bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Agrarian Populism Progressive? Russia Then, India Now
Authors: Brass Tom
Published: November 2019

Examined here is the claim that agrarian populism can be – and is currently – progressive, a view evaluated in relation to recent pro-peasant/farmer-first accounts of rural mobilization in Russia at the start of the 20th century and India at its end. Against this it is argued that agrarian populism cannot be regarded as progressive, for two reasons in particular. First, it overlooks or downplays the fact that capitalism requires of peasant households only their labour-power, as components of an increasingly global industrial reserve army. Opposed merely to certain forms of capitalism (foreign, large-scale) and not to accumulation per se, populists were and are unable to address this contradiction. And second, agrarian populism unleashes – or, once unleashed, endorses – discourses about the innateness of national/ethnic/religious difference associated historically and currently with the political right.
Measures of dynamic balance during level walking in healthy adult subjects: Relationship with age, anthropometry and spatio-temporal gait parameters
Authors: Lencioni Tiziana , Carpinella Ilaria , Rabuffetti Marco , Cattaneo Davide , Ferrarin Maurizio
Published: November 2019

The maintenance of balance in dynamic conditions (e.g. during walking) is a necessary requirement that motor control must reach to avoid falls. However, this is a challenging situation, since to ensure the forward progression of the body, the center of mass must stay outside the base of support in the sagittal plane, and simultaneously remain inside the lateral borders in the frontal plane. Deviation from normative data of healthy subjects in dynamic balance could be used to quantify gait stability, fall risk and to provide hints for rehabilitation. However, normative data can be influenced by age, sex, anthropometry and spatio-temporal gait parameters, and such differences among subjects and leg side can hamper accurate assessment. The aims of this study were to investigate, in a group of healthy subjects: (1) possible asymmetry in dynamic balance maintenance strategies between leg sides, (2) the influence of age, sex and anthropometry on stability and (3) its dependence by spatio-temporal gait parameters. A total of 34 healthy subjects aged between 21 and 71 years, and ranging from 50.1 to 101.6 kg of body mass and from 155.0 to 188.9 cm of height were assessed on spatio-temporal and dynamic balance parameters (Foot Placement Estimator at heel strike and Margin of Stability at mid-stance) during self-selected gait. No parameter showed differences between legs. Dynamic balance parameters were influenced by sex, age, body mass and height mainly in the frontal plane. These measures were also correlated with gait speed and stride length both in the antero-posterior and medio-lateral directions. In addition also cadence and step width influenced the stability in the sagittal and frontal planes, respectively. The findings of this study confirm the symmetry in motor control of dynamic balance during self-selected gait in healthy subjects. Sex, anthropometry and spatio-temporal gait parameters have a significant effect on stability parameters, and this should be taken into account in dynamic balance studies.
A comparative study of heat-cured and gamma-cured fiber-reinforced denture-base acrylic resins: Residual monomer and flexural strength
Authors: Ergun Ece , Ergun Ümit , Kalıpçılar Betül
Published: November 2019

This study was performed to determine and compare the effect of heat and gamma-ray polymerization methods on the residual monomer and flexural strength of polyethylene fiber-reinforced denture-base acrylic resins. Four groups ( n = 10) of specimens of polyethylene fiber-reinforced denture-base material were prepared in the form of thin disks. The first group was subjected to heat-curing and the other three groups were polymerized with gamma irradiation at doses of 15, 25, and 35 kGy, respectively. Fourier-transform infrared (FTIR) spectrometer was used to monitor the corresponding polymerization processes. The analysis of residual monomer was carried out by high-performance liquid chromatography–photodiode array detector. A three-point bending test was used to evaluate the flexural strength of the samples. The one-way analysis of variance test was performed to determine the significant differences between the groups. The absence of the bands related to carbon–carbon double bond in the FTIR spectra of all test groups was an evidence of polymerization. The mean weight percentage of residual monomer was successively ranked from highest to lowest in; heat-cured, gamma-cured at 15–35 kGy. However, no significant difference ( p = 0.462) was found between gamma-cured samples at 25 and 35 kGy. Mechanical test results revealed that heat-cured samples had higher flexural strength than gamma-cured specimens ( p < 0.001). Within the limitations of this study, polymerization with gamma-rays at 15 kGy was proposed as a promising technique in terms of the residual monomer and flexural strength results.
Axial behaviour of slender concrete-filled steel tube square columns strengthened with square concrete-filled steel tube jackets
Authors: Zhu Tao , Liang Hongjun , Lu Yiyan , Li Weijie , Zhang Hong
Published: November 2019

This article investigates the behaviour of slender concrete-filled steel tube square columns strengthened by concrete-filled steel tube jacketing. The columns were realised by placing a square outer steel tube around the original slender concrete-filled steel tube column and pouring strengthening concrete into the gap between the inner and outer steel tubes. Three concrete-filled steel tube square columns and seven retrofitted columns ranging from 1200 to 2000 mm were tested to failure under axial compression. The experimental parameters included three length-to-width ( L/ B1) ratios, three width-to-thickness ( B1/ t1) ratios and three strengths of concrete jacket (C50-grade, C60-grade and C70-grade). Experimentally, the retrofitted columns failed in a similar manner to traditional slender concrete-filled steel tube columns. After strengthening, the retrofitted columns benefitted greatly from the component materials, with their load-bearing capacity and ductility notably enhanced. These enhancements were mainly brought about by sectional enlargement and good confinement of concrete. A finite element model was developed using ABAQUS to better understand the axial behaviour of the retrofitted specimens. A parametric study was conducted, with parameters including the length of the column, thickness of the outer steel tube, strength of the concrete jacket, yield strength of the outer steel tube, thickness of the inner steel tube and strength of the inner concrete. Furthermore, the finite element model was adopted to study the behaviour of rust-damaged and post-fire slender concrete-filled steel tube square columns strengthened by square concrete-filled steel tube jacketing. A modified formula was proposed to predict the load-bearing capacity of retrofitted specimens, and the numerical results agreed well with the experiments and the finite element results of undamaged, rust-damaged and post-fire specimens. It could be used as a reference for practical application.
Social media is not real: The effect of ‘Instagram vs reality’ images on women’s social comparison and body image
Authors: Tiggemann Marika , Anderberg Isabella
Published: November 2019

One recent trend on Instagram consists of posting ‘Instagram vs reality’ images containing side-by-side photographs of the same woman, one an idealized depiction and the other a more natural depiction. This study aimed to experimentally investigate the effect of such images on body image. Participants were 305 women aged 18–30 years who were randomly assigned to view one of three sets of Instagram images: ‘Instagram vs reality’ images, the ‘ideal’ side alone or the ‘real’ side alone. As predicted, viewing the ‘Instagram vs reality’ and real images resulted in decreased body dissatisfaction relative to the ideal images. Furthermore, the detrimental effects of appearance comparison were much less marked for the ‘Instagram vs reality’ and real images than for the ideal images. It was concluded that ‘Instagram vs reality’ and real posts have the potential to bolster women’s body satisfaction, but more research is needed to assess their longer-term impact.
Heroes or criminals: discursive representation of cancer patients in health awareness advertisements
Authors: Ho Janet
Published: November 2019

This article compares the use of metaphors in breast and lung cancer awareness advertisements in order to examine the positioning and identity construction of the respective cancer patients. A semantic annotation software tool was used to identify the overuse of semantic fields in each corpus of cancer awareness advertisements and multimodal metaphors were identified following the protocols of Bounegru and Forceville’s (2011) article, ‘Metaphors in editorial cartoons representing global financial crisis’, Forceville’s (2009) essay, ‘Non-verbal and multimodal metaphor in a cognitivist framework: Agendas for research’ and Pérez-Sobrino’s (2017) book, Multimodal Metaphor and Metonymy in Advertising. Findings showed that breast cancer awareness advertisements deployed more positive words than did the lung cancer awareness advertisements and they used a wide range of source domains such as WILD ANIMALS and FIGHTERS, showing the creative representation of deeply entrenched conventional metaphors as well as the use of humour and euphemism. On the other hand, lung cancer awareness advertisements were much less metaphorical and mostly sought to persuade people to quit smoking. The metaphorical use of military weapons showed that ‘shockvertising’ was recurrent in lung cancer awareness advertisements. The present study argues that both types of advertisements partially present the facts of breast cancer and lung cancer, and the guilt-loading of smokers in the lung cancer awareness advertisements invisibly transformed the physical threat appeals into social threat appeals.
Brief, Intensive Treatment for Separation Anxiety in an 8-Year-Old Boy: A Case Study
Authors: McFayden Tyler C. , White Susan W.
Published: November 2019

Cognitive behavioral therapy (CBT) is the evidence-based treatment modality for children with anxiety disorders; yet, many youth do not receive treatment. To overcome barriers associated with standardized CBT approaches, brief, intensive treatments have been proposed. This case study illustrates a brief, intensive CBT intervention for a preadolescent male client who presented with severe separation anxiety. The intervention consisted of five sessions (one each day for five consecutive days) and a follow-up assessment 4 months later to evaluate treatment outcomes. The intervention strategies were based in CBTs and included exposures, cognitive reappraisal work with both the client and the parents, and reduction of parental accommodation. Reliable Change Indices were calculated to evaluate change from preintervention to the follow-up assessment. There were large and statistically significant decreases in the main outcome measure of separation anxiety symptoms, indicating significant improvements in separation symptoms over treatment per the client’s and parents’ reports. At the follow-up session, the client no longer met diagnostic criteria for separation anxiety disorder. The results highlight the utility of brief, intensive interventions for separation anxiety in young children.
Online joint power control for cooperative jamming systems with energy harvesting
Authors: Lei Weijia , Wang Ziwei , Lei Hongjiang
Published: November 2019

To maximize the long-term time-averaged secrecy rate of an energy harvesting wireless communication system, an online power control algorithm based on the Lyapunov optimization framework is proposed. The system is composed of a source node, a cooperative jamming node, and two destination nodes. The source node and the jamming node are powered by the energy harvesting device. Information sent to the two destination nodes is mutually confidential. Using the Lyapunov optimization framework, the original stochastic optimization problem is transformed into a per-time-slot optimization problem, and the power of the signal and that of the artificial noise are determined based on the current system state such as the power level of the batteries and channel coefficients. The fairness between the two destination nodes is considered too. Simulation results demonstrate that the proposed algorithm can effectively utilize the harvested energy and significantly improve the long-term averaged secrecy rate.
Safety of Intra-Articular Hyaluronic Acid for Knee Osteoarthritis: Systematic Review and Meta-Analysis of Randomized Trials Involving More than 8,000 Patients
Authors: Miller Larry E. , Bhattacharyya Samir , Parrish William R. , Fredericson Michael , Bisson Brad , Altman Roy D.
Published: November 2019

Objective

The objective of this systematic review and meta-analysis was to report the safety of intra-articular hyaluronic acid (IAHA) in patients with symptomatic knee osteoarthritis (OA).

Methods

We identified randomized controlled trials reporting the safety of IAHA versus IA saline in adults with symptomatic knee OA. Main safety outcomes were adverse events (AEs), local AEs, serious adverse events (SAEs), study withdrawals, and AE-related study withdrawals.

Results

A total of 35 randomized controlled trials with 38 group comparisons comprising 8,078 unique patients (IAHA: 4,295, IA saline: 3,783) were included in the meta-analysis. Comparing IAHA with IA saline over a median of 6 months follow-up, there were no differences in the risk of AEs (42.4% vs. 39.7%, risk ratio [RR] = 1.01, 95% CI = 0.96-1.07, P = 0.61), SAEs (1.8% vs. 1.2%, RR = 1.44, 95% CI = 0.91-2.26, P=0.12), study withdrawals (12.3% vs. 12.7%, RR = 0.99, 95% CI = 0.87-1.12, P = 0.83), or AE-related study withdrawals (2.7% vs. 2.1%, RR = 1.37, 95% CI = 0.97-1.93, P = 0.08). Local AEs, all of which were nonserious, were more common with IAHA vs. IA saline (14.5% vs. 11.7%, RR = 1.21, 95% CI = 1.07-1.36, P = 0.003) and typically resolved within days.

Conclusion

IAHA was shown to be safe for use in patients with symptomatic knee OA. Compared with IA saline, IAHA is associated with an increased risk of nonserious, transient local reactions. There was no evidence to suggest any additional safety risks of IAHA.
LINC01534 Promotes the Aberrant Metabolic Dysfunction and Inflammation in IL-1β-Simulated Osteoarthritic Chondrocytes by Targeting miR-140-5p
Authors: wei Wei , He Shaoxuan , Wang Zhihua , Dong Junjie , Xiang Dong , Li Yunxuan , Ren Lirong , Kou Nannan , Lv Jia
Published: November 2019

Objective

Long non-coding RNA 01534 (LINC01534) is highly expressed in the tissues of patients with osteoarthritis (OA). This study investigated the mechanism of LINC01534 on abnormal metabolic dysfunction in OA chondrocytes induced by interleukin-1β (IL-1β).

Methods

The quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expressions of LINC01534, aggrecan, collagen II, and matrix metalloproteinase (MMPs) in OA cartilage tissue or OA chondrocyte model induced by IL-1β. The expressions of aggrecan and collagen II in the chondrocyte were detected by Western blot. The levels of tumor necrosis factor–α (TNF-α), IL-8, IL-6, MMP-13, MMP-9, MMP-3, and prostaglandin E2 (PGE2) in chondrocyte were determined by enzyme-linked immunosorbernt assay. Bioinformatics, dual luciferin gene reporting, RNA pulldown, and Northern blot were used to determine the interaction between LINC01534 and miR-140-5p.

Results

The results showed that LINC01534 was upregulated in both OA cartilage tissue and OA chondrocyte model. In addition, silencing LINC01534 significantly alleviated the inhibitory effect of IL-1β on expressions of aggrecan and collagen II in chondrocytes, and significantly downregulated the expression of matrix metalloproteinases in IL-1β-induced chondrocytes. Meanwhile, silencing LINC01534 also significantly inhibited the productions of proinflammatory factors NO, PGE2, TNF-α, IL-6, and IL-8 in the IL-1β-induced chondrocytes. Furthermore, miR-140-5p was confirmed to be a direct target of LINC01534. More importantly, inhibition of miR-140-5p significantly reversed the inhibitory effect of silencing LINC01534 on abnormal matrix degradation in the IL-1β-induced chondrocyte model of OA.

Conclusion

Therefore, LINC01534 could promote the abnormal matrix degradation and inflammatory response of OA chondrocytes through the targeted binding of miR-140-5p.
Sino-Russian negotiation styles: A cross-cultural analysis of situated patterns
Authors: Malik Tariq H
Published: November 2019

China and Russia have transitioned from centralised economies to mixed markets, they have developed institutions and economic sectors and they joined hands in the strategic partnership in economic and political paths through the Belt and Road Initiative (BRI). Most writers compare or contrast their political and economic powers and preferences vis-a-vis Western cultures and countries; none assess the cultural and contextual styles between the two partners. We build on this question to assess whether and how the two neighbours differ in negotiation style rather than how their institutions shape their behaviour. Based on the behavioural negotiation framework proposed in the early 1990s, we gathered evidence through two surveys: one in Russia and the other in China. We received 988 responses from China and 708 responses from Russia, which we analysed in correlational statistics. The statistical analysis shows negative correlations for four styles of negotiation and positive correlations for six styles of negotiation. We interpreted the negative correlation as divergence between the two cultures and positive correlation as convergence between the two cultures on those styles. The magnitude of the correlation further supports the competing positions of the two cultures on the semantic spectrums. We offer theoretical and policy suggestions at the end of the article. In concluding remarks, we draw attention to multiple gaps which can be filled in future research.
Prediction of Cardiac Complications in SCD
Authors: Pepe Alessia , Pistoia Laura , Gamberini Maria Rita , Macchi Silvia , Commendatore Francesca Valeria , Facchini Elena , Pitrolo Lorella , Celli Mauro , Maggio Aurelio , Preziosi Paolo , Positano Vincenzo , Meloni Antonella
Published: November 2019

Introduction: Cardiac magnetic resonance (CMR) is the non-invasive gold standard for the quantification of biventricular functional parameters and for myocardial tissue characterization.

The aim of this study was to prospectively assess the predictive value of CMR parameters for cardiovascular complications in sickle cell disease (SCD) patients.

Methods: We considered 102 white SCD patients (34.38±12.67 years, 53 females) consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network.

Myocardial iron overload (MIO) was measured by the multislice multiecho T2* technique. Atrial dimensions and biventricular function parameters were quantified by cine images.

Results: At baseline CMR only two patients had MIO (global heart T2*<20 ms).

During a mean follow-up was of 63.29±24.41 months, 10 cardiac events (9.8%) were registered: 3 pulmonary hypertension, 1 pulmonary embolism, 1 peripheral vascular disease, 1 transient ischemic attack, 2 supraventricular arrhythmias, 1 heart failure, and 1 death after acute chest syndrome.

CMR predictors of cardiovascular events at univariate analysis were left ventricular ejection fraction and right ventricular mass index (see Table). Both variables remained independent predictors at multivariate analysis (see Table).

Conclusions: Reduced left ventricular ejection fraction and increased right ventricular mass index showed a significant prognostic value in patients with SCD. Our data seem to suggest that also CMR could be added as screening tool for identifying SCD patients at high risk for pulmonary and systemic vasculopathy and death.

Table

Disclosures

Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.
Going Down the Tubes: A Multidisciplinary Root Cause Analysis on a Patient Safety Event Involving Delayed Transfusions
Authors: Ono Yuho , Stravitz Pamela , Heher Yael , Mohammed Monique , O'Brien Kerry , Uhl Lynne
Published: November 2019

Background

The pneumatic tube delivery system (PTDS) has been an integral part of blood bank (BB) operations at our institution ever since its implementation in the early 2000s. Its reliable performance is essential for rapid and accurate delivery of blood products, impacting patient safety and product integrity. However, malfunctioning operational events are not uncommon given PTDS complexity and hospital-wide utilization. In 2018, 33 of 285 (12%) blood products were wasted due to PTDS events at our institution. Here we review the root cause analysis (RCA) of a patient safety event involving delayed transfusions and a wasted blood product causing temporary harm to two patients.

Methods

Two patients, both hospitalized on the same floor, simultaneously experienced significant delays in red blood cell (RBC) transfusions. One patient with active bleeding experienced a 2-hour delay and another patient with anemia experienced a 50-minute delay before appropriate transfusion occurred. The two patients did not receive their transfusions until their nurses physically retrieved RBC units from the BB. An incident report was filed by a floor nurse, which prompted a RCA involving the laboratory quality and patient safety team, the BB, the hospital maintenance department overseeing the PTDS, and the information systems service controlling programming of the PTDS.

Results

Operational challenges surrounding the PTDS were central to the multiple root causes identified (see Table). RBC units sent to the floor from the BB were electronically directed to another floor or returned to the BB, which resulted in a waste of one RBC unit. Despite multiple potential contributing factors identified, deeper investigation did not uncover evidence for any specific root cause and the electronic tube transaction history showed normal PTDS operations during the time of the incident, with all transactions appearing as successfully completed within expected timeframes. Neither of the patients involved in this safety event experienced permanent harm. The findings of this investigation were reviewed at our departmental Pathology Morbidity and Mortality conference together with stakeholders from hospital maintenance.

Conclusion

The root causes for PTDS technical malfunctioning leading to this safety event remain uncertain despite a collaborative RCA. This multidisciplinary retrospective RCA process, however, provided an opportunity for greater awareness of the complex mechanism of the PTDS, promoted awareness of the roles of the various stakeholders involved, and fostered interdepartmental collaboration to prevent future patient safety incidents using quality improvement principles.

Table

Disclosures

No relevant conflicts of interest to declare.
Ibrutinib Selects for Cells with Elevated Reactive Oxygen Species and Downregulated Phosphatases
Authors: Camp Nathan , Garrett Meghan , Gopal Ajay K. , James Richard
Published: November 2019

Signals from the B-cell receptor are inappropriately activated in B-cell malignancies, including Chronic lymphocytic leukemia (CLL), Mantle cell lymphoma (MCL), and Diffuse large B-cell lymphoma (DLBCL). In CLL, 90% of patients respond to treatment with ibrutinib, an inhibitor of Bruton's Tyrosine Kinase (BTK), with a mean three-year progression free survival rate of approximately 60%. Despite these promising numbers, patients who do not initially respond to ibrutinib have extremely poor outcomes, and nearly all patients eventually become resistant to ibrutinib due to mutations in BTK and its downstream effector Phospholipase C gamma 2 (PLCG2), with a median survival time of 23 months. In order to identify salvage therapies for ibrutinib-resistant patients, we employed several quantitative proteomic methods to identify signaling pathways and proteins that are essential in ibrutinib-resistant patient cells and cell lines. Total proteomic analysis of lymphoma cell lines selected with ibrutinib in vitro revealed that multiple mitochondrial proteins are increased in B cells exposed to ibrutinib. Next, we found that ibrutinib-treated B cells also exhibited increases in reactive oxygen species (ROS), which potently inhibit several protein phosphatases, including B cell receptor signaling regulators PTPN6 and INPP5D. We next looked at tyrosine phosphorylation in patient B cells collected at several time points during ibrutinib treatment and found decreased phosphorylation of both PTPN6 (Y536) and INPP5D (Y944 and Y865) during treatment. Furthermore, total levels of PTPN6 are decreased in patients within 3 months of initiating treatment, and disruption of PTPN6 in cell lines by CRISPR provided a selective advantage in ibrutinib-treated cell populations. Finally, we found that ibrutinib-treated and ibrutinib-naïve primary CLL cells are sensitive to compounds that prevent reactive oxygen species generation (SOD and PHOX inhibitors). Combined, we propose a mechanism by which ibrutinib treatment leads to increased levels of ROS and decreased phosphatase activity, ultimately leading to a growth advantage in the presence of ibrutinib without concomitant mutations in PLCG2 and BTK. We hypothesize that targeting proteins important for reactive oxygen species generation would also be useful in patients and could result in regained disease control and/or prevention of acquired resistance.

Disclosures

Gopal: Seattle Genetics, Pfizer, Janssen, Gilead, Sanofi, Spectrum, Amgen, Aptevo, BRIM bio, Acerta, I-Mab-pharma, Takeda, Compliment, Asana Bio, and Incyte.: Consultancy; Teva, Bristol-Myers Squibb, Merck, Takeda, Seattle Genetics, Pfizer, Janssen, Takeda, and Effector: Research Funding; Seattle Genetics, Pfizer, Janssen, Gilead, Sanofi, Spectrum, Amgen, Aptevo, BRIM bio, Acerta, I-Mab-pharma, Takeda, Compliment, Asana Bio, and Incyte: Honoraria.
The Small Molecule IODVA1 Inhibits the Rac Guanine Nucleotide Exchange Factor Vav3 and Overcomes TKI-Resistance in Ph+(BCR-ABL1) B-ALL
Authors: Nassar Nicolas , Hegde Shailaja N , Gasilina Anjelika , Wunderlich Mark , Premnauth Gurdat , Merino Edward , Lin Yuan , Ahmadian Reza , Zheng Yi , Mizukawa Benjamin , Privette Vinnedge Lisa , Cancelas Jose A
Published: November 2019

Aberrant activation of Rho guanine nucleotide exchange factors (RhoGEFs) is a chief mechanism driving abnormal activation of their RhoGTPase targets in cancer. Thus, small molecule inhibitor of RhoGEF activities can be used as a drug lead to treat leukemia and other malignancies. We have identified an active small molecule, IODVA1, in several xenograft mouse models of cancer including Ras-driven cancers. Here, we used cellular and mouse models of Ph+(BCR-ABL1) B-ALL to identify Vav3, the multi-domain tyrosine phosphorylation-dependent RacGEF as the target of the small molecule IODVA1.

IODVA1 specifically reduces the proliferation and survival of p190-BCR-ABL but not of empty vector expressing human CD34+ blood cells. IODVA1 binds tightly to recombinant Vav3 (Kd= 400 nM) but not to Rac1 or to the RhoGEF LARG. In Ba/F3 cells expressing p190-BCR-ABL, IODVA1 inhibits Rac activation and signaling within minutes of exposure. The decrease in Rac activity is not due to the activation of p50GAP or RhoGDI1 and is accompanied by a decrease in the activity of the pro-survival effectors PAK, JNK, and 4EBP and an increase in pro-apoptotic BAD activity. IODVA1prevents leukemia-related death and eliminates the leukemia burden in a BCR-ABL-induced murine model with no apparent toxicity. It eradicates leukemic propagating activity assessed by serial transplantation. Most importantly, IODVA1 increases the survival of a mouse model of TKI-resistant p210-BCR-ABL1(T315I) B-ALL better than ABL1-TKI imatinib and eliminates leukemic burden. p210-T315 leukemic mice survive 45 days after treatment has ended. Vav3- and Rac1/Rac2-deficient leukemic cells do not respond to IODVA1 in colony formation assay consistent with Vav3 being IODVA1's target. A mouse model of BCR-ABL leukemia deficient in Vav3 also does not respond to IODVA1. Cells from PDX models representing pediatric ALL patients including Ph+ (BCR-ABL(T315I) were found to be highly sensitive to IODVA1 ex vivo. Based on the described mechanism of action, we propose that IODVA1 is an allosteric inhibitor of Vav3 that holds promise as an anti-leukemic agent.

Disclosures

Cancelas: Hemanext: Consultancy, Research Funding; Fresenius-Kabi: Research Funding; Cerus Co.: Research Funding; TerumoBCT: Consultancy, Research Funding; Velico: Consultancy, Research Funding; Macopharma Inc: Research Funding; Cytosorbents: Research Funding; Cellphire: Research Funding.
Trend and Geographic Variations in the Incidence of Mantle Cell Lymphoma in the United States over 30 Years from 1975 to 2004.
Authors: Zhou Yuhong , Wang Haijun , Du Xin , Yi Qing , Zhang Yanxia , Romaguera Jorge , Wang Michael
Published: November 2019

Background: Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin’s lymphoma (NHL). To better understand the incidence and epidemiological features of MCL in the United States, we conducted a population-based study with 2635 patients (pts) of MCL identified from 9 Surveillance, Epidemiology, and End Results (SEER) tumor registries over 30 years.

Methods: From SEER public database, we identified 111 424 pts of all ages diagnosed with NHL between 1975 and 2004 in 9 SEER areas. Of these pts, 2635 had histologically confirmed MCL, accounting for 2.36% of NHL. The incidence with 95% confidence intervals were generated from SEER*Stat Software. Incidence was age-adjusted to the U.S. 2000 standard population. Annual percent change (APC) for the incidence was calculated and considered to be statistically significant if P<0.05. The crude 1-year survival rate was calculated as the ratio of the number of pts who survived over 1 year and the number of pts diagnosed with MCL.

Results: Of 2,635 pts with MCL, 68.1% were late-stages (stages III IV), 25.6% were early-stages (stages I–II), and 6.3% were unstaged. Median age at diagnosis for MCL was 68.0. Overall incidence was 0.41/100,000/year, which increased by age from 0.06 in pts aged <50 to 2.11 for 70–79 and 2.02 in pts aged 80 or older. The age-adjusted incidence increased from 0.08 in 1975 to 0.67 in 2004. APC was 4.64% (P<0.05). Incidence of MCL was higher in men (0.60) than in women (0.27) (P<0.05). Annual increase was greater in men (5.67%) than in women (2.93%). There were also substantial geographic variations (P<0.05) in the incidence of MCL. The age-adjusted incidence was highest in Seattle (0.49) and the lowest in Hawaii (0.33). The incidence appeared to be higher in Caucasians (0.44) than in African-Americans (0.25) and other races (0.25). Annual increase(from 1987–2004) was 8.68% in Caucasians, and 1.64% in African-Americans and other races.

Conclusions: The incidence of MCL increased progressively from 1975 to 2004, and was significantly higher in males and in Caucasians. There were substantial geographical variations in the incidence of MCL.
Distribution and Pathology Characteristics of Non Hodgkin Lymphoma in Peru: A Study of 1014 Cases Using WHO Classification of Lymphoid Neoplasm.
Authors: Beltran Brady , Morales Domingo , Quiñones Pilar , Salas R. , Carrasco-Yalan Antonio A.
Published: November 2019

BACKGROUND: The frequency of various subtypes of non-Hodgkin’s lymphoma (NHL) differs in various regions worldwide.

OBJECTIVE: To investigate the clinical and pathological features of non-Hodgkin’s lymphoma (NHL) and to evaluate the applicability of the new WHO classification of lymphoid neoplasms.

METHODS: According to the new WHO classification, a total of 1014 cases of non-Hodgkin’s lymphoma diagnosed during the period 2002–2006 were reviewed and reappraised with their morphological, immunological and clinical characteristics in one general hospital from Lima, Peru. All cases corresponded >18 years old.

RESULTS: There were 535 males and 479 females, mean age was 62.1 years (range 18 – 97 years) and the median was 64 years. B-cell neoplasms accounted for 763 cases (75.2%) and T/NK-cell neoplasms for 189 (18.6%). Sixty two cases (6.1%) were not classified. It was seen compared to that in the other Asian countries. Indolent lymphomas accounted for 17%, and aggressive ones for 83%. Among indolent lymphomas follicular grade I and II were the most common subset while MALT was second with low frequency. Among the aggressive lymphomas diffuse large cell lymphoma (DLCL) was the most common subtype, and accounted for 58.8% of all B cell lymphomas. Mantle and Burkitt lymphoma were very low incidence. Among the T cell lymphomas, peripheral T cell lymphomas, mycosis fungoides, Adult T Lymphoma/Leukemia (ATLL), T/NK nasal type Lymphoma were the most common subtypes. Nodal NHL occurred in 52% and extranodal in 48% of the cases. The more common extranodal presentation was stomach (14.1%), skin (8.1%), small intestine (2.9%) and nose (2.3%)

CONCLUSIONS: The high incidence of T cell lymphomas, extranodal presentation and reduced frequency of indolent lymphoma in the current study is comparable to that reported from Asian countries.
Posttransplant Lymphoproliferative Disorder in Adult Lung Transplant Recipients: A Report on Twenty-Seven Patients.
Authors: Stein Sophie D. , Misleh Jamal , Ahya Vivek , Kotloff Robert , Christie Jason , Tsai Donald E.
Published: November 2019

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation. We report a case series on the diagnosis, treatment and outcome of PTLD in lung transplant recipients. From 1991 to 2006, 27 (5%) of the 502 lung transplant recipients at our institution developed PTLD. The median age at transplant was 51.5 years (range 21–65 years) and the median time from transplant to PTLD diagnosis was 33.7 months (range 1–174 months). Most cases had an elevated LDH (86%) and were EBV-positive (85%). Of the cases tested (n=14), 64% were monoclonal. PTLD was most commonly diagnosed in the lung (56%) and gastrointestinal tract (26%). Three patients were diagnosed at autopsy, while the remaining 24 received therapy. Eight patients were initially treated with reduced immunosuppression (RI) alone, but only 3 (38%) obtained a complete response (CR). Rituxan (R) was used alone (n=3) or in combination with RI (n=3) as initial therapy in six patients, four of whom obtained a CR. Five patients utilized RI +/− surgical resection as a primary treatment modality, all of whom achieved a CR. However, all of them relapsed and required further treatment. Of these five patients initially treated with RI +/− surgical resection, a CR was reestablished in 3 using rituxan alone (1/3), combined rituxan and reduced immunosuppression (1/3) and radiation treatment alone (1/3). The remaining five patients from the 24 patients receiving induction therapy for PTLD were given other treatments. With an average follow-up of 28 months (range 1-130 months), 81% of patients have died. However, only 18% of deaths were directly related to progressive PTLD. The remaining 17 deaths were due to: infection unrelated to PTLD treatment (15%), multi-organ failure (7%), graft failure not due to RI (30%), stroke (4%), and renal failure (4%). Most deaths can be attributed to disease specific and posttransplant complications rather than PTLD. Although an unfortunate diagnosis, PTLD is responsive to therapy, particularly reduced immunosuppression and rituximab.
Correlation of Multiparameter Flow Cytometry and Fluorescence In Situ Hybridization in Quantifying Malignant Cells at Low Frequencies in B-Cell Lymphoproliferative Diseases.
Authors: Kern Wolfgang , Haferlach Torsten , Schnittger Susanne , Haferlach Claudia
Published: November 2019

Diagnostic and follow-up evaluation of patients with B-cell lymphoproliferative diseases includes the assessment of peripheral blood and bone marrow samples by both multiparameter flow cytometry (MFC) and fluorescence in situ hybridization (FISH) for the detection and quantification of malignant cells. Depending on the type of aberrant immunophenotype and on the probes applied for FISH sensitivity may vary particularly if small populations of malignant cells are present. We evaluated 61 peripheral blood (n=20) and bone marrow (n=41) samples from patients with B-cell lymphoproliferative diseases in which malignant cell populations as quantified by MFC were <15% and in which chromosomal aberrations were identified by FISH analysis. The diagnoses included CLL and CLL/PL (n=23), follicular lymphoma (FL, n=16), mantle cell lymphoma (MCL, n=10), and other B-cell lymphoproliferative diseases comprizing mainly marginal zone lymphomas and lymphoplasmacytic lymphomas (B-NHL, n=12). A standardized panel was used for MFC including antibodies against CD5, CD10, CD11c, CD19, CD20, CD22, CD23, CD25, CD38, CD45, CD79b, CD103, FMC7, IgM, Kappa, and Lambda. FISH was performed including probes for del(6q), del(11q), trisomy 12, del(13q), del(17p), t(11;14), t(14;18), IGH, CMYC, and BCL6. The median number of malignant cells as quantified by MFC amounted to 8% (range, 2% to 14%). The median number of malignant cells as quantified by FISH amounted to 9% (range, 1% to 42%). Overall, there was a high degree of correlation between both methods (r=0.544, p<0.0001). In particular, there were good correlations within the subgroups CLL (r=0.402, p=0.057) and MCL (r=0.876, p=0.001). Accordingly, correlations were significant for results obtained by FISH probes for trisomy 12 (r=0.649, p=0.005) and for t(11;14) (r=0.693, p=0.009) while the correlation for cases with t(14;18) were less strong (r=0.411, p=0.101). The present results confirm that in patients with B-cell lymphoproliferative diseases malignant cells may be detected and quantified by both MFC and FISH with good correlation even if present at very low frequencies only. So far our data are not in favor of either MFC or FISH for analyzing low percentages of lymphoma infiltration. Future studies should assess the clinical relevance of low level infiltration of peripheral blood and bone marrow and the respective roles of MFC and FISH in their detection.
Clinical Profile of Patients with Primary Gastric Lymphoma: A Single Centre Experience.
Authors: Ambulkar Indumati B. , Goyle Sandeep , Borker Anupama , Tawde Bhairavi , Advani Suresh H.
Published: November 2019

BACKGROUND/AIMS: There are many controversies regarding the treatment for primary gastric non-Hodgkin’s lymphoma (PGL). We hypothesized that chemotherapy and local radiotherapy would improve patient survival in the treatment of with PGL.

METHODOLOGY: Between January 2003 and July 2007, retrospectively evaluated 15 patients with stage IE and IIE PGL. All patients clinical, biochemical, radiological and endoscopic features were evaluated. The histological diagnosis was established by endoscopic biopsies in all cases. All patients were treated with CHOP,RCHOP with or without radiotherapy. Patients with MALT as histopathology received H.pylori treatment. Upon the completion of chemotherapy, IFRT was given in the doses of 40.0 Gy. None of the patients underwent surgery. The response rates of chemotherapy and radiotherapy were analyzed.

RESULTS: We have treated 300 patients of non hodgkins lymphomas, extranodal NHLs were 80, GI lymphomas were 50,15 patients had PGL. The age rage was 39–71 years. Nine patients were males and 6 were females. The most common symptom was abdominal pain in 46.66% followed by abdominal mass in 33.33%,dyspepsia in 13.33% and weakess in 6.66% of patients. Duration of symptoms varied from 15 days to 6 months. Histological subtypes were diffuse large B-cell in 80% and marginal zone B-cell NHL of the mucosa-associated lymphoid tissue (MALT)-type in 20% of patients. Helicobacter pylori infection (HPI) was seen in all MALT type NHLs. Six patients(40%) received RCHOP with RT followed by RCHOP in 4(26.66%), CHOP in 3(20%) and R-CHOP with RT in 2 (13.33%) patients. Response was evaluated by repeat endoscopy after completion of 3 and 6 cycles. Fourteen (93.33%) patients showed complete response only after 3 cycles of chemotherapy. Only one (6.66%) relapsed who received CHOP alone. All patients are alive with a median follow-up of 30 months (range 2 to 54 months).

CONCLUSIONS: Primary chemotherapy with or without radiotherapy may produce complete remission in Stage IE-IIE PGL. The gastric function was well preserved with negligible stomach-related symptoms in all the patients. This organ-preserving combined treatment is highly effective and well tolerated for the patients with localized gastric DLBCL.
Results of a Nonrandomized, Open-Label, Phase II Study of Combined Gemcitabine, Mitoxantrone, and Rituximab in Relapsed or Refractory Mantle Cell Lymphoma.
Authors: Garbo Lawrence E. , Flynn Patrick J. , MacRae Margaret A. , Rauch Mary A. , Wang Yunfei , Kolibaba Kathryn S.
Published: November 2019

Mantle cell lymphoma (MCL) is an aggressive type of B-cell non-Hodgkin’s lymphoma that usually presents as disseminated disease. Prognosis is poor, and responses to chemotherapy are less durable than those achieved in other types of lymphoma. New treatment options are desperately needed. Gemcitabine has shown activity in MCL as a single agent. In addition, the combination of mitoxantrone and rituximab has also been shown to be active in MCL. However, the use of these drugs in combination has not been evaluated in the treatment of MCL. The primary objective of this study was to determine the efficacy of gemcitabine+mitoxantrone+rituximab in relapsed or refractory MCL; secondary objectives were duration of response, survival at 1-year, progression-free survival (PFS), and toxicity, especially myelotoxicity. Sixteen patients were enrolled between April 2005 and December 2006, and only 15 were evaluable due to one patient’s withdrawal of consent. Patients received gemcitabine 900 mg/m2 IV (30–60 min infusion), mitoxantrone 10 mg/m2 IV (5–10 min infusion), and rituximab 375 mg/m2 IV on Day 1 (max 400 mg/hr). Patients also received gemcitabine 900 mg/m2 on Day 8 of the 21-day cycle. Medication was administered in the following order: gemcitabine→mitoxantrone→rituximab. Patients were to be treated for a maximum of 8 cycles or until the patient had evidence of a response, progressive disease, or intolerable toxicity. The median patient age was 74 years, 100% were white, and 69% were male. Of all patients, 86% had Stage IV MCL at baseline. Patients received a median of 6 cycles (range, 3 – 8). Efficacy results for the evaluable population are CR 13%, PR 27%, PD 13%, and SD 47%. Median PFS was 8.72 months (range, 1.84 – 23.49); median overall survival was 10.03 months (range, 2.50 – 23.49). Grade 3–4 treatment related toxicities reported in >1 patient were neutropenia (93%), leukopenia or thrombocytopenia (53% each), anemia (20%), and asthenia (13%). 60% of patients are currently alive as of July 2007; 9 patients discontinued study treatment due to disease progression (13%), toxicity (27%), MD request (7%), or withdrawal of consent (13%). 7 patients had normal study completion (44%). The study was closed early due to slow accrual owing to alternative treatment which became available at the time. The combination of gemcitabine, mitoxantrone, and rituximab in MCL was well-tolerated with manageable adverse events in spite of 93% neutropenia. Supplemented growth factor use was able to minimize neutropenia. No Grade 3–4 infection was reported. This regimen holds promise in patients with MCL and further studies are warranted. Updated data will be presented.
Phase II Study of RCHOP with Pegylated Liposomal Doxorubicin (DRCOP) for Patients > 60 Years Old with Untreated Diffuse Large B Cell Lymphoma (DLBCL).
Authors: Rodriguez Maria Alma , Fanale Michelle , Hagemeister Fredrick , McLaughlin Peter , Pro Barbara , Romaguera Jorge , Kwak Larry , Fayad Luis , Huang Xuelin , Durand Jean Bernard
Published: November 2019

Background: DLBCL is a common lymphoma of older adults, and a potentially curable disorder with the regimen RCHOP (Coiffier, et.al. NEJM,2002). Doxorubicin, a key drug in the regimen, has risk for cardiotoxicity, and thus of concern in older patients (pts) with higher incidence of cardiovascular (CV) disease. In breast cancer pts pegylated liposomal doxorubicin (D) has shown greater cardiac safety and similar efficacy to doxorubicin. We thus replaced doxorubicin with D in RCHOP (DRCOP).

Methods: The regimen is: Rituximab 375 mg/m2 IV day (d) 1; D 40 mg/m2 IV d 1; cyclophosphamide 750 mg/m2 IV d 1; vincristine 2 mg IV d 1 total dose; prednisone 100 mg/d p.o. d 1–5. Eligibility criteria are: > 60 years of age; untreated confirmed DLBCL (no discordant histology); Ann Arbor stage II-IV; baseline LVEF 50%. CV disease is permitted, if symptoms controlled, but consult at baseline by Cardiologist and at follow-up required. Growth factor support recommended (not required).

Results: 34 pts are evaluable for toxicity; 30 evaluable for response (1 pt off study after 1 cycle; 3 too early for response). Characteristics of pts: age 62–92 (median 75); 18 female; IPI 1=1pt; IPI 2 = 2 pts; IPI 3 = 16 pts; IPI >3 = 15 pts. Responses are: 28/30 (93%) CR; 2/30 (7%) PR. At this time, 3/30 failed: 1 progression; 1 death due to non-neutropenic pneumonia; 1 death due to disease. Grade 3–4 adverse events were: 1 drop in LVEF; 8 atrial arrhythmias (reversed); 1 hypotension (reversed); 1 chest pain (reversed); 17 neutropenia (13 febrile, with 5 infections); 3 hand-foot syndrome; 4 fatigue; 2 DVT; 2 neuropathy.

Conclusions: DRCOP has a high CR rate in this study of older pts with DLBCL, despite intermediate/high risk IPI. We’ve noted only one case of low LVEF ; more common are atrial arrythmias (8 pts), reversible. Neutropenia is the most common grade 3–4 adverse event (17 pts), and thus we strongly recommend growth factor support.
Treatment of Diffuse Large B-Cell Lymphoma of the Liver with Yttrium-90 Microsphere Embolization.
Authors: Benjamin Heather L. , Fenske Timothy S. , Kroft Steven H. , Hohenwalter Eric J. , Rilling William S.
Published: November 2019

We present a case of successful treatment of chemoresistant hepatic lymphoma using yttrium-90 micropheres. A 41 year-old male with a history of hepatitis C presented with fatigue, night sweats, right upper quadrant pain, a 20 pound weight loss, and hypercalcemia. CT scan of the abdomen revealed a 13.4 x 10.0 cm mass involving the right hepatic lobe, along with portohepatic, celiac, and retroperitoneal lymphadenopathy. Ultrasound-guided core biopsy of the portohepatic mass showed diffuse large B-cell lymphoma (DLBCL). The patient had a partial response to R-CHOP, and was subsequently treated with 3 additional chemotherapeutic regimens. Despite this extensive therapy, as well as surgical resection of hepatic lesions, he had residual lymphoma within the liver. Due to inadequate chemosensitivity, he was not a candidate for stem cell transplantation. Repeat biopsy showed loss of CD20 expression, eliminating radioimmunotherapy as an option. Because the residual lymphoma was confined to the liver, the patient was treated with yttrium-90 microspheres (TheraSphere®). The patient had a significant improvement in his abdominal pain. Furthermore, six weeks after treatment, a complete response in the hepatic lesions was documented by PET/CT scan. Although the patient later developed recurrent disease outside of the liver, the case clearly demonstrates the potential clinical utility of this approach in properly selected lymphoma patients. To our knowledge, this is the first reported case documenting clinical activity of yttrium-90 microspheres for lymphoma.