tbuckley/cabot-search huggingface dataset:
Whole-genome sequencing of cholangiocarcinoma to reveal distinct profiles of patients with underlying cirrhosis or inflammatory disorders.
Authors: Nicholas Timothy Holzapfel, Amy Zhang, Robert Edward Denroche, Bernard Lam, Julie Wilson, Sandra Fischer, Faiyaz Notta, Steven Gallinger, Jennifer J. Knox, Grainne M. O'Kane
Journal: Journal of Clinical Oncology (2021)

340 Background: Cholangiocarcinoma (CCA) is a lethal malignancy with limited treatment options. Molecular profiling of these tumours has revealed a number of actionable mutations and four clusters have been defined through integrative genomic analysis. We sought to explore whole genome sequencing (WGS) data in 20 patients enriched for CCA arising in the setting of cirrhosis or inflammatory disorders. Methods: A previously established Biliary Tract Cancer (BTC) database at the Princess Margaret Cancer Centre (PMCC)/University Health Network (UHN) was used to identify patients of clinical interest including long-term survivors, those with germ-line mutations, and those with chronic inflammatory disorders. WGS and bioinformatic analyses were performed at the Ontario Institute for Cancer Research. Results: The 20 resected samples included 12 patients (pts) with intrahepatic CCA, 7 perihilar CCA, and 1 distal CCA. 8 pts were alive &gt; 8 years post resection and one patient harboured a germline MLH1 pathogenic variant (MLH1 G67R). 3 pts had documented cirrhosis (hepatitis B n = 2, haemochromatosis n = 1); other inflammatory disorders (n = 4) included ulcerative colitis (UC) without documented PSC (n = 1), PSC alone (n = 1), UC with PSC (n = 1), and ankylosing spondylitis (n = 1). The remaining cases were randomly selected. The predominant COSMIC single base substitution (SBS) mutational signatures were 1, 8 and 5, and the median TMB was 1.75 mutations per MB (0.73-33.23). The pt with an MLH1 mutation exhibited a TMB of 33.23 with predominance of SBS26. Actionable variants were enriched in the 8 pts who are alive and disease free including 2 predicted FGFR fusions and mutations in IDH1 (n = 1), BRAF V600E (n = 1), and BAP1 (n = 1). TP53 mutations (n = 7) were present exclusively in patients with cirrhosis or inflammatory disorders and the median survival in the group was 12 months (3 -21 months). Although SBS signatures were similar in this group, in the two cases of UC, SBS17 (unknown etiology) was evident. SBS17 was also dominant in one case where the TMB was 13 mutations per MB and the patient died within 3 months of diagnosis. A somatic case of homologous recombination deficiency, with no causative genetic alteration identified, was evident in a further patient receiving maintenance rituximab for a coexisting stage 4 mantle cell lymphoma. Conclusions: WGS may provide additional biological information in CCA particularly in patients with underlying inflammatory disorders, where TP53 mutations are prevalent and mutational signatures are distinct.
The implications of treatment delays in adjuvant therapy for cholangiocarcinoma patients.
Authors: Matthew Parsons, Shane Lloyd, Skyler B Johnson, Courtney L. Scaife, Ignacio Garrido-Laguna, Randa Tao
Journal: Journal of Clinical Oncology (2021)

291 Background: To understand the factors associated with timing of adjuvant therapy in the management of intrahepatic and extrahepatic cholangiocarcinoma and the impact of delays on overall survival (OS). Methods: Data from the NCDB for patients with pathologically proven non-metastatic adenocarcinoma of the bile ducts from 2004 to 2014 were pooled and screened. Patients were included only if they underwent surgery and adjuvant chemotherapy (CMT) and/or radiotherapy (RT). Patients who underwent neoadjuvant therapy or received CMT or RT with palliative intent were excluded. Pearson’s chi-squared test and multivariate logistic regression analyses were used to assess the distribution of demographic, clinical, and treatment factors. After propensity-score matching with inverse probability of treatment weighting, OS was compared between patients who had initiation of adjuvant therapy past various time points using Kaplan Meier analyses and doubly-robust estimation with multivariate Cox proportional hazards modeling. Results: In total, 7,422 patients in our analysis underwent adjuvant treatment. This represented 43% of the study cohort of 17,123 patients. Of the patients who underwent adjuvant treatment, 3,956 (53%) initiated adjuvant therapy by two months, 6,234 (84%) by 3 months and 6,987 (94%) by four months. High-grade disease, macroscopically positive margins, tumors larger than five centimeters, and unknown LVSI status, were associated with earlier initiation of adjuvant treatment at two months or earlier. Patients who received early adjuvant therapy were also more likely to be treated with a combination of CMT and RT. Factors associated with delay of adjuvant therapy beyond three months post-surgery included Charlson scores of one or greater and Hispanic race. After propensity score weighting, there was no survival difference between groups when comparing initiation of adjuvant therapy before or after two, three or four month time points Conclusions: We identified a number of patient characteristics related to the timing of initiating adjuvant therapy in patients with biliary cancers. There were no significant difference in OS associated with delaying adjuvant therapy beyond two, three or four month time-points. Our findings are relevant in the era of COVID-19 when minimizing patient exposure to health-care settings during a pandemic may need to be considered when deciding on the timing of adjuvant therapy. If a delay is necessary, our results suggest that there is no survival detriment to initiating adjuvant therapy beyond three or four months after surgery for biliary cancers.
FRI0103 The oral involvement in scleroderma (systemic sclerosis)
Authors: F Gharibdoost, M Sahebjami, M Khoshkhoonedjad, M Akbarian, F Shahram, A Nadji, AR Jamshidi, C Chams, F Davatchi
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Oral manifestations are a common feature of systemic sclerosis (scleroderma). <h3>Objectives</h3> The aim of this study was to find the frequency, characteristics, and the severity of oral involvement in Iranian patients with scleroderma, seen in the Scleroderma Unit, Rheumatology Research Centre. <h3>Methods</h3> Cases were selected consecutively according to the American Colledge of Rheumatology criteria. A complete oral examination was performed for all patients. Their data were compared with a control group by chi square test and fisher exact test. <h3>Results</h3> Forty scleroderma (Scl) patients (31 limited scleroderma, 9 diffuse form) and 40 healthy subjects (age and sex matched) were evaluated. The mean age in the Scl group was 40.83 (± 10.02 SD) and in the control group 40.30 (+ 10.43 SD) years. The mean duration of the disease was 8.3 (± 8.94 SD) years. The following sympotoms were seen more frequently in Scl than in the control group: reduced vertical lip distance (40.25 mm ± 7.26 SD versus 49.63 mm ± 7.38SD, p &lt; 0.0005), Xerostomy (subjective,%35 versus%75, P = 0.003), Raynaud's of oral region (27.5% vs. 5%, p &lt; 0.0001). The number of lost teeth (due to mobility or decays) was 9.59 ± 9.73 SD versus 4.3 ± 6.54SD (p = 0.006). Stiffness and depapillation of the tongue was 35% vs. 0% (each sign) (p &lt; 0.0005). Gingival Inflammation was 77.5% vs. 42.5% (p = 0.001). The atrophy of gingival surface (thin epithelium) was 70% vs. 2.5% (p &lt; 0.0005). Gingival stiffness was 30% vs. 0% (p &lt; 0.0005). Flattening and disappearance of the mucosal folds in the ruga region (on the hard palate) was 35% vs. 0% (p &lt; 0.0005). Gingival recessions were 42.5% vs. 2.5% (p &lt; 0.0005). Oral mucosal involvements (via clinical examination of regions in the oral cavity) including mucosal atrophy and thinning were seen more frequently in Scl than in normal controls (p &lt; 0.0005). The same was true for mucosal pallor (p = 0.002), mucosal telangiectasia (p &lt; 0.0005), mucosal erosions and ulcerations (p = 0.002). <h3>Conclusion</h3> Systemic sclerosis frequently involves different parts of the oral cavity. The teeth, tongue, gengiva and mucosal folds involvement were seen more than normal population. We recommend oral examination regularly in patients with scleroderma.
Clinical, virological and imaging profile in patients with Persistent or Resurgent forms of COVID-19: a cross-sectional study.
Authors: Dominique Salmon, Dorsaf Slama, Thomas De Broucker, Marina Karmochkine, Juliette Pavie, Emmanuel Sorbets, Nicolas Etienne, Dominique Batisse, Gabriela Spiridon, Valérie Le Baut, Jean-François Meritet, Eric Pichard, Florence Canouï-Poitrine
Journal: Journal of Infection (2020)
Clinical phenotype, fibrinogen supplementation, and health-related quality of life in patients with afibrinogenemia
Authors: Alessandro Casini, Sylvia von Mackensen, Cristina Santoro, Claudia Djambas Khayat, Meriem Belhani, Cecil Ross, Akbar Dorgalaleh, Arshi Naz, Ekrem Ünal, Magy Abdelwahab, Elise Dupuis Lozeron, Nathalie Trillot, Sophie Susen, Flora Peyvandi, Philippe de Moerloose
Journal: Blood (2021)
SP0151 Lobby-training
Authors: L Tillström
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> In August 2000, the Swedish Rheumatism Association, the SRA, started a new, exclusive training about how to influence political processes and public opinion. 55 members from our district federations take part in the training, which will continue for three terms. The main purpose is to strengthen the districts in their work for better conditions for the members and for everyone with arthritis/rheumatism. Contacts with media are a main bulk of the training. The need for good media strategies will be most important during the Year of Arthritis/Rheumatism in Sweden 2002, when our association co-operates with the Swedish pharmacies to focus on rheumatic diseases. In Sweden, medicine and health is the third most exposed subject in media just now. A media analysis we have done shows that publicity about arthritis/rheumatism and the SRA generated about 60 millions possible occasions for media-consumers to pay attention to these subjects during the first six months in 2000. The analysis is based on 365 newspaper articles and broadcasting reports. Most of these (75 percent) were common information about people with rheumatic diseases and different applications of treatments. The SRA was exposed in 25 percent of the articles and reports. When media pays attention to rheumatic diseases, the most frequent subject is pharmaceutical drugs followed by personal interviews with people suffering from arthritis/rheumatism and facts about the diseases. Even when the Rheumatism Association is exposed, the main subject is pharmaceutical drugs. People with arthritis/rheumatism are the main figures, followed by doctors and scientists/experts. When attention is paid to the association, local representatives and members are important figures. The analysis shows that there is good ground and many possibilities for the SRA to increase the media attention, take a larger part of the total publicity and focus on a strong and clear image. Main items in the lobby-training is: Civics Rhetoric and argumentation, How to influence political processes Contacts with media The training is partly IT-based and includes four meetings on a national level (each for two days), mixed with regional meetings and homework. Between the meetings, Intranet connects participants and coaches, where they chat, ask questions, discuss and learn from each other. Memos, working papers, subjects for homework, etc are available on Intranet.
The Effect of Preconception-Initiated Low-Dose Aspirin on Human Chorionic Gonadotropin–Detected Pregnancy, Pregnancy Loss, and Live Birth
Authors: Ashley I. Naimi, Neil J. Perkins, Lindsey A. Sjaarda, Sunni L. Mumford, Robert W. Platt, Robert M. Silver, Enrique F. Schisterman
Journal: Annals of Internal Medicine (2021)

A previous large randomized trial indicated that preconception-initiated low-dose aspirin (LDA) therapy did not have a positive effect on pregnancy outcomes. However, this trial was subject to nonadherence, which was not taken into account by the intention-to-treat approach.To estimate per protocol effects of preconception-initiated LDA on pregnancy loss and live birth.The EAGeR (Effects of Aspirin on Gestation and Reproduction) trial was used to construct a prospective cohort for a post hoc analysis. (ClinicalTrials.gov: NCT00467363).4 university medical centers in the United States.1227 women between the ages of 18 and 40 years who had 1 or 2 previous pregnancy losses and were attempting pregnancy.Adherence to LDA or placebo, assessed by measuring pill bottle weights at regular intervals during follow-up. Primary outcomes were human chorionic gonadotropin (hCG)-detected pregnancies, pregnancy losses, and live births, determined by pregnancy tests and medical records.Relative to placebo, adhering to LDA for 5 of 7 days per week led to 8 more hCG-detected pregnancies (95% CI, 4.64 to 10.96 pregnancies), 15 more live births (CI, 7.65 to 21.15 births), and 6 fewer pregnancy losses (CI, -12.00 to -0.20 losses) for every 100 women in the trial. In addition, compared with placebo, postconception initiation of LDA therapy led to a reduction in the estimated effects. Furthermore, effects were obtained in a minimum of 4 of 7 days per week.The EAGeR trial data for this study were analyzed as observational data, thus are subject to the limitations of prospective observational studies.Per protocol results suggest that preconception use of LDA at least 4 days per week may improve reproductive outcomes for women who have had 1 or 2 pregnancy losses. Increasing adherence to daily LDA seems to be key to improving effectiveness.National Institutes of Health.
Abstract 15424: Low Prevalence of Ideal Cardiovascular Health in India: Results From a Large Community-Based Study
Authors: Sailesh Mohan, Nikhil Srinivasapura Venkateshmurthy, Prashant Jarhyan, Ruby Gupta, Bhaskara Rao Malipeddi, K Srinath Reddy, Nikhil Tandon, Dorairaj Prabhakaran
Journal: Circulation (2018)

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality in India. Ideal health factors (normal cholesterol, blood pressure (BP) and blood glucose) and ideal health behaviors (n...
FRI0105 Prevalence of thyroid disorders in systemic lupus erythematosus: a study in 100 brazilian patients
Authors: AM Kakehasi, VN Dias, JE Duarte, CC Lanna, MA Carvalho
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The association of thyroid dysfunction with autoimmune diseases is well known, however its prevalence in patients with systemic lupus erythematosus (SLE) is not well established. <h3>Objectives</h3> The objective of this study was to determine the prevalence of thyroid disorders in 100 Brazilian lupus patients, including laboratorial and clinical manifestations suggesting thyroid abnormalities and its possible relation with lupus activity. <h3>Methods</h3> We evaluated 100 Brazilian patients, 93 females and 7 males, with mean age of 34,2 years. All of them had the diagnosis of SLE, according to the criteria of the American College of Rheumatology, and did not had a previous history of thyroid disease. <h3>Results</h3> Laboratory findings of thyroid dysfunction were found in sixteen (16%) patients. In nine patients (9%) the exams indicated subclinical hypothyroidism, in two patients (2%) the results were compatible with subclinical hyperthyroidism and in four patients (4%), primary hypothyroidism was diagnosed. One patient had the level of free thyroxin (T4 l) below the normal range. Positive anti-thyroid auto-antibodies was found in six patients (6%), being anti-peroxidase in four patients (4%), anti-thyroglobulin in one patient (1%) and both in one patient (1%). The diagnosis of concomitant hypothyroidism was confirmed in only one patient who presented positive anti-peroxidase antibodies. Seventy-six patients (76%) reported clinical complaints suggestive of thyroid dysfunction, such as: emotional liability, anxiety, weight loss, increased appetite, fatigue and astenia. The evaluation of activity criteria, based on the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index), did not show statistically significant difference between the groups with and without alterations of the thyroid function (7,44 and 5,26 respectively). <h3>Conclusion</h3> The authors conclude that thyroid disorder, especially the subclinical form, is a frequent finding in patients with SLE. However, they emphasise that, based on the results of the studied group, positive laboratory findings of thyroid dysfunction are not related to the activity of lupus disease. <h3>References</h3> Miller FW, Moore GF, Weintraub BD, Steinberg AD. Prevalence of thyroid disease and abnormal thyroid function test results in patients with systemic lupus erythematosus. Arthritis Rheum. 1987;30:1120–31 Tsai RT, Chang TC, Wang CR, Chuang CY, Chen CY. Thyroid disorders in chinese patients with systemic lupus erythematosus. Rheumatol Int. 1993;13:9–13 Vianna JL, Haga HJ, Asherson RA, Swana G, Hughes GRV. A prospective evaluation of antithyroid antibody prevalence in 100 patients with systemic lupus erythematosus. J Rheumatol. 1991;18:1193–5 Weetman AP, Walport MJ. The association of auto-immune thyroiditis with systemic lupus erythematosus. Br J Rheumatol. 1987;26(5):359–61
Association of Early-Phase In-Hospital Glycemic Fluctuation With Mortality in Adult Patients With Coronavirus Disease 2019
Authors: Liangkai Chen, Wenwu Sun, Yanli Liu, Lijuan Zhang, Yanling Lv, Qiang Wang, Ding Long, Yujun Wang, Su Zhao, Shuang Rong, Li Yu, Liegang Liu
Journal: Diabetes Care (2021)

OBJECTIVE To investigate the association of in-hospital early-phase glycemic control with adverse outcomes among inpatients with coronavirus disease 2019 (COVID-19) in Wuhan, China. RESEARCH DESIGN AND METHODS The study is a large case series, and data were obtained regarding consecutive patients hospitalized with COVID-19 in the Central Hospital of Wuhan between 2 January and 15 February 2020. All patients with definite outcomes (death or discharge) were included. Demographic, clinical, treatment, and laboratory information were extracted from electronic medical records. We collected daily fasting glucose data from standard morning fasting blood biochemistry to determine glycemic status and fluctuation (calculated as the square root of the variance of daily fasting glucose levels) during the 1st week of hospitalization. RESULTS A total of 548 patients were included in the study (median age 57 years; 298 [54%] were women, and n = 99 had diabetes [18%]), 215 suffered acute respiratory distress syndrome (ARDS), 489 survived, and 59 died. Patients who had higher mean levels of glucose during their 1st week of hospitalization were older and more likely to have a comorbidity and abnormal laboratory markers, prolonged hospital stays, increased expenses, and greater risks of severe pneumonia, ARDS, and death. Compared with patients with the lowest quartile of glycemic fluctuation, those who had the highest quartile of fluctuation magnitude had an increased risk of ARDS (risk ratio 1.97 [95% CI 1.01, 4.04]) and mortality (hazard ratio 2.73 [95% CI 1.06, 7.73]). CONCLUSIONS These results may have implications for optimizing glycemic control strategies in COVID-19 patients during the early phase of hospitalization.
SCRUM-Japan genesis virtual sequencing (VSQ) project: A novel algorithm combining deep learning (DL) with pathological diagnostics to enable the prediction of <i>BRAF </i>mutations and microsatellite instability (MSI) in advanced colorectal cancer (CRC).
Authors: Satoshi Fujii, Daisuke Kotani, Masahiro Hattori, Nishihara Masato, Toshihide Shikanai, Junji Hashimoto, Yuki Hama, Takuya Nishino, Mizuto Suzuki, Ayatoshi Yoshidumi, Tomoyuki Yamada, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2021)

112 Background: Numerous genetic and epigenetic abnormalities may lead to various morphologies of cancer. However, exactly which gene abnormality causes which morphology is unknown. The VSQ Project aims at investigating a novel algorithm by synergistically fusing DL technology and pathological diagnostics for the prediction of cancer genome abnormalities. This was achieved by elucidating the association between the morphological findings and genetic abnormalities, including BRAF V600E mutations and MSI status directly linked to the therapeutic strategies for advanced CRC patients (pts). Methods: Clinicopathological-genomic integrated DB derived from SCRUM-Japan GI-SCREEN, a nation-wide cancer genome screening project including CRC, were used. A total of 1,657 images of thin sections (one representative image per pt) cut from formalin-fixed and paraffin-embedded (FFPE) tissue specimens from primary or metastatic tumors with genetic abnormalities confirmed by next-generation sequencing (NGS) were investigated; 1,234 and 423 images (one per pt) were used for training and validation cohorts, respectively. First, we developed image-prediction models based on the morphological features precisely annotated by the single central pathologist, and then constructed the DL algorithms (gene-prediction models) that enabled the prediction of gene abnormalities by using images filtered by the image-prediction models. Results: We achieved high accuracy of AUC &gt; 0.90 for 12 features among the 33 morphological features analyzed. Next, we created several DL algorithms that enabled the prediction of BRAF mutations and MSI. The prediction level reached a high accuracy of AUC = 0.955 for the BRAF mutations and AUC = 0.857 for MSI in the training cohort. We verified the AUCs in the validation cohort and achieved AUC = 0.831 and 0.883 for BRAF mutations and MSI, respectively. Conclusions: Our findings suggest that VSQ can appropriately predict BRAF mutation and MSI status in advanced CRC, potentially without performing NGS tests. VSQ may also enable prompt initiation of systemic treatments in CRC patients as well as establish an unprecedented next-generation pathology in the near future.
FRI0237 Assessment of a functional restoration program for patients with chronic low back pain
Authors: G Casso, C Cachin, JC Gerster
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> The aim of this open study was to evaluate the effectiveness of a functional restoration program for patients suffering from chronic disabling low back pain. Return to work 12 months after the end of the program was chosen as the main outcome. <h3>Methods</h3> A questionnaire was sent to 125 patients (115 M, 10 F, mean age 40 years). The mean duration of absence from work before entry in the program was 4 months. All patients had followed an identical functional restoration program in a hospital setting 12 months before. The program included 6 h of physical therapy and ergonomics, 5 days per week for 3 weeks. <h3>Results</h3> 109 questionnaires could be assessed. 57 patients (52%) were back to work, 39 (36%) full time and 18 (17%) at half time. 42 patients were not working. A shorter duration out of work before entry in the program, an improvement of the isokinetic trunk strength at the end of the program, a positive self assessment of the program and the absence of psychiatric comorbidity were all separate predictors of a favourable outcome. <h3>Conclusion</h3> Our results are in agreement with those of the European literature. An intensive restoration functional program had positive effects in 53% of our selected population.
MA21.03 The International Association for the Study of Lung Cancer (IASLC) Global Survey on Molecular Testing in Lung Cancer
Authors: M. Smeltzer, M. Wynes, M. Taylor, K. Richeimer, K. Wood, K. Howell, M. Dalurzo, E. Felip, K. Kerr, E. Kim, S. Lantuejoul, C. Mathias, P. Postmus, C. Powell, S. Ramalingam, R. Soo, M. Tsuboi, I. Wistuba, M. Varella-Garcia, G. Scagliotti, F.R. Hirsch
Journal: Journal of Thoracic Oncology (2019)