tbuckley/cabot-search huggingface dataset:
AB0055 INFECTIONS WITH ANTI TNF ALPHA: PROSPECTIVE STUDY OVER 12 YEARS
Authors: Bilal Bengana, Abdenour Boukabous, Naima Bahaz, Salima Lefkir
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Anti Tumor Necrosis Factor alpha (TNFα) has significantly improved the prognosis of some chronic inflammatory diseases (CID). Nevertheless, they carry with them a significant risk of opportunistic infections, imposing a rigorous surveillance and an adequate education of the patients. In a context of endemic tuberculosis, it is imperative to take the appropriate precautions to detect this kind of infection in rheumatisers under anti TNFα. <h3>Objectives</h3> The aim of our work was to study the profile of infectious incidents in patients treated with anti TNFα. <h3>Methods</h3> This is a prospective and descriptive study in patients treated with anti-TNFα over a 12-year period (2006- 2018). We examined all infectious complications for each patient who received an anti-TNFα for with CID while assessing the level of severity, the type of infection and the risk factors that may be related to this type of incident. <h3>Results</h3> During the study period, 134 patients were identified, these patients were followed for ankylosing spondylitis (AS) for 58 cases, 36 for enteric rheumatism, 23 for psoriatic arthritis and 17 for rheumatoid arthritis. The mean age was 46.3 years (19-64 years), the mean age of the disease was 44.2 months (8-140). The molecules used were: infliximab, etanercept, adalimumab with a respective number n (%) = 29 (21), 44 (33), 61 (46). Of the 134 patients evaluated, 71 were diagnosed and treated by a physician (in 47 patients), only 5 were serious: 2 cases of tuberculosis were reported (intestinal and ganglionic tuberculosis), 1 case of chickenpox of the adult, 1 case with perianal abscess, 1 case of erysipelas of the lower limb. The infection was bacterial, viral or mycotic [n (%) = 38 (53), 61 (86), 7 (8)]. A large proportion of the patients were on conventional immunosuppressive therapy. The factors related to the occurrence of infectious incidents were: use of corticosteroids p &lt;0.0001,habitat in rural areas p= 0,042. <h3>Conclusion</h3> More than a third of patients have infectious complications after TNFα treatment in our study sometimes with serious issue. Thus, with the emergence of these accidents, the physician has to be very vigilant when instituting this biotherapy, and secondly, a rigorous and prolonged monitoring of the patients. <h3>Disclosure of Interests</h3> None declared
Loss of nuclear UBE3A causes electrophysiological and behavioral deficits in mice and is associated with Angelman syndrome
Authors: Rossella Avagliano Trezza, Monica Sonzogni, Stijn N. V. Bossuyt, F. Isabella Zampeta, A. Mattijs Punt, Marlene van den Berg, Diana C. Rotaru, Linda M. C. Koene, Shashini T. Munshi, Jeffrey Stedehouder, Johan M. Kros, Mark Williams, Helen Heussler, Femke M. S. de Vrij, Edwin J. Mientjes, Geeske M. van Woerden, Steven A. Kushner, Ben Distel, Ype Elgersma
Journal: Nature Neuroscience (2019)
Unbiased Estimate of Synonymous and Nonsynonymous Substitution Rates with Nonstationary Base Composition
Authors: Laurent Guéguen, Laurent Duret
Journal: Molecular Biology and Evolution (2017)

The measurement of synonymous and nonsynonymous substitution rates (dS and dN) is useful for assessing selection operating on protein sequences or for investigating mutational processes affecting genomes. In particular, the ratio dNdS is expected to be a good proxy for ω, the ratio of fixation probabilities of nonsynonymous mutations relative to that of neutral mutations. Standard methods for estimating dN, dS, or ω rely on the assumption that the base composition of sequences is at the equilibrium of the evolutionary process. In many clades, this assumption of stationarity is in fact incorrect, and we show here through simulations and analyses of empirical data that nonstationarity biases the estimate of dN, dS, and ω. We show that the bias in the estimate of ω can be fixed by explicitly taking into consideration nonstationarity in the modeling of codon evolution, in a maximum likelihood framework. Moreover, we propose an exact method for estimating dN and dS on branches, based on stochastic mapping, that can take into account nonstationarity. This method can be directly applied to any kind of codon evolution model, as long as neutrality is clearly parameterized.
AB1031 ETANERCEPT-INDUCED LUPUS-LIKE SYNDROME IN THE BOY WITH IDIOPATHIC DERMATOMYOSITIS OR DELAYED MANIFESTATION OF SYSTEMIC LUPUS ERYTHEMATOSUS?
Authors: Maria Kaleda, Irina Nikishina
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Treatment of juvenile onset rheumatic diseases (RD) is an ongoing problem because of the more aggressive disease course and more various clinical manifestations than adult-onset RD. Since the main clinical symptoms may overlap between well-known various RD, in some cases the path to diagnosis and the search for optimal therapy takes longer, especially in patients of pre-adolescence and adolescence. <h3>Objectives</h3> We described a rare case of one boy with RD who presented initially with severe dermatomyositis with sequential evolution to systemic lupus erythematosus. <h3>Methods</h3> Case report. <h3>Results</h3> A 8 yo male patient with normal physical, psychosocial and cognitive development experienced muscle weakness, periorbital erythema, Gottron symptom, dysphagia in September 2015 y, which developed after insolation. When he was admitted to hospital, increased levels of muscle-derived enzymes and positivity of ANA 1:640 were found. He was diagnosed as having juvenile dermatomyositis and was treated with prednisolone (Pr) for 3 years (IV courses repeated and per os constantly, max dose 1.5 mg/kg/day, min dose 0.5 mg/g/day), IVIG courses repeated and sequentially methotrexate, hydroxychloroquine, cyclosporine with short time of remission. Muscle weakness disappeared after the treatment, but in October 2015 y he experienced new eruptions on his face, heavy aphtosis stomatitis, lymphadenopathy, distal polyneuropathy, weight loss without strong effect after increase the dose of Pr, IVIG courses repeated, cyclosporine and added of abatacept during 6 months. Because the response to this treatment was low, etanercept was started in June 2016 y, but after two injections he had flare of disease: bright rash on the face, scalp and legs, hard aphthosis stomatitis, cheilitis, cognitive disorders, diffuse alopecia. He received IV course of Pr without significant stable effect. We reviewed diagnosis as systemic lupus erythematosus and changed therapy in November of 2016. Because he had steroid's osteoporosis with spondylopathy, this combination that made us initiate treatment with mycophenolate mofetil and repeating courses of rituximab (3 courses in total) without increased dose of Pr. Clinical features gradually improved and now he feel goog and receive mycophenolate mofetil and Pr 5 mg/day. <h3>Conclusion</h3> This clinical observation can be considered as a course of overlap-syndrome with a successive phase change that could be triggered by anti-TNF therapy, or as an unusual course of SLE in a male patient with a predominance of myositis at onset. Treatment strategy, including of Pr, mycophenolate mofetil and rituximab in a young patient proved successful for treatment and seems to be justified in similar cases. <h3>Disclosure of Interests</h3> None declared
Catatonia and the immune system: a review
Authors: Jonathan P Rogers, Thomas A Pollak, Graham Blackman, Anthony S David
Journal: The Lancet Psychiatry (2019)

Catatonia is a psychomotor disorder featuring stupor, posturing, and echophenomena. This Series paper examines the evidence for immune dysregulation in catatonia. Activation of the innate immune system is associated with mutism, withdrawal, and psychomotor retardation, which constitute the neurovegetative features of catatonia. Evidence is sparse and conflicting for acute-phase activation in catatonia, and whether this feature is secondary to immobility is unclear. Various viral, bacterial, and parasitic infections have been associated with catatonia, but it is primarily linked to CNS infections. The most common cause of autoimmune catatonia is N-methyl-D-aspartate receptor (NMDAR) encephalitis, which can account for the full spectrum of catatonic features. Autoimmunity appears to cause catatonia less by systemic inflammation than by the downstream effects of specific actions on extracellular antigens. The specific association with NMDAR encephalitis supports a hypothesis of glutamatergic hypofunction in catatonia.
PS1104 EPIDEMIOLOGICAL STUDY OF IDIOPATHIC THROMBOCYTOPENIC PURPURA AMONG THE ADULT POPULATION OF THE RUSSIAN FEDERATION
Authors: A. Melikyan, E. Egorova, E. Pustovaya, T. Kolosheinova, E. Ladygina, E. Volodicheva, T. Kaporskaia, R. Ilyasov, T. Shelekhova, N. Fedorova, I. Zotova, T. Sycheva, I. Kontievskii, I. Shestopalova, N. Kurkina, E. Syrtseva, E. Tarasenko, O. Meresiy, Z. Cherkashenko, Y. Chabaeva, S. Kulikov
Journal: HemaSphere (2019)

Background: Primary immune thrombocytopenia (idiopathic thrombocytopenic purpura ‐ ITP) is a rare autoimmune disease, the main clinical manifestations of which are hemorrhagic syndrome of varying severity. The incidence of ITP in the adult population of different countries varies from 1.6 to 12.5/100,000 person‐years. ITP register started in the Russian Federation (RF) In December 2014. This is multicenter, prospective observational cohort study “Epidemiological and clinical characteristics of ITP in adults in Russia”. Aims: Assessment of the epidemiological characteristics of ITP in the adult population of the RF. Methods: Clinical and laboratory data of the register “Epidemiological and clinical characteristics of ITP in adults in Russia”. Methods of descriptive statistics, frequency, variance analysis and event analysis used in statistical processing. Results: The incidence of ITP in the adult population of the Russian Federation averaged 2.09/100,000 people. The highest morbidity of 2.7/100,000 recorded among women under 40 years of age. While in men there was a gradual increase in the incidence from 1.09 to 2.5/100,000 people over the age of 60 years. The result obtained is comparable with the data of the registers of other European countries. An analysis of incidence in the sex‐age strata showed that men have a tendency to an increase in the incidence of ITP from 1.09 at the age of 40, to 2.98 at the age of 60. Similar changes in the incidence in women of different age groups not detected. It is noteworthy that in the age group over 60 years, the incidence in men and women is almost the same, whereas data from epidemiological studies in other European countries showed a significant predominance in this group of men. There was a significant relationship between the risk of development, the degree of bleeding and the number of platelets in the onset of the disease: the severity of hemorrhagic syndrome increases with the number of platelets below 50x10 9 /l ( p &lt; 0.0001). In 92.2% of cases glucocorticosteroid hormones prescribed as the first line of therapy. Analysis of methods of treatment used as a second line therapy demonstrated that the probability of splenectomy the last 3 years decreased from 26 to 17%, while the number of patients receiving thrombopoetin receptors agonists increased from 5.9 to 45.7%. Summary/Conclusion: The epidemiological data are comparable with those in other European countries. Geographical variations of incidence in different regions of the Russian Federation require further study.
Laying the foundation for genomically-based risk assessment in chronic myeloid leukemia
Authors: Susan Branford, Dennis Dong Hwan Kim, Jane F. Apperley, Christopher A. Eide, Satu Mustjoki, S. Tiong Ong, Georgios Nteliopoulos, Thomas Ernst, Charles Chuah, Carlo Gambacorti-Passerini, Michael J. Mauro, Brian J. Druker, Dong-Wook Kim, Francois-Xavier Mahon, Jorge Cortes, Jerry P. Radich, Andreas Hochhaus, Timothy P. Hughes
Journal: Leukemia (2019)
PB2102 A SAME DAY ASSAY USING CYTOCHROME C RELEASE DETERMINES SENSITIVITY TO COOPERATIVE BCL‐2 AND MCL‐1 TARGETING IN MULTIPLE MYELOMA CELL LINES AND PRIMARY SAMPLES
Authors: M. Grundy, J. Cull, F. Al‐Kaisi, C. Williams, D. Smith, C. Seedhouse
Journal: HemaSphere (2019)

Background: Multiple myeloma is an incurable haematological malignancy with remarkable clonal and genetic heterogeneity. Although both MCL‐1 and BCL‐2 are necessary for myeloma survival, most myelomas are dependent on MCL‐1 for survival such that BCL‐2 inhibition alone only yields significant cytotoxicty in a minority and cooperative inhibition of both proteins is required. Knowing which patients will respond can be challenging since cytotoxicty assessment of primary patient samples is significantly hampered by the lack of longevity of those cells in culture ex vivo. Aims: We aimed to study whether a short term flow cytometric assay could be used to determine cytotoxicity in myeloma cell lines and primary samples after cooperative inhibition of BCL‐2 and MCL‐1 by the BH3 mimetics (venetoclax and S63845). Methods Myeloma cell lines and patient samples were treated with venetoclax and S63845 alone and in combinations. Sub‐toxic doses of drugs were determined for each cell line. Samples were fixed after 4 hours drug incubation thus precluding the need to keep those cells alive in culture for prolonged periods and then assayed for cytochrome c release using flow cytometry. The Bliss independence model was used to demonstrate synergy. Results: The cytochrome C release assay demonstrated that the combination of venetoclax and S63845 was synergistic as compared to controls and single agent treatment in all six cell lines tested (Combination index values 7.8‐80). All three cyclin D2 translocated cell lines were particularly sensitive to the combination and synergy was p53 independent. Furthermore, the same day assay was used on CD138‐selected primary myeloma cells also demonstrating effective cooperative targeting in patient samples. Summary/Conclusion: The attractiveness in this assay lies in its ability as a predictor of apoptotic response to chemotherapy and molecular targeting agents providing rapid results. Here, we have demonstrated for the first time in myeloma that using the cytochrome C release assay we can quickly predict apoptosis in cell lines. Importantly we are now demonstrating that this assay can also be used in primary samples. This can set the steps for an individualised assay to determine patient responses to targeted molecular therapies.
습관성 공업용 접착제(본드) 흡입에 의해 유발된 간염 1예
Authors: 박창근 ( Park Changgeun ), 권기태 ( Kwon Gitae ), 이동석 ( Lee Dongseog ), 조창민 ( Jo Changmin ), 탁원영 ( Tag Wonyeong ), 권영오 ( Kwon Yeongo ), 김성국 ( Kim Seonggug ), 최용환 ( Choe Yonghwan )
Journal: Clinical and Molecular Hepatology (2003)

The link between toxic hepatitis and exposure to organic solvents is relatively well-documented, but there are no specific laboratory or histologic findings diagnostic of chemical-induced hepatitis. Clinical history, therefore, is very important in making a diagnosis. A history of glue sniffing is sometimes overlooked and glue sniffing has not received much attention as a cause of hepatitis. Toluene, a main organic solvent in glue, is known to cause disturbances in various organs such as the heart, nervous system, liver and kidneys. We present a case of hepatitis in an individual who has sniffed glue for euphoria for 3 years. There is an increasing tendency towards glue sniffing among young adolescents today, so toxicity caused by exposure to organic solvents should be considered as one possible cause of hepatitis in young adolescents.
CSN and CAVA: variant annotation tools for rapid, robust next-generation sequencing analysis in the clinical setting
Authors: Márton Münz, Elise Ruark, Anthony Renwick, Emma Ramsay, Matthew Clarke, Shazia Mahamdallie, Victoria Cloke, Sheila Seal, Ann Strydom, Gerton Lunter, Nazneen Rahman
Journal: Genome Medicine (2015)
PB1915 CD14 AS A POTENTIAL PROGNOSTIC FACTOR AND BCL‐2 AS A THERAPEUTIC TARGET IN EGYPTIAN B‐CELL CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS
Authors: M. Elkhawanky, M. Morsy
Journal: HemaSphere (2019)

Please indicate where the abstract has been published before: Journal of Applied Hematology. Background: B‐cell chronic lymphocytic leukemia (B‐CLL) is a unique lymphoproliferative disorder that scarcely occurs under the age of 40. B‐CLL represents a neoplastic disorder caused primarily by defective programmed cell death and accompanied by a myriad of cellular and humoral immune defects. Aims: This study aimed to assess Bcl‐2 and CD14 expression in B‐CLL patients and their study as probable prognostic and therapy targeting factors. Methods: In this study, we assessed Bcl‐2 and cluster of differentiation (CD14) expression in a group of Egyptian patients with B‐CLL. Forty B‐CLL patients and 20 apparently healthy individuals served as the control group were included in this study. Results: Aberrant expression of Bcl‐2 protein appeared in all B‐CLL patients (100%). Bcl‐2 expression showed a highly positive correlation with total lymphocyte count and lymphocyte count ( P = .000 for both) and a positive correlation with lactate dehydrogenase ( P = 0.044). The expression of myelomonocytic antigen “CD14” above the cutoff value 5 × 109/L was reported in 70% (28/40) of B‐CLL patients, 55.6% (10/18) of the intermediate‐risk group, and 81.8% (18/22) of high‐risk group. Summary/Conclusion: There was a significant increase in Bcl‐2 protein and CD14 in B‐CLL patients. Bcl‐2 was highly increased in all patients and CD14 more observed in the high‐risk group than that of the intermediate risk group.
PB2439 CAN THROMBOELASTOGRAPHY (TEG) EFFECTIVELY EVALUATE COAGULATION BALANCE IN PATIENTS WITH ACUTE LEUKAEMIA UNDER CHEMOTHERAPY?
Authors: S. Raso, M. Napolitano, S. Mancuso, M. Santoro, M. Carlisi, G. Tarantino, G. Franco, M. G. Lipari, S. Siragusa
Journal: HemaSphere (2019)

Background: Clinical course of AL may be complicated by thrombosis o major bleeding. Basal coagulation tests and platelet count (PLT) alone have been shown to not adequately identify thrombotic or risk. Aims: prospective study investigates the role of TEG, in patients with AL for predicting bleeding or thrombosis either at the presentation o during chemotherapy (CHT). Methods: This prospective study was conducted on 11 consecutive patients (PTs) with AL. Assessment of blood count cell (CBC) and conventional coagulation tests (CCT),PT,a‐PTT,DD,FBGandTEG(TEG®5000, Thromboelastograph Haemostasis System) were collected at the diagnosis and during 1 st cycle of CHT. TEG parameters R‐time(min), a‐angle(°), K‐time(min), MA (maximum amplitude) (mm) were recorded and normal ranges were considered as R 9‐27, K 2‐9, a‐angle 22‐58, MA 44‐64. Results: Overall, 8 PTs with AML and 3 with ALL were evaluated with a median age of 54 y (range 18 –80). CHT administered were intensive in all but 2 PTs, treated with hypomethylating agent (HP). CCTs resulted normal in all cases with the exception of DD levels that were increased. 6 patients developed blood cloting disorders on CHT:3 thrombotic events [1 portal vein thrombosis,1 thrombosis of the lower limbs, 1 myocardial infarction]; 3 haemorrhages [2 of urinary tract (WHO grade 2) and 1 of central nervous system (WHO grade 3)]. TEG assay at diagnosis resulted normal in 9 patients. In PTs with thrombosis, TEG resulted markedly shortened, with an increased rate of a‐angle and a higher MA, when compared to bleeding PTs and to aymptomatic PTs(Table 1).TEG in PTs receiving HP showed no significant alterations, also in presence of thrombocytopenia. Summary/Conclusion: In our cohort, TEG showed a hypercoagulable state, characterized by a reduction of R value during CHT in PTs with thrombosis. MA and a‐angle resulted increased, compared to diagnosis, only in patients with thrombosis, while they were decreased in all the other PTs. These results were no in relationship to PLT or FBG levels. Our findings suggest that TEG may be useful to identify PTs with AL at higher thrombotic risk. image
Population-Based Study on Cancer Subtypes, Guideline-Concordant Adjuvant Therapy, and Survival Among Women With Stage I–III Breast Cancer
Authors: Mei-Chin Hsieh, Lu Zhang, Xiao-Cheng Wu, Mary B. Davidson, Michelle Loch, Vivien W. Chen
Journal: Journal of the National Comprehensive Cancer Network (2019)

Breast cancer subtype is a key determinant in treatment decision-making, and also effects survival outcome. In this population-based study, in-depth analyses were performed to examine the impact that breast cancer subtype and receipt of guideline-concordant adjuvant systemic therapy (AST) have on survival using a population-based cancer registry's data.Women aged ≥20 years with microscopically confirmed stage I-III breast cancer diagnosed in 2011 were identified from the Louisiana Tumor Registry. Breast cancer subtypes were categorized based on hormone receptor (HR) and HER2 status. Guideline-concordant treatment was defined using the NCCN Guidelines for Breast Cancer. Logistic regression was applied to identify factors associated with guideline-concordant AST receipt. Kaplan-Meier survival curves were generated to compare survival among subtypes by AST receipt status, and a semiparametric additive hazard model was used to verify the factors impacting survival outcome.Of 2,214 eligible patients, most (70.8%) were HR+/HER2- followed by HR-/HER2- (14.4%), and 78.6% received guideline-concordant AST. Compared with patients with the HR+/HER2+ subtype, women with other subtypes were more likely to be guideline-concordant after adjusting for sociodemographic and clinical variables. Women with the HR-/HER2+ or HR-/HER2- subtype had a higher risk of any-cause and breast cancer-specific death than those with the HR+/HER2+ subtype. Those who did not receive AST had an additional adjusted hazard of 0.0191 (P=.0001) in overall survival and 0.0126 (P=.0011) in cause-specific survival compared with those who received AST.Most patients received guideline-concordant AST, except for those with the HR+/HER2+ subtype. Patients receiving guideline-adherent adjuvant therapy had better survival outcomes across all breast cancer subtypes.
Applicability of the Mutation–Selection Balance Model to Population Genetics of Heterozygous Protein-Truncating Variants in Humans
Authors: Donate Weghorn, Daniel J Balick, Christopher Cassa, Jack A Kosmicki, Mark J Daly, David R Beier, Shamil R Sunyaev
Journal: Molecular Biology and Evolution (2019)

Abstract The fate of alleles in the human population is believed to be highly affected by the stochastic force of genetic drift. Estimation of the strength of natural selection in humans generally necessitates a careful modeling of drift including complex effects of the population history and structure. Protein-truncating variants (PTVs) are expected to evolve under strong purifying selection and to have a relatively high per-gene mutation rate. Thus, it is appealing to model the population genetics of PTVs under a simple deterministic mutation–selection balance, as has been proposed earlier (Cassa et al. 2017). Here, we investigated the limits of this approximation using both computer simulations and data-driven approaches. Our simulations rely on a model of demographic history estimated from 33,370 individual exomes of the Non-Finnish European subset of the ExAC data set (Lek et al. 2016). Additionally, we compared the African and European subset of the ExAC study and analyzed de novo PTVs. We show that the mutation–selection balance model is applicable to the majority of human genes, but not to genes under the weakest selection.