tbuckley/cabot-search huggingface dataset:
PS1480 INTERLEUKIN‐37 REDUCES INFLAMMATION AND IMPAIRS PHAGOCYTOSIS OF PLATELETS IN IMMUNE THROMBOCYTOPENIA
Authors: Y. Zhao, G. Li, X. Liu, J. Peng, M. Hou
Journal: HemaSphere (2019)

Background: Immune thrombocytopenia (ITP) is an autoimmune and inflammatory disease characterized by low platelet count with heterogeneous bleeding manifestations. Severe bleeding in ITP is not completely related with low platelet count. Thus, there is a great need for reliable indicators of the susceptibility of bleeding in ITP patients. Interleukin‐37 (IL‐37) is an anti‐inflammatory cytokine that participates in the process of several inflammatory and autoimmune diseases. However, the role of IL‐37 in the pathogenesis of ITP is unknown. Aims: Our study aimed to evaluate the regulatory role of IL‐37 in the process of ITP and its association with disease severity. Methods: Plasma IL‐37 was detected by enzyme‐linked immunosorbent assay (ELISA). We cultured the monocytes/macrophages from ITP patients to investigate the regulatory role of IL‐37 on monocytes/macrophages. Fcγ receptors (FcγRs) of macrophages were analyzed using flow cytometry and q‐PCR. Signaling pathways were determined by western blotting. Phagocytic capacity of macrophages was measured by the engulfment of opsonized platelets. Results: Plasma and mRNA levels of the anti‐inflammatory cytokine IL‐37 were elevated in ITP patients with platelet counts below 30 × 10 9 /L compared to healthy controls and to ITP patients with platelet counts above 30 × 10 9 /L. Furthermore, plasma IL‐37 levels correlated with the platelet number and IBLS bleeding scores of ITP patients. Specifically, ITP patients with skin and oral bleeding symptoms had higher plasma IL‐37 levels than patients without these bleeding symptoms. Patients with more severe skin and oral bleeding exhibited higher plasma IL‐37 levels, indicating that IL‐37 could be a candidate in evaluating disease severity of ITP. IL‐37 initiated an anti‐inflammatory effect on monocytes/macrophages from ITP patients by down‐regulating the phosphorylation of MAPK, AKT, and NF‐κB signaling pathways, which are pivotal in mediating inflammation. Moreover, IL‐37 restored the balance of activating and inhibitory FcγRs (Figure 1) and decreased antibody‐mediated platelet phagocytosis by monocytes/macrophages, suggesting that IL‐37 might be a potential therapeutic agent in ITP. Summary/Conclusion: Our study demonstrated that ITP patients exhibited higher IL‐37 expression, especially patients with severe hemorrhage or low platelet count. IL‐37 decreased antibody‐mediated platelet phagocytosis, restored the balance of activating and inhibitory FcγRs, and inhibited inflammatory activity via MAPK, AKT, and NF‐κB signaling pathways among monocytes/macrophages. Therefore, IL‐37 might be a candidate in evaluating the severity of ITP and a promising therapeutic agent for the management of ITP. image
PB2200 PREVALENCE OF JAK2V617F, CALR AND MPL MUTATIONS IN PATIENTS OF MYELOPROLIFERATIVE NEOPLASMS AND SPLANCHNIC VEIN THROMBOSIS IN INDIA
Authors: None J., V. Arya, N. Gupta, A. Arora, A. Sharma, J. Kotwal
Journal: HemaSphere (2019)

Background: Recurrent somatic mutations in the JAK2, MPL, and CALR genes have been described in patients diagnosed with Philadelphia‐negative Myeloproliferative neoplasms (MPNs), including Polycythemia vera (PV), Essential thrombocythemia (ET) and Primary myelofibrosis (PMF). MPN is also the most common etiology in splanchnic vein thrombosis (SVT). MPNs account for approximately 40% of Budd Chiari syndrome (BCS) and 31% of portal vein thrombosis (PVT). The present study was aimed at studying the prevalence of JAK‐2V617F, MPLW515L/K and CALR exon 9 mutations in BCR‐ABL1 negative myeloproliferative neoplasms (MPNs) and splanchnic vein thrombosis (SVT) patients. There is paucity of such data in the Indian patients. Aims: The study had two aims: Identification of incidence of JAK2V617F, CALR exon 9 mutations and MPLW515L/K mutations in BCR‐ABL1 negative MPNs in India Identification of incidence of JAK2V617F, CALR exon 9 mutations and MPLW515L/K mutations in Indian patients of SVT Methods A total number of 60 patients of SVT and 59 MPN patients (10 PV, 19 ET, and 30 PMF) were included in the study. The mutation analysis for JAK2V617F, CALR exon 9 and MPLW515L/K mutations were performed using the Allele specific oligonucleotide‐polymerase chain reaction (ASO‐PCR) was used to detect JAK‐2, CALR and MPL mutations. Results: Among 59 patients of MPNs and 60 SVT; JAK‐2 mutation was found in 61.0% (36/59) and 23.3% (14/60) respectively. On sub‐classification, JAK‐2 mutation was detected in 80.0% (8/10) of PV; 42.1% (8/19) of ET and 66.7% (20/30) of PMF patients. All the patients of MPNs and SVT were subjected to CALR mutation analysis. The overall rate of CALR mutations in PMF and ET was 10% (3/30) and 21.0% (4/19) respectively. Limiting the analysis to JAK2V617F negative patients of PMF and ET, it was seen that 30% (3/10) PMF and ∼36.36% (4/11) ET cases were CALR mutated. Of these 7 CALR mutations; L367fs∗46 (type‐1) and K385fs∗47 (type‐2) mutations were found in 5 and 2 patients respectively. MPL mutation was identified in 5.26% (1/19) ET cases. Triple negative ET and PMF were ∼31.5% (∼6/19) and ∼23.3% (7/30) respectively. None of the SVT patients were observed to be CALR mutated and none showed the MPLW515L/K mutations. Summary/Conclusion: Indian patients exhibit a lower incidence of CALR mutations in Primary myelofibrosis than that seen in the western literature. However, the incidence of CALR mutations is the same as that reported earlier in Indian patients of Essential thrombocythemia. Triple negative cases constitute 31.5% of all cases of Essential thrombocythemia and 23.3% of Primary myelofibrosis Indian patients show a Testing for CALR mutations and MPLW515L/K mutations in splanchnic vein thrombosis is not justified.
Congenital Extrahepatic Portosystemic Shunts (Abernethy Malformation): An International Observational Study
Authors: Anna Baiges, Fanny Turon, Macarena Simón‐Talero, Stephanie Tasayco, Javier Bueno, Kamal Zekrini, Aurélie Plessier, Stéphanie Franchi‐Abella, Florent Guerin, Amar Mukund, C.E. Eapen, Ashish Goel, Nidugala Keshava Shyamkumar, Sandra Coenen, Andrea De Gottardi, Avik Majumdar, Simona Onali, Akash Shukla, Flair José Carrilho, Lucas Nacif, Massimo Primignani, Giulia Tosetti, Vicenzo La Mura, Frederik Nevens, Peter Witters, Dhiraj Tripathi, Luis Tellez, Javier Martínez, Carmen Álvarez‐Navascués, Miguel López Fraile López, Bogdan Procopet, Fabio Piscaglia, Barbara de Koning, Elba Llop, Mario Romero‐Cristobal, Eric Tjwa, Alberto Monescillo‐Francia, Marco Senzolo, Mercedes Perez‐LaFuente, Antonio Segarra, Shiv Kumar Sarin, Virginia Hernández‐Gea, David Patch, Wim Laleman, Hermien Hartog, Dominique Valla, Joan Genescà, Juan Carlos García‐Pagán
Journal: Hepatology (2019)

Congenital extrahepatic portosystemic shunt (CEPS) or Abernethy malformation is a rare condition in which splanchnic venous blood bypasses the liver draining directly into systemic circulation through a congenital shunt. Patients may develop hepatic encephalopathy (HE), pulmonary hypertension (PaHT), or liver tumors, among other complications. However, the actual incidence of such complications is unknown, mainly because of the lack of a protocolized approach to these patients. This study characterizes the clinical manifestations and outcome of a large cohort of CEPS patients with the aim of proposing a guide for their management. This is an observational, multicenter, international study. Sixty-six patients were included; median age at the end of follow-up was 30 years. Nineteen patients (28%) presented HE. Ten-, 20-, and 30-year HE incidence rates were 13%, 24%, and 28%, respectively. No clinical factors predicted HE. Twenty-five patients had benign nodular lesions. Ten patients developed adenomas (median age, 18 years), and another 8 developed HCC (median age, 39 years). Of 10 patients with dyspnea, PaHT was diagnosed in 8 and hepatopulmonary syndrome in 2. Pulmonary complications were only screened for in 19 asymptomatic patients, and PaHT was identified in 2. Six patients underwent liver transplantation for hepatocellular carcinoma or adenoma. Shunt closure was performed in 15 patients with improvement/stability/cure of CEPS manifestations. Conclusion: CEPS patients may develop severe complications. Screening for asymptomatic complications and close surveillance is needed. Shunt closure should be considered both as a therapeutic and prophylactic approach.
State Efforts to Lower Health Care Prices Paid by Private Insurers
Authors: Aditi P. Sen, Amber Willink, Gerard F. Anderson
Journal: JAMA (2019)

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PB2237 THE RED BLOOD CELL COUNT AND THE SEDIMENTATION RATE IN THE DIAGNOSIS OF POLYCYTHAEMIA VERA?
Authors: V. Skov, V. Nersesjan, K. A. Zervides, L. Kjaer, A. L. Sørensen, H. C. Hasselbalch
Journal: HemaSphere (2019)

Background: This retrospective cross‐sectional study investigated the effects of microcytosis on the hematocrit (HCT) value in Polycythemia Vera (PV) patients. Since iron deficiency is frequent in PV, and the HCT is a derived value from the Red Blood cell Count x Mean Corpuscular Volume (RBC x MCV), it is reasonable to question if low MCV in PV affects the validity of the HCT value. In addition, we evaluated the Erythrocyte Sedimentation Rate (ESR) as a possible additional diagnostic marker for PV. Aims: To evaluate RBC, hematocrit and the ESR in the diagnosis of PV. Methods: This study included 182 subjects (39 with PV, 27 with Essential Thrombocythemia (ET) and 116 suspected of MPN disease with a secondary cause for either thrombocytosis or erythrocytosis (hereafter named “MPN‐suspects”). The frequencies of microcytosis and low ferritin (&lt;15ug/L) in PV patients were compared to subjects suspected of having a MPN disease. Correlation studies were performed to compare the HCT versus RBC in all subgroups. The ESR was evaluated as a diagnostic marker for PV by a contingency table and a ROC‐curve analysis. Results: In the MPN suspects, 4 of 117 (3 %) had plasma ferritin &lt; 15 ug/L, compared with 6 of 38 (16 %) in the PV‐group (P &lt; 0.05). In the MPN suspects, we found that 3 of 115 (3%) as compared to 6 of 39 (15%) in the PV‐group had MCV &lt; 82 (p &lt; 0.05). Poor linear correlations of RBC versus HCT were found in the PV group compared to the MPN suspects (R 2 = 0.62 and R 2 = 0.76, respectively). When subjects with microcytosis were excluded, better correlations were observed (R 2 = 0.87 in PV and R 2 = 0.82 in the MPN suspect group). We found a specificity of 97,7% and a sensitivity of 37,1% for ESR &lt; 2 mm by a ROC‐curve analysis when used for diagnosing PV when PV was suspected. The area under the curve (AUC) was 0,71 (95% CI: 0.60‐0.82), indicating a fair test accuracy for ESR as a diagnostic test. Summary/Conclusion: The HCT is not a valuable parameter in the assessment of expanded RCM in PV, since HCT is falsely lowered due to iron deficiency with microcytosis, which are common findings in patients with PV. The RBC is a simple measurement that may more precisely reflect the total red cell mass which also impacts the ESR as reflected by a low ESR (&lt; 2 mm) in 13 of 35 (37 %) of PV patients at the time of diagnosis. Importantly, the ESR might also be a valuable diagnostic biomarker for PV with a high specificity in patients with elevated HCT, Hb or RBC. A combination of RBC and ESR as simple measures to substitute the Hb‐concentration and the HCT in the diagnosis of PV should be addressed in future well‐designed prospective studies, including the value of the RBC and the ESR in deciding when to phlebotomize patients with PV.
A Network Meta-Analysis of Surgical Treatment in Patients With Early Breast Cancer
Authors: Yu Gui, Xunzhou Liu, Xianchun Chen, Xi Yang, Shichao Li, Qingwen Pan, Xiangdong Luo, Li Chen
Journal: JNCI Journal of the National Cancer Institute (2019)

In early breast cancer treatment, the preferred surgical regimen remains a topic of controversy, and conventional pairwise meta-analysis cannot provide a hierarchy based on clinical trial evidence. Therefore, a network meta-analysis was performed both for direct and indirect comparisons and to assess the survival outcomes of surgical regimens.Randomized clinical trials comparing different surgical regimens for the treatment of early breast cancer were identified. Overall survival (OS) and disease-free-survival (DFS) were analyzed using random-effects network meta-analysis on the hazard ratio (HR) scale and calculated as combined HRs and 95% confidence intervals (CIs). All statistical tests were two-sided.The network meta-analysis compared 11 different surgical regimens that consisted of 13 and 17 direct comparisons between strategies for OS (34 trials; n = 23 587 patients) and DFS (32 trials; n = 22 552 patients), respectively. The values of surface under the cumulative ranking for OS and DFS after mastectomy (M)+radiotherapy (RT) were observed to be the largest. Breast-conserving surgery (BCS)+axillary node sampling+RT almost achieved the threshold for inferiority compared with the other surgical treatment arms and was statistically significantly associated with worse OS (HR = 0.51, 95% CI = 0.24 to 0.94; HR = 0.48, 95% CI = 0.22 to 0.92; HR = 0.51, 95% CI = 0.23 to 0.96). No statistically significant difference between BCS+sentinel lymph node biopsy (SLNB)+RT vs BCS+SLNB+intraoperative RT was observed in carrying out network meta-analysis (HR = 0.95, 95% CI = 0.64 to 1.36).M+RT has the most favorable survival outcomes among the various surgical regimens for the treatment of early breast cancer patients. For patients who receive BCS, SNLB has more favorable outcomes than axillary node sampling. Intraoperative RT and postoperative RT have similar outcomes in patients who receive SLNB.
Abstract 14519: Relation Between Myocardial Edema and Left Ventricular Wall Motion Recovery in Patients With Takotsubo Cardiomyopathy
Authors: Ken Kato, Yoshiaki Sakai, Iwao Ishibashi, Yoshio Kobayashi
Journal: Circulation (2013)

Background: Takotsubo cardiomyopathy is characterized by transient reversible systolic dysfunction of the apical and/or mid segments of the left ventricle (LV). However, there is little information...
PF639 IMMUNE ELECTRON MICROSCOPY AND MASS SPECTROMETRY FOR CLASSIFICATION OF AMYLOID DEPOSITS
Authors: N. Abildgaard, A.M. Rojek, H.E. Møller, C.T. Hansen, N.B. Palstrøm, L.M. Rasmussen, H.C. Beck, N. Marcussen
Journal: HemaSphere (2019)

Background: Amyloidosis is a shared name for a number of rare, complex and serious disease entities with an annual incidence in Denmark of about 2 per 100,000. Amyloidosis is caused by extra‐cellular deposits of amyloid substance created by accumulation of different misfolded proteins. Accurate characterization of the amyloid protein is essential. Amyloid light chain (AL) amyloidosis is a plasma cell dyscrasia that can be treated with chemotherapy, whereas transthyretin (ATTR) and secondary Amyloid A (AA) amyloidosis are other entities that are not treated within haematology. It is generally recognized that conventional immunohistochemistry has limitations, particular due to unspecific staining. Immune electron microscopy (IEM) and laser dissection microscopy followed by tandem mass spectrometry (LDM‐MS) are the new gold standards. It has not been established if one of the methods is superior; each method have some strengths and weaknesses. At Odense Amyloidosis Center, IEM and LDM‐MS have been established for standard diagnostics in 2017. Aims: To compare the sensitivity and specificity of IEM and MS for sybtyping amyloid deposits in different organs Methods: We performed a retrospective study of 106 Congo red positive biopsies from a number of different involved organs; heart, kidney, lung, gut mucosa, subcutaneous fat, bone marrow. IEM was performed with gold‐labeled antibodies against kappa, lambda, transthyretin and amyloid A. Results: IEM identified specific staining of amyloid fibrils in 91.6% of the biopsies; in 6 biopsies amyloid fibrils were not identified, and in 2 biopsies the subtype of the amyloid fibrils could not be established. MS identified an amyloigenic protein signature in 104/106 biopsies but in 9 of the biopsies the amyloid subtype could not be clearly identified. Protein subtype was established in 95 biopsies (89.6%). The concordance of the results ranged from 89.6–100% for the different subtypes. Importantly, the combined use of both methods increased the diagnostic sensitivity to 100%. Some variety in performances of the methods was observed on organ level. Summary/Conclusion: In conclusion, we demonstrate that both IEM and LDM‐MS are sensitive and specific methods for the identification of amyloidogenic proteins in amyloid deposits in biopsies from various organs.
PB2287 REFERENCE INTERVALS OF BLOOD COUNT IN HEALTHY FULL‐TERM PREGNANT GREEK WOMEN
Authors: K. Karantani, G. Petassis, K. Tsioni, M. Issa, E. Tsamis, E. Vagdatli
Journal: HemaSphere (2019)

Background: Since blood count reference intervals are generally based on samples collected from non pregnant women, these should not be used for the evaluation of pregnant women. Aims: The aim of this study was to determine White Blood Cells (WBC), Neutrophils (NEU) and Lymphocytes (LY) reference ranges in healthy Greek full‐term pregnant women and to evaluate them before and after delivery. Methods: Blood samples from 278 healthy pregnant women, before and after labour were collected using EDTA anticoagulated tubes. WBC, NEU and LY were determined in COULTER LH780 analyzer pre and one or two days post partum. 5% of the upper and lower results concerning WBC, NEU and LY were excluded. A normality test was performed using SPSS 21 statistical software and median, minimum and maximum ranges were calculated. Results: The WBC, NEU and LY mean, median, maximum and minimum values in healthy prepartum women are showed in Table I. Out of 278 pregnant women, only in 112 (40,3%), there was a statistically significant (p = 0.001) decrease in WBC post partum with a simultaneous fall of NEU in 84,8% of them. Furthermore, there was a post partum NEU decrease, only in 129 (46,4%) out of them, albeit not statistically significant (p = 0.283), whereas there was a LY significant fall (p = 0.004) in 114 (41,64%) of them. Summary/Conclusion: WBC and NEU in healthy full term pregnant women prepartum are elevated, while LY are within normal range.40,3% reduce WBC post partum. Nevertheless, in an excessive number women post partum develop elevated WBC due to possible infection. image
S844 KDM5 INHIBITION OFFERS A NOVEL THERAPEUTIC STRATEGY FOR THE TREATMENT OF KMT2D MUTANT LYMPHOMAS
Authors: J. Heward, L. Koniali, A. D’Avola, K. Close, A. Yeomans, P. Johnson, J. Okosun, R. Neve, J. Gribben, U. Oppermann, G. Packham, J. Fitzgibbon
Journal: HemaSphere (2019)
Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics
Authors: Christopher W. McAleer, Christopher J. Long, Daniel Elbrecht, Trevor Sasserath, L. Richard Bridges, John W. Rumsey, Candace Martin, Mark Schnepper, Ying Wang, Franz Schuler, Adrian B. Roth, Christoph Funk, Michael L. Shuler, James J. Hickman
Journal: Science Translational Medicine (2019)

A pumpless, reconfigurable, multi-organ-on-a-chip system containing recirculating serum-free medium can be used to predict preclinical on-target efficacy, metabolic conversion, and measurement of off-target toxicity of drugs using functional biological microelectromechanical systems. In the first configuration of the system, primary human hepatocytes were cultured with two cancer-derived human bone marrow cell lines for antileukemia drug analysis in which diclofenac and imatinib demonstrated a cytostatic effect on bone marrow cancer proliferation. Liver viability was not affected by imatinib; however, diclofenac reduced liver viability by 30%. The second configuration housed a multidrug-resistant vulva cancer line, a non-multidrug-resistant breast cancer line, primary hepatocytes, and induced pluripotent stem cell-derived cardiomyocytes. Tamoxifen reduced viability of the breast cancer cells only after metabolite generation but did not affect the vulva cancer cells except when coadministered with verapamil, a permeability glycoprotein inhibitor. Both tamoxifen alone and coadministration with verapamil produced off-target cardiac effects as indicated by a reduction of contractile force, beat frequency, and conduction velocity but did not affect viability. These systems demonstrate the utility of a human cell-based in vitro culture system to evaluate both on-target efficacy and off-target toxicity for parent drugs and their metabolites; these systems can augment and reduce the use of animals and increase the efficiency of drug evaluations in preclinical studies.
Abstract P082: Prevalence and Trends in Dietary Supplement Use Among Diabetic Adults: The National Health and Nutrition Examination Surveys, 1999-2014
Authors: Jing Li, Wambui Gathirua-Mwangi, Yiqing Song
Journal: Circulation (2018)

With increasing diabetes prevalence in the US general population, many nutritional supplements are taken as alternative medicine by diabetic patients. However, serial trends or patterns in their dietary supplement use are unknown. Using the nationally representative data from the National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2014, we evaluated prevalence and trends of use of any supplements, multi-vitamins/multi-minerals (MVMM), individual vitamins, minerals, and non-vitamin, non-mineral supplements. Information on supplement use in the preceding 30 days was collected during the interview over 8 continuous 2-year waves. Analyses were conducted among 6,348 US diabetic adults aged 20 to 85 years (pregnant women excluded) and also stratified by age, race/ethnicity, gender, educational backgrounds, comorbidity status, and comorbidity status. Overall, the prevalence of use of any supplement (52%-59%; P for trend=.09) and that of any mineral (47%-51%; P for trend=.24) seemed stable. Use of MVMM decreased from 36% of reported use in 1999-2000 to 32% in 2013-2014 ( P for trend=.008). Use of any vitamin products increased from 47% to 53% ( P for trend=.04). Use of a few individual supplements including lycopene, vitamin D, and vitamin B12 significantly increased. The trend of supplement use varied by sex and race/ethnicity. In conclusion, among diabetic patients in the United States, use of any dietary supplements or any minerals remained stable, use of MVMM slightly decreased, and use of any vitamins and several individual supplements increased over the past 16 years.