tbuckley/cabot-search huggingface dataset:
Outcome of pregnancy in women on imatinib for CML.
Authors: Sadashivudu Gundeti, Vamshi Krishna Reddy Goteke, Rahul Narayan Maddi, Vijay Gandhi Linga, Raghunadharao Digumarti
Journal: Journal of Clinical Oncology (2013)

7061 Background: The use of imatinib (IM) now offers most patients with CML lengthy remissions and the hope of normal life expectancy. Majority of our CML patients are in the reproductive age group, and these improved survivals have resulted in issues relating to fertility and procreation. There is limited literature on the outcomes of pregnancy in women who continued IM during conception and through antenatal period. Methods: All women with CML who wished to conceive were counselled about the risks of pregnancy while on IM. They were given the choice of termination or stopping IM until delivery or continuing on IM with attendant risk to mother and baby. The records of all patients with CML treated with IM at our institute were retrospectively analysed over a period of 10 years. A total of 28 pregnancies in 25 women were documented. Only those women who were exposed to imatinib during conception and first trimester were included for this analysis. We report the outcome of 24 pregnancies in 22 women who had continued on IM in antenatal period. Results: Of the total of 24 pregnancies, 23 occurred in chronic phase and 1 in Blast phase. 21 of these conceptions occurred at IM dose of 400mg/ day, 1 at 600mg/ day and 2 at 800mg/ day. The median age at conception was 24.5 years (19-38). Mean time on IM at conception was 24.25 months (3-81). 19 patients (86.4%) were in CHR at conception and 11 of 22 patients (50%) attained complete cytogenetic response. The mean exposure to IM during pregnancy was 18.08 weeks (6-39 weeks).After explaining the pros and cons of continuation of pregnancy 6 women had stopped IM and 7 patients opted for termination of pregnancy. Conclusions: IM at higher dose appears to increase the risk of fetal loss. IM at standard dose of 400 mg does not appear to increase the incidence of congenital malformations or worsen foetal outcome. [Table: see text]
Abstract 21314: Glutaredoxin-1: An Endothelial Protector in Hyperlipidemia
Authors: Jingyan Han, Huijie Fan, Naomi Hamburg
Journal: Circulation (2017)

Background: Hypercholesterolemia (HC) dominates the risk factors for atherosclerosis. Sustained oxidative stress is a central mechanism driving endothelial dysfunction (ED) in HC. But the underlying redox mechanism remains unclear. Protein S-glutathionylation, a reversible oxidative modification of cysteine residues is tightly controlled by a specific de-glutathionylation enzyme: glutaredoxin-1 (Glrx-1), which thereby plays a critical role in redox regulation of cellular function. Methods and Results: The protein levels of Glrx1 in aorta and lung tissues are inversely correlated with circulating cholesterol in WT and ApoE -/- mice. Overexpression of Glrx1 in ApoE -/- mice attenuates HC-induced ED as measured by flow-mediated dilation of femoral artery using a new vascular imaging method with optical coherence tomography technique, and impaired eNOS function as evidenced by increased eNOS monomer to dimer ratio and suppressed phosphorylation of vasodilator-stimulated phosphoprotein in the aorta. In HAECs oxidized LDL promotes downregulation of Glrx1 without altering its mRNA level. The consequent elevated PrS-SG inactivates Akt/eNOS and stimulates degradation of Rac1, a key regulator of eNOS. All of these deteriorate effects of oxLDL are prevented by adenoviral overexpression of Glrx1. Conclusions: HC-induced downregulation of Glrx1 promotes ED by redox inactivation of eNOS and its upstream regulators: Akt1 and Rac1.
PS1300 A NURSE LED IRON INFUSION CLINIC REDUCES POTENTIAL PATIENT HARM AND IMPROVES HOSPITAL EFFICIENCY
Authors: L. Newman, T. Wright
Journal: HemaSphere (2019)

Background: The introduction of a rapid iron infusion protocol (ferric carboxymaltose) whilst more convenient and safe for patients has the potential to change the management of iron deficiency anaemia (IDA) away from best practice guidelines. Latrobe Regional Hospital (LRH) deliver all outpatient intravenous (IV) iron infusions through their chemotherapy day unit (CDU), providing an opportunity to study the total prescribing practices in a busy rural referral centre. Aims: To assess the appropriateness of intravenous iron prescribing in a regional setting and implement service improvement projects where deviations from best practice were identified. Methods: Baseline data of all IV iron infusions was collected from May 2017 to January 2018 (PRE phase 9 months). From February to October 2018 (POST‐phase 9 months), referrals from primary care physicians requesting an iron infusion were assessed by a haematology clinical nurse consultant (CNC) iron infusion clinic with physician supervision. All internal medicine specialist requests for iron infusions were coordinated by the haematology CNC. Iron infusion and prescribing rates were summarised for three groups, physician, local medical officer (LMO) and obstetrics and gynaecology (O &amp; G). All requests for iron infusions were assessed according to best practice guidelines. Results: Table one summarises the total 311 iron infusions delivered over the 9‐month pre‐phase data collection period. The physician group referred an older population of both males and females. The LMO referral group were predominantly female. Figure one shows the average monthly IV iron infusions delivered for the entire collection period and as per each referral group. There was a significant reduction in the average monthly IV iron infusions from 38 to 23. Monthly infusions delivered following referrals from the LMO group reduced significantly from 17 to 6. Whilst referrals from the physician group increased and O &amp; G group decreased, these were not significant. Summary/Conclusion: The development of an iron infusion clinic led by a haematology CNC provides a safe evidenced based assessment of patient referrals. This model significantly reduced the rate of iron infusions in our regional hospital, allowing more efficient use of the expert outpatient infusion centre services and reducing potential harm related to an inappropriate therapy. image
FRI0339 CLINICAL CHARACTERISTICS OF ANTI-RO52α AND ANTI-RO52β ANTIBODIES IN DERMATOMYOSITIS/POLYMYOSITIS
Authors: Mariko Ogawa-Momohara, Yoshinao Muro, Masashi Akiyama
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The anti-Ro52 antibody, found in numerous systemic autoimmune conditions, is one of the most common autoantibodies in inflammatory myositis. It is known to be associated with interstitial lung disease (ILD) and to coexist with anti-Jo-1<sup>1</sup>. There are two spliced forms: Ro52α and Ro52β. Ro52β was originally reported in 1995 as a spliced form of Ro52α in the human heart<sup>2</sup>. Ro52β antigen cDNA has a defective exon 4, which encodes part of an autoepitope hotspot<sup>2</sup>. <h3>Objectives</h3> We investigated the clinical and laboratory characteristics of anti-Ro52α and anti-Ro52β. We also analyzed the characteristics of anti-Ro52α/β within each coexisting inflammatory myositis specific autoantibody (MSA) group to reduce the influences of coexisting MSA characteristics. <h3>Methods</h3> Among 229 dermatomyositis (DM) and polymyositis (PM) patients, 167 patients (DM 152, PM 10, juvenile DM 5) fulfilled the criteria of Bohan and Peter, and 62 clinical amyopathic DM cases fulfilled the criteria of Sontheimer. Anti-Ro52α and anti-Ro52β antibodies were detected by ELISA. <h3>Results</h3> 46 of the 229 patients were anti-Ro52α-positive (20%). ILD was a frequent complication in the anti-Ro52α-positive patients (35/42: 76%) (P=0.0016), and anti-Ro52α was highly positive in the anti-aminoacyl tRNA synthetase (ARS) antibody-positive group (19/32: 60%) (P&lt;0.0001) (Table 1). However, the ILD frequencies of anti-Ro52α-positive and anti-Ro52α-negative patients within each group of coexisting MSA (anti-ARS, anti-TIF, anti-MDA5, etc.) were almost same (P=1). The anti-Ro52α-positive rates were similar to the positive rates of anti-Jo1 (61%) and other anti-ARSs (52%) (P=0.7). Of the 46 anti-Ro52α-positive patients, 26 patients were anti-Ro52β-positive. No patient was only anti-Ro52β positive. The anti-Ro52α-positive and anti-Ro52β-positive groups were older than the anti-Ro52α-only-positive group (P=0.009), and the average of maximum creatine kinase was higher in both of the positive groups (P=0.065). The 6 patients without coexisting MSA were all both anti-Ro52α-positive and anti-Ro52β-positive (P=0.03) (Table 2). <h3>Conclusion</h3> Anti-Ro52 is highly positive when anti-ARS antibodies are present, but it is not anti-Jo-1-specific. Anti-Ro52 positivity is not associated with elevated risk of ILD in any of the MSA-positive groups. The anti-Ro52β antibody might be an indicator of myositis. <h3>References</h3> [1] Lee AYS. A review of the role and clinical utility of anti-Ro52/TRIM21 in systemic autoimmunity. Rheumatol Int. 2017;37(8):1323-1333. [2] Chan EK, Di Donato F, Hamel JC, Tseng CE, Buyon JP. 52-kD SS-A/Ro: genomic structure and identification of an alternatively spliced transcript encoding a novel leucine zipper-minus autoantigen expressed in fetal and adult heart. J Exp Med. 1995;182(4):983-92. <h3>Disclosure of Interests</h3> None declared
PB2004 A 15 YEAR RETROSPECTIVE STUDY OF HODGKIN LYMPHOMA PATIENTS IN ALBANIA
Authors: A. Cili, B. Leart, E. Petrela, A. Perolla, R. Tozharaku, P. Polikron, E. Calliku, T. Caja, A. Ivanaj
Journal: HemaSphere (2019)

Background: Hodgkin lymphoma (HL) is a lymphoid malignancy of B‐cell origin. HL is a rare neoplasm with an incidence that varies significantly by age, sex, ethnicity, geographic location and socioeconomic status. Aims: We have made a 15 year retrospective study in Albania where we studied the incidence, treatment, treatment response and OS (overall survival) of Hodgkin Lymphoma Methods: We have analysed the adult patients with Hodgkin Lymphoma from 2003 till 2018 registered in the statistic center in the University Hospital Center “Mother Teresa” and in the “Cancer registry” at ISHP (Public Health Institute) at the moment of diagnosis, the protocol treatment used, the patients response and the overall survival. Overall survival was calculated with Kaplan‐Meier method. Results: From the 2003‐2018 in Albania are diagnosed and treated for the first time 331 patients with Hodgkin Lymphoma and 169 of them were male patients (51%) and 162 were female patients (49%) with M/F ratio of 1.04. The median age was 37 years old (Range 14‐65 years old).The highest incidence was in 2012 with 0.82 per 100000 adult residents. According to Ann Arbour classification 17 patients (5.1%) were classified stage IA, 4 patients (1.2%) were classified stage IB, 113 patients (34.1%) were classified stage IIA, 72 patients (21.7%) were classified stage IIB, 20 patients (6.0 %) were classified stage IIIA, 61 patients (18.4%) were classified stage IIIB,6 patients (1.81 %) were classified stage IVA, and 38 patients (11.4%) were classified stage IVB. Histology classification : 63% of patients were classified as nodular sclerosis (NS), 12% were classified as nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), 22 % were classified as mixed cellularity (MC),and 3 % were classified as lymphocyte‐depleted (LD). Treatment protocols . As first line treatment protocol in Albania we use ABVD protocol (adriamycin, bleomycin, vinblastine, dacarbazine) and ABVD plus RT (radiotherapy). From all the patients 160 (48.3%) were treated with ABVD and 165 (49.7%) were treated with ABVD plud RT. Response data was available for all patients; complete response in 84% of patients; partial response in 10 % of our patients and progressive disease in 6% of our patients. Summary/Conclusion: Conclusion : Lymphoma incidence in Albania is 0.8 per 100 000 adult residents. ABVD is widely accepted as a standard treatment option for Hodgkin's lymphoma, and this study shows that comparable results can be reproduced in our patients with acceptable tolerance. There is no difference in OS (overall survival) between patients treated with ABVD and patients treated with ABVD + RT. OS (Overall survival) is 59% at 14.1 years of follow up realizing that ABVD is a good regimen. The most important information of this study lies in the fact that this is the largest data from Albania on patients diagnosed with Hodgkin Lymphoma on ABVD protocol treatment. image OS (Overall survival) is 59% at 14.1 years
China’s forced organ harvesting constitutes crimes against humanity, informal London tribunal finds
Authors: Richard Hurley
Journal: BMJ (2019)

Mass forced organ harvesting from prisoners of conscience in China over years constitutes crimes against humanity under international law, an informal, independent “people’s tribunal” has concluded.

In a final judgment in London on 17 June,1 the tribunal’s seven member panel said that it had found evidence beyond reasonable doubt of state sponsored or sanctioned murder, extermination, imprisonment, rape, and torture; ethnic, racial, or religious persecution; and enforced disappearance. The tribunal did not establish that the crimes amounted to genocide.

The panel’s chair, Geoffrey Nice QC, who previously led the prosecution of the former Yugoslav president Slobodan Milosevic in the Hague, compared the “wicked” crimes to “the worst atrocities of the 20th century.”

In response, the International Coalition to End Transplant Abuse in China (ETAC), the pressure group that had convened the tribunal, called for doctors and organisations worldwide to stop all collaboration with China related to transplantation.

Susie Hughes, executive director and cofounder of ETAC, said, “It is horrendous to think that many of our hospitals and universities are, perhaps unknowingly, …
PS1522 CENTRAL PHYSIOLOGIC MECHANISMS WHICH AUGMENT OXYGEN RELEASE (BOHR EFFECT AND 2,3‐DPG BINDING) ARE PRESERVED IN THE PRESENCE OF VOXELOTOR AT THE THERAPEUTIC TARGET OF 30% HB MODIFICATION
Authors: M. Pochron, V. Siu, D. Oksenberg, K. Dufu
Journal: HemaSphere (2019)

Background: Key physiologic mechanisms that drive O 2 offloading to tissues in vivo include the Bohr effect and 2,3‐DPG binding. The Bohr effect is the capacity of Hb to offload more O 2 in hypoxic peripheral tissues in response to conditions of increased H + concentrations (or acidosis). Similarly, the binding of 2,3‐DPG to Hb stabilizes the deoxyHb state, reduces the Hb‐O 2 affinity and facilitates O 2 release to tissues. Aims: To investigate oxygen off‐loading dynamics from voxelotor‐modified hemoglobin in vitro under increased acidity or increased DPG content. Methods: In this study, the Oxygen Dissociation Assay (ODA) and oxygen equilibrium curves (OECs) were used to determine the effect of voxelotor on Hb‐O 2 affinity in response to H + and 2,3‐DPG (5 mM). The ODA is a spectrophotometric assay that measures the time dependences of O 2 release, while Hb‐O 2 affinities can be measured using OECs. Studies in the ODA were conducted with purified Hb (3 μM), while OEC determinations were conducted with both purified Hb (25 μM) and whole blood. Results: Relative to Hb alone, voxelotor‐modified Hb dose‐dependently increased the proportion of oxygenated Hb (oxyHb) molecules during two hours of deoxygenation consistent with stabilization of hemoglobin in the oxy, or R‐ state. Under deoxygenated conditions, the percentage of oxygenated voxelotor‐modified Hb decreased over time, demonstrating oxygen release (offloading) by voxelotor‐modified Hb. With increased acidity (down to 6.8), there was an acceleration of oxygen release from voxelotor‐modified Hb under deoxygenated conditions. This resulted in an increase in the p50 of voxelotor‐modified blood and thus demonstrates a pH‐dependent decrease in the affinity of Hb for O 2 in the presence of voxelotor at the therapeutic target Hb modification of 30% (Figure 1A). Similarly, the response of Hb to 2,3‐DPG effect was not inhibited in the presence of voxelotor at the 30% modification target (Figure 1B). Summary/Conclusion: The results of this study indicate that the central physiologic mechanisms which augment oxygen release to metabolically active tissues, such as the Bohr effect and 2,3‐DPG binding, are preserved when voxelotor is bound to Hb. image
Indian doctors’ leaders demand national law to reduce violence in hospitals
Authors: Dinsa Sachan
Journal: BMJ (2019)

The Indian Medical Association (IMA) has called for a nationwide law criminalising violence against doctors and imposing a minimum of seven years in prison, after an attack in West Bengal left two doctors requiring surgery.

The attack on 10 June, by relatives of a 75 year old man who had died at NRS Medical College and Hospital in Kolkata, targeted junior doctors, one of whom needed a craniotomy for a fractured skull.

The incident led to widespread protests and a national boycott of all but emergency services by the country’s 800 000 doctors on 17 June.1 …
Encircling the regions of the pharmacogenomic landscape that determine drug response
Authors: Adrià Fernández-Torras, Miquel Duran-Frigola, Patrick Aloy
Journal: Genome Medicine (2019)

The integration of large-scale drug sensitivity screens and genome-wide experiments is changing the field of pharmacogenomics, revealing molecular determinants of drug response without the need for previous knowledge about drug action. In particular, transcriptional signatures of drug sensitivity may guide drug repositioning, prioritize drug combinations, and point to new therapeutic biomarkers. However, the inherent complexity of transcriptional signatures, with thousands of differentially expressed genes, makes them hard to interpret, thus giving poor mechanistic insights and hampering translation to clinics. To simplify drug signatures, we have developed a network-based methodology to identify functionally coherent gene modules. Our strategy starts with the calculation of drug-gene correlations and is followed by a pathway-oriented filtering and a network-diffusion analysis across the interactome. We apply our approach to 189 drugs tested in 671 cancer cell lines and observe a connection between gene expression levels of the modules and mechanisms of action of the drugs. Further, we characterize multiple aspects of the modules, including their functional categories, tissue-specificity, and prevalence in clinics. Finally, we prove the predictive capability of the modules and demonstrate how they can be used as gene sets in conventional enrichment analyses. Network biology strategies like module detection are able to digest the outcome of large-scale pharmacogenomic initiatives, thereby contributing to their interpretability and improving the characterization of the drugs screened.
AB1127 ULTRASOUND INTER-READER RELIABILITY OF INFLAMMATORY FINDINGS IN PATIENTS WITH POLYARTHRITIS
Authors: Luisa Brites, Mariana Santiago, João Rovisco, João Dinis de Freitas, José Antonio P. Da Silva, Inês Silva, Filipa Teixeira, Daniela Faria, Cândida G. Silva, Sandra Falcão
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Ultrasonography is an imaging technique that allows rheumatologists to visualise structural and inflammatory changes within a joint. <h3>Objectives</h3> The objective of this study was to assess the inter-reader reliability of interpretation of inflammatory and destructive changes in a wide range of joints in patients with polyarthritis. <h3>Methods</h3> This study was divided in two parts: 1) consensus process and 2) reliability exercise. For the first part, a written questionnaire was sent by email to 6 sonographers from 3 portuguese hospitals with the highest level of competence (EULAR competency assessment level 2). The questionnaire included 17 questions divided in two groups: 1) elementary components in B-mode and Doppler assessment (effusion, synovial hypertrophy (SH), power Doppler (PD), erosions and synovitis definition) and 2) approach at the joint level (the definition of which plan and recess will be assessed in each joint). The participants were asked to rate their level of agreement/disagreement for each statement using a 1-5 Likert scale (1=strongly disagree to 5-strongly agree). For the reliability exercise, video clips of US examinations of 40 joints (wrist, metacarpophalangeal (MCP) from 1 to 5, proximal interphalangeal (PIP) from 1 to 5, knee, tibiotarsal (TT) and metatarsophalangeal (MTP) joints from 1 to 5, elbow and shoulder) from each of 15 patients were collected (showing a multiplanar bilateral ultrasound approach). Each joint in each video was scored by individual ultrasonographers for the presence/absence of elementary components: effusion (Yes/No), SH (No/Grade 1 to 3), PD (No/Grade 1 to 3) and erosions (Yes/No). Inter-reader agreement analysis was assessed through Fleiss' kappa coefficient and classified according to Landis and Koch[8]: κ values &lt; 0 were considered poor, 0-0.20 slight, 0.21-0.40 fair, 0.41-0.60 moderate, 0.61-0.80 good and 0.81-1.00 excellent. Statistical significance was defined as p&lt;0.05. Statistical analysis was performed using STATA V.14. <h3>Results</h3> Thirty seven joints of the 600 joints were excluded due to dislocation of the joint or presence of objects (rings/catheters) and the videos of a total of 563 joints were analysed by the 6 ultrasound experts. Inter-reader agreement was superior for TT joints and inferior for wrist; the identification of the erosions had the better agreement in the elementary components (Table 1). <h3>Conclusion</h3> The reliability of interpretation of inflammatory and destructive changes using video clips was in general good to excellent and it was better for erosions and tibiotarsal joint (regarding elementary component and anatomical region, respectively). <h3>Disclosure of Interests</h3> None declared
Quartz-Seq2: a high-throughput single-cell RNA-sequencing method that effectively uses limited sequence reads
Authors: Yohei Sasagawa, Hiroki Danno, Hitomi Takada, Masashi Ebisawa, Kaori Tanaka, Tetsutaro Hayashi, Akira Kurisaki, Itoshi Nikaido
Journal: Genome biology (2018)

High-throughput single-cell RNA-seq methods assign limited unique molecular identifier (UMI) counts as gene expression values to single cells from shallow sequence reads and detect limited gene counts. We thus developed a high-throughput single-cell RNA-seq method, Quartz-Seq2, to overcome these issues. Our improvements in the reaction steps make it possible to effectively convert initial reads to UMI counts, at a rate of 30–50%, and detect more genes. To demonstrate the power of Quartz-Seq2, we analyzed approximately 10,000 transcriptomes from in vitro embryonic stem cells and an in vivo stromal vascular fraction with a limited number of reads.
Sex Differences in Patient Characteristics, Treatment Strategies, and Outcomes for Type 2 Myocardial Infarction
Authors: Cian P. McCarthy, Sean Murphy, Joshua A. Cohen, Saad Rehman, Maeve Jones-O’Connor, David S. Olshan, Avinainder Singh, Muthiah Vaduganathan, James L. Januzzi, Jason H. Wasfy
Journal: Journal of the American College of Cardiology (2019)