tbuckley/cabot-search huggingface dataset:
Extracranial Metastases From Glioblastoma With Primitive Neuronal Components on FDG PET/CT
Authors: Matthew D. Kay, Holly E. Pariury, Arie Perry, Blair A. Winegar, Phillip H. Kuo
Journal: Clinical Nuclear Medicine (2019)

Abstract A 17-year-old girl with World Health Organization grade IV glioblastoma with primitive neuronal components (histone H3 G34-mutant and IDH1 wild type) underwent whole-body FDG PET/CT staging due to vertebral metastases on initial MRI. PET/CT revealed extracranial metastatic disease with spinal leptomeningeal dissemination, osseous metastases, and peritoneal seeding via a ventriculoperitoneal shunt. Glioblastoma is uncommon in pediatric patients and particularly those with primitive neuronal components. Extracranial metastases from glioblastoma are more common in those with primitive neuronal components. This case demonstrates the utility of FDG PET/CT for revealing distant metastases from glioblastoma.
Efficacy of JAK 1/2 inhibition in the treatment of diffuse non-scarring alopecia due to systemic lupus erythematosus
Authors: Keisuke Maeshima, Hirotaka Shibata
Journal: Annals of the Rheumatic Diseases (2020)

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is crucial for the autocrine loop of type I interferons (IFNs) and is located upstream of important systemic lupus erythematosus (SLE)-associated pathogenic proinflammatory cytokines and chemokines. Baricitinib is a JAK 1/2 inhibitor approved for treating rheumatoid arthritis and is also being tested in other diseases, including SLE. Baricitinib improved the proportion of patients with SLE who achieved arthritis or rash resolution; however, the subset of patients with skin involvement was not reported in the study.1 Alopecia is one of the most common cutaneous symptoms in SLE. Patients can exhibit different subtypes of alopecia.2 Diffuse non-scarring hair loss, which is the most frequently observed type of alopecia in patients with SLE, is not life-threatening, but substantially affects quality of life for cosmetic reasons and may reflect latent …
The David Sign
Authors: Daniel M. Gelfman
Journal: JAMA Cardiology (2019)

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Abstract 168: Relation Between the Prehospital Administrated Doses of Epinephrine and the Acquisition of Return of Spontaneous Circulation in Patients With Cardiopulmonary Arrest
Authors: Kiyohiro Oshima, Makoto Aoki, Masato Murata, Jun Nakajima, Yusuke Sawada, Yuta Isshiki, Yumi Ichikawa, Kazunori Fukushima, Yuto Aramaki
Journal: Circulation (2019)

Introduction: The efficacy of epinephrine (Ep) administration to cardiopulmonary arrest (CPA) patients is still controversial, and correlation between plasma Ep levels of and prognosis in CPA patients is unclear. Hypothesis: We hypothesized that the more EP is administered, the higher the rate of ROSC becomes in CPA patients. The purpose of this study is to evaluate whether a dose of Ep influenced the prognosis in CPA patients. Methods: This was a prospective, observational clinical study, approved by the ethics committee of Gunma University Hospital (IRB #14-13). CPA patients transferred to our hospital were enrolled prospectively between July 2014 and July 2017. The levels of Ep in the plasma were measured using blood samples immediately obtained at the time of arrival to our hospital. Patients were divided into the four groups based on the prehospital administered dose of EP; patients without prehospital Ep administration (group Z), prehospital administration of 1mg Ep (group O), 2mg Ep (group T) and 4mg Ep (group F). The plasma Ep levels and the conditions of resuscitation were compared among those groups. The IBM SPSS Statistics 25 software was used for statistical analysis. Data are shown as median (Q1, Q3). The Kruskal-Wallis or chi-square tests were used to conduct the comparisons among four groups. P&lt;0.05 denoted statistical significance. Results: We analyzed 150 patients. There were 96 patients in group Z, 38 in group O, 11 in group T and 5 in group F. There was no significant difference in prehospital resuscitation time among 4 groups, and the level of Ep in the plasma obtained immediately after arrival at hospital was the highest in the group F with a significant difference {286.0 (247.2, 424.9) ng/ml in group F, 244.0 (22.1, 620.3) ng/ml in group T, 1.6 (0.5, 4.5) ng/ml in group O and 2.0 (0.4, 4.5) ng/ml in group Z, respectively, p&lt;0.001}. However, the ratio of ROSC acquisition was the lowest in the group F with a significant difference (0 in group F, 18.2% in group T, 15.8% in group O and 35.4% in group Z). Conclusions: Our results suggest that the prehospital administered dose of Ep is not relates with the acquisition of ROSC in patients with CPA.
Spectrum of Genetic Defects and Phenotype-Genotype Correlation in Dyserythropoietic Anemias: Bench to Bedside Approach in the Indian Scenario
Authors: Reena Das, Manu Jamwal, Anu Aggarwal, Prashant Sharma, Man Updesh Singh Sachdeva, Deepak Bansal, Sreejesh Sreedharanunni, Narender Kumar, Shano Naseem, Jasmina Ahluwalia, Neelam Varma, Pankaj Malhotra, Arindam Maitra
Journal: Blood (2019)
Testosterone Treatment in Adult Men With Age-Related Low Testosterone: A Clinical Guideline From the American College of Physicians
Authors: Amir Qaseem, Carrie A. Horwitch, Sandeep Vijan, Itziar Etxeandia-Ikobaltzeta, Devan Kansagara
Journal: Annals of Internal Medicine (2020)

The American College of Physicians (ACP) developed this guideline to provide clinical recommendations based on the current evidence of the benefits and harms of testosterone treatment in adult men with age-related low testosterone. This guideline is endorsed by the American Academy of Family Physicians.The ACP Clinical Guidelines Committee based these recommendations on a systematic review on the efficacy and safety of testosterone treatment in adult men with age-related low testosterone. Clinical outcomes were evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system and included sexual function, physical function, quality of life, energy and vitality, depression, cognition, serious adverse events, major adverse cardiovascular events, and other adverse events.The target audience includes all clinicians, and the target patient population includes adult men with age-related low testosterone.ACP suggests that clinicians discuss whether to initiate testosterone treatment in men with age-related low testosterone with sexual dysfunction who want to improve sexual function (conditional recommendation; low-certainty evidence). The discussion should include the potential benefits, harms, costs, and patient's preferences.ACP suggests that clinicians should reevaluate symptoms within 12 months and periodically thereafter. Clinicians should discontinue testosterone treatment in men with age-related low testosterone with sexual dysfunction in whom there is no improvement in sexual function (conditional recommendation; low-certainty evidence).ACP suggests that clinicians consider intramuscular rather than transdermal formulations when initiating testosterone treatment to improve sexual function in men with age-related low testosterone, as costs are considerably lower for the intramuscular formulation and clinical effectiveness and harms are similar.ACP suggests that clinicians not initiate testosterone treatment in men with age-related low testosterone to improve energy, vitality, physical function, or cognition (conditional recommendation; low-certainty evidence).
High residual C-peptide likely contributes to glycemic control in type 1 diabetes
Authors: Michael R. Rickels, Carmella Evans-Molina, Henry T. Bahnson, Alyssa Ylescupidez, Kristen J. Nadeau, Wei Hao, Mark A. Clements, Jennifer L. Sherr, Richard E. Pratley, Tamara S. Hannon, Viral N. Shah, Kellee M. Miller, Carla J. Greenbaum
Journal: Journal of Clinical Investigation (2020)

BACKGROUNDResidual C-peptide is detected in many people for years following the diagnosis of type 1 diabetes; however, the physiologic significance of low levels of detectable C-peptide is not known.METHODSWe studied 63 adults with type 1 diabetes classified by peak mixed-meal tolerance test (MMTT) C-peptide as negative (<0.007 pmol/mL; n = 15), low (0.017-0.200; n = 16), intermediate (>0.200-0.400; n = 15), or high (>0.400; n = 17). We compared the groups' glycemia from continuous glucose monitoring (CGM), β cell secretory responses from a glucose-potentiated arginine (GPA) test, insulin sensitivity from a hyperinsulinemic-euglycemic (EU) clamp, and glucose counterregulatory responses from a subsequent hypoglycemic (HYPO) clamp.RESULTSLow and intermediate MMTT C-peptide groups did not exhibit β cell secretory responses to hyperglycemia, whereas the high C-peptide group showed increases in both C-peptide and proinsulin (P ≤ 0.01). All groups with detectable MMTT C-peptide demonstrated acute C-peptide and proinsulin responses to arginine that were positively correlated with peak MMTT C-peptide (P < 0.0001 for both analytes). During the EU-HYPO clamp, C-peptide levels were proportionately suppressed in the low, intermediate, and high C-peptide compared with the negative group (P ≤ 0.0001), whereas glucagon increased from EU to HYPO only in the high C-peptide group compared with negative (P = 0.01). CGM demonstrated lower mean glucose and more time in range for the high C-peptide group.CONCLUSIONThese results indicate that in adults with type 1 diabetes, β cell responsiveness to hyperglycemia and α cell responsiveness to hypoglycemia are observed only at high levels of residual C-peptide that likely contribute to glycemic control.FUNDINGFunding for this work was provided by the Leona M. and Harry B. Helmsley Charitable Trust, the National Center for Advancing Translational Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases.
Rational drug design, synthesis, and biological evaluation of novel chiral tetrahydronaphthalene-fused spirooxindole as MDM2-CDK4 dual inhibitor against glioblastoma
Authors: Biao Wang, Fu Peng, Wei Huang, Jin Zhou, Nan Zhang, Jia Sheng, Phensinee Haruehanroengra, Gu He, Bo Han
Journal: Acta Pharmaceutica Sinica B (2019)

Simultaneous inhibition of MDM2 and CDK4 may be an effective treatment against glioblastoma. A collection of chiral spirocyclic tetrahydronaphthalene (THN)-oxindole hybrids for this purpose have been developed. Appropriate stereochemistry in THN-fused spirooxindole compounds is key to their inhibitory activity: selectivity differed by over 40-fold between the least and most potent stereoisomers in time-resolved FRET and KINOMEscan® in vitro assays. Studies in glioblastoma cell lines showed that the most active compound ent-4g induced apoptosis and cell cycle arrest by interfering with MDM2 -P53 interaction and CDK4 activation. Cells treated with ent-4g showed up-regulation of proteins involved in P53 and cell cycle pathways. The compound showed good anti-tumor efficacy against glioblastoma xenografts in mice. These results suggested that rational design, asymmetric synthesis and biological evaluation of novel tetrahydronaphthalene fused spirooxindoles could generate promising MDM2-CDK4 dual inhibitors in glioblastoma therapy.
Interaction between filaggrin mutations and neonatal cat exposure in atopic dermatitis
Authors: Jacob P. Thyssen, Tarunveer S. Ahluwalia, Lavinia Paternoster, Natalia Ballardini, Anna Bergström, Erik Melén, Bo L. Chawes, Jakob Stokholm, Jonathan O'B Hourihane, Donnchadh M. O'Sullivan, Peter Bager, Mads Melbye, Mariona Bustamante, Maties Torrent, Ana Esplugues, Liesbeth Duijts, Chen Hu, Niels J. Elbert, Suzanne G. M. A. Pasmans, Tamar E. C. Nijsten, Andrea von Berg, Marie Standl, Tamara Schikowski, Gunda Herberth, Joachim Heinrich, Young‐Ae Lee, Ingo Marenholz, Susanne Lau, John A. Curtin, Angela Simpson, Adnan Custovic, Craig E. Pennell, Carol A. Wang, Patrick G. Holt, Hans Bisgaard, Klaus Bønnelykke
Journal: Allergy (2019)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Functional common genetic polymorphisms interact to predict breast cancer risk
Authors: Christopher E. Aston, David A. Ralph, Sharmila Manjeshwar, Amy D. West, Dannielle E. Branam, Bobby A. Gramling, Daniele C. Defreese, Linda F. Thompson, Melissa A. Craft, Debra S. Mitchell, Craig D. Shimasaki, John J. Mulvihill, Eldon R. Jupe
Journal: Cancer Research (2004)

4494  The proportion of breast cancer in the general population attributable to germline mutations in highly penetrant genes (e.g., BRCA1/2) is small because of the low frequency of these mutations. Common, but weakly penetrant, functional genetic polymorphisms are likely to account for most of the genetic risk for breast cancer in the general population. Current polygenic risk models assume, perhaps erroneously, that the effects of the component genes act independently. Potential gene-gene interactions among ten genes, with known or predicted functional consequences in development of breast carcinoma, were examined in a case-control study of more than 1000 Caucasian women with breast cancer and more than 2000 controls. Association of breast cancer risk with variation in single genes and two- and three- gene combinations was analyzed for two age groups: 53 years and under, and over 53 years. The OR for a genotype was calculated and compared to a null distribution of ORs generated for this genotype by randomizing (10,000 times in these analyses) the case-control status of the individuals in the sample to give an empirical estimate for the p-value for the observed OR. Re-sampling was performed to give an empirical estimate of the 95% confidence interval and a likely more stable estimate of the OR for the genotype, particularly for the less common genotypes. In these analyses the population of individuals was resampled 10,000 times with each repetition composed of 80% of the controls and 80% of the cases selected at random from the whole sample. Over 100 genotypes met stringent criteria for significance (α=1/10,000) with ORs ranging from 0.20 to 5.2. The majority of the significant ORs were two- and three-gene combinations. Comparing observed ORs to ORs predicted by an independent gene model showed that about 25% of the significant multigenic combinations differed markedly from the predicted value. Thus, combinations of genes interact to affect risk for breast cancer in a manner that is not predictable by combining the effects of the individual component genes. While independent genes are a valid starting point in a polygenic model, identifying and incorporating modification of risks associated with gene-gene interactions will improve accuracy of the model and should be taken into consideration when building polygenic models for breast cancer risk. In addition, further exploration of the biologic basis for these multigenic interactions might reveal etiologic or therapeutic insights into breast cancer and other cancers.
Abstract 13440: Atrial Remodeling Caused by Sustained Atrial Flutter in a Novel Chronic Dog Model and Interactions With Atrial Fibrillation
Authors: Jean B Guichard, Feng Xiong, Yoshihiro Sobue, Xiaoyan Qi, Antoine Da Costa, Stanley Nattel
Journal: Circulation (2018)

Introduction: Atrial flutter (AFL) causes clinical atrial remodeling (RMOD), but no experimental studies have addressed the RMOD effects of sustained AFL. Hypothesis: 1. Sustained AFL in dogs leads...
Biliary Atresia: Biliary‐Enteric Drainage or Primary Liver Transplant?
Authors: Heung Bae Kim, Scott A. Elisofon
Journal: Hepatology (2019)

Kim, Heung Bae M.D.; Elisofon, Scott A. M.D.Editor(s): Corey, Kathleen E.3; Malhi, Harmeet4 Author Information
Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab
Authors: Emily Z. Keung, Melissa Burgess, Ruth Salazar, Edwin R. Parra, Jaime Rodrigues-Canales, Vanessa Bolejack, Brian A. Van Tine, Scott M. Schuetze, Steven Attia, Richard F. Riedel, James Hu, Scott H. Okuno, Dennis A. Priebat, Sujana Movva, Lara E. Davis, Damon R. Reed, Alexandre Reuben, Christina L. Roland, Denise Reinke, Alexander J. Lazar, Wei-Lien Wang, Jennifer A. Wargo, Hussein A. Tawbi
Journal: Clinical Cancer Research (2020)

Abstract Purpose: We recently reported a 17.5% objective RECIST 1.1 response rate in a phase II study of pembrolizumab in patients with advanced sarcoma (SARC028). The majority of responses occurred in undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLPS). We sought to determine whether we can identify immune features that correlate with clinical outcomes from tumor tissues obtained pre- and on-treatment. Patients and Methods: Pretreatment (n = 78) and 8-week on-treatment (n = 68) tumor biopsies were stained for PD-L1 and multiplex immunofluorescence panels. The density of positive cells was quantified to determine associations with anti–PD-1 response. Results: Patients that responded to pembrolizumab were more likely to have higher densities of activated T cells (CD8+ CD3+ PD-1+) and increased percentage of tumor-associated macrophages (TAM) expressing PD-L1 pre-treatment compared with non-responders. Pre-treatment tumors from responders also exhibited higher densities of effector memory cytotoxic T cells and regulatory T cells compared with non-responders. In addition, higher density of cytotoxic tumor-infiltrating T cells at baseline correlated with a better progression-free survival (PFS). Conclusions: We show that quantitative assessments of CD8+ CD3+ PD-1+ T cells, percentage of TAMs expressing PD-L1, and other T-cell densities correlate with sarcoma response to pembrolizumab and improved PFS. Our findings support that multiple cell types present at the start of treatment may enhance tumor regression following anti–PD-1 therapy in specific advanced sarcomas. Efforts to confirm the activity of pembrolizumab in an expansion cohort of patients with UPS/DDLPS are underway.
18F-FDG PET in Giant Cell Arteritis
Authors: Niloefar Ahmadi Bidakhvidi, Karolien Goffin, Koen Van Laere, Olivier Gheysens, Daniel Blockmans
Journal: Clinical Nuclear Medicine (2019)

An 87-year-old man, without significant history, presented at the emergency department with recurrent episodes of fever and weight loss for several weeks without diagnosis, despite extensive routine investigations including conventional imaging. F-FDG PET/CT revealed strongly increased uptake in the peripheral vessels of the upper and lower limbs with relative sparing of the larger vessels. Temporal artery biopsy was positive for arteritis. The diagnosis of giant cell arteritis with mainly involvement of upper and lower limbs was made, and treatment with high-dose oral methylprednisolone was started, resulting in a rapid clinical and biochemical improvement.
Use of Immunotherapy With Programmed Cell Death 1 vs Programmed Cell Death Ligand 1 Inhibitors in Patients With Cancer
Authors: Jianchun Duan, Longgang Cui, Xiaochen Zhao, Hua Bai, Shangli Cai, Guoqiang Wang, Zhengyi Zhao, Jing Zhao, Shiqing Chen, Jia Song, Chuang Qi, Qing Wang, Mengli Huang, Yuzi Zhang, Depei Huang, Yuezong Bai, Feng Sun, J. Jack Lee, Zhijie Wang, Jie Wang
Journal: JAMA Oncology (2019)

Immune checkpoint inhibitors of programmed cell death 1 (PD-1) and its ligand (PD-L1) have led to a paradigm shift in cancer treatment. Understanding the clinical efficacy and safety profile of these drugs is necessary for treatment strategy in clinical practice.To assess the differences between anti-PD-1 and anti-PD-L1 regarding efficacy and safety shown in randomized clinical trials across various tumor types.Systematic searches of PubMed, Cochrane CENTRAL, and Embase were conducted from January 1, 2000, to March 1, 2019. In addition, abstracts and presentations from all major conference proceedings were reviewed.All randomized clinical trials that compared anti-PD-1 and anti-PD-L1 with standard treatment in patients with cancer were selected as candidates. Retrospective studies, single-arm phase 1/2 studies, and trials comparing anti-PD-1 and anti-PD-L1 with other immunotherapies were excluded. Studies of anti-PD-1 and anti-PD-L1 therapy were screened and paired by the matching of clinical characteristics as mirror groups.Three investigators independently extracted data from each study following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline. Trial names, first author, year of publication, study design, National Clinical Trial identifier number, blinding status, study phase, pathologic characteristics, number of patients, patients' age and sex distribution, Eastern Cooperative Oncology Group Performance Status, lines of treatment, study drugs, biomarker status, follow-up time, incidence of adverse events, and hazard ratios (HRs) with 95% CIs for overall survival and progression-free survival were extracted. A random-effects model was applied for data analysis.Differences in OS between anti-PD-1 and anti-PD-L1 across different cancer types were assessed. An effect size was derived from each mirror group and then pooled across all groups using a random-effects model.Nineteen randomized clinical trials involving 11 379 patients were included in the meta-analysis. Overall, anti-PD-1 exhibited superior overall survival (HR, 0.75; 95% CI, 0.65-0.86; P < .001) and progression-free survival (HR, 0.73; 95% CI, 0.56-0.96; P = .02) compared with anti-PD-L1. No significant difference was observed in their safety profiles. Sensitivity analysis presented consistency in the overall estimates across these analyses. Consistent results were observed through frequentist and bayesian approaches with the same studies.Comprehensive analysis suggests that anti-PD-1 exhibited favorable survival outcomes and a safety profile comparable to that of anti-PD-L1, which may provide a useful guide for clinicians.
Infographic. Is running associated with a lower risk of all-cause, cardiovascular and cancer mortality, and is more better? A systematic review and meta-analysis
Authors: Zeljko Pedisic, Nipun Shrestha, Jozo Grgic, Stephanie Kovalchik, Emmanuel Stamatakis, Nucharapon Liangruenrom, Sylvia Titze, Stuart Biddle, Adrian E Bauman, Adam Virgile, Pekka Oja
Journal: British Journal of Sports Medicine (2020)

Running and jogging are among the most popular types of exercise globally. Running is associated with improved indicators of cardiometabolic health.1–3 However, findings from previous studies showed inconsistent associations between running participation and all-cause, cancer and cardiovascular mortality. In our recent systematic review,4 published in the British Journal of Sports Medicine , we therefore synthesised the results of previous studies on this topic.



We found 14 studies from six prospective …