bluuebunny/crossref_metadata_2025 huggingface dataset:
performance circense no primeiro cinema
Authors: Magalhães Raquel
Published: November 2020

Este artigo tem por objetivo analisar de que maneiras a performance circense e a imagem-movimento se aproximam no contexto do primeiro cinema. Para tanto, foram analisados 6 filmes americanos exibindo atos de circo entre 1894-1901.
discurso cinematográfico sobre Brasília e a ideologia desenvolvimentista
Authors: Oliveira João Gabriel de
Published: November 2020

A produção audiovisual sobre Brasília, importante veículo ideológico do nacional-desenvolvimentismo, passa a criticar este projeto nas décadas de 1960 e 1970. Relacionando cinema, história e o debate sobre Teoria Marxista da Dependência, as limitações do projeto desenvolvimentista são discutidas.
Brasileiras por trás das câmeras do cinema
Authors: Marques Barbara , Weinmann Amadeu
Published: November 2020

Nesta pesquisa, articulamos a teoria psicanalítica com teóricas feministas do cinema os quais evidenciam as relações de domínio e submissão entre homens e mulheres presentes no inconsciente patriarcal e na cultura, onde o cinema surge como tecnologia de gênero, engendrando formas de subjetivação de homens e de mulheres por processos de identificação.
Morphological and molecular characterisation of populations of Longidorus longicaudatus Siddiqi, 1962 and L. americanus Handoo, Carta, Skantar, Ye, Robbins, Subbotin, Fraedrich & Cram, 2005 from Florida, USA
Authors: Inserra Renato N. , Troccoli Alberto , Vau Silvia , Subbotin Sergei A.
Published: November 2020

Two populations of needle nematode, Longidorus longicaudatus Siddiqi, 1962, are described from Quercus hemisphaerica, Q. nigra and Q. virginiana from north Florida, USA. These populations are characterised morphologically by females having a body shorter than 3800 μm, a rounded or slightly flattened lip region, an amphidial fovea pouch-like often with two symmetrical lobes, an odontostyle 99-110 μm long, a conoid tail ending in a bluntly pointed terminus, ranging values of ratio c′ greater than 2, and males very rare. The polytomous code for these populations is A34, B23, C2, D23, E2, F12, G12, H6, I12, J1, K6. Although the morphology and morphometrics of these two populations fit the original description of Longidorus longicaudatus, Florida specimens have greater diameters of lip region, mid and anal body than those of the five type specimens used for the description of this species. The Florida L. longicaudatus is similar to L. paralongicaudatus, but differs from the paratypes of this species in having smaller and greater values of ratios c (53.8 (43.8-64.5) vs 79.2 (61.9-103.5)) and c′ (2.4 (2.1-2.9) vs 1.8 (1.5-2.0)), respectively, and longer tail (60 (53-67) vs 46 (36-53) μm). Molecular characterisation of one of the two Florida L. longicaudatus populations was made based on the D2-D3 of 28S rRNA, ITS1 rRNA and COI gene sequences. The results of the ITS1 rRNA gene sequence analysis indicated that it is genetically different from L. paralongicaudatus. A few specimens of a needle nematode associated with L. longicaudatus were identified morphologically and molecularly as the pine needle nematode, L. americanus. This detection is a new record of the occurrence of the pine needle nematode in Florida.
Historical Rupture or Continuity?
Authors: Edres Nijmi
Published: November 2020

From the point of view of the institutional legal history of shariʿa courts in Israel, the article focuses on the elements of rupture and/or continuity introduced by the appointment of Hanāʾ Manṣūr-Khaṭīb as the first female judge in Israeli religious courts against the background of three main elements, the subordination of shariʿa courts to the Israeli legal system, the reaction of shariʿa courts to the challenges posed by secular and conservative Muslim actors inside the Palestinian minority, and the definition of gender roles in the Muslim judiciary in Israel. Despite some elements of rupture with the past, the article argues that the appointment is part and continuation of an active strategy of the pragmatic use of “the past” of Islamic legal tradition already pursued by shariʿa courts since 1995, and that the appointment of Manṣūr-Khaṭīb can be inscribed in a framework of “patriarchal liberalism,” following the definition of Moussa Abou Ramadan, proving that, still, gender is anything but irrelevant.
An Analysis of Jordanian Jurisdiction as a Seat for International Arbitration
Authors: Aladwan Zaid M. , Aladwan Mutaz M.
Published: November 2020

Arbitration is the best method to resolve a dispute, due to the flexibility in its mechanism and issuing of a final judgment, known as an ‘award’. The winning party usually seeks to apply that award in the state where the assets of the losing party exist. In this regard, the New York Convention 1958 guarantees that the award is enforceable in the state where the winning party sought to apply. Jordan is party to the Convention; it has regulated its own arbitration law and has adopted the UNCITRAL Model Law 1985. However, not all provisions were adopted where specific provisions in Jordanian law relating to certain matters differed from the Model Law provisions. These differences may positively or adversely affect the arbitration procedure in Jordan.
By Grace: Recognition of Religious Minority Associations in Denmark from the Reformation until 2018
Authors: Warburg Margit
Published: November 2020

In Denmark, the recognition of religious minority associations dates back to absolutism in the late 1600s when it was exerted by royal grace. However, the legal basis was not established as foreseen in the constitution of 1849, and recognition continued to be an ad hoc administrative act, which was modelled over the acts of grace during absolutism. By tradition, the cases were handled by the bishop of Copenhagen. After a criticism of this practice, the government established an expert committee in 1998 to take over the work of the bishop. In the absence of a dedicated law, the committee developed rules for recognition. The considerations and experiences of the expert committee are discussed in light of theories of contemporary public governance and with a view to the ‘by grace’ principle of absolutism. The article also discusses the preparation of the first law on recognition of religious minority associations from 2018.
Ixodidae (Acari: Ixodoidea): descriptions and redescriptions of all known species from 1758 to December 31, 2019
Authors: GUGLIELMONE ALBERTO A. , PETNEY TREVOR N. , ROBBINS RICHARD G.
Published: November 2020

References to the descriptions and redescriptions of the 742 species of Ixodidae published from 1758 to December 31, 2019 are compiled, with the goal of enabling tick taxonomists to readily access this diffuse and often confusing literature. Additionally, data resulting from this effort are critically analyzed to demonstrate the problems attending correct identification of several tick species that are of medical, veterinary and/or evolutionary importance, and to highlight the need for new or enhanced diagnostic techniques. Recent morphological and molecular studies indicate that some ixodid species names represent more than one taxon; therefore, it is expected that new species will be described in the near future, based partly on material already deposited in museums around the world.
Role of the Atmospheric Moisture Budget in Defining the Precipitation Seasonality of the Great Lakes Region
Authors: Minallah Samar , Steiner Allison L.
Published: November 2020

Precipitation in the Great Lakes region has a distinct seasonal cycle that peaks in early summer, followed by a decline in August and a secondary peak in September. This seasonality is often not captured by models, which necessitates understanding of the driving mechanisms to ascertain the model biases. This study analyzes the atmospheric moisture budget using reanalysis datasets to assess the role of regional evapotranspiration and moisture influx from remote origins in defining the precipitation seasonality, and to understand how the Great Lakes modulate spatial patterns and magnitudes of these components. Specifically, the land–water thermal contrast yields large seasonal variations in the evaporative fluxes and creates distinctive localized spatial patterns of moisture flux divergence. We find considerable month-to-month variations in both evapotranspiration and the net moisture transport through the boundaries, where they play a cooperative (contrasting) role in amplifying (dampening) the moisture content available for precipitation and total precipitable water. Our seasonal analysis suggests that the misrepresentation of the budget quantities in models, for example, in simulation of moisture transport processes and parameterization schemes, can result in an anomalous precipitation behavior and, in some cases, violation of the atmospheric moisture mass balance, resulting in large residual magnitudes. We also identify conspicuous differences in the representation of moisture budget components in the various reanalyses, which can alter their representation of the regional hydroclimates.
Variability of Multisite Decadal Running Means Arising from Year-To-Year Fluctuations
Authors: Zheng Xiaogu , Frederiksen Carsten S.
Published: November 2020

Decadal mean variables are frequently used to characterize decadal climate variabilities. Decadal means are often calculated using yearly data, which can represent variability at time scales from annual to centennial. Residuals from interannual fluctuations may contribute to the variability in decadal time series. Such variability is more difficult to be predicted at the long range. Removing it from the decadal variability means that the remaining variability is more likely to arise from slowly varying multidecadal or longer time scale external forcing and internal climate dynamics, which are more likely to be predicted. Here, a new approach is proposed to understand the uncertainty, potential predictability, and drivers of decadal mean variables. The covariance matrix of multivariate decadal running means is decomposed into unpredictable fast decadal variability and the potentially predictable slow decadal variability. EOF analysis is then applied to the decomposed matrices to find the dominant modes, which may be related to the drivers of the two types of variabilities in the multivariate decadal means. The methodology has been applied to 140-yr datasets of North Pacific sea surface temperature and the Northern Hemisphere 1000-hPa geopotential height. For sea surface temperature, the Pacific decadal oscillation is the major driver of the fast decadal variability, while the radiative forcing and the Atlantic multidecadal oscillation are major drivers of the slow decadal variability. For the 1000-hPa geopotential height, fast decadal variability is associated with the northern annular mode, the east Atlantic mode, and the Pacific decadal oscillation. Slow decadal variability is associated with the northern annular mode and the Atlantic multidecadal oscillation.
Microstructure Mixing Observations and Finescale Parameterizations in the Beaufort Sea
Authors: Fine Elizabeth C. , Alford Matthew H. , MacKinnon Jennifer A. , Mickett John B.
Published: November 2020

In the Beaufort Sea in September of 2015, concurrent mooring and microstructure observations were used to assess dissipation rates in the vicinity of 72°35′N, 145°1′W. Microstructure measurements from a free-falling profiler survey showed very low [(10−10) W kg−1] turbulent kinetic energy dissipation rates ε. A finescale parameterization based on both shear and strain measurements was applied to estimate the ratio of shear to strain Rω and ε at the mooring location, and a strain-based parameterization was applied to the microstructure survey (which occurred approximately 100 km away from the mooring site) for direct comparison with microstructure results. The finescale parameterization worked well, with discrepancies ranging from a factor of 1–2.5 depending on depth. The largest discrepancies occurred at depths with high shear. Mean Rω was 17, and Rω showed high variability with values ranging from 3 to 50 over 8 days. Observed ε was slightly elevated (factor of 2–3 compared with a later survey of 11 profiles taken over 3 h) from 25 to 125 m following a wind event which occurred at the beginning of the mooring deployment, reaching a maximum of ε= 6 × 10−10 W kg−1 at 30-m depth. Velocity signals associated with near-inertial waves (NIWs) were observed at depths greater than 200 m, where the Atlantic Water mass represents a reservoir of oceanic heat. However, no evidence of elevated ε or heat fluxes was observed in association with NIWs at these depths in either the microstructure survey or the finescale parameterization estimates.
Nb-Ti-Zr alloys for orthopedic implants
Authors: Zhang Taomei , Ou Pinghua , Ruan Jianming , Yang Hailin
Published: November 2020

Niobium (Nb), Titanium (Ti), and Zirconium (Zr) have attracted much attention as implant materials due to it’s excellent mechanical properties and biocompatibility. However, little attention has been paid to high Nb-containing biomedical alloys. Here, the 50 wt.%Nb-XTi-Zr ternary alloy(x = 20wt.%, 30 wt.%, 40 wt.%) with relative density over 90% was prepared by powder metallurgy method. The massive α(Zr) distributed along the grain boundaries and lamellar β(Zr) appeared in the grains of β(Nb) in the 50 wt.%Nb-20wt.%Ti-Zr alloy. The acicular α phase is mainly distributed in the β-grain of 50 wt.%Nb-30wt.%Ti-Zr alloy. And α(Ti)-colonies in the β-grains and continuous α(Ti)GB at β-grain boundary can be observed in the 50 wt.%Nb-40wt.%Ti-Zr alloy. Comparing with Nb-20wt.%Ti-Zr alloy and 50 wt.%Nb-40wt.%Ti-Zr alloy, the 50 wt.%Nb-30wt.%Ti-Zr alloy showed lower Vickers hardness and elastic modulus. Furthermore, the as-sintered 50 wt.%Nb-XTi-Zr alloy promoted the cell proliferation and cell adhesion of MG-63 cells on the surface of alloys. In conclusion, the 50 wt.%Nb-XTi-Zr alloy combines excellent mechanical and biological properties, and the 50 wt.%Nb-30wt.%Ti-Zr alloy with lower elastic modulus (close to the bone) is a more promising candidate for bone implant material.
Age-Based Probability of Ten-Year Overall Survival (OS) of Acute Myeloid Leukemia (AML): A National Cancer Database (NCDB) Analysis
Authors: Bhatt Vijaya R. , Shostrom Valerie K , Khanal Nabin , Chaulagain Chakra P , He Fiona , Gundabolu Krishna
Published: November 2020

Background: Clinical trial data suggest excellent short-term outcomes for younger patients and a subset of fit older patients. Translating findings of clinical trials into the real-world practice has challenges, and longer-term data are often not available. Hence, we utilized NCDB to determine age-based probability of ten-year OS of unselected cohorts of adults with AML.

Methods: NCDB captures about 70% of all new diagnosis of cancer. We utilized NCDB to analyze ten-year OS of 15,646 patients aged ≥18 years, who were diagnosed with AML during the years 2004-2007. Univariate and multiple logistic regression models were used to determine factors associated with ten-year OS. Kaplan Meier curves were generated for OS analysis.

Results: Ten-year OS was 12.7% for patients aged 18-59 years treated with chemotherapy without hematopoietic cell transplant (HCT) (Table 1, Fig. 1). Older age, male, Charlson-Deyo comorbidity score >0, insurance other than private, subtypes other than core-binding factor AML were associated with lower ten-year OS. Ten-year OS was 24.3% for patients aged 18-59 years treated with chemotherapy and HCT (Fig 2). Older age, male, and insurance other than private were associated with lower ten-year OS. Ten-year OS was 16.1% and 2.2% for patients older than 60 years and treated with and without HCT, respectively; multivariate analysis was not performed for older patients because of low sample size (HCT group) or low survival (non-HCT group). Detailed analysis will be presented.

Conclusions: Long-term OS of adults with AML is low with less than a quarter of patients being alive at ten years. Ten-year OS is particularly poor for older patients who are treated with chemotherapy alone. Whereas recent advances and approval of eight new drugs will likely improve short-term OS at 2-3 years, innovative strategies are necessary to improve long-term OS and cure. Further study to identify the cause of death will be insightful.

Disclosures

Bhatt: Takeda: Consultancy; Partnership for health analytic research: Consultancy; Jazz: Research Funding; National Marrow Donor Program: Research Funding; Oncoceutics: Other; Abbvie: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Research Funding; Tolero: Research Funding; Rigel: Consultancy; Agios: Consultancy; Omeros: Consultancy. Chaulagain:Sanofi Genzyme: Honoraria. Gundabolu:BioMarin: Consultancy; Bristol Myers Squibb pharmaceuticals: Consultancy.
Comparative Efficacy of First-Line Regimens in Relapsed/Refractory Mantle Cell Lymphoma (MCL): A Proportional Meta-Analysis
Authors: Haddad Philip A , Hammoud Dalia , Gallagher Kevin M.
Published: November 2020

Introduction:

Mantle cell lymphoma (MCL) is an incurable B-cell malignancy that disproportionately affects the elderly. After first-line therapy failure, relapsed/refractory MCL assumes a more aggressive and universally fatal course. Currently, several classes of chemo/biologic therapies are approved in the second line. However, these agents and their combinations have not been compared head-to-head. We conducted this proportional meta-analysis to evaluate their relative impact on selected clinical outcomes.

Methods:

A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language; diagnosis of relapsed/refractory MCL; trials that explored the efficacy of first-line approved antineoplastic agents and their combinations that comprised: BTK-inhibitors (Ibrutininb (IB), Acalabrutinib, Zanubrutinib), Bortezomib (Velcade, VEL), Venetoclax (VEN), Lenalidomide (LEN), and Bendamustine+Rituximab (B-R); and studies reporting types of responses and duration of response. Proportional meta-analysis was conducted using random-effects model. The respective 95% confidence intervals were calculated, and funnel plots were constructed.

Results:

Thirteen studies comprising a total of 1,264 participants were included. The pooled overall response rates, ORR (95%CI), of the regimens were: 74% (66,81) BTK-inhibitors, 39% (25,53) VEL, 34% (24,46) LEN, 85% (78,92) B-R, 75% (58,92) VEN-IB, and 88% (79,97) IB-R. The pooled complete responses, CR (95%CI), of the regimens were: 33% (20,47) BTK-inhibitors, 9% (5,13) VEL, 6% (4,9) LEN, 45% (36,54) B-R, 42% (22,63) VEN-IB, and 44% (30,58) IB-R. There were no significant differences in ORR and CR between BTK-inhibitors, B-R, VEN-IB, and IB-R. ORR of VEL and LEN also did not significantly differ. However, ORR and CR of the former group were significantly higher than those of the latter. The pooled partial responses, PR (95%CI), of the regimens were: 41% (32,50) BTK-inhibitors, 28% (20,38) VEL, 28% (15,43) LEN, 41% (35,47) B-R, 34% (15,53) VEN-IB, and 44% (30,58) IB-R. There were no significant differences between PR of the regimens. The weighted duration of responses in months, DOR (95%CI), of the regimens were: 20 BTK-inhibitors, 9 VEL, 16 LEN, and 20 B-R.

Conclusions:

This proportional meta-analysis is the first to compare the current regimens in first-line relapsed/refractory MCL. It indicates that BTK-inhibitors monotherapy, IB combinations with R or VEN, and B-R provide equivalent ORR and CR rates that are significantly better than VEL and LEN with notably longer duration of response. It also raises questions about whether there is an additional ORR and CR benefits when adding VEN or R to IB in this clinical setting.

Disclosures

No relevant conflicts of interest to declare.
Periprocedural Interruption of Edoxaban in Real World Setting: Results from the Emit AF/VTE Study
Authors: Santamaria Amparo , Colonna Paolo , von Heymann Christian , Saxena Manish , Vanassche Thomas , Jin James , Wilkins Robert , Chen Cathy , Unverdorben Martin
Published: November 2020

Background: The optimal interruption schedule for NOACs in patients undergoing invasive procedures has not been determined. This analysis describes periprocedural interruption of edoxaban in real world EMIT AF/VTE study.

Methods: EMIT AF/VTE was a prospective, non-interventional study conducted in 7 European countries that collected detailed information on periprocedural management of edoxaban from 5 days before to 30 days after procedure in patients with AF or VTE.

Results: Among 1155 patients, pre-procedural interruption occurred in 781 (68%) patients (median 2 days, IQR 1.0-2.0) and post-procedural interruption in 308 (27%) patients (median 3 days, IQR 1.0-8.0); 279 (24.2%) patients had both pre- and post-procedural interruption. Edoxaban interruption in some patients differed from 2018 EHRA Recommendations for NOAC use in AF. Of 294 patients receiving minor risk procedures, for whom no interruption is recommended, 173 (58.8%) had preprocedural interruption (median 1 day). Of 581 patients with low bleeding risk procedures, for whom ≥24h preprocedural interruption is recommended, 188 (32.4%) had no interruption. Of 280 patients receiving high bleeding risk procedures, for whom ≥48h interruption is recommended, 46 (16.4%) had no interruption. Clinical events are shown in Table.

Conclusion: Edoxaban interruption schedules in routine practice were not always consistent with EHRA guidelines; nevertheless, rates of clinically significant bleeding or acute thromboembolic events or coronary syndromes were low in the EMIT study.

Table

Disclosures

Colonna: Boehringer Ingelheim: Honoraria; Daiichi Sankyo: Honoraria; BayerAG: Honoraria; Italian Cardiology Association: Other: Non-financial support; European Society of Cardiology: Other: Non-financial support; Pfizer/BMS: Honoraria. von Heymann:Daiichi Sankyo: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria; Bayer AG: Honoraria; Pfizer GmBH: Honoraria; CSL Behring: Honoraria; NovoNordisk Pharma: Honoraria; EACTA and EACTS: Other; DGGG: Other; Mitsubishi Pharma: Honoraria; Ferring GmbH: Honoraria; Biotest GmbH: Honoraria; Leo Pharma GmBH: Honoraria; German Society of Anaesthesiology and Intensive Care Medicine: Other. Saxena:Daiichi Sankyo: Honoraria, Research Funding. Vanassche:Boehringer Ingelheim: Honoraria; 367 Leo Pharma: Honoraria; Bayer: Honoraria; Daiichi Sankyo: Honoraria, Research Funding. Jin:Daiichi Sankyo: Current Employment. Wilkins:Daiichi Sankyo: Honoraria. Chen:Daiichi Sankyo: Current Employment. Unverdorben:Daiichi Sankyo: Current Employment.
Immunoglobulin Sub-Typing and Quantification in Coombs Positive Hemolysis
Authors: Chetty Thirosha , Bouwer Nikki , Wan Yuen On , Mahlangu Johnny
Published: November 2020

Key words:immunoglobulin, coombs test, hemolysis, HIV, quantification

Introduction

A positive direct antiglobulin test (DAT, Coombs test) is valuable in identifying the etiology of autoimmune hemolysis and in guiding an immunomodulatory therapeutic intervention strategy. However, in HIV positive individuals with background polyclonal gammopathy, a false positive DAT is common. In this setting, immunoglobulin quantification and subtyping may be of value in characterizing the autoimmune hemolysis. There is paucity of published literature evaluating the diagnostic usefulness of IgG subtyping and quantification in HIV positive individuals who are investigated for possible autoimmune haemolysis (AIHA). The recently introduced gel card used for AIHA diagnosis can subtype and quantify the IgG antibody titre. This study evaluated the usefulness of IgG quantification and subtyping in the diagnostic workup of autoimmune hemolysis in patients who were DAT positive with and without HIV infection.

Methods:

This retrospective, cross sectional study was reviewed and approved by the institutional Ethics Committee. The study population included HIV positive and HIV negative patients who were investigated for autoimmune hemolysis in a quaternary care hospital as part of their diagnostic workup. Those with a positive DAT had their IgG subtyped and quantified using the ID -Card DAT IgG1/IgG3 and IgG-dilution cards (Bio-Rad©, Cressier, Switzerland).

Results:

From December 2019 to March 2020, 90 patients admitted in our hospital were investigated for AIHA. Forty four (49%) were found to be DAT positive. Of those who were DAT positive, 26 (59%) had biochemical evidence of haemolysis (raised LDH, raised unconjugated bilirubin). Of the total DAT positive population, 16 (36%) were HIV positive. Concurrent HIV and haemolysis was present in 8 patients. Four of the 8 had antibody titre≤1:30. Most patients had IgG 1 subtype. None of the HIV positive patients without features of haemolysis had IgG1 or IgG3 subtypes present and 2 of the 8 had antibody titres≤1:30.

Conclusion:

IgG quantification and subtyping was found to be of limited value in the diagnostic characterization of AIHA in HIV positive patients with false positive DAT.

Disclosures

Mahlangu: CSL Behring, Catalyst Biosciences, Freeline Therapeutics, Novo Nordisk, F. Hoffmann-La Roche Ltd, Sanofi, Spark and Takeda:Consultancy;CSL Behring, Catalyst Biosciences, Novo Nordisk, F. Hoffmann-La Roche Ltd, Sanofi, Spark and Takeda:Speakers Bureau;South Africa Medical Research Council, Wits Health Consortium, Colleges of Medicine of South Africa:Membership on an entity's Board of Directors or advisory committees;BioMarin, CSL Behring, Freeline Therapeutics, Novo Nordisk, Novartis, Pfizer, Sanofi, F. Hoffmann-La Roche Ltd, uniQure:Research Funding.
Follicular Lymphoma Masquerading As a Neuroendocrine Tumor
Authors: Dhami Dana Victoria , Dhami Sabina , Kapur Dinesh , Coletti David , Sreedevi Kurella , Dhami Mandeep
Published: November 2020

A 73 y/o Caucasian female presented with abdominal pain for 2 years, gradually worsening in the recent past. The pain was more severe at night, especially while sleeping on her abdomen. An A/P CT scan showed a mid-abdominal mesenteric mass measuring 8 x 4 cm, which was new since prior examinations. The new mass was accompanied by prominent retro-peritoneal lymph nodes, the largest along the left paraaortic region measuring 1.9 x 1.6 cm. She reported good appetite and denied fever, chills, night sweats or unexplained weight loss. She admitted to a 6-month history of diarrhea consisting of 2-3 loose stools daily. Her clinical presentation was felt to be concerning for Carcinoid tumor.

A GA-68 dotatate PET/CT showed uptake within the known mesenteric mass, most likely representing carcinoid tumor. Minimal uptake observed in retroperitoneal lymph nodes felt to represent early metastatic disease.

The patient underwent laparotomy, small bowel resection and retroperitoneal lymph node resection.

Pertinent laboratory studies -

Chromogranin level, pre op - 625 (ref 25 - 140)

Chromogranin level post op - 54

Pathology showed grade 2, follicular lymphoma. The neoplastic cells predominantly composed of small, irregular cleaved centrocytes mixed with a minor population of centroblasts (less than 15 per high-power field). Neoplastic follicles were diffusely positive for CD20, PAX5, CD10, BCL6, and BCL2. Ki67 showed 10-20% proliferation index. Cyclin D1 was negative. Flow cytometry identified monoclonal B-cell population positive for CD10, CD19 (dim), and CD20, which expressed dim monotypic lambda light chain. CD5 negative.

Discussion: There is evidence that lymphoma cells express somatostatin receptors (SSTR). Octreotide scan (111In-pentetreotide - binds to SSTR2 and SSTR5) uptake has been described in lymphomas with variable degree of avidity. Gallium Dotatate scan (68Ga-Dotatate - binds selectively to SSTR2) uptake has been previously described in a patient with large cell lymphoma. Here we describe a case of follicular lymphoma presenting with symptoms suggestive of carcinoid that showed uptake on Gallium Dotatae scan. This finding therefore warrants recognition by clinicians for potential of lymphoma presenting with positive Gallium Dotatate scan.

Ruuska et al* have shown that 62% of various PET positive lymphomas (DLBCL, follicular and Hodgkin's) were also 68Ga-DOTONAC PET/CT positive and there was concordance between SSTR2 positivity by IHC and 68Ga-DOTONAC PET/CT. If this finding is confirmed in further studies, perhaps this may lead to a possible therapeutic application for 177Lu-DOTA-TATE in management of some refractory lymphomas.

*Tina Ruuska et al, Acta Oncologica, 2018, vol 57, no. 2. 283-289

Figure

Disclosures

No relevant conflicts of interest to declare.
B7-H6 Is Associated with Poor Prognosis and a Potential Therapeutic Target of T-Lymphoblastic Lymphoma
Authors: Yuan Lei , Sun Lu , Zhao Yu , Jing Hongmei , Ke Xiaoyan
Published: November 2020

Background:B7-H6 is a novel co-stimulatory protein that is exclusively expressed on a variety of cancer cells and associated with poor prognosis. T cell lymphoblastic lymphoma (T-LBL) is a highly aggressive hematological malignancy whose treatment requires reliable prognostic biomarkers and therapeutic targets. The rare nature and delayed progression of T-LBL has limited its clinical management.

Methods:B7-H6 expression was analyzed by immunohistochemistry (IHC) in 65 T-LBL samples, and its association with clinicopathological characteristics and prognosis was analyzed. Jurkat cell with B7-H6 depletion was constructed to investigate the impact of B7-H6 on cell proliferation, migration, and invasion ability. RNA sequencing was used to explore aberrantly expressing genes.

Results:In this study, we used immunohistochemistry to show the expression of B7-H6 in 61.5% (40/65) of the cohort, including 38.5% (25/65) patients with membrane/cytoplasmic expression of B7-H6. Although B7-H6 expression varied across samples and did not correlate with patient survival, it was significantly associated with B symptoms, higher ECOG score (3-4), elevated serum lactate dehydrogenase, and reduced complete remission at interim evaluation. B7-H6 underwent translocation into the nucleus of T-LBL cells and had a specific nuclear localization sequence in the C-terminus. Depleting Jurkat cells of B7-H6 impaired cell proliferation, migration, and invasion. RNAseq showed the differential expression of RAG-1 that could be involved in the tumorigenesis of T-LBL.

Conclusions:B7-H6 may serve as a novel prognostic biomarker and therapeutic target of T-LBL.

Disclosures

Ke: Peking University Third Hospital:Current Employment.
Anti-GDF11Treatment of β-Thalassemia Intermedia Mice Does Not Improve Erythropoiesis
Authors: Lob Heinrich E , Kravets Leah , Miloscio Lawrence , Mastaitis Jason , Economides Aris N , Hatsell Sarah J
Published: November 2020

Beta-thalassemia is a hereditary iron-independent anemia, caused by a reduction of β-globin, affecting millions of people globally. Current treatments such as blood transfusions and iron chelation show significant toxicities and add to organ damage. Luspatercept (Acvr2b(L79D)-Fc) is a novel treatment for transfusion-dependent β-thalassemia patients that improves erythropoiesis independent of erythropoietin. The exact mechanism of action remains unknown, and it is controversially discussed if growth differentiation factor 11 (GDF11) is the main target of this drug. Genetic models raised doubts that GDF11 is the target of Acvr2b(L79D)-Fc. Here we tested if a GDF11 specific blocking antibody improves β-thalassemia intermedia in mice. Our findings support the genetic data that GDF11 does not play a role in the ineffective erythropoiesis in β-thalassemia. Anti-GDF11 treatment did not change hematocrit, hemoglobin and red blood cell number and it did not improve erythropoiesis. Ex vivo treatment of erythroblasts with recombinant GDF11 did not inhibit red blood cell maturation. Lastly, we identified that inhibiting GDF8 in β-thalassemia mice has a small effect on erythropoiesis and increased hemoglobin levels without being as effective as Acvr2b(L79D)-Fc. Of note, wild-type animals treated with anti-GDF8 did not show changes in any hematology parameters and therefore the small effect we observed might be due to the disease phenotype, but not due to a physiological mechanism involved in erythropoiesis. Taken together, GDF11 is not involved in erythropoiesis but GDF8 may have a minor role in the regulation of ineffective erythropoiesis. Given the small effect of anti-GDF8 on erythropoiesis compared to Acvr2b(L79D)-Fc, we conclude that either there is another target or several targets of Acvr2b(L79D)-Fc driving ineffective erythropoiesis, or that Acvr2b(L79D)-Fc efficacy is due to it altering the overall BMP/GDF/Activin ligand and receptor balance.

Disclosures

Lob: Regeneron Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Kravets:Regeneron Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Miloscio:Regeneron Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Mastaitis:Regeneron Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Economides:Regeneron Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Hatsell:Regeneron Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company.
The Effect of Macrophage Polarization on Cytokine Release in CAR-T Antitumor Response
Authors: Zmievskaya Ekaterina , Valiullina Aigul , Zhuravleva Margarita , Rakhmatullina Aigul R , Ganeeva Irina , Zaikova Ekaterina , Petukhov Alexey , Miftakhova Regina R , Rizvanov Albert A , Bulatov Emil
Published: November 2020

Immunotherapy of cancer using T-lymphocytes with chimeric antigen receptor (CAR-T) is highly promising. CAR-T therapy is approved by FDA for the treatment of B-cell (CD19+) hemoblastoses, however it faced a number of major difficulties in application to solid tumors. One of the main problems of CAR-T therapy is the possibility of developing a serious complication - cytokine release syndrome (CRS), which in extreme cases becomes a life-threatening condition. CRS is often caused by the direct contact of tumor cell with T-lymphocyte and its subsequent activation. However, there is growing amount of evidence suggesting substantial participation of macrophages in this process.

We established the effect of macrophages of different phenotypes on secretion of cytokines during cocultivation with CAR-T cells. Initially, isolated monocytes were differentiation into M1 and M2 macrophages. After that M1, M2, and CAR-T cells were co-cultured with prostate adenocarcinoma PC-3M(Kat+CD19+) cells for 5 days. Supernatants were analyzed using multiplex assay.

Confocal microscopy revealed that co-cultivation of PC-3M(Kat+CD19+) cells with CAR-T cells decreases the number of tumor cells. Multiplex analysis revealed that macrophages of both populations did not affect the secretion levels of IFNγ and TNFα. However, M1 population promoted IL-1b, and M2 lowered IL-6 and IL-17F. Increase in sCD40L levels was also detected upon addition of both macrophage populations.

Results suggest that interaction of M1 and M2 macrophages with CAR-T cells leads to release of various pro-inflammatory cytokines and might be the cause of CRS in patients.

Work was funded by RSF 19-74-20026 and performed according to the Russian Government Program of Competitive Growth of Kazan Federal University. A.V. was supported by stipend of President of Russian Federation СП-227.2019.4.

References

Titov, et al. "Advancing CAR T-Cell Therapy for Solid Tumors: Lessons Learned from Lymphoma Treatment." Cancers 12, 1 (2020): 125. DOI: 10.3390/cancers12010125

Disclosures

No relevant conflicts of interest to declare.
Analysis of the Short-Term Efficacy of Decitabine Combined with Low-Dose Cytarabine in the Treatment of JMML
Authors: Cai Yuli , Liang Weiru , Yi Meihui , Zhang Xiaoyan , Liu Fang , Chang Lixian , Guo Ye , Chen Yumei , Zou Yao , Yang Wenyu , Zhu Xiaofan
Published: November 2020

Objective: Juvenile myelomonocytic leukemia (JMML) has both the disease characteristics of myelodysplastic syndrome and myeloproliferative neoplasm. Currently, hematopoietic stem cell transplantation (HSCT) is the only possible cure. Most of the newly diagnosed pediatric patients with JMML have high tumor burden, rapid disease progression, and may not tolerate HSCT. This study explored the short-term efficacy of decitabine combined with low-dose chemotherapy in the treatment of JMML before transplantation.

Methods: A retrospective analysis of the patient files of 9 cases of JMML was performed from January 2019 to May 2020. All patients were given decitabine 20mg/m2× 5 days, supplemented with a small dose of cytarabine (50-100mg/m2×3~5 days), and/or etoposide (50mg/m2×3~5 days) chemotherapy. Each treatment interval is 3~4 weeks, bridging with HSCT after 3~4 treatment courses.

Results: The median age of onset of 9 cases of JMML was 2 years old (0.5~4 y), male to female ratio was 8:1, the median size of spleen was 6.4cm (2.9~9.8cm) under the costal arch, and WBC was 28.03×109/L (7.3~127.69×109/L), monocytes were 9.25×109/L (1.66~15.79×109/L) at diagnosis. There were 8 cases in the high-risk group and 1 case in the low-risk group. Second-generation sequencing results show that 7 cases carried PTPN11 somatic mutations. Five in 9 cases had two kinds of classic JMML mutations, and 1 case had only NRAS mutation. Seven patients had normal chromosomal karyotypes, and 3 patients had abnormal 8, 11, and 18 chromosomes, respectively. Median treatment courses with decitabine are 3 courses (1~5 courses), the response rate of one course is 77.8% (7/9), the response rate of three courses is 80% (4/5), one case from high-risk group achieved complete remission after treated with 4 courses of decitabine and low-dose chemotherapy. The five-month progression-free survival rate was 77.8% (7/9).

Conclusion: Treating JMML with decitabine combined with low-dose chemotherapy, can reduce patients' tumor burden, improve the general condition, and obtain approximately 80% clinical response rate. Decitabine combined with low-dose chemotherapy can be used as a treatment option for JMML before HSCT.

Disclosures

No relevant conflicts of interest to declare.

OffLabel Disclosure:

Safety and effecacy of decitabine applicated in JMML patients have not been confirmed.
Apixaban Anti-Xa Level Monitoring in Treatment of Provoked Acute Upper Extremity Deep Vein Thrombosis for Patient on Dialysis: A Case Report
Authors: Roberge Guillaume , Wells Philip S.
Published: November 2020

Background. Patients with end stage renal disease on dialysis are at higher risk of major bleeding and recurrent thrombosis and as such, treatment of acute venous thromboembolism (VTE) is challenging. Ideally, treatment would avoid inpatient admission as for most other patients with acute VTE. DOACs represent the easiest option but there are concerns over bioaccumulation increasing bleeding risk. Despite the absence of a standardized therapeutic range, anti-Xa trough level is measured to monitor potential DOACs bioaccumulation and thus, used for safety surveillance.

Methods. We describe a case of a 51 yo female, 36 kg, on chronic hemodialysis with a provoked acute upper extremity deep vein thrombosis. Due to a lack of subcutaneous fat and calciphylaxis we were reluctant to use low molecular weight heparin and warfarin. She was treated with apixaban 2,5 mg twice daily for 6 weeks. Over 4 weeks, the apixaban anti-Xa trough levels were measured on dialysis days 12 hours after the morning dose.

Results. The anti-Xa trough levels ranged from 58 to 84 ng/mL, similar to what is expected in patients with normal kidney function. There were no adverse events in the 3 months after anticoagulation initiation.

Conclusion. We saw no evidence of bioaccumulation. This indicates a potential role for apixaban low doses in acute venous thromboembolism for patients on dialysis.

Disclosures

No relevant conflicts of interest to declare.

OffLabel Disclosure:

The use of Apixaban for treatment of acute venous thromboembolism in patient on dialysis has not been approved.
Combining the mTOR Inhibitor Everolimus and Gemcitabine in Relapsed/Refractory Peripheral T-Cell Lymphomas
Authors: Huang Ling , Jiang Xinmiao , Li Wenyu , Guo Hanguo , Wei Xiaojuan , Liu Sichu , Chen Feili , Liang Zhanli
Published: November 2020

Background: Relapsed/refractory Peripheral T-cell lymphomas (PTCL) is an aggressive and heterogeneous Non-Hodgkin's T cell lymphoma, which is resistant to conventional chemotherapy with poor prognosis. Therefore, there is an urgent need to exploit potential therapeutics and novel treatment for R/R PTCL. Targeting PI3K/AKT/mTOR pathway is an effective therapy for PTCL. However, recent research demonstrated that the mTOR inhibitor everolimus monotherapy has low response rate and short duration time in treating with R/R PTCL.

Methods:We retrospectively reviewed 18 patients with pathologically diagnosed T cell lymphoma who received the mTOR inhibitor everolimus combined with gemcitabine for six cycles (everolimus 10mg qd, gemcitabine 1000mg/m2 d1, every 21 days a cycle) and sequential autologous stem cell transplantation, at Guangdong Provincial People's Hospital from November 2015 through October 2019. We evaluated the objective response rate (ORR), progressive free survival (PFS) and safety.

Results:Of the 18 patients, 33.3% (n=6) had PTCL-not otherwise specified (PTCL-NOS), 27.8% (n=5) had angioimmunoblastic T-cell lymphoma(AITL), 27.8% (n=5) had anaplastic large cell lymphoma(ALCL) (anaplastic lymphoma kinase positive ALCL: 20.0%, n=1; anaplastic lymphoma kinase negative ALCL: 80.0%, n=4), and 11.1%(n=2) had other subtypes. The median age was 46.5 years (range 26-64) old and most patients were males (66.7%) with advanced stage disease (III/IV, 73.7%). The ORR was 55.6% (n=10), with complete response rate of 50% and partial response rate of 5.6%. One patient was stable disease (5.6%), and seven patients were progressive disease (33.8%). For subtypes, the ORR was 80% in ALCL, 66.7% in PTCL-NOS and 20% in AITL, respectively. With a median follow-up time of 18.9 months (range 3.1-99.6), the median PFS was 4.5 months and overall survival(OS) was 18.9 months, respectively. The most frequent hematological adverse events were thrombocytopenia (27.8%), anemia (22.2%), leukopenia (11.1%). The non-hematological adverse events were inappetence (22.2%), diarrhea (11.1%), rash(11.1%), fatigue (11.1%).

Conclusions:Our pilot studies have shown that combined everolimus with gemcitabine have better efficacy than monotherapy reported previously for R/R PTCL patients, but the mechanism is still unclear. It suggests that further investigation for mechanisms and predictive biomarker is needed.

Figure

Disclosures

No relevant conflicts of interest to declare.
Isavuconazonium Sulfate Use in Multi-Modal Management of Invasive Zygomycosis in Four Pediatric Allogeneic Hematopoietic Cell Transplant Patients
Authors: Ferdjallah Asmaa , Nelson Kristina M , Meyer Kailey , Jennissen Cathryn A , Ebens Christen L.
Published: November 2020

Prolonged neutropenia increases risk for lethal invasive fungal infection (IFI) such as Rhizopus. Isavuconazonium sulfate is a new triazole that lacks pediatric dosing recommendations. Clinical courses of 4 pediatric patients with IFI in the peri-allogeneic hematopoietic cell transplantation (alloHCT) period between 2015 and 2017 were reviewed, including previously unreported pharmacokinetic and safety data. IFI included Rhizopus and presumed fungal meningitis. Isavuconazonium sulfate was initiated with a loading dose followed by daily dosing, adjusted to a goal trough >3 ug/mL based on adult literature. This target was achieved at a median of 7 days, demonstrating varying rates of metabolism. Renal insufficiency, electrolyte disturbances, and transaminitis were noted, though attribution was confounded by other alloHCT complications. 1 patient survived infection-free to hospital discharge and 1 of 3 deceased patients had evidence of unresolved IFI (Case 2). Case 2 was subtherapeutic for 39% of the duration of treatment, compared to others at an average of 29%, suggesting this target trough to be clinically relevant. We recommend initiation of isavuconazonium sulfate at 10 mg/kg with a max dose of 372 mg. A loading dose of 10 mg/kg is utilized every 8 hours for 6 doses followed by 10 mg/kg dosing every 24 hours. Monitoring must continue beyond steady state. If early monitoring is not possible, we recommend a first drug level at week 3. If dose increases are required, a partial reload has been more successful instead of increasing daily doses. Further larger studies are needed to demonstrate optimum dosing in pediatric patients.

Figure 1

Disclosures

No relevant conflicts of interest to declare.
Defining the Super Massive Transfusion in Pediatric Casualties during Combat Operations in Afghanistan and Iraq
Authors: Schauer Steven Gremel , Fisher Andrew , Borgman Matthew , Cap Andrew P. , Bynum James
Published: November 2020

Introduction: Hemorrhage is the leading cause of potentially preventable death on the battlefield. We previously published data defining the pediatric massive transfusion at 40mL/kg of total blood products. However, there is a subset of casualties that require large volumes of blood products - super massive transfusions - which remains unclear. We seek to determine what defines a super massive transfusion within the pediatric population as understanding this unique group would help mobilize resources early in their clinical course.

Methods: This is a secondary analysis of a previously described dataset from the Department of Defense Trauma Registry. In this analysis, we sought all casualties within our dataset that met inclusion for MT. To describe the super MT, we sought the top quartile of total products administered within the first 24 hours on a volume per weight basis.

Results: Within our original dataset of 3439 pediatric casualties, we identified 543 that met inclusion for massive transfusion, with the 75th percentile at 120.6 mL/kg - we rounded this to 120mL/kg for simplicity which left 137 for analysis. Most of the casualties were in the 5-9 and 10-14 age groups (24% and 39%, respectively) and were most frequently injured by explosive (71%). Those in the super MT group had lower survival (75% versus 84%, p=0.015), longer ventilator courses (median 3 days versus 2 days, p=0.029) despite similar median injury severity scores (17 versus 17, p=0.100). However, they more frequently had serious injuries to the extremities (62% versus 35%, p<0.001). Super MT casualties more frequently had age-adjusted hypotension (45% versus 26%, p<0.001) but no difference in age-adjusted tachycardia (88% versus 86%, p=0.514). Super MT casualties had worse international normalized ratios (2.06 versus 1.65, p=0.006), and worse base deficits (-11.3 versus -8.5, p<0.001).

Conclusions: In our analysis, we found that 120 mL/kg of total blood products administered within the first 24 hours was the threshold for the top 25th percentile of pediatric blood product consumers. More data is needed to define this unique population that requires mobilization of extensive resources.

Disclosures

No relevant conflicts of interest to declare.