tbuckley/cabot-search huggingface dataset:
Immune checkpoint inhibitor-associated celiac disease
Authors: Yousef Badran, Angela Shih, Donna Leet, Meghan J Mooradian, Alexandra Coromilas, Jonathan Chen, Marina Kem, Hui Zheng, Jennifer Borowsky, Joseph Misdraji, Mari Mino-Kenudson, Michael Dougan
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Rare cases of immune checkpoint inhibitor (ICI)-associated celiac disease (ICI-CeD) have been reported, suggesting that disruption of tolerance mechanisms by ICIs can unmask celiac disease (CeD). This study aims to characterize the clinicopathological and immunophenotypic features of ICI-CeD in comparison to ICI-associated duodenitis (ICI-Duo) and usual CeD. Methods A medical and pathological records search between 2015 and 2019 identified eight cases of ICI-CeD, confirmed by tTG-IgA. Nine cases of ICI-Duo, 28 cases of moderate CeD, as well as 5 normal controls were used as comparison groups. Clinical information was collected from the electronic medical records. Immunohistochemistry for CD3, CD8, T-cell receptor gamma/delta (γδ), programmed death ligand 1 (PD-L1), and programmed death 1 (PD-1) were performed, with quantification of intraepithelial lymphocyte (IEL) subsets in three well-oriented villi. CD68, PD-L1, and PD-1 were assessed as a percentage of lamina propria surface area infiltrated by positive cells. Statistical significance was calculated by the Student’s t-test and Fisher’s exact test. Results The eight patients with ICI-CeD (F:M=1:3) and nine patients with ICI-Duo (F:M=5:4) presented similarly with diarrhea (13/17) and abdominal pain (11/17) after a median of 1.6 months on ICI therapy. In patients with ICI-CeD, tTG-IgA ranged from 104 to &gt;300 IU/mL. Histological findings in ICI-CeD and ICI-Duo were similar and included expansion of the lamina propria, active neutrophilic duodenitis, variably increased IELs, and villous blunting. Immunohistochemistry showed that the average number of IELs per 100 enterocytes is comparable between ICI-CeD and ICI-Duo, with increased CD3 + CD8 + T cells compared with normal duodenum but decreased γδ T cells compared with CeD. Average PD-L1 percentage was 9% in ICI-CeD and 18% in ICI-Duo, in comparison to &lt;1% in CeD and normal duodenum; average PD-1 percentage was very low to absent in all cases (&lt;3%). On follow-up, five patients with ICI-CeD improved on a gluten-free diet (GFD) as the sole therapeutic intervention (with down-trending tTG-IgA) while the other three required immunosuppression. All patients who developed ICI-Duo received immunosuppression with variable improvement in symptoms. Conclusions ICI-CeD resembles ICI-Duo clinically and histologically but shares the serological features and response to gluten withdrawal with classic CeD. Immunophenotyping of IELs in ICI-CeD and ICI-Duo also shows similar CD3, CD8, γδ T cell subsets, and PD-L1 populations, all of which differed quantitatively from usual CeD. We conclude that ICI-CeD is biologically similar to ICI-Duo and is likely a variant of ICI-Duo, but treatment strategies differ, with ICI-CeD often improving with GFD alone, whereas ICI-Duo requires systemic immunosuppression.
Abstract 94: Are Longer Resuscitation Efforts Associated with Improved Survival During In-Hospital Arrest? An Analysis from the GWTG--Resuscitation
Authors: Zachary D Goldberger, Paul S Chan, Robert A Berg, Steven L Kronick, Mingrui Lu, Mousumi Banerjee, Rodney A Hayward, Harlan M Krumholz, Brahmajee K Nallamothu
Journal: Circulation (2011)

Background How long resuscitation attempts should continue prior to the termination of efforts is unknown for in-hospital cardiac arrests. We hypothesized that resuscitation duration in non-survivors varies across hospitals and that patients at hospitals with longer attempts have improved survival. Methods We identified 70,156 patients with in-hospital cardiac arrests between 2000 and 2009 at 440 hospitals within a large national registry. We stratified hospitals into quartiles of equal size based on their median duration of resuscitation attempts prior to the termination of efforts in patients who did not achieve return of spontaneous circulation (ROSC). Through hierarchical modeling, we then assessed whether patients at hospitals with longer median resuscitation durations among their non-survivors had higher risk-adjusted survival. Results The overall proportion of patients achieving ROSC was 48.5%. Among non-survivors, the median resuscitation duration was 20 minutes, with efforts terminated within 10 minutes in 15.5% and within 30 minutes in 76.3%. Compared with patients at hospitals in the quartile with the shortest resuscitation duration among their non-survivors, patients at hospitals with longer resuscitation durations had an increasing likelihood of achieving ROSC (p&lt;0.001 for trend, Table). These findings were driven largely by a higher likelihood of achieving ROSC at later points during the cardiac arrest for patients at hospitals with longer resuscitation durations, and were most pronounced for cardiac arrests due to pulseless electrical activity and asystole. Rates of survival to discharge showed a similar pattern of results. Conclusions Duration of resuscitation attempts varies substantially across hospitals during in-hospital cardiac arrest. Patients at hospitals with longer resuscitation durations have a higher likelihood of ROSC and survival to discharge.
Nuclear antigen–reactive CD4+ T cells expand in active systemic lupus erythematosus, produce effector cytokines, and invade the kidneys
Authors: Dimas Abdirama, Sebastian Tesch, Anna-Sophie Grießbach, Caroline von Spee-Mayer, Jens Y. Humrich, Ulrik Stervbo, Nina Babel, Christian Meisel, Tobias Alexander, Robert Biesen, Petra Bacher, Alexander Scheffold, Kai-Uwe Eckardt, Falk Hiepe, Andreas Radbruch, Gerd-Rüdiger Burmester, Gabriela Riemekasten, Philipp Enghard
Journal: Kidney International (2020)

Systemic lupus erythematosus is a systemic and chronic autoimmune disease characterized by loss of tolerance towards nuclear antigens with autoreactive CD4+ T cells implicated in disease pathogenesis. However, very little is known about their receptor specificity since the detection of human autoantigen specific CD4+ T cells has been extremely challenging. Here we present an analysis of CD4+ T cells reactive to nuclear antigens using two complementary methods: T cell libraries and antigen-reactive T cell enrichment. The frequencies of nuclear antigen specific CD4+ T cells correlated with disease severity. These autoreactive T cells produce effector cytokines such as interferon-γ, interleukin-17, and interleukin-10. Compared to blood, these cells were enriched in the urine of patients with active lupus nephritis, suggesting an infiltration of the inflamed kidneys. Thus, these previously unrecognized characteristics support a role for nuclear antigen-specific CD4+ T cells in systemic lupus erythematosus.
The evolutionarily conserved piRNA-producing locus pi6 is required for male mouse fertility
Authors: Pei-Hsuan Wu, Yu Fu, Katharine Cecchini, Deniz M. Özata, Amena Arif, Tianxiong Yu, Cansu Colpan, Ildar Gainetdinov, Zhiping Weng, Phillip D. Zamore
Journal: Nature Genetics (2020)
Risk-Benefit Comparisons Between Shorter and Longer Durations of Adjuvant Chemotherapy in High-Risk Stage II Colorectal Cancer
Authors: Zachary R. McCaw, Dae Hyun Kim, Lee-Jen Wei
Journal: JAMA Oncology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Comment on ‘Successful remission with tofacitinib in a patient with refractory Takayasu arteritis complicated by ulcerative colitis’ by Kuwabara<i>et al</i>
Authors: Valeria Rios Rodriguez, Judith Rademacher, Mikhail Protopopov, Murat Torgutalp, Hildrun Haibel, Janis Lucas Vahldiek, Ann-Christin von Brünneck, Safwan Omran, Denis Poddubnyy, Fabian Proft
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the case report by Kuwabara et al .1 With this comment, we want to share the case of a 38-year-old male patient with a long history of radiographic axial spondyloarthritis (r-axSpA)—with HLA-B27 positivity, peripheral joint involvement and skin psoriasis—complicated by Takayasu arteritis (TAK), showing a favourable response to a combination therapy of Tofacitinib (TOF) and methotrexate (MTX) with the readers of the ‘Annals of the Rheumatic Diseases’ .

The r-axSpA was well-controlled under tumour necrosis factor alpha inhibiton with infliximab and MTX between 2013 and 2017 (figure 1). At the beginning of 2017, he presented a worsening of his disease with peripheral arthritis/enthesitis in addition to fatigue and myalgia of the neck and shoulder region. Therefore, in 2017/2018, the treatment was changed to golimumab, and then—due to persistent symptoms—to etanercept, secukinumab and certolizumab pegol and additionally MTX was switched to sulfasalazine (SSZ). All treatment courses failed to achieve an adequate disease control (figure 1). Additionally, the patient self-administered oral prednisolone (PSL) (between 50 and 15 mg daily) during that period.



Figure 1 
Treatment and CRP courses overview of the different treatment strategies and the CRP course over time. bDMARDs, biological disease modifying antirheumatic …
A gender-sensitised weight-loss and healthy living program for men with overweight and obesity in Australian Football League settings (Aussie-FIT): A pilot randomised controlled trial
Authors: Dominika Kwasnicka, Nikos Ntoumanis, Kate Hunt, Cindy M. Gray, Robert U. Newton, Daniel F. Gucciardi, Cecilie Thøgersen-Ntoumani, Jenny L. Olson, Joanne McVeigh, Deborah A. Kerr, Sally Wyke, Philip J. Morgan, Suzanne Robinson, Marshall Makate, Eleanor Quested
Journal: PLoS Medicine (2020)

Background Recent evidence shows that sport settings can act as a powerful draw to engage men in weight loss. The primary objective of this pilot study was to test the feasibility of delivering and to evaluate preliminary efficacy of Aussie-FIT, a weight-loss program for men with overweight/obesity delivered in Australian Football League (AFL) settings, in preparation for a future definitive trial. Methods and findings This 6-month pilot trial took place in Perth, Australia. Participants were overweight/obese (Body Mass Index [BMI] ≥ 28 kg/m2), middle-aged (35–65 years old) men. Participants were recruited in May 2018, and the intervention took place between June and December 2018. The intervention involved 12 weekly 90-min face-to-face sessions, incorporating physical activity, nutrition, and behaviour change information and practical activities delivered by coaches at 2 clubs. Data were collected at baseline and immediately postintervention. For trial feasibility purposes, 6-month follow-ups were completed. Outcomes were differences in weight loss (primary outcome) and recruitment and retention rates, self-reported measures (for example, psychological well-being), device-measured physical activity, waist size, and blood pressure at 3 months. Within 3 days of advertising at each club, 426 men registered interest; 306 (72%) were eligible. Men were selected on a first-come first-served basis (n = 130; M age = 45.8, SD = 8; M BMI = 34.48 kg/m2, SD = 4.87) and randomised by a blinded researcher. Trial retention was 86% and 63% at 3- and 6-month follow-ups (respectively). No adverse events were reported. At 3 months, mean difference in weight between groups, adjusted for baseline weight and group, was 3.3 kg (95% CI 1.9, 4.8) in favour of the intervention group (p < 0.001). The intervention group's moderate-to-vigorous physical activity (MVPA) was higher than the control group by 8.54 min/day (95% CI 1.37, 15.71, p = 0.02). MVPA among men attracted to Aussie-FIT was high at baseline (intervention arm 35.61 min/day, control arm 38.38 min/day), which may have limited the scope for improvement. Conclusions Aussie-FIT was feasible to deliver; participants increased physical activity, decreased weight, and reported improvements in other outcomes. Issues with retention were a limitation of this trial. In a future, fully powered randomised controlled trial (RCT), retention could be improved by conducting assessments outside of holiday seasons. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12617000515392.
Inclusive innovation in telehealth
Authors: Kimberly Noel, Brooke Ellison
Journal: npj Digital Medicine (2020)

It has been 30 years since the passage of the Americans with Disabilities Act and technological development has drastically changed the future for those with disabilities. As healthcare evolves toward promoting telehealth and patient-centered care, leaders must embrace persons with disabilities and caregivers as valued partners in design and implementation, not as passive "end-users". We call for a new era of inclusive innovation, a term proposed in this publication to describe accessible technological design for all. The next 30 years of the ADA leading to year 2050, should reflect a new era of access, whereby digital health surmounts geographic, social, and economic barriers toward an inclusive virtual society.
Therapy-related myelodysplastic syndromes deserve specific diagnostic sub-classification and risk-stratification—an approach to classification of patients with t-MDS
Authors: A. Kuendgen, M. Nomdedeu, H. Tuechler, G. Garcia-Manero, R. S. Komrokji, M. A. Sekeres, M. G. Della Porta, M. Cazzola, A. E. DeZern, G. J. Roboz, D. P. Steensma, A. A. Van de Loosdrecht, R. F. Schlenk, J. Grau, X. Calvo, S. Blum, A. Pereira, P. Valent, D. Costa, A. Giagounidis, B. Xicoy, H. Döhner, U. Platzbecker, C. Pedro, M. Lübbert, I. Oiartzabal, M. Díez-Campelo, M. T. Cedena, S. Machherndl-Spandl, M. López-Pavía, C. D. Baldus, M. Martinez-de-Sola, R. Stauder, B. Merchan, A. List, C. Ganster, T. Schroeder, M. T. Voso, M. Pfeilstöcker, H. Sill, B. Hildebrandt, J. Esteve, B. Nomdedeu, F. Cobo, R. Haas, F. Sole, U. Germing, P. L. Greenberg, D. Haase, G. Sanz
Journal: Leukemia (2020)

Abstract In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p &lt; 0.001). The results regarding carefully reviewed cytogenetic data, classifications, and prognostic scores confirmed that t-MDS are similarly heterogeneous as p-MDS and therefore deserve the same careful differentiation regarding risk. As reference, these results were compared with 4593 primary MDS (p-MDS) patients represented in the International Working Group for Prognosis in MDS database (IWG-PM). Although a less favorable clinical outcome occurred in each t-MDS subset compared with p-MDS subgroups, FAB and WHO-classification, IPSS-R, and WPSS-R separated t-MDS patients into differing risk groups effectively, indicating that all established risk factors for p-MDS maintained relevance in t-MDS, with cytogenetic features having enhanced predictive power. These data strongly argue to classify t-MDS as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies.
Cancer therapy with iron oxide nanoparticles: Agents of thermal and immune therapies
Authors: Frederik Soetaert, Preethi Korangath, David Serantes, Steven Fiering, Robert Ivkov
Journal: Advanced Drug Delivery Reviews (2020)

Significant research and preclinical investment in cancer nanomedicine has produced several products, which have improved cancer care. Nevertheless, there exists a perception that cancer nanomedicine 'has not lived up to its promise' because the number of approved products and their clinical performance are modest. Many of these analyses do not consider the long clinical history and many clinical products developed from iron oxide nanoparticles. Iron oxide nanoparticles have enjoyed clinical use for about nine decades demonstrating safety, and considerable clinical utility and versatility. FDA-approved applications of iron oxide nanoparticles include cancer diagnosis, cancer hyperthermia therapy, and iron deficiency anemia. For cancer nanomedicine, this wealth of clinical experience is invaluable to provide key lessons and highlight pitfalls in the pursuit of nanotechnology-based cancer therapeutics. We review the clinical experience with systemic liposomal drug delivery and parenteral therapy of iron deficiency anemia (IDA) with iron oxide nanoparticles. We note that the clinical success of injectable iron exploits the inherent interaction between nanoparticles and the (innate) immune system, which designers of liposomal drug delivery seek to avoid. Magnetic fluid hyperthermia, a cancer therapy that harnesses magnetic hysteresis heating is approved for treating humans only with iron oxide nanoparticles. Despite its successful demonstration to enhance overall survival in clinical trials, this nanotechnology-based thermal medicine struggles to establish a clinical presence. We review the physical and biological attributes of this approach, and suggest reasons for barriers to its acceptance. Finally, despite the extensive clinical experience with iron oxide nanoparticles new and exciting research points to surprising immune-modulating potential. Recent data demonstrate the interactions between immune cells and iron oxide nanoparticles can induce anti-tumor immune responses. These present new and exciting opportunities to explore additional applications with this venerable technology. Clinical applications of iron oxide nanoparticles present poignant case studies of the opportunities, complexities, and challenges in cancer nanomedicine. They also illustrate the need for revised paradigms and multidisciplinary approaches to develop and translate nanomedicines into clinical cancer care.
Safety and efficacy of chimeric antigen receptor (CAR)-T-cell therapy in persons with advanced B-cell cancers and hepatitis B virus-infection
Authors: Ying Wang, Yang Liu, Xu Tan, Bin Pan, Jian Ge, Kunming Qi, Hai Cheng, Jiang Cao, Ming Shi, Zhiling Yan, Jianlin Qiao, Guangjun Jing, Xue Wang, Wei Sang, Ruixiang Xia, Xi Zhang, Zhenyu Li, Robert Peter Gale, Junnian Zheng, Feng Zhu, Kailin Xu
Journal: Leukemia (2020)
Effect of weight loss on survival in esophageal cancer patients undergoing neoadjuvant chemoradiotherapy and surgery.
Authors: Tao Li
Journal: Journal of Clinical Oncology (2020)

e24076 Background: This study aimed to determine the impact of weight loss during neoadjuvant chemoradiotherapy on the survival of patients with esophageal carcinoma. Methods: We retrospectively examined 102 consecutive patients with esophageal carcinoma who underwent neoadjuvant chemoradiotherapy followed by radical resection at Sichuan Cancer Hospital &amp; Institute between 2003 and 2017. The patients were divided into three groups based on the amount of body weight lost during neoadjuvant chemoradiotherapy: severe weight loss (&gt;10%), high weight loss (5%–10%), and low weight loss (&lt;5%). The correlations of weight loss with toxicity, progression-free survival, and overall survival were investigated. Results: The median overall survival was 49.7 months in the low weight loss group compared with 35.4 and 25.1 months in the high and severe weight loss groups ( P = 0.041). The 1-year overall survival rates in the severe, high, and low weight loss groups were 62.5%, 85.0%, and 90.7%, respectively; the corresponding 3-year overall survival rates were 21.9%, 47.3%, and 68.8%, respectively, and the corresponding 5-year overall survival rates were 21.9%, 31.0%, and 44.4%, respectively. The multivariate analysis indicated that a pathological complete response and severe weight loss were independent prognostic factors for overall survival. Any leukopenia ( P = 0.024), leukopenia of at least grade 3 ( P = 0.021), and anemia ( P = 0.042) occurred more frequently in the severe weight loss group. Conclusions: Weight loss during neoadjuvant CRT is an independent and adverse prognostic factor in esophageal carcinoma patients, whereas a stable weight confers a better prognosis. Keywords: esophageal cancer, prognosis, weight loss, neoadjuvant chemoradiotherapy, toxicity.
Rb and p53 Execute Distinct Roles in the Development of Pancreatic Neuroendocrine Tumors
Authors: Yuki Yamauchi, Yuzo Kodama, Masahiro Shiokawa, Nobuyuki Kakiuchi, Saiko Marui, Takeshi Kuwada, Yuko Sogabe, Teruko Tomono, Atsushi Mima, Toshihiro Morita, Tomoaki Matsumori, Tatsuki Ueda, Motoyuki Tsuda, Yoshihiro Nishikawa, Katsutoshi Kuriyama, Yojiro Sakuma, Yuji Ota, Takahisa Maruno, Norimitsu Uza, Atsuhiro Masuda, Hisato Tatsuoka, Daisuke Yabe, Sachiko Minamiguchi, Toshihiko Masui, Nobuya Inagaki, Shinji Uemoto, Tsutomu Chiba, Hiroshi Seno
Journal: Cancer Research (2020)

Pancreatic neuroendocrine tumors (PanNET) were classified into grades (G) 1 to 3 by the World Health Organization in 2017, but the precise mechanisms of PanNET initiation and progression have remained unclear. In this study, we used a genetically engineered mouse model to investigate the mechanisms of PanNET formation. Although pancreas-specific deletion of the Rb gene (Pdx1-Cre;Rbf/f ) in mice did not affect pancreatic exocrine cells, the α-cell/β-cell ratio of islet cells was decreased at 8 months of age. During long-term observation (18-20 months), mice formed well-differentiated PanNET with a Ki67-labeling index of 2.7%. In contrast, pancreas-specific induction of a p53 mutation (Pdx1-Cre;Trp53R172H ) had no effect on pancreatic exocrine and endocrine tissues, but simultaneous induction of a p53 mutation with Rb gene deletion (Pdx1-Cre;Trp53R172H;Rb f/f ) resulted in the formation of aggressive PanNET with a Ki67-labeling index of 24.7% over the short-term (4 months). In Pdx1-Cre;Trp53R172H;Rbf/f mice, mRNA expression of Pten and Tsc2, negative regulators of the mTOR pathway, significantly decreased in the islet cells, and activation of the mTOR pathway was confirmed in subsequently formed PanNET. Thus, by manipulating Rb and p53 genes, we established a multistep progression model from dysplastic islet to indolent PanNET and aggressive metastatic PanNET in mice. These observations suggest that Rb and p53 have distinct roles in the development of PanNET. SIGNIFICANCE: Pancreas-specific manipulation of Rb and p53 genes induced malignant transformation of islet cells, reproducing stepwise progression from microadenomas to indolent (grade 1) and subsequent aggressive PanNETs (grade 2-3).
Mutational and phenotypic characterization of hereditary hemorrhagic telangiectasia
Authors: Claire L. Shovlin, Ilenia Simeoni, Kate Downes, Zoe C. Frazer, Karyn Megy, Maria E. Bernabeu-Herrero, Abigail Shurr, Jennifer Brimley, Dilipkumar Patel, Loren Kell, Jonathan Stephens, Isobel G. Turbin, Micheala A. Aldred, Christopher J. Penkett, Willem H. Ouwehand, Luca Jovine, Ernest Turro
Journal: Blood (2020)