tbuckley/cabot-search huggingface dataset:
PF694 TREATMENT‐FREE REMISSION AFTER TPO RECEPTOR AGONISTS IN ADULT ITP PATIENTS IN BELGIUM
Authors: A. Janssens, Y. Beguin, C. Lambert, D. Breems, D. Deeren, A. Efira, K. Fostier, M. Janssen, A. Kentos, V. Maertens, P. Mineur, L. Schauvliege, C. Schuermans, K. Theunissen, M. Vaes, A. Van de Velde, K. Van Eygen, A. Vantilborgh, D. Selleslag
Journal: HemaSphere (2019)

Background: Since 2009 treatment of chronic ITP patients with thrombopoietin receptor agonists (TPO‐RA) (romiplostim‐eltrombopag) has been reimbursed in Belgium. Despite the initial assumption that this would be a life‐long therapy, practical experience has shown that a significant number of patients do stop treatment. Reasons of TPO‐RA discontinuation can be no efficacy, adverse events, ITP or non‐ITP related death or spontaneous remission. Spontaneous remission (SR) or treatment free‐remission (TFR) is defined as a treatment‐free period of 3 6 months (mo) with platelets 3 50000/ml and no need of ITP rescue medication. Aims: We performed a survey to know how many patients were treated with TPO‐RA (trial, reimbursed, medical need) and how many of these had stopped this treatment. More details were gathered of patients who discontinued treatment. Methods: The survey was sent by mail to all hematologists who were member of the Belgian Hematological Society. Results: 20 Belgian centers participated in our survey and sent data. 42 patients fulfilled the definition of TFR, while 3 of these patients had several episodes of TFR. The baseline characteristics of the patients obtaining TFR were as follows: 26 patients were male and 16 were female; diagnosis of primary ITP was made in 34 patients; the 8 patients with secondary ITP had an underlying lymphoma (n = 5), an Evans syndrome (n = 2) or a previous transplant (n = 1); mean age at ITP diagnosis was 50.5 years (y) (range 1–87y); median platelet count at ITP diagnosis was 5000/ml; median time between ITP diagnosis and the start of TPO‐RA was 5 y (range 1 mo‐24y); at start of TPO‐RA 5 patients fulfilled the definition of acute, 8 of persistent and 28 of chronic ITP; 54% (22/41) were splenectomized; 55% (22/40) needed 3 3 ITP treatments before the start of the TPO‐RA (corticosteroids, intravenous immunoglobulins, rituximab, cyclophosphamide, cyclosporin, fansidar…); median platelet count at start of TPO‐RA was 11000/ml; median time on TPO‐RA was 8 mo (range 0–74 mo); median platelet count was 267000/ml at discontinuation of TPO‐RA and 177000/ml 6 mo later. 178 patients (provided by 15 centers) were treated with TPO‐RA. Of these 100 patients discontinued treatment. 21% of the total cohort discontinued TPO‐RA because of TFR and 37% of the discontinuations was due to TFR. Summary/Conclusion: Our survey confirmed that SR or TFR on TPO‐RA is seen in about 20% of ITP patients treated in daily clinical practice in Belgium. TFR is seen not only in acute or persistent ITP but also in chronic ITP. TFR is seen in patients independent of splenectomy and independent of the number of treatments given before. In the future the incidence of TFR is thought to be even higher when the use of a forced tapering schedule will become common practice.
Development of a Biocompatible Copolymer Nanocomplex to Deliver VEGF siRNA for Triple Negative Breast Cancer
Authors: Zhen Zhao, Yuanke Li, Ravi Shukla, Hao Liu, Akshay Jain, Ashutosh Barve, Kun Cheng
Journal: Theranostics (2019)

Triple negative breast cancer (TNBC) is the most difficult breast cancer subtype to treat.TNBC patients have significantly higher expression of vascular endothelial growth factor (VEGF) in tumors compared to non-TNBC patients.VEGF not only exerts its pro-angiogenic effects on endothelial cells but also acts as a survival and autocrine growth factor for VEGF receptor (VEGFR) expressing cancer cells.Silencing the expression of VEGF is therefore a potential therapy for TNBC.Methods: A novel biocompatible linear copolymer poly[bis(ε-Lys-PEI)Glut-PEG] (PLEGP) was developed to deliver VEGF siRNA for TNBC therapy.The copolymer is composed of lysine and glutaric acid, a natural metabolite of amino acids in the body.Low-molecular weight polyethyleneimine (PEI) was grafted to the copolymer to efficiently condense siRNA into nanocomplex without inducing cytotoxicity.Various in vitro studies were performed to evaluate the stability, cellular uptake, tumor penetration, and biological activities of the VEGF siRNA nanocomplex.The anti-tumor activities of the nanocomplex was also evaluated in an orthotopic TNBC mouse model.Results: PEIs with different molecular weights were evaluated, and the copolymer PLEGP 1800 was able to easily form a stable nanocomplex with siRNAs and protect them from serum degradation.The siRNA/PLEGP 1800 nanocomplex exhibited negligible cytotoxicity but showed high cellular uptake, high transfection efficiency, and high tumor penetration.In vitro activity studies showed that the siRNA nanocomplex significantly inhibited migration and invasion of TNBC cells.Moreover, the VEGF siRNA nanocomplex efficiently inhibited tumor growth in an orthotopic TNBC mouse model and down-regulated VEGF expression in the tumor.Conclusion: PLEGP 1800 is a safe and efficient copolymer to deliver siRNAs for TNBC therapy.It could potentially be applied to other cancers by changing the cargo and incorporating tumor-specific ligands.
Ending AIDS in the United States—If Not Now, When?
Authors: Diane V. Havlir, Susan P. Buchbinder
Journal: JAMA Internal Medicine (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Trust is good, control is better: technical considerations in blood microbiome analysis
Authors: Robert Schierwagen, Camila Alvarez-Silva, Florence Servant, Jonel Trebicka, Benjamin Lelouvier, Manimozhiyan Arumugam
Journal: Gut (2019)

We agree with Hornung et al 1 that studying blood microbiome is a major technical challenge with potential artefacts. At least three important challenges must be tackled:

1.  Low amount of bacterial DNA in blood.2 

2.  High amounts of PCR inhibitors.

3.  Bacterial DNA contaminants from environment, reagents and consumables.

Measuring, reducing and controlling bacterial contaminants are key elements of optimisations made on the molecular pipeline used in our study3 as well as eight published studies on blood microbiome.2 4–7 The studies from Salter et al 8 and Laurence et al 9 are useful to understand the burden of bacterial contaminants when working with low bacterial abundance samples. In former publications,2 10 we have described our procedure and the controls performed to address such contamination. One must be careful when using a fixed list of bacterial contaminants, as each experiment has its own contamination burden. Therefore, two different experiments done under different conditions, will not have the same contaminants. What is essential, as pointed out by Hornung et al , is to include and analyse negative controls in each experiment. Although not explicitly mentioned before, our study3 included the following negative controls:

1.  Extraction negative controls (water at DNA extraction step).

2.  PCR negative controls (water at first PCR step).

We …
Screening for HIV Infection in Pregnant Women
Authors: Shelley S. Selph, Christina Bougatsos, Tracy Dana, Sara Grusing, Roger Chou
Journal: JAMA (2019)

Prenatal screening for HIV can inform use of interventions to reduce the risk of mother-to-child transmission. The US Preventive Services Task Force (USPSTF) previously found strong evidence that prenatal HIV screening reduced risk of mother-to-child transmission. The previous evidence review was conducted in 2012.To update the 2012 review on prenatal HIV screening to inform the USPSTF.Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from 2012 to June 2018, with surveillance through January 2019.Pregnant persons 13 years and older; randomized clinical trials and cohort studies of screening vs no screening; risk of mother-to-child transmission or maternal or infant harms associated with antiretroviral therapy (ART) during pregnancy; screening yield at different intervals or in different risk groups.One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality.Mother-to-child transmission; harms of screening and treatment; screening yield.Sixty-two studies were included in this review, including 29 new studies. There remains no direct evidence on effects of prenatal screening vs no screening on risk of mother-to-child HIV transmission, maternal or infant clinical outcomes, or the yield of repeat or alternative screening strategies. New evidence confirms that combination ART is highly effective at reducing the risk of mother-to-child transmission, with some new cohort studies reporting rates of mother-to-child transmission less than 1% when combination ART was started early in pregnancy (when begun in first trimester, 0%-0.4%; when begun after first trimester, or at any time if timing of ART initiation not reported, 0.4%-2.8%). New evidence on harms of ART was also largely consistent with the previous review. Evidence from primarily observational studies found prenatal combination ART with a boosted protease inhibitor associated with increased risk of preterm delivery (range, 14.4%-26.1%). For other birth outcomes (low birth weight, small for gestational age, stillbirth, birth defects, neonatal death), results were mixed and depended on the specific antiretroviral drug or drug regimen given and timing of prenatal therapy.Combination ART was highly effective at reducing risk of mother-to-child HIV transmission. Use of certain ART regimens during pregnancy was associated with increased risk of harms that may be mitigated by selection of ART regimen. The 2012 review found that avoidance of breastfeeding and cesarean delivery in women with viremia also reduced risk of transmission and that prenatal screening accurately diagnosed HIV infection.
PS1278 LACTATE CLEARANCE AS A SURVIVAL PREDICTOR IN PATIENTS WITH HEMATOLOGIC DISEASES WITH SEPTIC SHOCK
Authors: I. Osipov, G. Salogub, V. Bezrukikh, V. Ivanov, E. Mikhaylov, N. Shnalieva, N. Stepanova
Journal: HemaSphere (2019)

Background: Infectious complications are one of the main causes of mortality in patients with hematological diseases. Neutropenia is common adverse effect of antitumor treatment. These patients have high risks of development severe infectious complications (sepsis and septic shock). It is known, that poor lactate clearance is associated with increased mortality in the general population of patient's. We evaluated the prognostic value of lactate clearance in patients with neutropenia grade 4 (CTCAE v4.0) Aims: To evaluate the clinical outcomes of septic shock treatment in patients with myelotoxic agranulocytosis depending on the clearance of lactate. Methods: 127 patients with septic shock were included (between July 2015 and December 2018). A prospective and retrospective diagnosis of septic shock was established on the basis of Sepsis 3 criteria: arterial hypotension in combination with an increase in lactate of more than 2.0 mmol / l. The highest incidence of septic shock (up to 35%) was registered in high‐risk group patients: during the induction remission of acute myeloid leukemia and recipients of allogeneic hematopoietic stem cells. 88 percent cases were associated with gram‐negative bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, Serratia spp. and E. coli). The median duration of neutropenia before the development of septic shock was 15.1 (13.26–17.06) and 17.72 (16.33–19.12) days in patients who died and survived (p = 0.03, Log Rank). The levels of C‐reactive protein and procalcitonin did not differ. Results: The median lactate values at the time of diagnosis of septic shock in survivors and non‐survivors patients were 2.9 (3.071 ‐ 3.997) and 4.26 (3.665–4.867) mmol / l (p = 0.05, Log rank). 30 ‐ day overall survival (OS) in patients with a lactate level of more than 4.0 mmol/l was 34%, with a lactate level of 2.0–4.0 mmol/l was 56% (p &lt;0.001, Log Rank). All patients received serial lactate measurements were divided into lactate clearance &gt;10% (n = 26), &gt;20% (n = 46), and &lt;10% (n = 55) groups. Patients with a lactate clearance of more than 10% had higher 30‐day OS (68% vs. 29%, p &lt; 0.01, Log Rank). The rate of lactate elimination (more than 10% versus more than 20%) did not have an additional effect on OS. In multivariate analysis with an additional assessment of the venous‐to‐arterial carbon dioxide tension, absolute lactate values, the prognostic value was shown only for the lactate clearance. Summary/Conclusion: Achieving lactate clearance during the first 6 hours treatment septic shock more than 10% is associated with improved 30‐day OS in patients with severe neutropenia. The advantage of this marker is an early assessment of the effectiveness of therapy. In the future, on the basis of lactate kinetics, it is possible to create the strategy of ”Early Goal‐Directed Therapy“. image
Cell-free DNA profiling of metastatic prostate cancer reveals microsatellite instability, structural rearrangements and clonal hematopoiesis
Authors: Markus Mayrhofer, Bram De Laere, Tom Whitington, Peter Van Oyen, Christophe Ghysel, Jozef Ampe, Piet Ost, Wim Demey, Lucien Hoekx, Dirk Schrijvers, Barbara Brouwers, Willem Lybaert, Els Everaert, Daan De Maeseneer, Michiel Strijbos, Alain Bols, Karen Fransis, Steffi Oeyen, Pieter-Jan van Dam, Gert Van den Eynden, Annemie Rutten, Markus Aly, Tobias Nordström, Steven Van Laere, Mattias Rantalainen, Prabhakar Rajan, Lars Egevad, Anders Ullén, Jeffrey Yachnin, Luc Dirix, Henrik Grönberg, Johan Lindberg
Journal: Genome Medicine (2018)

There are multiple existing and emerging therapeutic avenues for metastatic prostate cancer, with a common denominator, which is the need for predictive biomarkers. Circulating tumor DNA (ctDNA) has the potential to cost-efficiently accelerate precision medicine trials to improve clinical efficacy and diminish costs and toxicity. However, comprehensive ctDNA profiling in metastatic prostate cancer to date has been limited. A combination of targeted and low-pass whole genome sequencing was performed on plasma cell-free DNA and matched white blood cell germline DNA in 364 blood samples from 217 metastatic prostate cancer patients. ctDNA was detected in 85.9% of baseline samples, correlated to line of therapy and was mirrored by circulating tumor cell enumeration of synchronous blood samples. Comprehensive profiling of the androgen receptor (AR) revealed a continuous increase in the fraction of patients with intra-AR structural variation, from 15.4% during first-line metastatic castration-resistant prostate cancer therapy to 45.2% in fourth line, indicating a continuous evolution of AR during the course of the disease. Patients displayed frequent alterations in DNA repair deficiency genes (18.0%). Additionally, the microsatellite instability phenotype was identified in 3.81% of eligible samples (≥ 0.1 ctDNA fraction). Sequencing of non-repetitive intronic and exonic regions of PTEN, RB1, and TP53 detected biallelic inactivation in 47.5%, 20.3%, and 44.1% of samples with ≥ 0.2 ctDNA fraction, respectively. Only one patient carried a clonal high-impact variant without a detectable second hit. Intronic high-impact structural variation was twice as common as exonic mutations in PTEN and RB1. Finally, 14.6% of patients presented false positive variants due to clonal hematopoiesis, commonly ignored in commercially available assays. ctDNA profiles appear to mirror the genomic landscape of metastatic prostate cancer tissue and may cost-efficiently provide somatic information in clinical trials designed to identify predictive biomarkers. However, intronic sequencing of the interrogated tumor suppressors challenges the ubiquitous focus on coding regions and is vital, together with profiling of synchronous white blood cells, to minimize erroneous assignments which in turn may confound results and impede true associations in clinical trials.
Using Speech Markers to Diagnose PTSD
Authors: Jennifer Abbasi
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
PS1062 PEDIATRIC ACUTE MYELOID LEUKEMIA (AML) IN DEVELOPING COUNTRIES, BARRIERS AGAINST BETTER OUTCOME 10 YEARS’ EXPERIENCE AMONG EGYPTIAN PEDIATRIC ACUTE MYELOID LEUKEMIA
Authors: Y. Madney, N. Ezzelden, N. Elsharkawy
Journal: HemaSphere (2019)

Background: Pediatric AML outcome improved significantly with current survival rates of 70% in developed countries. The outcome of childhood AML in developing countries still lacking. Aims: The aim of the study to assess the causes of mortality and survival outcomes among pediatric AML patients in countries with limited resources. Methods: Retrospective analysis of 344 pediatric AML (2007 ‐ 2016) treated at National Cancer Institute, Egypt including 3 phases protocols with different aims and hypothesis. Results: From 2007–2010, Less intensified induction chemotherapy without antimicrobial prophylaxis ,103 patients enrolled, Complete remission (CR) post induction 1(55%), Refractory disease (34%) and induction mortality (11%). End of study; Relapse 40 %. Mortality 63 patients (61%):(42%) disease‐related (DRM), (42%) infection related (IRM) and (14%) toxicity related (TRM). 70% had fungal infections. 2 years DFS 27% and OS 30%. From 2011‐ 2013, Hypothesis was Antimicrobial prophylaxis can help for a better outcome, 136 patients enrolled used less intensified induction but with levofloxacin and voriconazole prophylaxis. CR rate induction 1 was 75%, refractory disease (17%) and induction mortality was 8%. End of study : Relapse 16%. Mortality in 86(63%) patients: 57 % IRM mostly multidrug resistance (MDR) gram‐negative bacteremia while DRM 33%. 10% had fungal infections but still poor 3y DFS (34%) and OS (37%). From 2014–2016, Hypothesis was intensified induction chemotherapy with antimicrobial prophylaxis can be a better solution; 105 patients enrolled, Post induction1, CR 48%, refractory disease 8% and induction mortality 44%. End of study; Relapse rate 6%, Mortality 88(80%) patients: IRM was 72% with MDR gram‐negative bacteremia was the main cause of deaths (62%), DRM 4% and TRM 4% with poor 2y DFS 34% and OS 24%. Summary/Conclusion: A significant gap in the outcomes of pediatric AML as compared to those reported developed countries. The balance between treatment intensification and toxicity are needed. Infections are the major barrier against better outcome needs more strict guidelines protocols.
PB2393 FROM NON‐TRANSFUSION DEPENDENCY TO TRANSFUSION DEPENDENCY: LIGHTS AND SHADOWS IN THALASSEMIA
Authors: P. Ricchi, A. Meloni, L. Pistoia, D. D’Ascola, L. Pitrolo, A. Barone, P. M. G. Sanna, L. Cuccia, R. Righi, G. Peritore, V. Positano, A. Pepe
Journal: HemaSphere (2019)

Background: Patients with non‐transfusion dependent thalassaemia (NTDT) can be placed on regular transfusional therapy either for the prevention or for the management of different complications. Aims: We retrospectively evaluated the effects of blood transfusions (BT) in the real‐life and quite extensive context of the Myocardial Iron Overload in Thalassaemia (MIOT) network where most of biochemical, cardiac, hepatic parameters and morbidities typical of the NTDT patients could be analysed and compared in a chronologically manner. Methods: 147 NTDT patients (46.49 ± 12.27 years; 92 females) who started regular BT at the mean age of 21.84 ± 17.85 years were considered. Magnetic Resonance Imaging (MRI) was used to quantify iron overload (T2∗ technique) and biventricular morphological and functional parameters (cine sequences). Results: For the 40% of the patients there were more than two indications for the transition to regular BT, with anemia being present in the 92.5% of the cases. The patients reached a pre‐transfusion hemoglobin of 9.64 ± 0.72 g/dl. The percentage of chelated patients increased significantly after starting regular BT (52.5% vs 91.7%; P &lt; 0.00001). Table 1 shows the changes (6 months before vs 6 months after starting regular BT) in the haematochemical and iron‐overload parameters. A down‐regulation of all erythropoietic and/or haemolysis indices and a drop‐in platelets and white blood cell count were detected. No changes in serum ferritin, MRI liver iron concentration (LIC) and global heart T2∗ values were detected. There was a significant decrease of the left ventricular end‐diastolic volume index (101.58 ± 19.67 ml/m2 vs 91.65 ± 20.99; P = 0.050). After the start of regular BT, patients were followed‐up for 24.08 ± 15.62 years. There was a significant increase in the frequency of endocrinopathies (diabetes, hypogonadism, hypothyroidism and osteopenia), bone pain, infections, and alloimunization, but their prevalence remained lower than 20%. A positive impact on patients’ health‐related quality of life was detected, with the sense of well‐being passing from 16.4% to 73.0% (P &lt; 0.0001). Summary/Conclusion: Following the use of regular BT and chelation therapy, only a mild increase in most of the complications evaluated in the analysis was recorded; we cannot exclude that it could be ascribable to aging per se, as it happens for general population. No increase in iron overload parameters was detected and conversely, we recorded a positive cardiac remodelling. Therefore, in the Italian context, the decision to regularly transfuse patients with NTDT, despite sometimes complex and problematic, may represent a way to prevent or slow down the natural progression of the disease and improve the patients overall quality of life. image