tbuckley/cabot-search huggingface dataset:
OP0149 VISUAL LOSS IN PATIENTS WITH GIANT CELL ARTERITIS TREATED WITH TOCILIZUMAB
Authors: J. Amsler, I. Kysela, L. Christ, C. Tappeiner, L. Seitz, G. Scholz, F. Kollert, S. Reichenbach, P. Villiger
Journal: Annals of the Rheumatic Diseases (2020)

Background: Whether Tocilizumab (TCZ) may prevent vision loss in Giant Cell Arteritis (GCA) to the same extent as glucocorticoids remains a key and unanswered question. A patient cohort observed over up to 8 years addresses this issue. Objectives: To investigate the frequency of vision loss/visual impariment in a GCA cohort treated with TCZ. Methods: In this observational monocentric study, the courses of 192 patients with GCA treated with TCZ between 01.01.2011 and 31.12.2018 were analyzed. Data were extracted from medical records and collected in a Clinical Trial Unit (CTU) - based registry. Demographic, clinical and laboratory data were analyzed. Results: 192 patients with GCA were treated with TCZ; 121 (63%) were female, 112 (58%) fulfilled 1990 American College of Rheumatology (ACR) criteria, all others had large vessel vasculitis based on magnetic resonance-angiography (MRA). The cumulative duration of TCZ treatment was 3467 months; the median treatment duration was 13.8 (8.5; 22.8) months. At baseline, visual impairment was present in 71 (37%) and vision loss in 21 (7.8%) patients. Visual loss was associated with higher age (74 (70; 82) vs. 70 (63; 76) years; p=0.029), lower C-reactive protein at baseline (14.0 (3.5; 42.0) vs. 54.5 (21.0; 101.0) mg/l; p&lt;0.001), cranial symptoms (p&lt;0.0001), jaw claudication (p=0.030) and negative MRA of the aorta (p=0.020). Over the observed time span only one patient taking part in a clinical trial developed vision loss. In total 4 (2%) patients with vision impairment showed deterioration and 61 (32%) improvement. Conclusion: Collectively, our data suggest that TCZ is able to prevent visual loss and may have a favorable effect on visual impairment. Disclosure of Interests: Jennifer Amsler: None declared, Iveta Kysela: None declared, Lisa Christ Consultant of: BMS, Christoph Tappeiner: None declared, Luca Seitz: None declared, Godehard Scholz: None declared, Florian Kollert Employee of: Novartis, Stephan Reichenbach: None declared, Peter Villiger Consultant of: MSD, Abbvie, Roche, Pfizer, Sanofi, Speakers bureau: Roche, MSD, Pfizer
New Ebola outbreak in DRC has killed 20 people so far
Authors: Elisabeth Mahase
Journal: BMJ (2020)

A new outbreak of Ebola virus disease in the Democratic Republic of Congo, the 11th in the country, has so far infected 49 people and killed 20, the World Health Organization has announced.1

The 11th outbreak was announced on 1 June, just days after the 10th outbreak was declared over.2 The country is also battling covid-19 and the world’s worst measles epidemic.3

The latest figures from WHO (12 …
The Clinical-Stage sGC Stimulator IW-1701 Prevents Increase of Plasma Biomarkers of Intravascular Inflammation and Suppresses Leukocyte-Endothelial Interactions in Tnfα-Treated Mice
Authors: Boris Tchernychev, Susanne Feil, Peter Germano, William Warren, Elisabeth Lonie, Robert Feil, Todd G Milne, John Hadcock, Yueh-Tyng Chien, Mark G Currie, Regina Margaret Graul
Journal: Blood (2017)
The mevalonate pathway is an actionable vulnerability of t(4;14)-positive multiple myeloma
Authors: Joseph Longo, Petr Smirnov, Zhihua Li, Emily Branchard, Jenna E. van Leeuwen, Jonathan D. Licht, Benjamin Haibe-Kains, David W. Andrews, Jonathan J. Keats, Trevor J. Pugh, Suzanne Trudel, Linda Z. Penn
Journal: Leukemia (2020)

Abstract Multiple myeloma (MM) is a plasma cell malignancy that is often driven by chromosomal translocations. In particular, patients with t (4;14)-positive disease have worse prognosis compared to other MM subtypes. Herein, we demonstrated that t (4;14)-positive cells are highly dependent on the mevalonate (MVA) pathway for survival. Moreover, we showed that this metabolic vulnerability is immediately actionable, as inhibiting the MVA pathway with a statin preferentially induced apoptosis in t (4;14)-positive cells. In response to statin treatment, t (4;14)-positive cells activated the integrated stress response (ISR), which was augmented by co-treatment with bortezomib, a proteasome inhibitor. We identified that t (4;14)-positive cells depend on the MVA pathway for the synthesis of geranylgeranyl pyrophosphate (GGPP), as exogenous GGPP fully rescued statin-induced ISR activation and apoptosis. Inhibiting protein geranylgeranylation similarly induced the ISR in t (4;14)-positive cells, suggesting that this subtype of MM depends on GGPP, at least in part, for protein geranylgeranylation. Notably, fluvastatin treatment synergized with bortezomib to induce apoptosis in t (4;14)-positive cells and potentiated the anti-tumor activity of bortezomib in vivo. Our data implicate the t (4;14) translocation as a biomarker of statin sensitivity and warrant further clinical evaluation of a statin in combination with bortezomib for the treatment of t (4;14)-positive disease.
Abstract 13811: An Automated Natural Language Processing Algorithm to Classify Magnetic Resonance Imaging Reports Containing Positive Diagnoses of Hypertrophic Cardiomyopathy
Authors: Sungrim Moon, Elham Sagheb, Sijia Liu, David Chen, Martijn Bos, Jeffrey B Geske, Peter A Noseworthy, Michael J Ackerman, Jane L Shellum, Rajeev Chaudhry, Steve R Ommen, Philip A Araoz, Rick A Nishimura, Hongfang Liu, Adelaide Arruda-Olson
Journal: Circulation (2019)

Introduction: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and the leading cause of sudden cardiac death in young adults. Cardiac magnetic resonance imaging (MRI) i...
Classical monocyte transcriptomes reveal significant anti-inflammatory statin effect in women with chronic HIV
Authors: Erik Ehinger, Yanal Ghosheh, Akula Bala Pramod, Juan Lin, David B Hanna, Karin Mueller, Christopher P Durant, Livia Baas, Qibin Qi, Tao Wang, Konrad Buscher, Kathryn Anastos, Jason M Lazar, Wendy J Mack, Phyllis C Tien, Mardge H Cohen, Igho Ofotokun, Stephen Gange, Sonya L Heath, Howard N Hodis, Russell P Tracy, Alan L Landay, Robert C Kaplan, Klaus Ley
Journal: Cardiovascular Research (2020)

Abstract Aims During virally suppressed chronic HIV infection, persistent inflammation contributes to the development of cardiovascular disease (CVD), a major comorbidity in people living with HIV (LWH). Classical blood monocytes (CMs) remain activated during antiretroviral therapy and are a major source of pro-inflammatory and pro-thrombotic factors that contribute to atherosclerotic plaque development and instability. Methods and results Here, we identify transcriptomic changes in circulating CMs in peripheral blood mononuclear cell samples from participants of the Women’s Interagency HIV Study, selected by HIV and subclinical CVD (sCVD) status. We flow-sorted CM from participants of the Women’s Interagency HIV Study and deep-sequenced their mRNA (n = 92). CMs of HIV+ participants showed elevated interleukin (IL)-6, IL-1β, and IL-12β, overlapping with many transcripts identified in sCVD+ participants. In sCVD+ participants LWH, those reporting statin use showed reduced pro-inflammatory gene expression to a level comparable with healthy (HIV−sCVD−) participants. Statin non-users maintained an elevated inflammatory profile and increased cytokine production. Conclusion Statin therapy has been associated with a lower risk of cardiac events, such as myocardial infarction in the general population, but not in those LWH. Our data suggest that women LWH may benefit from statin therapy even in the absence of overt CVD.
Assembly of the threespine stickleback Y chromosome reveals convergent signatures of sex chromosome evolution
Authors: Catherine L. Peichel, Shaugnessy R. McCann, Joseph A. Ross, Alice F. S. Naftaly, James R. Urton, Jennifer N. Cech, Jane Grimwood, Jeremy Schmutz, Richard M. Myers, David M. Kingsley, Michael A. White
Journal: Genome biology (2020)

Abstract Background Heteromorphic sex chromosomes have evolved repeatedly across diverse species. Suppression of recombination between X and Y chromosomes leads to degeneration of the Y chromosome. The progression of degeneration is not well understood, as complete sequence assemblies of heteromorphic Y chromosomes have only been generated across a handful of taxa with highly degenerate sex chromosomes. Here, we describe the assembly of the threespine stickleback ( Gasterosteus aculeatus ) Y chromosome, which is less than 26 million years old and at an intermediate stage of degeneration. Our previous work identified that the non-recombining region between the X and the Y spans approximately 17.5 Mb on the X chromosome. Results We combine long-read sequencing with a Hi-C-based proximity guided assembly to generate a 15.87 Mb assembly of the Y chromosome. Our assembly is concordant with cytogenetic maps and Sanger sequences of over 90 Y chromosome BAC clones. We find three evolutionary strata on the Y chromosome, consistent with the three inversions identified by our previous cytogenetic analyses. The threespine stickleback Y shows convergence with more degenerate sex chromosomes in the retention of haploinsufficient genes and the accumulation of genes with testis-biased expression, many of which are recent duplicates. However, we find no evidence for large amplicons identified in other sex chromosome systems. We also report an excellent candidate for the master sex-determination gene: a translocated copy of Amh ( Amhy ). Conclusions Together, our work shows that the evolutionary forces shaping sex chromosomes can cause relatively rapid changes in the overall genetic architecture of Y chromosomes.
Discrepancies in the Reporting of Pathology Workforce Data—Is Reevaluation Also Needed for Other Medical Specialties?
Authors: Christopher J. VandenBussche
Journal: JAMA Network Open (2020)

Stanley J. Robboy, MD; David Gross, PhD; Jason Y. Park, MD, PhD; Elizabeth Kittrie, MMHS; James M. Crawford, MD, PhD; Rebecca L. Johnson, MD; Michael B. Cohen, MD; Donald S. Karcher, MD; Robert D. Hoffman II, MD, PhD; Anthony T. Smith, MLS; W. Stephen Black-Schaffer, MD
Endoscopic closure of a perforated rectum with an over-the-scope clip following diagnostic colonoscopy
Authors: Erol Barbur, Gurhan Sisman
Journal: Endoscopy (2020)

Our patient is a 77-year-old-woman who underwent colonoscopy for rectal bleeding which revealed hemorrhoids. A day after the colonoscopy, the patient attended our hospital’s emergency room with severe lower abdominal pain. Computed tomography (CT) with rectal contrast revealed free air and extravasation of the contrast material into the abdominal cavity ([Fig. 1]). As there was no abscess nor ascites, after discussion with general surgeons endoscopic closure of the perforation was decided upon.
Abstract 19406: Amelioration of Streptozotocin-Induced Diabetic Hypertriglyceridemia in the Absence of Hormone-Sensitive Lipase
Authors: Mikio Takanashi, Satoru Takase, Yoshino Taira, Takeshi Kimura, Sachiko Okazaki, Pengfei Xu, Chengcheng Li, Futoshi Shionoiri, Yoko Iizuka, Jun-ichi Osuga, Shun Ishibashi, Takashi Kadowaki, Hiroaki Okazaki
Journal: Circulation (2016)

Background: The molecular mechanism of diabetic lipemia in the setting of insulin deficiency is not fully understood. We unexpectedly found the role of hormone-sensitive lipase (HSL) in diabetic li...
"Avez-vous eu la grippe la semaine dernière ?" Une enquête téléphonique visant à évaluer le point de prévalence de la grippe dans la population suédoise
Authors: L Payne, S Kühlmann-Berenzon, K Ekdahl, J Giesecke, L Högberg, P Penttinen
Journal: Eurosurveillance (2005)

La surveillance sentinelle sous-estime souvent le vrai poids de la grippe dans une population compte-tenu du fait que ce systeme se base sur les consultations dans les etablissements medicaux. Une enquete telephonique a ete realisee dans la population sue
Enhanced inhibitory effect of (-) -epigallocatechin-3-gallate on intestinal tumor formation in ApcMin/+ mice by the combination with voluntary exercise or calcium supplementation
Authors: Jihyeung Ju, Xingpei Hao, Mousumi Bose, Bonnie Nolan, Michelle Cheh, George Wagner, Chung Yang
Journal: Cancer Research (2007)

4208  Previously, we reported that oral administration of (-)-epigallocatechin-3-gallate (EGCG), a major catechin in green tea, not only inhibited small intestinal tumor formation in ApcMin/+ mice, but also resulted in decreases of nuclear β-catenin and c-Myc levels and increases of E-cadherin levels in both the small intestinal tumors and HT29 human colon cancer cells (Cancer Res, 2005; 65(22):10623). The decreased nuclear β-catenin and increased E-cadherin levels in the small intestinal tumors was also occurred by short-term treatments of ApcMin/+ mice with EGCG (75 mg/kg i.g. 3h before sacrifice or 0.32% in the drinking fluid for 1 or 2 weeks), suggesting that the inhibition of aberrant β-catenin signaling is a relatively early event after EGCG administration. We then investigated effects of the combination of EGCG with voluntary exercise or calcium supplementation on intestinal tumor formation. In female ApcMin/+ mice maintained on the AIN93G diet, the combination of voluntary exercise with oral administration of 0.32% EGCG for 6 weeks significantly reduced small intestinal tumor formation by 45% (p
Stem Cell Pluripotency Genes Klf4 and Oct4 Regulate Complex SMC Phenotypic Changes Critical in Late-Stage Atherosclerotic Lesion Pathogenesis
Authors: Gabriel F. Alencar, Katherine M. Owsiany, Santosh Karnewar, Katyayani Sukhavasi, Giuseppe Mocci, Anh T. Nguyen, Corey M. Williams, Sohel Shamsuzzaman, Michal Mokry, Christopher A. Henderson, Ryan Haskins, Richard A. Baylis, Aloke V. Finn, Coleen A. McNamara, Eli R. Zunder, Vamsidhar Venkata, Gerard Pasterkamp, Johan Björkegren, Stefan Bekiranov, Gary K. Owens
Journal: Circulation (2020)

Rupture and erosion of advanced atherosclerotic lesions with a resultant myocardial infarction or stroke are the leading worldwide cause of death. However, we have a limited understanding of the identity, origin, and function of many cells that make up late-stage atherosclerotic lesions, as well as the mechanisms by which they control plaque stability.
Abstract 10825: Vascular Endothelial Growth Factor D and Mortality in Patients With Diabetes and Stable Coronary Heart Disease: From the ANOX Study
Authors: Hiromichi Wada, Masahiro Suzuki, Morihiro Matsuda, Yoichi Ajiro, Tsuyoshi Shinozaki, Satoru Sakagami, Kazuya Yonezawa, Masatoshi Shimizu, Junichi Funada, Takashi Takenaka, Yukiko Morita, Toshihiro Nakamura, Kazuteru Fujimoto, Hiromi Matsubara, Toru Kato, Takashi Unoki, Daisuke Takagi, Kyohma Wada, Miyaka Wada, Moritake Iguchi, Nobutoyo Masunaga, Mitsuru Ishii, Kazuhiko Kotani, Mitsuru Abe, Masaharu Akao, Koji Hasegawa
Journal: Circulation (2019)

Background: Vascular endothelial growth factor D (VEGF-D) is a secreted glycoprotein that can induce lymphangiogenesis and angiogenesis by binding to its specific receptors, VEGF receptor (VEGFR)-2...
Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus–Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial
Authors: Ravindra Uppaluri, Katie M. Campbell, Ann Marie Egloff, Paul Zolkind, Zachary L. Skidmore, Brian Nussenbaum, Randal C. Paniello, Jason T. Rich, Ryan Jackson, Patrik Pipkorn, Loren S. Michel, Jessica Ley, Peter Oppelt, Gavin P. Dunn, Erica K. Barnell, Nicholas C. Spies, Tianxiang Lin, Tiantian Li, David T. Mulder, Youstina Hanna, Iulia Cirlan, Trevor J. Pugh, Tenny Mudianto, Rachel Riley, Liye Zhou, Vickie Y. Jo, Matthew D. Stachler, Glenn J. Hanna, Jason Kass, Robert Haddad, Jonathan D. Schoenfeld, Evisa Gjini, Ana Lako, Wade Thorstad, Hiram A. Gay, Mackenzie Daly, Scott J. Rodig, Ian S. Hagemann, Dorina Kallogjeri, Jay F. Piccirillo, Rebecca D. Chernock, Malachi Griffith, Obi L. Griffith, Douglas R. Adkins
Journal: Clinical Cancer Research (2020)

Pembrolizumab improved survival in patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this study were to determine if pembrolizumab would be safe, result in pathologic tumor response (pTR), and lower the relapse rate in patients with resectable human papillomavirus (HPV)-unrelated HNSCC.Neoadjuvant pembrolizumab (200 mg) was administered and followed 2 to 3 weeks later by surgical tumor ablation. Postoperative (chemo)radiation was planned. Patients with high-risk pathology (positive margins and/or extranodal extension) received adjuvant pembrolizumab. pTR was quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cells/histiocytes: pTR-0 (<10%), pTR-1 (10%-49%), and pTR-2 (≥50%). Coprimary endpoints were pTR-2 among all patients and 1-year relapse rate in patients with high-risk pathology (historical: 35%). Correlations of baseline PD-L1 and T-cell infiltration with pTR were assessed. Tumor clonal dynamics were evaluated (ClinicalTrials.gov NCT02296684).Thirty-six patients enrolled. After neoadjuvant pembrolizumab, serious (grades 3-4) adverse events and unexpected surgical delays/complications did not occur. pTR-2 occurred in eight patients (22%), and pTR-1 in eight other patients (22%). One-year relapse rate among 18 patients with high-risk pathology was 16.7% (95% confidence interval, 3.6%-41.4%). pTR ≥10% correlated with baseline tumor PD-L1, immune infiltrate, and IFNγ activity. Matched samples showed upregulation of inhibitory checkpoints in patients with pTR-0 and confirmed clonal loss in some patients.Among patients with locally advanced, HPV-unrelated HNSCC, pembrolizumab was safe, and any pathologic response was observed in 44% of patients with 0% pathologic complete responses. The 1-year relapse rate in patients with high-risk pathology was lower than historical.
Cancer-protective effect of a synbiotic combination between <i>Lactobacillus gasseri</i> 505 and a <i>Cudrania tricuspidata</i> leaf extract on colitis-associated colorectal cancer
Authors: Nam Su Oh, Ji Young Lee, You-Tae Kim, Sae Hun Kim, Ju-Hoon Lee
Journal: Gut Microbes (2020)

Previously, a synbiotic combination of probiotic Lactobacillus gasseri 505 (LG) and a new prebiotic, Cudrania tricuspidata leaf extract (CT) in fermented milk, designated FCT, showed an in vitro immunomodulatory effect and antioxidant activity. Although synbiotic combination might have cancer-protective effects, these activities have not been fully validated in vivo. Ten-week treatment of LG, CT, or FCT to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated colorectal cancer (CAC) mouse model reduced both the incidence of colonic tumors and damage to the colonic mucosa effectively, suggesting a cancer-protective effect. To understand these, biomarkers associated with inflammation, colon barrier, apoptosis, and cancer cell proliferation were monitored in AOM/DSS group versus LG/CT/FCT groups. A synbiotic combination (FCT) down-regulated pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) and inflammation-associated enzymes (iNOS and COX-2), and up-regulated anti-inflammatory cytokines (IL-4 and IL-10). In addition, colon barrier experiment revealed that biomarkers of mucus layer (MUC-2 and TFF3) and tight junction (occludin and ZO-1) were up-regulated. Subsequent apoptosis experiment showed that pro-apoptotic factors (p53, p21, and Bax) were up-regulated and anti-apoptotic factors (Bcl-2 and Bcl-xL) were down-regulated. Furthermore, comparative metagenome analysis of gut microbiota revealed that Staphylococcus decreased but Lactobacillus, Bifidobacterium, and Akkermansia increased, supporting their protective effects, accompanied by increased short-chain fatty acids (SCFAs). Taken together, the FCT administration showed cancer-protective effects by reducing the risk of colitis-associated colon cancer via regulation of inflammation, carcinogenesis, and compositional change of gut microbiota. Consequently, the synbiotic combination (FCT) could be a novel potential health-protective natural agent against CAC.
Food‐induced immediate response of the esophagus—A newly identified syndrome in patients with eosinophilic esophagitis
Authors: Luc Biedermann, Mark Holbreich, Dan Atkins, Mirna Chehade, Evan S. Dellon, Glenn T. Furuta, Ikuo Hirano, Nirmala Gonsalves, Thomas Greuter, Sandeep Gupta, David A. Katzka, Willemijn De Rooij, Ekaterina Safroneeva, Alain Schoepfer, Philipp Schreiner, Dagmar Simon, Hans Uwe Simon, Marijn Warners, Albert‐Jan Bredenoord, Alex Straumann
Journal: Allergy (2020)

Abstract Background Dysphagia is the main symptom of adult eosinophilic esophagitis (EoE). We describe a novel syndrome, referred to as “food‐induced immediate response of the esophagus” (FIRE), observed in EoE patients. Methods Food‐induced immediate response of the esophagus is an unpleasant/painful sensation, unrelated to dysphagia, occurring immediately after esophageal contact with specific foods. Eosinophilic esophagitis experts were surveyed to estimate the prevalence of FIRE, characterize symptoms, and identify food triggers. We also surveyed a large group of EoE patients enrolled in the Swiss EoE Cohort Study for FIRE. Results Response rates were 82% (47/57) for the expert and 65% (239/368) for the patient survey, respectively. Almost, 90% of EoE experts had observed the FIRE symptom complex in their patients. Forty percent of EoE patients reported experiencing FIRE, more commonly in patients who developed EoE symptoms at a younger age (mean age of 46.4 years vs 54.1 years without FIRE; P &lt; .01) and in those with high allergic comorbidity. Food‐induced immediate response of the esophagus symptoms included narrowing, burning, choking, and pressure in the esophagus appearing within 5 minutes of ingesting a provoking food that lasted less than 2 hours. Symptom severity rated a median 7 points on a visual analogue scale from 1 to 10. Fresh fruits/vegetables and wine were the most frequent triggers. Endoscopic food removal was significantly more commonly reported in male patients with vs without FIRE (44.3% vs 27.6%; P = .03). Conclusions Food‐induced immediate response of the esophagus is a novel syndrome frequently reported in EoE patients, characterized by an intense, unpleasant/painful sensation occurring rapidly and reproducibly in 40% of surveyed EoE patients after esophageal contact with specific foods.