bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultra-local model based prescribed performance adaptive control of overhead cranes under uncertainties
Authors: Hou Ming , Xu Weimin
Published: December 2024

In this paper, a model-free adaptive control scheme is proposed to address the problem of system performance variations due to inaccurate models of overhead cranes, and external disturbances. First, an adaptive fast integral terminal sliding mode controller with a prespecified performance setting is proposed to accelerate the convergence of the sliding mode surface. In addition, an improved form of performance function is introduced to ensure the high accuracy convergence of state errors, while effectively enhance response performance and state tracking accuracy. Second, a prespecified performance nonlinear disturbance observer is introduced to estimate the lumped dynamics part of the ultra-local model, which can guarantee effective model-free properties. Finally, the stability of the closed-loop control scheme is analyzed by means of Lyapunov stability theory, and the effectiveness and superiority of the proposed method is proved by means of numerical simulation results.
Intraclass Correlation in Cluster Randomized Controlled Trials: A Meta-Analysis of Studies on Major Depression
Authors: Bhaskarapillai Binukumar , Malo Palash Kumar , Kishore M. Thomas , Joseph Anoop , Majhi Gobinda , Jaisoorya T S , Kandavel Thennarasu
Published: December 2024

Background:

Though cluster randomized trials (CRTs) provide robust evidence for intervention by controlling contamination of interventions, there could be some loss of statistical efficiency. The Consolidated Standards of Reporting Trials (CONSORT) recommends reporting intraclass correlation coefficients (ICC) to understand this phenomenon, though not many studies follow this. This meta-analysis explored the compliance of CRTs in major depression for reporting ICC besides deriving the pooled ICC and pooled mean differences of intervention outcomes.

Methods:

Thirty-four articles on CRTs in major depression were identified from PubMed, Cochrane Library, PsychINFO, and Embase, and relevant data were extracted. Only 20 studies were eligible for meta-analysis of intervention, among which 8 reported ICC. We used DerSimonian and Laird’s inverse variance method to calculate the pooled estimates.

Results:

Only eight (40%) of the CRTs reported using ICC both for designing the study and examining intervention outcomes. The pooled ICC was 0.07 (95% confidence interval [CI]: 0.05, 0.09) with a low heterogeneity (I2 = 28%). Among the 20 studies, 65% used different psychosocial methods alone as intervention, with substantial heterogeneity. The pooled standardized mean difference of depression scores (–0.46; 95% CI: –0.79, –0.13) indicated the effectiveness of psychosocial interventions irrespective of combined pharmacotherapy (z = 2.71, p value = 0.01). Further, a subgroup analysis of intervention effects revealed that the results were significant only for the CRTs with ICC conformity.

Conclusions:

The ICCs can affect the intervention outcomes. Therefore, as indicated by this meta-analysis, CRTs must adhere to the CONSORT guidelines on reporting ICC. Future CRTs on major depression can utilize the pooled ICC estimate from this study, especially for sample size estimations.
Unlocking Liquidity: The Role of Market Makers in Kuwait’s Emerging Market
Authors: Alsabah Khaled , Althaqeb Saud Asaad
Published: December 2024

This study uses a difference-in-differences approach to examine the influence of market-maker agreements on liquidity alterations in Boursa Kuwait. Our research indicates that signing a market-maker agreement augments the number of executed trades, turnover, and trading volume while decreasing instances of zero trades, bid–ask spread, and Amihud Illiquidity within the first week. Interestingly, these agreements do not affect stock return volatility.

 Our study extends the knowledge about the role of market makers in emerging markets.

JEL Codes: G10, G18, O53
The Impact of Community-Based Micro-Hydroelectric Plants on Sustainable Development in the Gilgit–Baltistan Region of Pakistan
Authors: Khan Muhammad Ammad , Yousuf Najma , Bashawri Yasir M.
Published: December 2024

This paper reflects on Pakistan’s current energy scenario and focuses on the Gilgit–Baltistan (GB) region where electrification remains a critical issue, particularly for the rural and remote communities. Aiming to evaluate the viability of hydropower as a sustainable energy source, the study involves an empirical investigation into the social, economic, and environmental impacts of two community-based micro-hydroelectric plants (CBMHPs) in Ahmadabad village, Hunza district. Employing an ethnographic methodology, data was collected through interviews with 21 households and 8 community members, supplemented by a focus group discussion. However, photographic data supported thematic analysis for data triangulation. Findings indicate that CBMHPs provide notable benefits, including continuous electricity, improved education, enhanced income opportunities, and a boost in tourism. These plants also lessen firewood usage, thereby cutting carbon emissions and aiding environmental conservation. The study advocates for the expansion of CBMHPs both in Pakistan and internationally to replicate these positive outcomes.
Telemedicine in Alzheimer's disease and other dementias: Where we are?
Authors: Angelopoulou Efthalia , Papageorgiou Sokratis G
Published: December 2024

The prevalence and global health burden of dementia including Alzheimer's disease (AD) is rising, while patients living in remote and underserved areas face significant challenges in reaching specialized care. Telemedicine offers a valuable solution in bridging this widening gap, by providing equal and timely access to tertiary-specialized centers. Accumulating evidence highlights that most parts of the remote neuropsychological and neurological evaluation are feasible, with patients, healthcare professionals and caregivers being generally satisfied with this means of care. Herein, we provide an updated overview of the available evidence on the use of telemedicine for patients with cognitive disorders, focusing on the different applications and settings, the remote, video-based neurological and neuropsychological assessment, current recommendations, non-pharmacological interventions, as well as legal and ethical considerations. Based on the literature review and our three-year experience in the “Specialized Outpatient Clinic of Memory, Dementia and Parkinson's disease through the National Telemedicine Network” in the Aiginition University Hospital of Athens, we propose a brief guide for assessing patients with cognitive impairment via telemedicine and suggest future research directions for the more effective and appropriate use of telemedicine in dementia assessment and care.
Utilization and perceived usefulness of monitoring technology for family caregivers of people living with Alzheimer's disease and related dementias
Authors: Smith Matthew Lee , Wilson Ashley D , Knebl Janice , Hilsabeck Robin C , Reuter Kristen , Aguirre Alyssa , Harty Barbara , Kew Chung Lin , Lee Shinduk , Ory Marcia G
Published: December 2024

Background

Caregivers of people living with dementia (PLWD) often experience burden based on their care recipients’ symptoms of wandering, disorientation, and agitation.

Objective

To examine the utilization and perceived value of technology-based solutions for caregiving among caregivers of PLWD.

Methods

In collaboration with three Texas sites, PLWD and family caregiver dyads were recruited from clinical and community sites to assess the feasibility of a caregiving technology. PLWDs were asked to wear a GPS-based wearable device, which was paired with caregivers’ smartphone application, that enabled location monitoring and was equipped with call functions. After three months, researchers called caregivers to ask about their utilization of the “system” (i.e., wearable paired with smartphone application) and the perceived value of this technology. Forty-one caregivers completed follow-up telephone interviews.

Results

About 70% of caregivers reported their care recipient wore the wearable device daily, and 39.1% used the smartphone application daily. Approximately 31% of caregivers reported daily use of the tracking feature, 30.8% reported daily use of the “safe zone” feature (i.e., geo-fencing), and 17.1% reported daily use of the two-way calling feature. About 39% of caregivers were extremely satisfied with the “system,” 43.6% found it extremely easy to use, and 46.2% found it extremely useful for caregiving. On average, caregivers with higher baseline Zarit Burden Interview scores found the “system” to be more useful with their caregiving (f = 5.97, p = 0.006) and were more satisfied with the “system” (f = 3.75, p = 0.034).

Conclusions

Findings suggest caregiver burden may drive the perceived usefulness of, and satisfaction with, technology-based solutions.
Knowing and Caring About the Impact of Crime on Victims: Results From an Intervention for Justice-Involved Youth
Authors: Hay Carter , Hargrove Emily , Davidson Kimberly M. , Cobb Ashton
Published: December 2024

Impact of crime (IOC) interventions are delivered to justice-involved populations to increase sensitivity to and awareness of the harm experienced by crime victims. Such programs are common, but empirical evaluations have been rare. This study addressed that gap by evaluating an IOC intervention used with residential youth in Florida. The study focused on two questions. First, did IOC participants experience improvement on key outcomes? Second, was improvement affected by key individual qualities of youth? Pre- and post-intervention survey data were collected for 419 IOC participants on five outcomes: Sensitivity to victim impact, willingness to take responsibility, antisocial thinking, readiness to make life changes, and factual awareness of victim impact. The analysis revealed that all five outcomes were marked by significant pre-to-post improvements. There was individual variation, with some youth showing substantial improvement and others showing modest improvement or iatrogenic effects. This pattern included modest evidence of greater improvement among those with extensive prior offending and lower improvement among Black youth. We conclude by describing the implications of these findings for the policy and practice of juvenile correctional treatment.
Is Artificial Intelligence the Future of Radiology? Accuracy of ChatGPT in Radiologic Diagnosis of Upper Extremity Bony Pathology
Authors: Hiredesai Annika N. , Martinez Casey J. , Anderson Megan L. , Howlett Carina P. , Unadkat Krishna D. , Noland Shelley S.
Published: December 2024

Background:

Artificial intelligence (AI) is a promising tool to aid in diagnostic accuracy and patient communication. Prior literature has shown that ChatGPT answers medical questions and can accurately diagnose surgical conditions. The purpose of this study was to determine the accuracy of ChatGPT 4.0 in evaluating radiologic imaging of common orthopedic upper extremity bony pathologies, including identifying the imaging modality and diagnostic accuracy.

Methods:

Diagnostic imaging was sourced from an open-source radiology database for 6 common upper extremity bony pathologies: distal radius fracture (DRF), metacarpal fracture (MFX), carpometacarpal osteoarthritis (CMC), humerus fracture (HFX), scaphoid fracture (SFX), and scaphoid nonunion (SN). X-ray, computed tomography (CT), and magnetic resonance imaging (MRI) modalities were included. Fifty images were randomly selected from each pathology where possible. Images were uploaded to ChatGPT 4.0 and queried for imaging modality, laterality, and diagnosis. Each image query was completed in a new ChatGPT search tab. Multinomial linear regression was used to identify variations in ChatGPT’s diagnostic accuracy across imaging modalities and medical conditions.

Results:

Overall, ChatGPT provided a diagnosis for 52% of images, with accuracy ranging from 0% to 55%. Diagnostic accuracy was significantly lower for SFX and MFX relative to HFX. ChatGPT was significantly less likely to provide a diagnosis for MRI relative to CT. Diagnostic accuracy ranged from 0% to 40% with regard to imaging modality (x-ray, CT, MRI) though this difference was not statistically significant.

Conclusions:

ChatGPT’s accuracy varied significantly between conditions and imaging modalities, though its iterative learning capabilities suggest potential for future diagnostic utility within hand surgery.
“I am happy to take the lead”. A ventriloquial perspective on leadership and authority: What authorises organisational players to take the lead?
Authors: Clifton Jonathan
Published: December 2024

Authority has long been associated with leadership, but the relationship between authority and leadership has remained elusive. Addressing the issue of the interplay between authority and leadership, this paper builds on limited recent work that has considered leadership to be an in situ accomplishment in which the doing of authority is interwoven with the doing of leadership. Using transcripts of real-time interaction taken from a Board meeting of an NGO, and applying the Montreal School’s ventriloquial approach to the analysis of organisational communication, the research question this paper asks is: what authorises one of the Board members to ‘take the lead’ in establishing measures to ensure that the actions of the NGO are sustainable? Findings suggest that it is neither position, nor expertise, that authorise leadership. Rather, it is the articulation of the ideal of sustainability. Leadership is thus shown to be both a question of human leaders and ideals that they are able to mobilise which authorise their claim to leadership.
Can encryption save lives? Secure messaging and its infrastructure as loci of convergence between cyber warfare and conventional warfare: The case of Ukraine
Authors: Ermoshina Ksenia , Musiani Francesca
Published: December 2024

The controversies surrounding the right to privacy of individuals in a hyperconnected world are longstanding debates, where particular emphasis is placed on encryption technologies, which encode information by converting its original representations into alternative forms that computers cannot decipher, thus ensuring the security of communications. These technologies are at the heart of a public controversy, in which privacy advocates a clash with claims that encryption is a threat to general security as an enabler of subversive action. Recent developments in the armed conflict in Ukraine open up or renew questions such as: in times of war, what is the role of encryption and privacy technologies? How does armed conflict challenge existing threat models, what are the new risks for civil society? Can encryption save lives? This article addresses these questions by showing that encrypted messaging is the subject of convergence between the informational and physical aspects ‘in the field’ of war in the 21st century. The aim is to show how these messaging tools and the digital ecosystem that makes their deployment possible (interfaces, access providers, telecom operators) are now an integral part of a war and resistance infrastructure where the borders between cyber warfare and conventional warfare are becoming more and more blurred. However, we will also underline the limits of a tool-centred approach and demonstrate how, in the case of the war in Ukraine, physical threats to civilians and infrastructure damage mean that encrypted messaging is one among several innovative technical and social practices of holistic self-defence deployed by Ukrainians.
Anatomical neuromuscular variations determined by magnetic resonance imaging in chronic pelvic pain
Authors: Peng Yuanyuan , Sach Toos , Chow Jason , Abbott Jason
Published: December 2024

Background:

The diagnosis of neuromuscular pelvic pain is challenging. Despite the increasing use of magnetic resonance imaging (MRI) in the assessment of pudendal neuralgia, there are limited data describing radiological variations of the nerve. Additionally, the utility of MRI in the assessment of pelvic floor tension myalgia is unknown.

Aims:

To describe the anatomical variations of the pudendal nerve and dimensions of pelvic muscles in patients investigated for neuromuscular pelvic pain using a combined MRI protocol.

Materials and methods:

A retrospective audit of MRI reports for 136 patients referred to a single radiologist was conducted. Reported data included the appearances of the pudendal nerve and its perineural structures, and the maximal thicknesses of pelvic muscles.

Results:

Several anatomical variations were identified in the course of the pudendal nerve at or above the ischial spine. Likely/highly likely nerve compression at this level was present in 34.6% of hemipelves. Variations associated with compression included delayed separation of the sacrospinous and sacrotuberous ligaments ( p < 0.0001), close apposition of ligaments ( p < 0.0001), interligamentous bands ( p = 0.033), coccygeal muscle contributions to the sacrospinous ligament ( p = 0.014) and proximal ( p < 0.0001) and thickened falciform ligaments ( p < 0.0001). Variations below the ischial spine were uncommon.

Conclusions:

This study represents a quantitative and qualitative expansion to the radioanatomical basis of pudendal nerve entrapment on MRI, and highlights the limitations of MRI obtaining reproducible measurements of pelvic muscles. Images from asymptomatic controls and further prospective evaluation of treatment outcomes is required to determine the clinical significance of MRI findings in the assessment of pudendal neuralgia.
Multicellular Derived S100A8/A9 Maintains Megakaryocytes in an Immature State in Immune Thrombocytopenia
Authors: Qi Jiaqian , Yin Jie , Zhou Meng , Han Haohao , Wu Depei , Han Yue
Published: December 2024

Immune thrombocytopenia (ITP) is a common acquired autoimmune bleeding disorder characterized by reduced platelet count. Impaired maturation of megakaryocyte (MK) plays an important role, although the exact mechanisms are not fully understood. In this study, we performed 10x Genomics single-cell sequencing (SC-seq) on bone marrow samples from ITP patients and validated the data through in vitro models of megakaryocyte generation and an ITP mouse model. The results showed elevated levels of S100A8/A9 in ITP patients and it was further confirmed using RNA-seq data in the GEO database. Cell communication analysis via SC-seq revealed that neutrophils, megakaryocytes, platelets, and hematopoietic stem cells can produce S100A8/A9 and act on the TLR4 receptor of megakaryocytes. An in vitro ITP system constructed using patient plasma and primary CD34+ cells demonstrated that impaired megakaryocyte maturation and platelet reduction could be reversed by inhibiting S100A8/A9. Single-cell sequencing analysis of the in vitro system further classified megakaryocytes into four types: Immature MK, Cycling MK, Immune MK, and Thrombopoiesis-biased MK, and Pseudo-time analysis revealed S100A8/A9 decreases gradually with the maturation of megakaryocytes. High levels of S100A8/A9 were found to maintain megakaryocytes in an Immature MK state. Pathway analysis identified inhibition of the MAPK signaling pathway in the ITP group, regulated by the Raf protein, and blocking S100A8/A9 restored the MAPK pathway. Active and passive ITP mouse models treated with S100A8/A9 inhibitors demonstrated increased platelet recovery rate and the number of mature megakaryocytes in the bone marrow, highlighting the potential therapeutic value of S100A8/A9 inhibitors in ITP patients.
Impact of Protein Energy Malnutrition on Hospitalized Patients with Hodgkin's Lymphoma: A United States Population-Based Cohort Study
Authors: Syal Arshi , Arya Yajur , Byfield Karecia , Casipit Bruce Adrian , Dourado Claudia , Varadi Gabor
Published: December 2024

Background

Advances in chemotherapeutics have increased survival in patients with Hodgkin's lymphoma. With prolonged survival, these patients are often predisposed to co-morbidities, including cancer-related cachexia, muscle wasting, and adverse effects of chemotherapy. As a result, these patients suffer from varying degrees of protein-energy malnutrition (PEM). However, the impact of PEM on outcomes among patients with Hodgkin's lymphoma needs further exploration.

Methods

We utilized the 2020 National Inpatient Sample (NIS) Database to conduct this retrospective cohort study. We identified patients with Hodgkin's lymphoma and PEM using appropriate ICD-10 diagnostic codes. We stratified patients with Hodgkin's lymphoma based on the presence or absence of PEM. A survey multivariable logistic and linear regression analysis was used to calculate adjusted odds ratios (ORs) for the primary and secondary outcomes. A p-value of <0.05 was considered statistically significant. The aim of this study was to investigate the impact of PEM on in-hospital mortality, hospital length of stay (LOS), and total hospitalization charges among hospitalized patients with Hodgkin's lymphoma.

Results

We identified a total of 3705 hospitalized patients with Hodgkin's lymphoma, of which 13.36% (495/3705) had comorbid PEM. The overall in-hospital mortality among patients with Hodgkin's lymphoma was 2.97% (110/3705). Among those with concomitant PEM, the mortality rate was significantly higher at 9.09% (45/495, p<0.001). Utilizing a stepwise survey multivariable logistic regression model that adjusted for patient and hospital level confounders, PEM was found to be an independent predictor of increased in-hospital mortality (adjusted OR 3.71; 95% (confidence interval [CI] 1.23-11.21; p=0.02), longer LOS (coefficient 2.88; CI 0.49-5.28; p=0.018), higher total hospitalization charges ($41649; CI $4818-$78481; p=0.027), as well as increased need for mechanical ventilation (adjusted OR 4.28; CI 1.50-12.18; p=0.006).

Conclusion

Our analysis demonstrated that PEM was widely prevalent in patients with Hodgkin's lymphoma. It was associated with worse outcomes, including significantly increased in-hospital mortality, longer LOS, total cost of healthcare utilization, as well as increased need for mechanical ventilation. Efforts should be made to promote nutritional assessment and screening mechanisms to include early nutritional support as indicated. Prospective studies with larger sample size are needed to better understand these associations.
A CD38xCD28 Costimulatory Bispecific Antibody Demonstrates Potent Preclinical Combinatorial Activity with a BCMAxCD3 T Cell-Engager
Authors: Olson Kara , DiLillo David , Sineshchekova Olga , Mohrs Katja , McCarthy Craig , Ahmed Hassan , Rizvi Sahar , Quatela Steven , Navarro Elizabeth , Lin Cuiyan , Dorvilliers Amanda , Kroog Glenn S. , Rodriguez Lorenc Karen , Ullman Erica , Hermann Aynur , Smith Eric , Kirshner Jessica , Olson William , Lin John
Published: December 2024

Improving therapies for relapsed/refractory multiple myeloma (RRMM) remains an unmet medical need, as despite improvements in treatment management, there is still no curative therapy and relapse remains a persistent problem. The emergence of T cell targeted immunotherapies, including BCMAxCD3 bispecific antibodies (bsAbs), has marked a significant advancement in patient outcomes. Among these, the BCMAxCD3 bispecific antibody, linvoseltamab, has emerged as a potential best-in-class option for RRMM; however, deeper and more durable responses in this patient population are still required.

In RRMM, linvoseltamab activates T cells by engaging the T cell receptor (TCR)/CD3 complex in the presence of BCMA-expressing MM tumor cells leading to tumor cell killing. However, for optimal activation, T cells require engagement of costimulatory receptor signaling (e.g., CD28) in addition to the TCR/CD3 complex. CD28-targeting bsAbs, including REGN5668 (MUC16xCD28) and REGN5837 (CD22xCD28), are an emerging class of therapeutics capable of providing targeted costimulation and enhancing T cell effector function in combination with CD3-targeted bsAbs. In MM, CD38 is a cell-surface, multifunctional ectoenzyme that is highly expressed on MM blasts, making it a good candidate for a CD28-targeted bsAb. Thus, here we examine whether providing CD28 costimulatory signaling via a novel CD38xCD28 bsAb in the context of BCMAxCD3 bsAb therapy (linvoseltamab) can drive enhanced antitumor activity in preclinical models.

We explored combining a novel CD38xCD28 bsAb antibody, REGN7945, with linvoseltamab. This combination potently enhanced linvoseltamab's anti-tumor activity by delivering a critical costimulatory signal to CD28-expressing T cells, augmenting T cell activation, cytokine production, and cytotoxicity in vitro. We demonstrated strong enhancement of linvoseltamab's anti-tumor activity with REGN7945 in multiple in vivo murine xenograft MM models. Further, in immunocompetent mice genetically engineered to express human CD3, CD28, BCMA, and CD38, we demonstrated potent combinatorial efficacy of linvoseltamab and REGN7945 to treat syngeneic murine tumors.

Based on these promising preclinical results, a Phase 1 clinical trial is planned to evaluate the safety, tolerability, and preliminary efficacy of the CD38xCD28 bsAb REGN7945 and the BCMAxCD3 bsAb linvoseltamab in patients with RRMM. This innovative approach, leveraging the combinatorial potential of CD38xCD28 costimulation with linvoseltamab's targeted cytolytic activity, represents a novel therapeutic strategy with the potential to improve RRMM treatment outcomes.
CircFUT8 Promotes Megakaryocyte Proplatelet Formation By Regulating Actin Cytoskeleton Reorganization
Authors: Wu Huang , Lu Yao , Sun Denglian , Lin Huayu , Xia Wenjun , Chen Ruichi , Chen Jun , Xie Jiaying , Feng Rong , Ren Lijie , Miao Zeqing , Liu Junling , Yu Yang , Wen Aiqing
Published: December 2024

Megakaryocytes (MKs) are large cells derived from hematopoietic stem cells (HSCs) through a process of differentiation and maturation. Mature MKs extend long processes called proplatelets, which are released into bone marrow sinusoids under the shear forces of blood flow. These proplatelets also form platelets in the lungs. Platelets are small cell fragments that play crucial roles in hemostasis, thrombosis, and immunity. The process of platelet generation from megakaryocytes is intricately orchestrated by non-coding RNAs, such as miRNAs. Another non-coding RNA, circRNA, is highly abundant in platelets, but its role in platelet production remains unclear. We performed RNA-seq and bioinformatics analysis to identify circRNAs during the differentiation of megakaryocytes from umbilical cord blood hematopoietic stem cells. We found that circFUT8, a novel circRNA, increases with megakaryocyte differentiation and is enriched in mature megakaryocytes. Knockdown and overexpression studies showed that circFUT8 promotes human megakaryocyte proplatelet formation (PPF) in vitro. We also found that circFUT8 is highly conserved between humans and mice. In vitro, knockdown of circFUT8 decreases mouse megakaryocyte PPF. In vivo, it reduces murine platelet counts, prolongs tail bleeding time, and reduces the number of MKs in contact with sinusoids. Furthermore, knockdown of circFUT8 reduces F-actin polymerization and impairs spreading on collagen. Additionally, we revealed that circFUT8 interacts with insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) and stabilizes tensin 1 (TNS1) mRNA. We observed that knockdown of TNS1 disrupts the actin cytoskeleton and decreases PPF. Our study highlights the crucial functions of circRNAs in platelet production and the rearrangement of the actin cytoskeleton.
Shengxuening Tablets for the Treatment of Cancer Related Anemia in Hematologic Malignancies: A Multicenter, Prospective, Randomized Controlled Clinical Trial
Authors: Fang Jiamin , Liu Xiaoyan , Zhou Fuling
Published: December 2024

Abstract I ntroduction : Cancer related anemia (CRA) is a prevalent comorbidity associated with malignant tumors. Presently, treatments for CRA primarily comprise blood transfusion therapy, erythropoiesis-stimulating agent therapy, and iron supplementation. Conventional oral iron exhibits low bioavailability and significant gastrointestinal irritation, whereas intravenous iron offers rapid iron replenishment. However, excessive iron supplementation may lead to iron overload, and intravenous drug delivery is less accepted among hematological oncology patients. Shengxuening tablets demonstrate clinical efficacy in treating CRA among patients with hematologic malignancies by enhancing endogenous EPO production, stimulating bone marrow hematopoiesis, and regulating iron metabolism.To evaluate the effect of Shengxuening tablets on improving anemia and regulating iron metabolism in patients with hematologic malignancies combined with CRA.

Methods: Patients who met the enrollment criteria were randomly divided into the trial group and the control group. Patients in the trial group received oral treatment with Shengxuening tablets 1 week before chemotherapy, while those in the control group received oral treatment with ferrous succinate 1 week before chemotherapy. The primary endpoints were changes in blood routine after 1 month of treatment. The secondary endpoints were iron metabolism indexes related indexes.

Results:Until July 20, 2024, a total of 48 patients were enrolled in the multiple myeloma group and randomized into two groups: a trial group consisting of 31 patients and a control group consisting of 17 patients. Since the enrollment process has not yet been completed, we only statistically analyzed part of the data that have been obtained so far. Prior to treatment initiation, there was no statistically significant difference in blood routine and iron metabolism indexes between the two groups (P>0.05). After treatment, the mean corpuscular hemoglobin concentration (MCHC) of the trial group increased significantly (P<0.05), while no statistically significant difference was observed in the blood routine indexes of the control group before and after treatment. As of now, apart from two cases of gastrointestinal adverse reactions observed in the control group, no other evident drug-related adverse reactions have been noted.

C onclusion :The use of Shengxuening tablets for the treatment of CRA in patients with multiple myeloma can achieve more ideal efficacy than ferrous succinate and has a manageable safety profile.
Teclistamab in Relapsed and Refractory Multiple Myeloma Patients - Czech Multi-Center Real World Evidence Analysis
Authors: Stork Martin , Radocha Jakub , Jelinek Tomas , Spicka Ivan , Pika Tomas , Jungova Alexandra , Straub Jan , Minarik Jiri , Boichuk Ivanna , Fric Dominik , Novakova Denisa , Popkova Tereza , Polcerova Lenka , Maisnar Vladimir , Pour Ludek , Hajek Roman
Published: December 2024

Background

Teclistamab is a bispecific antibody designed to target multiple myeloma (MM) cells by simultaneously binding to B-cell maturation antigen (BCMA) on MM cells and CD3 on T cells, facilitating a T-cell-mediated anti-tumor immune response. In the MajesTEC-1 clinical trial, teclistamab demonstrated high efficacy in heavily pretreated relapsed and refractory MM (RRMM) patients. As approximately 40% of MM patients are ineligible for clinical trials, the importance of real-world evidence (RWE) data on the efficacy and safety of teclistamab becomes increasingly significant.

Aims

We conducted a RWE analysis of teclistamab monotherapy in heavily pretreated RRMM patients. Additionally, we evaluated the efficacy of teclistamab in patients with a reduced dosing frequency.

Patients and methods

A total of 48 RRMM patients were treated with teclistamab between 2023 and 2024 outside clinical trials across all major Czech hematology centers. Teclistamab was administered either on a standard schedule (weekly for at least six months) or a reduced frequency schedule (every other week), based on the physician's decision. The response was evaluated according to the IMWG Response Criteria. Patient data were collected and analyzed from the Czech Registry of Monoclonal Gammopathies (RMG).

Results

The median age at the first teclistamab administration was 65.5 years (range 46-76). The median number of previous treatment lines was 5 (range 3-13), with 66.7% (32/48) of patients being penta-refractory (refractory to 2 proteasome inhibitors, 2 IMiDs, and an anti-CD38 antibody). The overall response rate (ORR), defined as partial response (PR) or better was 61.7% (27/44 evaluable patients) and the rate of very good partial response (VGPR) or better was 54.5% (24/44). The median follow-up was 4 months (range 1-13). The median progression-free survival (PFS) was 9.4 months (95% CI: 6.4-NA). Median overall survival (OS) was not reached with 58.9% (95% CI: 43.8-79.2) survival after 12 months. In 25.0% (12/48) of patients, teclistamab was administered every other week. The estimated proportion of patients without a PFS event at 6 months of follow-up was comparable regardless of the dosing schedule (weekly: 62.3% (95% CI: 47.4-81.9) vs. non-weekly: 81.5% (95% CI: 61.1-100.0); p=0.226). The OS data, based on the dosing scheme, were immature.

Conclusion

Our RWE data demonstrate high efficacy of teclistamab monotherapy in heavily pretreated RRMM population, comparable to MajesTEC-1 registration trial results. Preliminary data suggest that non-weekly dosing could be similarly effective compared to the standard protocol.
IDH-1 Somatic Mutations Are More Commonly Observed Among Patients with Concomitant Myelodysplastic Syndromes (MDS) and Autoimmune Rheumatoid Diseases (AIRD)
Authors: Komrokji Rami S. , Al Ali Najla H. , Xie Zhuoer , Komrokji Zena , Jabbour Joseph E. , Chan Onyee , Yun Seongseok , Kuykendall Andrew T. , Walker Alison R. , Lancet Jeffrey E , Padron Eric , Sallman David
Published: December 2024

Introduction

We previously reported that autoimmune diseases (AID) are commonly observed in MDS patients (pts) (28%) including autoimmune rheumatic diseases (AIRD). There is increase recognition of the association of certain acquired somatic mutations and inflammation. Recent study reported enrichment of AIRD among chronic myeloid neoplasms (MN) pts with high prevalence of IDH mutations suggestive causative association particularly between IDH mutations and seronegative rheumatoid arthritis (Hong et al, Blood 2024). Here, we compare the genomic landscape of MDS pts with concomitant defined AIRD to those without.

Methods

We identified MDS pts with concomitant AIRD. We selected Rheumatoid arthritis (RA) and systemic lupus (SLE) as AIRD given more objective diagnostic criteria and accurate data capturing. We compared those MDS pts with AIRD to MDS pts without.

Results

We compared 79 MDS pts with AIRD to 2469 MDS pts without in our database. AIRD were more observed among female MDS pts compared to non-AIRD MDS pts (59% vs 32%, p < 0.0005). There was no difference in age, race, t-MDS, WHO 2022 classification, IPSS-M risk stratification. There was no difference in baseline myeloblasts% or blood counts.

Among 21 common somatic mutations tested, IDH-1 somatic mutation was the only mutation observed more among AIRD MDS pts compared to non-AIRD MDS pts (11% vs 3%, p <0.0005). Among male AIRD MDS pts rate of IDH-1 was 15% vs 3% and 8% vs 3% among females AIRD MDS pts compared to non-AIRD MDS pts. (p <.0005)

There was no difference among AIRD- MDS pts and non-AIRD MDS pts in median overall survival. There was a non-statistically significant trend for worse median OS among AIRD MDS pts with IDH-1 mutation (30 mo vs 40 mo).

Conclusions

Our data confirm recently reported observation that IDH-1 somatic mutations are enriched among myeloid neoplasms patients with AIRD. Further studies to explore the underlying mechanism, and potential therapeutic implications with targeted IDH-1 inhibitors are warranted.
Real-World Data of Maintenance Therapy for Newly Diagnosed Multiple Myeloma: Ixazomib Versus Lenalidomide
Authors: Xu Yang , Zhang Xuzhao , Wang Luyao , Fan Yili , Chen Boxiao , Yang Luyu , Zhang Jiawei
Published: December 2024

Introduction: Lenalidomide and ixazomib are both effective maintenance therapy options for patients with multiple myeloma (MM). However, there is a lack of clinical studies directly comparing the efficacy and safety of these two agents. In this report, we present real-world data on the maintenance therapy of lenalidomide versus ixazomib in patients with newly-diagnosed MM (NDMM).

Methods: A retrospective real-world analysis was carried out between September 25, 2019 and June 20, 2023. The study included multiple myeloma patients who achieved a best response of partial response (PR) or higher following induction and/or consolidation therapy. Ixazomib was administered at a weekly dose of 3-4mg for 3 doses within a 28-day cycle, and lenalidomide was given at a daily dose of 10-25mg until disease progression. Adverse events were graded based on CTCAEv4.0 criteria, with the primary endpoints focusing on progression-free survival (PFS) and the incidence of adverse events.

Results: A total of 115 patients with NDMM were included, with 60 patients receiving ixazomib and 55 patients on lenalidomide maintenance. The patients' characteristics, cytogenetics, and disease staging between groups were well-balanced. The median follow-up periods were 33 and 29 months for the ixazomib and lenalidomide groups, respectively. There was no significant difference in PFS between the ixazomib and lenalidomide groups, with a median PFS of 39 versus 35 months, P=0.706. Following ixazomib maintenance, 35 out of 60 patients (58.3%) reached a response of ≥CR, while 56 patients (93.3%) achieved ≥VGPR, and 23 patients (38.3%) experienced a deepened response. After lenalidomide maintenance, 29 patients (52.7%) achieved ≥CR, 49 patients (89.1%) achieved ≥VGPR, and 15 patients (27.3%) showed an improved response. Subgroup analysis revealed that cytogenetic risk, R-ISS staging, ASCT, extramedullary disease, and remission status prior to maintenance did not have a significant impact on median PFS between the lenalidomide and ixazomib groups. In the lenalidomide group, high-risk cytogenetics were correlated with a shorter median PFS compared to standard-risk (SR) ,18 months vs. 35 months, P=0.022; whereas this association was not observed in the ixazomib group, HR vs. SR: 35 months vs. not reached, P=0.543. The incidence of neutropenia in the ixazomib group was lower than in the lenalidomide group, 35.1% vs. 58.5%, P=0.014. No severe drug-related AEs were reported in either group, and there were no statistically significant differences in non-hematological AEs between the two groups.

Conclusion: In patients with NDMM, maintenance therapy utilizing ixazomib or lenalidomide results in similar response rates and progression-free survival (PFS). Ixazomib appears to mitigate the adverse impacts of high-risk cytogenetics while maintaining a manageable toxicity profile.
Clinical Characteristics and Prognostic Analysis of Non-Amyloid Monoclonal Gammopathy of Renal Significance (MGRS) in China
Authors: Song Yuhang , Liu Yang , Liu Junru , Li Juan , Lu Jin , Zhuang Junling
Published: December 2024

Objective: To analyze the treatment efficacy and prognostic factors of patients with non-amyloid monoclonal gammopathy of renal significance (MGRS) across multiple centers, aiming to inform clinical management and improve patient outcomes.

Methods: A retrospective study was conducted on 136 non-amyloid MGRS patients from four major hospitals in China. Patients were diagnosed through kidney biopsy, and clinical data were collected, including demographics, laboratory results, pathology types, genetic testing results, and treatment regimens. Median follow-up period was 33.5 months. The endpoints included renal response, progression, and hematologic efficacy according to the International Society of Amyloidosis (ISA) criteria.

Results: The study included 136 patients, with a variety of MGRS pathologies , among which MIDD was the most frequent type (64 patients), followed by 20 PGNMID, 19 LCPT and 19 cryoglobulinemic nephropathy There were 104 patients receiving anti-plasma cell therapies, among which 71 were treated with bortezomib-based regimens. Baseline serum free light chain level >400mg/L were found to be an independent risk factor for poor hematologic response to first-line therapy (P=0.042, HR=5.98). Deep hematologic remission was a significant protective factor (p=0.006, HR=20) for renal response. The presence of t (11; 14) translocation was identified as an independent risk factor (p=0.029, HR=0.138) for poor renal response . Patients achieving deep hematologic remission (not achieved vs 104m, p=0.001) and negative t (11; 14) translocation (104m vs 43m, p=0.001) had better renal progression-free survival rates.

Conclusion: Although MGRS composes heterogenous diseases, this study underscores the significance of baseline serum free light chain and t(11; 14) translocation in predicting treatment response in non-amyloid MGRS patients , and the connection between hematological response and renal response.

Keywords: Non-amyloid MGRS, renal response, hematologic efficacy, serum free light chain, t (11; 14) translocation, personalized treatment.
High Rates of Undetectable MRD By Phased-Seq on Interim and End of Treatment Timepoints in Untreated Advanced Stage Chl Treated with Pembrolizumab + AVD
Authors: Lynch Ryan C , Alig Stefan K. , Ujjani Chaitra S. , Poh Christina , Warren Edus H. , Smith Stephen D. , Shadman Mazyar , Till Brian G. , Raghunathan Vikram , Tseng Yolanda D , Ottemiller Susan , Joy Bonnie , Fessel Melissa Mary , Du Hongyan , Vandermeer Jacquelin , Kelly Alyssa , Rasmussen Heather , Voutsinas Jenna M. , Alizadeh Ash A. , Gopal Ajay K.
Published: December 2024

Introduction

We previously reported initial (n=30) efficacy results of a frontline study of pembrolizumab + AVD (Lynch et al Blood 2023, ASH 2023) in classic Hodgkin lymphoma (CHL). Despite finding surprisingly high rates of positive interim and EOT PET/CT compared to historical data, observed outcomes were excellent. Herein we present updated clinical data for our full 50-patient study including interim and end of treatment (EOT) MRD testing by PhasED-Seq

Methods

We examined additional long-term follow up of patients with pembrolizumab combined with concurrent AVD in previously untreated CHL as previously described (NCT03331341). Samples were analyzed for ctDNA at baseline, post cycle 1 (if available), post cycle 2, and end of treatment. ctDNA levels were quantified as haploid genome equivalents/mL plasma using PhasED-Seq (Kurtz et al. Nat Biotech 2021).

Results

50 patients were enrolled between Feb 1, 2019, and Apr 13, 2023, with a median follow up of 3.1 years; 3-year PFS and OS were 98% and 100%, respectively. Among advanced stage patients (n=38), 3-year PFS and OS were 97% and 100%, respectively.

In patients where samples were available for analysis, baseline ctDNA was detectable in 11/12 (92%) of early-stage patients, and 36/37 (97%) of advanced stage patients. 7/8 (88%) early-stage patients had undetectable MRD (uMRD) at C3D1, and all cleared ctDNA by EOT and none have relapsed to date. Among advanced stage patients, 22/29 (76%) of samples at C2D1 and 29/35 (83%) samples at C3D1 had uMRD. In contrast, the PET CR rate at C3D1 in advanced stage patients was only 58%. At EOT, 31/34 (91%) advanced stage samples had uMRD compared to a PET CR rate of 73%. The only patient in the study to relapse had a negative interim PET but did not clear ctDNA at any timepoint. Two additional patients had minute amounts of ctDNA detectable at the end of treatment after levels dropped >20,000 fold when compared to baseline. Both patients have not relapsed 3 years and 14 months after completion of treatment, respectively. Some timepoints did not have plasma samples available, and no samples were drawn for sequencing during follow-up,

Conclusion

Pembrolizumab + AVD continues to demonstrate durable efficacy in previously untreated CHL. No patient who has cleared ctDNA as measured by PhasED-Seq has relapsed to date despite high rates of interim-PET and EOT PET positivity. The role of PhasED-Seq will be further examined in the upcoming Phase 2 MRD-adapted PRECISE-HL study in untreated advanced stage CHL.
Preliminary Efficacy of Orelabrutinib Targeted Therapy in Induction Therapy of Primary Central Nervous System Diffuse B-Cell Lymphoma
Authors: Zhou Sha , Rao Jun , Xiang Xixi , Zeng Yunjing , Li Jiali , Yang Hanshan , Liu Bo , Zhang Xi , Gao Li
Published: December 2024

Objective: To evaluate the efficacy and safety of the induction regimen of targeted therapy of Orelabrutinib combined with chemotherapy in primary central nervous system diffuse B-cell lymphoma.

Methods: Patients aged 18 years and above with primary central nervous system diffuse B-cell lymphoma received ROM induction regimen (Orelabrutinib 150mg qd，rituximab 375mg/m2 day1, high-dose MTX 3.5 g/m2 day2, /28 days) for 3 courses. Patients who did not achieve partial remission (PR) or complete remission (CR) after 3 courses were excluded from the study. Patients who achieved PR or CR received consolidate treatment of autologous stem cell transplantation (ASCT), whole brain radiotherapy, or another 3 courses of ROM chemotherapy. Preliminary exploration the efficacy and safety of ROM induction therapy.

Results: From March 2021 to April 2024, a total of 30 patients with primary central nervous system diffuse B-cell lymphoma in our hospital received ROM induction regimen. The median age was 56 years (34-72), with 15 males and 15 females. Two patients experienced disease progression and died after two courses of treatment. After three courses of ROM induction therapy, 14 patients achieved CR, 11 patients achieved PR, and 3 patients had stable disease. The overall response rate (ORR) for all patients was 83.3%. The median onset time for PR is 1 course, and the median onset time for CR is 2 courses. After induction therapy, 9 patients received ASCT consolidation, 6 patients received whole brain radiotherapy consolidation, and 15 patients continued consolidation chemotherapy. After a median follow-up of 10 (2-37) months, the estimated 1-year OS was 84.6% and PFS was 76.0%. No grade III-IV hematological or non-hematological adverse events were observed in all patients.

Conclusion: The ROM regimen is an effective and safe induction therapy for primary central nervous system diffuse B-cell lymphoma, with a total response rate of 83.3% and a median onset time of 1 course for PR and 2 courses for CR. It is a promising induction therapy for primary central nervous system diffuse B-cell lymphoma.