tbuckley/cabot-search huggingface dataset:
Long-term efficacy and safety of brodalumab in the treatment of psoriasis: 120-week results from the randomized, double-blind, placebo- and active comparator–controlled phase 3 AMAGINE-2 trial
Authors: Luis Puig, Mark Lebwohl, Hervé Bachelez, Jeffrey Sobell, Abby A. Jacobson
Journal: Journal of the American Academy of Dermatology (2019)

Randomized controlled trials have shown the efficacy and safety of brodalumab in patients with moderate to severe plaque psoriasis.To evaluate the efficacy and safety of brodalumab through 120 weeks of treatment in the AMAGINE-2 trial.Patients received ustekinumab through week 52 followed by brodalumab 210 mg every 2 weeks, continuous brodalumab 210 mg every 2 weeks, or any dose of brodalumab. Efficacy data were reported through 120 weeks by using observed data, last observation carried forward, and nonresponder imputation analyses.Of patients who received brodalumab 210 mg every 2 weeks, 84.4%, 75.6%, and 61.1% achieved 75%, 90%, and 100% improvement from baseline in Psoriasis Area and Severity Index at 120 weeks (observed data analysis), respectively. Patients who received brodalumab 210 mg every 2 weeks after receiving ustekinumab through 52 weeks achieved a similar skin clearance response as patients who received continuous brodalumab 210 mg every 2 weeks. Safety through 120 weeks was comparable to that of the blinded study periods.A large number of discontinuations toward the end of the study (31% in the final 6 months) were due to early termination and led to differences between observed data and nonresponder imputation results.Brodalumab is well tolerated and showed robust efficacy for more than 2 years.
Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range
Authors: Tadej Battelino, Thomas Danne, Richard M. Bergenstal, Stephanie A. Amiel, Roy Beck, Torben Biester, Emanuele Bosi, Bruce A. Buckingham, William T. Cefalu, Kelly L. Close, Claudio Cobelli, Eyal Dassau, J. Hans DeVries, Kim C. Donaghue, Klemen Dovc, Francis J. Doyle, Satish Garg, George Grunberger, Simon Heller, Lutz Heinemann, Irl B. Hirsch, Roman Hovorka, Weiping Jia, Olga Kordonouri, Boris Kovatchev, Aaron Kowalski, Lori Laffel, Brian Levine, Alexander Mayorov, Chantal Mathieu, Helen R. Murphy, Revital Nimri, Kirsten Nørgaard, Christopher G. Parkin, Eric Renard, David Rodbard, Banshi Saboo, Desmond Schatz, Keaton Stoner, Tatsuiko Urakami, Stuart A. Weinzimer, Moshe Phillip
Journal: Diabetes Care (2019)

Improvements in sensor accuracy, greater convenience and ease of use, and expanding reimbursement have led to growing adoption of continuous glucose monitoring (CGM). However, successful utilization of CGM technology in routine clinical practice remains relatively low. This may be due in part to the lack of clear and agreed-upon glycemic targets that both diabetes teams and people with diabetes can work toward. Although unified recommendations for use of key CGM metrics have been established in three separate peer-reviewed articles, formal adoption by diabetes professional organizations and guidance in the practical application of these metrics in clinical practice have been lacking. In February 2019, the Advanced Technologies & Treatments for Diabetes (ATTD) Congress convened an international panel of physicians, researchers, and individuals with diabetes who are expert in CGM technologies to address this issue. This article summarizes the ATTD consensus recommendations for relevant aspects of CGM data utilization and reporting among the various diabetes populations.
Conservative management of retinoblastoma: Challenging orthodoxy without compromising the state of metastatic grace. “Alive, with good vision and no comorbidity”
Authors: Francis L. Munier, Maja Beck-Popovic, Guillermo L. Chantada, David Cobrinik, Tero T. Kivelä, Dietmar Lohmann, Philippe Maeder, Annette C. Moll, Angel Montero Carcaboso, Alexandre Moulin, Paula Schaiquevich, Ciara Bergin, Paul J. Dyson, Susan Houghton, Francesco Puccinelli, Yvan Vial, Marie-Claire Gaillard, Christina Stathopoulos
Journal: Progress in Retinal and Eye Research (2019)
A pilot study of safety and efficacy of HCV retreatment with sofosbuvir/velpatasvir/voxilaprevir in patients with or without HIV (RESOLVE STUDY)
Authors: Eleanor Wilson, Emily Covert, Jennifer Hoffmann, Emily Comstock, Benjamin Emmanuel, Lydia Tang, Jennifer Husson, Joel Chua, Angie Price, Poonam Mathur, Elana Rosenthal, Sarah Kattakuzhy, Henry Masur, Shyam Kottilil
Journal: Journal of Hepatology (2019)
适用于斑块状银屑病的 risankizumab 与 ustekinumab:严格评读
Authors: A. Al‐Janabi, Z.K. Jabbar‐Lopez, C.E.M. Griffiths, Z.Z.N. Yiu
Journal: British Journal of Dermatology (2019)

银屑病是一种导致鳞片状、红疹的皮肤病,其受累部位从仅小面积(如肘关节和膝关节)到更大面积不等。在英国约2%的人患有银屑病。该疾病有许多治疗方法,包括药膏、片剂和注射剂。注射剂称为生物制剂,免疫系统的这种靶向特异性成分对银屑病非常有效。本文的英国作者旨在评估两项比较两种这类生物制剂 risankizumab 和 ustekinumab 的试验(称为 UltIMMa‐1 和 UltIMMa‐2)的质量。上述试验包括来自 14个国家的患者,而且表明risankzizumab较ustekinumab对治疗中度或重度银屑病患者更有效。作者发现上述试验实施良好,这是因为他们招募了大量患者,而且所使用的方法很恰当且进行明确报告。他们采用适当方式分析了数据,该方式保守且未过度估计新疗法risankizumab的疗效。对这些试验的一项批判是在临床环境下(即在实际治疗中而非试验中)可能很难使结果适用于某些患者群体。例如,尚不明确接受片剂或某些其他注射剂治疗并失败的患者是否会出现与从未接受这类治疗的患者不同的反应。此外,某些其他疾病患者被从研究中排除,尽管未说明患有哪些疾病会被排除。作者总结,本次研究明确证明risankizumab比ustekinumab更有效,尽管需要更多工作要做,以确认其中的原因。
The balance of power: innate lymphoid cells in tissue inflammation and repair
Authors: Jim G. Castellanos, Randy S. Longman
Journal: Journal of Clinical Investigation (2019)

Over the last ten years, immunologists have recognized the central importance of an emerging group of innate lymphoid cells (ILCs) in health and disease. Characterization of these cells has provided a molecular definition of ILCs and their tissue-specific functions. Although the lineage-defining transcription factors, cytokine production, and nomenclature parallel those of T helper cells, ILCs do not require adaptive immune programming. Both environmental and host-derived signals shape the function of these evolutionarily ancient cells, which provide pathogen protection and promote tissue restoration. As such, ILCs function as a double-edged sword, balancing the inflammatory and reparative responses that arise during injury and disease. This Review highlights our recent understanding of tissue-resident ILCs and the signals that regulate their contribution to inflammation and tissue repair in health and disease.
Single-cell activity tracking reveals that orbitofrontal neurons acquire and maintain a long-term memory to guide behavioral adaptation
Authors: Vijay Mohan K. Namboodiri, James M. Otis, Kay van Heeswijk, Elisa S. Voets, Rizk A. Alghorazi, Jose Rodriguez-Romaguera, Stefan Mihalas, Garret D. Stuber
Journal: Nature Neuroscience (2019)
Dectin-2–induced CCL2 production in tissue-resident macrophages ignites cardiac arteritis
Authors: Chie Miyabe, Yoshishige Miyabe, Laura Bricio-Moreno, Jeffrey Lian, Rod A. Rahimi, Noriko N. Miura, Naohito Ohno, Yoichiro Iwakura, Tamihiro Kawakami, Andrew D. Luster
Journal: Journal of Clinical Investigation (2019)

Environmental triggers, including those from pathogens, are thought to play an important role in triggering autoimmune diseases, such as vasculitis, in genetically susceptible individuals. The mechanism by which activation of the innate immune system contributes to vessel-specific autoimmunity in vasculitis is not known. Systemic administration of Candida albicans water-soluble extract (CAWS) induces vasculitis in the aortic root and coronary arteries of mice that mimics human Kawasaki disease. We found that Dectin-2 signaling in macrophages resident in the aortic root of the heart induced early CCL2 production and the initial recruitment of CCR2+ inflammatory monocytes (iMo) into the aortic root and coronary arteries. iMo differentiated into monocyte-derived dendritic cells (Mo-DC) in the vessel wall and were induced to release IL-1β in a Dectin-2-Syk-NLRP3 inflammasome dependent pathway. IL-1β then activated cardiac endothelial cells to express CXCL1 and CCL2 and adhesion molecules that induced neutrophil and further iMo recruitment and accumulation in the aortic root and coronary arteries. Our findings demonstrate that Dectin-2-mediated induction of CCL2 production by macrophages resident in the aortic root and coronary arteries initiates vascular inflammation in a model of Kawasaki disease, suggesting an important role for the innate immune system in initiating vasculitis.
Serotonin and Antiserotonins
Authors: WILLIAM HOLLANDER, ALAN L. MICHELSON, ROBERT W. WILKINS
Journal: Circulation (1957)

Serotonin, (5 hydroxy-tryptamine), a naturally occurring compound, is pharmacologically active on intravenous injection in man. It consistently increases the pulse rate but has a variable pressor depressor, or biphasic effect on the arterial pressure. The mode of action of serotonin on these functions is not clear. Serotonin consistently and characteristically increases ventilation. However, it does not cause striking circulatory changes in the kidney although it usually produces moderate antidiuresis. The benzyl analog of serotonin (BAS) (1-benzyl-2-methyl-3-methoxy-tryptamine), both intravenously and orally, reduces or prevents the symptoms caused by serotonin. Intravenously, BAS in addition has demonstrable "antiserotonin" effects on the characteristic blood pressure and respiratory responses to serotonin.
Publisher Correction: Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
Authors: Rainer Malik, Ganesh Chauhan, Matthew Traylor, Muralidharan Sargurupremraj, Yukinori Okada, Aniket Mishra, Loes Rutten-Jacobs, Anne-Katrin Giese, Sander W van der Laan, Solveig Gretarsdottir, Christopher D Anderson, Michael Chong, Hieab H H Adams, Tetsuro Ago, Peter Almgren, Philippe Amouyel, Hakan Ay, Traci M Bartz, Oscar R Benavente, Steve Bevan, Giorgio B Boncoraglio, Robert D Brown, Adam S Butterworth, Caty Carrera, Cara L Carty, Daniel I Chasman, Wei-Min Chen, John W Cole, Adolfo Correa, Ioana Cotlarciuc, Carlos Cruchaga, John Danesh, Paul I W de Bakker, Anita L DeStefano, Marcel den Hoed, Qing Duan, Stefan T Engelter, Guido J Falcone, Rebecca F Gottesman, Raji P Grewal, Vilmundur Gudnason, Stefan Gustafsson, Jeffrey Haessler, Tamara B Harris, Ahamad Hassan, Aki S Havulinna, Susan R Heckbert, Elizabeth G Holliday, George Howard, Fang-Chi Hsu, Hyacinth I Hyacinth, M Arfan Ikram, Erik Ingelsson, Marguerite R Irvin, Xueqiu Jian, Jordi Jiménez-Conde, Julie A Johnson, J Wouter Jukema, Masahiro Kanai, Keith L Keene, Brett M Kissela, Dawn O Kleindorfer, Charles Kooperberg, Michiaki Kubo, Leslie A Lange, Carl D Langefeld, Claudia Langenberg, Lenore J Launer, Jin-Moo Lee, Robin Lemmens, Didier Leys, Cathryn M Lewis, Wei-Yu Lin, Arne G Lindgren, Erik Lorentzen, Patrik K Magnusson, Jane Maguire, Ani Manichaikul, Patrick F McArdle, James F Meschia, Braxton D Mitchell, Thomas H Mosley, Michael A Nalls, Toshiharu Ninomiya, Martin J O'Donnell, Bruce M Psaty, Sara L Pulit, Kristiina Rannikmäe, Alexander P Reiner, Kathryn M Rexrode, Kenneth Rice, Stephen S Rich, Paul M Ridker, Natalia S Rost, Peter M Rothwell, Jerome I Rotter, Tatjana Rundek, Ralph L Sacco, Saori Sakaue, Michele M Sale, Veikko Salomaa, Bishwa R Sapkota, Reinhold Schmidt, Carsten O Schmidt, Ulf Schminke, Pankaj Sharma, Agnieszka Slowik, Cathie L M Sudlow, Christian Tanislav, Turgut Tatlisumak, Kent D Taylor, Vincent N S Thijs, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Steffen Tiedt, Stella Trompet, Christophe Tzourio, Cornelia M van Duijn, Matthew Walters, Nicholas J Wareham, Sylvia Wassertheil-Smoller, James G Wilson, Kerri L Wiggins, Qiong Yang, Salim Yusuf, Joshua C Bis, Tomi Pastinen, Arno Ruusalepp, Eric E Schadt, Simon Koplev, Johan L M Björkegren, Veronica Codoni, Mete Civelek, Nicholas L Smith, David A Trégouët, Ingrid E Christophersen, Carolina Roselli, Steven A Lubitz, Patrick T Ellinor, E Shyong Tai, Jaspal S Kooner, Norihiro Kato, Jiang He, Pim van der Harst, Paul Elliott, John C Chambers, Fumihiko Takeuchi, Andrew D Johnson, Dharambir K Sanghera, Olle Melander, Christina Jern, Daniel Strbian, Israel Fernandez-Cadenas, W T Longstreth, Arndt Rolfs, Jun Hata, Daniel Woo, Jonathan Rosand, Guillaume Pare, Jemma C Hopewell, Danish Saleheen, Kari Stefansson, Bradford B Worrall, Steven J Kittner, Sudha Seshadri, Myriam Fornage, Hugh S Markus, Joanna M M Howson, Yoichiro Kamatani, Stephanie Debette, Martin Dichgans
Journal: Nature Genetics (2019)
Resistance Mechanisms Underlying Venetoclax Resistance in Mantle Cell Lymphoma
Authors: Shengjian Huang, Changying Jiang, Hui Guo, Jeffrey Wang, Yang Liu, Carrie Li, Elyse Lopez, Hui Zhang, Elizabeth A Lorence, Maria Merolle, Swathi Balaji, Makhdum Ahmed, Krystle Nomie, Liang Zhang, Michael Wang
Journal: Blood (2017)
Controversies for Glucose Control Targets in Type 2 Diabetes: Exposing the Common Ground
Authors: Philip Home
Journal: Diabetes Care (2019)

Glycated hemoglobin targets have been given in guidelines for the last three decades, mostly without change at around 6.5-7.0% (47-53 mmol/mol). Personalization of such targets has also long been advocated, but often with little and inappropriate guidance. More recently some have suggested higher targets might be indicated, and more specifically lower targets avoided, even in those in whom they are easily attained without seeming burden or risk. Prospective data from randomized and observational studies, in people with type 2 diabetes and indeed those without diabetes, find cardiovascular and mortality risk are uniformly lowest at lower levels including into the normal range. In some studies with large populations, a high proportion of people are found to attain such levels, and the UK Prospective Diabetes Study (UKPDS) and more recent studies appear to confirm the importance of starting low and continuing long. Studies of cardiovascular events and mortality in people with diabetes will already factor in any effect of hypoglycemia, which therefore should not be double-counted in setting targets. Nevertheless, some factors should lead to modification of target levels, and these will include experience of hypoglycemia where therapy change and glucose monitoring cannot ameliorate it and sometimes prospectively in those at social or occupational risk. The fact that clinical experience will modify targets emphasizes that targets will not be stable over time but will change, for example, with occurrence of adverse events or perceptions of increase/decreased burden of therapy. The evidence suggests that glucose control takes 5 years or more to have any impact on vascular outcomes or mortality, so targets may also be higher in those with shorter life expectancy or higher health burden or simply reflect individual preferences. This article discusses the evidence behind these conclusions.
Abstract 19183: Insulin Resistance Develops after the Onset of Heart Failure in Dogs
Authors: Mauricio Velez, Gupta Ramesh, Bipin Sunkara, David E Lanfear, Hani N Sabbah
Journal: Circulation (2012)

Background: Heart failure (HF) is a condition associated with increased plasma norepinephrine levels. Norepinephrine is known to affect glucose homeostasis by decreasing insulin sensitivity. We have previously reported an increase in plasma norepinephrine levels in coronary microembolization-induced HF dogs. However, the status of plasma insulin and glucose levels is unknown in large animal models of HF. In the present study, we examined insulin and glucose levels in fasted plasma from dogs before and after the onset of HF. Methods: 12 healthy mongrel dogs weighing 20-30 kg underwent serial coronary microembolization to produce HF. Embolization was performed every 1-2 weeks until angiographic left ventricular ejection fraction (LVEF) was &lt;35%. All procedures were performed during cardiac catheterization, under general anesthesia and sterile conditions. Fasted plasma was collected before and after inducing HF and was stored at -80 o C. Insulin and glucose levels were determined using commercially available ELISA kits for insulin and colorimetric assay kits for glucose, and expressed in microunits/mL and mg/dL, respectively. Homeostasis assessment model for insulin resistance (HOMA-IR) ([fasting insulin in microunits/mL * fasting glucose in mg/dL] * 0.5551/22.5) was calculated in all dogs at baseline and after inducing HF. Data were analyzed using paired t-tests. Results: Baseline LVEF was &gt; 55% in all dogs. Once HF was established, mean LVEF was 31 ± 1%. Baseline mean fasting blood glucose and fasting plasma insulin were 84 ± 17 mg/dL and 9.7 ± 3.6 microunits/mL, respectively. Once HF was established, fasting blood glucose rose to 161 ± 44 mg/dL (p&lt;0.0001) and fasting plasma insulin increased to 16.5 ± 4.0 microunits/mL (p=0.0008). HOMA-IR score increased from 2.0 ± 0.8 at baseline to 6.7 ± 3.0 with HF (p=0.0002). Conclusions: Hyperglycemia, hyperinsulinemia and insulin resistance develop after the onset of heart failure due to coronary microembolization in dogs consistent with observations previously reported in patients with chronic HF. This large animal model of HF can serve as a useful tool in exploring the underlying causes and consequences of insulin resistance in the setting of chronic HF.
Risankizumab vs. ustekinumab for plaque psoriasis
Authors: A. Al‐Janabi, Z.K. Jabbar‐Lopez, C.E.M. Griffiths, Z.Z.N. Yiu
Journal: British Journal of Dermatology (2019)

Psoriasis is a skin condition that causes a scaly, red rash which can vary from affecting only small areas of the body, such as the elbows and knees, to affecting a larger area of the body. It affects approximately 2% of people in the U.K. There are many treatments for psoriasis, including creams, tablets and injections. The injections are known as biologics and these target specific parts of the immune system that can be very active in psoriasis. The authors of this paper, based in the U.K., aimed to assess the quality of two trials (called UltIMMa‐1 and UltIMMa‐2) that compared two of these biologics, risankizumab and ustekinumab. These trials included patients from 14 countries, and showed that risankzizumab is more effective than ustekinumab for treating patients with moderate or severe psoriasis. The authors found that these trials were well‐conducted because they recruited a large number of patients and the methods used were sound and clearly reported. They analysed the data in a way which is conservative and doesn't over‐estimate the effect of the new treatment, risankizumab. One criticism of the trials is that it could be difficult to apply the results to some groups of patients in the clinical setting (i.e. in real life treatment rather than in a trial). For example, it's not clear whether patients who have failed tablet or some other injection treatments would respond differently from those who have never had such treatments. Additionally, some patients with other illnesses were excluded from the study, though it was not specified which illnesses lead to exclusion. The authors conclude that this study does clearly demonstrate that risankizumab is more effective than ustekinumab, though more work needs to be done to identify why this is the case.
Pyrin mutations in complex hidradenitis suppurativa
Authors: S. Vural, M. Gündoğdu, E. Gökpınar İli, C.D. Durmaz, A. Vural, L. Steinmüller‐Magin, A. Kleinhempel, L.M. Holdt, T. Ruzicka, K.A. Giehl, H.I. Ruhi, A. Boyvat
Journal: British Journal of Dermatology (2019)
Cancer therapy and risk of congenital malformations in children fathered by men treated for testicular germ-cell cancer: A nationwide register study
Authors: Yahia Al-Jebari, Ingrid Glimelius, Carina Berglund Nord, Gabriella Cohn-Cedermark, Olof Ståhl, Torgrim Tandstad, Allan Jensen, Hege Sagstuen Haugnes, Gedske Daugaard, Lars Rylander, Aleksander Giwercman
Journal: PLoS Medicine (2019)

Because of the potential mutagenic effects of chemo- and radiotherapy, there is concern regarding increased risk of congenital malformations (CMs) among children of fathers with cancer. Previous register studies indicate increased CM risk among children conceived after paternal cancer but lack data on oncological treatment. Increased CM risk was recently reported in children born before paternal cancer. This study aims to investigate whether anti-neoplastic treatment for testicular germ-cell cancer (TGCC) implies additional CM risk.In this nationwide register study, all singletons born in Sweden 1994-2014 (n = 2,027,997) were included. Paternal TGCC diagnoses (n = 2,380), anti-neoplastic treatment, and offspring CMs were gathered from the Swedish Norwegian Testicular Cancer Group (SWENOTECA) and the Swedish Medical Birth Register. Children were grouped based on +/- paternal TGCC; treatment regimen: surveillance (n = 1,340), chemotherapy (n = 2,533), or radiotherapy (n = 360); and according to time of conception: pre- (n = 2,770) or post-treatment (n = 1,437). Odds ratios (ORs) for CMs were calculated using logistic regression with adjustment for parental ages, maternal body mass index (BMI), and maternal smoking. Children conceived before a specific treatment acted as reference for children conceived after the same treatment. Among children fathered by men with TGCC (n = 4,207), 184 had a CM. The risk of malformations was higher among children of fathers with TGCC compared with children fathered by men without TGCC (OR 1.28, 95% confidence interval [CI] 1.19-1.38, p = 0.001, 4.4% versus 3.5%). However, no additional risk increase was associated with oncological treatment when comparing post-treatment-to pretreatment-conceived children (chemotherapy, OR = 0.82, 95% CI 0.54-1.25, p = 0.37, 4.1% versus 4.6%; radiotherapy, OR = 1.01, 95% CI 0.25-4.12, p = 0.98, 3.2% versus 3.0%). Study limitations include lack of data on use of cryopreserved or donor sperm and on seminoma patients for the period 1995-2000-both tending to decrease the difference between the groups with TGCC and without TGCC. Furthermore, the power of analyses on chemotherapy intensity and radiotherapy was limited.No additional increased risk of CMs was observed in children of men with TGCC treated with radio- or chemotherapy. However, paternal TGCC per se was associated with modestly increased risk for offspring malformations. Clinically, this information can reassure concerned patients.
Gabriel Weston: Looking out for others
Authors: Gabriel Weston
Journal: BMJ (2019)

It’s the annual camping trip. Every summer half term we congregate in a field with a big group of other families, pitch tents, roast a pig, and try to let go for a couple of days. Over the 10 years we’ve been doing this, the first aid pack I bring with me has grown as the medley of minor ailments and injuries I’ve had to attend to—often in the dark, with a torch—has become more elaborate. This year, however, I’ve realised that my most important piece of kit won’t go in the bag.

Last month …