tbuckley/cabot-search huggingface dataset:
AB1332 COST EFFECTIVE BIOMARKER IN PREDICTING SLE IN DEVELOPING COUNTRIES – NEUTROPHIL LYMPHOCYTE RATIO (NLR), PLATELET LYMPHOCYTE RATIO (PLR), MPV
Authors: V S. Srikanth, M Gopala Krishna Pillai, (Col.) Vishal Marwaha, Shruthi Rajkumar
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> SLE is a disease which is easily missed in regular clinical practice. In developing countries due to lack of investigation modalities and rheumatologist, early identification of the diseases process is delayed. By the time the patient reaches a higher medical care centre there is a significant time loss and advancement of the disease. NLR, PLR, RDW and MPV can be calculated from a complete blood count which will be available at any grass route heath centre. <h3>Objectives</h3> To identify Cost effective biomarkers in predicting SLE in developing countries. Focussing on markers - Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), MPV. <h3>Methods</h3> This is a retrospective hospital based observational study conducted screening patients admitted from January 2016- November 2018 in with a diagnosis of SLE. We identified 150 patients with SLE and their NLR, PLR, and MPV data were collected and were correlated with equal control group without SLE <h3>Results</h3> We found that NLR, PLR, and MPV were highly significant with a p-value of 0.001 to be used as bio marker and also when further analysis was done using ROC curve with an area under curve of 76%, 81% and 78% respectively when compared with the control group. <h3>Conclusion</h3> We conclude that NLR,PLR,and MPV is cost-effective bio marker which costs (&lt; 1 Euro) in predicting SLE and also play a great in monitoring following up referring patient to higher centre for biopsy at a golden period which will aid in early management which will limit the mortality and morbidity associated with the disease <h3>References</h3> [1] Qin B, Ma N, Tang Q, Wei T, Yang M, Fu H, Hu Z, Ling Y, Yang Z, Zhong R Neutrophil, to Lymphocyte ratio (NLR) and Platelet to Lymphocyte Ratio (PLR) were useful markers in assessment of inflammatory response and disease activity in SLE patients. ModRhematol.2016;26(3):372-6. doi: 10.3109/14397595.2015.1091136. Epub 2016 Mar 4. [2] Wu Y1, Chen Y1, Yang X2, Chen L1, Yang Y3 Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were associated with disease activity in patients with systemic lupus erythematosus.Int Immunopharmacol. 2016 Jul;36:94-99. doi: 10.1016/j.intimp.2016.04.006. Epub 2016 Apr 22. [3] Soliman WM1, Sherif NM1, Ghanima IM1, El-Badawy MA2. Neutrophil to Lymphocyte and Platelet to Lymphocyte Ratios in Systemic Lupus Erythematosus: Relation With Disease Activity and Lupus Nephritis. [4] Reumatol Clin. 2018 Aug 27. pii: S1699-258X(18)30167-0. doi: 10.1016/j.reuma.2018.07.008. [Epub ahead of print] <h3>Disclosure of Interests</h3> None declared
PB2352 PROPHYLACTIC PROSTAGLANDIN E1 PREVENT SINUSOIDAL OBSTRUCTION SYNDROME/VENO‐OCCLUSIVE DISEASE OF THE LIVER AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: S.‐N. Lim, S. Ko, S. Park, B. Sohn
Journal: HemaSphere (2019)

Background: Prostglandin E1 (PGE1) was used to prevent sinusoidal obstruction/veno‐occlusive disease (SOS/VOD) of the liver after allogeneic hematopoietic stem cell transplantation (HSCT) for hematologic malignancies. Aims: We evaluated retrospectively that prophylactic using of prostaglandin E1 prevent SOS/VOD of the liver in patients received allogeneic hematopoietic stem cell transplantation. Methods: It was given in continuous intravenous infusion from day ‐8 to day 14 after allogeneic HSCT at a dose of 0.3 micrograms/kg/hour. The patients were studied according to the risk factors for SOS/VOD: diagnosis, intensification of the conditioning and previous liver abnormalities. The diagnosis of SOS/VOD was made on revised diagnosis and severity criteria for SOS/VOD in new classification from the European society for blood and marrow transplantation. Seventy‐eight patients underwent allogeneic HSCT between September 2010 and November 2017 and 71 were treated by PEG1 and seven did not receive it. Results: The median age of included patients was 45‐year‐old (range, 18‐64 year‐old) and the male was 36 patients (46%). The actual incidence of SOS/VOD was 1.3% (one patient) in the PGE1 group and 14.3% (one patient) in the non PGE1 group (P &lt; 0.001). SOS/VOD developed in two of 78 patients (2.6%) with diagnosis day 7 and day 11 after hematopoietic stem cell infusion. of two patients, one had moderate SOS/VOD and one had severe SOS/VOD as new EBMT criteria for severity grading. Two patients who were diagnosed in SOS/VOD were in acute leukemia. Survival at day +100 for Summary/Conclusion: The prophylactic PGE1 treatment may decrease the incidence of SOS/VOD in patients by allogeneic hematopoietic stem cell transplantation.
Guiding interoperable electronic health records through patient-sharing networks
Authors: Jonathan M. Clarke, Leigh R. Warren, Sonal Arora, Mauricio Barahona, Ara W. Darzi
Journal: npj Digital Medicine (2018)

Effective sharing of clinical information between care providers is a critical component of a safe, efficient health system. National data-sharing systems may be costly, politically contentious and do not reflect local patterns of care delivery. This study examines hospital attendances in England from 2013 to 2015 to identify instances of patient sharing between hospitals. Of 19.6 million patients receiving care from 155 hospital care providers, 130 million presentations were identified. On 14.7 million occasions (12%), patients attended a different hospital to the one they attended on their previous interaction. A network of hospitals was constructed based on the frequency of patient sharing between hospitals which was partitioned using the Louvain algorithm into ten distinct data-sharing communities, improving the continuity of data sharing in such instances from 0 to 65-95%. Locally implemented data-sharing communities of hospitals may achieve effective accessibility of clinical information without a large-scale national interoperable information system.
Genetic Ablation of the Cystine Transporter xCT in PDAC Cells Inhibits mTORC1, Growth, Survival, and Tumor Formation via Nutrient and Oxidative Stresses
Authors: Boutaina Daher, Scott K. Parks, Jerome Durivault, Yann Cormerais, Hanane Baidarjad, Eric Tambutte, Jacques Pouysségur, Milica Vučetić
Journal: Cancer Research (2019)

Although chemoresistance remains a primary challenge in the treatment of pancreatic ductal adenocarcinoma (PDAC), exploiting oxidative stress might offer novel therapeutic clues. Here we explored the potential of targeting cystine/glutamate exchanger (SLC7A11/xCT), which contributes to the maintenance of intracellular glutathione (GSH). Genomic disruption of xCT via CRISPR-Cas9 was achieved in two PDAC cell lines, MiaPaCa-2 and Capan-2, and xCT-KO clones were cultivated in the presence of N-acetylcysteine. Although several cystine/cysteine transporters have been identified, our findings demonstrate that, in vitro, xCT plays the major role in intracellular cysteine balance and GSH biosynthesis. As a consequence, both xCT-KO cell lines exhibited amino acid stress with activation of GCN2 and subsequent induction of ATF4, inhibition of mTORC1, proliferation arrest, and cell death. Tumor xenograft growth was delayed but not suppressed in xCT-KO cells, which indicated both the key role of xCT and also the presence of additional mechanisms for cysteine homeostasis in vivo. Moreover, rapid depletion of intracellular GSH in xCT-KO cells led to accumulation of lipid peroxides and cell swelling. These two hallmarks of ferroptotic cell death were prevented by vitamin E or iron chelation. Finally, in vitro pharmacologic inhibition of xCT by low concentrations of erastin phenocopied xCT-KO and potentiated the cytotoxic effects of both gemcitabine and cisplatin in PDAC cell lines. In conclusion, our findings strongly support that inhibition of xCT, by its dual induction of nutritional and oxidative cellular stresses, has great potential as an anticancer strategy. SIGNIFICANCE: The cystine/glutamate exchanger xCT is essential for amino acid and redox homeostasis and its inhibition has potential for anticancer therapy by inducing ferroptosis.
Safe Use of Immune Checkpoint Inhibitors in the Multidisciplinary Management of Urological Cancer: The European Association of Urology Position in 2019
Authors: Marc-Oliver Grimm, Axel Bex, Maria De Santis, Börje Ljungberg, James W.F. Catto, Morgan Rouprêt, Syed A. Hussain, Joaquim Bellmunt, Tom Powles, Manfred Wirth, Hendrik Van Poppel
Journal: European Urology (2019)
SAT0196 RENAL FLARE IN CLASS V LUPUS NEPHRITIS: INCREASED RISK IN PATIENTS WITH TUBULOINTERSTITIAL LESIONS
Authors: Oh Chan Kwon, Wook Jang Seo, Ji Seon Oh, Min-Chan Park, Seokchan Hong, Chang-Keun Lee, Bin Yoo, Yong-Gil Kim
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Lupus nephritis leads to considerable morbidity and mortality in patients with systemic lupus erythematosus. Although membranous lupus nephritis has a better renal prognosis than proliferative lupus nephritis, progression to end-stage renal disease does occur. Renal flare is an independent predictor of renal prognosis in membranous lupus nephritis. <h3>Objectives:</h3> To investigate the risk factors of renal flare in patients with membranous lupus nephritis. <h3>Methods:</h3> Biopsy-proven pure membranous lupus nephritis patients diagnosed between January 1997 and September 2017 were studied. We assessed and compared the clinical and pathological parameters between patients who experienced renal flare and those who did not. To identify risk factors of renal flare, multivariable Cox proportional hazard regression analysis with stepwise backward elimination was performed. <h3>Results:</h3> Out of the 53 patients with pure membranous lupus nephritis, 17 patients (32.1%) experienced renal flare during a median follow-up of 121.5 months (range, 44.4 – 196.9). Patients who experienced renal flare had significantly higher proportion of tubulointerstitial inflammation at baseline (76.5% vs. 36.1%, p = 0.006) and tubular atrophy/interstitial fibrosis (70.6% vs. 27.8%, p = 0.003). In multivariable Cox proportional hazard regression analysis, presence of tubulointerstitial inflammation (adjusted hazard ratio (HR) 5.532, 95% confidence interval (CI) 1.722 – 17.776, p = 0.004) and tubular atrophy/interstitial fibrosis (adjusted HR 4.328, 95% CI 1.450 – 12.916, p = 0.009) at baseline were significantly associated with increased risk of renal flare. <h3>Conclusion:</h3> Presence of tubulointerstitial inflammation and tubular atrophy/interstitial fibrosis is associated with increased risk of renal flare in patients with membranous lupus nephritis. Closer monitoring of membranous lupus nephritis patients with tubulointerstitial lesions could lead to earlier treatments and better outcomes. <h3>Disclosure of Interests:</h3> None declared
Review: Automated office BP measures are similar to awake ambulatory BP and lower than other office BP measures
Authors: Panagiotis I. Georgianos, Rajiv Agarwal
Journal: Annals of Internal Medicine (2019)

Source Citation Roerecke M, Kaczorowski J, Myers MG. Comparing automated office blood pressure readings with other methods of blood pressure measurement for identifying patients with possible hypertension: a systematic review and meta-analysis. JAMA Intern Med. 2019. [Epub ahead of print]. 30715088
AB0297 HOW OFTEN IS THE COMBINATION OF NSAID-INDUCED LESIONS OF THE UPPER AND LOWER GI TRACT?
Authors: Anna Balabantseva, Andrey Karateev
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Non-steroidal anti-inflammatory drugs (NSAIDs) can damage all parts of the gastrointestinal tract (GIT). However, the frequency of the combination of lesions in different parts of the gastrointestinal tract has not been studied. <h3>Objectives</h3> To assess the frequency of the combination of NSAID-induced lesions of the upper GI tract, small and large intestine. <h3>Methods</h3> The study group consisted of 112 patients with rheumatic diseases (62.5% of women, 56.2 + 14.6 years), who regularly took NSAIDs. All patients underwent endoscopy of the upper GI tract and colon. Capsule endoscopy was performed in 35 patients with signs of NSAID-gastropathy. <h3>Results</h3> NSAID-gastropathy (erosions and/or gastric or duodenum ulcers) were detected in 43.8%, NSAID enteropathy (hemorrhages, erosions and ulcers of the small intestine) in 68.6%, NSAIDs-colopathy (hemorrhages, erosions and ulcers of the colon) - 14.3% patients. The combination of NSAID-gastro- and colonopathy was detected in 28.6% of patients (odds ratio 12.2, 95% CI 2.619-56.84), the combination of NSAID-gastro, entero- and colopathy - in 10 patients (20.4% of the number of patients with NSAID-gastropathy). There was a significant risk association for the development of NSAID-induced lesions in all parts of the GI tract with a diagnosis of spondyloarthritis, the presence of abdominal pain, small intestine bacterial overgrowth, as well as in the polymorphism of the CYP2C19 gene (CYP2C19 * 17 * 1/* 17 allele). <h3>Conclusion</h3> The combined NSAID-induced damage of various parts of the GI tract is a frequent and serious pathology requiring complex diagnostics and the combined use of prophylactic agents with a different mechanism of action. <h3>Disclosure of Interests</h3> None declared
AB0431 EFFECTS OF LOW-LOAD RESISTANCE EXERCISE OF LOW EXTREMITY IN WOMEN WITH RHEUMATOID ARTHRITIS
Authors: Satoshi Nakazaki, Takashi Murayama, Shinichi Kato
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Some skeletal muscles communicate with other organ by secreting proteins and peptides called myokine. Some myokines have anti-inflammatory effect<sup>1)</sup>. As regards rheumatoid arthritis (RA), many studies have shown that aerobic and resistance exercise programs do not change the number of inflammatory joints and RA disease activity, whereas other studies showed improved the marker. And almost studies were performed by high-load resistance training protocols. Meanwhile lately Schoenfeild showed that muscle hypertrophy can be equally achieved across a spectrum of load ranges with meta-analysis<sup>2)</sup>. <h3>Objectives</h3> To investigate the efficacy of low-load resistance exercise of low extremity protocol on RA. <h3>Methods</h3> Twenty-four patients with RA were enrolled. Inclusion criteria were receipt of a stable dose of biologics, JAK inhibitory, and conventional DMARDs more than 3months prior to the first exercise, and corticosteroid and NSAIDs more than one month prior to the first exercise. The exercise circuits consisted of 6 different low extremity exercises intended to improve arthritis. Within the exercise circuits, each exercise was repeated 8-12 times and less than 50% of the 1-repitition maximum. The exercise circuits were performed 3 times a week. Disease activity parameters and inflamed joint of upper extremity and lower extremity were collected at base line and 2 months after exercise started. The Wilcoxon signed-rank test was used to examine the difference between the parameter of the base line and the 2 months. <h3>Results</h3> All patients were female. Mean age was 68.7 years., and mean disease duration 15.3 years. Seven patients (29%) used methotrexate, 5 patients (21%) used prednisolone and 13 patients (54%) used biologics. Mean DAS28(ESR) was 3.98 at base line and 3.58 at 2 months, mean DAS28(CRP) 3.46 and 3.06, mean SDAI 15.4 and 12.5, and mean CDAI 14.5 and 11.5, and mean upper extremity joint tenderness 4.7 and 3.7, mean upper extremity joint swelling 1.6 and 1.8, mean lower extremity joint tenderness 5.8 and 2.2, mean lower extremity joint swelling 4.0 and 2.0 respectively. Every index except upper extremity joint swelling improved significantly (p&lt;0.05) at 2 months than baseline. <h3>Conclusion</h3> Low intensity exercise of low extremity was efficacious against not only lower extremity arthritis but also upper extremity joint arthritis in patients with rheumatoid arthritis <h3>References</h3> [1] Fabiana B Benatti, Bente K Pedersen: Exercise as an anti-inflammatory therapy for rheumatic diseases-myokine regulation. Nat Rev Rheumatol 11: 86-97, 2015. [2] Brad J Schoenfeld, et al.: Strength and hypertrophy adaptations low- vs. high-load resistance training a systemic review and meta-analysis. Strength Cond Res 31(12): 3508-3523, 2017 <h3>Disclosure of Interests</h3> None declared
Reconstruction of the pulmonary artery by a novel biodegradable conduit engineered with perinatal stem cell-derived vascular smooth muscle cells enables physiological vascular growth in a large animal model of congenital heart disease
Authors: Mohamed T. Ghorbel, Huidong Jia, Megan M. Swim, Dominga Iacobazzi, Ambra Albertario, Carlo Zebele, Delphine Holopherne-Doran, Anthony Hollander, Paolo Madeddu, Massimo Caputo
Journal: Biomaterials (2019)
Opportunities and challenges of active immunotherapy in dogs with B-cell lymphoma: a 5-year experience in two veterinary oncology centers
Authors: Laura Marconato, Luca Aresu, Damiano Stefanello, Stefano Comazzi, Valeria Martini, Roberta Ferrari, Fulvio Riondato, Nicole Rouquet, Patrick Frayssinet, Silvia Sabattini
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Pet dogs spontaneously develop lymphoma. An anthracycline-based multidrug chemotherapy regimen represents the treatment cornerstone; however, cure is rarely achieved. We have been treating dogs with B-cell lymphoma with an autologous vaccine (APAVAC®) and CHOP-based chemotherapy since 2011. <h3>Methods</h3> To better characterize the safety and efficacy of APAVAC®, and to find the best candidates for immunotherapy, we designed a retrospective study on all dogs treated with chemo-immunotherapy to date and compared them with those dogs treated with chemotherapy only. All dogs were completely staged and re-staged at the end of treatment. The primary endpoint was the effectiveness of chemo-immunotherapy, measured as time to progression (TTP), lymphoma-specific survival (LSS), and 1-, 2-, and 3-year survival rates. The secondary objective was safety. <h3>Results</h3> Three hundred dogs were included: 148 (49.3%) received chemotherapy and 152 (50.7%) chemo-immunotherapy. Overall, the latter survived significantly longer (median LSS, 401 vs 220; <i>P</i> &lt; &nbsp;0.001). Among dogs with diffuse large B-cell lymphoma, the 1-, 2- and 3-year survival rates were 20, 13 and 8% for chemotherapy, and 51, 19 and 10% for chemo-immunotherapy. The benefit of chemo-immunotherapy was particularly relevant in dogs with concurrent high serum LDH, stage V, substage a disease and not previously treated with steroids (median LSS, 480 vs 85 days; <i>P</i> &lt; &nbsp;0.001). Among dogs with nodal marginal zone lymphoma, those having at least 3 of the aforementioned characteristics significantly benefited from chemo-immunotherapy (median LSS, 680 vs 160 days, <i>P</i> &lt; &nbsp;0.001). The 1-, 2- and 3-year survival rates were 30, 16 and 10% for chemotherapy, and 55, 28 and 10% for chemo-immunotherapy. Among dogs with follicular lymphoma, lack of immunotherapy administration was the only variable significantly associated with increased risk of tumor-related death. Chemo-immunotherapy was remarkably well tolerated, with no local or systemic adverse events. <h3>Conclusions</h3> Overall, the addition of immunotherapy to a traditional CHOP protocol is associated with improved outcome in dogs with B-cell lymphoma, regardless of histotype and evaluated prognostic factors. Moreover, the identikit of the best candidate for immune-therapy was delineated for the most common histotypes. The study also confirms the excellent tolerability of the vaccine.
Sestrin 3 Protects Against Diet‐Induced Nonalcoholic Steatohepatitis in Mice Through Suppression of Transforming Growth Factor β Signal Transduction
Authors: Menghao Huang, Hyeong Geug Kim, Xiaolin Zhong, Chuanpeng Dong, Brian Zhang, Zhigang Fang, Yang Zhang, Xiaoyu Lu, Romil Saxena, Yunlong Liu, Chi Zhang, Suthat Liangpunsakul, X. Charlie Dong
Journal: Hepatology (2019)

Sestrin 3 (Sesn3) belongs to the three‐member sestrin protein family. Sestrins have been implicated in antioxidative stress, adenosine monophosphate–activated protein kinase and mammalian target of rapamycin signal transduction, and metabolic homeostasis. However, the role of Sesn3 in the development of nonalcoholic steatohepatitis (NASH) has not been previously studied. In this work, we generated Sesn3 whole‐body knockout and liver‐specific transgenic mice to investigate the hepatic function of Sesn3 in diet‐induced NASH. With only 4 weeks of dietary treatment, Sesn3 knockout mice developed severe NASH phenotype as characterized by hepatic steatosis, inflammation, and fibrosis. Strikingly, after 8‐week feeding with a NASH‐inducing diet, Sesn3 transgenic mice were largely protected against NASH development. Transcriptomic analysis revealed that multiple extracellular matrix–related processes were up‐regulated, including transforming growth factor β (TGF‐β) signaling and collagen production. Further biochemical and cell biological analyses have illustrated a critical control of the TGF‐β–mothers against decapentaplegic homolog (Smad) pathway by Sesn3 at the TGF‐β receptor and Smad3 levels. First, Sesn3 inhibits the TGF‐β receptor through an interaction with Smad7; second, Sesn3 directly inhibits the Smad3 function through protein–protein interaction and cytosolic retention. Conclusion: Sesn3 is a critical regulator of the extracellular matrix and hepatic fibrosis by suppression of TGF‐β–Smad3 signaling.
Relative Evolutionary Rates in Proteins Are Largely Insensitive to the Substitution Model
Authors: Stephanie J Spielman, Sergei L Kosakovsky Pond
Journal: Molecular Biology and Evolution (2018)

The relative evolutionary rates at individual sites in proteins are informative measures of conservation or adaptation. Often used as evolutionarily aware conservation scores, relative rates reveal key functional or strongly selected residues. Estimating rates in a phylogenetic context requires specifying a protein substitution model, which is typically a phenomenological model trained on a large empirical data set. A strong emphasis has traditionally been placed on selecting the "best-fit" model, with the implicit understanding that suboptimal or otherwise ill-fitting models might bias inferences. However, the pervasiveness and degree of such bias has not been systematically examined. We investigated how model choice impacts site-wise relative rates in a large set of empirical protein alignments. We compared models designed for use on any general protein, models designed for specific domains of life, and the simple equal-rates Jukes Cantor-style model (JC). As expected, information theoretic measures showed overwhelming evidence that some models fit the data decidedly better than others. By contrast, estimates of site-specific evolutionary rates were impressively insensitive to the substitution model used, revealing an unexpected degree of robustness to potential model misspecification. A deeper examination of the fewer than 5% of sites for which model inferences differed in a meaningful way showed that the JC model could uniquely identify rapidly evolving sites that models with empirically derived exchangeabilities failed to detect. We conclude that relative protein rates appear robust to the applied substitution model, and any sensible model of protein evolution, regardless of its fit to the data, should produce broadly consistent evolutionary rates.
Abstract 14977: Multipolar Ablation With Simultaneous versus Bipolar Radiofrequency Delivery Have Different Ablation Lesion Characteristics
Authors: Ryan Borne, William H Sauer, Matthew Zipse, Lijun Zheng, Wendy Tzou, Duy T Nguyen
Journal: Circulation (2017)

Introduction: Both bipolar and simultaneous radiofrequency ablation (bRFA, simRFA) have been used in circular, multipolar irrigated catheters for pulmonary vein isolation in the treatment of atrial...