tbuckley/cabot-search huggingface dataset:
PB2160 REAL LIFE EXPERIENCE OF TREATMENT WITH POMALIDOMIDE, CYCLOPHOSPHAMIDE AND DEXAMETHASONE COMBINATION IN ADULT PATIENTS WITH RELAPSED AND REFRACTORY MULTIPLE MYELOMA
Authors: C. Alarcón‐Payer, M. E. Clavero Sánchez, C. García Collado, M. Jurado Chacón, A. Jiménez Morales
Journal: HemaSphere (2019)

Background: Multiple myeloma is a plasma cell malignancy that accounts for 1% of all cancers. Despite available therapies, the disease remains uniformly fatal, and patients who have received prior lenalidomide and bortezomib have a median overall survival of 9 months. Pomalidomide and low‐dose dexamethasone (PomDex) is standard treatment of lenalidomide refractory myeloma patients who have received &gt;2 prior therapies. Combination therapy is often used in clinical practice in an attempt to overcome drug/clone resistance. Aims: Evaluate in daily clinical practice the effectiveness and safety of the combination pomalidomide, cyclophosphamide and dexamethasone (PomCyDex) in adult patients with relapsed and refractory multiple myeloma (RRMM). Methods Four‐year prospective observational study on 33 cases of RRMM. To measure the health outcomes obtained with the PomCyDex combination in a third level hospital we used the median progression free survival (PFS) as the main variable to assess if the combination is effective. Age, number of previous treatment lines and most frequent adverse reactions were also measured. Results: 33 RRMM cases were analyzed, (57.6%: women; 42.4%: men). The mean age was 68 years. The health outcomes measured in our clinical practice were as follows: 39.4% of the patients were treated with PomCyDex in the 3rd line, 15.1% in the 4th line, 24.3% in the 5th line, 18.2% in the 6th line and 3% in the 7th line. The mean number of PomCyDex cycles received was 9. The median PFS was 5.5 months. PomCydex combination was shown to improve PFS by an additional 1.5 months compared to PomDex‐only patients receiving a 4 month PFS (MM‐003). The most frequent adverse reactions observed were neutropenia (38%), anaemia (11%) and thrombocytopenia (5%). Summary/Conclusion: Treatment with PomCyDex is an effective combination in the treatment of adult patients with RRMM. Also, PomCyDex combination is well tolerated in most patients and is therefore considered a safe treatment.
PF502 A PROPOSAL OF AN ALGORITHM FOR THE DIAGNOSIS OF TYPE 1 GAUCHER DISEASE STARTING FROM HYPERFERRITINEMIA IN ADULTS
Authors: G. Marchi, F. Busti, A. Lira Zidanes, A. Castagna, D. Girelli
Journal: HemaSphere (2019)

Background: Type 1 Gaucher disease (GD) is a pleiotropic disease due to biallelic mutations in GBA gene, causing a reduction or absence of the activity of beta-glucocerebrosidase and accumulation of glucocerebroside in macrophages of several organs, mainly in the spleen, liver and bone marrow. A high degree of suspicion based on “high risk clinical patterns” is required for the diagnosis. Splenomegaly, low platelets and anemia are major clues to suspect GD. However recent studies have shown that, particularly when classical features of GD are mild, only a minority of physicians considers GD in the differential diagnosis. Hyperferritinemia is another biochemical abnormality frequently found in GD, and an increasing reason for consultation in Internal Medicine or Hematology. Aims: To improve clinical sensitivity for the suspicion of Gaucher Disease, starting from “unexplained hyperferritinemia” in adults. Methods: We created an algorithm for the differential diagnosis of hyperferritinemia based on clinical evaluation and widely available first level tests (who to screen for Gaucher disease). We applied this algorithm to patients referred to our EuroBloodNet tertiary center for Iron Metabolism for “unexplained hyperferritinemia”. Results: In the last year we diagnosed 2 cases of type 1 GD in adults, in which “unexplained” hyperferritinemia was the clue that led to the right interpretation of the clinical picture and guided diagnosis. Patient 1 was a 60 years old men referred because of persistent hyperferritinemia (near 1,000 mg/l) and normal TSAT (35%) with provisional diagnosis of “non-HFE Hemochromatosis”. History revealed mild anemia (Hb 12.7 g/dl) and thrombocytopenia (127,000/mmc), which had undergone unnoticed, mild splenomegaly (diameter at US: 12.7 cm). He was assuming L-Dopa because of a 2-years history of mild “parkinsonism”. Patient 2 was a 23 years old female referred for “unexplained hyperferritinemia (600 mg/l). History revealed persistent and fluctuant thrombocytopenia (118,000/mmc at our observation) previously attributed to immune thrombocytopenic purpura (ITP), but unresponsive to steroids. Physical examination revealed a mild splenomegaly. Both patients underwent extensive diagnostic evaluation, and were eventually found homozygous for the classical N370S mutation on GBA.Summary/Conclusion: Type 1 GD has to be considered in the differential diagnosis of unexplained hyperferritinemia. Given its marked clinical heterogeneity in adults, certain clues are often under-estimated, especially when they are mild. We propose a diagnostic algorithm that should help its recognition by centers specialized in iron metabolism, when patients are referred for “unexplained hyperferritinemia”.
CYP3A5 gene expression is associated with early recurrence of non-small cell lung cancer
Authors: Ranjana Mitra, Clementina Mesaros, Anjaiah Srirangam, Ahmed Mohiuddin, Todd Skaar, Beth Juliar, Lang Li, Sunil Badve, Oscar Cummings, Dafydd Thomas, Jeanette McClintick, Howard Edenberg, Ian Blair, David Potter
Journal: Cancer Research (2008)

5551    Purpose:  Recent clinical trials suggest a survival advantage for adjuvant chemotherapy in non-small cell lung cancer (NSCLC). This study’s aim is to identify genes associated with NSCLC recurrence in patients not receiving adjuvant chemotherapy.   Experimental design:  Banked NSCLC tumors of patients who underwent resection of stage Ia-IIIb disease were identified. Patients were stratified into two groups: recurrent (R, n=11) or non-recurrent (NR, n=16) at two years following surgery. Microarray profiling and Cox multivariate analysis were performed.   Results:  Unsupervised clustering analysis using 51 probe sets separated the R and NR tumors. The CYP3A5 gene exhibited the greatest differential expression and was increased 18.7-fold in Group R (P=0.00013). Risk of NSCLC recurrence was highly associated with the ln of CYP3A5 gene expression (hazard ratio [HR] 2.80; 95% CI 1.58, 4.95; P=0.0004) and higher CYP3A5 was associated with a shorter time to recurrence (TTR). Older age at the time of surgery was marginally associated with decreased recurrence (HR 0.96; 95% CI 0.92, 1.00; P=0.033), while smoking history, race and sex were not significant. CYP3A5 was predominantly expressed in the NSCLC tumor epithelium. siRNA knock down of CYP3A5 in the A549 and H358 NSCLC lines inhibits proliferation. A potential mechanism of CYP3A5 in NSCLC progression involves CYP3A5 conversion of arachidonate to epoxyeicosatrienoic acids (EET’s), which are mitogenic for NSCLC lines under conditions of hypoxia.   Conclusion:  CYP3A5 gene expression is correlated with NSCLC recurrence and synthesizes EET, which promotes NSCLC growth. While the mechanisms of CYP3A5 in NSCLC recurrence remain to be identified, they may involve, in part, its epoxygenase activity.
PF326 VITAMIN D INSUFFICIENCY AND PROGNOSIS IN LYMPHOMA
Authors: B. Sanchez‐Gonzalez, J. Platero, A. Ortuño, F. Garcia‐Pallarols, S. Perez, E. Torres, L. Bento, I. Parraga, E. Gimeno, A. Gutierrez, A. Salar
Journal: HemaSphere (2019)

Background: Vitamin D deficiency has been recently associated, as an independent risk factor, with lower rates of progression‐free survival (PFS) and overall survival (OS) in patients with Hodgkin (HL) and non‐Hodgkin's lymphoma (NHL). Aims: To investigated the impact of vitamin D status on the outcome of lymphoma patients in two Institutions. Methods: From 2015 to 2018, we tested circulating 25‐hydroxyvitamin D3 (25[OH]D3) levels in a prospective cohort of 135 newly diagnosed patients with NHL and HL in two Institutions in Spain. 25[OH]D3 levels were measured by chemoluminescent immunoassay. Determinations were based on guidelines from the Food and Nutrition Board of the Institute of Medicine. According to current guidelines, we considered the following thresholds: vitamin D deficient (&lt;10 ng/ml), vitamin D insufficiency (10 to 30 ng/ml) and normal vitamin D level (&gt;30 ng/ml). Patients with &lt;20 ng/ml from one Institution had vitamin D substitution. OS and PFS were calculated using Kaplan‐Meier estimators, comparison between categories performed by log‐rank test and Cox PH regression, and the effect of covariates reported with 95% confidence interval (95 CI). Results: 135 newly diagnosed patients with NHL and HL were included. Median age at diagnosis was 67 years (range, 20 to 91 years). NHL subtypes: 47% diffuse large b cell lymphoma (DBCL), 30% Indolent lymphoma, 5% mantle cell lymphoma, 6% Tcell lymphoma, 10% Hodgkin lymphoma and 3% others NHL 34% had advanced stage and and 39% of NHL patient had ≥ 3score of International Pronostic Index (IPI).55% of the patients were diagnosed in spring or summer. Median 25(OH)D levels at diagnosis were 18 ng/ml. 11% of patients had normal 25(OH)D levels, 77% had insufficient 25(OH)D levels and 12% were deficient at lymphoma diagnosis. Median follow‐up was 12 months and 22 deaths were observed. The three groups of vitamin D levels were associated with OS, but this difference was not statistically significant (Figure 1). In the DLBCL subset, we inspected in a Cox Model the effect of Vitamin D levels for OS/PFS, adjusting for IPI Score and vitamin D substitution. Vitamin D levels did not achieve statistical significance for PFS (hazard ratio [HR], 1.02; 95% CI, 0.99 to 1.04) and OS (HR: 0.99; 95% CI, 0.94 to 1.06). Remarkably, there was a tendency towards a better statistically significant outcome in patients supplemented (HR for PFS: 0.36; 95% CI, 0.10 to 1.29; p = 0.10). Summary/Conclusion: Most of our patients present with low levels of vitamin D[JPD1]. In our limited series, with the current follow‐up time, baseline vitamin D values did not significantly impact PFS and OS. Further studies are needed to confirm our data. image
Abstract 13582: Fetal Cardiac Intervention for Hypoplastic Left Heart Syndrome With Intact or Restrictive Atrial Septum: A Report From the International Fetal Cardiac Intervention Registry
Authors: David Jantzen, Anita J Moon-Grady, Aimee Armstrong, Christoph Berg, Joanna Dangel, Carlen Fifer, Michele Frommelt, Ulrich Gembruch, Ulrike Herberg, Edgar Jaeggi, Eftichia Kontopoulos, Owen Miller, Shaine A Morris, Renate Oberhoffer, Carlos Pedra, Simone Pedra, Ruben Quintero, Sarah Gelehrter
Journal: Circulation (2015)

Background: Fetal cardiac intervention (FCI) for fetuses with hypoplastic left heart syndrome with restrictive or intact atrial septum (HLHS/IAS) has been reported in single-institution series as a modality that may improve outcomes in a high-risk subset of HLHS patients who historically have very high neonatal mortality. Methods: The International Fetal Cardiac Intervention Registry was established in 2010. For this descriptive analysis, the database was queried for fetuses with HLHS/IAS. Maternal-fetal dyads from 2001 through March 2015 were included. Results: Data from 15 institutions were submitted by data harvest. Of 87 cases of HLHS/IAS entered, 46 cases from 8 sites underwent FCI: 27 with atrial septal perforation/ balloon dilation and 19 with atrial septal stent placement. There were 34 procedural successes with a similar success rate between stents and balloons dilations (12/19=63% stent, 22/27=81% balloon dilation, p=0.19). Fetal complications were common (64% of cases), most frequently a pericardial effusion requiring treatment (51%), but no maternal complications. Procedure-related fetal demise occurred in 6 (13%). Seventeen had a clinical success (atrial septum not requiring urgent intervention at delivery), which was more likely in fetuses with a successful stent (75% stent vs 36% balloon dilation, p=0.03). Delivery by scheduled Cesarean section to facilitate immediate post-natal intervention was less common in those who underwent successful FCI compared with those with unsuccessful FCI or no FCI (3/34=8% FCI vs 18/46=39%, p=0.002). There was a trend toward improved survival to discharge for liveborn infants with HLHS/IAS in those who underwent successful FCI compared with those with unsuccessful FCI or no FCI (16/34=47% FCI vs 13/46=28%, p=0.10). Survival to hospital discharge was greater in those with clinical success compared to a procedural success but no clinical success (71% vs 24%, p=0.01). Conclusion: The early multicenter experience of FCI for HLHS/IAS has good procedural success, with atrial septal stent placement more likely to result in clinical success at delivery. There was a trend toward better survival if FCI was successful, and significantly improved survival if FCI resulted in clinical success at delivery.
PB2342 SAFETY AND EFFICACY OF 4 CYCLES OF BRENTUXIMAB VEDOTIN AS CONSOLIDATION AFTER AUTOLOGOUS PERIPHERAL STEM CELL TRANSPLANTION IN RELAPSED/REFRACTORY HODGKIN'S LYMPHOMA
Authors: J. Kort, A. Chidiac, R. massoud, N. Ghaoui, A. bazarbachi, J. El-Cheikh
Journal: HemaSphere (2019)

Background: Brentuximab Vedotin (BV) is a chimeric anti CD30 IgG1 antibody, conjugated to synthetic antitubulin momomethyl auristatin. BV is approved for the treatment of classical Hodgkin lymphoma (HL) in relapse either after autologous stem cell transplantation (ASCT) or after two lines of combination chemotherapy in transplant ineligible patients. The AETHERA trial revealed increased PFS when BV is used as maintenance therapy for 16 cycles in high risk patients after ASCT. However, this schedule is associated with a high cost and significant toxicity particularly in term of peripheral neuropathy. Aims: Our primary objective is to assess the efficacy of 4 cycles Brentuximab as consolidation therapy after ASCT for relapsed/refractory (R/R) HL. Secondary objectives include side effects, progression free survival (PFS), and overall Survival (OS). Methods: Patients and Methods: This is a retrospective single center analysis approved by the IRB of the American University of Beirut Medical Center. We included in this study consecutive patients with R/R HL who underwent ASCT between 2014 and 2017, and received BV consolidation post-ASCT. Results: We identified 18 consecutive adult patients with R/R HL treated with BV 1.8 mg/kg IV every 4 weeks as consolidation therapy after ASCT. The indications for BV consolidation was primary refractory disease in 9 patients (50%), early relapse in 8 patients (44%) (after a median time of 10 months; range, 3-11) and extranodal involvement in one patient (6%). The median number of lines of therapy pre-ASCT was 3 (range, 2-5). The median time to BV initiation post-ASCT was 68 days (range, 35-188). Patients received a median of 4 cycles (range, 1-5) of BV post-ASCT. After a median follow up of 32 months (range, 20-53), three (17%) patients relapsed after ASCT. The median time to relapse was 6 months (range, 4-8). Median PFS and OS were not reached. We did not observe any significant toxicities during or after therapy. Summary/Conclusion: Conclusion: 4 cycles of BV consolidation after ASCT seem to be safe and effective in preventing relapse, however our findings need to be confirmed with larger prospective studies.
BMA to hold conference on gender bias in response to sexism allegations
Authors: Elisabeth Mahase
Journal: BMJ (2019)

The BMA will co-host its first conference on gender bias with the Medical Women’s Federation this November, the association’s chair of council, Chaand Nagpaul, has announced.

Speaking at the BMA’s annual representative meeting in Belfast, Nagpaul said he was “deeply saddened” by the recent sexism allegations and affirmed his commitment to making the BMA an inclusive organisation.

All BMA elected members will also undertake equality and diversity training, and all members will be able to access online modules on equality, he said.

The announcement came after senior BMA General …
Harnessing the HDAC–histone deacetylase enzymes, inhibitors and how these can be utilised in tissue engineering
Authors: Liam Lawlor, Xuebin B. Yang
Journal: International Journal of Oral Science (2019)

There are large knowledge gaps regarding how to control stem cells growth and differentiation. The limitations of currently available technologies, such as growth factors and/or gene therapies has led to the search of alternatives. We explore here how a cell's epigenome influences determination of cell type, and potential applications in tissue engineering. A prevalent epigenetic modification is the acetylation of DNA core histone proteins. Acetylation levels heavily influence gene transcription. Histone deacetylase (HDAC) enzymes can remove these acetyl groups, leading to the formation of a condensed and more transcriptionally silenced chromatin. Histone deacetylase inhibitors (HDACis) can inhibit these enzymes, resulting in the increased acetylation of histones, thereby affecting gene expression. There is strong evidence to suggest that HDACis can be utilised in stem cell therapies and tissue engineering, potentially providing novel tools to control stem cell fate. This review introduces the structure/function of HDAC enzymes and their links to different tissue types (specifically bone, cardiac, neural tissues), including the history, current status and future perspectives of using HDACis for stem cell research and tissue engineering, with particular attention paid to how different HDAC isoforms may be integral to this field.
Abstract 16028: Intracoronary Compared with Intravenous Bolus Abciximab Application During Primary Percutaneous Coronary Intervention - ST-Segment Resolution Substudy of the AIDA STEMI Trial
Authors: Holger Thiele, Annet Baum, Karl-Philipp Rommel, Jochen Wöhrle, Petra Neuhaus, Oana Brosteanu, Steffen Desch, Gerhard Schuler, Ingo Eitel, Aida Stemi Investigators
Journal: Circulation (2012)

The AIDA STEMI trial compared i.c. versus i.v. abciximab bolus during primary PCI in STEMI patients. At 90-day follow-up i.c. as compared to i.v. abciximab resulted in a similar 90-day rate of the ...
Oral and Penile Lesions in a Young Man
Authors: Gordon T. Moffat, Franco Falcone
Journal: JAMA (2019)

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THU0710-HPR IMPACT OF SPONDYLOARTHRITIS ON FAMILY AND SOCIAL LIFE IN TUNISIAN PATIENTS
Authors: Kawther Ben Abdelghani, Leila Rouached, Alia Fazaa, Saoussen Miladi, Leila Souabni, Kmar Ouenniche, Salma Kassab, Selma Chekili, Zakraoui Leith, Ahmed Laatar
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Spondyloarthritis (SA) is a chronic inflammatory disease that could significantly affects the patient's quality of life and alter the social activities and relationship. <h3>Objectives:</h3> Here, we aimed to investigate the impact of spondyloarthritis on quality of the social and family life in Tunisian patients. <h3>Methods:</h3> This is a cross sectional study including patients with SA (ASAS criteria). A survey comprising questions about family and social relations and the impact of flare on it, were applied between November 2018 and January 2019. Demographic data, marital status, the disease activity (BASDAI and ASDAS) and the function index (BASFI) were obtained. For statistical analysis, we used Khi<sup>2</sup>-test for qualitative variables and Student-test for quantitative variables. A p value ≤0.05 was considered significant. <h3>Results:</h3> We included forty patients. The average age was 41 years-old (±12.9) and the sex ratio was 12.3. 60% of patients were married. The SA was axial in 25%, peripheral in 20% and both in 55%. 17.5% had psoriatic arthritis, 55% had ankylosing spondylitis and 27.5% had inflammatory bowel disease spondyloarthritis. coxitis was found in 47.4% of patients. Most of patients had a moderat activity (29.4%) and the mean activity scores were :(BASDAI =2.75±2.3, ASDAScrp=2.24±1.07), and the mean function index (BASFI) was 2.57±2.5. 57.5% of patients were on biologics (25% Adalimumab, 22.5% infliximab, 10% Etanercept). 67.5% of patients declared having difficulty in accepting their illnesses. Social relationship were deteriorated after the diagnosis of SA in: 27.5% with partners and 20% family members, 15% with friends and 20% with colleagues in work. Moreover, SA reduced the frequency of social activities like sport in 62.5%, traveling in 62.5%, cultural activities in 77.5% and sex practice in 37.5%. The impact of flares was also evaluated, the patients declared having difficulties in: crossing the street (57.5%), corporal hygiene (30%), sleeping (70%), private life (32.5%) and doing daily tasks (77.5%) and professional activity (81.8%). No significant relationship was found between social relationship and activities regarding biologic treatment (p=0.74, p=0.68). However presence of coxitis was significantly associated with a lack of friends (p=0.05), and a bad impact in the professional activities (absenteeism and drop job performance) (p=0.05) and the self-esteem (p=0.06). <h3>Conclusion:</h3> Our results suggest that family and social relations are deteriorated in Tunisian SA patients due to their illness. Moreover, coxitis has substantial impact on the self-esteem and the social life. <h3>Disclosure of Interests:</h3> None declared
Does Adaptive Protein Evolution Proceed by Large or Small Steps at the Amino Acid Level?
Authors: Juraj Bergman, Adam Eyre-Walker
Journal: Molecular Biology and Evolution (2019)

A long-standing question in evolutionary biology is the relative contribution of large and small effect mutations to the adaptive process. We have investigated this question in proteins by estimating the rate of adaptive evolution between all pairs of amino acids separated by one mutational step using a McDonald–Kreitman type approach and genome-wide data from several Drosophila species. We find that the rate of adaptive evolution is highest among amino acids that are more similar. This is partly due to the fact that the proportion of mutations that are adaptive is higher among more similar amino acids. We also find that the rate of neutral evolution between amino acids is higher among more similar amino acids. Overall our results suggest that both the adaptive and nonadaptive evolution of proteins are dominated by substitutions between similar amino acids.