tbuckley/cabot-search huggingface dataset:
Lack of EULAR/ERA-EDTA response at 1 year predicts poor long-term renal outcome in patients with lupus nephritis
Authors: Gabriella Moroni, Mariele Gatto, Francesco Tamborini, Silvana Quaglini, Francesca Radice, Francesca Saccon, Giulia Frontini, Federico Alberici, Lucia Sacchi, Valentina Binda, Barbara Trezzi, Augusto Vaglio, Piergiorgio Messa, Renato Alberto Sinico, Andrea Doria
Journal: Annals of the Rheumatic Diseases (2020)

Short-term predictive endpoints of chronic kidney disease (CKD) are needed in lupus nephritis (LN). We tested response to therapy at 1 year.We considered patients with LN who underwent renal biopsy followed by induction therapy between January 1970 and December 2016. LN was assessed using the International Society of Nephrology/Renal Pathology Society (2003) criteria and the National Institute of Health (NIH) activity and chronicity index. The renal outcome was CKD. Response was defined according to EULAR/European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations: complete: proteinuria <0.5 g/24 hours, (near) normal estimated glomerular filtration rate (eGFR); partial: ≥50% proteinuria reduction to subnephrotic levels, (near) normal eGFR; and no response: all the other cases. Logistic regression analysis was employed for 12-month response and Cox regression for CKD prediction.We studied 381 patients (90.5% Caucasians). After 12-month therapy, 58%, 26% and 16% of patients achieved complete, partial and no response, respectively, according to EULAR/ERA-EDTA. During a median follow-up of 10.7 (IQR: 4.97-18.80) years, 53 patients developed CKD. At 15 years, CKD-free survival rate was 95.2%, 87.6% and 55.4% in patients with complete, partial and no response at 12 months, respectively (p<0.0001). CKD-free survival rates did not differ between complete and partial responders (p=0.067). Serum creatinine (HR: 1.485, 95% CI 1.276 to 1.625), eGFR (HR 0.967, 95% CI 0.957 to 0.977) and proteinuria at 12 months (HR 1.234, 95% CI 1.111 to 1.379) were associated with CKD, yet no reliable cut-offs were identified on the receiver operating characteristic curve. In multivariable analysis, no EULAR/ERA-EDTA response at 12 months (HR 5.165, 95% CI 2.770 to 7.628), low C4 (HR 1.053, 95% CI 1.019 to 1.089) and persistent arterial hypertension (HR 3.154, 95% CI 1.500 to 4.547) independently predicted CKD.Lack of EULAR/ERA-EDTA response at 12 months predicts CKD.
More countries report on antibiotic resistance but results are “worrying,” says WHO
Authors: Elisabeth Mahase
Journal: BMJ (2020)

In a positive step in the fight against antibiotic resistance the number of countries tracking the issue has tripled since 2018, but they are finding that bacterial infections are becoming increasingly resistant to the medicines available to treat them, the World Health Organization has warned.

Tedros Adhanom Ghebreyesus, WHO director general, said that as more evidence was gathered WHO was seeing “more clearly and more worryingly …
Abstract A16: The potential of circulating cell-free tumor DNA as a diagnostic marker of ovarian cancer
Authors: Misa Yamamoto, Kenjiro Sawada, Aasa Shimizu, Yuri Matsumoto, Michiko Kodama, Kae Hashimoto, Tadashi Kimura
Journal: Clinical Cancer Research (2020)

Abstract Objective: Circulating cell-free tumor DNA (ctDNA) is fragmented DNA released from cancer cells into the circulation. Technological development of digital PCR allows us to detect a small quantity of ctDNA in the circulation, suggesting its possibility for a future noninvasive biomarker. The aim of this study is to pursue its potential as a diagnostic biomarker to detect ovarian cancer using patients’ plasma. Methods: Twenty-five plasma samples from patients were collected before treatment. The corresponding tumors were also collected, and DNA was extracted. As nonmalignant controls, 10 samples were collected from patients with benign endometrial cysts. Three primers to detect PIK3CA mutations for endometriosis-related carcinoma and three primers to detect TP53 mutations for serous carcinoma were prepared. The presence of these mutations in ctDNA existing in patients’ plasma was confirmed with digital PCR method. PCR data were validated with tumor DNAs. Results: There were 7 cases of clear cell carcinoma,1 endometrioid carcinoma, and 7 serous carcinoma. Among 8 patients with endometriosis-related cancers (clear cell and endometrioid), PIK3CA mutations in plasma were detected in 6 cases, while mutations were not detected in benign endometrial cysts. Among 7 patients with high-grade serous carcinoma, TP53 mutations in patients’ plasma were detected in all cases. The presence of these mutations was confirmed by tumor DNAs. Conclusion: PIK3CA mutation in endometriosis-related cancer and p53 mutation in serous carcinoma were successfully detected in patients’ plasma, suggesting the potential of ctDNAs as a future noninvasive biomarker for ovarian cancer. Citation Format: Misa Yamamoto, Kenjiro Sawada, Aasa Shimizu, Yuri Matsumoto, Michiko Kodama, Kae Hashimoto, Tadashi Kimura. The potential of circulating cell-free tumor DNA as a diagnostic marker of ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A16.
Abstract IA10: Modeling sensitivity and resistance to systemic therapies in lung cancer
Authors: Katerina A. Politi
Journal: Cancer Research (2020)

Abstract Targeted therapies have transformed the landscape for the treatment of metastatic lung cancer. Despite their success, targeted therapies are not curative and acquired resistance is a major impediment to cures for patients treated with these therapies. A paradigm for the success of targeted therapies in lung cancer comes from epidermal growth factor receptor (EGFR) mutant lung cancer where mutations in exons encoding the tyrosine kinase domain of EGFR confer sensitivity to tyrosine kinase inhibitors (TKIs), and several TKIs are currently approved for the first-line treatment of EGFR mutant lung cancer. Moreover, there is heterogeneity in the durability and depth of responses between patients and at different metastatic sites within individual patients. Therefore, there is a need to understand the biology of EGFR mutant tumors and identify factors that affect TKI sensitivity. We developed transgenic mouse models of EGFR mutant lung cancer and have used them to study tumor progression and TKI resistance. When we modeled acquired resistance to the TKI osimertinib as a first-line therapy in transgenic mouse models of EGFRL858R-induced lung adenocarcinoma, we found that it is mediated largely through secondary mutations in EGFR—either C797S or L718V/Q or Kras mutations. We also identified a therapeutic approach to prevent the emergence of secondary mutations in EGFR. To determine whether the presence of co-occurring genetic alterations contributes to a more complex spectrum of resistance mechanisms in vivo, we have developed new mouse models to specifically evaluate the consequences of co-occurring tumor suppressor gene alterations on the progression and TKI sensitivity of EGFR mutant tumors. Collectively, our findings highlight how genetically engineered mouse models of lung cancer, including those with complex genotypes, can be leveraged to study tumor progression and drug resistance in vivo. Citation Format: Katerina A. Politi. Modeling sensitivity and resistance to systemic therapies in lung cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr IA10.
Acid-suppressive medications in the first year of life and risk of childhood asthma: a population-based birth cohort study
Authors: Claudio Barbiellini Amidei, Rosanna Comoretto, Loris Zanier, Daniele Donà, Anna Cantarutti, Cristina Canova
Journal: European Respiratory Journal (2020)

<b>Exposure to acid-suppressive medications in the first year of life is associated with a marked increase in the risk of developing childhood asthma; further studies are required to assess the causal relationship that underlies this association</b>https://bit.ly/2BdAzaJ
Transglutaminase 2 is overexpressed in ovarian cancer and facilitates the adhesion of cancer cells to fibronectin
Authors: Minati Satpathy, Harikrishna Nakshatri, Daniela Matei
Journal: Cancer Research (2006)

3407  Background: Tissue transglutaminase (TG2) is an enzyme involved in Ca++-dependent aggregation and polymerization of proteins through cross-linking of glutamine residues. Recent reports have noted increased TG2 expression in epithelial malignancies. Using microarray hybridization, we found that TG2 is over-expressed in ovarian cancer cells compared to normal surface ovarian cells (11-fold difference, p-value=0.0000). The role of TG2 in epithelial ovarian cancer is not known. Materials and Methods: Western Blotting and immunohistochemistry were used to determine TG2 expression in ovarian tumors and in ascites fluid from patients with ovarian cancer. Adhesion to fibronectin (FN) was measured using a solid-phase adhesion assay in ovarian cancer cells. Results: TG2 was detected in 8 of 10 ovarian tumors at protein level, but not in 3 samples of normal ovarian tissue. TG2 expression was detected by immunohistochemistry in 65% of 26 ovarian tumors. In contrast, none of the 6 normal ovarian samples stained for TG2. TG2 is a secreted protein and was detected in 25 of 30 specimens of peritoneal fluid collected from patients with ovarian cancer. In contrast small amounts or no TG2 was found in ascites fluid from patients with inflammatory conditions. To determine the function of TG2 in human ovarian epithelial cells, the protein was knocked down by stable transfection with an anti-sense TG2 construct (SkOv3 cells) and was stably overexpressed using WT TG2 cloned in pCDNA3.1 (OV90 cells). Adhesion to fibronectin was decreased by 50% in SKOV3 cells lacking TG2 compared to cells transfected with pCDNA3.1. Cells transfected with anti-TG failed to spread on FN, as assessed by immunoflourescent staining for phalloidin and microscopic examination. Similarly, pre-incubation with a neutralizing antibody against the integrin binding domain of TG2 significantly reduced the adhesion of cells to fibronectin (∼ 30%). In contrast, stable TG2 overexpression lead to increased adhesion to FN in OV90 cells. Phosphorylation of the focal adhesion kinase (FAK), engaged upon cell adhesion, was inhibited in cells where TG2 was knocked down. Transient over-expression of TG2 led to increased adhesion-induced FAK phosphorylation. Specific association of TG2 with β1 integrin was demonstrated by co-immunoprecipitation. Knock-down of TG2 lead to decreased levels of β1 integrin, which was reversed in the presence of cycloheximide and MG132, suggesting that TG2 is necessary for stabilizing β1 integrin. Conclusion: These data suggest that transglutaminase 2 is expressed in epithelial ovarian tumors, in a cancer-restricted manner. TG2 is necessary for ovarian cancer cell adhesion to the extracellular matrix by binding to and stabilizing the β1 integrin complex.
Inactivation of paracellular cation-selective claudin-2 channels attenuates immune-mediated experimental colitis in mice
Authors: Preeti Raju, Nitesh Shashikanth, Pei-Yun Tsai, Pawin Pongkorpsakol, Sandra Chanez-Paredes, Peter R. Steinhagen, Wei-Ting Kuo, Gurminder Singh, Sachiko Tsukita, Jerrold R. Turner
Journal: Journal of Clinical Investigation (2020)

The tight junction protein claudin-2 is upregulated in disease. Although many studies have linked intestinal barrier loss to local and systemic disease, these have relied on macromolecular probes. In vitro analyses show, however, that these probes cannot be accommodated by size- and charge-selective claudin-2 channels. We sought to define the impact of claudin-2 channels on disease. Transgenic claudin-2 overexpression or IL-13–induced claudin-2 upregulation increased intestinal small cation permeability in vivo. IL-13 did not, however, affect permeability in claudin-2–knockout mice. Claudin-2 is therefore necessary and sufficient to effect size- and charge-selective permeability increases in vivo. In chronic disease, T cell transfer colitis severity was augmented or diminished in claudin-2–transgenic or –knockout mice, respectively. We translated the in vitro observation that casein kinase-2 (CK2) inhibition blocks claudin-2 channel function to prevent acute, IL-13–induced, claudin-2–mediated permeability increases in vivo. In chronic immune-mediated colitis, CK2 inhibition attenuated progression in claudin-2–sufficient, but not claudin-2–knockout, mice, i.e., the effect was claudin-2 dependent. Paracellular flux mediated by claudin-2 channels can therefore promote immune-mediated colitis progression. Although the mechanisms by which claudin-2 channels intensify disease remain to be defined, these data suggest that claudin-2 may be an accessible target in immune-mediated disorders, including inflammatory bowel disease.
Clinical efficacy of surgical versus conservative treatment for multiple rib fractures: A meta-analysis of randomized controlled trials
Authors: Rui Long, Junying Tian, Shasha Wu, Yang Li, Xiuhua Yang, Jun Fei
Journal: International Journal of Surgery (2020)

There are still controversies between surgical treatment and conservative treatment for multiple rib fractures (MRFs). No consensus has been reached concerning the indications and timing of surgery. In this meta-analysis, we aimed to determine the optimal treatment for MRFs.Six databases (PubMed, Medline, Embase, Cochrane, Cnki, Wanfang Database) were retrieved for all eligible randomized controlled trials (RCTs) published before January 2020. MRFs were treated either with operative reduction and internal fixation or conservative treatment. The pertinent data were retrieved. The quality of RCTs was evaluated by the modified Jadad rating scale and meta-analysis was performed using RevMan 5.3 software.Seven RCTs involving 538 MRFs patients (260 were treated surgically vs. 278 conservatively) were included in this meta-analysis. Compared with conservative treatment, surgical treatment resulted in shorter length of hospital stay (WMD -8.48; 95% CI -11.34 to -5.63; P < 0.001), length of ICU stay (WMD -5.72; 95% CI -7.31 to -4.13; P < 0.001) and duration of mechanical ventilation (WMD -4.93; 95% CI -8.79 to -1.07; P = 0.01), with a lower risk of complications including pneumonia (RR 0.40; 95% CI 0.30 to 0.53; P < 0.001) and chest wall deformity (RR 0.07; 95% CI 0.03 to 0.14; P < 0.001). The sensitivity analysis carried out by excluding one study with significant heterogeneity showed that the rate of tracheostomy was lower in the surgical group than in the conservative group (RR 0.44; 95% CI 0.28 to 0.71; P = 0.0008).For patients with MRFs, surgical treatment resulted in faster recovery, a lower risk of complications and better prognosis than conservative treatment.
FRI0619-HPR INVESTIGATION OF THE RELATIONSHIP BETWEEN BIOPSYCHOSOCIAL STATUS AND QUALITY OF LIFE, EMOTION - STATUS AND FUNCTIONALITY IN INDIVIDUALS WITH PSORIATIC ARTHRITIS.
Authors: S. Bulut, E. Ünal, A. Özçadirci, U. Kalyoncu
Journal: Annals of the Rheumatic Diseases (2020)

Background: Due to the chronic processes of rheumatological diseases, patients’ biopsychosocial effects are revealed. Objectives: The aim of this study is to evaluate the biopsychosocial status of individuals diagnosed with psoriatic arthritis; to examine the relationship between quality of life, emotion - status and functionality. Methods: 105 individuals were included in the study. To evaluate the biopsychosocial situation, BETY-BQ (Bilişsel Egzersiz Terapi Yaklaşimi – Biopsychosocial Questionnaire)(1); Psoriatic Arthritis Quality of Life (PsAQoL) Scale to assess quality of life; For the emotion-status assessment; Hospital Anxiety and Depression Scale (HADS-A, HADS-D); Health Assessment Questionnaire (HAQ) was used for functionality. Pearson Correlation Analysis was used in statistical analysis. Results: Descriptive data of the individuals participating in the study were recorded (Table 1).While BETY-BQ was highly correlated with PSAQoL Scale(r = 0.826, p &lt;0.001), moderate correlations were found with HADS-A and HADS-D (HADS-A (r = 0.618, p &lt;0.001), HADS-D (r = 0.507, p &lt;0.001)). Low correlation was found between BETY-BQ and HAQ (r = 286, p = 0.003) (Table 2). Table 1. Descriptive Statistics Minimum Maximum Mean Standart Deviation Age (years) 20 60 44.98 11.04 Height (cm) 145.00 190.00 165.61 8.88 Weight (kg) 44 138 75.54 17.36 VKI (kg/m 2 ) 17.85 49.00 27.54 6.02 Table 2. PsAQoL HADS-A HADS-D HAQ BETY-BQ r 0.826 ** p&lt;0.001 r=0.618 ** p&lt;0.001 r=0.507 ** p&lt;0.001 r=286 ** p=0.003 ** Correlation is significant at the 0.01 level (2-tailed) Conclusion: In this study, it was found that BETY-BQ is a scale that can be used in total to evaluate the quality of life, emotion-status level and functionality of individuals diagnosed with PsA. It was thought that BETY-BQ could be considered and preferred by clinicians when individuals with PsA should be evaluated from a biopsychosocial point of view. References: [1] Unal E, Arin G, Karaca Nb, Kiraz S, Akdogan A, Kalyoncu U, et al. Development of a quality of life measurement for rheumatic patients: item pool construction Journal of Exercise Therapy and Rehabilitation. 2017; 4 (2): 67-75. Disclosure of Interests: Senem Bulut: None declared, Edibe Ünal: None declared, Aykut Özçadirci: None declared, Umut Kalyoncu Consultant of: Abbvie, Amgen, Janssen, Lilly, Novartis, UCB
AB0047 T-CELL IMMUNOGLOBULIN AND MUCIN DOMAIN–CONTAINING PROTEIN 3 EXPRESSION IN REGULATORY T CELLS OF ANKYLOSING SPONDYLITIS PATIENTS AND THE CORRELATION WITH DISEASE ACTIVITY
Authors: Y. Wang, X. Huang, J. Chen, M. Liu, W. Deng, Z. Huang, T. Li
Journal: Annals of the Rheumatic Diseases (2020)

Background: Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease. Regulatory T cells have been found in peripheral blood of AS patients. However, there is a controversy regarding the relative number and function of regulatory T cells in AS. T-cell immunoglobulin and mucin domain–containing protein 3 (Tim-3) is a negative immune regulator that participates in immune responses and widely expresses on a variety of immune cells. Many studies have shown that Tim-3 participates in tumors, infections, hematological system diseases and autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, autoimmune hepatitis, etc). While there has not yet clinical trials with large samples to verify whether or not Tim-3 is involved in the incidence of AS and the relationship between the disease activity of AS and the expression of Tim-3 in regulatory T cells. Objectives: The present study aimed to identify the Tim-3 expression in regulatory T cells in AS patients, and the association between Tim-3 and the disease activity of AS. Methods: There were 47 patients diagnosed as AS and 51 age- and sex-matched healthy controls (HCs) from Guangdong Second Provincial Central Hospital enrolled in the study. The clinical information of the AS patients was recorded in detail and the disease activity was calculated. The positive expression rates and medium fuorescence intensity (MFI) of Tim-3 in regulatory T cells were examined by fow cytometry. Statistical approaches were used to analyze the experimental data of patients and controls. Results: The Treg cells level was significantly decreased in AS patients compared to the healthy controls (5.14±0.27 vs 4.38±0.23, P = 0.032, Fig 1 A). Tim-3 expression in regulatory T cells was lower in AS patients than the HCs (63.29±2.39 vs 52.56±3.49, P = 0.013, Fig1 B). And Tim-3 MFI in regulatory T cells was significantly decreased too(1355.04±171.44 vs 859.19±105.11, P = 0.016, Fig1 C). The Treg cells ratio negatively correlated with BASDAI (r=-0395, p=0.014) and BASFI (r=-0391, p=0.015) in AS patients. However, the Tim-3 expression in the Treg cells has no correlation with diseases activity in patients. Conclusion: According to the test results, we could confirm that regulatory T cells participate in the progression of AS, and it has negative relationship with disease activity. Tim-3 can express in Treg, but whether Tim-3 can be used as a potential target for AS treatment in future need further verified. Disclosure of Interests: None declared
Impact of Intrathecal Triple Therapy Versus Intrathecal Methotrexate on Disease-Free Survival for High-Risk B-Lymphoblastic Leukemia: Children’s Oncology Group Study AALL1131
Authors: Wanda L. Salzer, Michael J. Burke, Meenakshi Devidas, Yunfeng Dai, Kristina K. Hardy, John A. Kairalla, Lia Gore, Joanne M. Hilden, Eric Larsen, Karen R. Rabin, Patrick A. Zweidler-McKay, Michael J. Borowitz, Brent Wood, Nyla A. Heerema, Andrew J. Carroll, Naomi Winick, William L. Carroll, Elizabeth A. Raetz, Mignon L. Loh, Stephen P. Hunger
Journal: Journal of Clinical Oncology (2020)

PURPOSE The high-risk stratum of Children’s Oncology Group Study AALL1131 was designed to test the hypothesis that postinduction CNS prophylaxis with intrathecal triple therapy (ITT) including methotrexate, hydrocortisone, and cytarabine would improve the postinduction 5-year disease-free survival (DFS) compared with intrathecal methotrexate (IT MTX), when given on a modified augmented Berlin-Frankfurt-Münster backbone. PATIENTS AND METHODS Children with newly diagnosed National Cancer Institute (NCI) high-risk B-cell acute lymphoblastic leukemia (HR B-ALL) or NCI standard-risk B-ALL with defined minimal residual disease thresholds during induction were randomly assigned to receive postinduction IT MTX or ITT. Patients with CNS3-status disease were not eligible. Postinduction IT therapy was given for a total of 21 to 26 doses. Neurocognitive assessments were performed during therapy and during 1 year off therapy. RESULTS Random assignment was closed to accrual in March 2018 after a futility boundary had been crossed, concluding that ITT could not be shown to be superior to IT MTX. The 5-year postinduction DFS and overall survival rates (± SE) of children randomly assigned to IT MTX versus ITT were 93.2% ± 2.1% v 90.6% ± 2.3% ( P = .85), and 96.3% ± 1.5% v 96.7% ± 1.4% ( P = .77), respectively. There were no differences in the cumulative incidence of isolated bone marrow relapse, isolated CNS relapse, or combined bone marrow and CNS relapse rates, or in toxicities observed for patients receiving IT MTX compared with ITT. There were no significant differences in neurocognitive outcomes for patients receiving IT MTX compared with ITT. CONCLUSION Postinduction CNS prophylaxis with ITT did not improve 5-year DFS for children with HR B-ALL. The standard of care for CNS prophylaxis for children with B-ALL and no overt CNS involvement remains IT MTX.
Clonal Evolution in Newly Diagnosed Multiple Myeloma Patients: A Follow-up Study from the Mmrf Commpass Genomics Project
Authors: Alessandro Lagana, David Melnekoff, Itai Beno, Violetta Leshchenko, Deepak Perumal, Jonathan J. Keats, Mary DeRome, Jennifer Yesil, Daniel Auclair, Deepu Madduri, Ajai Chari, Hearn Jay Cho, Bart Barlogie, Sundar Jagannath, Joel Dudley, Samir Parekh
Journal: Blood (2017)
Trichoscopic findings of discoid lupus erythematosus alopecia: A cross-sectional study
Authors: Heidy Gómez-Quispe, María Elena de las Heras-Alonso, Alejandro Lobato-Berezo, Virginia Velasco-Tamariz, Cristina Pindado-Ortega, Oscar Muñoz Moreno-Arrones, Sergio Vañó-Galván, David Saceda-Corralo
Journal: Journal of the American Academy of Dermatology (2020)
Association of Prenatal Opioid Exposure With Precentral Gyrus Volume in Children
Authors: Micah L. Hartwell, Julie M. Croff, Amanda Sheffield Morris, Florence J. Breslin, Kelly Dunn
Journal: JAMA Pediatrics (2020)

This cross-sectional study identifies structural differences of the precentral gyrus among children with reported prenatal opioid exposure compared with children with no reported exposure, controlling for present social factors.