tbuckley/cabot-search huggingface dataset:
Biomarkers Associating with PARP Inhibitor Benefit in Prostate Cancer in the TOPARP-B Trial
Authors: Suzanne Carreira, Nuria Porta, Sara Arce-Gallego, George Seed, Alba Llop-Guevara, Diletta Bianchini, Pasquale Rescigno, Alec Paschalis, Claudia Bertan, Chloe Baker, Jane Goodall, Susana Miranda, Ruth Riisnaes, Ines Figueiredo, Ana Ferreira, Rita Pereira, Mateus Crespo, Bora Gurel, Daniel Nava Rodrigues, Stephen J. Pettitt, Wei Yuan, Violeta Serra, Jan Rekowski, Christopher J. Lord, Emma Hall, Joaquin Mateo, Johann S. de Bono
Journal: Cancer Discovery (2021)

Abstract PARP inhibitors are approved for treating advanced prostate cancers (APC) with various defective DNA repair genes; however, further studies to clinically qualify predictive biomarkers are warranted. Herein we analyzed TOPARP-B phase II clinical trial samples, evaluating whole-exome and low-pass whole-genome sequencing and IHC and IF assays evaluating ATM and RAD51 foci (testing homologous recombination repair function). BRCA1/2 germline and somatic pathogenic mutations associated with similar benefit from olaparib; greater benefit was observed with homozygous BRCA2 deletion. Biallelic, but not monoallelic, PALB2 deleterious alterations were associated with clinical benefit. In the ATM cohort, loss of ATM protein by IHC was associated with a better outcome. RAD51 foci loss identified tumors with biallelic BRCA and PALB2 alterations while most ATM- and CDK12-altered APCs had higher RAD51 foci levels. Overall, APCs with homozygous BRCA2 deletion are exceptional responders; PALB2 biallelic loss and loss of ATM IHC expression associated with clinical benefit. Significance: Not all APCs with DNA repair defects derive similar benefit from PARP inhibition. Most benefit was seen among patients with BRCA2 homozygous deletions, biallelic loss of PALB2, and loss of ATM protein. Loss of RAD51 foci, evaluating homologous recombination repair function, was found primarily in tumors with biallelic BRCA1/2 and PALB2 alterations. This article is highlighted in the In This Issue feature, p. 2659
Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial
Authors: Sara M. Tolaney, Nabihah Tayob, Chau Dang, Denise A. Yardley, Steven J. Isakoff, Vicente Valero, Meredith Faggen, Therese Mulvey, Ron Bose, Jiani Hu, Douglas Weckstein, Antonio C. Wolff, Katherine Reeder-Hayes, Hope S. Rugo, Bhuvaneswari Ramaswamy, Dan Zuckerman, Lowell Hart, Vijayakrishna K. Gadi, Michael Constantine, Kit Cheng, Frederick Briccetti, Bryan Schneider, Audrey Merrill Garrett, Kelly Marcom, Kathy Albain, Patricia DeFusco, Nadine Tung, Blair Ardman, Rita Nanda, Rachel C. Jankowitz, Mothaffar Rimawi, Vandana Abramson, Paula R. Pohlmann, Catherine Van Poznak, Andres Forero-Torres, Minetta Liu, Kathryn Ruddy, Yue Zheng, Shoshana M. Rosenberg, Richard D. Gelber, Lorenzo Trippa, William Barry, Michelle DeMeo, Harold Burstein, Ann Partridge, Eric P. Winer, Ian Krop
Journal: Journal of Clinical Oncology (2021)

The ATEMPT trial was designed to determine if treatment with trastuzumab emtansine (T-DM1) caused less toxicity than paclitaxel plus trastuzumab (TH) and yielded clinically acceptable invasive disease-free survival (iDFS) among patients with stage I human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC).Patients with stage I centrally confirmed HER2+ BC were randomly assigned 3:1 to T-DM1 or TH and received T-DM1 3.6 mg/kg IV every 3 weeks for 17 cycles or T 80 mg/m2 IV with H once every week × 12 weeks (4 mg/kg load →2 mg/kg), followed by H × 39 weeks (6 mg/kg once every 3 weeks). The co-primary objectives were to compare the incidence of clinically relevant toxicities (CRTs) in patients treated with T-DM1 versus TH and to evaluate iDFS in patients receiving T-DM1.The analysis population includes all 497 patients who initiated protocol therapy (383 T-DM1 and 114 TH). CRTs were experienced by 46% of patients on T-DM1 and 47% of patients on TH (P = .83). The 3-year iDFS for T-DM1 was 97.8% (95% CI, 96.3 to 99.3), which rejected the null hypothesis (P < .0001). Serially collected patient-reported outcomes indicated that patients treated with T-DM1 had less neuropathy and alopecia and better work productivity compared with patients on TH.Among patients with stage I HER2+ BC, one year of adjuvant T-DM1 was associated with excellent 3-year iDFS, but was not associated with fewer CRT compared with TH.
Abstract 14640: Role of Lipid Phosphate Phosphatase3 in Cardiac Inflammation
Authors: Himi Tripathi, Ahmed Al-Darraji, Erhe Gao, Lakshman Chelvarajan, Bryana Levitan, Andrew J Morris, Susan S Smyth, Ahmed Abdel-Latif
Journal: Circulation (2018)

Introduction: The increased inflammatory response following myocardial infarction (MI)can have harmful effects on cardiac function. This pathological inflammation aggravates tissue damage and is co...
Abstract 13291: Decreased Inspired Oxygen Stimulates New Collateral Formation in the Heart
Authors: Amir Aghajanian, Hua Zhang, Brian Buckley, Erika S Wittchen, Mark D Levin, James Faber
Journal: Circulation (2019)

Background: Coronary collaterals allow blood to bypass occluded vasculature. This protective effect has been recognized for many years in patients with ischemic heart disease (IHD). However, little...
A Practical Approach to the Management of Digital Ulcers in Patients With Systemic Sclerosis
Authors: Michael Hughes, Yannick Allanore, Khadija El Aoufy, Christopher P. Denton, Dinesh Khanna, Thomas Krieg, Marco Matucci-Cerinic
Journal: JAMA Dermatology (2021)

<h3>Importance</h3> Digital ulcers (DUs) occurring on the fingers in patients with systemic sclerosis (SSc) are associated with substantial pain and disability and are often challenging to treat. However, careful clinical assessment and prompt intervention (wound bed management and systemic pharmacologic treatment) may modify the clinical course. <h3>Objectives</h3> To provide a practical approach to the assessment and management of SSc-DUs and highlight unmet needs and research priorities. <h3>Evidence Review</h3> A narrative review of the extant literature was undertaken to provide a broad overview of current knowledge and augmented by expert opinion. <h3>Findings</h3> Half of the patients with SSc have a history of DUs, and there is a point of prevalence of approximately 10%. Digital ulcers are often very painful and affect all aspects of physical, social, and family life as well as occupation. Digital ulcers are associated with a severe disease course. Systemic sclerosis DUs, particularly those occurring on the fingertips, represent a vascular ischemic complication, although other etiopathogenic factors play an important role. To guide management, a structured clinical approach is required, including DU definition, classification, and categorization. Digital ulcers require a multidisciplinary approach with close cooperation between physicians and specialist nursing and other allied health professionals to guarantee the appropriate treatment and provide patient education. Local wound bed management is necessary for all DUs and is combined with systemic (pharmacologic) treatments. When treating a DU, the clinician should actively review the therapeutic strategy to prevent further DUs, including the level of systemic disease control, and monitor closely for the development of DU complications, including infection and progression to gangrene. Despite a wide available therapeutic armory, a number of unmet needs and challenges remain that that require resolution to optimize DU management. <h3>Conclusions and Relevance</h3> A practical approach to DU management, including local wound bed management and systemic treatments, is useful. Digital ulcers are of interest to a broad range of dermatologists, rheumatologists, and other physicians providing care for patients with SSc. Careful clinical assessment and prompt intervention can substantially modify the clinical course of DUs in SSc.
AB0616 RISK FACTORS FOR PREVALENT VERTEBRAL FRAGILITY FRACTURES - STUDY IN A LONDON URBAN BOROUGH
Authors: N. Mothojakan, M. Zaman, A. Perren, S. Mahendrakar, R. Rajak
Journal: Annals of the Rheumatic Diseases (2021)

Background: Vertebral fragility fractures (VFFs) are commonly underdiagnosed, often resulting in chronic pain and reduced quality of life. It is particularly important to identify and manage VFFs, as they are important predictors of future VFFs and non-VFFs. Patients with VFFs often have multiple risk factors, which are important to identify to formulate a tailored and appropriate management plan. There is a paucity of studies that have investigated risk factors specifically for VFFs. Objectives: To identify the prevalence of osteoporosis risk factors in patients with VFFs. Methods: Retrospective review of patients seen between July 2018 and July 2019 at Purley Memorial Hospital, covering a large urban borough. Patients included in the study had prevalent moderate and severe VFFs (defined by Ghent criteria). Results: 84 patients were included, of which there were 71 females and 13 males. Median age was 76 (IQR 67 – 82) and BMI was 25 (IQR 21 – 27), with 6% of patients noted to be underweight (BMI &lt;18.5). 38% of patients had a family history of osteoporosis and 21% of patients reported a history of parental hip fracture. 21% of patients had experienced recurrent falls. Over half (56%) of patients were noted to have had 2-or-more previous fragility fractures. Of the female cohort, 24% had early menopause, 13% were nulliparous and 1% had late menarche. Of the modifiable risk factors, alcohol (24%), sedentary lifestyle (21%) and smoking (13%) were the most common. Thyroid-disease (18%) was the most common medical condition associated, followed by coeliac/malabsorption (7%), endocrinopathy (6%) and COPD (6%). Proton Pump Inhibitors (PPIs) and steroids were the most common medications associated with 16% and 14% of cases respectively. 73% of patients had good calcium intake and 62% had calcium supplements. Overall, 27 patients had 3-or-fewer risk factors, 35 patients had 4-to-6 risk factors, 19 had 7-to-9 risk factors, and 3 had greater than 10 risk factors. Conclusion: Our study identified several risk factors and their prevalence. The majority of patients were female, of which 24% had early menopause. Several modifiable risk factors such as low BMI, alcohol, smoking and sedentary lifestyle were commonly seen, emphasising the need to identify these risk factors in the initial consultation. Over half of patients (56%) had had 2-or-more previous non-VFFs, suggesting the need to screen for VFFs in patients with multiple fragility fractures at baseline assessment. A number of co-existing medical conditions were also observed with thyroid disease being the most prevalent. PPIs and steroids were found to be important risk factors, which may lead to the consideration of alternative medications. Overall, it was found that patients had multiple risk factors, thus it is important to have a holistic assessment of VFF patients and a multi-system management approach to prevent future fractures. Disclosure of Interests: None declared.
Overexpression of Gata4, Mef2c, and Tbx5 Generates Induced Cardiomyocytes Via Direct Reprogramming and Rare Fusion in the Heart
Authors: Mari Isomi, Taketaro Sadahiro, Hiroyuki Yamakawa, Ryo Fujita, Yu Yamada, Yuto Abe, Yoshiko Murakata, Tatsuya Akiyama, Tsugumine Shu, Hiroaki Mizukami, Keiichi Fukuda, Masaki Ieda
Journal: Circulation (2021)
POS0380 HORMONES OF ADIPOSE TISSUE IN PATIENTS WITH RHEUMATOID ARTHRITIS WHO HAVE REDUCED BODY WEIGHT
Authors: L. Arefeva, G. Kravtsov, V. Polyakov, V. Kravtsov, L. Seewordova
Journal: Annals of the Rheumatic Diseases (2021)

Background: Overweight in patients with rheumatic diseases is a condition that prolongs chronic inflammation and promotes synthesis and secretion of pro-inflammatory factors by adipose tissue, such as classical cytokines, tumor necrosis factor-α (TNF-α), adipokines (leptin, adiponektin, resistin) and other newly identified proinflammatory factors (fetuin A, nesfatin, hemerin, lipokain, serum amyloid protein 3) [1,2,3,4]. Objectives: We investigated the relationship the effect of weight loss over 5 kg on the clinical manifestations of arthritis and hormones of adipose tissue serum levels in patients with rheumatoid arthritis (RA). Methods: We observed 80 female patients with RA (EULAR/ARA 2010 criteria) ranged in age from 39 to 69 years (mean age 51,72 ± 5,83 years) and the control group (60 healthy persons) with no complaints of pain in the joints over a lifetime, and without clinical signs of RA. Fetuin A, nesfatin, hemerin, leptin, adiponektin, resistin, visfatin level in serum was determined by ELISA-test using a commercial test systems. Results: As overweight patients were recruited in the study, hypocaloric diet low in animal fats and physiotherapy has been recommended to all participants. The positive dynamics in body weight loss over 5kg within 3 months has been achieved by 34 patients (27,2%). In RA patients with weight loss, a significant decrease in the serum level of pro-inflammatory cytokines (fetuin A, nesfatin, hemerin, leptin, adiponektin, resistin, visfatin (p&lt;0.01)) and an increase in the quality of life according to the EQ-5D-5L (p&lt;0.001) index were observed. This fact is probably explained by the decreased activity of inflammatory process after RA therapy and weight reduction. Conclusion: Thus, as a result of our study patients with RA with weight loss of more than 5 kg had more obvious pain relief than patients with the original weight. These findings suggest that there is a possible role of tissue pro-inflammatory cytokines in the pathogenesis of rheumatoid arthritis. All patients with RA with a BMI over 25 kg / m 2 are recommended to lower their weight to decrease the mechanical stress on the joints, and also to reduce the severity of inflammation and metabolic disorders. References: [1]Akhverdyan, Y. et al. The nicotinamide-phosphoribosiltransferase as a marker of systemic inflammation under osteoarthrosis // Klin Lab Diagn. 2017; 62(10):606-610. [2]Kravtcov, V. et al. High level of adipokines and overweight as factors contributing to osteoarthritis progression // Osteoporosis International, 2019. V.30 (2). S. 408. [3]Papichev, E. V. et al. Parameters of mineral-bone metabolism and fetuin-А level in patients with rheumatoid arthritis // Osteoporosis International, 2019. V.30 (2), S.381. [4]Polyakova J. et al. Tissue cytokines and their role in the pathogenesis of rheumatic diseases // Annal.Rheum.Diseases, 2019. Т. 30 (2), № S.387. Disclosure of Interests: None declared
Reply to Lorenzo et al.
Authors: Dongwook Oh, Sung Woo Ko, Dong-Wan Seo, Seung-Mo Hong, Jin Hee Kim, Tae Jun Song, Do Hyun Park, Sung Koo Lee, Myung-Hwan Kim
Journal: Endoscopy (2021)

See also: Radiofrequency ablation of pancreatic serous cystic neoplasms: feasibility, but for the wrong indicationEndoscopy 2021; 53(06): 666-666DOI: 10.1055/a-1323-2782 See also: Endoscopic ultrasound-guided radiofrequency ablation of pancreatic microcystic serous cystic neoplasms: a retrospective study Endoscopy 2021; 53(07): 739-743DOI: 10.1055/a-1250-7786
One-year durability of anti-spike IgG to SARS-CoV-2: Preliminary data from the anticrown prospective observational study one year durability of COVID-19 anti-spike IgG
Authors: Amedeo F. Capetti, Fabio Borgonovo, Davide Mileto, Gloria Gagliardi, Chiara Mariani, Angelica Lupo, Gianfranco Dedivitiis, Paola Meraviglia, Martina Pellicciotta, Luciana Armiento, Maria V. Cossu, Giuliano Rizzardini
Journal: Journal of Infection (2021)

Data are presented of 368/503 post-COVID-19 outpatients followed within the AntiCROWN Cohort who have a one-year control and a baseline assessment of anti-S1/S2 antibodies, detected with the The LIAISON® SARS-CoV-2 S1/S2 IgG solution by DiaSorin. Loss of response occurred in 4 subjects having a baseline level below 50 AU/mL.
AB0452 GENDER FEATURES IN PSYCHOLOGICAL STATUS IN PATIENTS WITH LUNG ULTRASOUND SYNDROME
Authors: N. Shamsutdinova, D. Abdulganieva, E. Kirillova, D. Gaisina, A. Fatikhova
Journal: Annals of the Rheumatic Diseases (2021)

Background: The use of lung ultrasound (LUS) in the management of patients with ILD has the advantage of lower cost and the absence of x-ray radiation. Objectives: to establish the relationship between ultrasound manifestations of interstitial syndrome and indicators of psychological status in patients with secondary ILD in patients with rheumatic diseases. Methods: 25 patients with secondary ILD in patients with rheumatic diseases (15 patients with systemic scleroderma, 8 patients with ANCA associated systemic vasculitis, 2 patients with dermatomyositis) were investigated. All patients underwent a standard clinical examination, high-resolution RCT of lungs. To assess depression and anxiety were used the following scales: State-Trait Anxiety Inventory, symptomatic questionnaire SCL-90-R, Beck Depression Inventory. LUS was carried out for the evaluation of the location and number of B-lines on both right and left hemithoraces using commercially available echographic equipment with a 5-12 MHz linear transducer (Accuvix A30, Samsung Medison). Results: Most patients had an average number of B-lines 24,5[11,5;34,0]. In woman the total number of В-lines correlated with the situational anxiety (r=-0,71, р&lt;0,05), with the personal anxiety (r=-0,6, р&lt;0,05) and with somatization (r=-0,67, р&lt;0,05). Also there was a trend between somatic (r=-0,49, р=0,08) and affective (r=-0,51, р=0,07) subscales, general depression (r=-0,48, р=0,1), but did not achieve statistical significance, probably due to the small number of patients. Among patients, including men and women, no statistically significant correlation was found. Conclusion: The relationship between situational, personal anxiety, somatization and the total number of В-linesamong women with secondary ILDwas found. More research is needed to clarify details. References: [1]Dietrich CF, Mathis G, Blaivas M, Volpicelli G, Seibel A, Wastl D, Atkinson NS, Cui XW, Fan M, Yi D. Lung B-line artefacts and their use. J Thorac Dis 2016;8(6):1356-1365. doi: 10.21037/jtd.2016.04.55 [2]Tatiana Barskova, Luna Gargani, Serena Guiducci, et al. Lung ultrasound for the screening of interstitial lung disease in very early systemic sclerosis Ann Rheum Dis 2013;72:390–395. doi:10.1136/annrheumdis-2011-201072 Disclosure of Interests: None declared.
Engraftment of strictly anaerobic oxygen-sensitive bacteria in irritable bowel syndrome patients following fecal microbiota transplantation does not improve symptoms
Authors: Patrick Denis Browne, Frederik Cold, Andreas Munk Petersen, Sofie Ingdam Halkjær, Alice Højer Christensen, Stig Günther, Lars Hestbjerg Hansen
Journal: Gut Microbes (2021)

Dysbiosis of the gut microbiome has been correlated with irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) is being explored as a therapeutic option. Little is known of the mechanisms of engraftment of microbes following FMT and whether the engraftment of certain microbes correlate with clinical improvement in IBS. Microbiome data, from a previously reported placebo-controlled trial of treatment of IBS with FMT or placebo capsules, were used to investigate microbial engraftment 15 days, 1, 3 and 6 months after treatment through assessment of gains, losses and changes in abundance of amplicon sequence variants (ASVs) and microbial diversity (CHAO-1 richness) between the FMT group and the placebo group. These data were compared to changes in IBS Symptom Severity Scores (IBS-SSS). Twelve days of treatment with 25 daily multi-donor FMT capsules induced significant short- and long-term changes in the recipients' microbiomes for at least 6 months, with persistent engraftment of a variety of anaerobic bacteria from keystone genera, such as Faecalibacterium, Prevotella and Bacteroides and increased microbial diversity, particularly in patients with low initial diversity. FMT recipients lost ASVs after treatment, which was seen to a much lesser extent in the placebo group. No ASVs increased to a greater extent between FMT responders and non-responders following treatment. Major long-term changes, lasting for at least 6 months, in the gut microbiomes of IBS patients are seen following treatment with FMT capsules. None of these changes correlated with clinical improvement. The relationship between the microbiome and the etiology of IBS still remains unsolved.
Hidden Biomass of Intact Malaria Parasites in the Human Spleen
Authors: Steven Kho, Labibah Qotrunnada, Leo Leonardo, Benediktus Andries, Putu A I Wardani, Aurelie Fricot, Benoit Henry, David Hardy, Nur I Margyaningsih, Dwi Apriyanti, Agatha M Puspitasari, Pak Prayoga, Leily Trianty, Enny Kenangalem, Fabrice Chretien, Innocent Safeukui, Hernando A Del Portillo, Carmen Fernandez-Becerra, Elamaran Meibalan, Matthias Marti, Ric N Price, Tonia Woodberry, Papa A Ndour, Bruce M Russell, Tsin W Yeo, Gabriela Minigo, Rintis Noviyanti, Jeanne R Poespoprodjo, Nurjati C Siregar, Pierre A Buffet, Nicholas M Anstey
Journal: New England Journal of Medicine (2021)

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Risk of Cancer-Specific Death for Patients Diagnosed With Neuroendocrine Tumors: A Population-Based Analysis
Authors: Julie Hallet, Calvin Law, Simron Singh, Alyson Mahar, Sten Myrehaug, Victoria Zuk, Haoyu Zhao, Wing Chan, Angela Assal, Natalie Coburn
Journal: Journal of the National Comprehensive Cancer Network (2021)

Background: Although patients with neuroendocrine tumors (NETs) are known to have prolonged overall survival, the contribution of cancer-specific and noncancer deaths is undefined. This study examined cancer-specific and noncancer death after NET diagnosis. Methods: We conducted a population-based retrospective cohort study of adult patients with NETs from 2001 through 2015. Using competing risks methods, we estimated the cumulative incidence of cancer-specific and noncancer death and stratified by primary NET site and metastatic status. Subdistribution hazard models examined prognostic factors. Results: Among 8,607 included patients, median follow-up was 42 months (interquartile range, 17–82). Risk of cancer-specific death was higher than that of noncancer death, at 27.3% (95% CI, 26.3%–28.4%) and 5.6% (95% CI, 5.1%–6.1%), respectively, at 5 years. Cancer-specific deaths largely exceeded noncancer deaths in synchronous and metachronous metastatic NETs. Patterns varied by primary tumor site, with highest risks of cancer-specific death in bronchopulmonary and pancreatic NETs. For nonmetastatic gastric, small intestine, colonic, and rectal NETs, the risk of noncancer death exceeded that of cancer-specific deaths. Advancing age, higher material deprivation, and metastases were independently associated with higher hazards, and female sex and high comorbidity burden with lower hazards of cancer-specific death. Conclusions: Among all NETs, the risk of dying of cancer was higher than that of dying of other causes. Heterogeneity exists by primary NET site. Some patients with nonmetastatic NETs are more likely to die of noncancer causes than of cancer causes. This information is important for counseling, decision-making, and design of future trials. Cancer-specific mortality should be included in outcomes when assessing treatment strategies.
Retrospective Analysis of High-Dose Melphalan and Autologous Stem Cell Transplantation for Systemic Light-Chain Amyloidosis: A Single Center 63 Cases
Authors: Kiyoshi Okazuka, Nobuhiro Tsukada, Kota Sato, Kanji Miyazaki, Yumiko Yoshiki, Yu Abe, Tadao Ishida, Kenshi Suzuki
Journal: Blood (2017)