tbuckley/cabot-search huggingface dataset:
Pox Parties for Grannies? Chickenpox, Exogenous Boosting, and Harmful Injustices
Authors: Heidi Malm, Mark Christopher Navin
Journal: The American Journal of Bioethics (2020)

Some societies tolerate or encourage high levels of chickenpox infection among children to reduce rates of shingles among older adults. This tradeoff is unethical. The varicella zoster virus (VZV) causes both chickenpox and shingles. After people recover from chickenpox, VZV remains in their nerve cells. If their immune systems become unable to suppress the virus, they develop shingles. According to the Exogenous Boosting Hypothesis (EBH), a person's ability to keep VZV suppressed can be 'boosted' through exposure to active chickenpox infections. We argue that even if this hypothesis were true, immunization policies that discourage routine childhood varicella vaccination in order to prevent shingles for other people are unethical. Such policies harm children and treat them as mere means for the benefit of others, and are inconsistent with how parents should treat their children and physicians should treat their patients. These policies also seem incompatible with institutional transparency.
Predictors of prostate cancer-specific mortality in elderly men with intermediate-risk prostate cancer treated with radiation therapy
Authors: A. Nanda, M. Chen, B. J. Moran, M. H. Braccioforte, D. Dosoretz, S. Salenius, M. Katin, R. Ross, A. V. D'Amico
Journal: Journal of Clinical Oncology (2009)

9543 Background: To identify clinical factors associated with prostate cancer-specific mortality (PCSM), adjusting for co-morbidity, in elderly men with intermediate-risk prostate cancer treated with brachytherapy alone or in conjunction with external beam radiation therapy (EBRT). Methods: The study cohort comprised 1,978 men of median age 71 (interquartile range [IQR], 66–75) years with intermediate-risk prostate cancer (Gleason score 7 with PSA 20 ng/mL or less and tumor category T2c or less). Fine and Gray's multivariable competing risks regression was used to assess whether presence of cardiovascular disease (CVD), age, treatment, year of brachytherapy, PSA level, or tumor category were associated with the risk of PCSM. Results: After a median follow up of 3.2 (IQR, 1.7 - 5.4) years, 15 men were observed to experience PCSM. The presence of CVD was significantly associated with a decreased risk of PCSM (AHR 0.20, 95% CI 0.04 - 0.99, P = 0.05), whereas an increasing PSA level was significantly associated with an increased risk of PCSM (AHR 1.14, 95% CI 1.02 - 1.27, P = 0.02). In the absence of CVD, cumulative incidence estimates of PCSM were higher (P = 0.03) in men with PSA levels above as compared to the median PSA level (7.3 ng/mL) or less; however, in the setting of CVD there was no difference (P = 0.27) in these estimates stratified by the median PSA level (6.9 ng/mL). Conclusions: Detection of intermediate-risk prostate cancer in elderly men without CVD at lower PSA levels is associated with a lower risk of PCSM; this risk reduction is not observed in men with known CVD. [Table: see text] No significant financial relationships to disclose.
AB1161 ARTIFICIAL INTELLIGENCE FOR RHEUMATOLOGY
Authors: A. C. Genç, F. Turkoglu Genc, A. B. Kara, L. Genc Kaya, Z. Ozturk, D. Karatas, Y. Gunduz, E. Gönüllü
Journal: Annals of the Rheumatic Diseases (2020)

Background: Magnetic resonance imaging (MRI) of sacroiliac (SI) joints is used to detect early sacroiliitis(1). There can be an interobserver disagreement in MRI findings of SI joints of spondyloarthropathy patients between a rheumatologist, a local radiologist, and an expert radiologist(2). Artificial Intelligence and deep learning methods to detect abnormalities have become popular in radiology and other medical fields in recent years(3). Search for “artificial intelligence” and “radiology” in Pubmed for the last five years returned around 1500 clinical studies yet no results were retrieved for “artificial intelligence” and “rheumatology”. Objectives: Artificial Intelligence (AI) can help to detect the pathological area like sacroiliitis or not and also allows us to characterize it as quantitatively rather than qualitatively in the SI-MRI. Methods: Between the years of 2015 and 2019, 8100 sacroiliac MRIs were taken at our center. The MRIs of 1150 patients who were reported as active or chronic sacroiliitis from these sacroiliac MRIs or whose MRIs were considered by the primary physician in favor of sacroiliitis was included in the study. 1441 MRI coronal STIR sequence of 1150 patients were tagged as ‘’active sacroiliitis’’ and trained to detect and localize active sacroiliitis and provide prediction performance. This model is available for various operating systems. (Image1) Results: Precision score, the percentage of sacroiliac images of the trained model, is 87.1%. Recall, the percentage of the total sacroiliac MRIs correctly classified by the model, is 82.1% and the mean average precision (mAP) of the model is 89%. Conclusion: There are gray areas in medicine like sacroiliitis. Inter-observer variability can be reduced by AI and deep learning methods. The efficiency and reliability of health services can be increased in this way. References: [1]Jans L, Egund N, Eshed I, Sudoł-Szopińska I, Jurik AG. Sacroiliitis in Axial Spondyloarthritis: Assessing Morphology and Activity. Semin Musculoskelet Radiol. 2018;22: 180–188. [2]B. Arnbak, T. S. Jensen, C. Manniche, A. Zejden, N. Egund, and A. G. Jurik, “Spondyloarthritis-related and degenerative MRI changes in the axial skeleton—an inter- and intra-observer agreement study,” BMC Musculoskeletal Disorders , vol. 14, article 274, 2013. [3]Rueda, Juan C et al. “Interobserver Agreement in Magnetic Resonance of the Sacroiliac Joints in Patients with Spondyloarthritis.” International journal of rheumatology (2017). Image1. Bilateral active sacroiliitis detected automatically by AI model (in right sacroiliac joint 75.6%&gt; (50%), in left sacroiliac joint 65% (&gt;50%)) Disclosure of Interests: None declared
Abstract 4353: The Fibrolamellar Registry: A patient-based medical registry can address medical care
Authors: Julie Latone Newcomb, Siobhan Lett, Rachael D. Migler, Elana P. Simon, Sanford M. Simon
Journal: Cancer Research (2020)

Abstract Advances in genomics and proteomics have enabled more precise characterizations of tumors with the consequence that many cancers are being segregated into smaller categories. With this larger number of categories, more cancers are being categorized as rare. The downside to such categorizations is that the reduced numbers of patients in each category makes it difficult to gather enough information about each cancer. We are a group of patients and caregivers who have joined together to form a repository for patient-shared data and reports in an IRB-approved, non-profit medical registry for the rare and usually lethal childhood liver cancer fibrolamellar hepatocellular carcinoma (FLC). Since the Fibrolamellar Registry is patient-run and patient-owned, we have the trust of the patient community that the records will not be sold for profit. This has enabled us, in our first 3 years, to gather detailed medical records, scans and tests from over 170 patients. With input from scientists and clinicians who study FLC, we have written 600 questions of specific interest to this disease. Most of our patients have also opted to allow these medical records to be shared with a tissue FLC repository that already has samples from 110 patients. Many of patients with FLC get hyperammonenic encephalopathy. These patients do not respond to lactulose and, unfortunately, often enter a coma and die from the condition. From evaluation of our medical records the results indicate that patients do not have hyperammonenic encephalopathy as a result of liver failure. Instead, it is the result of an alteration of the expression of ornithine transcarbamylase, as a consequence of the expression of oncokinase that drives fibrolamellar. These alterations of ornithine transcarbamylase shift the urea acid cycle, resulting in the buildup of ammonia. This suggests that hyperammonemic encephalopathy should be treated with agents that modulate the urea acid cycle rather than lactulose. These results are an example of the power of a patient-run medical registry. Citation Format: Julie Latone Newcomb, Siobhan Lett, Rachael D. Migler, Elana P. Simon, Sanford M. Simon. The Fibrolamellar Registry: A patient-based medical registry can address medical care [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4353.
AB1328-HPR INCREASED BODY MASS INDEX AFFECTS SPINAL MOBILITY RATHER THAN DISEASE ACTIVITY IN ANKYLOSING SPONDYLITIS
Authors: M. He, Y. Bao, Y. Yang, S. Liu, C. Dong, W. Zhou, J. Guo, J. Liu, Y. Chen, Z. Gu
Journal: Annals of the Rheumatic Diseases (2020)

Background: Studies have reported the association between overweight or obesity and ankylosing spondylitis (AS), but their relation is still unclear in China. Objectives: To explore the prevalence of overweight or obesity and its effect on other indicators and their relationships in Chinese AS patients. Methods: Demographic and clinical variables were collected from 207 AS patients. Patients were categorized to normal BMI group (BMI &lt; 23kg/m 2 ) and overweight group (BMI ≥ 23kg/m 2 ). We used Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Health Assessment Questionnaire (HAQ), Ankylosing Spondylitis Quality of Life (ASQoL) and Medical Outcomes Study Short Form 36 (SF-36) to evaluate disease activity, physical function, spinal mobility, functional limitation and health-related quality of life, respectively. Statistical analysis used independent t test, Mann-Whitney U test, Chi-square test and Spearman’s rank correlation test. Results: 56.5% (117) AS patients were overweight or obese, among which 80.3% (94) were male. In the overweight group, patients were older, more being married, and have higher BMI, higher waist circumference, higher waist-to-hip ratio, longer disease duration, higher BASMI score, higher white blood cell count (WBC), higher lymphocyte and higher platelet count compared to the non-overweight group ( P ≤ 0.038). However, there was no distinct difference in BASDAI score between the two groups ( P = 0.891). In the correlation analyses, gender and marital status ( P ≤ 0.036) were correlated negatively with BMI; while age, waist circumference, waist-to-hip ratio, WBC, lymphocyte count and red blood cell ( P ≤ 0.036) were correlated positively with BMI. Conclusion: Overweight or obesity is common in Chinese AS patients. Increased BMI affects not disease activity but spinal mobility, which indicates that patients with high BMI are more likely to have limitations in flexion, extension, lateral bending and torsion of spine. References: [1]Bowness P. Hla-B27. Annu Rev Immunol. 2015;33:29-48. [2]de Araújo TA, Mota MC, Crispim CA. Obesity and sleepiness in women with fibromyalgia. Rheumatology International. 2014;35(2):281-7. Acknowledgments: This study was funded by Science and technology Project of Nantong City (Grant/Award Number: MSZ18217), Postgraduate Research &amp; Practice Innovation Program of Jiangsu Province (Grant/Award number: KYCX19_2071 and KYCX18_2410), National Natural Science Foundation of China (Grant/Award number: 81671616 and 81871278), Science and technology Project of Jiangsu Province (Grant/Award number: BE2018671) and Clinical Research Center of Stem Cells, Affiliated Hospital of Nantong University, Nantong (Grant/Award number: HS2018001). Disclosure of Interests: None declared
p53 activation during ribosome biogenesis regulates normal erythroid differentiation
Authors: Salomé Le Goff, Ismael Boussaid, Celia Floquet, Anna Raimbault, Isabelle Hatin, Charlotte Andrieu-Soler, Mohammad Salma, Marjorie Leduc, Emilie-Fleur Gautier, Boris Guyot, Diane d’Allard, Nathalie Montel-Lehry, Sarah Ducamp, Amandine Houvert, François Guillonneau, Stéphane Giraudier, Elisabeth Cramer-Bordé, François Morlé, Jean-Jacques Diaz, Olivier Hermine, Naomi Taylor, Sandrina Kinet, Frédérique Verdier, Rose-Ann Padua, Narla Mohandas, Pierre-Emmanuel Gleizes, Eric Soler, Patrick Mayeux, Michaela Fontenay
Journal: Blood (2020)
Anthracycline-rechallenge using pegylated liposomal doxorubicin (PLD) in previously treated patients with metastatic breast cancer (MBC): A meta-analysis using pooled individual data from four prospective trials
Authors: S. Al-Batran, M. Scholz, E. Jäger
Journal: Journal of Clinical Oncology (2009)

1047 Background: Few data are available on the efficacy of anthracycline rechallenge using PLD. Methods: Pooled individual data from 4 prospective trials (Keller, J Clin Oncol. 2004; O'Brien, Ann Oncol. 2004; Al-Batran, Br J Cancer. 2006; and Al-Batran, Oncology. 2006) were utilized to evaluate the activity of PLD in pts with MBC previously treated with conventional anthracyclines. Primary endpoint was clinical benefit rate (CBR), defined as objective response or stable disease, both lasting ≥ 6 months. CBR was assessed in the entire group (primary hypothesis CBR ≥ 30%) and in pre-defined subgroups of pts depending on the most important features of their prior anthracycline-based therapy. Results: The studies comprised a total 935 pts, of whom 274 pts had received PLD after prior exposure to conventional anthracyclines. At the time of PLD therapy, these (274) pts were heavily pre-treated for MBC (median lines of previous chemotherapy 4, range 1 to 9, and 93.4% of pts received PLD after ≥ 2 previous chemotherapies for MBC). Prior anthracycline treatment was adjuvant, anti-metastatic, or both in 14%, 46%, or 40% of pts, respectively. The overall CBR from PLD was 32.2% (95% CI, 26.7%-37.8%), with no difference between pts who were considered anthracycline resistant (based on the study records) and those who were not (31.9% vs. 31.6%, respectively; p = 1). There was also no difference in CBR from PLD between pts who received prior anthracyclines adjuvant only (33.3%), anti-metastatic only (34.4%) or both (29.4%; p = 0.71). There was a trend towards a higher CBR in pts who received PLD at &gt; 12 months vs ≤ 12 months since the end of their prior conventional anthracycline treatment (34.2% vs. 26.3%, respectively; p = 0.21). Higher CBR (up to 47%) and longer survival times were observed in pts without taxane pretreatment or with a low number of previous chemotherapies, most likely reflecting a less advanced disease in these pts. Conclusions: This meta-analysis demonstrates a clinical benefit from PLD in MBC pts previously treated with multiple chemotherapies, including anthracyclines. Interestingly, the CBR was independent of resistance to, setting of, or time since previous conventional anthracycline therapy. [Table: see text]
THU0009 Fibronectin gene polymorphism in severe and mild rheumatoid arthritis
Authors: M Fabris, S Sacco, E Di Poi, G Favret, GF Ferraccioli
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The importance of Fibronectin (Fn) in RA chronic synovial inflammation is increasing. There are at least 6 restriction fragment length polymorphisms (RFLPs) described so far in the Fn gene, but very few is known about their possible functional relevance. <h3>Objectives</h3> In this study we assessed the role of the Msp-I Fn gene polymorphism in a series of patients with severe aggressive disease who were treated with anti-TNF-α therapy because of their poor response to a DMARDs combination strategy. The phenotype of these patients were compared to those of a cohort of patients who had a good response to Methotrexate (MTX), thus revealing a mild/moderate disease. <h3>Methods</h3> Seventy-nine (79) RA patients and sixty-one (61) controls (Healthy Blood Donors, HBD) entered the study. RA patients were split into 2 subgroups: 57 rheumatoids in stable partial remission (less than 3 swollen joints and a morning stiffness of less than 20') since at least six months after MTX treatment (15 mg/w weekly, range 10–25 mg/w), thus called MTX-responders (MTX-R) and 22 rheumatoids with still active disease (more than 6 swollen joints and a morning stiffness of at least 60') despite 6 months of combination therapy (MTX + Sulphasalazine + Hydroxychloquine or MTX + Cyclosporine, including low doses of prednisone, 5 mg/day). This latter group received anti-TNF-α therapy and was then labelled anti-TNF-treated (TNF-T). Genotyping for the Msp-I Fn gene polymorphism was made according to Avila <i>et al</i>.,<sup>1</sup> who named C the allele resistant to enzyme's digestion and D the variant susceptible. Statistical analyses (Odds Ratio, 95% Confidence Interval) were performed using Prism software (Graph-Pad, S. Diego, CA 92121-USA). <h3>Results</h3> MTX-R had an overall frequency of DD homozygousity of 56.1% vs 52.5% in HBD, while in TNF-T subgroup the DD genotype had a frequency of 81.8% (OR = 4.1, CI = 1.2–13, p = 0.008 vs HBD). The comparison between TNF-T and MTX-R is similarly striking (OR = 3.5, CI = 1.1–12, p = 0.01). <h3>Conclusion</h3> The DD genotype for Msp-I Fn gene polymorphism marks the patients who received anti-TNF-α therapy and may lead to a more aggressive phenotype in RA. <h3>Reference</h3> Avila JJ, <i>et al</i>. Am J Respir Cell Mol Biol. 1999;20:106
Prevalence of phenotypes of acute respiratory distress syndrome in critically ill patients with COVID-19: a prospective observational study
Authors: Pratik Sinha, Carolyn S Calfee, Shiney Cherian, David Brealey, Sean Cutler, Charles King, Charlotte Killick, Owen Richards, Yusuf Cheema, Catherine Bailey, Kiran Reddy, Kevin L Delucchi, Manu Shankar-Hari, Anthony C Gordon, Murali Shyamsundar, Cecilia M O'Kane, Daniel F McAuley, Tamas Szakmany
Journal: The Lancet Respiratory Medicine (2020)
Oncological outcomes of radical cystectomy for bladder cancer: Laparoscopy versus open surgery
Authors: J. Guillotreau, X. Gamé, M. Mouzin, N. Doumerc, B. Malavaud, P. Rischmann
Journal: Journal of Clinical Oncology (2009)

e16059 Background: To compare the oncological outcomes of laparoscopic versus open surgery in radical cystectomy for bladder cancer. Methods: A prospective non-randomized study was conducted between January 2003 and November 2008 in 52 patients, 2 women and 50 men, who underwent radical cystectomy for bladder cancer. Thirty seven cystectomies were carried out by laparoscopic surgery (LS) and 15 by open surgery (OS). Mean patient age was 67.3 ± 9.7 years. The median preoperative ASA score was 2 (1–3) in both groups. Kaplan-Meier curves were constructed to estimate the survival rate for the whole sample. Datas were compared by Log-rank test. Current followup, overall and specific deaths were used as endpoints. The survival time was defined as the time elapsed from the date of radical cystectomy to the endpoint. Results: All tumours were transitional cell carcinoma, high-grade and stage &lt; pT3b pN0. One patient of OS group had a positive surgical margin. Eight patients (15.4%), 7 of LS group and 1 of OS group, completed 5 years of follow-up. At the last follow-up 40 patients (76.9%) were alive with no evidence of disease and 5 (9.6%) died, two patients (3.8%) from metastasis and 3 (5.7%) from different causes. No patient developed port- site metastasis. Overall survival was significantly better in LS group than in the OS group (p=0.039). No statistical difference was noted for Specific survival. Mean patient follow-up was 30.9 ± 20.3 months. Conclusions: The data suggest that LRC provides oncological outcomes comparable to contemporary series of open RC. No significant financial relationships to disclose.
Investigation of a nonsense mutation located in the complex KIV-2 copy number variation region of apolipoprotein(a) in 10,910 individuals
Authors: Silvia Di Maio, Rebecca Grüneis, Gertraud Streiter, Claudia Lamina, Manuel Maglione, Sebastian Schoenherr, Dietmar Öfner, Barbara Thorand, Annette Peters, Kai-Uwe Eckardt, Anna Köttgen, Florian Kronenberg, Stefan Coassin
Journal: Genome Medicine (2020)

Abstract Background The concentrations of the highly atherogenic lipoprotein(a) [Lp(a)] are mainly genetically determined by the LPA gene locus. However, up to 70% of the coding sequence is located in the complex so-called kringle IV type 2 (KIV-2) copy number variation, a region hardly accessible by common genotyping and sequencing technologies. Despite its size, little is known about genetic variants in this complex region. The R21X variant is a functional variant located in this region, but it has never been analyzed in large cohorts. Methods We typed R21X in 10,910 individuals from three European populations using a newly developed high-throughput allele-specific qPCR assay. R21X allelic location was determined by separating the LPA alleles using pulsed-field gel electrophoresis (PFGE) and typing them separately. Using GWAS data, we identified a proxy SNP located outside of the KIV-2. Linkage disequilibrium was determined both statistically and by long-range haplotyping using PFGE. Worldwide frequencies were determined by reanalyzing the sequencing data of the 1000 Genomes Project with a dedicated pipeline. Results R21X carriers (frequency 0.016–0.021) showed significantly lower mean Lp(a) concentrations (− 11.7 mg/dL [− 15.5; − 7.82], p = 3.39e−32). The variant is located mostly on medium-sized LPA alleles. In the 1000 Genome data, R21X mostly occurs in Europeans and South Asians, is absent in Africans, and shows varying frequencies in South American populations (0 to 0.022). Of note, the best proxy SNP was another LPA null mutation (rs41272114, D ′ = 0.958, R 2 = 0.281). D ′ was very high in all 1000G populations (0.986–0.996), although rs41272114 frequency varies considerably (0–0.182). Co-localization of both null mutations on the same allele was confirmed by PFGE-based long-range haplotyping. Conclusions We performed the largest epidemiological study on an LPA KIV-2 variant so far, showing that it is possible to assess LPA KIV-2 mutations on a large scale. Surprisingly, in all analyzed populations, R21X was located on the same haplotype as the splice mutation rs41272114, creating “double-null” LPA alleles. Despite being a nonsense variant, the R21X status does not provide additional information beyond the rs41272114 genotype. This has important implications for studies using LPA loss-of-function mutations as genetic instruments and emphasizes the complexity of LPA genetics.
CKD is a key risk factor for COVID-19 mortality
Authors: Ron T. Gansevoort, Luuk B. Hilbrands
Journal: Nature Reviews Nephrology (2020)

A new study uses the OpenSAFELY health analytics platform to identify risk factors for COVID-19 mortality. This analysis, which includes data for more than 17 million people in the UK, suggests that patients with chronic kidney disease are at higher risk than those with other known risk factors, including chronic heart and lung disease.