tbuckley/cabot-search huggingface dataset:
The Impact of HLA Mismatch Direction on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in AML Patients
Authors: Wen-Chun Chen, Jyh-Pyng Gau, Liang-Tsai Hsiao, Chia-Jen Liu, Yao-Chung LIU, Hao-Yuan Wang, Po-Shen Ko, Jin-Hwang Liu, Tzeon-Jye Chiou
Journal: Blood (2019)
Selinexor Combined with Ibrutinib Demonstrates Tolerability and Efficacy in Advanced B-Cell Malignancies: A Phase I Study
Authors: Deborah M. Stephens, Ying Huang, Akwasi Agyeman, Amy S. Ruppert, Boyu Hu, Natalie Turner, Renee Vadeboncoeur, Kerry A Rogers, Seema A. Bhat, Basem M. William, Samantha Jaglowski, Hank Lockman, Martha Glenn, Rosa Lapalombella, John C. Byrd, Jennifer Woyach
Journal: Blood (2019)
Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial
Authors: Désirée van der Heijde, In-Ho Song, Aileen L Pangan, Atul Deodhar, Filip van den Bosch, Walter P Maksymowych, Tae-Hwan Kim, Mitsumasa Kishimoto, Andrea Everding, Yunxia Sui, Xin Wang, Alvina D Chu, Joachim Sieper
Journal: The Lancet (2019)
痣数和 <i>MC1R R</i> 等位基因对黑色素瘤风险有一定贡献
Authors: D.L. Duffy, K.J. Lee, K. Jagirdar, A. Pflugfelder, M.S. Stark, E.K. McMeniman, H.P. Soyer, R.A. Sturm
Journal: British Journal of Dermatology (2019)

黑色素瘤是皮肤癌的最危险形式:全世界约 15% 的病例致死,但通过早期发现,其生存率可优于 95%。多痣或红色毛发会增加患黑色素瘤的风险;拥有某些特定类型的MC1R基因(称为R等位基因)是红色毛发的主要原因,也使黑色素瘤风险增加。这项来自澳大利亚的研究旨在发现这两个危险因素共同增加的黑色素瘤风险是否比简单地将这两个风险水平相加得到的风险更大。611 名黑色素瘤患者和 656 名未患黑色素瘤的患者捐赠 DNA 样本,研究人员记录他们在 21 岁时大痣的数目、皮肤和眼睛颜色以及毛发颜色。作者发现,红色毛发和超过 20 颗大痣的人患黑色素瘤的可能性是0‐4颗痣和黑褐色毛发的人的 10 倍。特别是从人们携带的 MC1R 基因的类型来看,有超过 20 颗痣和 MC1R R/R 基因型的人患黑色素瘤的可能性是 0‐4 颗痣和有 MC1R 野生型/野生型(一致)基因型的人的 25 倍。R/R 基因型(有或没有红色毛发表型)和高痣数本身都是很强的黑色素瘤危险因素,但将它们组合在一起会导致黑色素瘤的极高风险。在澳大利亚,年龄 75 岁以下的男性发生黑色素瘤的终生绝对风险是,有超过 20 颗痣和 MC1R R/R 基因型的男性为 23.3%,女性为 19.3%,而有 0‐4 颗痣和有 MC1R 野生型/野生型基因型的男性为 0.8%,女性为 0.7%。这高于其他癌症中的筛查风险阈值,因此,作者建议医生应定期检查多痣和红色毛发的患者中是否出现黑色素瘤,并建议对多痣但非红色毛发的患者也应进行检查,以确定他们是否有 MC1R R/R 基因型。
Sierra Clinical Trial Dosimetry Results Support Low Dose Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] for Targeted Lymphodepletion Prior to Adoptive Cell Therapy
Authors: Rajneesh Nath, Eileen M Geoghegan, Matthew L. Ulrickson, Jennifer A Spross, Renee H Lichtenstein, Sandy Konerth, Darrell R. Fisher, Qing Liang, Dale Ludwig, Vijay Reddy, Mark S. Berger, Boglarka Gyurkocza
Journal: Blood (2019)
The MEK Inhibitor Trametinib Enhances Diverse T Cell Reconstitution with Suppressing Xenogeneic Graft-Versus-Host-Disease
Authors: Hidekazu Itamura, Hiroyuki Muranushi, Takero Shindo, Kazutaka Kitaura, Seiji Okada, Tadasu Shin-I, Ryuji Suzuki, Akifumi Takaori-Kondo, Shinya Kimura
Journal: Blood (2019)
Transgenic Expression of IL15 in CD123-Specific BiTE-Secreting Engager T-Cells Results in Improved Anti-AML Activity
Authors: Hong Mu-Mosley, Lauren B Ostermann, Muharrem Muftuoglu, Wendy Schober, Nalini B Patel, Abishek Vaidya, Challice L. Bonifant, Stephen Gottschalk, Mireya Paulina Velasquez, Michael Andreeff
Journal: Blood (2019)
IMMU-27. IMMUNE CHECKPOINT BLOCKADE OF EX VIVO EXPANDED T CELLS FOR USE IN ADOPTIVE CELLULAR THERAPY (ACT) FOR GLIOBLASTOMA
Authors: Elizabeth Ogando-Rivas, Changlin Yang, Paul Castillo, Anjelika Dechkovskaia, Duane Mitchell
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Despite aggressive treatments, GBM continues to have unacceptably high mortality rates. Immune-checkpoint blockade and ACT have shown excellent results in other solid tumors, especially in melanoma. Unfortunately, these results have not been extrapolated to GBM. We have developed a novel platform for ACT using tumor mRNA-pulsed dendritic cells(DCs) to in-vitro expand polyclonal populations of tumor-reactive T-cells. This platform has shown promising effects in preclinical brain tumor models (Flores et al OncoImmunology 2015, Wildes et al CCR 2018, Flores et al NatureComm 2018) and being evaluated in clinical trials at UF Health (NCT02465268,NCT03334305). STUDY OBJECTIVE Evaluate whether immune-checkpoint blockade during ex-vivo expansion of antigen-specific T-cells impact their use in ACT. METHODS CMVpp65 was used as model antigen for in-vitro activation of T-cells. Mature pp65 mRNA-pulsed DCs from CMV+ healthy donors were co-cultured with T-cells in IL2-containing medium for 15days. We tested four checkpoint inhibitor groups: PD1(n= 6), PDL1(n= 4), TIM3(n= 7) and PD1+TIM3(n= 6) that were compared with non-blockade group, respectively. Checkpoint blockade was performed every 3days. T-cell proliferation, immune-phenotyping, and IFN-g release were analyzed. RESULTS Cell proliferation was lower in all the blockade groups but significantly lower in the TIM3 (p= 0.03) and TIM3+PD1 (p= 0.01) blockade groups. TIM3 expression was significantly lower in the TIM3 (p= 0.006) and PD1+TIM3 blockade groups (p= 0.0001). There was a trend of reduced pp65 tetramer positive in the TIM3 and PD1+TIM3 blockade groups (PD1+TIM3 subgroup at 3mcg/mL, p= 0.02) and lower INFg release in the TIM3 and PD1+TIM3 blockade groups. CONCLUSION The exact role of checkpoints during expansion of T-cells for ACT is not well understood. In our study checkpoint blockade with PD-1 or TIM-3 alone or in combination did not enhance T-cell expansion or function, in fact, appeared to have an inhibitory effect on measured parameters. Our results suggest that TIM-3 may have an activating role in our system.
Historical Analysis of a Cohort of Chilean Patients Treated with Autologous Stem Cell Transplantation Since 1993: Optimization of Stem Cell Collections, Risk Factors for Poor Mobilizers and Efficient Plerixafor Use
Authors: Mauricio Sarmiento Maldonado, Jara Veronica, Silvana Arellano, Soto Katherine, Carla Lorca, Isabel Pizarro, Pablo Bertin, Mauricio Galleguillos, Elizabeth Rivera, Isabel Rodriguez, Nicole Beffermann, Mauricio Ocqueteau, Jaime Pereira
Journal: Blood (2019)
Safe and Efficient Peripheral Blood Stem Cell Collection in Patients with Sickle Cell Disease Using Plerixafor
Authors: Alexis Leonard, Naoya Uchida, David F. Stroncek, Sandhya R. Panch, Kamille West, Eoghan George Molloy, Tom Hughes, Sara Hauffe, Tiffani Taylor, Courtney D. Fitzhugh, Jane S. Hankins, Megan Wilson, Akshay Sharma, Shengdar Q. Tsai, Mitchell J. Weiss, Matthew Hsieh, John F. Tisdale
Journal: Blood (2019)
GENE-16. NEXT GENERATION SEQUENCING IDENTIFIES IDH-1, ATRX, TP53 MUTATION AND MYCN AMPLIFICATION IN GLIOBLASTOMA WITH EXTENSIVE SUBARACHNOID SPREAD: A CASE REPORT
Authors: Kyu Sang Lee, Gheeyoung Choe
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma showing primarily extensive subarachnoid spreading has much worse prognosis than intracortical glioblastoma. Nevertheless, their genetic pathogenesis is still unknown due to its low incidence. Present report is a rare case of glioblastoma with primitive neuroectodermal tumor (PNET)-like feature, showing extensive subarachnoid spread, as well as the distinguishing result of its molecular analysis using next generation sequencing (NGS). A 37-year-old male presented with a new onset, severe headache. Magnetic resonance imaging test revealed a diffuse infiltrative mass in the right frontal lobe. The tumor was also spread broadly in subarachnoid space. The patient underwent craniotomy and tumorectomy. Microscopically, glioblastoma showed PNET-like feature. Tumor cells had high nuclear/cytoplasmic ratios, oval, slightly elongated or angulated hyperchromatic nuclei, markedly increased mitotic activity, and obvious apoptotic bodies. Immunohistochemical test showed partly positivity of GFAP, CD56 and synaptophysin. For comprehensive genomic profiling, we assessed NGS based on the SNUBH Brain v1.0 (Macrogen, Seoul, South Korea) panel. This panel is designed to include all genes known to be somatically altered in human brain tumor. IDH-1 (p.Arg132His) mutation and two frame shift genetic alteration including ATRX (p.Tyr2208fs) and TP53 (p.Pro301fs) were found. Additionally, MYCN (2p24.3) amplification was identified. Estimated MYCN copy number was 18. Despite the post-operative therapy including temozolomide and radiotherapy, the tumor aggressively progressed and the patient expired nine months after the first symptom onset. Although there have been several previous reports of MYCN amplification in glioblastoma with PNET-like feature, this is the first case report which finding in glioblastoma, IDH-mutant type. IDH-1 mutation and younger age are usually associated with a better prognosis in glioblastoma patients. However, our case may suggest that when MYCN amplification coexists in IDH-mutant type, the tumor behavior could be contrarily aggressive.
Identifying patients with NTRK fusion cancer
Authors: J.P. Solomon, R. Benayed, J.F. Hechtman, M. Ladanyi
Journal: Annals of Oncology (2019)

Due to the efficacy of tropomyosin receptor kinase (TRK) inhibitor therapy and the recent Food and Drug Administration approval of larotrectinib, it is now clinically important to accurately and efficiently identify patients with neurotrophic TRK (NTRK) fusion-driven cancer. These oncogenic fusions occur when the kinase domain of NTRK1, NTRK2 or NTRK3 fuse with any of a number of N-terminal partners. NTRK fusions are characteristic of a few rare types of cancer, such as secretory carcinoma of the breast or salivary gland and infantile fibrosarcoma, but they are also infrequently seen in some common cancers, such as melanoma, glioma and carcinomas of the thyroid, lung and colon. There are multiple methods for identifying NTRK fusions, including pan-TRK immunohistochemistry, fluorescence in situ hybridisation and sequencing methods, and the advantages and drawbacks of each are reviewed here. While testing algorithms will obviously depend on availability of various testing modalities and economic considerations for each individual laboratory, we propose triaging specimens based on histology and other molecular findings to most efficiently identify tumours harbouring these treatable oncogenic fusions.
Elevated Plasma sIL-2Rα Levels in Primary Myelofibrosis Play a Distinct Role on Disease Progression in JAK2V617F and Calr Mutants
Authors: Giovanni Barosi, Rita Campanelli, Paolo Catarsi, Mara De Amici, Carlotta Abbà, Gianluca Viarengo, Laura Villani, Margherita Massa, Vittorio Rosti
Journal: Blood (2019)
Mutation of the CD28 Co-Stimulatory Domain Confers Enhanced CAR T Cell Function
Authors: Justin C. Boucher, Gongbo Li, Hiroshi Kotani, Maria Cabral, Dylan Morrissey, Sae Bom Lee, Kristen Spitler, Nolan Beatty, Bishwas Shrestha, Bin Yu, Aslamuzzaman Kazi, Xuefeng Wang, Said Sebti, Marco L. Davila
Journal: Blood (2019)
Human CD83 Targeted Chimeric Antigen Receptor T Cell for the Prevention of Graft Versus Host Disease and Treatment of Myeloid Leukemia
Authors: Bishwas Shrestha, Kelly Walton, Jordan Reff, Elizabeth M. Sagatys, Nhan Tu, Justin C. Boucher, Tayyeb Ghafoor, Joseph Pidala, Bruce R. Blazar, Claudio Anasetti, Brian C. Betts, Marco L. Davila
Journal: Blood (2019)
A Phase I/II Dose-Escalation Study of Thiotepa-Based Immunochemotherapy in Relapsed/Refractory Primary Central Nervous System Lymphoma; The Tier Trial
Authors: Christopher P Fox, Ayesha S Ali, Dorothee Auer, Steffi Thust, Aimee E Jackson, Louise Hopkins, Catherine Thomas, Nicolas Martinez-Calle, Graham P. Collins, Shireen Kassam, Josh Wright, David Lewis, Andres JM Ferreri, Sridhar Chaganti, Jeffery Smith, Kim Linton, Ian Chau, Dominic J. Culligan, Andrew Davies, Roderick Johnson, Kate Cwynarski
Journal: Blood (2019)
INNV-33. BARRIERS TO ACCRUAL AND ENROLLMENT IN BRAIN TUMOR TRIALS
Authors: Eudocia Lee, Ugonma Chukwueke, Shawn Hervey-Jumper, John DeGroot, Pablo Leone, Terri Armstrong, Susan Chang, David Arons, Kathy Oliver, Kay Verble, Al Musella, Nicole Willmarth, Brian Alexander, Amanda Bates, Lisa Doherty, Evanthia Galanis, Sarah Gaffey, Thomas Halkin, Bret Friday, Maryam Fouladi, Nancy Lin, David Macdonald, Minesh Mehta, Marta Penas-Prado, Michael Vogelbaum, Solmaz Sahebjam, David Sandak, Martin van den Bent, Michael Weller, David Reardon, Patrick Wen
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND A major impediment to improving neuro-oncology outcomes is poor clinical trial accrual. METHODS We convened a multi-stakeholder group including Society for Neuro-Oncology, Response Assessment in Neuro-Oncology, patient advocacy groups, clinical trial cooperative groups, and other partners to determine how we can improve trial accrual. RESULTS We described selected factors contributing to poor trial accrual and possible solutions. We focused on patient and community factors, disparities, physician and provider factors, clinical trial factors, and site and organizational factors CONCLUSIONS We will implement strategies with the intent to double accrual to neuro-oncology trials over the next 5 years.
Diffuse Large B Cell Lymphoma (DLBCL) Expresses ROR1 and a ROR1 Small Molecule Inhibitor (KAN0441571C) Induced Significant Apoptosis of Tumor Cells
Authors: Mohammad Hojjat-Farsangi, Amineh Ghaderi, AmirHossein Daneshmanesh, Jemina Lehto, Ali Moshfegh, Parviz Kokhaei, Jan Vågberg, Elisabeth Olsson, Charlotta Löfberg, Charlotta Carina Norström, Johan Schultz, Martin Norin, Thomas Olin, Elias Drakos, George Z. Rassidakis, Anders Österborg, Håkan Mellstedt
Journal: Blood (2019)
EXTH-15. INCREASING THE TRAFFICKING OF DENDRITIC CELLS VIA CXC CHEMOKINE SIGNALING PATHWAY LEADS TO IMPROVED ANTI-TUMOR EFFICACY OF DENDRITIC CELL VACCINES
Authors: Farhad Dastmalchi, Aida Karachi, Changlin Yang, Hassan Azari, Alex Vlasak, Megan Saia, Duane Mitchell, Maryam Rahman
Journal: Neuro-Oncology (2019)

Abstract Dendritic cell (DC) vaccine efficacy is directly related to the efficiency of DC migration to the lymph node after delivery to the patient. In this research we discovered increasing cell migration by utilizing sarcosine improved anti-tumor efficacy. We hypothesized that sarcosine induced cell migration was due to chemokine or cytokine signaling. METHODS To generate DC vaccines, DCs were harvested from bone marrow of wild type C57BL/6 mice and electroporated with OVA-mRNA. Human DCs were isolated from PBMCs. DCs were treated with sarcosine at 20mM. OT-I T cells were isolated from transgenic mice and injected intravenously into B16F10-OVA tumor bearing mice. Following T cell transfer, DC vaccines were injected intradermal. In vitro migration was analyzed via transwell migration assay. In vivo migration was evaluated by flow-cytometry and immunofluorescence microscopy. Gene expression in RNA was investigated in DCs via RT-PCR and Nanostring. RESULTS Sarcosine significantly increases human and murine DC migration in vitro. In vivo murine model, sarcosine-loaded DCs had significantly increased migration to both the lymph nodes and spleen after intradermal delivery. B16F10-OVA tumor bearing mice were treated with the sarcosine-loaded DC vaccines resulted in a significant survival advantage over control and naïve DC vaccines. Gene expression in RNA was investigated in DCs. CXCR2,CXCL3 and CXCL1 were found to be upregulated in sarcosine-loaded DCs. Further metabolic analysis demonstrated the upregulation of cyclooxygenase-1 and Pik3cg. In vitro DC migration in presence of CXCR2 neutralizing antibody showed sarcosine induced migration was abrogated by adding the CXCR2 neutralizing antibody in both human and murine DCs. Animals that treated with sarcosine-loaded DC showed significantly better tumor control compares to the animals receiving anti-CXCR2 antibody one hour before DC injection. CONCLUSION Sarcosine increases the migration of murine and human DCs via the CXC chemokine pathway. This platform can be utilized to improve existing DC vaccine strategies.
Anti-MiR-126 Therapy for Inv(16) Acute Myeloid Leukemia
Authors: Lianjun Zhang, Le Xuan Truong Nguyen, Dijiong Wu, Casey J Brewer, Xin He, Man Li, Dandan Zhao, Guerry Jeanne Cook, Jing Qi, Herman Wu, Bin Zhang, Ling Li, Marcin Kortylewski, Guido Marcucci, Ya-Huei Kuo
Journal: Blood (2019)
Out of Focus: Increase of the Excess Longitudinal Range in Coronary Computed Tomographic Angiography
Authors: Thomas J. Stocker, Mathias Heckner, Jonathon Leipsic, Martin Hadamitzky, Simon Deseive, Stephan Achenbach, Marcus Y. Chen, Ronen Rubinshtein, Jeroen J. Bax, Marcio S. Bittencourt, Uday M. Jadhav, Thomas Schlosser, Subramaniyan Ramanathan, Jeannie H. Yu, Steffen Massberg, Jörg Hausleiter
Journal: JACC. Cardiovascular imaging (2019)
Childhood Pancreatitis and Risk for Incident Diabetes in Adulthood
Authors: Cole D. Bendor, Aya Bardugo, Inbar Zucker, Tali Cukierman-Yaffe, Miri Lutski, Estela Derazne, Tammy Shohat, Ofri Mosenzon, Dorit Tzur, Ari Sapir, Orit Pinhas-Hamiel, Richard G. Kibbey, Itamar Raz, Arnon Afek, Hertzel C. Gerstein, Amir Tirosh, Gilad Twig
Journal: Diabetes Care (2019)

OBJECTIVE The relationship between acute pancreatitis and incident diabetes is unclear. We assessed whether a resolved single event of acute pancreatitis in childhood was associated with incident diabetes in adulthood. RESEARCH DESIGN AND METHODS A nationwide, population-based study of 1,802,110 Israeli adolescents (mean age 17.4 years [range 16–20]) who were examined before compulsory military service between 1979 and 2008 and whose data were linked to the Israeli National Diabetes Registry (INDR). Resolved pancreatitis was defined as a history of a single event of acute pancreatitis with normal pancreatic function at enrollment. Logistic regression analysis was applied. RESULTS Incident diabetes developed in 4.6% of subjects with resolved pancreatitis (13 of 281; none of these cases were identified as type 1 diabetes) and 2.5% among the unexposed group (44,463 of 1,801,716). Resolved acute pancreatitis was associated with incident diabetes with an odds ratio (OR) of 2.23 (95% CI 1.25–3.98) with adjustment for age, sex, and birth year. Findings persisted after further adjustments for baseline BMI and sociodemographic confounders (OR 2.10 [95% CI 1.15–3.84]). Childhood pancreatitis was associated with a diagnosis of diabetes at a younger age, with 92% of diabetes case subjects diagnosed before 40 years of age compared with 47% in the unexposed group (P = 0.002). The association accentuated when the study sample was limited to individuals of unimpaired health or normal BMI at baseline. CONCLUSIONS A history of acute pancreatitis in childhood with normal pancreatic function in late adolescence is a risk factor for incident type 2 diabetes, especially at young adulthood.
Sharing data safely while preserving privacy
Authors: Giske Ursin, Nea Malila, Jenny Chang-Claude, Marc Gunter, Rudolf Kaaks, Ellen Kampman, Mats Lambe, Flora van Leeuwen, Patrik Magnusson, Mef C Nilbert, Pål R Romundstad, Martin Röösli, Anne Lise Ryel, Isabel dos-Santos-Silva, Magnus Stenbeck, Hans H Storm, Anthony Swerdlow, Paolo Vineis, Gun Peggy S Knudsen
Journal: The Lancet (2019)
Ruxolitinib Shows Efficacy in Patients with Newly-Diagnosed Polycythemia Vera: Futility Analysis of the Randomized Ruxo-BEAT Clinical Trial of the German Study Group for Myeloproliferative Neoplasms
Authors: Steffen Koschmieder, Susanne Isfort, Dominik Wolf, Florian H. Heidel, Philippe Schafhausen, Martin Griesshammer, Denise Wolleschak, Uwe Platzbecker, Konstanze Döhner, Philipp J. Jost, Stefani B. Parmentier, Nikolas von Bubnoff, Frank Stegelmann, Angela Maurer, Jeremy Franklin, Martina Crysandt, Deniz Gezer, Martin Hellmich, Tim H Brümmendorf
Journal: Blood (2019)
Pregenomic HBV RNA and Hepatitis B Core‐Related Antigen Predict Outcomes in Hepatitis B e Antigen–Negative Chronic Hepatitis B Patients Suppressed on Nucleos(T)ide Analogue Therapy
Authors: Ivana Carey, Jeffrey Gersch, Bo Wang, Christiana Moigboi, Mary Kuhns, Gavin Cloherty, Geoffrey Dusheiko, Kosh Agarwal
Journal: Hepatology (2019)

A dichotomous separation of hepatitis B viral DNA and hepatitis B surface antigen (HBsAg) concentrations occurs during the natural history and treatment of chronic hepatitis B. We have evaluated the ability of hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg) as surrogates of silencing of covalently closed circular DNA (cccDNA), to characterize this dissociation, and virological outcomes.Three cohorts of hepatitis B e antigen (HBeAg)-negative patients were studied: cohort A: 66 HBeAg-negative patients on long-term nucleos(t)ide analogue (NA) therapy; cohort B: 23 antibodies against hepatitis B e antigen (anti-HBe)-positive patients who stopped treatment; and Cohort C: 19 anti-HBe-positive patients on long-term NA treatment who achieved HBsAg loss and in whom treatment was withdrawn. Concentrations of HBV serological/virological biomarkers (HBV DNA, HBsAg, HBcrAg, and HBV RNA) were measured in sequential samples at different time points on/off therapy. Cohort A: After 3 years of antiviral therapy, 33% and 30% had detectable HBcrAg and HBV RNA, respectively, despite all being HBV-DNA negative. After 5 years' therapy with NA, 27% and 14% had detectable HBcrAg and HBV RNA. Detectable HBcrAg and HBV RNA at the time of treatment withdrawal was only observed in those patients who developed a severe aminotransferase flare. Only those patients with HBV reactivation in cohort C had detectable HBV RNA at treatment withdrawal, but HBcrAg and HBV DNA were not detected.HBcrAg and HBV RNA are sensitive biomarkers of continued transcription of cccDNA in HBeAg-negative patients despite marked HBV-DNA suppression by NA. These markers were predictors of severe alanine transaminase flares, after treatment withdrawal, and HBV-DNA reactivation. Their measurement during the natural history of hepatitis B, and on treatment with current and new agents, could characterize residual HBV-RNA transcription from cccDNA and assist drug development and disease management.
Next-Generation Sequencing of HLA Loci Identifies Predisposing and Protective Factors for Immune-Mediated Thrombotic Thrombocytopenic Purpura in a Japanese Population
Authors: Kazuya Sakai, Masataka Kuwana, Hiroto Kojima, Hidenori Tanaka, Masayuki Kubo, Hideo Yagi, Masanori Matsumoto
Journal: Blood (2019)
Does surgery reduce knee osteoarthritis, meniscal injury and subsequent complications compared with non-surgery after ACL rupture with at least 10 years follow-up? A systematic review and meta-analysis
Authors: Teodor Lien-Iversen, Daniel Barklin Morgan, Carsten Jensen, May Arna Risberg, Lars Engebretsen, Bjarke Viberg
Journal: British Journal of Sports Medicine (2019)

Objective We compared long-term follow-up from surgical versus non-surgical treatment of ACL rupture regarding radiographic knee osteoarthritis (OA), secondary surgery, laxity and patient-reported outcome measures (PROMs). Design Systematic review and meta-analysis. Data sources Embase, MEDLINE, CINAHL and the Cochrane Library databases. Eligibility criteria for selecting studies Studies directly comparing the minimally invasive surgical (arthroscopy or miniarthrotomy) and non-surgical treatment of ACL rupture with at least 10 years of follow-up in adult patients were included. Results Five studies met the eligibility criteria. A meta-analysis revealed a higher risk of radiographic knee OA and a lower risk of secondary meniscal surgery for patients in the surgical group. The risk of graft rupture/secondary ACL revision and secondary ACL reconstruction was equal in the surgical and non-surgical groups. Knee laxity was lower among patients in the surgical group in four studies. No difference was found in the PROMs (ie, International Knee Documentation Committee, Tegner, Knee Injury and Osteoarthritis Outcome, and Lysholm scores). Conclusion The risk of radiographic knee OA was higher, but the risk of secondary meniscal injury was lower 10 years after surgical treatment of ACL rupture. The risk of graft rupture/secondary ACL revision or secondary reconstruction was unrelated to treatment type. The degree of knee laxity was reduced after surgical treatment in comparison with non-surgical treatment, while PROMs were similar. However, due to the methodological challenges highlighted in this systematic review, these findings must be interpreted with caution. PROSPERO registration number CRD42019119468