tbuckley/cabot-search huggingface dataset:
Is kinesiophobia and pain catastrophising at baseline associated with chronic pain and disability in whiplash-associated disorders? A systematic review
Authors: Alejandro Luque-Suarez, Deborah Falla, Jose Miguel Morales-Asencio, Javier Martinez-Calderon
Journal: British Journal of Sports Medicine (2019)

Background Kinesiophobia and pain catastrophising may be associated with patients’ transition from having acute to chronic pain following a whiplash injury. Objective To systematically review and critically appraise the literature to determine whether kinesiophobia and pain catastrophising are associated with greater likelihood of patients developing chronic pain and disability following a whiplash injury. Design A systematic review of the literature Data sources Electronic searches of PubMed, AMED, CINAHL, PsycINFO, and PubPsych, and grey literature were undertaken from inception to September 2017. Eligibility criteria for selecting studies Study selection was based on longitudinal studies evaluating how kinesiophobia and/or pain catastrophising at baseline are associated with pain intensity, disability or both after a whiplash injury. Results We included 14 longitudinal studies that described 12 independent cohorts with a total sample of 2733 participants with whiplash-associated disorder. Kinesiophobia at baseline was not associated with pain intensity over time (three studies). Whether kinesiophobia at baseline was associated with disability was unclear as results were conflicting (six studies). There were also conflicting results when we examined the association between pain catastrophising and both pain intensity (five studies) and disability (eight studies). Summary/conclusions Kinesiophobia at baseline was not associated with pain intensity over time. There were conflicting results for the remaining analyses. The size of the associations was small. The overall quality of the evidence was very low. Trial registration number CRD42016053864.
Hematologic Response to Romiplostim Treatment Is Associated with Stimulation of Primitive Stem/Progenitor Cells and Stromal Cells in Patients with Aplastic Anemia Refractory to Immunosuppressive Therapy: A 2-Year Interim Exploratory Analysis of a Phase 2 Clinical Trial
Authors: Jong-Wook Lee, Sung-Eun Lee, Chul Won Jung, Silvia Park, Jin-A Kim, Il-Hoan Oh, Jun Ho Jang
Journal: Blood (2017)
PF343 CRISPR/CAS9 MEDIATED ELANE KNOCKOUT ENABLES NEUTROPHILIC MATURATION OF HSPCS AND IPSCS OF SEVERE CONGENITAL NEUTROPENIA PATIENTS
Authors: M. Nasri, M. Ritter, P. Mir, B. Dannenmann, D. Amend, V. Makaryan, Y. Xu, C. Zeidler, D.C. Dale, M. Klimiankou, K. Welte, J. Skokowa
Journal: HemaSphere (2019)

Background: Autosomal‐dominant ELANE mutations are the most common cause of severe congenital neutropenia (CN). Although the majority of CN patients respond to daily granulocyte colony stimulating factor (G‐CSF), approximately 15 % do not respond to this cytokine at doses up to 50 μg/kg/day and approximately 15% of G‐CSF treated patients will develop myelodysplasia (MDS) or acute myeloid leukemia (AML). Aims: “Maturation arrest,” the failure of the marrow myeloid progenitors to form mature neutrophils, is a consistent feature of ELANE associated CN. Because mutant neutrophil elastase is the cause of this abnormality, we hypothesized that ELANE associated neutropenia could be treated and “maturation arrest” corrected by CRISPR/Cas9 mediated gene editing. Methods: We applied CRISPR/Cas9‐sgRNA ribonucleoprotein (RNP) mediated ELANE knockout ( ELANE KO) in induced pluripotent stem cells (iPSC) and primary hematopoietic stem and progenitor cells (HSPC). Results: We used iPSC from 2 CN patients and HSPC from 4 CN patients harboring ELANE mutations as well as HL60 cells expressing mutant ELANE . We observed that granulocytic differentiation of ELANE KO iPSC and HSPCs was comparable to healthy individuals and phagocytic function of the ELANE KO neutrophils was also normal. Knock down of ELANE in the mutant ELANE expressing HL60 cells also allowed full maturation and formation of abundant neutrophils. Summary/Conclusion: These observations suggest that ex vivo CRISPR/Cas9 RNP based ELANE knockout of patients’ HSPCs followed by autologous transplantation may be an alternative therapy for CN.
Abstract 20505: Endothelium Specific Mitochondrial ROS in Ischemic Myocardium
Authors: Bonnie Colantuono, Elizabeth O Harrington, Frank W Sellke, M. Ruhul Abid
Journal: Circulation (2016)

Introduction: Ischemic heart disease (IHD) is one of the leading causes of death in the United States. Reactive oxygen species (ROS) are increased during cardiovascular diseases including IHD. Rece...
KLRG1 and NKp46 discriminate subpopulations of human CD117+CRTH2− ILCs biased toward ILC2 or ILC3
Authors: Maho Nagasawa, Balthasar A. Heesters, Chantal M.A. Kradolfer, Lisette Krabbendam, Itziar Martinez-Gonzalez, Marjolein J.W. de Bruijn, Korneliusz Golebski, Rudi W. Hendriks, Ralph Stadhouders, Hergen Spits, Suzanne M. Bal
Journal: The Journal of Experimental Medicine (2019)

Recently, human ILCs that express CD117 and CD127 but lack CRTH2 and NKp44 have been shown to contain precursors of ILC1, ILC2, and ILC3. However, these ILCs have not been extensively characterized. We performed an unbiased hierarchical stochastic neighbor embedding (HSNE) analysis of the phenotype of peripheral blood CD117+ ILCs, which revealed the presence of three major subsets: the first expressed NKp46, the second expressed both NKp46 and CD56, and the third expressed KLRG1, but not NKp46 or CD56. Analysis of their cytokine production profiles and transcriptome revealed that NKp46+ ILCs predominantly develop into ILC3s; some of them can differentiate into ILC1/NK-like cells, but they are unable to develop into ILC2s. In contrast, KLRG1+ ILCs predominantly differentiate into ILC2s. Single-cell cultures demonstrate that KLRG1+ ILCs can also differentiate into other ILC subsets depending on the signals they receive. Epigenetic profiling of KLRG1+ ILCs is consistent with the broad differentiation potential of these cells.
Abstract 15506: Inhibition of the NLRP3 Inflammasome Limits the Inflammatory Injury Following Myocardial Ischemia-reperfusion in the Mouse
Authors: Stefano Toldo, Carlo Marchetti, Adolfo G Mauro, Eleonora Mezzaroma, Salvatore Carbone, Shijun Zhang, Fadi Salloum, Benjamin W Van Tassell, Antonio Abbate
Journal: Circulation (2015)

Introduction: Acute myocardial infarction (AMI) initiates as a result of severe ischemia, and while reperfusion relieves ischemic injury, limiting the overall infarct size (IS), it also triggers a secondary ischemia-independent myocardial injury occurs contributing to the final IS. Hypothesis: We hypothesize that inhibition of the Nod-like Receptor Protein-3 (NLRP3) inflammasome limits the progression of IS following myocardial ischemia/reperfusion (I/R). Methods: Adult CD1 male mice were subjected to transient ligation the left coronary artery for 30 minutes followed by reperfusion (N=3-6 per each group). IS was measured by triphenyl tetrazolium chloride (TTC) staining method at 1, 3 and 24 hours, and with serum cardiac troponin I (cTnI) levels 24 hours after surgery. Myocardial NLPR3 expression was quantified at 3, 6 and 24 hours of reperfusion. A novel pharmacologic NLRP3 inhibitor (NLRP3inh) or vehicle were administrated intraperitoneally at time of reperfusion, or with a delay of 1 or 3 hours. Results: IS measured at TTC was significantly larger at 24 hours (43±4% of the area at risk) vs 3 hours (30±5%) and 1 hour (11±2%, P&lt;0.001 for trend). NLRP3 myocardial expression was also significantly increased at 24 hours (1,097±382% of sham, P&lt;0.001) and 6 hours (928±380%, P&lt;0.001) vs 3 hours (111±15%). When compared with vehicle, the NLRP3inh given at reperfusion did not significantly reduce IS at 3 hours, while it significantly reduced IS at 24 hours (Figure). Administration of the NLRP3inh 1 hour after reperfusion significantly reduced IS at 24 hours, while it did not when given with a delay of 3 hours (Figure). Conclusions: Inhibition of the NLRP3 inflammasome within 1 hour of reperfusion limits the secondary inflammatory injury following myocardial ischemia-reperfusion.
Favorable Response After Only One Cycle of Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE in a Patient With Metastatic Merkel Cell Carcinoma
Authors: Soroush Zarehparvar Moghadam, Ghasemali Divband, Sara Shakeri, Kamran Aryana
Journal: Clinical Nuclear Medicine (2019)

Abstract A 77-year-old man with a history of metastatic Merkel cell carcinoma and debilitating painful cutaneous lesions was referred to our nuclear medicine department for peptide receptor radionuclide therapy with 177 Lu-DOTATATE as ultimate therapeutic option. Post-treatment whole body scan showed multiple zones of 177 Lu-DOTATATE uptake in the metastatic regions, which revealed significant improvement within the next 10 days of therapy. Peptide receptor radionuclide therapy in metastatic Merkel cell carcinoma is an effective therapeutic option that should be considered in earlier stages of the disease.
Vcfanno: fast, flexible annotation of genetic variants
Authors: Brent S. Pedersen, Ryan M. Layer, Aaron R. Quinlan
Journal: Genome biology (2016)

The integration of genome annotations is critical to the identification of genetic variants that are relevant to studies of disease or other traits. However, comprehensive variant annotation with diverse file formats is difficult with existing methods. Here we describe vcfanno, which flexibly extracts and summarizes attributes from multiple annotation files and integrates the annotations within the INFO column of the original VCF file. By leveraging a parallel "chromosome sweeping" algorithm, we demonstrate substantial performance gains by annotating ~85,000 variants per second with 50 attributes from 17 commonly used genome annotation resources. Vcfanno is available at https://github.com/brentp/vcfanno under the MIT license.
Polydopamine coated multifunctional lanthanide theranostic agent for vascular malformation and tumor vessel imaging beyond 1500 nm and imaging-guided photothermal therapy
Authors: Xiaolong Li, Mingyang Jiang, Songjun Zeng, Hongrong Liu
Journal: Theranostics (2019)

The optical imaging guided tumor vessels and vascular malformation visualization by using the second near infrared emission beyond 1500 nm (NIR-II) is emerged as the next generation fluorescence imaging technique for early tumor diagnosis and identification of tumor-associated vascular features. On the other hand, developing theranostic probes for NIR-II imaging guided photothermal therapy (PTT) is of great significance, which is rarely explored. Herein, a high performance theranostic nanoplatform based on the core-shell structured NaLuF4 nanorods@polydopamine (denoted as NRs@PDA) by integrating the new advanced NIR-II imaging beyond 1500 nm with PTT function was developed for tumor-associated vascular malformation visualization and imaging-guided PTT. Methods: In this work, the hydrophilic NaLuF4 NRs@PDA therapeutic probe was synthesized by using a reverse microemulsion method. The crystal phase, morphology, emission spectra and photothermal performance of the synthesized samples were systematically characterized. The NIR-II optical imaging and photothermal properties were investigated by in vitro and in vivo experiments. Results: The NaLuF4 NRs@PDA therapeutic probe possessed efficient NIR-II emission centered at 1525 nm with high quantum yield (QY), good photo-stability and high biocompatibility. In vivo NIR-IIb imaging based on the designed probe can clearly visualize the whole-body vessel and brain vessel with high spatial resolution, especially tumor-associated vessels. In addition, in vitro and in vivo experiments also demonstrated that the designed NaLuF4 NRs@PDA probe possessed efficient photothermal conversion efficiency (40.18%) for PTT ablation of tumor. Conclusion: With the excellent NIR-II imaging ability and PTT of tumor, the designed theranostic nanoplatform successfully realize the simultaneous tumor vessel diagnosis and tumor therapy, which may provide the opportunity of designing new theranostic bioprobes with combination of the NIR-II optical imaging technique and PTT function for tumor diagnosis and therapy.
THU0070 WHAT IS THE ADDITIONAL VALUE OF MRI OF THE FOOT TO THE HAND IN UNDIFFERENTIATED ARTHRITIS TO PREDICT RHEUMATOID ARTHRITIS DEVELOPMENT?
Authors: Yousra Dakkak, Debbie Boeters, Aleid Boer, Monique Reijnierse, Annette van der Helm - van Mil
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> MRI-detected subclinical joint inflammation in hand-joints of patients with undifferentiated arthritis (UA) predicts progression to rheumatoid arthritis (RA). It is unknown if adding MRI of the foot increases predictive accuracy compared to the hand alone. <h3>Objectives</h3> To assess whether MRI-detected inflammation of the foot is predictive for RA-development, and whether combining MRI-detected inflammation of the foot to that of the hand is of additional value. <h3>Methods</h3> 1.5T-contrast-enhanced MRI of unilateral foot (MTP-1-5), and hand (MCP-2-5 and wrist) was performed in 123 patients presenting with UA (not fulfilling 2010 RA-criteria) and scored for bone marrow edema (BME), synovitis and tenosynovitis. Symptom-free controls (n=193) served as a reference for defining an abnormal MRI. Patients were followed for RA-development ≤1-year, defined as fulfilling classification criteria or initiation of disease modifying anti-rheumatic drugs because of the expert opinion of RA. The added predictive value of foot-MRI to hand-MRI was evaluated. <h3>Results</h3> 52% developed RA. Foot tenosynovitis was predictive (OR 2.55, 95%CI 1.01-6.43), independent of BME and synovitis (OR 3.29, 95%CI 1.03-10.53), but not independent of CRP and number of swollen joints (OR 2.14, 95%CI 0.77-5.95). Hand tenosynovitis was also predictive independent of BME and synovitis (OR 3.99, 95%CI 1.64-9.69) and independent of CRP and swollen joints (OR 2.36, 95%CI 1.04-5.38). Adding foot tenosynovitis to hand tenosynovitis changed sensitivity from 72% to 73%, specificity from 59% to 54% and AUC from 0.66 to 0.64, the net reclassification index was -3.5. <h3>Conclusion</h3> MRI-detected tenosynovitis of the foot predicts progression to RA. However adding MRI of the foot does not improve predictive accuracy compared to MRI of the hand alone. In view of cost-reduction, performance of foot-MRI for prognostic purposes in UA can be omitted. <h3>Disclosure of Interests</h3> Yousra Dakkak: None declared, Debbie Boeters: None declared, Aleid Boer: None declared, Monique Reijnierse Grant/research support from: Funding from the Dutch Arthritis Foundation. The funding source had no role in the design and conduct of the study., Annette van der Helm - van Mil Grant/research support from: The research leading to these results has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Starting grant, agreement No 714312) and from the Dutch Arthritis Foundation.&nbsp; The funding source had no role in the design and conduct of the study.
Abstract 20609: CD11c Affinity Modulates Monocyte Recruitment and a Phenotypic Shift That Correlates With Increased Risk of Recurrent Myocardial Infarction
Authors: Alfredo A Hernandez, Scott I Simon, Greg Foster, Andrea Fernandez, Gagan D Singh
Journal: Circulation (2017)

Monocytes are comprised of three functionally distinct sub-populations of mononuclear phagocytes that circulate and recruit to sites of arterial inflammation. Intermediate monocytes (CD14+CD16+, Mo...
PF765 RESULTS OF AUTOLOGOUS STEM CELL TRANSPLANT (ASCT) IN PATIENTS ABOVE THE AGE OF 70 ARE COMPARABLE TO THE RESULTS IN YOUNGER PATIENTS
Authors: K. Mamat, J. Murray, A. Bloor, J. Cavet, M. Dennis, A. Castleton, D. Wiseman, T. Somervaille, S. Kulkarni
Journal: HemaSphere (2019)

Background: High dose chemotherapy and autologous stem cell transplant is an important therapeutic procedure for select solid tumours and haematological malignancies providing chance of durable remission following induction therapy and in some patient potential cure. Increasing numbers of patients above the age of 70 are offered high dose chemotherapy and Auto‐PBSCT. This retrospective analysis compares the outcomes, morbidity and mortality of Auto‐PBSCT in patients above the age of 70 to those in the age group of 65‐69. Aims: To evaluate the results of ASCT in patients with lymphoma or myeloma who were above the age of 70 yrs to the reults in matched group in the age group of 65 to 70 yr. with the aim to compare engraftment data, morbidity, mortality and overall survival. Methods: Retrospective evaluation using case notes, electonic patient records and haematology database. Results: We analysed 54 patients, ages 70 and over, and 56 patients, ages between 65 and 69 years, who received AutoPSCT from 1990 to 2018 in Haematology and Transplant Unit, The Christie NHS Foundation Trust, Manchester, UK. Median age was 71yr(70–75) and 67yr(65–69). Male to female ratio are 38:16 (&gt;70yr) and 41:15 (65–69). The two indications for transplants are Myeloma and lymphoma. The proportions are similar for both age groups, Myeloma:Lymphoma 37(68.5%):17(31.5%) in &gt;70yrs and 40(71.4%):16(28.6%) in 65–69yr The numbers of patients undergoing second Auto‐PBSCT are 9(17%) in &gt;70yr and 11(20%) in 65–69yrs. The follow up period was 2 years (43d‐14.1years) in &gt;70yrs and 4 years (41d‐16.3years) in the 65–69yrs. Median time to neutrophil engraftment (ANC&gt;0.5) was 12 days(9–19days) and 12 days(9–21days). Median platelet recovery (&gt;25) was 21days(10–195days) and 29 days (10–694 days). Median hospitalisation was 27 days (14–91days) and 21days (14–60days). In terms of morbidity during transplant, patients needing intensive or high dependency care was 8 (15%) in &gt;70yr and 5(9%) in 65–69yrs). Patients requiring readmission post discharge was 14(26%) in &gt;70yrs and 9 (16%) in younger age group. here was no difference in treatment related mortality and less than 3% in both groups. Summary/Conclusion: It is feasible to offer ASCT to patients above the age of 70 yr. Patient selection is crucial and should be based not only on the objective organ function evaluation but also the subjective assessment of transplant physician about appropriateness to undergo the ASCT therapy. The decision should be based on the individualised risk benefit ratio, risk of morbidity and expected survival benefit. image
AB0923 EFFECTS OF EXON 10 MUTATIONS VS NON-EXON 10 MUTATIONS ON FMF PHENOTYPE AND RESPONSE TO TREATMENT
Authors: Hatice Adiguzel Dundar, Ozge Altug Gucenmez, Ceyhun Acari, Serkan Turkucar, Balahan Makay, Erbil Unsal
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Familial Mediterranean fever (FMF) is the most common monogenic periodic fever syndrome. The MEFV gene mutation encoding the pyrin protein results in an uncontrolled increase in interleukin-1. Today, more than 333 MEFV mutations have been identified; however, exon 10 mutations are still seem to be best correlated with clinical findings. <h3>Objectives</h3> In this study, we aim to investigate the role of exon 10 mutations vs non-exon 10 mutations on clinical features and response to treatment in patients with FMF. <h3>Methods</h3> Data charts of children (n=935) with FMF from Dokuz Eylul University childrens' hospital and Dr.B.Uz childrens' hospital were reviewed. Patients were divided into two groups with regard to having exon 10 mutation or non-exon 10 mutations. Genotype-phenotype features and response to treatment were compared. <h3>Results</h3> There were exon 10 mutations in 631 (67.5%) patients and non-exon 10 mutations in 304 (32.5) patients. The follow-up period was 50 (26-83.2) months. The age of symptoms onset was significantly lower in group with exon 10 positive than compared group with non-exon 10 mutation. There was no difference between the age of diagnosis and colchicine onset and the diagnosis delay time. The symptoms of fever, chest pain, and arthritis were significantly higher in the exon 10 mutation group than compared other group. Biological agent need was statiscally higher in exon 10 mutation group (4.8%) than group with non-exon 10 mutation (1.3%) (Table 1). <h3>Conclusion</h3> In our study, it was observed that cases with exon 10 mutation have early symptoms of disease. Fever, chest pain and joint findings were more prominent in cases with exon 10 mutation than cases with non-exon 10 mutation. Additionally, colchicine resistance should be kept in mind in cases with exon 10 mutation. <h3>References</h3> [1] Wang DQH, Bonfrate L, de Bari O, Wang TY, Portincasa P (2014) Familial Mediterranean fever: from pathogenesis to treatment. J Genet Syndr Gene Ther5:248. [2] Ozen S, Demirkaya E, Amaryan G, et all. Results from a multicentre international registry of familial Mediterranean fever: impact of environment on the expression of a monogenic disease in children. Ann Rheum Dis. 2014Apr;73(4):662-7 <h3>Disclosure of Interests</h3> Hatice Adiguzel Dundar: None declared, ozge altug gucenmez Speakers bureau: Novartis, Abbvie, Ceyhun Acari: None declared, Serkan Turkucar: None declared, Balahan Makay Speakers bureau: Enzyvant, Novartis, Roche, Abbvie, Erbil Unsal Grant/research support from: Novartis, AbbVie, Roche, Koçak Pharma, Speakers bureau: Novartis, AbbVie, Roche, Koçak Pharma
Safety and Efficacy of Nivolumab in Brain Metastases From Renal Cell Carcinoma: Results of the GETUG-AFU 26 NIVOREN Multicenter Phase II Study
Authors: Ronan Flippot, Cécile Dalban, Brigitte Laguerre, Delphine Borchiellini, Gwénaelle Gravis, Sylvie Négrier, Christine Chevreau, Florence Joly, Lionnel Geoffrois, Sylvain Ladoire, Hakim Mahammedi, Frédéric Rolland, Marine Gross-Goupil, Elise Deluche, Frank Priou, Mathieu Laramas, Philippe Barthélémy, Bérengère Narciso, Nadine Houedé, Stéphane Culine, Stéphane Oudard, Marina Chenot, Florence Tantot, Sylvie Chabaud, Bernard Escudier, Laurence Albiges
Journal: Journal of Clinical Oncology (2019)

Nivolumab is standard of care for patients with metastatic clear cell renal cell carcinoma (ccRCC) after failure of antiangiogenic therapies, but its activity on brain metastases from ccRCC remains unknown, because these patients were excluded from pivotal studies. We aimed to assess the activity of nivolumab in this population.The GETUG-AFU 26 NIVOREN phase II trial assessed the activity and safety of nivolumab in patients with metastatic ccRCC who failed vascular endothelial growth factor-directed therapies (ClinicalTrials.gov identifier: NCT03013335). Patients with asymptomatic brain metastases were prospectively identified and underwent dedicated brain evaluation. Two cohorts were constituted: cohort A comprised patients with previously untreated brain metastases, and cohort B comprised patients whose brain metastases underwent prior therapy. The primary end point was intracranial response rate in cohort A.Seventy-three patients with brain metastases were included: 39 in cohort A and 34 in cohort B. Intracranial response rate was 12% in cohort A; no objective response was reported in patients with brain lesions that were multiple or larger than 1 cm. Median intracranial progression-free survival was 2.7 months (95% CI, 2.3 to 4.6 months) in cohort A and 4.8 months (95% CI, 3.0 to 8.0 months) in cohort B, with adjusted hazard ratio of 2.04 (95% CI, 1.08 to 3.83). Overall survival rate at 12 months was 67% (95% CI, 49.6% to 79.1%) in cohort A and 59% (95% CI, 40.6% to 73.2%) in cohort B. Most patients in cohort A (72%) needed subsequent focal brain therapy. Nivolumab was well tolerated, with no unexpected toxicity.Nivolumab activity is limited in patients with untreated brain metastases from ccRCC. Brain imaging and focal therapy should be considered before immune checkpoint inhibitors in patients with metastatic ccRCC.