tbuckley/cabot-search huggingface dataset:
AB1302B CHRONIC KIDNEY DISEASE IN RHEUMATOID ARTHRITIS: PREVALENCE AND RISK FACTORS
Authors: Natalia Chebotareva, Tatyana Androsova, Ekaterina Kuznezova
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The problem of chronic kidney diseases (CKD) in rheumatoid arthritis (RA) patients have not been fully studied. The role of biological therapy (BT) is poorly understood. <h3>Objectives</h3> Aim of the study was to examine the prevalence, risk factors and histological variants of CKD in RA, and impact of pharmacotherapy. <h3>Methods</h3> 135 patients with RA from 2013 to 2018 were enrolled in this study. Age, gender, duration of RA, drug therapy, ESR, CRP, DAS28, renal function, proteinuria (PU), histological variants were analyzed. Arterial hypertension, weight index, serum lipids and glucose levels were also assessed. <h3>Results</h3> The incidence of CKD in RA was 30.4% (41 from 135). CKD 3-4 stages with eGFR &lt; 60ml/min/1.73m<sup>2</sup> was detected in 14.8% patients. The duration of the disease, high ESR and DAS28 score, NSAIDs treatment and hyperlipidemia were risk factors for CKD in RA (Fig 1). We also found negative correlation between the DAS28 and eGFR (Fig. 2). Amyloidosis was the most common histologic pattern (51.52%), followed by chronic glomerulonephritis (CGN) (24.24%) and tubulo-interstitial nephritis (24.24%). Among CGN mesangial glomerulonephritis was the most frequent (Table 1). Renal amyloidosis was associated with a duration of RA, presence of systemic symptoms and CRP level. The levels of PU were lower, and eGFR levels were higher in patients treated with BT than in patients treated with synthetic disease-modifying anti-rheumatic drugs (DMARDs) (Fig 3). <h3>Conclusion</h3> CKD is often developed in patients with high RA activity. Treatment with biological agents is associated with a lower PU and higher GFR levels. <h3>References</h3> [1] Tokoroyama T, Ando M, Setoguchi K, Tsuchiya K, Nitta. K. Prevalence, incidence and prognosis of chronic kidney disease classified according to current guidelines: a large retrospective cohort study of rheumatoid arthritis patients. Nephrol Dial Transplant (2016) 0: 1–8 doi: 10.1093/ndt/gfw315 [2] Masako Kochi, Kentaro Kohagura, Yoshiki Shiohira,Kunitoshi Iseki, and Yusuke Ohya Inflammation as a Risk of Developing Chronic Kidney Disease in Rheumatoid Arthritis. PLoS One. 2016; 11(8): e0160225 [3] Kim HW, Lee CK, Cha HS, Choe JY, Park EJ, Kim J. Effect of anti-tumor necrosis factor alpha treatment of rheumatoid arthritis and chronic kidney disease. Rheumatol Int. 2015 Apr;35(4):727-34. doi: 10.1007/s00296-014-3146-4. <h3>Disclosure of Interests</h3> None declared
Thermal sensors improve wrist-worn position tracking
Authors: Jake J. Son, Jon C. Clucas, Curt White, Anirudh Krishnakumar, Joshua T. Vogelstein, Michael P. Milham, Arno Klein
Journal: npj Digital Medicine (2019)

Wearable devices provide a means of tracking hand position in relation to the head, but have mostly relied on wrist-worn inertial measurement unit sensors and proximity sensors, which are inadequate for identifying specific locations. This limits their utility for accurate and precise monitoring of behaviors or providing feedback to guide behaviors. A potential clinical application is monitoring body-focused repetitive behaviors (BFRBs), recurrent, injurious behaviors directed toward the body, such as nail biting and hair pulling, which are often misdiagnosed and undertreated. Here, we demonstrate that including thermal sensors achieves higher accuracy in position tracking when compared against inertial measurement unit and proximity sensor data alone. Our Tingle device distinguished between behaviors from six locations on the head across 39 adult participants, with high AUROC values (best was back of the head: median (1.0), median absolute deviation (0.0); worst was on the cheek: median (0.93), median absolute deviation (0.09)). This study presents preliminary evidence of the advantage of including thermal sensors for position tracking and the Tingle wearable device's potential use in a wide variety of settings, including BFRB diagnosis and management.
PB2397 THROMBOEMBOLIC EVENTS IN THALASSEMIA: 20-YEAR EXPERIENCE OF A GREEK THALASSEMIA CENTER
Authors: S. Kyriakaki, K. Pyrovolaki, E. Klironomos, K. Sfyridaki
Journal: HemaSphere (2019)

Background: Thalassemia is a congenital hemolytic anemia. As standards of medical care have improved in recent years, life expectancy has increased significantly and new complications are becoming evident, such as thromboembolic events. Aims: To estimate the prevalence of thromboembolic events in thalassemia patients at our Thalassemia Center and to determine the frequency of thrombophilic disorders in this population of patients. Methods: We prospectively collected data for all thromboembolic events during the last 20 year. Thrombophilia workup was carried out in 57 of the 91 thalassemia patients. The statistical analyses were performed using the test x2. Results: Data were obtained from 91 patients, 70 patients with thalassemia major (TM) and 21 patients with thalassemia intermedia (TI). Of the 70 patients with TM, 5.7% (4/70) and of the 21 patients with TI, 4.7% (1/21) expressed thromboembolic event. Thrombotic events included: pulmonary embolism and stroke in a patient, priapism in two patients, acute myocardial infarction in a patient and superficial thrombophlebitis in a patient. Most patients who had a thromboembolic event were splenectomized (80%). The median time for expression of thrombosis after splenectomy was 17.4 years. Clotting factors X, II, XI, V, VII, and coagulation inhibitors (protein S, protein C, antithrombin 3)were often decreased while 60% of patients with thrombosis were found to have thrombosis predisposing genetic factors. Summary/Conclusion: We observed a clinically relevant prevalence of thromboembolic events (5.5%). Splenectomy is an important risk factor for thromboembolic events. Several clotting factors and coagulation inhibitors are depleted. The prevalence of genetic factors predisposing to thrombosis is similar in thalassemic and non-thalassemic populations.
All-in-one adeno-associated virus delivery and genome editing by Neisseria meningitidis Cas9 in vivo
Authors: Raed Ibraheim, Chun-Qing Song, Aamir Mir, Nadia Amrani, Wen Xue, Erik J. Sontheimer
Journal: Genome biology (2018)

Clustered, regularly interspaced, short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) have recently opened a new avenue for gene therapy. Cas9 nuclease guided by a single-guide RNA (sgRNA) has been extensively used for genome editing. Currently, three Cas9 orthologs have been adapted for in vivo genome engineering applications: Streptococcus pyogenes Cas9 (SpyCas9), Staphylococcus aureus Cas9 (SauCas9), and Campylobacter jejuni (CjeCas9). However, additional in vivo editing platforms are needed, in part to enable a greater range of sequences to be accessed via viral vectors, especially those in which Cas9 and sgRNA are combined into a single vector genome.Here, we present in vivo editing using Neisseria meningitidis Cas9 (NmeCas9). NmeCas9 is compact, edits with high accuracy, and possesses a distinct protospacer adjacent motif (PAM), making it an excellent candidate for safe gene therapy applications. We find that NmeCas9 can be used to target the Pcsk9 and Hpd genes in mice. Using tail-vein hydrodynamic-based delivery of NmeCas9 plasmid to target the Hpd gene, we successfully reprogram the tyrosine degradation pathway in Hereditary Tyrosinemia Type I mice. More importantly, we deliver NmeCas9 with its sgRNA in a single recombinant adeno-associated vector (rAAV) to target Pcsk9, resulting in lower cholesterol levels in mice. This all-in-one vector yielded > 35% gene modification after two weeks of vector administration, with minimal off-target cleavage in vivo.Our findings indicate that NmeCas9 can enable the editing of disease-causing loci in vivo, expanding the targeting scope of RNA-guided nucleases.
Wild goose chase – no predictable patient subgroups benefit from meniscal surgery: patient-reported outcomes of 641 patients 1 year after surgery
Authors: Kenneth Pihl, Joie Ensor, George Peat, Martin Englund, Stefan Lohmander, Uffe Jørgensen, Nis Nissen, Jakob Vium Fristed, Jonas Bloch Thorlund
Journal: British Journal of Sports Medicine (2019)

Background Despite absence of evidence of a clinical benefit of arthroscopic partial meniscectomy (APM), many surgeons claim that subgroups of patients benefit from APM. Objective We developed a prognostic model predicting change in patient-reported outcome 1 year following arthroscopic meniscal surgery to identify such subgroups. Methods We included 641 patients (age 48.7 years (SD 13), 56% men) undergoing arthroscopic meniscal surgery from the Knee Arthroscopy Cohort Southern Denmark. 18 preoperative factors identified from literature and/or orthopaedic surgeons (patient demographics, medical history, symptom onset and duration, knee-related symptoms, etc) were combined in a multivariable linear regression model. The outcome was change in Knee injury and Osteoarthritis Outcome Score (KOOS 4 ) (average score of 4 of 5 KOOS subscales excluding the activities of daily living subscale) from presurgery to 52 weeks after surgery. A positive KOOS 4 change score constitutes improvement. Prognostic performance was assessed using R 2 statistics and calibration plots and was internally validated by adjusting for optimism using 1000 bootstrap samples. Results Patients improved on average 18.6 (SD 19.7, range −38.0 to 87.8) in KOOS 4 . The strongest prognostic factors for improvement were (1) no previous meniscal surgery on index knee and (2) more severe preoperative knee-related symptoms. The model’s overall predictive performance was low (apparent R 2 =0.162, optimism adjusted R 2 =0.080) and it showed poor calibration (calibration-in-the-large=0.205, calibration slope=0.772). Conclusion Despite combining a large number of preoperative factors presumed clinically relevant, change in patient-reported outcome 1 year following meniscal surgery was not predictable. This essentially quashes the existence of ‘subgroups’ with certain characteristics having a particularly favourable outcome after meniscal surgery. Trial registration number NCT01871272 .
Abstract 15675: Variability in Post-Arrest Targeted Temperature Management Practice in the US: 33°C vs. 36°C
Authors: Marion Leary, Gail Delfin, Anne Grossestreuer, Bentley Bobrow, Jillianne Santos, David Buckler, Benjamin S Abella, Audrey Blewer
Journal: Circulation (2015)

Background: A recent study examining 33C vs 36C use in Targeted Temperature Management (TTM) after cardiac arrest showed equivalent outcomes. However, it is unclear whether providers are changing goal target temperature based on these findings. Objectives: To characterize the state of TTM practice in US hospitals and to assess whether institutions are using a goal temperature of 33C or 36C. Methods: A 10-question internet-based survey was sent to a convenience sample of healthcare providers throughout the US. Providers associated with the Penn Alliance for Therapeutic Hypothermia database, Hypothermia and Resuscitation Training Institute, and other resuscitation specific email lists were included. Participants were queried regarding their institution’s TTM protocol. Descriptive analyses were performed. Results: Between 12/2014-05/2015, 219 healthcare providers responded from 112 institutions in 35 states. Respondents were staff nurses (39%), advanced practice nurses (28%), physicians (22%) and other providers (11%). Respondents represented medical ICU (25%), cardiac ICU (21%), ED (15%), and other ICUs (39%). When asked about their institution’s TTM protocol, of those who responded (204/219), 65% reported a goal temperature of 33C, 8% reported 36C, 25% reported either 33C or 36C, and 3% were unknown. When asked how the target temperature was selected, 30% stated there were only adequate data to support 33C, 3% stated there were only adequate data supporting 36C, 42% stated they were reevaluating 33C v 36C, and 25% stated unknown. A median of 2 (IQR 2-3.5) clinicians from the same institution completed the survey. Of those, 5/39 (13%) of the respondents from the same institution did not agree on or were unsure whether their institution had a TTM protocol; 33% did not agree on the target temperature within their hospital; 64% did not agree or did not know if data supported the instruction’s choice of target temperature. Conclusions: Across hospitals in the US, and even within the same institution, the target temperature for post-arrest patients varies widely. More research is required to understand the choice of TTM target temperature for specific patient indications to improve outcomes.
PB2284 PSYCHOLOGICAL DISTRESS IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES: PREVALENCE AND ASSOCIATED FACTORS
Authors: K. Kacem, H. ghedira, M. sayadi, H. stambouli, J. eddhib, F. m'sadek, S. zriba
Journal: HemaSphere (2019)

Background: The diagnosis of hematological malignancy (HM) is associated with psychological suffering for patients who graft on their physical suffering. Psychological distress (PD) affects patient's quality of life and their ability to adhere to treatment. Aims: The exact prevalence of this event among patients with HM is not well specified. In this work, it is proposed to determine the prevalence of PD in patients with HM and the factors predicting its occurrence. Methods: We conducted a retrospective descriptive study that included 100 patients with HM followed in 2 Clinical Hematology departments in Tunis between 2010 and 2017. The DP was explored by the Distress Thermometer Scale (DTS) and by the validated Arabic version of the Hospital Anxiety and Depression Scale (HADS). Results: PD was detected in 40 patients byDTS and 43 patients by HADS. 18 patients had an anxiety disorder alone, 5 patients had depressive disorder alone and 18 had concurrent anxiety and depression. DTS was significantly correlated with the global HADS, HADS‐depression and HADS‐Anxiety. In multivariate analysis, the associated comorbidities, the governorate of residence and the lack of complete response after treatment were predictive of PD occurrence. Summary/Conclusion: This study has shown a high prevalence of PD among patients with HM. Tunisian hematologists need to know how to detect these disorders as early intervention enhance their psychological wellbeing and improve their disease outcome.
First Strike–Second Strike Strategies in Metastatic Cancer: Lessons from the Evolutionary Dynamics of Extinction
Authors: Robert A. Gatenby, Jingsong Zhang, Joel S. Brown
Journal: Cancer Research (2019)

Abstract While clinical cancer research has produced many highly effective drugs, the diversity and evolutionary capacity of most cancer populations remain insurmountable barriers to cure. Here, we propose that curative outcomes may, nevertheless, be achieved by sequencing therapies that are individually effective but noncurative. Basic principles for such an approach are derived from the eco-evolutionary dynamics of background extinctions in which a “first strike” reduces the size and heterogeneity of the population. When followed immediately by demographic and ecological “second strikes,” the population can be reduced below some minimum threshold, leading inevitably to extinction. This strategy bears strong similarity to the empirically-derived curative therapy in childhood acute lymphocytic leukemia.
Abstract 15327: Revascularization in Elderly Patients With Non-st-Segment Elevation Acute Coronary Syndrome: Effect an Impact on Six Months Mortality
Authors: Ignacio Ferreira-Gonzalez, Alfredo Bardají, Hector Bueno, Jaume Marrugat, Antonio Fernandez-Ortiz, Aida Riebera, Josep R Marsal, Gerard Oristrell, Jose Barrabes
Journal: Circulation (2017)

Introduction and hypothesis: Although revascularization (RV) in non-ST-segment elevation acute coronary syndrome (NSTEACS) is associated with better outcomes, its impact in elderly (≥75 years) is u...
Publisher Correction: Exome sequencing highlights the role of wild-relative introgression in shaping the adaptive landscape of the wheat genome
Authors: Fei He, Raj Pasam, Fan Shi, Surya Kant, Gabriel Keeble-Gagnere, Pippa Kay, Kerrie Forrest, Allan Fritz, Pierre Hucl, Krystalee Wiebe, Ron Knox, Richard Cuthbert, Curtis Pozniak, Alina Akhunova, Peter L. Morrell, John P. Davies, Steve R. Webb, German Spangenberg, Ben Hayes, Hans Daetwyler, Josquin Tibbits, Matthew Hayden, Eduard Akhunov
Journal: Nature Genetics (2019)
SAT0138 PREDICTORS OF CLINICAL EFFICACY OF ABATACEPT IN RHEUMATOID ARTHRITIS: DATA FROM A LARGE OBSERVATIONAL STUDY
Authors: Giovanni Cagnotto, Minna Willim, Lennart Jacobsson, Michele Compagno, Saedis Saevarsdottir, Carl Turesson
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Abatacept (ABA) is a biologic DMARD (bDMARD) used to treat rheumatoid arthritis (RA) since 2006. There are limited data on real life efficacy of ABA, and on predictors for ABA treatment response. <h3>Objectives</h3> Objectives: To compare the effectiveness of ABA in the treatment of RA between bionaïve patients and patients with previous bDMARDs and to investigate predictors of clinical response to ABA. <h3>Methods</h3> In an observational cohort study, based on data from a large national quality register database, patients with RA diagnosis who initiated treatment with ABA between April 2006 and November 2017 were included. LUNDEX corrected response was defined as the fractions remaining on the drug and achieving the outcome among all who initiated treatment (1). Clinical response at 6 and 12 months was evaluated by means of LUNDEX corrected EULAR (L-EULAR) Good Response and LUNDEX corrected HAQ response (change of ≥0.3 from baseline) (L-HAQ). Predictors for clinical response were investigated using logistic regression, with significance based backwards selection of variables for the final multivariate model. The study was supported by an unrestricted grant from Bristol Myers-Squibb. <h3>Results</h3> 2716 RA patients were included in the study. More patients in the bionaïve population achieved L-EULAR Good Response and L-HAQ response at 6 and 12 months than bDMARDs experienced patients (Fig. 1a and 1b). Male sex, no previous bDMARD exposure and a low HAQ score were independent predictors of L-EULAR Good Response at 6 and 12 months (Table 1). Lack of previous bDMARD exposure also predicted L-HAQ response at 6 and 12 months. There was a positive associations between baseline HAQ and L-HAQ response at 6 months (multivariate adjusted odds ratio 1.73; 95% CI 1.46-2.05). <h3>Conclusion</h3> In patients with RA, response rates for treatment with abatacept were substantially higher in bionaïve patients than in those with previous bDMARD experience. Male sex also predicted LUNDEX corrected EULAR good response to abatacept. Patients with extensive disability, measured by HAQ, were less likely to remain on treatment and achieve a EULAR Good Response, but more likely to have significant HAQ improvement. <h3>Reference</h3> [1] Kristensen, et al. Arthritis Rheum. 2006;54(2):600-6. <h3>Disclosure of Interests</h3> Giovanni Cagnotto Consultant for: Novartis, less than 3000 Euro, Minna Willim: None declared, Lennart Jacobsson Consultant for: Eli-Lily, Janssen, Novartis, Pfizer, Speakers bureau: Abbvie., Michele Compagno: None declared, Saedis Saevarsdottir Employee of: Part-time employee at deCODE Genetics/Amgen Inc, working on genetic research unrelated to this project., Carl Turesson: None declared
Abstract 14317: Kvβ2 Mediates Cardiac Repolarization and Injury: Role of Pyridine Nucleotides
Authors: Kalyan C Chapalamadugu, Jared Tur, Javier Cuevas, Chris Katnik, Srinivas M Tipparaju
Journal: Circulation (2015)

Background: Voltage-gated potassium channel (Kv) β2 subunits (Kvβ2) belong to the aldoketo-reductase superfamily and associate with the Kv channel modulating its function. Also, Kvβ2 binds pyridine nucleotides (NAD[P] + /NAD[P]H) with high affinity altering Kv channel gating. However, the physiological relevance of Kvβ2 in cardiac health and disease is unknown. Hypothesis: We tested the hypothesis that Kvβ2 is essential to both basal and pyridine nucleotide mediated regulation of cardiac repolarization. Methods and Results: Kvβ2 knockout (KO) and wild type (Wt) mice were utilized for this study. ECG analysis showed prolonged QTc interval (74.7± 3.7 vs. 65.6 ± 3, n=3 , p&lt;0.05 ) in KO mice when compared to Wt. Monophasic action potential (MAP) data also showed prolonged duration (ms) at 50% repolarization level in KO mouse hearts vs. Wt (MAPD50; 13.2 ± 0.3 vs. 9.7 ± 0.6, n=5-6 , p&lt;0.05 ). To test the obligatory role of Kvβ2 in pyridine nucleotide modulation of cardiac repolarization, we exposed ex vivo perfused hearts or isolated cardiomyocytes to higher lactate levels. These data revealed that acute lactate exposure leads to significant but similar raise in NADH concentration [NADH] i in both KO and Wt heart tissue. However, marked repolarization deficits appeared only in Wt group when tested utilizing ex vivo perfused hearts (MAPD50 - Wt:11.5 ± 0.7 vs. 8.3 ± 0.5, p&lt;0.05 ; KO:12.6 ± 0.7 vs. 12± 0.5, p=0.5 , ms) or isolated myocytes (ΔAPD50 – Wt: 4.7±1.6 ms, p&lt;0.05 ; KO:1.5 ± 0.7 ms, p=0.1 ). Perfusion with high pyruvate levels returned both [NADH] i and MAPD50 to basal levels in Wt mouse hearts. Similarly, we observed that a 14 day isoproterenol treatment also leads to significant increase in cardiac [NADH] i , but only the Wt mouse hearts showed significant repolarization deficits; ex-MAPD50 (5.5 ± 1.6, p&lt; 0.01 ), when compared to no changes in KO (1.9 ± 0.9, p&lt; 0.1) . Conclusions: Our results suggest that Kvβ2 regulates cardiac repolarization. Further, the differential repolarization changes despite similar increases in cardiac [NADH] i indicates an obligatory role of Kvβ2 in the pyridine nucleotide modulation of cardiac repolarization.
Dual-Channel Fluorescence Imaging of Hydrogel Degradation and Tissue Regeneration in the Brain
Authors: G. Kate Park, Su-Hwan Kim, Kyungmin Kim, Priyanka Das, Byung-Gee Kim, Satoshi Kashiwagi, Hak Soo Choi, Nathaniel S. Hwang
Journal: Theranostics (2019)

The ability of brain tissue to regenerate is limited; therefore, brain diseases (i.e., trauma, stroke, tumors) often lead to irreversible motor and cognitive impairments.Therapeutic interventions using various types of injectable biomaterials have been investigated to promote endogenous neural differentiation.Despite promising results in pre-clinical studies, the translation of regenerative medicine to the clinic has many challenges due to the lack of reliable imaging systems to achieve accurate evaluation of the treatment efficacy.Methods: In this study, we developed a dual-channel fluorescence imaging technique to simultaneously monitor tissue ingrowth and scaffold disintegration.Enzymatically crosslinked gelatin-hyaluronic acid hydrogel was labeled with 800 nm fluorophore, ZW800-3a, while the regenerated tissue was highlighted with 700 nm brain-specific contrast agent, Ox1.Results: Using the multichannel fluorescence imaging system, tissue growth and degradation of the NIR hydrogel were simultaneously imaged in the brain of mice.Images were further analyzed and reconstructed to show both visual and quantitative information of each stage of a therapeutic period.Conclusion: Dual-channel in vivo imaging systems can provide highly accurate visual and quantitative information of the brain tissue ingrowth for the evaluation of the therapeutic effect of NIR hydrogel through a simple and fast operating procedure.