tbuckley/cabot-search huggingface dataset:
SAT0240 Cost effectiveness of cyclosporine (sandimmunneoral<sup>®</sup>) treatment in early severe rheumatoid arthritis: the grisar study
Authors: LG Mantovani, A Belisari, M Pisani, G Pasero, E Marubini, F Priolo, R Ferrara, O Della Casa Alberighi
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Rheumatoid Arthritis (RA) is a chronic, degenerative, disabling and costly disease, particularly in its early form. There is evidence that cyclosporine A (CsA) is a disease modifying antirheumatic drug (DMARD) and is effective in slowing down the joint damage progression of early RA. <h3>Objectives</h3> To assess the economic profile of CsA. <h3>Methods</h3> TECHNIQUE: Incremental cost effectiveness analysis (CEA). PATIENTS AND DATA: collected from the GRISAR study, a multicenter, prospective, long-term, open-label with a blinded radiological end-point, randomised study of CsA vs conventional DMARDs. ALTERNATIVES: CsA vs conventional DMARDs. PERSPECTIVE: Italian National Health Service. COSTS: direct healthcare costs (drugs, diagnostics, hospitalisations for serious a dverse events -SAEs-) expressed in Euro 2000. EFFECTS: progression in the eroded joint count (PEJC) according to the Larsen-Dale method and reduction in working capacity due to RA. OTUCOME: Incremental cost effectiveness ratio [ICERpejc = (Ccsa-Cdmards)/(PEJC csa-PEJC dmards)]. <h3>Results</h3> 248 early severe RA patients (F/M 196/52; mean age 48.7+11.9 yrs) were considered in this analysis. The mean duration of f-up was 3.9 years. Compared to conventional DMARDs, CsA patients showed higher costs for drugs (Euro 12340 vs 1300, p &lt; 0.05), SAE and diagnostics (Euro 2540 vs 2430, P = NS), and total cost (Euro 14880 vs 3730, p &lt; 0.05). The progression of RA measured through PEJC was slower in CsA patients compared to conventional DMARDs (1.9 vs 3.2, p &lt; 0.05), resulting in an ICER of Euro 8,570 per erosion avoided. Compared to conventinal DMARDs, less patients in the CsA group stopped working because of RA (2.7% compared to 7.8%). <h3>Conclusion</h3> This is one of the first prospective CEAs based on a prospective, long-term, randomised clinical trial with a pragmatic design in early RA. Our estimates show that CsA incremental effectiveness is achieved at a reasonable incremental cost. When considered in the perspective of early severe RA, CsA has a favourable pharmacoeconomic profile since CsA.
Population-based, real-world prognostic factors related to survival among patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).
Authors: Kenneth H. Yu, Paul Cockrum, Andy Surinach, Shu Wang, Bong Chul Chu
Journal: Journal of Clinical Oncology (2021)

389 Background: Pancreatic cancer is expected to be the third deadliest cancer in the US in 2020. Many real-world studies of pts with mPDAC are restricted to single centers, limiting the generalizability of the insights they generate. There is a need to understand prognostic factors of survival in a broader setting to aid in tailoring treatment strategies for pts. This study aimed to identify important population-based predictors related to survival among pts diagnosed with mPDAC. Methods: Data were extracted for pts diagnosed with mPDAC between Jan 2017 and Dec 2019 from the Flatiron Health database. Predictive models for overall survival from the start of each treatment were developed using multivariable Cox proportional hazards regression. Treatment specific predictive models were generated for pts treated with first line (1L) gemcitabine + nab-paclitaxel (GNP), 1L FOLFIRINOX, 1L gemcitabine monotherapy (gem-mono), and 2L liposomal irinotecan-based regimens. The holdout method was used for cross-validation, splitting the data into 70% training / 30% validation. Age at diagnosis, sex, body mass index, smoking status, and ECOG performance score (PS) were included in all models due to clinical importance. Demographic, clinical characteristics, hematological labs, liver function tests (LFTs), and serum bilirubin levels were assessed for inclusion into the models. Uno’s concordance statistic (c-statistic) was used to assess the predictive accuracy of the models. Results: Of the 3,572 pts included in the study, 44% (n = 1,557) received 1L GNP, 27% (n = 954) received 1L FOLFIRINOX, 7% (n = 265) received gem-mono, and 22% (n = 796) received other regimens. 38% (n = 1,345) pts received 2L and of those, 17% (n = 222) received liposomal irinotecan-based regimens. Among all 1L pts, the following were included in the final model: prior surgery, white blood cell (WBC) counts, serum albumin, LFTs (ALP and ALT), serum bilirubin, and ascites (c-statistic: 0.65). The model for pts treated with GNP differed from the overall model via the addition of neutrophil counts and removal of serum bilirubin and ascites (c-statistic: 0.67). Stage at initial diagnosis was included in the model only for pts treated with 1L FOLFIRINOX (c-statistic: 0.68). Among pts treated with gem-mono the LFTs were not included in the model (c-statistic: 0.78). ALP, serum albumin, and WBC counts were important predictors of survival among pts treated with 2L liposomal irinotecan-based regimens (c-statistic: 0.70). Across all regimens the strongest predictors of survival were ECOG PS, serum albumin, and ALP. Conclusions: In one of the largest contemporary real-world studies of patients with mPDAC to date, important population predictors of survival in pts receiving systemic treatment were identified. Further validation studies are needed to understand the generalizability of these results.
Trends in the incidence of young-onset colorectal cancer with a focus on years approaching screening age: A population-based longitudinal study
Authors: Alyssa Howren, Eric C Sayre, Jonathan M Loree, Sharlene Gill, Carl J Brown, Manoj J Raval, Ameer Farooq, Mary A De Vera
Journal: JNCI Journal of the National Cancer Institute (2021)

With recent evidence for the increasing risk of young-onset colorectal cancer (yCRC), we had the objective to evaluate the incidence of yCRC in 1-year age increments, particularly focusing around the screening age of 50 years.We conducted a longitudinal study using linked administrative health databases in British Columbia, Canada, including a provincial cancer registry, inpatient and outpatient visits, and vital statistics from January 1, 1986, to December 31, 2016. We calculated incidence rates per 100 000 at every age from 20 to 60 years and estimated annual percent change in incidence (APCi) of yCRC using joinpoint regression analysis.We identified 3614 individuals with yCRC (49.9% women). The incidence of CRC steadily increased from 20 to 60 years, with a marked increase from 49 to 50 years (incidence rate ratio = 1.19, 95% confidence interval [CI] = 1.04 to 1.34). Furthermore, there was a trend of increased incidence of yCRC among women (APCi = 0.79%, 95% CI = 0.22% to 1.36%) and men (APCi = 2.17%, 95% CI = 1.59% to 2.76%). Analyses stratified by age yielded APCis of 2.49% (95% CI = 1.36% to 3.63%) and 0.12% (95% CI = -0.54% to 0.79%) for women aged 30-39 years and 40-49 years, respectively, and 2.97% (95% CI = 1.65% to 4.31%) and 1.86% (95% CI = 1.19% to 2.53%) for men.Our findings indicate a steady increase over 1-year age increments in the risk of yCRC during the years approaching and beyond screening age. These findings highlight the need to raise awareness as well as continue discussions regarding considerations of lowering the screening age.
AB0023 <i>in vitro</i>peripheral blood mononuclear cells autoreactivity against autologous epidermal cells and the presence of anti-skin autoantibodies in patients with rheumatoid arthritis
Authors: IJ Hromadnikova, P Vavrincova, K Stechova, M Cermakova-Frantlova, D Chudoba, J Vavrinec
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> We discuss the ability of peripheral blood mononuclear cells (PBMN) of patients with rheumatoid arthritis (RA) or juvenile idiopathic arthritis to damage autologous skin or lyse autologous keratinocytes if co-cultured <i>in vitro</i>. We discuss a well as the presence of anti-skin anti-intercellular (ASA-IC), anti-skin anti-basement membrane (ASA-BM) and anti-keratin (AKA) antibodies of IgG class in patients´ sera without clinical features of vesicular bullous diseases. <h3>Objectives</h3> <h3>Methods</h3> A modified <i>in vitro</i> skin explant assay originally developed to predict acute graft versus host disease (GvHD) in allogeneic stem cell transplants was used in order to see if GvHR-like histopathological changes occur when patients´ PMNC would be co-cultured with autologous skin. 51Cr release cytotoxic assay was used to prove if observed skin damage was really of an autoimmune origin. An indirect immunofluorescence test on rat, monkey and guinea pig oesophagus substrates was used for the detection and quantification of ASA-IC, ASA-BM and AKA antibodies. <h3>Results</h3> We found out that PBMN of 29 out of 34 patients with RA or JIA (85,3%) were able to induce histopathological changes of grade II or above in autologous skin explants. Similarly, we observed that PBMN lysed autologous keratinocytes, but not autologous lymphoblasts when co-cultured <i>in vitro</i>. No skin damage or keratinocytes lysis was observed in healthy controls. Overall ASA-IC were detected in 50 out of 57 studied patients´ sera samples (87,7%, p = 0,0003). No ASA-BM &nbsp;positivity was observed in a studied cohort. AKA were detectable in 33 out of 60 patients (55%, p = 0,0001). <h3>Conclusion</h3> We suggest that PBMN of patients with RA or JIA might recognise similar autoantigen (s) expressed on epidermal cells that give rise an autoimmune response in synovium. However we observed a high incidence of ASA-IC antibodies in patients with RA and JIA we suppose that subclinical pemphigus occurring in this group might be exacerbated with different stimulus including pemphigus inducing drugs. <h3>References</h3> Osteolog Bull. 2000;2:70–11 Czech Rheumatol. 1999;4:166–74
THU0405 SERUM METABOLIC PROFILING ANALYSIS OF GOUT PATIENTS BASED ON UHPLC-Q-TOF/MS
Authors: T. W. LI, Y. Huang, Z. Zhong, Q. Huang
Journal: Annals of the Rheumatic Diseases (2020)

Background: Gout is a common kind of inflammatory arthritis with metabolic disorders. The detailed pathogenesis of gout remains largely unknown. Metabolomics has become an important tool in detecting the new pathogenesis and biomarkers. However, few studies have focused on the serum metabolic profiling of gout. Objectives: The study aims to investigate the metabolic profiling of gout patients with ultra-performance liquid chromatograph quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), and explore the potential pathological mechanisms and biomarkers. Methods: Serum samples from 31 gout patients and 31 healthy controls were analyzed by UPLC-Q-TOF-MS. Principal components analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA) and Hierarchical clustering analysis were performed to detect different compounds between the two groups. Receiver operating characteristic (ROC) curve analysis and pathway analysis of the different metabolites were conducted. Results: A total of 9192 compounds were detected, of which 138 significantly different compounds were selected, according to the criteria of (Variable importance in projection (VIP)&gt;3, P &lt;0.05). Eventually, 96 reliable metabolites matched the HMDB database were confirmed. ROC curve results showed that the area under the curve (AUC) value of 4-hydroxytriazolam for gout was 0.933 (CI95%: 0.875-0.992), yielding a highest AUC value, with the sensitivity of 83.9% and specificity of 93.5%. The pathway analysis results indicated that the significantly different metabolites were mainly involved in “primary bile acid biosynthesis”, “purine metabolism” and “glycerophospholipid metabolism”. Conclusion: The serum metabolic profiling in gout patients were significantly different from healthy subjects. 4-hydroxytriazolam was the potential biomarkers. Primary bile acid biosynthesis may be a novel metabolic pathway of gout. References: [1]Banoei MM, et al. Metabolomics and Biomarker Discovery in Traumatic Brain Injury. J Neurotrauma, 2018. 35(16): p. 1831-1848. Disclosure of Interests: : None declared
Abstract 15714: Evaluation of the Primary Care Heart Failure Billing Code on Cardiovascular Clinical Outcomes
Authors: Harsukh Benipal, Faizan Amin, Joshua Cerasuolo, Richard Perez, John You, Douglas Lee, Catherine Demers
Journal: Circulation (2018)

Introduction: Financial incentives are sometimes implemented to improve the delivery of evidence-based care. The Ontario Ministry of Health and Long-Term Care introduced the Heart Failure (HF) Mana...
Recent Advances of DNA Nanostructure‐Based Cell Membrane Engineering
Authors: Lingyu Feng, Jiang Li, Jielin Sun, Lihua Wang, Chunhai Fan, Jianlei Shen
Journal: Advanced Healthcare Materials (2021)

Abstract Materials that can regulate the composition and structure of the cell membrane to fabricate engineered cells with defined functions are in high demand. Compared with other biomolecules, DNA has unique advantages in cell membrane engineering due to its excellent programmability and biocompatibility. Especially, the near‐atomic scale precision of DNA nanostructures facilitates the investigation of structure–property relations on the cell membrane. In this review, first the state of the art of functional DNA nanostructures is summarized, and then the overview of the use of DNA nanostructures to engineer the cell membrane is presented. Subsequently, applications of DNA nanostructures in modifying cell membrane morphology, controlling ions transport, and synthesizing high precise liposomes are highlighted. Finally, the challenges and outlook on using DNA nanostructures for cell membrane engineering are discussed.
An 18-Month History of Dorsal Foot Lesions
Authors: Gordon T. Moffat, Zhe Ren, Andrew A. Simone
Journal: JAMA (2021)

A 32-year-old Nigerian woman with a childhood transfusion history developed scaly plaques with cobblestone surfaces on the dorsum of the forefoot and midfoot bilaterally; serologic testing was negative for HIV and positive for hepatitis C virus. What is the diagnosis and what would you do next?
SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4
Authors: Fanny Onodi, Lucie Bonnet-Madin, Laurent Meertens, Léa Karpf, Justine Poirot, Shen-Ying Zhang, Capucine Picard, Anne Puel, Emmanuelle Jouanguy, Qian Zhang, Jérôme Le Goff, Jean-Michel Molina, Constance Delaugerre, Jean-Laurent Casanova, Ali Amara, Vassili Soumelis
Journal: The Journal of Experimental Medicine (2021)

Several studies have analyzed antiviral immune pathways in late-stage severe COVID-19. However, the initial steps of SARS-CoV-2 antiviral immunity are poorly understood. Here we have isolated primary SARS-CoV-2 viral strains and studied their interaction with human plasmacytoid predendritic cells (pDCs), a key player in antiviral immunity. We show that pDCs are not productively infected by SARS-CoV-2. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in response to viral stimulation. They expressed CD80, CD86, CCR7, and OX40 ligand at levels similar to influenza virus–induced activation. They rapidly produced high levels of interferon-α, interferon-λ1, IL-6, IP-10, and IL-8. All major aspects of SARS-CoV-2–induced pDC activation were inhibited by hydroxychloroquine. Mechanistically, SARS-CoV-2–induced pDC activation critically depended on IRAK4 and UNC93B1, as established using pDC from genetically deficient patients. Overall, our data indicate that human pDC are efficiently activated by SARS-CoV-2 particles and may thus contribute to type I IFN–dependent immunity against SARS-CoV-2 infection.
Incidence and patterns of secondary malignancies in patients with neuroendocrine neoplasms: A SEER database analysis.
Authors: Meena Sadaps, Neal Mehta, Hong Li, Bassam N. Estfan
Journal: Journal of Clinical Oncology (2021)

374 Background: Neuroendocrine tumors (NETs) are comprised of a group of biologically and clinically heterogenous malignancies arising from a variety of anatomic sites, the majority of which lie within the gastrointestinal tract. Prior literature has reported on the association between NETs and other primary malignancies (OPM), most of which also end up being within the gastrointestinal tract, but these studies are limited by small sample sizes. We aim to further analyze the association of NETs and OPM on a larger scale using a population-based cancer registry. Methods: Malignant primary cancer with NET features were identified from the Surveillance Epidemiology and Ends Results (SEER) registry between 1975 and 2017. The histology/behavior of NET included carcinoid tumor, neuroendocrine carcinoma, pancreatic endocrine tumor, atypical carcinoid tumor, and other including insulinoma, glucagonoma, gastrinoma, VIPoma, somatostatinoma and enterochromaffin cell carcinoid. First NET observation from each patient was examined. Patients with NET were grouped into three categories: only one primary cancer with NET, first primary cancer with NET and first primary cancer without NET based on sequence number of primary cancer recorded in SEER. Distribution of NET between gastrointestinal (GI) and non-GI sites was described. Demographics were compared by NET sequence group and between GI and non-GI sites. Results: 45,896 patients with NET were analyzed (77.9% Caucasian, 47.0% male, median age 62.0 years). More than half (65.7%) of the NETs were observed in GI sites. Within the GI tract, 31.3% were in the small intestine, 25.1% in the rectum, 16.6% in pancreatobiliary, and &lt; 11% in other GI locations. Age at NET diagnosis was younger in those with GI NETs (median 60.0 vs 65.0, p &lt; 0.001 ). 71.2% of NET found in only cancer diagnosis, 10.4% of NET in first followed by a second primary malignancy, and 18.4% in a non-NET primary followed by NET. Mean age was 58.9 for NET primary only, 61.0 for NET primary first and 68.3 for non-NET primary first (p &lt; 0.0001). More Caucasian patients had non-NET primary first (82.3%) compared to NET primary only (76.9%) and NET primary first (75.5%). No gender differences were observed amongst the three groups. Carcinoid tumor histology was more prevalent in NET primary first (78.6%) compared to NET primary only (67.3%) and non-NET primary first (66.6%), while neuroendocrine carcinoma histology was more prevalent in NET only (27.4%) and non-NET first (29.3%) compared to NET first. Conclusions: 28.8% of patients with NETs were found to have OPM, either preceding or following their NET diagnosis. It is imperative that patients with NET undergo age-appropriate cancer screening to help identify any concurrent malignancies. Further research is warranted to identify the location of such additional malignancies and the timeframe in which they occur in relation to the NET.
Residential air pollution increases the risk for persistent pulmonary hypertension after pulmonary endarterectomy
Authors: Katleen Swinnen, Esmée Bijnens, Lidia Casas, Tim S. Nawrot, Marion Delcroix, Rozenn Quarck, Catharina Belge
Journal: European Respiratory Journal (2021)

<b>This retrospective cohort study showed that both persistent postoperative pulmonary hypertension and systemic inflammation were associated with previous exposure to air pollutants in CTEPH patients</b>https://bit.ly/39tUy2l
Changes in the Diagnosis and Management of Diabetes in Mexico City Between 1998–2004 and 2015–2019
Authors: Diego Aguilar-Ramirez, Jesus Alegre-Díaz, Louisa Gnatiuc, Raúl Ramirez-Reyes, Rachel Wade, Michael Hill, Rory Collins, Richard Peto, Jonathan R. Emberson, William G. Herrington, Pablo Kuri-Morales, Roberto Tapia-Conyer
Journal: Diabetes Care (2021)

OBJECTIVE To investigate the trends in diabetes prevalence, diagnosis, and management among Mexican adults who were participants in a long-term prospective study. RESEARCH DESIGN AND METHODS From 1998 to 2004, 159,755 adults from Mexico City were recruited to a prospective study, and from 2015 to 2019, 10,144 survivors were resurveyed. Diabetes was defined as self-reported diagnosis, glucose-lowering medication use, or HbA1c ≥6.5%. Controlled diabetes was defined as HbA1c &amp;lt;7%. Prevalence estimates were uniformly standardized for age, sex, and residential district. Cox models explored the relevance of controlled and inadequately controlled diabetes to cause-specific mortality. RESULTS During 1998–2004 and 2015–2019, 99,623 and 8,986 participants were aged 45–84 years. Diabetes prevalence had increased from 26% in 1998–2004 to 35% by 2015–2019. Of those with diabetes, the proportion previously diagnosed had increased from 76% to 89%, and glucose-lowering medication use among them had increased from 80% to 94%. Median HbA1c among those with diabetes had decreased from 8.2% to 7.3%, and the proportion of participants with controlled diabetes had increased from 16% to 37%. Use of blood pressure–lowering medication among those with previously diagnosed diabetes had increased from 35% to 51%, and their use of lipid-lowering therapy had increased from 1% to 14%. The excess mortality risk associated with diabetes accounted for 34% of deaths at ages 35–74 years, of which 5% were attributable to controlled and 29% to inadequately controlled diabetes. CONCLUSIONS Inadequately controlled diabetes is a leading cause of premature adult death in Mexico. Improvements in diabetes management have increased diagnosis and control, but substantial opportunities remain to improve treatment, particularly with lipid-lowering therapy.
Ropeginterferon alfa-2b versus phlebotomy in low-risk patients with polycythaemia vera (Low-PV study): a multicentre, randomised phase 2 trial
Authors: Tiziano Barbui, Alessandro Maria Vannucchi, Valerio De Stefano, Arianna Masciulli, Alessandra Carobbio, Alberto Ferrari, Arianna Ghirardi, Elena Rossi, Fabio Ciceri, Massimiliano Bonifacio, Alessandra Iurlo, Francesca Palandri, Giulia Benevolo, Fabrizio Pane, Alessandra Ricco, Giuseppe Carli, Marianna Caramella, Davide Rapezzi, Caterina Musolino, Sergio Siragusa, Elisa Rumi, Andrea Patriarca, Nicola Cascavilla, Barbara Mora, Emma Cacciola, Carmela Mannarelli, Giuseppe Gaetano Loscocco, Paola Guglielmelli, Silvia Betti, Francesca Lunghi, Luigi Scaffidi, Cristina Bucelli, Nicola Vianelli, Marta Bellini, Maria Chiara Finazzi, Gianni Tognoni, Alessandro Rambaldi
Journal: The Lancet Haematology (2021)
Non-steroidal anti-inflammatory drugs (NSAIDs) for musculoskeletal pain
Authors: Gustavo C Machado, Christina Abdel-Shaheed, Martin Underwood, Richard O Day
Journal: BMJ (2021)

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Ex Vivo T Cell-Depleted and In Vivo T Cell-Depleted Allogeneic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia in First Complete Remission Resulted in Similar Overall Survival Survival: On Behalf of the ALWP of the EBMT and the MSKCC
Authors: Florent Malard, Myriam Labopin, Christina Cho, Didier Blaise, Esperanza B. Papadopoulos, Jakob R. Passweg, Richard O'Reilly, Noel Milpied, Molly Maloy, Liisa Volin, H.R. Castro-Malaspina, Yosr Hicheri, Ann A. Jakubowski, Sylvie François, Sergio A. Giralt, Mohamad Mohty, Arnon Nagler, Miguel-Angel Perales
Journal: Blood (2017)