State-of-the-Art Management of Complications of Myeloma and Its Treatment

Multiple myeloma is an incurable disease, although patient survival has increased with the availability of novel agents. Both multiple myeloma and its therapies often affect the renal, immune, skeletal, hematologic, and nervous systems. The resulting organ dysfunctions often impair the quality of life of affected patients, complicate and limit subsequent therapies, and may result in significant mortality. Research on the treatment of complications of multiple myeloma has been limited; hence, preventative and management strategies for patients with these complications are heterogeneous and often based on anecdotal experience. In this paper, we review the effects of myeloma and the novel therapies on organ systems and suggest management strategies.

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Evidence Based Recommendations for Supportive Care in Multiple Myeloma

Blood ◽

10.1182/blood-2018-99-110748 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1952-1952

Author(s):

Anum Qureshi ◽

Muhammad Junaid Tariq ◽

Zunairah Shah ◽

Muhammad Abu Zar ◽

Shehroz Aslam ◽

...

Keyword(s):

Quality Of Life ◽

Multiple Myeloma ◽

Supportive Care ◽

Conflicts Of Interest ◽

Control Group ◽

Cell Transplant ◽

Clodronic Acid ◽

Management Of Complications ◽

Reduced Risk

Abstract Introduction: Multiple myeloma (MM) is associated with end organ damage that negatively impacts the quality of life (QOL)and supportive care has a potential to improve symptoms. Methods: After detailed search on Pubmed, Cochrane, Embase and Clinical Trials.gov, we finalized total 36 articles on supportive care published after 2004. Results: Management of skeletal events: Mhaskar et al. (2017, n=3257) compared bisphosphonates (BPs) with placebo (PBO) in preventing pathological vertebral fractures, skeletal-related events (SRE), reported risk ratio (RR) of 0.74 in each; 95% CI 0.62-0.89 and 0.63-0.88 respectively. Both zoledronic acid (ZA) and clodronic acid prevent SRE, but mortality rate was better reduced with ZA (hazard ratio [HR]=0.84; p=0.0118), (Gareth et al. 2010, n=1960). In a study by Zuradelli et al. (2009, n= 240); hypocalcemia developed in 93 (38.8%) patients on ZA for a median of 2.3 months (range, 0-34.9). Vitamin D and calcium replacement is essential in patients developing hypocalcemia with BPs, (Kennel et al. 2009). Vertebral augmentation procedures improved pain after compression fracture (n=923) by 4.8, 4.6 and 4.4 points at 1 week, 1 year and beyond 1 year respectively, (Khan et al. 2014). Valerie et al. (2011, n=84) analyzed improvement in bone pain with radiotherapy (median 45 grays) in 92 % patients. Prophylaxis of infections: Leng et al. (2018, n=70,687) observed reduced risk of herpes zoster (HZ) reactivation in patients on bortezomib or carfilzomib + HZ prophylaxis (2.4%) vs 5.8% in non-prophylactic group, (attributable risk reduction: 0.42; 95% CI 0.31-0.56). Teh et al. (2016, n=199) reported reduced risk of varicella zoster virus reactivation with valacyclovir (500 mg) in patients on bortezomib based therapy and following autologous stem cell transplant (ASCT) vs no prophylaxis (HR=0.06 vs 16.9; p<0.01). Dimopoulos et al. (2016, n=569) found higher risk of pneumonia, 8.2% in daratumumab group (n=286) vs 7.8% in control group (n=283). Prophylactic trimethoprim-sulfamethoxazole reduced risk of PCP in 85% patients after ASCT (RR=0.15; 95% CI 0.04-0.62), Stern et al. (2014, n=1000). Incidence of Community-acquired pneumonia (CAP), noninvasive CAP and invasive pneumococcal disease in elderly population (≥65 years) was seen in 49, 33 and 7 patients on Pneumococcal polysaccharide conjugate vaccine group as compared to 90, 60 and 28 patients in placebo group respectively, (Bonten et al. 2015, n=84,496). Role of plasmapheresis in renal impairment (RI): Alkhatib et al. (2017) showed that plasmapheresis reduced dialysis dependency by removing serum free light chains (sFLC) in patients with RI (n=147), (RR 0.45; P = 0.02). Yu-X et al. (2015, n=147), showed lower 6-month dialysis dependency ratio with plasmapheresis and chemotherapy (PP + CTH) vs CTH alone, (15.6% vs 37.2%; RR=2.02; p = 0.04). High cut-off hemodialysis lowered sFLC level in 61% (n=42) and 63% patients at day 12 and 21 respectively. Out of these, 71% and 69% patients became dialysis independent, (Hutchison et al. 2012, n=67). Peripheral neuropathy (PN): Bortezomib caused PN in 124/331 (37%) patients (Richardson et al. 2009) whereas with thalidomide, the incidence of PN was 38% and 73% at 6 and 12 months, respectively, (Mileshkin et al. 2006, n=75). PN improved in 68% patients on bortezomib with dose modifications (n=72) vs 47% patients, without dose modification (n=19). (Table 1 and 2). Significant improvement in PN was seen with duloxetine vs placebo (1.06 vs. 0.34; p= 0.003), (Smith et al. 2013, n=231). Arbaiza et al. (2007, n=36) showed improvement in neuropathic pain with tramadol (p= < 0.001). Epoetin and derivates for anemia: Castelli et al. (2017, n= 31; median creatinine 1.2 mg/dL (0.8-3.0)) reported hemoglobin (Hb) increase of ≥1g/dL and ≥2g/dL in 71% and 31.7% patients respectively with epoetin α, transfusions requirement reduced from 2.39 ± 1.05 to 1.23 ± 1.36 (p < 0.001). Begiun et al. (2013, n= 72) compared the effect of darbepoetin (D) ± iron (Fe) vs placebo on erythroid recovery after ASCT. All patients receiving D + Fe achieved Hb ≥13 g/dL (p<0.0001). Tonia et al. (2012, n= 16,093) showed 35% decrease in transfusion need with erythropoietin stimulating agents (RR=0.65; 95% CI 0.62-0.68). (Table 3) Conclusion: Along with anti-myeloma chemotherapy therapy, management of complications (anemia, infections, renal insufficiency) and other associated symptoms is necessary to improve the quality of life. Disclosures No relevant conflicts of interest to declare.

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The role of angiogenesis in multiple myeloma treatment

Diagnostyka Laboratoryjna ◽

10.5604/01.3001.0014.4722 ◽

2020 ◽

Vol 56 (2) ◽

pp. 1-6

Author(s):

Magdalena Zduńska ◽

Sylwia Ziółkowska ◽

Danuta Rość

Keyword(s):

Multiple Myeloma ◽

Clinical Research ◽

Plasma Cells ◽

Bone Lesions ◽

Direct Production ◽

Incurable Disease ◽

Health And Disease ◽

Tumor Growth And Metastasis

Angiogenesis is an important biological process of the formation of new blood vessels from pre-existing ones. It occurs throughout life in health and disease, beginning in the prenatal stage and continuing through old age. Angiogenesis is regulated, by both activator and inhibitor molecules. Physiological angiogenesis is under the control of angioinhibitory molecules. Unregulated angiogenesis may lead to several angiogenic diseases and is thought to be indispensable for solid tumor growth and metastasis. Multiple myeloma is an incurable disease characterized by clonal plasma cell proliferation and overproduction of monoclonal paraprotein, hypercalcemia, renal failure, anemia, osteolytic bone lesions, and infections. Angiogenesis plays an important role in the biology of multiple myeloma and has a prognostic value in this disease. The pathophysiology of multiple myeloma-induced angiogenesis involves both direct production of angiogenic cytokines by plasma cells and their induction within the bone marrow microenvironment cells. Multiple myeloma has been the most intractable hematological disease for many years. Recently, basic and clinical research has advanced remarkably and a new therapeutic strategy has been established. Despite unusual progress in the therapy of multiple myeloma none of the available drugs are curative. Present clinical research focuses on the balance between treatment efficacy and quality of life. In this review, we summarize recent data about myeloma-induces angiogenesis, the mechanism involved in this process, and the treatment of multiple myeloma.

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New proteasome inhibitors in the management of multiple myeloma

Oncohematology ◽

10.17650/1818-8346-2019-14-2-29-40 ◽

2019 ◽

Vol 14 (2) ◽

pp. 29-40 ◽

Cited By ~ 2

Author(s):

S. V. Semochkin

Keyword(s):

Multiple Myeloma ◽

Drug Resistance ◽

Clonal Evolution ◽

Proteasome Inhibitors ◽

The Novel ◽

Hematopoietic Stem ◽

Refractory Multiple Myeloma ◽

Incurable Disease ◽

Oral Method

The landscape of multiple myeloma treatment transformed at the last 15 years by the introduction of novel agents (bortezomib, lenalidomide) and wide application of autologous hematopoietic stem cell transplantation, which have prolonged the survival of multiple myeloma patients. Despite the fact that multiple myeloma remains an incurable disease due to the new options, the median overall survival of patients with multiple myeloma in Russia in 2006–2016 was about 55–68 months. Drug resistance and clonal evolution remain a problem. The novel proteasome inhibitors (carfilzomib, ixazomib) differ in chemical structure and pharmacological characteristics. Thereby the next-generation proteasome inhibitor (IPs)-based regimens (KRd (carfilzomib, lenalidomide, dexamethasone), IRd (ixazomib, lenalidomide, dexamethasone), and Kd (carfilzomib, dexamethasone)) are emerging as new standards for the treatment of patients with relapsed and/or refractory multiple myeloma. In a randomized trial phase 3 ENDEAVOR, carfilzomib demonstrated improved survival in direct comparison to bortezomib. The dose-dependent activity of carfilzomib demonstrated in the study of A.R.R.O.W. Аctivity of ixazomib is comparable to that of bortezomib, the oral method of administration and the absence of neurological toxicity, allow for long-term control of the disease. The new PIs are an important advance in relapsed and/or refractory multiple myeloma treatment, increasing survival, response rate and quality of life, even in subgroups of patients with poor prognosis. This review summarizes the main pharmacological properties, mechanisms of action and clinical outcomes of major clinical studies with these agents. A separate issue discusses the problem of overcoming new proteasome inhibitors of drug resistance to bortezomib.

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Dual-Embedding based Deep Latent Factor Models for Recommendation

ACM Transactions on Knowledge Discovery from Data ◽

10.1145/3447395 ◽

2021 ◽

Vol 15 (5) ◽

pp. 1-24

Author(s):

Weiyu Cheng ◽

Yanyan Shen ◽

Linpeng Huang ◽

Yanmin Zhu

Keyword(s):

Collaborative Filtering ◽

State Of The Art ◽

Factor Models ◽

Superior Performance ◽

Implicit Feedback ◽

The Novel ◽

Latent Factor ◽

Latent Factor Models ◽

Real World Datasets

Among various recommendation methods, latent factor models are usually considered to be state-of-the-art techniques, which aim to learn user and item embeddings for predicting user-item preferences. When applying latent factor models to the recommendation with implicit feedback, the quality of embeddings always suffers from inadequate positive feedback and noisy negative feedback. Inspired by the idea of NSVD that represents users based on their interacted items, this article proposes a dual-embedding based deep latent factor method for recommendation with implicit feedback. In addition to learning a primitive embedding for a user (resp. item), we represent each user (resp. item) with an additional embedding from the perspective of the interacted items (resp. users) and propose attentive neural methods to discriminate the importance of interacted users/items for dual-embedding learning. We design two dual-embedding based deep latent factor models, DELF and DESEQ, for pure collaborative filtering and temporal collaborative filtering (i.e., sequential recommendation), respectively. The novel attempt of the proposed models is to capture each user-item interaction with four deep representations that are subtly fused for preference prediction. We conducted extensive experiments on four real-world datasets. The results verify the effectiveness of user/item dual embeddings and the superior performance of our methods on item recommendation.

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A Graphical and Attentional Framework for Dual-Target Cross-Domain Recommendation

Proceedings of the Twenty-Ninth International Joint Conference on Artificial Intelligence ◽

10.24963/ijcai.2020/415 ◽

2020 ◽

Author(s):

Feng Zhu ◽

Yan Wang ◽

Chaochao Chen ◽

Guanfeng Liu ◽

Xiaolin Zheng

Keyword(s):

State Of The Art ◽

The Novel ◽

Target Domain ◽

Cross Domain ◽

Single Target ◽

Recommendation Accuracy ◽

Real World Datasets ◽

Content Information ◽

Dual Target

The conventional single-target Cross-Domain Recommendation (CDR) only improves the recommendation accuracy on a target domain with the help of a source domain (with relatively richer information). In contrast, the novel dual-target CDR has been proposed to improve the recommendation accuracies on both domains simultaneously. However, dual-target CDR faces two new challenges: (1) how to generate more representative user and item embeddings, and (2) how to effectively optimize the user/item embeddings on each domain. To address these challenges, in this paper, we propose a graphical and attentional framework, called GA-DTCDR. In GA-DTCDR, we first construct two separate heterogeneous graphs based on the rating and content information from two domains to generate more representative user and item embeddings. Then, we propose an element-wise attention mechanism to effectively combine the embeddings of common users learned from both domains. Both steps significantly enhance the quality of user and item embeddings and thus improve the recommendation accuracy on each domain. Extensive experiments conducted on four real-world datasets demonstrate that GA-DTCDR significantly outperforms the state-of-the-art approaches.

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Sport and Physical Education at Abdelmalek Essaâdi University: State of the Art

International Journal of Information Technology and Applied Sciences (IJITAS) ◽

10.52502/ijitas.v3i2.40 ◽

2021 ◽

Vol 3 (2) ◽

pp. 94-102

Author(s):

SOULAIMAN HARFOUF

Keyword(s):

Higher Education ◽

Physical Education ◽

Functional Organization ◽

State Of The Art ◽

Management Strategies ◽

The Other ◽

Public Higher Education ◽

Sport Activities ◽

Lack Of Commitment

This research deals with the issue of Physical Education (PE) and Sport at Abdelmalek Essaâdi University, Tetouan, Morrocco. It adopts a problem related to the diagnosis and development of the Physical Education/sport system in this Moroccan institution of public higher education. After verifying whether certain factors are responsible for the dysfunction of this system at the UAE, this study subsequently makes proposals that could contribute to improving its performance. The results of this study show that the PE/sport system in the UAE suffers from a more or less significant lack, in number and quality, of human, financial, material and infrastructural resources. On the other hand, a deficient and non-functional organization, the absence of management strategies, the omission of regular evaluation of the system, the low motivation and the lack of commitment of the administrative and associative actors mark the managerial approach of the sports sector in the majority of schools and faculties of the UAE. Consequently, we conclude that all of these elements are responsible for the dysfunctional situation that PE and sport are currently experiencing in the UAE. Also, the conclusions of this study reveal the way in which the leaders in this university represent the importance of sport activities among the educational, academic and para-academic offer. All of them are in favor of developing sports in their institutions, but without being really determined and equipped to make it happen.

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Data Science in Economics: Comprehensive Review of Advanced Machine Learning and Deep Learning Methods

Mathematics ◽

10.3390/math8101799 ◽

2020 ◽

Vol 8 (10) ◽

pp. 1799 ◽

Cited By ~ 2

Author(s):

Saeed Nosratabadi ◽

Amirhosein Mosavi ◽

Puhong Duan ◽

Pedram Ghamisi ◽

Ferdinand Filip ◽

...

Keyword(s):

Machine Learning ◽

Deep Learning ◽

Data Science ◽

State Of The Art ◽

Science Methods ◽

The Novel ◽

Learning Models ◽

Diverse Range ◽

Hybrid Machine

This paper provides a comprehensive state-of-the-art investigation of the recent advances in data science in emerging economic applications. The analysis is performed on the novel data science methods in four individual classes of deep learning models, hybrid deep learning models, hybrid machine learning, and ensemble models. Application domains include a broad and diverse range of economics research from the stock market, marketing, and e-commerce to corporate banking and cryptocurrency. Prisma method, a systematic literature review methodology, is used to ensure the quality of the survey. The findings reveal that the trends follow the advancement of hybrid models, which outperform other learning algorithms. It is further expected that the trends will converge toward the evolution of sophisticated hybrid deep learning models.

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Data Science in Economics

10.21203/rs.3.rs-27318/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Saeed Nosratabadi ◽

Amir Mosavi ◽

Puhong Duan ◽

Pedram Ghamisi ◽

Ferdinand Filip

Keyword(s):

Deep Learning ◽

Data Science ◽

State Of The Art ◽

Hybrid Models ◽

Science Methods ◽

The Novel ◽

Learning Models ◽

Wide Range ◽

Hybrid Machine

Abstract This paper provides the state of the art of data science in economics. Through a novel taxonomy of applications and methods advances in data science are investigated. The novel data science methods and applications are investigated in four individual classes of deep learning models, hybrid deep learning models, hybrid machine learning, and ensemble models. Application domains include a wide range of economics research, from stock market, marketing, E-commerce, to corporate banking, and cryptocurrency. Prisma method, a systematic literature review methodology is used to ensure the quality of the survey. The findings revealed that the trends are on the advancement of hybrid models. On the other hand, based on the accuracy metric it is also reported that the hybrid models outperform other learning algorithms. It is further expected that the trends would go toward the advancements of sophisticated hybrid deep learning models.

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