tbuckley/cabot-search huggingface dataset:
PB1680 SURVIVAL OF ADULT PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA (PH NEG) WHO DEVELOP HYPERGLYCEMIA DURING THE INDUCTION OF REMISSION IN AN INTENSIVE CHEMOTHERAPY PROTOCOL IN MEXICO
Authors: M. Alvarado, F. Rojas, J. L. Alvarez, M. Ortiz, V. Mena, A. de la Peña, M.E. Espitia, J. M. Perez
Journal: HemaSphere (2019)

Background: During the induction phase of the treatment exist several factors, besides glycemia control, that predisposed to severe infections like decreased immunity, aplasia of the epithelia, disease activity and chemotoxicity.13 But the effect of hyperglycemia during induction to remission have impact the leukemia‐free survival (LFS) results. Aims: The purpose of this study is to determine the incidence of hyperglycemia in therapeutic programs that include dexamethasone during the induction, and compare leukemia free survival (LFS) and disease‐free survival (DFS) in patients older than 15 years Methods: We performed a unicentric, longitudinal, case control study in ALL patients older than 15 years old admitted to the adult hematology Service of the CMN “20 de Noviembre” during the period from 2000 to 2014 treatment with the chemotherapy. Exclusion criteria: history of myelodysplastic syndrome, previous chemotherapy and / or radiotherapy, HIV infection or any condition that precluded their inclusion in chemotherapy (CT) protocols. Patients who abandoned the treatment, who violated the chemotherapy protocol or went to BMT due to high risk disease, were eliminated. Both therapeutic programs (LAL‐6 and LAL‐10) included 4 days of IV dexamethasone (pre‐induction phase) before the start of CT. Results: We included 159 patients, 77 women and 82 men; 77 patients presented hyperglycemia during induction phase. The mean follow‐up was 19 months (2 to 61). Hyperglycemia incidence was 51.5%. The LAL‐6 protocol was received by 56 patients (53% of the group without hyperglycemia and 17% in the hyperglycemia group). The LAL‐10 protocol was used in 102 patients (47% and 83% respectably). The highest elevations occur immediately after concluding the use of dexamethasone, with hyperglycemia in 91 patients and without in 68. This phenomenon maintained until the end of induction and the levels of glucose start to decrease in the following phases (p = 0.0001). In patients with hyperglycemia at the end of the induction, the average age was 44 years (SD 13) and in those who did not have it was 31 years (SD 12), p = 0. 0001. Summary/Conclusion: In the multivariate analysis, the factors that predict the appearance of hyperglycemia, in our experience, were age, female sex, the existence of diabetes and the basal glucose level (&gt; 135 mg / dL). O
PF418 TREATMENT-FREE REMISSION IN REAL-WORLD CHRONIC MYELOID LEUKEMIA PATIENTS: INSIGHTS FROM GERMAN CLINICAL HEMATOLOGY PRACTICES
Authors: J. Dengler, H. Tesch, K. Jentsch-Ullrich, A. Gerhardt, C. Schulte, J. Lipke, G. Löwe, I. Holder, A. Kiani
Journal: HemaSphere (2019)

Background: Recent trials show that about 40–60% of patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) who have achieved stable deep molecular response (DMR) can discontinue tyrosine kinase inhibitor (TKI) therapy without relapsing (treatment free remission, TFR). TFR strategies are now increasingly being integrated into routine clinical practice, but “real world” information about discontinuation policies and patient outcome is scarce. Aims: To evaluate treatment characteristics and outcome of pts with CML-CP in DMR and/or after an attempt of TFR in clinical practice in Germany. Methods: Data from CML-CP pts were retrospectively collected from german hematologists by means of a questionnaire. Patients were eligible if they had either had achieved DMR of at least MR4 (BCR-ABL1IS ≤0.01%) or had discontinued TKI therapy prior to the time-point of data collection. Data on molecular monitoring as well as on discontinuation characteristics and TFR were assessed. Results: 1503 pts from 31 hematology practices in Germany were screened for the study, out of which 771 pts were included in the analysis. In total, 268 pts discontinued TKI treatment. The number of pts with TKI discontinuation was highly variable among practices, ranging from 0 to 36. Mean time from TKI initiation to discontinuation was 7.3 years (yrs). At the time of entering TFR, most pts (91.0%) had achieved DMR: 101 pts (37.8%) were in MR5 (BCR-ABL1IS ≤0.001%), 116 pts (43.5%) in MR4.5 (BCR-ABL1IS ≤0.032%), and 26 pts (9.7%) in MR4. The mean time between achieving MR4 and entering TFR was 3.7 yrs. 13 pts discontinued TKI while they were in major molecular remission (BCR-ABL1IS ≤0.1%, MMR), and the molecular status of 11 pts was reported as unknown. Molecular monitoring of BCR-ABL during the first 6 months after TKI discontinuation was heterogenous among practices: 17 of the hematologists (60.7%) reported mean monitoring intervals of 4 to <6 weeks, while monitoring intervals of 6 to 8 weeks and >8 weeks were employed by 6 (21.4%) and 5 (17.9%) of the hematologists, respectively. 144/264 (54.6%) of the pts remained in MR4 after TKI discontinuation. In 106 pts, treatment with a TKI was re-initiated, in most of the cases (70 pts) because of the loss of MMR. In 71.3% of the pts, the same TKI was used for re-treatment, while for the others an alternative TKI was chosen. At the time-point of data collection, 703 of the 771 pts included in the analysis (91.2%) were reported to be in MR4 or better, 46 pts were in MMR. In 9 pts BCR-ABL1IS was >0.1 to 1%, in 7 pts >1–10%, and in 2 pts >10%. Summary/Conclusion: These clinical data from a German real-life population show that TKI discontinuation has become part of daily clinical practice. Outcomes appear to be comparable to those reported in clinical trials, although monitoring of TFR is rather variable.
PB1793 REATMENT OUTCOME FOR PRIMARY CERVIX LARGE B‐CELL LYMPHOMA: A CLINICAL ANALYSIS OF 37 CASES.
Authors: X. Liu, Z. Xia, Y. Liu, J. Cao
Journal: HemaSphere (2019)

Background: Cervical lymphoma is a rare condition and may be difficult to diagnose and treatment. Large B‐cell lymphoma is among the most common sub‐type of Cervical Lymphoma.No standard treatments for patients with primary cervix large B‐cell lymphoma have been introduced currently. Only case reports published in the literature and indicated the R‐CHOP regimens in combination with involved field radiation therapy (RT) are effective. Shanghai Cancer Center is one of the top pathological consultant center in China. Aims: We retrospectively analyse the 37 patients with primary cervix large B‐cell lymphoma and outcome after R‐CHOP in combination with RT, explore the treatment outcome by combination chemetherapy in this very rare type of cervix entity. Methods: Thirty‐seven untreated primary cervix large B‐cell lymphoma patients received R‐CHOP like regimens. Fourteen of them underwent subsequent RT. Thirteen of them received subsequent salvage chemotherapy. Results: Of 37 patients underwent R‐CHOP chemotherapy, only 3 patients received the radical surgery. An overall response rate (ORR) was 78.3% after completion of chemotherapy.The PFS and OS rate at 5 years were 58% and 69%, respectively. For 14 patients who received RT after R‐CHOP, an estimated ORR were 89.2%. For all patients, The PFS reached the platform after 2 years follow up and the OS after 3 years according to the survival curve analysis. The international prognostic index (IPI) score were the only predictor of worse outcome. Summary/Conclusion: R‐CHOP regimens plus involved field radiation therapy led high response rate in primary cervix large B‐cell lymphoma. Patients with high IPI had a trend of less satisfied with R‐CHOP regimens plus IFRT. Future prospective and multicenter studies are needed. By the way, we are conducting a gene expression profile between DLBCL‐unspecified and primary cervix large B‐cell lymphoma by NGS in order to get the valuable information to improve the treatment outcome even by using some targeted drugs. The data will be show in the next few months. image
AB1003 DELAY IN DIAGNOSIS OF KAWASAKI DISEASE IS THE COMMONEST PROXIMATE REASON FOR DEVELOPMENT OF GIANT CORONARY ARTERY ANEURYSMS- OUR EXPERIENCE AT CHANDIGARH, NORTH INDIA
Authors: KUMAR RAKESH, Ankur Jindal, Anju Gupta, Deepti Suri, Manphool Singhal, Surjit Singh
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Long-term effects of Kawasaki disease (KD) depend primarily on development of coronary artery abnormalities. Giant coronary aneurysm (GCA) is the one of the most severe sequelae in KD. Regression of giant aneurysm is rare. Data from Indian subcontinent is limited. Herein, we review patients with KD who had GCA. <h3>Objectives</h3> To describe the profile of patients with KD who developed GCA from a cohort of KD patients at Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh. <h3>Methods</h3> Records of all children diagnosed to have KD during 1994-2017 were analysed. Out of the 680 patients with KD, clinical details of 17 (2.5%) children with GCA were retrieved. <h3>Results</h3> Diagnosis of GCA was based on coronary artery diameter ≥8 mm or ≥+10 z score. Six of 17 children (boys 13; girls 4) with GCA had incomplete KD. Diagnosis of KD was made at a mean of 17.2±12.2 days of fever. Eight (47%) children were &lt;1 year. Median age of diagnosis was 18 months (range 1.5 months-12 years). Left anterior descending (LAD) coronary artery was affected in 82% followed by right coronary artery (RCA) in 59%. Multiple GCA &gt;1) were seen in 65% patients. All patients had received first line therapy as IVIg. Median day of IVIg administration was 15.5 days. Twelve had received additional therapy with infliximab. Thromboses developed in 4 (23.5%) and most common coronary affected was LAD. All patients were started on anticoagulation therapy and there were no significant complications related to anticoagulation. <h3>Conclusion</h3> Results of this study suggest that GCA develop more commonly in infants and young children. Delay in diagnosis and consequent administration of IVIg appears to be the commonest proximate cause of development of GCA. <h3>References</h3> [1] Fukazawa R, Kobayashi T, Mikami M, et al. Nationwide Survey of Patients With Giant Coronary Aneurysm Secondary to Kawasaki Disease 1999-2010 in Japan. Circ J. 2017;25;82(1):239-246 [2] Gupta A, Singh S, Rohit M, et al. Giant coronary aneurysms in Kawasaki Disease. Indian J Pediatr. 2014;81(4):401-2. [3] Tsuda E, Hamaoka K,et al. A survey of the 3-decade outcome for patients with giant aneurysms caused by Kawasaki disease. Am Heart J. 2014;167(2):249-58. <h3>Disclosure of Interests</h3> None declared
The fitness cost of mis-splicing is the main determinant of alternative splicing patterns
Authors: Baptiste Saudemont, Alexandra Popa, Joanna L. Parmley, Vincent Rocher, Corinne Blugeon, Anamaria Necsulea, Eric Meyer, Laurent Duret
Journal: Genome biology (2017)

Most eukaryotic genes are subject to alternative splicing (AS), which may contribute to the production of protein variants or to the regulation of gene expression via nonsense-mediated messenger RNA (mRNA) decay (NMD). However, a fraction of splice variants might correspond to spurious transcripts and the question of the relative proportion of splicing errors to functional splice variants remains highly debated.We propose a test to quantify the fraction of AS events corresponding to errors. This test is based on the fact that the fitness cost of splicing errors increases with the number of introns in a gene and with expression level. We analyzed the transcriptome of the intron-rich eukaryote Paramecium tetraurelia. We show that in both normal and in NMD-deficient cells, AS rates strongly decrease with increasing expression level and with increasing number of introns. This relationship is observed for AS events that are detectable by NMD as well as for those that are not, which invalidates the hypothesis of a link with the regulation of gene expression. Our results show that in genes with a median expression level, 92-98% of observed splice variants correspond to errors. We observed the same patterns in human transcriptomes and we further show that AS rates correlate with the fitness cost of splicing errors.These observations indicate that genes under weaker selective pressure accumulate more maladaptive substitutions and are more prone to splicing errors. Thus, to a large extent, patterns of gene expression variants simply reflect the balance between selection, mutation, and drift.
AB1421-HPR VIRTUAL CLINICS IN THE PRESENT- A PREDICTOR FOR THE FUTURE?
Authors: Tina Parish, Maathu Ratnaraj, Tazeen J. Ahmed
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> There is great interest in non face to face (F2F), internet or app based outpatient interact at the moment. As these become established, we look at the non F2F appointments already happening in telephone and virtual clinics in a busy urban rheumatology department. Here we look at the type of diagnoses dealt with in a non F2F environment and potential outcomes from these non F2F appointments. <h3>Objectives</h3> To assess the efficiency and utilisation of virtual and telephone clinics in a general rheumatology department. <h3>Methods</h3> Data was collected from electronic (Cerner) patient records on 240 patients who had a virtual appointment in May 2018. The data was analysed using Excel 2010. <h3>Results</h3> 240 patients had virtual appointments in one month. 121 (50.4%) were via telephone and 119 (49.6%) via patient letter. 34 (14.1%) patients had multiple virtual/telephone appointments. 129 (54%) were carried out by consultants, 78 (32%) by nurses and 33 (14%) by registrars. 37% had rheumatoid arthritis. 32 (13%) appointments lead to a prescription. Virtual appointments produced 44 referrals, including 18 to another specialty, 16 to physiotherapy, and the rest to hand therapy or podiatry. Most patients had a F2F appointment before and after their virtual appointment in May 2018, 1 patient had died before having a second face to face appointment and 13 (5%) were discharged from their virtual appointment. <h3>Conclusion</h3> Consultants undertook the bulk of virtual clinics, and these appointments resulted in the majority of referrals and prescriptions. Virtual appointments reduce the waiting times for contact with a healthcare professional between appointments. Many patients had several virtual appointments between face to face appointments and this cohort may benefit from more scrutiny. Current technology already imporves communication and leads to significant changes in patient care without requiring F2F appointments. Internet based and app based interaction should face the same scrutiny. <h3>Disclosure of Interests</h3> None declared
Current trends in quantitative structure activity relationships on FXa inhibitors: Evaluation and comparative analysis
Authors: Christos A. Kontogiorgis, Dimitra Hadjipavlou‐Litina
Journal: Medicinal Research Reviews (2004)

Abstract This article evaluates the quantitative structure activity relationships of FXa inhibitors, using the C‐QSAR program of Biobyte. Diaryloxypyridines, aminophenols, biaryl isoxazoline derivatives, 1,2‐dibenzamidobenzenes, 3‐amidinophenylalanine derivatives, benzoxazinones, naphthoanilides, tetrazoles, glucolic and mandelic acid derivatives were included in this survey. Clog P plays a significant role in the QSAR, especially as hydrophilicity. In the most of the cases, CMR/MR molar refractivity as well as sterimol parameters (B 5 and L) are important. Electronic effects with the exception of the Hammett's constant σ m , are not found to govern the biological activity. Es was found to be important indicator variables were used after the best model was found to account for the usual structural features. © 2004 Wiley Periodicals, Inc. Med Res Rev, 24, No. 6, 687–747, 2004
Gabapentinoids associated with increased risk of suicidal behaviour
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Gabapentinoids—a group of drugs used to treat epilepsy, nerve pain, and anxiety disorders—are associated with an increased risk of suicidal behaviour, unintentional overdose, injuries, and road traffic incidents, new research published in The BMJ has found.1

Researchers looked at the associations between gabapentinoids and adverse outcomes related to coordination disturbances, mental health, and criminality, and found the risks were strongest among 15 to 24 year olds.

The study authors called for the guidance around prescribing of these drugs to younger …
Surgical Safety of Cytoreductive Nephrectomy Following Sunitinib: Results from the Multicentre, Randomised Controlled Trial of Immediate Versus Deferred Nephrectomy (SURTIME)
Authors: Roderick Emile De Bruijn, Peter Mulders, Michael A. Jewett, John Wagstaff, Johan V. Van Thienen, Christian U. Blank, Roland Van Velthoven, Lori Wood, Harm E. van Melick, Maureen J. Aarts, Jean B. Lattouf, Thomas Powles, Igle J. De Jong, Sylvie Rottey, Betrand Tombal, Sandrine Marreaud, Sandra Collette, Laurence Collette, John B. Haanen, Axel Bex
Journal: European Urology (2019)
PB1907 IBRUTINIB THERAPY IS ASSOCIATED WITH SERIOUS INFECTIONS IN PATIENTS WITH B‐CELL MALIGNANCIES ‐ A SINGLE CENTER EXPERIENCE
Authors: K. Misura Jakobac, V. Milunovic, M. Kursar, I. Mandac Rogulj, S. Ostojic Kolonic, D. Radic‐Kristo
Journal: HemaSphere (2019)

Background: Ibrutinib is an irreversible inhibitor of Bruton tyrosine kinase (BTK). Recently, ibrutinib has become available in Croatia for chronic lymphocytic leukemia (CLL) with del17p aberration or in early relapse and for relapsed/refractory mantle cell lymphoma (MCL) pretreated with bendamustine and rituximab. BTK inhibition can lead to immunosuppression through B‐ and T‐cell inhibition resulting in an increase in infections. In literature, systematic meta‐analyses have shown higher incidence of infections in B‐cell malignancies treated with ibrutinib, however the results for CLL are diverse. Aims: The main aim of this retrospective study was to retrospectively review all infections associated with ibrutinib in patients treated with B‐cell malignancies and characterized the grade and possible predisposing factors at single center institution. Methods: We retrospectively reviewed the medical charts for all patients treated with ibrutinib in era from 2015‐2018 to estimate the rate and grade of infections and possibly underlying factors predisposing these patients to infections. Results: A total number of patients included was 32, mainly the patients treated for CLL (28). Median line of previous therapies was 2 with only two patients being treatment naïve. The dosage of ibrutinib was according to the standard of care with median exposure to ibrutinib being 8.5 months. Any grade of infections occurred in 41.9% (N = 18) of our sample with median time to first infection being 82.5 days. The most common type of infection was sepsis (33.3%) followed by pneumonia (22.2%). The specific microbiological agents were isolated in 8 patients. Most of infections were mild (grade I/II according to NCI CTCAE nomenclature) estimated to be 41.2% in our sample. Grade III‐IV infections occurred in 35.3% of sample and grade V infections occurred in 4 patients. It is important to note that re‐infection occurred in 4 patients. Ibrutinib therapy was temporally withdrawn in 9 patients with median time off therapy being 30 days while it was discontinued indefinitely due to infection in 3 patients. Previous fludarabine therapy (p = 0.024) was the only factor associated with the occurrence of infection unlike previous number of therapy, neutropenia, leukopenia and levels of immunoglobulin G. In survival analysis, infections in general were not associated with poorer outcome (p = 0.265), but the grade of infection was associated with poorer outcome (p = 0.003) Summary/Conclusion: Our findings show, however, higher grade of serious infections than pivotal RESONATE trial with expected incidence early in the treatment course. The role of temporary ibrutinib withdrawal due to an infection should be explored in the greater samples possible through the larger observational studies.
Predictors of optimal pharmacological treatment in patients with heart failure and depressed ejection fraction. Results of the VIDA-IC study
Authors: Francisco José Hidalgo Lesmes, Manuel Anguita, Josep Comín, Javier Muñiz, María Generosa Crespo-Leiro, Francesc Formiga, Luis Manzano, Luis Almenar-Bonet, Trinidad de Frutos
Journal: European Journal of Heart Failure (2015)
Haplotype-aware diplotyping from noisy long reads
Authors: Jana Ebler, Marina Haukness, Trevor Pesout, Tobias Marschall, Benedict Paten
Journal: Genome biology (2019)

Current genotyping approaches for single-nucleotide variations rely on short, accurate reads from second-generation sequencing devices. Presently, third-generation sequencing platforms are rapidly becoming more widespread, yet approaches for leveraging their long but error-prone reads for genotyping are lacking. Here, we introduce a novel statistical framework for the joint inference of haplotypes and genotypes from noisy long reads, which we term diplotyping. Our technique takes full advantage of linkage information provided by long reads. We validate hundreds of thousands of candidate variants that have not yet been included in the high-confidence reference set of the Genome-in-a-Bottle effort.
PF732 AN INDEPENDENT OBSERVATIONAL STUDY OF REAL LIFE COSTS OF CARE TO MYELOMA PATIENTS IN THE ERA OF NOVEL THERAPIES
Authors: J. Thompson
Journal: HemaSphere (2019)

Background: Novel haematological therapies offer advantages in management of malignant and non‐malignant conditions, but treatment access is limited by cost, typically referenced as medication cost alone. The addition of real world costs of care provides a more complete cost‐benefit analysis, and limited published data and common perception have suggested additional costs are greater for novel agents. Aims: We analysed and compared total dollar value costs of care excluding the cost of the novel agent for myeloma patients treated first‐line with bortezomib and non‐novel agent based regimens in an inclusive (encompassing all patients within a local health network), real‐world cohort. Methods: We interrogated electronic and case note databases to record hospital admissions, outpatient visits, investigations, and non‐primary‐therapy medications and costed these using standard values using single payer government benchmarks. The primary end point was the real world cost of treatment per patient for the first year of treatment. Results: After using generalised linear models to adjust for patient age, gender, International Staging System (ISS) stage, trial status and transplant status, the mean yearly cost of care for patients receiving bortezomib‐based regimens was AU$24,162 (CI $20,207–28,118), which was 2.6% lower (CI −22.1–21.7, p = 0.814) than that for those receiving regimens not containing a novel agent ($26,300, CI $23,121–29,479) excluding the novel agent. Compared to patients at Stage 1 at baseline ($, CI$‐), costs of care were 62.2% higher (CI 50.1–81.8, p &lt; .0001) for patients at Stage 3 at baseline ($, CI$‐). Costs were 36.0% lower (CI 18.2–49.9, p &lt; .0001) for trial patients ($21,381, CI $17,404–25,358) compared to non‐trial patients ($25,130, CI $20,120–30,139). Yearly costs of care are estimated to be on average 51.5% higher (CI 22.0–88.1, p &lt; .0001) for transplant patients ($27,288, CI $23,351–31,226) compared to non‐transplant patients ($17,088, CI $10,980–23,196). Summary/Conclusion: Contrary to common perceptions and previously published data, bortezomib‐based regimens do not confer higher costs of care in the real world than conventional regimens. Subgroup analysis indicates significant cost differences based on ISS stage, trial involvement, transplant status and age.