tbuckley/cabot-search huggingface dataset:
Diagnosing and management of Waldenström macroglobulinemia
Authors: Monique C. Minnema
Journal: HemaSphere (2019)

Learning goals Understanding of the genomic landscape of Waldenström Macroglobulinemia (WM) and the way this may impact disease presentation. Guideline for first line treatment of WM: when to start and what to give to patients. Guideline for salvage treatment and how to sequence the several treatment options. Introduction Waldenström Macroglobulinemia (WM) is a fascinating disease with a wide area of clinical symptoms and furthermore a broad landscape of genetic abnormalities combined with one hallmark, the MYD88 L256P mutation. Professor Steve Treon has been instrumental in these discoveries and he will discuss the genomic mutations of WM and the implications these mutations have for aberrant pathway signaling inside the B cell. This knowledge will be the fundament for new therapeutic options. Dr Alessandra Tedeschi will provide us with tools to choose from several first line treatment options that can be used in current clinical practice. Treatment choices can be challenging since phase III clinical trials are rare in WM. In general, an anti-CD20 monoclonal antibody is advised alone or in combination with chemotherapy but the poorly understood phenomena of “IgM flare” may require another approach in patients with high IgM levels. The BTK inhibitor Ibrutinib is approved for fist line treatment in patients who cannot be treated with immune-chemotherapy and for salvage treatments. Professor Christian Buske will discuss these salvage treatments for patients with relapsed WM and will especially focus on practical issues to guide treatment choices like the fitness of patients, previously used lines of therapy and the duration of response to these lines of therapy.
AB0891 HYPERURICEMIA AND GOUT IN PATIENTS WITH PAGET’S DISEASE OF BONE
Authors: María Andreína Terán Tinedo, Cristina Pijoan Moratalla, Jose Renato Quiñones Torres
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Hyperuricemia and gout has been described as metabolic complications in patients with more extensive Paget's disease, with a very variable prevalence. However, there is no data about fluctuations of uric acid levels asociated with its treatment and its correlation with alkaline phosphatase variations during gout attacks. <h3>Objectives</h3> To analyze the frequency of hyperuricemia and gout in patients with a diagnosis of Paget's disease of bone (PD) and to establish the correlation between the activity of Paget's disease and its treatment in the fluctuations of uric acid levels. <h3>Methods</h3> Patients with Paget's disease and with scintigraphic uptake suggestive of activity were included. A database was created including demographic information, the presence of symptoms associated with PD, its type (monostotic or polyostotic), alkaline phosphatase (AP) and uric acid (UA) levels at diagnosis and the treatment received. AP and UA levels after treatment were also collected as well as the presence of possible hyperuricemic risk factors (HRF), history of gout and levels of AP and UA during gout attacks, if any. Finally data was analyzed using SPSS v21. <h3>Results</h3> A total of 95 patients were included with a mean age of 70.59 years (range 45-89), with 56% of them being women. The mean values of AP and UA at diagnosis were 178.05± 82.81 mg/dL and 5.84±1.74 mg/dL respectively. 58.9% of the patients had monostotic involvement (56/95) and only 53.12% had associated symptoms (51/95), whereas in the rest of the patients PD was an incidental finding. 70.83% did not present HRF and 56 patients (58.9%) had received treatment for their PD (41% of them with zoledronic acid). Pearson correlation between PA and UA levels was found moderatly positive (0.710 with p&lt;0.0005) and 50.52% of the patients (48/95) had UA levels above 6mg/dL at the time of diagnosis, with a mean of 7.10 mg/dl ±1.74. In 93.5% of the cases there was a decrease in UA levels after the treatment for PD, with a mean decrease of 0.78±1.3 mg/dL over the baseline value at one year of follow-up. Only 11.57% of the patients in our cohort presented gout symptoms during their follow-up, with an increase in AP levels at the time of the attack in 63.63% of the cases. <h3>Conclusion</h3> In our cohort, there was a moderate positive correlation between the elevation of AP and UA in patients with active Paget's disease. Treatment for PD produced a decrease in UA levels from baseline in most patients. Similarly, during gout attacks, an increase in AP levels could be. <h3>Reference</h3> [1] Lluberas-Acosta G, Hansell JR, Schumacher HR Jr. Paget's disease of bone in patients with gout. Arch Intern Med1986Dec; 146 (12):2389-92. <h3>Disclosure of Interests</h3> None declared
Abstract 18547: Utilization of Percutaneous Coronary Intervention in Cancer Patients With Acute Coronary Syndrome - A Nationwide Analysis
Authors: Nishi N Shah, Naga Venkata K Pothineni, Yogita Rochlani, Sabah Bhatti, Cesar Iliescu, Konstantinos Marmagkiolis, Abdul Hakeem
Journal: Circulation (2015)

Background: Patients with active cancer represent an increasingly significant subset of patients presenting with acute coronary syndromes (ST elevation and Non ST elevation myocardial infarction). These patients are underrepresented in clinical trials. We sought to identify utilization of percutaneous coronary intervention (PCI) in patients with various cancers. Methods: We used the Nationwide inpatient sample to identify all patients that presented with STEMI and NSTEMI from the years 2002-2012. Patients with various cancers were identified with appropriate ICD-9 codes. Results: There were an estimated 3,120,957 STEMI admissions during the study period, of which 4.9% (140,008) had an associated cancer diagnosis. PCI was done in 48.3% of STEMI patients without cancer, but only in 32.9% of patients with cancer. We identified a total of 5,422,406 NSTEMI admissions during the same period. 5.6% (303,751) of NSTEMI patients had cancer. PCI utilization in NSTEMI patients without cancer was 27.8% and 19% in patients with cancer. Among individual cancers, patients with pancreatic, liver and gastric cancers had the lowest rates of PCI (table) Conclusion: Our study demonstrates significantly lower rates of PCI in patients with various cancers. Malignancies with a poor overall survival seem to be associated with lower PCI rates. With lack of clinical trial data on management of ACS in patients with various cancers and with improvements in cancer survivors overall, further studies are required to identify gaps in knowledge in appropriate selection of cancer patients for PCI.
Synergistic substrate cofeeding stimulates reductive metabolism
Authors: Junyoung O. Park, Nian Liu, Kara M. Holinski, David F. Emerson, Kangjian Qiao, Benjamin M. Woolston, Jingyang Xu, Zbigniew Lazar, M. Ahsanul Islam, Charles Vidoudez, Peter R. Girguis, Gregory Stephanopoulos
Journal: Nature Metabolism (2019)
FRI0029 DEVELOPMENT OF AN ALGORITHM FOR THE CLASSIFICATION OF CARDIOVASCULAR COMORBIDITY IN RHEUMATOID ARTHRITIS: DATA FROM THE ONTARIO BEST PRACTICES RESEARCH INITIATIVE
Authors: Kangping Cui, Mohammad Movahedi, Claire Bombardier, Bindee Kuriya
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Cardiovascular disease (CVD) is increased in rheumatoid arthritis (RA). The ability to accurately identify CVD and its risk factors is important for primary and secondary prevention strategies. RA registries collect comorbidity data, but discordance between physician-reported and patient-reported comorbidities often exists. <h3>Objectives</h3> We aimed to develop an algorithm for the classification of CVD and CVD RF in a representative RA registry. <h3>Methods</h3> Data were collected from the Ontario Best-practices Research Initiative (OBRI), a clinical registry of RA patients followed in routine care in Ontario, Canada. Clinical information, including patient medication profile, was obtained at registry entry, through physician visits and patient telephone interviews. Cardiovascular disease (CVD) was defined as having ≥ 1 of myocardial infarction (MI), coronary artery disease (CAD), cerebral vascular accident (CVA, including transient ischemic attack and stroke), or peripheral arterial disease (PAD). CVD risk factors included hypertension (HTN), dyslipidemia (DLD), diabetes mellites (DM), and current smoking. <h3>Results</h3> An algorithm for classifying CVD and CVD risk factors was developed including the 2033 subjects with baseline data. At cohort entry, the prevalence of CVD was 5.4% (n=110), HTN 670 (32.9%), DLD 401 (19.7%), DM 165 (8.1%), and current smoking 346 (17%). Seventeen (15.7%) subjects were not identified as having CVD by physician-report but were classified as having CVD upon medication review. Discrepancy between physician and patient-reported CVD RF were: 207 for HTN (31%), 291 for DLD (73%), and 22 for DM (13%). Chart review of 55 patients showed sensitivity of 100% for CVD, 78% for HTN, and 42% for DLD classification. <h3>Conclusion</h3> An algorithm for classification of CVD has been successfully developed in a representative RA registry. The discrepancy between physician and patient-reported CVD highlights the importance of utilizing information from multiple sources when classifying comorbidities. <h3> Disclosure of Interests: </h3> Kangping Cui: None declared, Mohammad Movahedi Employee of: ONTARIO BEST PRACTICE RESEARCH INITIATIVE (OBRI), Claire Bombardier Grant/research support from: Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant for: AbbVie, Hospira, Janssen, Merck, Novartis, Pfizer Inc, Sanofi, Speakers bureau: Roche, Bindee Kuriya Consultant for: Advisory Board Member: Abbvie, Sanofi Genzyme, Eli Lilly, Pfizer Canada, Roche
Phase III randomized trial of sunitinib malate (SU11248) versus interferon-alfa (IFN-α) as first-line systemic therapy for patients with metastatic renal cell carcinoma (mRCC)
Authors: R. J. Motzer, T. E. Hutson, P. Tomczak, M. D. Michaelson, R. M. Bukowski, O. Rixe, S. Oudard, S. T. Kim, C. M. Baum, R. A. Figlin
Journal: Journal of Clinical Oncology (2006)

LBA3 Background: Two multicenter phase II trials of 2 nd line monotherapy with sunitinib (SU11248) in patients (pts) with mRCC showed a response rate of approximately 40% (JCO 2006;24:16–24; Proc ASCO 23, 380s). This international, randomized phase III trial compared the efficacy and safety of sunitinib to IFN-α in treatment naïve pts with mRCC. Methods: Untreated pts with clear-cell mRCC were randomized 1:1 to receive sunitinib (6-week cycles: 50 mg orally once daily for 4 weeks, followed by 2 weeks off) or IFN-α (6-week cycles: subcutaneous injection 9 MU given three times weekly). The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate, overall survival, and adverse events. Based on a planned sample size of 690 patients, the trial was designed to have 90% power to detect a 35% improvement in median PFS from 20 weeks to 27 weeks (4.6 months to 6.2 months; 2-sided unstratified log-rank test; significance level 0.05). Results of a planned analysis on the primary endpoint, PFS, are presented in this report. Results: From Aug 2004 to Oct 2005, 750 patients were randomized: 375 to sunitinib, 375 to IFN-α. Baseline characteristics were well balanced, and included pooled median age = 60 and prior nephrectomy = 90%. Median PFS assessed by third-party independent review was 47.3 weeks (95% CI 40.9, not yet reached) for sunitinib vs. 24.9 weeks (95% CI 21.9, 37.1) for IFN-α [hazard ratio 0.394 (95% CI 0.297, 0.521) (p &lt; 0.000001)]. The objective response rate by third-party independent review was 24.8% (95% CI 19.7, 30.5) for sunitinib vs. 4.9% (95% CI 2.7, 8.1) for IFN-α (p &lt; 0.000001). The objective response rate by investigator assessment was 35.7% (95% CI 30.9, 40.8) for sunitinib vs. 8.8% (95% CI 6.1, 12.1) for IFN-α (p &lt; 0.000001). 632 pts (85%) are alive, with 49 deaths on sunitinib arm and 65 deaths on IFN-α arm. 8% withdrew from the study due to adverse event on sunitinib arm vs. 13% on IFN-α arm. Conclusions: These results demonstrate a statistically significant improvement in PFS and objective response rate for sunitinib over IFN-α in first-line treatment of pts with mRCC. [Table: see text]
PB2443 AUDIT ON NOACS (APIXABAN AND RIVAROXABAN) PRESCRIPTION IN A DISTRICT GENERAL HOSPITAL
Authors: S. Lovato, T. Kanakam, P. Vajia, J. Dosanjh, D. Harford
Journal: HemaSphere (2019)

Background: Oral anticoagulation therapy is the treatment of choice to prevent stroke in patients with non valvular atrial fibrillation. Non‐vitamin K antagonist oral anticoagulants (NOACs) are often used as alternative to vitamin K antagonists as they do not require INR level monitoring. Before initiating the anticoagulant therapy the risk of stroke should be evaluated using the CHA2DS2‐VASc score and the bleeding risk using the HAS‐BLED score. In our institution the most used NOACs are Apixaban and Rivaroxaban. The recommended dose for Apixaban is 5 mg bd, reduced to 2.5 mg twice bd in patients with age &gt;80, weight &lt; 61 kg or serum creatinine &gt; 133 micromol/litre. The recommended dose for Rivaroxaban is 20 mg od. Aims: The aim of this study was to understand the appropriateness of NOACs use in our institution in terms of indication and dose compared to the national guidelines. Methods: We performed an audit including all new patients who attended our anticoagulation service in a period of six months and were started on either Apixaban or Rivaroxaban. To do this we evaluated if the indication for anticoagulation was appropriate, if CHA2DS2‐VASc score HAS‐BLED score were documented on the notes. We also evaluated the appropriateness of the dose adjusted for creatinine of Apixaban. Results: We included 57 patients, 29 of them were started on Apixaban and 28 on Rivaroxaban. All of the patients had a diagnosis of Non Valvular Atrial Fibrillation. CHA2DS2‐VASc score was documented in 31 patients (54%) and HAS‐BLED score in 32 patients (56%), only 22 patients (38%) had both score properly documented. Out of 31 patients 4 (13%) had a CHA2DS2‐VASc score of 0, and out of 32 patients 2 (6%) had a HAS‐BLED score &gt;3. This mean that in 19% of the patients the anticoagulation therapy was not indicated or contraindicated, but also that in 62% of the patients the appropriateness could not be properly evaluated. Creatinine was documented only in 11 of the patients on Apixaban (38%), in all of them the dose was appropriate for renal function. Summary/Conclusion: We included 57 patients, 29 of them were started on Apixaban and 28 on Rivaroxaban. All of the patients had a diagnosis of Non Valvular Atrial Fibrillation. CHA2DS2‐VASc score was documented in 31 patients (54%) and HAS‐BLED score in 32 patients (56%), only 22 patients (38%) had both score properly documented. Out of 31 patients 4 (13%) had a CHA2DS2‐VASc score of 0, and out of 32 patients 2 (6%) had a HAS‐BLED score &gt;3. This mean that in 19% of the patients the anticoagulation therapy was not indicated or contraindicated, but also that in 62% of the patients the appropriateness could not be properly evaluated. Creatinine was documented only in 11 of the patients on Apixaban (38%), in all of them the dose was appropriate for renal function.
Japanese women’s marks soar as medical school exam rigging ends
Authors: Owen Dyer
Journal: BMJ (2019)

Female applicants are outscoring males in the first fair entrance exams at Japanese medical schools that were rocked last year by revelations of widespread exam rigging against women.

Juntendo University in Tokyo reported a pass rate of 8.28% among the 1679 women who took its medical school entrance exam earlier this year. The pass rate among 2202 male candidates was 7.72%.

Hence the male pass rate is 7% lower than the female pass rate this year. Last year it was 93% higher.

An investigation by the ministry of education concluded in December that nine medical schools out of 81 investigated had discriminated against women in their entrance exams. Of the nine, Juntendo University had …
A simple genetic basis of adaptation to a novel thermal environment results in complex metabolic rewiring in Drosophila
Authors: François Mallard, Viola Nolte, Ray Tobler, Martin Kapun, Christian Schlötterer
Journal: Genome biology (2018)

Population genetic theory predicts that rapid adaptation is largely driven by complex traits encoded by many loci of small effect. Because large-effect loci are quickly fixed in natural populations, they should not contribute much to rapid adaptation.To investigate the genetic architecture of thermal adaptation - a highly complex trait - we performed experimental evolution on a natural Drosophila simulans population. Transcriptome and respiration measurements reveal extensive metabolic rewiring after only approximately 60 generations in a hot environment. Analysis of genome-wide polymorphisms identifies two interacting selection targets, Sestrin and SNF4Aγ, pointing to AMPK, a central metabolic switch, as a key factor for thermal adaptation.Our results demonstrate that large-effect loci segregating at intermediate allele frequencies can allow natural populations to rapidly respond to selection. Because SNF4Aγ also exhibits clinal variation in various Drosophila species, we suggest that this large-effect polymorphism is maintained by temporal and spatial temperature variation in natural environments.
SP0145 CASE 2 DISCUSSANT: ENTHESITIS AND THE CONCEPT OF MECHANICAL STRESS
Authors: Dirk Elewaut
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> The enthesis is a site crucial for mobility of the musculoskeletal system yet it is also commonly a target of inflammation, especially in spondyloarthritis. Because the enthesis is prone to high biomechanical forces, it has been hypothesized that biomechanical forces may be implicated in the onset of the enthesitis and spondyloarthritis in general. However, treatment recommendations involve exercise therapy which at first glance appears to pose a paradox. Using a case, we will discuss the current knowledge on enthesitis, the link with mechanical stress and the implications thereof in diagnosis and management of spondyloarthritis <h3>Disclosure of Interests:</h3> None declared
Quantitative evidence for early metastatic seeding in colorectal cancer
Authors: Zheng Hu, Jie Ding, Zhicheng Ma, Ruping Sun, Jose A. Seoane, J. Scott Shaffer, Carlos J. Suarez, Anna S. Berghoff, Chiara Cremolini, Alfredo Falcone, Fotios Loupakis, Peter Birner, Matthias Preusser, Heinz-Josef Lenz, Christina Curtis
Journal: Nature Genetics (2019)
PB2448 REASONS FOR BLOOD DONOR DEFERRAL AMONG VOLUNTARY BLOOD DONORS IN A TERTIARY CARE HOSPITAL IN KATHMANDU, NEPAL
Authors: B. Nepal
Journal: HemaSphere (2019)

Background: Ensuring the wellness of the voluntary blood donor is the main purpose of the donor deferral. It also minimizes the unwanted symptoms that may appear among blood donor recipient. Aims: To analyse the reasons for blood donor deferral among voluntary Blood Donors In A Tertiary Care Hospital In Kathmandu, Nepal Methods: This is the retrospective study carried out among voluntary blood donors at Grande International Hospital, a tertiary care hospital in Kathmandu, Nepal from January 2013 to January 2015. Results: The data were collected from previous records of the blood donor history forms. From a total of 8,550 blood donations, 302(3.53%) blood donor were deferred due to various reasons. Among all the deferred blood donors 189(62.58%) were female where as 113(37.42%) were male. Furthermore, 289(95.69%) were temporarily deferred and 13(4.31%) were permanently deferred. The mean age of deferred blood donor was 35 years. Out of total blood donor deferral; 101(33.48%) donor were rejected because of bed side hypertension (i.e. blood pressure‐ systolic &gt; 140 and diastolic &gt;90 mm hg) which was followed by anaemia(i.e. haemoglobin &lt; 12 gm/dl) 94(31.12%), vaccinations history 43(14.23%), hypotension (i.e. Systolic &lt; 90 mm hg and diastolic &lt; 60 mm hg) 35(11.58%), dental examination 10(3.32%) and medication history 6(1.98%). Permanent deferral namely, risk factor involving transfusion transmitted infections and chronic disease were 5(1.65%) and 8(2.64%) respectively. The prime cause of permanent deferral was risk factor involving transfusion transmitted infections while the temporary deferral was bed side hypertension. Gender wise, the leading cause of donor deferral in male was bed side hypertension and anaemia was the major cause in female. Summary/Conclusion: The findings of the survey aid to evaluate the significant causes of blood donor deferral. This study suggests that the restrictive criteria can be used for blood donor selection. This will in turn increase the blood supply of tertiary care hospital.
Direct and Indirect Effects of Fibroblast Growth Factor (FGF) 15 and FGF19 on Liver Fibrosis Development
Authors: Justin D. Schumacher, Bo Kong, Jason Wu, Daniel Rizzolo, Laura E. Armstrong, Monica D. Chow, Michael Goedken, Yi‐Horng Lee, Grace L. Guo
Journal: Hepatology (2019)

Farnesoid X receptor (FXR) induces fibroblast growth factor 15 (FGF15; human ortholog FGF19) in the gut to potently inhibit bile acid (BA) synthesis in the liver. FXR activation in hepatic stellate cells (HSCs) reduces liver fibrosis (LF). Fgf15 –/– mice develop attenuated LF, but the underlying mechanisms for this protection are unclear. We hypothesized that FGF15/19 functions as a profibrotic mediator or mitogen to HSCs and increased BAs in Fgf15 –/– mice leads to enhanced FXR activation in HSCs, subsequently reducing fibrogenesis. In this study, complimentary in vivo and in vitro approaches were used: (1) CCl 4 ‐induced LF model in wild type (WT), Fgf15 –/– , and Fgf15 transgenic (TG) mice with BA levels modulated by feeding cholestyramine‐ or cholic acid–containing diets; (2) analysis of primary HSCs isolated from WT and Fgf15–/– mice; and (3) treatment of a human HSC line, LX‐2, with FXR activators and/or recombinant FGF19 protein. The results showed that Fgf15–/– mice had lower basal collagen expression, which was increased by BA sequestration. CCl 4 induced fibrosis with similar severity in all genotypes; however, cholestyramine increased fibrosis severity only in Fgf15 –/– mice. HSCs from Fgf15–/– mice showed increased FXR activity and reduced expression of profibrotic mediators. In LX‐2 cells, FXR activation increased peroxisome proliferator‐activated receptor gamma activity and reduced proliferation. FGF19 activated both signal transducer and activator of transcription 3 and c‐Jun N‐terminal kinase pathways and reduced nuclear factor kappa‐light‐chain‐enhancer of activated B cells signaling without increasing fibrogenic gene expression or cell proliferation. Conclusion: FGF15/19 does not act as a direct profibrotic mediator or mitogen to HSCs in our models, and the protection against fibrosis by FGF15 deficiency may be mediated through increased BA activation of FXR in HSCs.