. The sensitivity in determining the disease status was 72.4%, which represented a considerable improvement on prior studies, and the specificity remained high at 80.6%. Compared to standard imaging and laboratory studies, earlier detection of residual disease and clinical benefits were shown on two cases by this cfDNA assay. We conclude this integrative framework of cfDNA analytical pipeline with a satisfactory sensitivity and specificity could be used in postoperative CRC surveillance.
THU0084 The cd14<sup>+</sup>/cd16<sup>+</sup>monocye subset in rheumatoid arthritis and systemic lupus erythematosus
Authors: AP Cairns, AD Crockard, AL Bell
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Most human peripheral blood monocytes strongly express surface CD14, and do not express CD16 (CD14<sup>+</sup>+/CD16-). A smaller group of monocytes express lower levels of CD14 and also express CD16 (CD14<sup>+</sup>/CD16<sup>+</sup>). This subgroup has different phagocytosing and antigen-presenting capabilities, and is expanded in a number of disease states.<sup>1</sup> Monocyte-derived macrophages and dendritic cells have important roles in the pathogenesis of both rheumatoid arthritis and SLE. <h3>Objectives</h3> To determine the percentage of circulating CD14<sup>+</sup>/CD16<sup>+</sup> monocytes in rheumatoid arthritis and systemic lupus erythematosus (SLE) and relate this to measures of disease activity and treatment. <h3>Methods</h3> Peripheral blood was sampled from 31 SLE patients, 19 rheumatoid arthritis patients and 19 healthy controls. The percentage of CD14<sup>+</sup>/CD16<sup>+</sup> monocytes was determined by immunofluorescence labelling and dual colour flow cytometry. <h3>Results</h3> The percentage of CD14<sup>+</sup>/CD16<sup>+</sup> monocytes was significantly reduced in rheumatoid arthritis (median = 4.90%) compared to normal subjects (median = 7.30%, p = 0.014), and in rheumatoid arthritis compared to SLE patients (median = 9.40%, p = 0.009). There was a trend towards a higher percentage of CD14<sup>+</sup>/CD16<sup>+</sup> monocytes in SLE compared to normal subjects, but this did not reach statistical significance. A negative correlation of percentage CD14<sup>+</sup>/CD16<sup>+</sup> monocytes with serum C-reactive protein level was observed (r = – 0.461, p = 0.001). Drug treatment (including corticosteroid dose) did not correlate with the percentage of CD14<sup>+</sup>/CD16<sup>+</sup> monocytes in rheumatoid arthritis or SLE. <h3>Conclusion</h3> The percentage of CD14<sup>+</sup>/CD16<sup>+</sup> monocytes in rheumatoid arthritis is lower than in normal subjects and in SLE, and this may contribute to the pathogenesis of rheumatoid arthritis. <h3>Reference</h3> Ziegler-Heitbrock HW. Immunol Today 1996;17(9):424–8
Itaconate controls the severity of pulmonary fibrosis
Authors: Patricia P. Ogger, Gesa J. Albers, Richard J. Hewitt, Brendan J. O’Sullivan, Joseph E. Powell, Emily Calamita, Poonam Ghai, Simone A. Walker, Peter McErlean, Peter Saunders, Shaun Kingston, Philip L. Molyneaux, John M. Halket, Robert Gray, Daniel C. Chambers, Toby M. Maher, Clare M. Lloyd, Adam J. Byrne
Journal: Science Immunology (2020)

The ACOD1/itaconate axis is a pulmonary regulatory pathway that controls the severity of fibrosis and is a potential therapeutic target in IPF.
TCT CONNECT-266 Cobalt Chromium Biolimus Drug-Eluting Stents Compared With Stainless Steel Biolimus Drug-Eluting Stents: Final Results of BMX Alpha
Authors: Ian Brian Alexander Menown, Mamas Mamas, James Cotton, David Hildick-Smith, Franz Eberli, Gregor Leibundgut, Damras Tresukosol, Carlos Macaya, Samuel Copt, Sara Sadozai Slama, Keith Oldroyd
Journal: Journal of the American College of Cardiology (2020)
Identifying the required degree of disease clearance to improve quality of life in pemphigus vulgaris
Authors: C.E. Bax, A. Ravishankar, D. Yan, J. Concha, C.J. Kushner, D. Zamalin, R. Feng, A.S. Payne, V.P. Werth
Journal: British Journal of Dermatology (2020)
Autologous Hematopoietic Stem Cell Transplant in Multiple Sclerosis
Authors: Aaron E. Miller, Tanuja Chitnis, Bruce A. Cohen, Kathleen Costello, Nancy L. Sicotte, Rachael Stacom
Journal: JAMA Neurology (2020)

<h3>Importance</h3> Autologous hematopoietic stem cell transplant (AHSCT) for multiple sclerosis has gained increasing interest in recent years. Despite the availability of many US Food and Drug Administration–approved disease-modifying therapies, some patients do not respond adequately and others may have very early aggressive disease that prompts consideration of alternative, highly effective, long-lasting therapy. The National Medical Advisory Committee of the National Multiple Sclerosis Society has reviewed recent literature on AHSCT for the purpose of making recommendations about its use based on current knowledge, as well as pointing out areas of controversy and issues requiring further research. <h3>Observations</h3> Studies on AHSCT have repeatedly demonstrated high efficacy and a durable outcome in people with relapsing multiple sclerosis. Recent studies have shown considerable improvement in the safety of the procedure, with much lower mortality rates than were reported earlier. Consensus is emerging about the characteristics of the best candidates for the procedure. Questions remain about the ideal protocol, particularly about the best conditioning regimen to be used to kill immune cells. Larger randomized clinical trials are needed to address the question of whether AHSCT has advantages over the most efficacious disease-modifying agents currently available. One such trial (Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Multiple Sclerosis [BEAT-MS) is currently in progress. <h3>Conclusions and Relevance</h3> The National Multiple Sclerosis Society believes that AHSCT may be a useful treatment option for people with relapsing multiple sclerosis who demonstrate substantial breakthrough disease activity (ie, new inflammatory central nervous system lesions and/or clinical relapses) despite treatment with high-efficacy disease-modifying therapy or have contraindications to high-efficacy disease-modifying therapies. The best candidates are likely people younger than 50 years with shorter durations of disease (&lt;10 years). The procedure should only be performed at centers with substantial experience and expertise. Ideally, recipients of the procedure should be entered into a single database, and further research is needed to establish ideal cell mobilization and immune-conditioning regimens.
Direct peroral cholangioscopic retrieval of an inward migrated plastic stent lodged in the cystic duct and liver hilum
Authors: Elmer Hoekstra, Roeland Veenendaal, Akin Inderson
Journal: Endoscopy (2020)

Endoscopic sphincterotomy and stone extraction are widely performed as a primary intervention for patients with common bile duct (CBD) stones, with or without cholangiosepsis, with a high success rate and a relatively low complication rate [1]. When CBD stone removal is not successful, a plastic stent can be placed as a salvage therapy to achieve drainage, especially in the septic patient. It has also been shown that placement of biliary plastic stent prevents stone impaction and cholangitis [2]. The most common problem is stent migration occurring up to 5 % proximal (into the duct) and 6 % distal (out of the duct) [3]. Several techniques have been described to retrieve inward migrated stents with high success rates [4] [5]. However, sometimes the endoprosthesis ends up in a very tricky position where your usual techniques might not be sufficient, as presented in the following case.
Offline: Science and politics in the era of COVID-19
Authors: Richard Horton
Journal: The Lancet (2020)

"How can we follow the science when scientists haven't the foggiest." "'Big mouth' scientists losing trust of Ministers." Headlines such as these are increasingly common in UK newspapers. Scientists are no longer seen as providing impartial, independent advice to government. They are seen as being responsible for crashing economies, driving up unemployment, and ruining livelihoods. Chris Whitty, England's Chief Medical Officer, and Patrick Vallance, Chief Scientific Adviser, have received the sharpest criticism.